pms-Trazodone Drug Interactions





Full Prescribing Info
Drug Interactions
Drug-Drug Interactions: CYP 3A4 Inhibitors and Inducers: In vitro studies reveal that trazodone is a substrate of the cytochrome P450 3A4 enzyme (CYP3A4) and trazodone metabolism can be inhibited by CYP3A4 inhibitors (e.g. ritonavir, ketoconazole). The effect of short-term administration of ritonavir (200 mg twice daily for four doses) on the pharmacokinetics of a single dose of trazodone (50 mg) has been studied in 10 healthy subjects. The Cmax of trazodone increased by 34%, the AUC increased 2.4-fold, the half-life increased by 2.2-fold, and the clearance decreased by 52%. Adverse effects including nausea, hypotension, and syncope were observed when ritonavir and trazodone were co-administered. If trazodone is used with a potent CYP3A4 inhibitor, a lower dose of trazodone should be considered.
Prolongation of the QTc interval by pms-TRAZODONE is anticipated to be increased in the presence of CYP3A4 inhibitors. Drugs that inhibit CYP3A4 include ketoconazole, itraconazole, voriconazole, clarithromycin, erythromycin, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, and amiodarone. The concomitant use of these drugs with pms-TRAZODONE is discouraged. If used concomitantly with a CYP3A4 inhibitor, pms-TRAZODONE should be started at a low dose and patients monitored closely.
Carbamazepine induces CYP3A4. Following co-administration of carbamazepine 400 mg/day with trazodone 100 mg to 300 mg daily, carbamazepine reduced plasma concentrations of trazodone as well as mCPP by 76 and 60%, respectively, compared to pre-carbamazepine values.
Drugs with a QTc prolongation effect: The concomitant use of pms-TRAZODONE with another QTc-prolonging drug is discouraged. If used concomitantly with these drugs, pms-TRAZODONE should be started at a low dose and patients monitored closely. Drugs that have been associated with QTc interval prolongation or torsade de pointes include, but are not limited to, the examples in the following list. Drugs classes are listed if some class members have been implicated in QTc prolongation or torsade de pointes: Class IA antiarrhythmics (e.g., quinidine, procainamide, disopyramide); Class III antiarrhythmics (e.g., amiodarone, sotalol, ibutilide); Class 1C antiarrhythmics (e.g., flecainide, propafenone); antipsychotics (e.g., chlorpromazine, pimozide, haloperidol, droperidol, ziprasidone); antidepressants (e.g., SSRI, venlafaxine, tricyclic/tetracyclic antidepressants); opioids (e.g., methadone); macrolide antibiotics and analogues (e.g., erythromycin, clarithromycin, tacrolimus); quinolone antibiotics (e.g., moxifloxacin, levofloxacin, ciprofloxacin); pentamidine; antimalarials (e.g., quinine, chloroquine); azole antifungals (e.g., ketoconazole, fluconazole, voriconazole); domperidone; 5-hydroxytryptamine receptor antagonists (e.g., dolasetron, ondansetron); tyrosine kinase inhibitors (e.g., sunitinib, nilotinib, lapatinib); histone deacetylase inhibitors (e.g., vorinostat); beta-2 agonists (e.g., salmeterol, formoterol).
Drugs with effect on electrolytes: The use of pms-TRAZODONE is discouraged with drugs that can disrupt electrolyte levels, including: loop, thiazide, and related diuretics; laxatives and enemas; amphotericin B; high dose corticosteroids. If used concomitantly with these drugs, pms-TRAZODONE should be started at a low dose and patients monitored closely.
Digoxin and Phenytoin: Increased serum digoxin or phenytoin levels have been reported to occur in patients receiving trazodone concurrently with either of these drugs.
Serotonergic drugs: Based on the mechanism of action of trazodone and the potential for serotonin syndrome, pms-TRAZODONE should not be used in combination with a MAO inhibitor or within 14 days of discontinuing treatment with a MAO inhibitor; similarly, at least 14 days should be allowed after stopping pms-TRAZODONE before starting treatment with a MAO inhibitor. Caution is advised when pms-TRAZODONE is co-administered with other drugs that may affect neurotransmitter systems, such as tryptophan, triptans, SSRIs, lithium, fentanyl, tramadol, or St. John's Wort (see Neurologic: Serotonin Syndrome under Precautions).
Drugs that affect coagulation or bleeding: Due to a possible association between serotonin modulating drugs and gastrointestinal bleeding, patients should be cautioned about potential risk of bleeding associated with the concomitant use of trazodone and NSAIDs, aspirin, or other drugs that affect coagulation or bleeding (see Hematologic: Abnormal Bleeding under Precautions).
Warfarin: There have been reports of increased and decreased prothrombin time occurring in warfarinized patients who take trazodone.
CNS depressants: Trazodone may enhance the response to alcohol and the effects of barbiturates and other CNS depressants and patients should be cautioned accordingly.
General anesthetics: Little is known about the interaction between trazodone and general anesthetics. As a precaution, pms-TRAZODONE should be discontinued for as long as clinically feasible prior to elective surgery.
Drug-Non-drug Therapy Interactions: Electroconvulsive therapy (ECT): The efficacy and safety of the concurrent use of pms-TRAZODONE and ECT have not been studied.
Drug-Food Interactions: Grapefruit, grapefruit juice, and products containing grapefruit extracts should not be used during treatment with pms-TRAZODONE because of the potential to inhibit CYP3A4 and increase plasma levels of trazodone.
Drug-Herb Interactions: Pharmacodynamic interactions between trazodone and St. John's Wort may occur and may result in an increase in undesirable effects (see Neurologic: Serotonin Syndrome under Precautions).
Drug-Laboratory Interactions: Interactions with laboratory tests have not been established.
Drug-Lifestyle Interactions: Trazodone may enhance the response to alcohol and the effects of barbiturates and other CNS depressants and patients should be cautioned accordingly.
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