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  • CLASSES

    Selective Serotonin 1B/1D Receptor Agonists (Triptans)

    DEA CLASS

    Rx

    DESCRIPTION

    Oral, serotonin (5HT1B/1D) receptor agonist (triptan)
    Used for acute treatment of migraine with or without aura in adults
    Safety of treating average of more than 3 migraine attacks in 30-day period not established

    COMMON BRAND NAMES

    Relpax

    HOW SUPPLIED

    Eletriptan/Eletriptan Hydrobromide/Relpax Oral Tab: 20mg, 40mg

    DOSAGE & INDICATIONS

    For the acute treatment of migraine with or without aura.
    Oral dosage
    Adults

    20 or 40 mg PO once. May repeat dose once after at least 2 hours after first dose if the headache has not resolved or returns after transient improvement. Max: 80 mg/day. The safety of treating an average of more than 3 headaches/30 days has not been evaluated. Guidelines classify eletriptan as having established efficacy for the treatment of acute migraine.

    MAXIMUM DOSAGE

    Adults

    80 mg/day PO.

    Elderly

    80 mg/day PO.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Eletriptan is converted to an active metabolite through N-demethylation. Eletriptan should not be used in patients with severe hepatic impairment; no dosage adjustments are needed in mild to moderate hepatic impairment.

    Renal Impairment

    Specific guidelines for dosage adjustments in patients with renal impairment receiving eletriptan are not available; it appears no dosage adjustments are required.
     
    Intermittent hemodialysis
    It is not known whether hemodialysis (or peritoneal dialysis) removes eletriptan from plasma.

    ADMINISTRATION

    Oral Administration

    Eletriptan should be taken orally with fluids.

    STORAGE

    Relpax:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Eletriptan is contraindicated in patients with a history of eletriptan hypersensitivity. There have been reports of anaphylaxis, anaphylactoid, and hypersensitivity reactions including angioedema in patients receiving eletriptan; such reactions can be life-threatening or fatal. In general, anaphylactic reactions are more likely to occur in patients with a history of sensitivity to multiple allergens.[29121]

    Angina, cardiac arrhythmias, coronary artery disease, diabetes mellitus, geriatric, myocardial infarction, obesity, tobacco smoking, vasospastic angina, Wolff-Parkinson-White syndrome

    Eletriptan is contraindicated in patients with ischemic coronary artery disease (CAD) (i.e., angina pectoris, history of myocardial infarction, documented silent ischemia), coronary artery vasospasm (vasospastic angina) such as Prinzmetal's angina, and Wolff-Parkinson-White syndrome or cardiac arrhythmias associated with other cardiac accessory conduction pathway disorders. There have been rare reports of serious cardiac adverse reactions, including sometimes fatal acute myocardial infarction, ventricular tachycardia, and ventricular fibrillation within a few hours after eletriptan administration. Some of these reactions occurred in patients without known cardiac disease. Eletriptan may cause coronary artery vasospasm even in patients without a history of CAD. Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., geriatric patients, diabetes mellitus, high blood pressure, tobacco smoking, obesity, strong family history of CAD) before administering eletriptan. For patients with risk factors who have a negative cardiovascular evaluation, consider administering the first dose of eletriptan in a medically-supervised setting and obtaining an ECG immediately after administration. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of eletriptan. Discontinue eletriptan if any cardiac rhythm disturbances occur.[29121]

    Hypertension

    Eletriptan is contraindicated in patients with uncontrolled hypertension. Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with eletriptan.

    Ischemic colitis, peripheral vascular disease, Raynaud's phenomenon

    Eletriptan is contraindicated in patients with peripheral vascular disease including ischemic bowel disease (ischemic colitis). Eletriptan may cause non-coronary vasospastic reactions including peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting as abdominal pain and bloody diarrhea), and Raynaud's phenomenon. Rule out a vasospastic reaction before administering additional eletriptan doses to patients who experience signs or symptoms suggestive of a vasospastic reaction.[29121]

    Basilar/hemiplegic migraine, stroke

    Eletriptan is contraindicated in patients with a history of stroke, transient ischemic attack (TIA), or history or current evidence of basilar/hemiplegic migraine because these patients are at higher risk of stroke. Exclude other potentially serious neurological conditions before treating headaches in patients not previously diagnosed as migraineurs and in migraineurs who present with atypical migraine symptoms. Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5HT1 agonists. In several cases, it appears possible that the cerebrovascular events were primary with the 5HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not.[29121]

    Driving or operating machinery

    Eletriptan can cause dizziness, weakness, or drowsiness. Advise patients to avoid engaging in tasks requiring mental alertness such as driving or operating machinery until they are aware of how the drug affects them.

    Hepatic disease

    Eletriptan is not recommended for use in patients with severe hepatic disease; the effects of severe hepatic impairment on the metabolism of eletriptan have not been evaluated.[29121]

    Pregnancy

    Available data on the use of eletriptan in human pregnancy are not sufficient to draw conclusions about the drug-associated risks for major birth defects and miscarriage. A study using linked data for the Medical Birth Registry of Norway to the Norwegian Prescription Database showed 2.1% (4/189) of women who redeemed prescriptions for eletriptan during their first trimester gave birth to infants with major congenital malformations compared to 6.3% (11/174) of women who redeemed prescriptions for eletriptan before, but not during, their pregnancy. This data does not allow for a thorough characterization of risk. In animal studies, eletriptan has been associated with developmental toxicity (decreased fetal and pup weights, increased incidence of fetal structural abnormalities, decreased pup viability) at clinically relevant doses. Several studies have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy.[29121]

    Breast-feeding

    Eletriptan is excreted into human breast milk. There are no data on the effects of eletriptan on the breast-fed infant or milk production. Consider the benefits of breast-feeding along with the mother's clinical need for eletriptan and any potential adverse effects on the breast-fed infant from eletriptan or the underlying maternal condition. Infant exposure can be minimized by avoiding breast-feeding for 24 hours after treatment.[29121] Very low concentrations of the drug in the breast milk suggest that eletriptan is compatible with breast-feeding. After 24 hours, 0.02% of a single 80 mg maternal dose was excreted in breast milk. The mean milk to plasma ratio was 1:4 but was variable. The concentration-time profile was similar to that seen in the plasma over 24 hours. Very low concentrations of drug (mean 1.7 ng/mL) remained in the breast milk at 18 to 24 hours post-dose. The active metabolite was not measured.[29121] [31866] Previous American Academy of Pediatrics (AAP) recommendations classified sumatriptan as compatible with breast-feeding and may be considered as an alternative to eletriptan.[27500]

    ADVERSE REACTIONS

    Severe

    visual impairment / Early / 0.1-1.0
    bronchospasm / Rapid / 0.1-1.0
    hematemesis / Delayed / 0-0.1
    bradycardia / Rapid / 0-0.1
    arrhythmia exacerbation / Early / 0-0.1
    AV block / Early / 0-0.1
    cyanosis / Early / 0-0.1
    ocular hemorrhage / Delayed / 0-0.1
    exfoliative dermatitis / Delayed / 0-0.1
    bowel ischemia / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    atrial fibrillation / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    ventricular fibrillation / Early / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    coronary vasospasm / Early / Incidence not known
    stroke / Early / Incidence not known
    intracranial bleeding / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    dysphagia / Delayed / 1.0-2.0
    glossitis / Early / 0.1-1.0
    gastritis / Delayed / 0.1-1.0
    esophagitis / Delayed / 0.1-1.0
    elevated hepatic enzymes / Delayed / 0.1-1.0
    constipation / Delayed / 0.1-1.0
    dysarthria / Delayed / 0.1-1.0
    hyperesthesia / Delayed / 0.1-1.0
    ataxia / Delayed / 0.1-1.0
    sinus tachycardia / Rapid / 0.1-1.0
    hypertension / Early / 0.1-1.0
    depression / Delayed / 0.1-1.0
    confusion / Early / 0.1-1.0
    euphoria / Early / 0.1-1.0
    bone pain / Delayed / 0.1-1.0
    myasthenia / Delayed / 0.1-1.0
    peripheral edema / Delayed / 0.1-1.0
    edema / Delayed / 0.1-1.0
    impotence (erectile dysfunction) / Delayed / 0.1-1.0
    photophobia / Early / 0.1-1.0
    conjunctivitis / Delayed / 0.1-1.0
    dyspnea / Early / 0.1-1.0
    stomatitis / Delayed / 0-0.1
    hyperalgesia / Delayed / 0-0.1
    aphasia / Delayed / 0-0.1
    dystonic reaction / Delayed / 0-0.1
    hypotension / Rapid / 0-0.1
    angina / Early / 0-0.1
    memory impairment / Delayed / 0-0.1
    mania / Early / 0-0.1
    hallucinations / Early / 0-0.1
    amnesia / Delayed / 0-0.1
    thyroid adenoma / Delayed / 0-0.1
    goiter / Delayed / 0-0.1
    leukopenia / Delayed / 0-0.1
    lymphadenopathy / Delayed / 0-0.1
    anemia / Delayed / 0-0.1
    myopathy / Delayed / 0-0.1
    hyperglycemia / Delayed / 0-0.1
    hyperbilirubinemia / Delayed / 0-0.1
    vaginitis / Delayed / 0-0.1
    atopic dermatitis / Delayed / 0-0.1
    psoriasis / Delayed / 0-0.1
    hypertonia / Delayed / 1.0
    palpitations / Early / 1.0
    colitis / Delayed / Incidence not known
    medication overuse headache / Delayed / Incidence not known
    hyperthermia / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    peripheral vasoconstriction / Rapid / Incidence not known
    chest pressure syndrome / Rapid / Incidence not known
    chest pain (unspecified) / Early / Incidence not known

    Mild

    asthenia / Delayed / 4.0-10.0
    nausea / Early / 4.0-8.0
    drowsiness / Early / 3.0-7.0
    dizziness / Early / 3.0-7.0
    xerostomia / Early / 2.0-4.0
    headache / Early / 3.0-4.0
    flushing / Rapid / 3.0-4.0
    dyspepsia / Early / 1.0-2.0
    abdominal pain / Early / 1.0-2.0
    paresthesias / Delayed / 2.0-2.0
    flatulence / Early / 0.1-1.0
    hypersalivation / Early / 0.1-1.0
    anorexia / Delayed / 0.1-1.0
    eructation / Early / 0.1-1.0
    hyperkinesis / Delayed / 0.1-1.0
    insomnia / Early / 0.1-1.0
    tremor / Early / 0.1-1.0
    agitation / Early / 0.1-1.0
    anxiety / Delayed / 0.1-1.0
    emotional lability / Early / 0.1-1.0
    arthralgia / Delayed / 0.1-1.0
    myalgia / Early / 0.1-1.0
    polydipsia / Early / 0.1-1.0
    polyuria / Early / 0.1-1.0
    increased urinary frequency / Early / 0.1-1.0
    dysgeusia / Early / 0.1-1.0
    lacrimation / Early / 0.1-1.0
    otalgia / Early / 0.1-1.0
    ocular pain / Early / 0.1-1.0
    tinnitus / Delayed / 0.1-1.0
    rhinitis / Early / 0.1-1.0
    yawning / Early / 0.1-1.0
    pruritus / Rapid / 0.1-1.0
    rash / Early / 0.1-1.0
    malaise / Early / 0.1-1.0
    appetite stimulation / Delayed / 0-0.1
    gingivitis / Delayed / 0-0.1
    syncope / Early / 0-0.1
    purpura / Delayed / 0-0.1
    weight gain / Delayed / 0-0.1
    weight loss / Delayed / 0-0.1
    mastalgia / Delayed / 0-0.1
    menstrual irregularity / Delayed / 0-0.1
    menorrhagia / Delayed / 0-0.1
    leukorrhea / Delayed / 0-0.1
    ptosis / Delayed / 0-0.1
    parosmia / Delayed / 0-0.1
    xerophthalmia / Early / 0-0.1
    diplopia / Early / 0-0.1
    cough / Delayed / 0-0.1
    sinusitis / Delayed / 0-0.1
    laryngitis / Delayed / 0-0.1
    epistaxis / Delayed / 0-0.1
    hyperventilation / Early / 0-0.1
    hiccups / Early / 0-0.1
    xerosis / Delayed / 0-0.1
    alopecia / Delayed / 0-0.1
    urticaria / Rapid / 0-0.1
    maculopapular rash / Early / 0-0.1
    skin discoloration / Delayed / 0-0.1
    influenza / Delayed / 0-0.1
    halitosis / Early / 0-0.1
    hypothermia / Delayed / 0-0.1
    fever / Early / 0-0.1
    hypoesthesia / Delayed / 1.0
    vertigo / Early / 1.0
    pharyngitis / Delayed / 1.0
    hyperhidrosis / Delayed / 1.0
    back pain / Delayed / 1.0
    chills / Rapid / 1.0
    diarrhea / Early / Incidence not known
    vomiting / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dihydrocodeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with eletriptan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Almotriptan: (Contraindicated) Almotriptan is contraindicated for use within 24 hours of treatment with eletriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
    Amiodarone: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with amiodarone. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and amiodarone is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of clarithromycin due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Amphetamine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Although unlikely to occur during monotherapy with serotonin-receptor agonists (or "triptans"), serotonin syndrome may occur from combining these drugs with other medications that potentiate serotonin activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Amphetamine; Dextroamphetamine Salts: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Although unlikely to occur during monotherapy with serotonin-receptor agonists (or "triptans"), serotonin syndrome may occur from combining these drugs with other medications that potentiate serotonin activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Amphetamine; Dextroamphetamine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Although unlikely to occur during monotherapy with serotonin-receptor agonists (or "triptans"), serotonin syndrome may occur from combining these drugs with other medications that potentiate serotonin activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Amprenavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Aprepitant, Fosaprepitant: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with oral, multi-day regimens of aprepitant. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dihydrocodeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Aspirin, ASA; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Atazanavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Atazanavir; Cobicistat: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity. (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of cobicistat due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Theoretically, concurrent use of methylene blue and serotonin-receptor agonists may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and serotonin-receptor agonists increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Benzhydrocodone; Acetaminophen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering benzhydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Theoretically, concurrent use of methylene blue and serotonin-receptor agonists may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and serotonin-receptor agonists increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Benzphetamine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Berotralstat: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with berotralstat. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4 and berotralstat is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering eletriptan with boceprevir due to an increased potential for eletriptan-related adverse events. If eletriptan 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 eletriptan. Eletriptan is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated eletriptan plasma concentrations.
    Bromocriptine: (Major) There are limited clinical trial data supporting the safety of giving a serotonin-receptor agonist ("triptan") with bromocriptine, an ergot derivative. The concomitant use of these agents with bromocriptine should be avoided. There is concern that prolonged vasospastic reactions, hypertension, tachycardia, or other side effects may occur.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Buprenorphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering buprenorphine with serotonergic-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Buprenorphine; Naloxone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering buprenorphine with serotonergic-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Buspirone: (Moderate) Buspirone should be used cautiously with serotonin-receptor agonists. Pharmacologically, buspirone is a serotonin agonist, and using in conjunction with other serotonin agonists could result in serotonin syndrome, which can be serious and consists of symptoms such as mental status changes, diaphoresis, tremor, myoclonus, hyperreflexia, and fever. Patients receiving serotonin-agonists and buspirone should be informed of the signs and symptoms of serotonin syndrome.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Cabergoline: (Major) When possible, avoid concomitant use of serotonin-receptor agonists (triptans) within 24 hours of cabergoline administration to minimize the risk for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. The risk for vasospastic adverse reactions may be less with cabergoline, a semisynthetic ergot alkaloid derivative, than with other ergot alkaloids as cabergoline is a relatively selective dopamine agonist. In select patients, the combination of cabergoline and "triptans" has been utilized in the management of some headache types, but more data are needed regarding safety and efficacy.
    Cabozantinib: (Minor) Monitor for an increase in eletriptan-related adverse events if concomitant use with cabozantinib is necessary, as plasma concentrations of eletriptan may be increased. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and eletriptan is a substrate of P-gp; the clinical relevance of this finding is unknown.
    Capsaicin; Metaxalone: (Moderate) Concomitant use of serotonin-receptor agonists ("triptans") and metaxalone may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Celecoxib; Tramadol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tramadol with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Ceritinib: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of ceritinib due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; ceritinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Chloramphenicol: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of chloramphenicol due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Chlordiazepoxide; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Chlorpheniramine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dihydrocodeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dihydrocodeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Ciprofloxacin: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with ciprofloxacin. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Citalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with citalopram. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue citalopram and eletriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Clarithromycin: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of clarithromycin due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Clomipramine: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Cobicistat: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of cobicistat due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Cocaine: (Moderate) Concomitant use of cocaine with other drugs that have CNS serotonergic properties, such as serotonin-receptor agonists, could potentiate serotonin neurotransmission, and result in serotonergic side effects or rarely, serotonin syndrome. The actions of cocaine are presumed to include inhibition of presynaptic reuptake of serotonin. In most medical use cases, cocaine would be administered topically, and this interaction would not be of concern, as serotonin-agonists for migraine are used mostly "as needed". Illicit use of cocaine is of potential concern for interactions.
    Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Phenylephrine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Conivaptan: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with conivaptan. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A, and conivaptan is a moderate CYP3A inhibitor. Coadministration of other moderate CYP3A inhibitors increased the eletriptan over all exposure by 2 to 4-fold.
    Crizotinib: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with crizotinib. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and crizotinib is a moderate CYP3A inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Cyclosporine: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with cyclosporine. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and cyclosporine is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Dabrafenib: (Major) The concomitant use of dabrafenib and eletriptan may lead to decreased eletriptan concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of eletriptan efficacy. Dabrafenib is a moderate CYP3A4 inducer and eletriptan is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
    Daclatasvir: (Moderate) Systemic exposure of eletriptan, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of eletriptan; monitor patients for potential adverse effects.
    Danazol: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with danazol. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and danazol is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Darunavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Darunavir; Cobicistat: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity. (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of cobicistat due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity. (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of cobicistat due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Delavirdine: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of delavirdine due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; delavirdine is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Desipramine: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Desvenlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering desvenlafaxine with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and serotonin norepinephrine reuptake inhibitors. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextroamphetamine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Although unlikely to occur during monotherapy with serotonin-receptor agonists (or "triptans"), serotonin syndrome may occur from combining these drugs with other medications that potentiate serotonin activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dextromethorphan; Quinidine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dihydrocodeine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Diltiazem: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with diltiazem. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and diltiazem is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Doxepin: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Dronedarone: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with dronedarone. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and dronedarone is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Droxidopa: (Major) Coadministration of droxidopa with other agents that increase blood pressure, such as serotonin-receptor agonists, would be expected to increase the risk for supine hypertension. Monitor supine blood pressure. Reduce or discontinue droxidopa if supine hypertension persists. If supine hypertension is not well-managed, droxidopa may increase the risk of cardiovascular events.
    Duloxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering duloxetine with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and serotonin norepinephrine reuptake inhibitors. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Duvelisib: (Moderate) Monitor for increased toxicity of eletriptan if coadministered with duvelisib. Coadministration may increase the exposure of eletriptan. Eletriptan is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor. In drug interaction studies, coadministration of eletriptan with another moderate CYP3A inhibitor increased the eletriptan AUC by 4-fold.
    Efavirenz: (Contraindicated) Concomitant use of eletriptan and efavirenz is not recommended. Eletriptan is metabolized by CYP3A4, and inhibition of CYP3A4 by efavirenz may result in elevated eletriptan concentrations and serious adverse events.
    Efavirenz; Emtricitabine; Tenofovir: (Contraindicated) Concomitant use of eletriptan and efavirenz is not recommended. Eletriptan is metabolized by CYP3A4, and inhibition of CYP3A4 by efavirenz may result in elevated eletriptan concentrations and serious adverse events.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concomitant use of eletriptan and efavirenz is not recommended. Eletriptan is metabolized by CYP3A4, and inhibition of CYP3A4 by efavirenz may result in elevated eletriptan concentrations and serious adverse events.
    Elbasvir; Grazoprevir: (Major) Administering eletriptan with grazoprevir may result in elevated eletriptan plasma concentrations. Eletriptan is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Elexacaftor; tezacaftor; ivacaftor: (Moderate) Use caution when administering ivacaftor and eletriptan concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as eletriptan, can increase eletriptan exposure leading to increased or prolonged therapeutic effects and adverse events.
    Eliglustat: (Moderate) Coadministration of eletriptan and eliglustat may result in increased plasma concentrations of eletriptan. Monitor patients closely for eletriptan-related adverse effects. Eletriptan is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of cobicistat due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of cobicistat due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Encorafenib: (Moderate) Coadministration of encorafenib with eletriptan may result in increased toxicity or decreased efficacy of eletriptan. Eletriptan is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
    Ergot alkaloids: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
    Erythromycin: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with erythromycin. Coadministration of erythromycin increased the eletriptan AUC by 4-fold in a drug interaction study. Eletriptan is a substrate for CYP3A4, and erythromycin is a moderate CYP3A4 inhibitor.
    Erythromycin; Sulfisoxazole: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with erythromycin. Coadministration of erythromycin increased the eletriptan AUC by 4-fold in a drug interaction study. Eletriptan is a substrate for CYP3A4, and erythromycin is a moderate CYP3A4 inhibitor.
    Escitalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with escitalopram. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue escitalopram and eletriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Etravirine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and eletriptan is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
    Fedratinib: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with fedratinib. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and fedratinib is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Fenfluramine: (Moderate) Use fenfluramine and serotonin receptor agonists with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Fentanyl: (Moderate) If concomitant use of fentanyl and eletriptan is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Fluconazole: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with fluconazole. Coadministration of fluconazole increase the eletriptan AUC by 2-fold in a drug interaction study. Eletriptan is a substrate for CYP3A4, and fluconazole is a moderate CYP3A4 inhibitor.
    Fluoxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with fluoxetine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue fluoxetine and eletriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Fluvoxamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with fluvoxamine; eletriptan exposure may also increase. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue fluvoxamine and eletriptan and initiate symptomatic treatment if serotonin syndrome occurs. Eletriptan is a substrate for CYP3A4, and fluvoxamine is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Fosamprenavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Frovatriptan: (Contraindicated) Eletriptan is contraindicated for use within 24 hours of treatment with frovatriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and eletriptan as coadministration may increase serum concentrations of eletriptan and increase the risk of adverse effects. Eletriptan is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor.
    Grapefruit juice: (Moderate) Eletriptan is metabolized via the hepatic cytochrome P-450 CYP 3A4. Grapefruit juice contains a compound that inhibits CYP3A4 in enterocytes. It is not clear what effect grapefruit juice has on eletriptan bioavailability or metabolism. Advise patients not to significantly alter their grapefruit juice intake while on eletriptan. The clinical significance of the potential interaction is not known.
    Guaifenesin; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Homatropine; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Ibuprofen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-recptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydromorphone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydromorphone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Theoretically, concurrent use of methylene blue and serotonin-receptor agonists may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and serotonin-receptor agonists increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Ibuprofen; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Idelalisib: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with eletriptan, a CYP3A substrate, as eletriptan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Eletriptan is contraindicated for use within 72 hours of usage of any drug that is a strong CYP3A4 inhibitor, including idelalisib.
    Imatinib: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with imatinib. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and imatinib is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Imipramine: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Indinavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Isavuconazonium: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with isavuconazonium. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Isocarboxazid: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with isocarboxazid. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue eletriptan with isocarboxazid and initiate symptomatic treatment if serotonin syndrome occurs.
    Itraconazole: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of itraconazole due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; itraconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Ivacaftor: (Moderate) Use caution when administering ivacaftor and eletriptan concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as eletriptan, can increase eletriptan exposure leading to increased or prolonged therapeutic effects and adverse events.
    Ivosidenib: (Moderate) Monitor for loss of efficacy of eletriptan during coadministration of ivosidenib; a eletriptan dose adjustment may be necessary. Eletriptan is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased eletriptan concentrations.
    Ixabepilone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Eletriptan is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in eletriptan concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Ketoconazole: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of ketoconazole due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; ketoconazole is a strong CYP3A4 inhibitor. Coadministration of ketoconazole increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of clarithromycin due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Lefamulin: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with oral lefamulin. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Letermovir: (Moderate) Eletriptan and letermovir may be administered concurrently with caution; however, if the patient is also receiving cyclosporine, eletriptan is contraindicated for use within 72 hours of receiving letermovir and cyclosporine because the magnitude of this interaction may be increased. Eletriptan is a sensitive substrate of CYP3A4. 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. Concurrent use with a strong CYP3A4 inhibitor increased the maximum plasma concentration (Cmax) and exposure (AUC) of eletriptan by 3- and 6-fold, respectively. When eletriptan was given with a moderate CYP3A4 inhibitor, the Cmax and AUC of eletriptan increased by 2- and 4-fold, respectively.
    Levoketoconazole: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of ketoconazole due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; ketoconazole is a strong CYP3A4 inhibitor. Coadministration of ketoconazole increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Levomilnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering levomilnacipran with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and serotonin norepinephrine reuptake inhibitors. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Levorphanol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering levorphanol with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Linezolid: (Major) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO and should not be administered with serotonin-receptor agonists. The monoamine oxidase type A enzyme metabolizes serotonin. Non-selective MAO inhibitors increase the plasma concentrations of these drugs and some of their active metabolites, thus increasing levels of serotonin. This interaction could lead to serotonin syndrome. The manufacturers of serotonin agonists contraindicate the administration of their drugs to patients receiving non-selective MAO inhibitors like linezolid or within 2 weeks of discontinuation of a MAO inhibitor.
    Lisdexamfetamine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as amphetamines and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Lithium: (Major) There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and serotonin-receptor agonists. Signs and symptoms of serotonin syndrome include autonomic instability (e.g., labile blood pressure, tachycardia, diaphoresis, dizziness, hyperthermia), mental status changes (e.g., delirium, confusion, coma), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), gastrointestinal effects (e.g., nausea, vomiting, diarrhea), seizures, and in rare cases, death. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
    Lonafarnib: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of lonafarnib due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; lonafarnib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Lopinavir; Ritonavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Lorcaserin: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, serotonin-receptor agonists. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Lumacaftor; Ivacaftor: (Minor) Lumacaftor; ivacaftor may alter the systemic exposure of eletriptan. Eletriptan is a primarily metabolized by CYP3A4 and is a P-glycoprotein (P-gp) substrate. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of eletriptan through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for decreased eletriptan efficacy or increased or prolonged therapeutic effects and adverse events.
    Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and eletriptan concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as eletriptan, can increase eletriptan exposure leading to increased or prolonged therapeutic effects and adverse events.
    Meperidine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering meperidine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Meperidine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering meperidine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Metaxalone: (Moderate) Concomitant use of serotonin-receptor agonists ("triptans") and metaxalone may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
    Methadone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering methadone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Methamphetamine: (Moderate) Serotonin syndrome may occur during coadministration of serotonergic drugs such as methamphetamine and serotonin-receptor agonists. At high doses, amphetamines can increase serotonin release, as well as act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Theoretically, concurrent use of methylene blue and serotonin-receptor agonists may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and serotonin-receptor agonists increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methylene Blue: (Major) Theoretically, concurrent use of methylene blue and serotonin-receptor agonists may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and serotonin-receptor agonists increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Mifepristone: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of chronic mifepristone therapy due to the potential for increased eletriptan exposure. The clinical significance of this interaction is not established when mifepristone is used for pregnancy termination. Eletriptan is a sensitive substrate of CYP3A4; mifepristone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Milnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering milnacipran with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and serotonin norepinephrine reuptake inhibitors. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Mirtazapine: (Major) Based on the mechanism of action of mirtazapine and the potential for serotonin syndrome, caution is advised when mirtazapine is coadministered with other drugs that may affect these neurotransmitter systems, including the serotonin-receptor agonists ("triptans"). The co-use of serotonergic antidepressants with serotonin-agonists has sometimes resulted in serotonin syndrome. Careful observation of the patient is advised, particularly during treatment initiation and dose increases. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, and diarrhea). Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Discontinue the serotonergic agents immediately if serotonin syndrome reactions occur and initiate supportive symptomatic treatment.
    Mitotane: (Major) Use caution if mitotane and eletriptan are used concomitantly, and monitor for decreased efficacy of eletriptan and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and eletriptan is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of eletriptan.
    Morphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Morphine; Naltrexone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Nalbuphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering nalbuphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Naratriptan: (Contraindicated) Eletriptan is contraindicated for use within 24 hours of treatment with naratriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
    Nefazodone: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of nefazodone due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; nefazodone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively. In addition, although clinical data for some interactions is lacking, medications that augment release, decrease the metabolism of, or decrease the reuptake of serotonin (e.g., serotonin-receptor agonists) may interact with nefazodone by causing serotonin-related side effects, including serotonin syndrome.
    Nelfinavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with netupitant. Systemic concentrations of eletriptan may be increased. Additive serotonergic-related side effects might also occur. Eletriptan is a substrate for CYP3A4, and netupitant is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Nilotinib: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with nilotinib. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and nilotinib is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Nirmatrelvir; Ritonavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Nortriptyline: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Olanzapine; Fluoxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with fluoxetine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue fluoxetine and eletriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Oliceridine: (Moderate) If concomitant use of oliceridine and serotonin-receptor agonists is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Oritavancin: (Minor) Eletriptan is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of eletriptan may be reduced if these drugs are administered concurrently.
    Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Oxymorphone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxymorphone with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Ozanimod: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
    Paroxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with paroxetine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue paroxetine and eletriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and eletriptan, a CYP3A4 substrate, may cause an increase in systemic concentrations of eletriptan. Use caution when administering these drugs concomitantly.
    Perphenazine; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Phenelzine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with phenelzine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue eletriptan with phenelzine and initiate symptomatic treatment if serotonin syndrome occurs.
    Posaconazole: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of posaconazole due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; posaconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Promethazine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Propranolol: (Minor) Periodically monitor blood pressure in patients who regularly use eletriptan and are taking propranolol. Monitor for the rare patient who might experience an increase in dose-related side effects of eletriptan, such as nausea, dizziness, and drowsiness. No dosage adjustment appears to be needed for eletriptan. The Cmax and AUC of eletriptan were increased by 10 and 33%, respectively, in the presence of propranolol. No interactive increases in blood pressure were observed. The interaction should not be significant for most patients.
    Propranolol; Hydrochlorothiazide, HCTZ: (Minor) Periodically monitor blood pressure in patients who regularly use eletriptan and are taking propranolol. Monitor for the rare patient who might experience an increase in dose-related side effects of eletriptan, such as nausea, dizziness, and drowsiness. No dosage adjustment appears to be needed for eletriptan. The Cmax and AUC of eletriptan were increased by 10 and 33%, respectively, in the presence of propranolol. No interactive increases in blood pressure were observed. The interaction should not be significant for most patients.
    Protease inhibitors: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Protriptyline: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Quinine: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with quinine. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and quinine is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Rasagiline: (Minor) Use together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists ("triptans") and non-selective monoamine oxidase inhibitors (MAOIs). Unlike some serotonin-receptor agonists, eletriptan is not a substrate for MAO; therefore, its metabolism is not affected by MAOIs. Therefore, MAOI-based interactions appear to be less likely with eletriptan. Since rasagiline selectively inhibits MAO-B at recommended doses, no interaction with eletriptan would be expected with normal prescription use. However, there is a decline in MAO-B selectivity with increasing rasagiline doses. Monitor for potential serotonin-related side effects. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
    Remifentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering remifentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Reserpine: (Major) Eletriptan may reduce the effectiveness of antihypertensive agents. Increased blood pressure may be an adverse effect of eletriptan, and the drug is contraindicated for use in patients with uncontrolled hypertension.
    Ribociclib: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of ribociclib due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; ribociclib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Ribociclib; Letrozole: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of ribociclib due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; ribociclib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Ritonavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Rizatriptan: (Contraindicated) Eletriptan is contraindicated for use within 24 hours of treatment with rizatriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
    Safinamide: (Moderate) Safinamide and serotonin-receptor agonists, also known as triptans, should be used together with caution. Serotonin syndrome has been reported during administration of serotonin-receptor agonists and non-selective monoamine oxidase inhibitors (MAOIs). Since safinamide selectively inhibits MAO-B at recommended doses, no interaction with serotonin-receptor agonists would be expected with normal prescription use. However, monitoring for serotonin-related side effects is advisable since the potential for serotonin syndrome exists. If serotonin syndrome occurs, discontinue all serotonergic agents and institute appropriate treatment.
    Saquinavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Selegiline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with eletriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue eletriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
    Sertraline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with sertraline. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue sertraline and eletriptan and initiate symptomatic treatment if serotonin syndrome occurs.
    Sibutramine: (Major) Sibutramine is a serotonin reuptake inhibitor. Concomitant use of two serotonin-augmenting drugs has been associated with serotonin syndrome, so concurrent use of the serotonin-receptor agonists with sibutramine is not recommended.
    Simeprevir: (Moderate) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of eletriptan, which is a CYP3A4 substrate. Monitor patients for adverse effects of eletriptan, such as cardiovascular events.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of eletriptan, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently.
    St. John's Wort, Hypericum perforatum: (Moderate) Although unlikely to occur during monotherapy with serotonin-receptor agonists ("triptans"), coadministration with serotonergic agents like St. John's Wort may increase the risk for serotonin syndrome. Inform the patient of the increased risk and monitor for the emergence of serotonin syndrome.
    Sufentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Sumatriptan: (Contraindicated) Eletriptan is contraindicated for use within 24 hours of treatment with sumatriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
    Sumatriptan; Naproxen: (Contraindicated) Eletriptan is contraindicated for use within 24 hours of treatment with sumatriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
    Tapentadol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tapentadol with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Tedizolid: (Minor) Caution is warranted with the concurrent use of tedizolid and serotonin-receptor agonists such as eletriptan. Tedizolid is an antibiotic that is also a weak reversible, non-selective inhibitor of MAO. The monoamine oxidase (MAO) type A enzyme metabolizes serotonin. Non-selective traditional MAO inhibitors increase the plasma concentrations of these drugs and some of their active metabolites, thus increasing levels of serotonin. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid, which is structurally similar to tedizolid, and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity. This interaction could lead to 'serotonin syndrome' (presenting as agitation, restlessness, aggressive behavior, insomnia, poor concentration, headache, paresthesia, incoordination, worsening of obsessive thoughts or compulsive behavior, nausea, abdominal cramps, diarrhea, palpitations, or chills). The manufacturers of serotonin agonists contraindicate the administration of their drugs to patients receiving non-selective MAO inhibitors or within 2 weeks of discontinuation of a MAO inhibitor.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering eletriptan with telaprevir due to an increased potential for eletriptan-related adverse events. If eletriptan 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 eletriptan. Eletriptan is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated eletriptan plasma concentrations.
    Telithromycin: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of telithromycin due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; telithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Tezacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and eletriptan concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as eletriptan, can increase eletriptan exposure leading to increased or prolonged therapeutic effects and adverse events.
    Tipranavir: (Contraindicated) Eletriptan is contraindicated for use within 72 hours of using any drug that is a potent CYP3A4 inhibitor as described in the prescribing information of the interacting drug including protease inhibitors. Eletriptan is metabolized via CYP3A4, and coadministration with protease inhibitors may cause increased eletriptan concentrations and thus toxicity.
    Tramadol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tramadol with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Tramadol; Acetaminophen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tramadol with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Trandolapril; Verapamil: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with verapamil. Coadministration of verapamil increased the eletriptan AUC by 3-fold in a drug interaction study. Eletriptan is a substrate for CYP3A4, and verapamil is a moderate CYP3A4 inhibitor.
    Tranylcypromine: (Contraindicated) Due to the risk of serotonin syndrome, tranylcypromine is contraindicated for use with eletriptan. Tranylcypromine should not be used within 4 to 5 half-lives of discontinuing treatment with eletriptan.
    Trazodone: (Moderate) Coadministration of trazodone and serotonin-receptor agonists may increase the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue the serotonin-receptor agonist and trazodone and initiate symptomatic treatment if serotonin syndrome occurs.
    Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Trimipramine: (Moderate) Tricyclic antidepressants (TCAs) should be used cautiously with drugs that also augment serotonin, like the serotonin-receptor agonists ("triptans") used for the treatment of migraine. Additive effects may occur, and the risk of serotonin syndrome may be increased. Tricyclic antidepressants inhibit norepinephrine and serotonin uptake, but rarely cause serotonin syndrome when used alone. However, the risk may be increased when combined with other serotonergic agents, especially at times of antidepressant dose increases.
    Tryptophan, 5-Hydroxytryptophan: (Contraindicated) Combining medications that potentiate serotonin neurotransmission, such as serotonin-receptor agonists and tryptophan, could result in serotonin syndrome. Serotonin syndrome, while uncommon, can be serious and consists of symptoms such as mental status changes, diaphoresis, tremor, myoclonus, hyperreflexia, and fever.
    Tucatinib: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of tucatinib due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; tucatinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Vemurafenib: (Major) Concomitant use of vemurafenib and eletriptan may result in altered concentrations of eletriptan. Vemurafenib is an inhibitor of P-glycoprotein (PGP) and an inducer of CYP3A4. Eletriptan is a substrate of PGP and CYP3A4. Use caution and monitor patients for toxicity and efficacy.
    Venlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering venlafaxine with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and serotonin norepinephrine reuptake inhibitors. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Verapamil: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with verapamil. Coadministration of verapamil increased the eletriptan AUC by 3-fold in a drug interaction study. Eletriptan is a substrate for CYP3A4, and verapamil is a moderate CYP3A4 inhibitor.
    Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vilazodone with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonin norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) with serotonin-receptor agonists. Of the 27 cases reviewed by the FDA, 2 were considered life-threatening and 13 required hospitalization. Some patients had used the combination previously without incident. Eight of 27 cases involved a recent dose increase or addition of another serotonergic drug to the regimen, with a median onset of 1 day (range: 10 minutes to 6 days). It is thought that the interaction between SNRIs or SSRIs and serotonin-receptor agonists is the result of increased serotonergic activity by each of the drug classes. Serotonin syndrome consists of symptoms such as mental status changes (e.g., agitation, confusion, hallucinations), diaphoresis, hyperreflexia, hypertension, diarrhea, fever, tremor, and, in some instances, respiratory failure. At least 6 patients taking an SSRI antidepressant are known to have received sumatriptan for migraine where no apparent adverse effects were seen. In another case report, the addition of fluoxetine lead to loss of migraine control with sumatriptan. Patients receiving vilazodone and a serotonin-receptor agonist should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Vilazodone and the serotonin-receptor agonist should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Voriconazole: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of voriconazole due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; voriconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
    Vortioxetine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vortioxetine with other drugs that have serotonergic properties such as serotonin-receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). Serotonin syndrome has been reported during concurrent use of serotonergic antidepressants with the serotonin-receptor agonists. Some patients had used the combination previously without incident when serotonin syndrome occurred. Some cases have involved hospitalization. Serotonin syndrome consists of symptoms such as mental status changes (e.g., agitation, confusion, hallucinations), diaphoresis, hyperreflexia, hypertension, diarrhea, fever, tremor, and, in some instances, respiratory failure. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Careful monitoring for serotonin syndrome is recommended if combination therapy with is required. Risk factors can include a recent dose increase of the sertonergic antidepressant or the addition of other serotonergic medications to an existing antidepressant regimen.
    Voxelotor: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with voxelotor. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A, and voxelotor is a moderate CYP3A inhibitor. Coadministration of other moderate CYP3A inhibitors increased the eletriptan AUC by 2 to 4-fold.
    Zolmitriptan: (Contraindicated) Eletriptan is contraindicated for use within 24 hours of treatment with zolmitriptan due to the risk for additive vasospastic reactions. Additive serotonergic effects, including serotonin syndrome, may also occur.
    Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and eletriptan is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Available data on the use of eletriptan in human pregnancy are not sufficient to draw conclusions about the drug-associated risks for major birth defects and miscarriage. A study using linked data for the Medical Birth Registry of Norway to the Norwegian Prescription Database showed 2.1% (4/189) of women who redeemed prescriptions for eletriptan during their first trimester gave birth to infants with major congenital malformations compared to 6.3% (11/174) of women who redeemed prescriptions for eletriptan before, but not during, their pregnancy. This data does not allow for a thorough characterization of risk. In animal studies, eletriptan has been associated with developmental toxicity (decreased fetal and pup weights, increased incidence of fetal structural abnormalities, decreased pup viability) at clinically relevant doses. Several studies have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy.[29121]

    Eletriptan is excreted into human breast milk. There are no data on the effects of eletriptan on the breast-fed infant or milk production. Consider the benefits of breast-feeding along with the mother's clinical need for eletriptan and any potential adverse effects on the breast-fed infant from eletriptan or the underlying maternal condition. Infant exposure can be minimized by avoiding breast-feeding for 24 hours after treatment.[29121] Very low concentrations of the drug in the breast milk suggest that eletriptan is compatible with breast-feeding. After 24 hours, 0.02% of a single 80 mg maternal dose was excreted in breast milk. The mean milk to plasma ratio was 1:4 but was variable. The concentration-time profile was similar to that seen in the plasma over 24 hours. Very low concentrations of drug (mean 1.7 ng/mL) remained in the breast milk at 18 to 24 hours post-dose. The active metabolite was not measured.[29121] [31866] Previous American Academy of Pediatrics (AAP) recommendations classified sumatriptan as compatible with breast-feeding and may be considered as an alternative to eletriptan.[27500]

    MECHANISM OF ACTION

    Eletriptan binds with high affinity to 5HT1B, 5HT1D, and 5HT1F receptors and has modest affinity for 5HT1A, 5HT1E, 5HT2B, and 5HT7 receptors. Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (i.e., vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide) through nerve endings in the trigeminal system. The therapeutic activity of eletriptan for the treatment of migraine headache is thought to be due to the agonist effects at the 5HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.[29121]

    PHARMACOKINETICS

    Eletriptan is administered orally. Protein binding is moderate and approximately 85%. It is metabolized primarily by the cytochrome P450 hepatic enzyme 3A4. The parent compound is demethylated to an active metabolite, which has a half-life of 13 hours and a plasma concentration of 10% to 20% of eletriptan. The metabolite is unlikely to contribute to the overall effect of the parent compound. The terminal elimination half-life of eletriptan is approximately 4 hours. Nonrenal clearance accounts for about 90% of total clearance.[29121]
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-gp
    In vitro studies indicate that eletriptan is primarily metabolized by CYP3A4. In vitro human liver microsome studies suggest eletriptan has little potential to inhibit CYP1A2, 2C9, 2E1, and 3A4 at concentrations up to 100 micromolar. While eletriptan has an effect on CYP2D6 at high concentration, this effect should not interfere with metabolism of other drugs when eletriptan is used at recommended doses. There is no in vitro or in vivo evidence that clinical doses of eletriptan will induce drug-metabolizing enzymes. Therefore, eletriptan is unlikely to cause clinically important drug interactions mediated by these enzymes.[29121] Eletriptan is a substrate of P-glycoprotein (P-gp).[57975]

    Oral Route

    Eletriptan is well absorbed after oral administration with peak plasma concentrations occurring approximately 1.5 hours after dosing to healthy subjects. In patients with moderate to severe migraine, the median Tmax is 2 hours. The mean absolute bioavailability of eletriptan is approximately 50%. The oral pharmacokinetics are slightly more than dose-proportional over the clinical dose range. The AUC and Cmax of eletriptan are increased by approximately 20% to 30% after oral administration with a high-fat meal. Mean renal clearance after oral administration is approximately 3.9 L/hour.[29121]

    Intravenous Route

    The volume of distribution of eletriptan after IV administration is 138 L.