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    Dihydropyridine Calcium Channel Blockers

    DEA CLASS

    Rx

    DESCRIPTION

    Dihydropyridine calcium-channel blocker
    Used for hypertension and angina
    More potent than nifedipine and amlodipine; longer-acting than regular-release nifedipine but shorter-acting than amlodipine

    COMMON BRAND NAMES

    DynaCirc

    HOW SUPPLIED

    DynaCirc/Isradipine Oral Cap: 2.5mg, 5mg

    DOSAGE & INDICATIONS

    For the treatment of hypertension.
    Oral dosage
    Adults

    2.5 mg PO twice daily initially; may increase by 5 mg increments at 2- to 4- week intervals (Max: 10 mg PO twice daily). Maximal therapeutic response may not be apparent for 2 to 4 weeks. The frequency of adverse effects is increased at doses exceeding 10 mg/day PO.

    Children† and Adolescents†

    0.05 to 0.1 mg/kg/dose PO given 2 to 3 times daily (Max: 0.6 mg/kg/day, not to exceed 10 mg/day). Alternatively, 0.15 to 0.2 mg/kg/day PO given in 3 to 4 divided doses (Max: 0.8 mg/kg/day, not to exceed 20 mg/day) has been recommended.

    Infants†

    Limited data are available. Final doses of 0.04 to 0.9 mg/kg/day PO divided 1 to 4 times per day have been reported in 2 retrospective studies (n = 127; age range: 1 day to 16 years); the daily dose was divided into every 6 or 8 hours dosing for 95 of the 127 patients. Mean dose in patients 0 to 1 year (n = 9) was 0.27 +/- 0.11 mg/kg/day in 1 of the studies. Maximum dosing has not been clearly defined in this age group.

    Neonates†

    Limited data are available. Final doses of 0.04 to 0.9 mg/kg/day PO divided 1 to 4 times per day have been reported in 2 retrospective studies (n = 127; age range: 1 day to 16 years); the daily dose was divided into every 6 or 8 hours dosing for 95 of the 127 patients. Mean dose in patients 0 to 1 year (n = 9) was 0.27 +/- 0.11 mg/kg/day in 1 of the studies. Maximum dosing has not been clearly defined in this age group.

    For the treatment of chronic stable angina†.
    Oral dosage
    Adults

    In 1 study, the initial isradipine dose was 2.5 mg PO 3 times daily, which was titrated up to 7.5 mg PO 3 times daily if tolerated. In this study, 33 patients with angina pectoris (stable for 3 months) were randomized to 3 times daily dosing of isradipine or nifedipine, with dosage titration. While the efficacy for both drugs was equivalent, the incidence of adverse reactions such as dizziness, vertigo, tachycardia, and fatigue was lower for isradipine.

    For the treatment of hypertensive urgency†.
    Oral dosage
    Children and Adolescents

    0.05 to 0.1 mg/kg/dose (Max: 5 mg/dose) PO every 6 to 8 hours.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    20 mg/day PO.

    Geriatric

    20 mg/day PO.

    Adolescents

    Safety and efficacy have not been established; however, doses up to 0.6 to 0.8 mg/kg/day PO, not to exceed 10 to 20 mg/day PO, have been recommended.

    Children

    Safety and efficacy have not been established; however, doses up to 0.6 to 0.8 mg/kg/day PO, not to exceed 10 to 20 mg/day PO, have been recommended.

    Infants

    Safety and efficacy have not been established; however, a mean dose of 0.27 +/- 0.11 mg/kg/day PO has been reported.

    Neonates

    Safety and efficacy have not been established; however, a mean dose of 0.27 +/- 0.11 mg/kg/day PO has been reported.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    In patients hepatic impairment, isradipine clearance is reduced and the AUC is increased. No change in the usual starting dose is recommended. Adjust dosage as needed to attain clinical goals.

    Renal Impairment

    In patients mild renal impairment (CrCl 30 to 80 mL/minute), isradipine clearance is reduced and the AUC is increased. No change in the usual starting dose is recommended. Adjust dosage as needed to attain clinical goals.
     
    Intermittent hemodialysis
    Isradipine is highly protein-bound and is not expected to be significantly removed by hemodialysis.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Regular-release capsules: Administer isradipine capsules without regard to meals. Food decreases the rate, but not the extent of GI absorption.
    Extended-release tablets: Swallow isradipine tablets whole; do not crush, break, or chew. Administer without regard to meals; however, food may decrease bioavailability by up to 25%.

    Extemporaneous Compounding-Oral

    Extemporaneous 1 mg/mL isradipine oral suspension:
    NOTE: Isradipine oral suspension is not a formulation approved by the FDA.
    Open ten 5 mg regular release isradipine capsules and empty the contents into a mortar.
    Add a sufficient amount of glycerin to wet the powder and triturate to a fine paste.
    Add approximately 15 mL Simple Syrup to the paste, triturate, and pour into an amber glass bottle.
    Rinse the mortar with approximately 10 mL Simple Syrup, and add the contents to the amber glass bottle.
    Add additional simple syrup to the amber glass bottle to bring the final volume to 50 mL.
    Shake well before each use. This suspension is stable 35 days under refrigeration (4 degrees C).

    STORAGE

    DynaCirc:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    DynaCirc CR:
    - Avoid excessive humidity
    - Protect from moisture
    - Store below 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Dihydropyridine hypersensitivity

    Isradipine is a dihydropyridine calcium-channel blocker and is contraindicated in patients with known serious dihydropyridine hypersensitivity.

    Pregnancy

    Isradipine is classified in FDA pregnancy category C. There are no adequate and well-controlled studies in pregnant women. According to the manufacturer, isradipine should only be used during pregnancy when its benefits to the mother clearly outweigh its risks to the fetus.

    Breast-feeding

    It is not known whether isradipine is excreted into human milk, and therefore, breast-feeding should be discontinued during isradipine administration. Excretion of the drug into breast milk should be expected due to its low molecular weight. The effect of this exposure on a nursing infant is unknown. Because neonatal myocardium is very sensitive to changes in calcium status, it would be prudent to avoid using isradipine in the breast-feeding mother until more safety data are available. Nifedipine is usually regarded as compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Acute myocardial infarction, bradycardia, cardiogenic shock, heart failure, ventricular dysfunction

    Isradipine should be used cautiously in patients with severe bradycardia, acute myocardial infarction with pulmonary congestion, cardiogenic shock, ventricular dysfunction, or congestive heart failure because it can precipitate or exacerbate heart failure due to its negative inotropic effects, particularly in patients receiving concomitant beta-blocker therapy. The development or worsening of pulmonary edema is a marker for discontinuation of isradipine. This reaction may occur less frequently with isradipine than with other dihydropyridines.

    Hypotension

    Isradipine decreases peripheral resistance and can worsen hypotension. Isradipine should not be used in patients with systolic blood pressure of less than 90 mm Hg (i.e., severe hypotension). Use isradipine with caution in patients with mild to moderate hypotension. Blood pressure should be monitored carefully in all patients receiving isradipine.

    Hepatic disease, renal disease

    In patients with renal impairment (CrCl 30 to 80 mL/minute) or hepatic impairment, the clearance of isradipine is reduced and the bioavailability is increased. The manufacturer recommends initiating isradipine therapy at the usual adult starting dosage for patients with renal disease (including renal impairment or renal failure), and patients with hepatic disease. Adjust dosage as needed to attain clinical goals.

    Gastroesophageal reflux disease (GERD), hiatal hernia

    Isradipine should be used cautiously in patients with gastroesophageal reflux disease (GERD) or hiatal hernia associated with reflux esophagitis. Calcium-channel blockers relax the lower esophageal sphincter.

    Geriatric

    In geriatric patients, the clearance of isradipine is reduced and the maximal concentrations (Cmax) and exposure (AUC) are increased. In most cases, the usual adult starting dosage may still be used for the elderly patient. Titrate carefully to efficacy and tolerance to attain clinical goals. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to the OBRA guidelines, antihypertensive regimens should be individualized to achieve the desired outcome while minimizing adverse effects. Antihypertensives may cause dizziness, postural hypotension, fatigue, and there is an increased risk for falls. In addition, calcium channel blockers may cause peripheral edema and clinically significant constipation; some agents may cause generalized aching, headache, and muscle pain. There are many drug interactions that can potentiate the effects of antihypertensives. Some antihypertensives require a gradual taper to avoid adverse consequences caused by abrupt discontinuation.

    ADVERSE REACTIONS

    Severe

    heart failure / Delayed / 0-1.0
    myocardial infarction / Delayed / 0-1.0
    ventricular fibrillation / Early / 0-1.0
    atrial fibrillation / Early / 0-1.0
    stroke / Early / 0-1.0
    angioedema / Rapid / 0-1.0

    Moderate

    peripheral edema / Delayed / 7.2-15.2
    palpitations / Early / 1.2-4.0
    angina / Early / 2.4-2.4
    dyspnea / Early / 1.8-1.8
    constipation / Delayed / 1.7-1.7
    sinus tachycardia / Rapid / 1.5-1.5
    hypotension / Rapid / 0-1.0
    elevated hepatic enzymes / Delayed / 0-1.0
    leukopenia / Delayed / 0-1.0
    impotence (erectile dysfunction) / Delayed / 0-1.0
    peripheral vasodilation / Rapid / Incidence not known

    Mild

    headache / Early / 13.0-13.0
    dizziness / Early / 4.7-7.3
    fatigue / Early / 4.0-4.0
    abdominal pain / Early / 1.7-2.8
    flushing / Rapid / 1.9-2.6
    nausea / Early / 1.2-1.8
    weakness / Early / 1.2-1.2
    asthenia / Delayed / 1.2-1.2
    vomiting / Early / 1.1-1.1
    diarrhea / Early / 1.1-1.1
    syncope / Early / 0-1.0
    increased urinary frequency / Early / 0-1.0
    libido decrease / Delayed / 0-1.0
    paresthesias / Delayed / 0-1.0
    gynecomastia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetaminophen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Adenosine: (Moderate) Use adenosine with caution in the presence of calcium-channel blockers due to the potential for additive or synergistic depressant effects on the sinoatrial and atrioventricular nodes.
    Aldesleukin, IL-2: (Moderate) Calcium channel blockers may potentiate the hypotension seen with aldesleukin, IL 2.
    Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
    Alfentanil: (Moderate) Monitor patients for bradycardia and hypotension when alfentanil is coadministered with isradipine. Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving isradipine.
    Alfuzosin: (Moderate) The concomitant administration of alpha-blockers with other antihypertensive agents can cause additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, like calcium channel blockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Amifostine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
    Aminolevulinic Acid: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Amiodarone: (Moderate) Caution should be used when CYP3A4 inhibitors, such as amiodarone, are co-administered with isradipine (CYP3A4 substrate).
    Amlodipine; Celecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Amobarbital: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin and isradipine, particularly in geriatric patients, due to an increased risk of hypotension and acute kidney injury. If the use of a macrolide antibiotic is necessary in a patient receiving isradipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely. Isradipine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
    Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Amprenavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Amyl Nitrite: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
    Apalutamide: (Major) Monitor for decreased efficacy of isradipine if coadministration with apalutamide is necessary. Isradipine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased isradipine levels to below detectable limits.
    Apomorphine: (Moderate) Use of calcium-channel blockers and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
    Apraclonidine: (Minor) Apraclonidine had minimal effects on heart rate and blood pressure during clinical studies in patients with glaucoma. However, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Use caution during concurrent use, especially in patients with severe, uncontrolled cardiovascular disease, including hypertension.
    Aprepitant, Fosaprepitant: (Moderate) Use caution if isradipine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in isradipine-related adverse effects for several days after administration of a multi-day aprepitant regimen. Isradipine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of isradipine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Articaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
    Asciminib: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with asciminib is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
    Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Atazanavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Atazanavir; Cobicistat: (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as isradipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised. (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Atenolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Atenolol; Chlorthalidone: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Avacopan: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with avacopan is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and avacopan is a weak CYP3A inhibitor.
    Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Barbiturates: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Belumosudil: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with belumosudil is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and belumosudil is a weak CYP3A inhibitor.
    Belzutifan: (Minor) Monitor for decreased efficacy of isradipine if coadministration with belzutifan is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A substrate and belzutifan is a weak CYP3A inducer.
    Bendroflumethiazide; Nadolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Benzphetamine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Berotralstat: (Moderate) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with berotralstat is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor.
    Beta-blockers: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Betaxolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Bicalutamide: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with bicalutamide is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and bicalutamide is a weak CYP3A inhibitor.
    Bisoprolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering isradipine with boceprevir due to an increased potential for isradipine-related adverse events. If isradipine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of isradipine. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated isradipine plasma concentrations.
    Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
    Bosentan: (Moderate) Closely monitor blood pressure if coadministration of isradipine with bosentan is necessary; decreased plasma concentrations of isradipine may occur. Isradipine is a CYP3A4 substrate and bosentan is a moderate CYP3A4 inducer.
    Brigatinib: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with brigatinib is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A4 substrate and brigatinib is a weak CYP3A4 inducer.
    Brimonidine; Timolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Brompheniramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Bupivacaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
    Bupivacaine; Meloxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Butabarbital: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Butalbital; Acetaminophen: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Butalbital; Acetaminophen; Caffeine: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including isradipine. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
    Carbamazepine: (Moderate) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that induce CYP3A4, such as carbamazepine, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbetapentane; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbetapentane; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Carbinoxamine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbinoxamine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
    Carteolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Carvedilol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Celecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Celecoxib; Tramadol: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Cenobamate: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with cenobamate is necessary. Isradipine is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. Coadministration may decrease isradipine plasma concentrations.
    Ceritinib: (Moderate) Monitor for hypotension if coadministration of ceritinib with isradipine is necessary. Ceritinib is a strong CYP3A4 inhibitor and isradipine is metabolized by CYP3A4. Concomitant use may increase isradipine exposure, increasing the risk for isradipine-related adverse reactions.
    Cetirizine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Chlorpheniramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Cimetidine: (Moderate) Cimetidine is a potent inhibitor of many of the isoenzymes of the hepatic CYP450 oxidative enzyme system and may decrease the metabolism of isradipine.
    Ciprofloxacin: (Moderate) Coadministration of ciprofloxacin, a CYP3A4 inhibitor, with isradipine, a CYP3A4 substrate, may result in elevated isradipine serum concentrations. If used concurrently, close clinical monitoring of blood pressure is advised.
    Clarithromycin: (Major) Avoid coadministration of clarithromycin and isradipine, particularly in geriatric patients, due to an increased risk of hypotension and acute kidney injury. If the use of a macrolide antibiotic is necessary in a patient receiving isradipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely. Isradipine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
    Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
    Cobicistat: (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as isradipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised.
    Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Codeine; Phenylephrine; Promethazine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10.
    Conivaptan: (Moderate) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with conivaptan is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
    Crizotinib: (Moderate) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with crizotinib is necessary. Isradipine is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor.
    Dalfopristin; Quinupristin: (Minor) Coadministration of dalfopristin; quinupristin and isradipine may cause an increase in systemic concentrations of isradipine. Use caution when administering these drugs concomitantly. Dalfopristin; quinupristin is a weak inhibitor of CYP3A4. Isradipine is a CYP3A4 substrate.
    Danazol: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
    Dantrolene: (Moderate) Concurrent use with skeletal muscle relaxants and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Darunavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Darunavir; Cobicistat: (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as isradipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised. (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as isradipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised. (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Delavirdine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as isradipine, should be expected with concurrent use of delavirdine.
    Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Desogestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Dexmedetomidine: (Moderate) Concomitant administration of dexmedetomidine and calcium-channel blockers could lead to additive hypotension and bradycardia; use together with caution. Dexmedetomidine can produce bradycardia or AV block and should be used cautiously in patients who are receiving antihypertensive drugs that may lower the heart rate such as calcium-channel blockers.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents.
    Diclofenac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Diclofenac; Misoprostol: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of calcium-channel blockers. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
    Diflunisal: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Diphenhydramine; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Diphenhydramine; Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Diphenhydramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Dorzolamide; Timolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Dronedarone: (Moderate) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with dronedarone is necessary. Isradipine is a CYP3A substrate and dronedarone is a moderate CYP3A inhibitor.
    Drospirenone; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. Monitor blood pressure if the combination is necessary.
    Dutasteride; Tamsulosin: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Duvelisib: (Moderate) Monitor for an increase in isradipine-related adverse reactions, including hypotension, if coadministration with duvelisib is necessary. Coadministration may increase the exposure of isradipine. Isradipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
    Efavirenz: (Moderate) Use caution and careful monitoring when coadministering efavirenz with calcium-channel blockers; efavirenz induces CYP3A4, potentially altering serum concentrations of drugs metabolized by this enzyme such as some calcium-channel blockers. When coadministered, efavirenz decreases the concentrations of diltiazem (decrease in Cmax by 60%, in AUC by 69%, and in Cmin by 63%) and its active metabolites, desacetyl diltiazem and N-monodesmethyl diltiazem; dose adjustments should be made for diltiazem based on clinical response. No data are available regarding coadministration of efavirenz with other calcium channel blockers that are CYP3A4 substrates (e.g., felodipine, nicardipine, and verapamil); as with diltiazem, calcium-channel blocker doses should be adjusted based on clinical response.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Use caution and careful monitoring when coadministering efavirenz with calcium-channel blockers; efavirenz induces CYP3A4, potentially altering serum concentrations of drugs metabolized by this enzyme such as some calcium-channel blockers. When coadministered, efavirenz decreases the concentrations of diltiazem (decrease in Cmax by 60%, in AUC by 69%, and in Cmin by 63%) and its active metabolites, desacetyl diltiazem and N-monodesmethyl diltiazem; dose adjustments should be made for diltiazem based on clinical response. No data are available regarding coadministration of efavirenz with other calcium channel blockers that are CYP3A4 substrates (e.g., felodipine, nicardipine, and verapamil); as with diltiazem, calcium-channel blocker doses should be adjusted based on clinical response.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Use caution and careful monitoring when coadministering efavirenz with calcium-channel blockers; efavirenz induces CYP3A4, potentially altering serum concentrations of drugs metabolized by this enzyme such as some calcium-channel blockers. When coadministered, efavirenz decreases the concentrations of diltiazem (decrease in Cmax by 60%, in AUC by 69%, and in Cmin by 63%) and its active metabolites, desacetyl diltiazem and N-monodesmethyl diltiazem; dose adjustments should be made for diltiazem based on clinical response. No data are available regarding coadministration of efavirenz with other calcium channel blockers that are CYP3A4 substrates (e.g., felodipine, nicardipine, and verapamil); as with diltiazem, calcium-channel blocker doses should be adjusted based on clinical response.
    Elbasvir; Grazoprevir: (Moderate) Administering isradipine with elbasvir; grazoprevir may result in elevated isradipine plasma concentrations. Isradipine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as isradipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of cobicistat (a strong CYP3A4 inhibitor) with calcium-channel blockers metabolized by CYP3A4, such as isradipine, may result in elevated calcium-channel blockers serum concentrations. If used concurrently, close clinical monitoring with appropriate reductions are advised.
    Empagliflozin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
    Empagliflozin; Linagliptin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
    Empagliflozin; Metformin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
    Enflurane: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
    Enzalutamide: (Major) Monitor for decreased efficacy of isradipine if coadministration with enzalutamide is necessary. Isradipine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased isradipine levels to below detectable limits.
    Ephedrine: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by calcium-channel blockers. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
    Ephedrine; Guaifenesin: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by calcium-channel blockers. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
    Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
    Epirubicin: (Moderate) Close cardiac monitoring is recommended throughout therapy in patients receiving concomitant therapy with epirubicin and calcium-channel blockers. Individuals receiving these medications together are at increased risk of developing heart failure.
    Eplerenone: (Moderate) Isradipine can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
    Epoprostenol: (Moderate) Calcium-channel blockers can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
    Ergonovine: (Major) Because of its potential to cause coronary vasospasm, ergonovine could theoretically antagonize the therapeutic effects of anti-anginal agents including calcium-channel blockers. In addition, calcium-channel blockers with CYP3A4 inhibitory properties, such as diltiazem, nicardipine, and verapamil, may also reduce the hepatic metabolism of ergonovine and increase the risk of ergot toxicity.
    Erythromycin: (Major) Avoid administration of erythromycin and isradipine, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock. Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving isradipine therapy. If coadministration is unavoidable, monitor blood pressure and heart rate. Isradipine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
    Erythromycin; Sulfisoxazole: (Major) Avoid administration of erythromycin and isradipine, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock. Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving isradipine therapy. If coadministration is unavoidable, monitor blood pressure and heart rate. Isradipine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
    Esmolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored for antihypertensive effectiveness.
    Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored for antihypertensive effectiveness.
    Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Ethinyl Estradiol; Norelgestromin: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Ethinyl Estradiol; Norgestrel: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Etodolac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Etomidate: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
    Etonogestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Everolimus: (Minor) Monitor for an increase in isradipine-related adverse reactions, including hypotension, if coadministration with everolimus is necessary. Isradipine is a CYP3A4 substrate and everolimus is a weak CYP3A4 inhibitor; concomitant use may increase plasma concentrations of isradipine.
    Famotidine; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Fedratinib: (Moderate) Caution and close monitoring are advised if these drugs are used together. Concomitant use of fedratinib with isradipine may result in increased serum concentrations of isradipine. Isradipine is a substrate of the hepatic isoenzyme CYP3A4; fedratinib, is a moderate inhibitor of this enzyme.
    Fenoprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Fentanyl: (Moderate) Monitor patients for bradycardia and hypotension when fentanyl is coadministered with isradipine. Fentanyl may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with fentanyl is increased in patients receiving isradipine.
    Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Fluconazole: (Moderate) Fluconazole may decrease the clearance of calcium-channel blockers, including isradipine, via inhibition of CYP3A4 metabolism. Monitor blood pressure closely during concurrent use of these medications.
    Fluoxetine: (Moderate) Fluoxetine may decrease the clearance of calcium-channel blockers, including isradipine, via inhibition of CYP3A4 metabolism.
    Flurbiprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Fluvoxamine: (Moderate) Caution should be used when CYP3A4 inhibitors, such as fluvoxamine, are co-administered with calcium-channel blockers, CYP3A4 substrates.
    Fosamprenavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Fospropofol: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
    Fostamatinib: (Minor) Coadministration of fostamatinib and isradipine may cause an increase in systemic concentrations of isradipine. Use caution when administering these drugs concomitantly. Fostamatinib is a weak inhibitor of CYP3A4. Isradipine is a CYP3A4 substrate.
    General anesthetics: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
    Ginkgo, Ginkgo biloba: (Moderate) Ginkgo biloba appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme. A non-controlled pharmacokinetic study in healthy volunteers found that the concurrent administration of ginkgo with nifedipine resulted in a 53% increase in nifedipine peak concentrations. More study is needed regarding ginkgo's effects on CYP3A4 and whether clinically significant drug interactions result.
    Ginseng, Panax ginseng: (Moderate) Ginseng appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme. A non-controlled pharmacokinetic study in healthy volunteers found that the concurrent administration of ginseng with nifedipine resulted in a 30% increase in nifedipine peak concentrations. More study is needed regarding ginseng's effects on CYP3A4 and whether clinically significant drug interactions result.
    Grapefruit juice: (Major) Grapefruit juice contains compounds that inhibit the cytochrome P-450 CYP3A4 isozyme in the gut wall. Although data are not available for isradipine, grapefruit juice can increase the serum concentrations and oral bioavailability of most calcium-channel blockers. It is generally recommended to avoid grapefruit juice ingestion during calcium-channel blocker therapy.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Haloperidol: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
    Halothane: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
    Hydantoins: (Moderate) Because isradipine is a substrate of CYP3A4 , the concomitant use of drugs that induce CYP3A4, such as hydantoin anticonvulsants (i.e., phenytoin, fosphenytoin, or ethotoin), may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Until more data are available, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
    Hydrocodone; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Hydrocodone; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Ibuprofen; Oxycodone: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Ibuprofen; Pseudoephedrine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with isradipine, a CYP3A substrate, as isradipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Iloprost: (Moderate) Calcium-channel blockers can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
    Imatinib: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme including isradipine.
    Indinavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Indomethacin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with isradipine may result in increased serum concentrations of isradipine. Isradipine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
    Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Isoflurane: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that induce CYP3A4, such as rifampin, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Isoniazid, INH; Rifampin: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that induce CYP3A4, such as rifampin, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Isoproterenol: (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
    Isosorbide Dinitrate, ISDN: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
    Isosorbide Mononitrate: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
    Itraconazole: (Moderate) Calcium-channel blockers can have a negative inotropic effect that may be additive to those of itraconazole. In addition, itraconazole may increase isradipine serum concentrations via inhibition of CYP3A4 with the potential for isradipine toxicity. Edema has been reported in patients receiving concomitantly itraconazole and dihydropyridine calcium-channel blockers; therefore, caution is recommended when administering these medications in combination. A dosage reduction of the calcium-channel blocker may be appropriate.
    Ketamine: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
    Ketoconazole: (Moderate) Ketoconazole may decrease the clearance of calcium-channel blockers, such as isradipine, via inhibition of CYP3A4 metabolism.
    Ketoprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Ketorolac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Labetalol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
    Lanreotide: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin and isradipine, particularly in geriatric patients, due to an increased risk of hypotension and acute kidney injury. If the use of a macrolide antibiotic is necessary in a patient receiving isradipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely. Isradipine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
    Lansoprazole; Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Lapatinib: (Moderate) Monitor blood pressure if coadministration of isradipine with lapatinib is necessary. Isradipine is a CYP3A4 substrate and lapatinib is a CYP3A4 inhibitor.
    Lasmiditan: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
    Lefamulin: (Moderate) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with oral lefamulin is necessary. Isradipine is a CYP3A substrate and oral lefamulin is a moderate CYP3A inhibitor; an interaction is not expected with intravenous lefamulin.
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of isradipine; monitor for potential reduction in efficacy. Isradipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of isradipine; monitor for potential reduction in efficacy. Isradipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of isradipine may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Isradipine is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
    Levobetaxolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Levobunolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Levoketoconazole: (Moderate) Ketoconazole may decrease the clearance of calcium-channel blockers, such as isradipine, via inhibition of CYP3A4 metabolism.
    Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Lidocaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
    Lisdexamfetamine: (Minor) Lisdexamfetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Lithium: (Moderate) Lithium neurotoxicity has been reported during co-administration of lithium and verapamil or diltiazem, and is possible during concurrent use of other calcium-channel blockers with lithium. Symptoms of toxicity have included ataxia, tremors, nausea, vomiting, diarrhea, and tinnitus. The interaction between verapamil and lithium is variable and unpredictable. Both decreased lithium concentrations and lithium toxicity have been reported after the addition of verapamil. The possibility of a loss of lithium's therapeutic effect due to lower serum lithium concentrations may be offset somewhat by the fact that calcium-channel blocking agents share some neuropharmacological actions with lithium; limited data suggest that oral verapamil is effective in controlling an acute manic episode either as a single agent or in combination with lithium. Regarding diltiazem, although neurotoxicity was reported after the addition of diltiazem, other drugs were administered concomitantly. Worsened psychosis has been reported with the combination of diltiazem and lithium. Until more data are available, diltiazem and verapamil should be used cautiously in patients receiving lithium.
    Lonafarnib: (Moderate) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with lonafarnib is necessary. Concomitant use may increase isradipine exposure. Lonafarnib is a strong CYP3A4 inhibitor and isradipine is metabolized by CYP3A4.
    Lopinavir; Ritonavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Lorlatinib: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with lorlatinib is necessary. Isradipine is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Coadministration may decrease isradipine plasma concentrations.
    Lovastatin: (Minor) Isradipine has been shown to increase the clearance of lovastatin. Lovastatin serum concentrations were correspondingly lower during isradipine administration. Lovastatin did not have any effect on isradipine pharmacokinetics. The clinical significance of this drug interaction is unclear at this time.
    Lovastatin; Niacin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. (Minor) Isradipine has been shown to increase the clearance of lovastatin. Lovastatin serum concentrations were correspondingly lower during isradipine administration. Lovastatin did not have any effect on isradipine pharmacokinetics. The clinical significance of this drug interaction is unclear at this time.
    Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of isradipine. If used together, monitor blood pressure closely; the dosage requirements of isradipine may be increased. Isradipine is a CYP3A substrate. Lumacaftor is a strong CYP3A inducer.
    Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Maribavir: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with maribavir is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and maribavir is a weak CYP3A inhibitor.
    Meclofenamate Sodium: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Mefenamic Acid: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Melatonin: (Moderate) Melatonin may impair the efficacy of some calcium-channel blockers, and caution is advised with concurrent use. In one placebo-controlled study, melatonin evening ingestion led to significant increases in blood pressure (6.5 mmHg systolic and 4.9 mmHg diastolic) and heart rate (3.9 bpm) throughout the day in patients taking nifedipine (GITS formulation). Melatonin appeared to antagonize the antihypertensive effects of nifedipine. The mechanism of this interaction is unclear. It may be prudent to avoid melatonin use during calcium-channel blocker therapy.
    Meloxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Mephobarbital: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Mestranol; Norethindrone: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients; monitor patients receiving concurrent therapy to confirm that the desired antihypertensive effect is being obtained.
    Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
    Methohexital: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Methoxsalen: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Methylphenidate Derivatives: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
    Methysergide: (Major) Because of the potential to cause coronary vasospasm , methysergide theoretically could antagonize the therapeutic effects of calcium-channel blockers. Clinicians should also note that calcium-channel blockers with CYP3A4 inhibitory properties, such as diltiazem, nicardipine, verapamil, may also reduce the hepatic metabolism of selected ergot alkaloids and increase the risk of ergot toxicity.
    Metoprolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Mifepristone: (Moderate) Monitor blood pressure and heart rate if coadministration of isradipine with mifepristone is necessary. Concurrent use may result in elevated isradipine concentrations. Isradipine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
    Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
    Mitapivat: (Minor) Monitor for decreased efficacy of isradipine if coadministration with mitapivat is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A substrate and mitapivat is a weak CYP3A inducer.
    Mitotane: (Moderate) Use caution if mitotane and isradipine are used concomitantly, and monitor for decreased efficacy of isradipine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and isradipine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of isradipine.
    Mobocertinib: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with mobocertinib is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A substrate and mobocertinib is a weak CYP3A inducer.
    Nabumetone: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Nadolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Naproxen; Esomeprazole: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Naproxen; Pseudoephedrine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Nebivolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Nebivolol; Valsartan: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Nefazodone: (Moderate) Caution should be used when CYP3A4 inhibitors, such as nefazodone, are co-administered with isradipine a CYP3A4 substrate.
    Nelfinavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
    Nevirapine: (Minor) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
    Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Nitrates: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
    Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
    Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Nonsteroidal antiinflammatory drugs: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Norethindrone; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Norgestimate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Octreotide: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Odevixibat: (Minor) Monitor for decreased efficacy of isradipine if coadministration with odevixibat is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A substrate and odevixibat is a weak CYP3A inducer.
    Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Olanzapine; Fluoxetine: (Moderate) Fluoxetine may decrease the clearance of calcium-channel blockers, including isradipine, via inhibition of CYP3A4 metabolism. (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that induce CYP3A4 such as rifabutin, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Until more data are available, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Oritavancin: (Moderate) Isradipine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of isradipine may be reduced if these drugs are administered concurrently.
    Osilodrostat: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with osilodrostat is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and osilodrostat is a weak CYP3A inhibitor.
    Oxaprozin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by calcium-channel blockers. If these drugs are used together, closely monitor for changes in blood pressure.
    Pacritinib: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with pacritinib is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and pacritinib is a weak CYP3A inhibitor.
    Palbociclib: (Moderate) Monitor blood pressure if coadministration of isradipine with palbociclib is necessary. Isradipine is a CYP3A4 substrate and palbociclib is a weak, time-dependent CYP3A4 inhibitor. Coadministration with another weak CYP3A4 inhibitor increased isradipine exposure by 50%.
    Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and calcium-channel blockers who are susceptible to hypotension.
    Pasireotide: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as calcium-channel blockers. Dose adjustments of calcium-channel blockers may be necessary.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and isradipine, a CYP3A4 substrate, may cause an increase in systemic concentrations of isradipine. Use caution when administering these drugs concomitantly.
    Penbutolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Pentobarbital: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
    Pexidartinib: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with pexidartinib is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
    Phenelzine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Phenobarbital: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Photosensitizing agents (topical): (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Pindolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Piroxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Posaconazole: (Moderate) Monitor blood pressure and heart rate if coadministration of isradipine with posaconazole is necessary. Concurrent use may result in elevated isradipine concentrations. Isradipine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
    Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used. The use of alpha-blockers with verapamil can lead to excessive hypotension; In addition, verapamil has been reported to increase the AUC and Cmax of prazosin.
    Prilocaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
    Primidone: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Procaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Promethazine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Propofol: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
    Propranolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Protease inhibitors: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Pseudoephedrine; Triprolidine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
    Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of an MAOI and a calcium-channel blocker.
    Red Yeast Rice: (Contraindicated) Since certain red yeast rice products (i.e., pre-2005 Cholestin formulations) contain lovastatin, clinicians should use red yeast rice cautiously in combination with drugs known to interact with lovastatin. CYP3A4 inhibitors have been shown to increase HMG-CoA reductase activity and potential for myopathy when coadministered with lovastatin. Because of these potential risks, red yeast rice is best avoided by patients taking CYP3A4 inhibitors, such as isradipine.
    Remifentanil: (Moderate) The risk of significant hypotension and/or bradycardia during therapy with remifentanil may be increased in patients receiving calcium-channel blockers due to additive hypotensive effects.
    Ribociclib: (Moderate) Monitor blood pressure if coadministration of isradipine with ribociclib is necessary. Isradipine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
    Ribociclib; Letrozole: (Moderate) Monitor blood pressure if coadministration of isradipine with ribociclib is necessary. Isradipine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
    Rifabutin: (Moderate) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that induce CYP3A4 such as rifabutin, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Until more data are available, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Rifampin: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that induce CYP3A4, such as rifampin, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Rifapentine: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with rifapentine is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
    Risperidone: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Ritonavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Rofecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Rucaparib: (Minor) Monitor blood pressure if coadministration of isradipine with rucaparib is necessary. Isradipine is a CYP3A4 substrate and rucaparib is a weak CYP3A4 inhibitor.
    Saquinavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Secobarbital: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
    Selpercatinib: (Minor) Monitor for an increase in isradipine-related adverse reactions, including hypotension, if coadministration with selpercatinib is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and selpercatinib is a weak CYP3A inhibitor.
    Sevoflurane: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
    Silodosin: (Moderate) Monitor for adverse effects if silodosin is coadministered with isradipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Simeprevir: (Moderate) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of isradipine, which is a CYP3A4 substrate. Monitor patients for adverse effects of isradipine, such as cardivascular effects, including hypotension.
    Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by calcium-channel blockers. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of results.
    Sotalol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Sotorasib: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with sotorasib is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer.
    Spironolactone: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with spironolactone is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with spironolactone is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and spironolactone is a weak CYP3A inhibitor.
    St. John's Wort, Hypericum perforatum: (Major) St. John's wort appears to induce the metabolism of the calcium-channel blockers, such as isradipine, apparently by the induction of the CYP3A4 isoenzyme leading to reduced clinical efficacy. The metabolism of calcium channel blockers may also be increased.
    Streptogramins: (Minor) Coadministration of dalfopristin; quinupristin and isradipine may cause an increase in systemic concentrations of isradipine. Use caution when administering these drugs concomitantly. Dalfopristin; quinupristin is a weak inhibitor of CYP3A4. Isradipine is a CYP3A4 substrate.
    Sufentanil: (Moderate) Monitor patients for bradycardia and hypotension when sufentanil is coadministered with isradipine. Sufentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with sufentanil is increased in patients receiving isradipine.
    Sulindac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Sumatriptan; Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Tamsulosin: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Tazemetostat: (Minor) Monitor for decreased efficacy of isradipine if coadministration with tazemetostat is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering isradipine with telaprevir due to an increased potential for isradipine-related adverse events. If isradipine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of isradipine. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated isradipine plasma concentrations.
    Telithromycin: (Moderate) Serious adverse events, including hypotension, have been reported in patients taking telithromycin concomitantly with calcium channel blockers metabolized by the cytochrome P450 CYP3A4 isoenzyme, such as isradipine. Telithromycin is a substrate and inhibitor of the CYP3A4 isozyme. Concurrent administration may result in increased serum concentrations of the calcium channel blocker and increased risk for adverse events.
    Telotristat Ethyl: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with telotristat is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A4 substrate and telotristat is a weak CYP3A4 inducer.
    Temsirolimus: (Moderate) Monitor for signs and symptoms of angioedema if temsirolimus is administered concomitantly with isradipine. Angioedema has been reported in patients taking mammalian target of rapamycin (mTOR) inhibitors in combination with another calcium channel blocker.
    Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
    Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
    Thiopental: (Major) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine. Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy.
    Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Timolol: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
    Tipranavir: (Moderate) Concurrent administration of isradipine with protease inhibitors may result in elevated isradipine plasma concentrations and increased hypotensive effects. Isradipine is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. In addition, ritonavir prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
    Tolmetin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Tranylcypromine: (Major) Avoid concomitant use of calcium-channel blockers and tranylcypromine due to the risk of additive hypotension. Potential for this interaction persists for up to 10 days after discontinuation of tranylcypromine (or 4 to 5 half-lives after discontinuation of the calcium-channel blocker). If a medication-free interval is not feasible, initiate therapy at the lowest appropriate dose and monitor blood pressure closely.
    Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
    Tucatinib: (Moderate) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with tucatinib is necessary. Concomitant use may increase isradipine exposure. Tucatinib is a strong CYP3A4 inhibitor and isradipine is metabolized by CYP3A4.
    Valdecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Vemurafenib: (Moderate) Vemurafenib is an inducer of CYP3A4 and decreased plasma concentrations of drugs metabolized by this enzyme, such as isradipine, could be expected with concurrent use. Use caution, and monitor therapeutic effects of isradipine when coadministered with vemurafenib.
    Verteporfin: (Moderate) Use caution if coadministration of verteporfin with calcium channel blockers is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use with calcium channel blockers could enhance the rate of verteporfin uptake by the vascular endothelium, resulting in enhanced photosensitivity.
    Viloxazine: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with viloxazine is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and viloxazine is a weak CYP3A inhibitor.
    Voriconazole: (Moderate) Monitor blood pressure and heart rate if coadministration of isradipine with voriconazole is necessary. Concurrent use may result in elevated isradipine concentrations. Isradipine is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor.
    Voxelotor: (Moderate) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with voxelotor is necessary. Concomitant use may increase isradipine exposure. Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with voxelotor is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
    Yohimbine: (Moderate) Yohimbine (a selective central alpha 2-adrenoceptor antagonist) can increase blood pressure, and therefore can antagonize the therapeutic action of antihypertensive drugs in general. One study in patients with essential hypertension (n = 25) reported an average rise of 5 mmHg in mean blood pressure and a 66% increase in plasma norepinephrine (NE) concentrations following yohimbine administration (4 x 5.4 mg tablets PO). Use with particular caution in hypertensive patients with high or uncontrolled BP.
    Zafirlukast: (Minor) Caution should be used when CYP3A4 inhibitors are co-administered with isradipine, a CYP3A4 substrates. This combination may reduce the metabolism and lead to increased effect of isradipine.
    Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.

    PREGNANCY AND LACTATION

    Pregnancy

    Isradipine is classified in FDA pregnancy category C. There are no adequate and well-controlled studies in pregnant women. According to the manufacturer, isradipine should only be used during pregnancy when its benefits to the mother clearly outweigh its risks to the fetus.

    It is not known whether isradipine is excreted into human milk, and therefore, breast-feeding should be discontinued during isradipine administration. Excretion of the drug into breast milk should be expected due to its low molecular weight. The effect of this exposure on a nursing infant is unknown. Because neonatal myocardium is very sensitive to changes in calcium status, it would be prudent to avoid using isradipine in the breast-feeding mother until more safety data are available. Nifedipine is usually regarded as compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Similar to other calcium-channel antagonists, isradipine acts by inhibiting the influx of extracellular calcium across the cell membranes of myocardial and vascular smooth muscle. Serum calcium levels remain unchanged. Isradipine inhibits this influx possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The resultant decrease in intracellular calcium inhibits the contractile processes of the smooth muscle cells, resulting in dilation of coronary and systemic arteries. These effects elicit an increase in oxygen delivery to the myocardial tissue, and a decrease in total peripheral resistance, systemic blood pressure, and afterload.
     
    Isradipine has no effect on atrioventricular (AV) or sinoatrial nodal conduction. Coronary vasodilation occurs at doses 12—14 times lower than those that affect AV node conduction. Negative inotropic effects are rarely noted clinically, presumably due to the lack of effect of isradipine on myocardial contractility, and, unlike with the other dihydropyridines. At doses that decrease blood pressure without increasing heart rate, isradipine therapy positively affects hemodynamic parameters in patients with normal and decreased left ventricular function, causing improvement in cardiac index with minimal decreases in pulmonary capillary wedge pressure. Thus, isradipine increases myocardial oxygen supply (secondary to coronary vasodilation) and also decreases myocardial oxygen demand (secondary to decreased afterload and lack of an increase in heart rate). These effects seem to best explain the benefit of isradipine and other dihydropyridines in the treatment of angina. Isradipine also causes vasodilation in coronary, skeletal, and cerebral vasculature. In general, calcium-channel blockers exert favorable effects on LVH, and do not worsen insulin resistance or exert detrimental effects on the lipid profile.

    PHARMACOKINETICS

    Isradipine is administered orally. Isradipine is well distributed throughout the body, with a distribution volume of approximately 3 L/kg. The drug is 95% bound to plasma proteins. It is not known if isradipine is distributed into breast milk. Isradipine is primarily metabolized by CYP3A4 isoenzymes. Hepatic metabolism of isradipine is complete and causes the formation of at least 6 inactive compounds that are excreted in the urine (60% to 65%) and feces (25% to 30%). The elimination half-life of isradipine is biphasic, presumably due to saturable first-pass metabolism; the initial or alpha half-life is approximately 1 to 1.5 hours, and the terminal elimination half-life is roughly 8 hours.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
    Isradipine is a CYP3A4 substrate, and its metabolism may theoretically be affected by CPY3A4 inhibitors or inducers.

    Oral Route

    Isradipine is rapidly and almost completely absorbed (90% to 95%) after an oral dose but undergoes extensive first-pass metabolism, resulting in a bioavailability of 15% to 24%. The rate but not the extent of absorption is decreased in the presence of food. Peak serum concentrations occur in about 1.5 hours after administration of the regular-release capsules. The duration of pharmacologic action is about 12 hours after a single oral dose of the regular-release capsules. The sustained-release tablets reduce blood pressure for 24 hours with the maximum single dose-response occurring 8 to 10 hours post-dose. The maximal pharmacodynamic effects at steady-state require 2 to 4 weeks to be observed.