Apo-Fluoxetine Drug Interactions

Combined use of fluoxetine and MAO inhibitors is contraindicated (see Contraindications).
There have been greater than 2-fold increases of previously stable plasma levels of other antidepressants when fluoxetine has been administered concomitantly.
Five patients receiving fluoxetine in combination with tryptophan experienced adverse reactions, including agitation, restlessness, and gastrointestinal distress.
The half-life of concurrently administered diazepam may be prolonged in some patients. Experience with the use of fluoxetine in combination with other CNS-active drugs is limited and caution is advised if such concomitant medication is required (see Warnings).
Drugs Tightly Bound to Plasma Protein: Because fluoxetine is highly bound to plasma protein, the administration of fluoxetine to a patient taking another drug which highly bound to proteins (e.g. warfarin, digoxin) may cause a shift in plasma concentration potentially resulting in an adverse effect. Conversely, adverse effect may result from displacement of protein bound fluoxetine by other tightly bound drugs.
P450 Isoenzyme (IID6): Like other selective serotonin reuptake inhibitors, fluoxetine inhibits the specific hepatic cytochrome P450 isozyme (IID6) which is responsible for the metabolism of debrisoquine and sparteine. Although the clinical significance of this effect has not been established, inhibition of IID6 may lead to elevated plasma levels of co-administered drugs which are metabolized by this isozyme. Drugs metabolized by cytochrome P450 IID6 include the tricyclic antidepressants (e.g. nortriptyline, amitriptyline, imipramine and desipramine), phenothiazine neuroleptics (e.g. perphenazine and thioridazine), and Type 1C antiarrhythmics (e.g. propafenone and flecainide).
Dependence Liability: Fluoxetine has not been systemically studied, in animals or humans, for its potential for abuse, tolerance or physical dependence. Physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of fluoxetine.