DRUG INTERACTIONS
Acebutolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Acetaminophen: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Caffeine: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Chlorpheniramine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Dextromethorphan: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Concurrent use of tizanidine and CNS depressants like dichloralphenazone can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Diphenhydramine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Guaifenesin; Phenylephrine: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Pentazocine: (Moderate) Concurrent use of tizanidine and CNS depressants like pentazocine can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Propoxyphene: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acetaminophen; Pseudoephedrine: (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Acrivastine; Pseudoephedrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Acyclovir: (Minor) Caution is advised when administering tizanidine with acyclovir. Tizanidine is primarily metabolized by CYP1A2; acyclovir is a weak inhibitor of CYP1A2. Taking these drugs together may increase the serum concentration of tizanidine, which could result in hypotension, bradycardia, or excessive drowsiness.
Alfentanil: (Major) Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a skeletal muscle relaxant, use a lower initial dose of the opiate and titrate to clinical response. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Aliskiren: (Moderate) Aliskiren can enhance the effects of tizanidine on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
Aliskiren; Amlodipine: (Moderate) Aliskiren can enhance the effects of tizanidine on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of tizanidine on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of tizanidine on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
Aliskiren; Valsartan: (Moderate) Aliskiren can enhance the effects of tizanidine on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
Alprazolam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Ambrisentan: (Moderate) Although no specific interactions have been documented, ambrisentan has vasodilatory effects and may contribute additive hypotensive effects when given with other antihypertensive agents. Patients receiving ambrisentan in combination with other antihypertensive agents should be monitored for decreases in blood pressure.
Amiloride: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Amiodarone: (Major) Avoid concomitant use of tizanidine and amiodarone as increased serum concentrations of tizanidine may occur. If use together is necessary, initiate tizanidine with the 2 mg dose and increase daily in 2 to 4 mg increments based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and amiodarone is a CYP1A2 inhibitor.
Amobarbital: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Anagrelide: (Moderate) Avoid concomitant use of tizanidine and anagrelide as increased serum concentrations of tizanidine may occur. If use together is necessary, initiate tizanidine with the 2 mg dose and increase daily in 2 to 4 mg increments based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate; anagrelide demonstrates some limited inhibitory activity towards CYP1A2 which may present a theoretical potential for interaction.
Angiotensin II receptor antagonists: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Angiotensin-converting enzyme inhibitors: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Concurrent use of tizanidine and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during co-administration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Aripiprazole: (Moderate) Use tizanidine and aripiprazole together with caution due to additive CNS depression. Monitor patients for symptoms of excess sedation.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Atenolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Atenolol; Chlorthalidone: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including skeletal muscle relaxants.
Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including skeletal muscle relaxants.
Bacitracin: (Minor) Tizanidine, which has skeletal muscle relaxant properties, should be used cautiously in patients receiving systemic bacitracin. If bacitracin is administered parenterally during surgery, there may be increased skeletal muscle relaxation, and postoperative use may reinstate neuromuscular blockade.
Baclofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of baclofen and tizanidine. Concurrent use may result in additive CNS depression.
Barbiturates: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Belladonna; Opium: (Major) Concomitant use of opium with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Bendroflumethiazide; Nadolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of benzhydrocodone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Benzodiazepines: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Beta-adrenergic blockers: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Betaxolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Bisoprolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Brimonidine; Timolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Brompheniramine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding skeletal muscle relaxants.
Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Brompheniramine; Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Brompheniramine; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Brompheniramine; Pseudoephedrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Buprenorphine: (Major) Concomitant use of buprenorphine and tizanidine can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Reserve concomitant use of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor patients closely for signs of respiratory depression and sedation.
Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine and tizanidine can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Reserve concomitant use of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor patients closely for signs of respiratory depression and sedation.
Buspirone: (Moderate) Concurrent use of tizanidine and CNS depressants like buspirone can cause additive CNS depression.
Butabarbital: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Butalbital; Acetaminophen: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Butalbital; Acetaminophen; Caffeine: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as tizanidine, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Avoid concomitant use of tizanidine and famotidine as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and famotidine is a weak CYP1A2 inhibitor.
Canakinumab: (Moderate) Monitor for reduced efficacy of tizanidine if coadministered with canakinumab. Inhibition of IL-1 signaling by canakinumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as tizanidine, may have fluctuations in drug levels and therapeutic effect when canakinumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping canakinumab. Tizanidine is a CYP1A2 substrate and narrow therapeutic index drug.
Cannabidiol: (Major) Avoid concomitant use of tizanidine and cannabidiol as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor.
Capmatinib: (Major) Avoid concomitant use of tizanidine and capmatinib as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and capmatinib is a weak CYP1A2 inhibitor.
Carbetapentane; Chlorpheniramine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding skeletal muscle relaxants.
Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding skeletal muscle relaxants.
Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding skeletal muscle relaxants.
Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding skeletal muscle relaxants.
Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding skeletal muscle relaxants.
Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding skeletal muscle relaxants.
Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding skeletal muscle relaxants.
Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding skeletal muscle relaxants.
Carbetapentane; Pyrilamine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression. (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding skeletal muscle relaxants.
Carbidopa; Levodopa; Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, such as tizanidine, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Carbinoxamine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Carbinoxamine; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Carbinoxamine; Pseudoephedrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Carteolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Carvedilol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Celecoxib; Tramadol: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and tizanidine. Concurrent use may result in additive CNS depression.
Central-acting adrenergic agents: (Major) The use of tizanidine with other alpha 2-adrenergic agonists (such as central-acting adrenergic agonist antihypertensive agents) should be avoided because hypotensive effects may be cumulative. Tizanidine is an alpha 2-adrenergic agonist that can produce hypotension. Syncope has been reported in the postmarketing setting.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorcyclizine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlordiazepoxide: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Chlordiazepoxide; Amitriptyline: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Chlordiazepoxide; Clidinium: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Chlorpheniramine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Dextromethorphan: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Chlorpheniramine; Pseudoephedrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Cimetidine: (Major) Avoid concomitant use of tizanidine and cimetidine as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and cimetidine is a weak CYP1A2 inhibitor.
Ciprofloxacin: (Contraindicated) Concomitant use of tizanidine and ciprofloxacin is contraindicated due to the risk of tizanidine toxicity, including clinically significant hypotension, bradycardia, and sedation. Tizanidine is a CYP1A2 substrate and ciprofloxacin is a strong CYP1A2 inhibitor. After a single 4 mg tizanidine dose, Cmax and AUC increased by 7-fold and 10-fold, respectively, when administered with ciprofloxacin during pharmacokinetic trials.
Clemastine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Clonazepam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Clorazepate: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Codeine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, such as tizanidine, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Cyclizine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Cyproheptadine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Desogestrel; Ethinyl Estradiol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Deutetrabenazine: (Moderate) Use tizanidine and deutetrabenazine together with caution due to additive CNS depression. Monitor patients for symptoms of excess sedation.
Dexchlorpheniramine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Dexmedetomidine: (Moderate) Due to the anesthetic effects of dexmedetomidine, concurrent use with other CNS depressants, such as skeletal muscle relaxants, could result in additive sedative effects and possibly prolong recovery from anesthesia.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Diazepam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Dienogest; Estradiol valerate: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Dimenhydrinate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dimenhydrinate and tizanidine. Concurrent use may result in additive CNS depression.
Diphenhydramine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine. (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Diphenhydramine; Ibuprofen: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Diphenhydramine; Naproxen: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Dorzolamide; Timolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Doxazosin: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Doxylamine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Doxylamine; Pyridoxine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Dronabinol: (Moderate) Concomitant use of dronabinol with other CNS depressants, like tizanidine, can potentiate the effects of dronabinol on respiratory depression.
Drospirenone: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Drospirenone; Estetrol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Drospirenone; Estradiol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Drospirenone; Ethinyl Estradiol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Elagolix; Estradiol; Norethindrone acetate: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Emapalumab: (Moderate) Monitor for decreased efficacy of tizanidine and adjust the dose as needed during coadministration with emapalumab. Tizanidine is a CYP1A2 substrate with a narrow therapeutic range. Emapalumab may normalize CYP450 activity, which may decrease the efficacy of drugs that are CYP450 substrates due to increased metabolism.
Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, such as tizanidine, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Eplerenone: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Epoprostenol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Esketamine: (Major) Closely monitor patients receiving esketamine and skeletal muscle relaxants for sedation and other CNS depressant effects. Patients who receive a dose of esketamine should not drive or engage in other activities requiring alertness until the next day after a restful sleep.
Esmolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Estazolam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Estradiol; Levonorgestrel: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Estradiol; Norethindrone: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Estradiol; Norgestimate: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Ethanol: (Major) Concurrent use of tizanidine and CNS depressants can cause additive CNS depression. It is best to limit the use of alcohol during treatment, due to additive drowsiness and dizziness. Hypotension may occur. Alcohol increases the overall amount of drug in the bloodstream after a dose of tizanidine. Ethanol increases the AUC and Cmax of tizanidine by about 20% and 15%, respectively, resulting in an increase in side effects associated with tizanidine.
Ethinyl Estradiol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Ethinyl Estradiol; Norelgestromin: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Ethinyl Estradiol; Norethindrone Acetate: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Ethinyl Estradiol; Norgestrel: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Etonogestrel; Ethinyl Estradiol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Famotidine: (Major) Avoid concomitant use of tizanidine and famotidine as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and famotidine is a weak CYP1A2 inhibitor.
Famotidine; Ibuprofen: (Major) Avoid concomitant use of tizanidine and famotidine as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and famotidine is a weak CYP1A2 inhibitor.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and tizanidine. Concurrent use may result in additive CNS depression.
Fentanyl: (Major) Concomitant use of fentanyl with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Fluphenazine: (Moderate) Use tizanidine and fluphenazine together with caution due to additive CNS depression. Monitor patients for symptoms of excess sedation.
Flurazepam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Fluvoxamine: (Contraindicated) Concomitant use of tizanidine and fluvoxamine is contraindicated due to the risk of tizanidine toxicity, including clinically significant hypotension, bradycardia, and sedation. Tizanidine is a CYP1A2 substrate and fluvoxamine is a strong CYP1A2 inhibitor. After a single 4 mg tizanidine dose, Cmax, AUC, and half-life increased by 12-fold, 33--fold, and 3-fold, respectively, when administered with fluvoxamine during pharmacokinetic trials.
Fosphenytoin: (Minor) One case of increased phenytoin serum concentrations and associated drowsiness has been reported with the addition of tizanidine therapy. The mechanism and significance of this potential interaction with phenytoin or fosphenytoin is unknown.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and tizanidine. Concomitant use of gabapentin with tizanidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Givosiran: (Major) Avoid concomitant use of givosiran and tizanidine due to the risk of increased tizanidine-related adverse reactions. If use is necessary, consider decreasing the tizanidine dose. Tizanidine is a sensitive CYP1A2 substrate. Givosiran may moderately reduce hepatic CYP1A2 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Hydrocodone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Hydrocodone; Potassium Guaiacolsulfonate: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking tizanidine.
Hydromorphone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Hydroxyzine: (Major) Use tizanidine and hydroxyzine together with caution due to additive CNS depression. Consider tizanidine dosage reduction and monitor patients for symptoms of excess sedation.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Iloprost: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Indapamide: (Moderate) The effects of indapamide may be additive when administered with other antihypertensive agents or diuretics. This may be desirable, but occasionally orthostatic hypotension may occur. Dosages should be adjusted based on clinical response.
Labetalol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and tizanidine. Concurrent use may result in additive CNS depression.
Leflunomide: (Moderate) Closely monitor for reduced efficacy of tizanidine if coadministered with leflunomide. An adjustment of the tizanidine dose may be required. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. In vivo data suggest that teriflunomide is a weak inducer of CYP1A2. Coadministration of teriflunomide with CYP1A2 substrates, such as tizanidine, may decrease tizanidine exposure and lead to a reduction in efficacy.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tizanidine. Dosage adjustments of lemborexant and tizanidine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Leuprolide; Norethindrone: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Levobetaxolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Levobunolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Levonorgestrel: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Levonorgestrel; Ethinyl Estradiol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Levorphanol: (Major) Concomitant use of opioid agonists with methocarbamol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with methocarbamol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial levorphanol dosage by 50% or more.
Lofexidine: (Moderate) Use tizanidine and lofexidine together with caution due to additive CNS depression. Monitor patients for symptoms of excess sedation and hypotension.
Loop diuretics: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Lorazepam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Loxapine: (Moderate) Loxapine is a central nervous system (CNS) depressant. The concurrent use of loxapine with other CNS depressants (e.g., muscle relaxants such as tizanidine) can increase the risk of respiratory depression, hypotension, profound sedation, and syncope. Therefore, consider reducing the dose of CNS depressants if used concomitantly with loxapine.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and tizanidine. Concurrent use may result in additive CNS depression.
Lurasidone: (Moderate) Concurrent use of tizanidine and CNS depressants can cause additive CNS depression. These agents include but are not limited to: antipsychotics.
Mecamylamine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Meclizine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Mepenzolate: (Moderate) CNS depression can be increased when mepenzolate is combined with other CNS depressants such as skeletal muscle relaxants.
Meperidine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Meperidine; Promethazine: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Mephobarbital: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Mestranol; Norethindrone: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Methadone: (Major) Concomitant use of methadone with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Methohexital: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Methscopolamine: (Moderate) CNS depression can be increased when methscopolamine is combined with other CNS depressants such as skeletal muscle relaxants.
Metoprolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Mexiletine: (Major) Tizanidine is primarily metabolized by CYP1A2. If possible, avoid the concurrent use of tizanidine with other CYP1A2 inhibitors, such as mexiletine, as concurrent use could lead to substantial increases in tizanidine blood concentrations. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Midazolam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Molindone: (Moderate) Concurrent use of tizanidine and antipsychotics like molindone can cause additive CNS depression.
Morphine: (Major) Concomitant use of morphine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
Morphine; Naltrexone: (Major) Concomitant use of morphine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants, like tizanidine, can potentiate the effects of nabilone on CNS and respiratory depression.
Nadolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Nalbuphine: (Major) Concomitant use of nalbuphine with tizanidine may cause excessive sedation and somnolence. Limit the use of nalbuphine with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Nebivolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Nebivolol; Valsartan: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Norethindrone: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Norethindrone; Ethinyl Estradiol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Norgestimate; Ethinyl Estradiol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Norgestrel: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Obeticholic Acid: (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as tizanidine. Therapeutic monitoring is recommended with coadministration as there is the potential for enhanced hypotensive and sedative effects.
Oliceridine: (Major) Concomitant use of oliceridine with tizanidine may cause excessive sedation and somnolence. Limit the use of oliceridine with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Opicapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, such as tizanidine, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Oral Contraceptives: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Osilodrostat: (Major) Avoid concomitant use of tizanidine and osilodrostat as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and osilodrostat is a moderate CYP1A2 inhibitor.
Oxazepam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Oxycodone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Oxymorphone: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxymorphone dosage by one-third to one-half.
Pacritinib: (Major) Avoid concomitant use of tizanidine and pacritinib as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg per day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and pacritinib is a weak CYP1A2 inhibitor.
Peginterferon Alfa-2b: (Major) Tizanidine is primarily metabolized by CYP1A2. The presystemic availability of tizanidine has been shown to be substantially increased by coadministration with CYP1A2 inhibitors, such as peginterferon alfa-2b. Average increases in tizanidine AUC of 10-fold and 33-fold have been reported following administration of strong CYP1A2 inhibitors. These increases in tizanidine concentrations have been associated with significant hypotensive and sedative effects. The use of potent CYP1A2 inhibitors with tizanidine is contraindicated. If possible, avoid the concurrent use of tizanidine with other CYP1A2 inhibitors, as concurrent use could lead to substantial increases in tizanidine blood concentrations. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Penbutolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Pentazocine: (Moderate) Concurrent use of tizanidine and CNS depressants like pentazocine can cause additive CNS depression.
Pentazocine; Naloxone: (Moderate) Concurrent use of tizanidine and CNS depressants like pentazocine can cause additive CNS depression.
Pentobarbital: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Phenobarbital: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Phenoxybenzamine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Phentolamine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Phenytoin: (Minor) One case of increased phenytoin serum concentrations and associated drowsiness has been reported with the addition of tizanidine therapy. The mechanism and significance of this potential interaction with phenytoin is unknown.
Pindolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Potassium-sparing diuretics: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Prazosin: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tizanidine. Concomitant use of pregabalin with tizanidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Primidone: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Propafenone: (Major) Avoid concomitant use of tizanidine and propafenone as increased serum concentrations of tizanidine may occur. If use together is necessary, initiate tizanidine with the 2 mg dose and increase daily in 2 to 4 mg increments based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and propafenone is a CYP1A2 inhibitor.
Propranolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Pseudoephedrine; Triprolidine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Pyrilamine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Quazepam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Ramelteon: (Moderate) Concurrent use of tizanidine and CNS depressants like ramelteon can cause additive CNS depression.
Relugolix; Estradiol; Norethindrone acetate: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Remifentanil: (Major) Concomitant use of remifentanil with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Remimazolam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Reserpine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Rucaparib: (Major) Avoid coadministration of tizanidine with rucaparib if possible due the risk of increased plasma concentrations of tizanidine. If concomitant use is unavoidable, monitor for an increase in tizanidine-related adverse reactions (e.g., hypotension, bradycardia, excessive drowsiness). Tizanidine is a sensitive CYP1A2 substrate and rucaparib is a moderate CYP1A2 inhibitor.
Sarilumab: (Moderate) Monitor for reduced efficacy of tizanidine if coadministered with sarilumab. Inhibition of IL-6 signaling by sarilmuab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as tizanidine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Tizanidine is a CYP1A2 substrate and narrow therapeutic index drug.
Secobarbital: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Secukinumab: (Moderate) If secukinumab is initiated or discontinued in a patient taking tizanidine, monitor for altered patient response to tizanidine; tizanidine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as tizanidine.
Segesterone Acetate; Ethinyl Estradiol: (Major) If possible, avoid the concurrent use of tizanidine with oral contraceptives (OC), as concurrent use could lead to substantial increases in tizanidine blood concentrations. A retrospective analysis of population pharmacokinetic data indicates that the clearance of tizanidine may be 50% lower in women who take combined hormonal OCs concurrently with tizanidine. Combined OCs increased tizanidine AUC by 4-fold and the mean Cmax by 3-fold in a parallel-group study in healthy women. Increased hypotensive effects were also noted in women taking tizanidine and OCs. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Siltuximab: (Moderate) Monitor for reduced efficacy of tizanidine if coadministered with siltuximab. Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as tizanidine, may have fluctuations in drug levels and therapeutic effect when siltuximab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping siltuximab. In vitro, siltuximab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Tizanidine is a CYP1A2 substrate and narrow therapeutic index drug.
Simeprevir: (Moderate) Tizanidine is primarily metabolized by CYP1A2. Tizanidine clearance may be reduced by coadministration of mild inhibitors of CYP1A2, such as simeprevir. Increased tizanidine concentrations may lead to oversedation, significant hypotension, potential liver problems, and other events.
Spironolactone: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Sufentanil: (Major) Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a skeletal muscle relaxant, use a lower initial dose of the opiate and titrate to clinical response. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tacrine: (Major) Tacrine is a substrate and inhibitor of CYP1A2, the primary isoenzyme responsible for the metabolism of tizanidine. Therefore, addition of tacrine to a stable tizanidine regimen may lead to tizanidine-related adverse effects such as oversedation, significant hypotension, or potential liver problems. Close monitoring for adverse effects is recommended during concomitant therapy
Tapentadol: (Major) Concomitant use of opioid agonists with tizanidine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tizanidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Temazepam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Terazosin: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Teriflunomide: (Moderate) Use caution when administering teriflunomide and tizanidine concurrently. In vivo data suggest that teriflunomide is a weak inducer of CYP1A2. Coadministration of teriflunomide with CYP1A2 substrates, such as tizanidine, may decrease tizanidine exposure and lead to a reduction in efficacy.
Thalidomide: (Moderate) Thalidomide frequently causes drowsiness and somnolence and may enhance the sedative activity of tizanidine.
Thiabendazole: (Contraindicated) Tizanidine is contraindicated for use with potent CYP1A2 inhibitors. Thiabendazole is a potent inhibitor of CYP1A2 hepatic enzymes. Thiabendazole may increase the plasma concentrations of tizanidine. Changes in the pharmacokinetics of tizanidine when administered with fluvoxamine, another strong CYP1A2 inhibitor, resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment.
Thiazide diuretics: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Thiopental: (Moderate) Concurrent use of tizanidine and CNS depressants like barbiturates can cause additive CNS depression.
Thiothixene: (Moderate) Concurrent use of tizanidine and antipsychotics like thiothixene can cause additive CNS depression.
Ticlopidine: (Major) Tizanidine is primarily metabolized by CYP1A2. If possible, avoid the concurrent use of tizanidine with other CYP1A2 inhibitors, such as ticlopidine, as concurrent use could lead to substantial increases in tizanidine blood concentrations. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Timolol: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Tocilizumab: (Moderate) Monitor for reduced efficacy of tizanidine if coadministered with tocilizumab. An adjustment of tizanidine dose may be required. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as tizanidine, may have fluctuations in drug levels and therapeutic effect when tocilizumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Tizanidine is a CYP1A2 substrate and narrow therapeutic index drug.
Tolcapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, such as tizanidine, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Tramadol: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tramadol; Acetaminophen: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Minor) Tizanidine delays the time to attain peak concentrations of acetaminophen by about 16 minutes. The clinical significance of this interaction is unknown.
Trandolapril; Verapamil: (Major) Avoid concomitant use of tizanidine and verapamil as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and verapamil is a weak CYP1A2 inhibitor.
Treprostinil: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Triamterene: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Triazolam: (Moderate) Concurrent use of tizanidine and CNS depressants like the benzodiazepines can cause additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given.
Triprolidine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Valerian, Valeriana officinalis: (Moderate) Concurrent use of tizanidine with the phytomedicinal valerian, Valeriana officinalis can cause additive CNS depression.
Vasodilators: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Vemurafenib: (Major) Avoid the use of vemurafenib with tizanidine; the tizanidine Cmax and AUC values were significantly increased when these agents were coadministered in a drug interaction study. If concomitant use of these drugs is required, initiate tizanidine at the 2-mg dose and increase in 2- to 4-mg increments daily based on the patient response. Monitor patients closely for tizanidine toxicity; if adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce or discontinue tizanidine therapy. Vemurafenib is a moderate CYP1A2 inhibitor and tizanidine is a CYP1A2 substrate with a narrow therapeutic index. In a drug interaction study (n = 16), the tizanidine Cmax increased 2.2-fold and the tizanidine AUC value increased 4.7-fold when a single 2-mg PO dose of tizanidine was given following 21 days of vemurafenib 960 mg PO twice daily in cancer patients.
Verapamil: (Major) Avoid concomitant use of tizanidine and verapamil as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and verapamil is a weak CYP1A2 inhibitor.
Viloxazine: (Contraindicated) Concomitant use of viloxazine and tizanidine is contraindicated due to the increased risk for tizanidine-related adverse effects and exposure. Tizanidine is a CYP1A2 substrate and viloxazine is a strong CYP1A2 inhibitor. Coadministration with other strong CYP1A2 inhibitors increased the exposure of tizanidine by 10 and 33-fold.
Zileuton: (Major) Tizanidine is primarily metabolized by CYP1A2. If possible, avoid the concurrent use of tizanidine with other CYP1A2 inhibitors, such as zileuton, as concurrent use could lead to substantial increases in tizanidine blood concentrations. If concurrent use cannot be avoided, initiate tizanidine therapy with the 2 mg dose and increase in 2 to 4 mg increments daily based on patient response to therapy. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.