Trazodoneinteractions

CNS Depressants: Trazodone may enhance effects of alcohol, barbiturates, or other CNS depressants.

CYP3A4 Inhibitors: Consider trazodone dose reduction based on tolerability.

CYP3A4 Inducers: Increase in trazodone dosage may be necessary.

Digoxin or Phenytoin: Monitor for increased digoxin or phenytoin serum levels.

Warfarin: Monitor for increased or decreased prothrombin time.

7.1 Drugs Having

Clinically Important Interactions with Trazodone Table 3 Clinically Important Drug Interactions with Trazodone Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of MAOIs and serotonergic drugs including trazodone increases the risk of serotonin syndrome. Intervention Trazodone is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue. Examples isocarboxazid, moclobemide, phenelzine, selegiline, tranylcypromine Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs including trazodone and other serotonergic drugs increases the risk of serotonin syndrome. Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during trazodone initiation. If serotonin syndrome occurs, consider discontinuation of trazodone and/or concomitant serotonergic drugs. Examples triptans, antidepressants (tricyclic and serotonin uptake inhibitors), fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort Antiplatelet Agents and Anticoagulants Clinical Impact Serotonin release by platelets plays an important role in hemostasis. The concurrent use of an antiplatelet agent or anticoagulant with trazodone may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding with the concomitant use of trazodone and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio (INR) when initiating or discontinuing trazodone. Examples warfarin, rivaroxaban, dabigatran, clopidogrel Strong CYP3A4 Inhibitors Clinical Impact The concomitant use of trazodone and strong CYP3A4 inhibitors increased the exposure of trazodone compared to the use of trazodone alone. Intervention If trazodone is used with a potent CYP3A4 inhibitor, the risk of adverse reactions, including cardiac arrhythmias, may be increased and a lower dose of trazodone should be considered. Examples itraconazole, ketoconazole, clarithromycin, indinavir Strong CYP3A4 Inducers Clinical Impact The concomitant use of trazodone and strong CYP3A4 inducers decreased the exposure of trazodone compared to the use of trazodone alone. Intervention Patients should be closely monitored to see if there is a need for an increased dose of trazodone when taking CYP3A4 inducers. Examples rifampin, carbamazepine, phenytoin, St. John's wort Digoxin and Phenytoin Clinical Impact Digoxin and phenytoin are narrow therapeutic index drugs. Concomitant use of trazodone can increase digoxin or phenytoin concentrations. Intervention Measure serum digoxin or phenytoin concentrations before initiating concomitant use of trazodone. Continue monitoring and reduce digoxin or phenytoin dose as necessary. Examples digoxin, phenytoin Central Nervous System (CNS) Depressants Clinical Impact Trazodone may enhance the response CNS depressants. Intervention Patients should be counseled that trazodone may enhance the response to alcohol, barbiturates, and other CNS depressants. Examples alcohol, barbiturates QT Interval Prolongation Clinical Impact Concomitant use of drugs that prolong the QT interval may add to the QT effects of trazodone and increase the risk of cardiac arrhythmia. Intervention Avoid the use of trazodone in combination with other drugs known to prolong QTc.

Examples Class 1A antiarrhythmics: quinidine, procainamide, disopyramide;

Class 3 antiarrhythmics: amiodarone, sotalol;

Antipsychotics: ziprasidone, chlorpromazine, thioridazine;

Antibiotics: gatifloxacin