RiteMED Fluoxetine Drug Interactions

SSRIs interact with other drugs mainly as a result of their inhibitory activity on hepatic cytochrome P450 isoenzymes. Individual SSRIs do not all exhibit the same degree of inhibition, nor do they react with the same isoenzymes. The drugs inhibited by specific SSRIs depends on the isoenzyme affected.
SSRIs should not generally be given to patients receiving MAOIs or for at least 2 weeks after their use. No treatment-free period is necessary after stopping a reversible inhibitor of monoamine oxidase type A (RIMA) and starting an SSRI. For Fluoxetine, the interval may need to be further extended if therapy has been prolonged or if high doses have been given.
Adverse effects such as the serotonin syndrome may also occur when the SSRIs are given with other drugs known to act on the same neurotransmitter, a consequence of synergistic interaction.
Antibacterials: Rapid development of delirium was reported in a patient when clarithromycin was added to existing regimen of Fluoxetine and Nitrazepam. It was suggested that this delirium was a result of increased plasma-Fluoxetine concentrations produced by the inhibition of cytochrome P450 enzymes by Clarithromycin. There have also been reports of serotonin syndrome when Linezolid was given with Fluoxetine, Sertraline, Paroxetine, and Citalopram.
Anticoagulants: SSRIs may increase the anticoagulant activity of some anticoagulants including acenocoumarol and warfarin.
Antidepressants: Combination therapy with differing classes of antidepressants has been used successfully in the treatment of drug-resistant depression. It should be emphasized, however, that such combinations may result in enhanced adverse reactions or interactions, and should be used only under expert supervision.
Anti-epileptics: Antidepressants may antagonize the activity of antiepileptics by lowering the convulsive threshold. There has been report of a serotonin syndrome developing in patient days after Fluoxetine had been added to carbamazepine therapy.
Antihistamines: Cyproheptadine given to male and female patients as treatment for sexual dysfunction induced by Fluoxetine or Paroxetine has produced re-emergence of previously controlled depressive symptoms or bulimia nervosa in some patients. Citalopram, Fluoxetine, and Fluvoxamine may increase plasma concentrations of Astemizole or Terfenadine by inhibition of their hepatic cytochrome P450 metabolism, increasing the risk of ventricular arrhythmias; use together should be avoided.
Antivirals: Plasma concentrations of Fluoxetine and other SSRIs are possibly increased by HIV-protease inhibitors, such as Ritonavir, which may inhibit metabolism of the SSRI. The serotonin syndrome has been described in a few patients given regimens that included Fluoxetine and antiretroviral-dose Ritonavir. The reaction also occurred in another patient given Fluoxetine and Efavirenz.
Anxiolytics: Fluoxetine and Fluvoxamine increase plasma concentrations of some benzodiazepines.
Beta-blockers.
Ciclosporin.
Cough suppressants: Effects with dextromethorphan.
Dopaminergics: Selegiline is an irreversible selective inhibitor of monoamine oxidase type B. Serious adverse effects have been reported when selegiline and SSRIs have been used together. In some instances, these reactions resemble the potentially fatal serotonin syndromes reported when SSRIs are given with non-selective MAOIs. SSRIs should not generally be given to patients receiving Selegiline, or at least 2 weeks after it has been stopped. Similarly, at least one week should elapse between withdrawing an SSRI and starting Selegiline; this interval should be increased to 2 weeks for Sertraline, and to 5 weeks for Fluoxetine because of their longer half-lives.
Gastro-intestinal Drug: Acute dystonia has been noted in patients given Fluoxetine, Fluvoxamine, Metoclopramide, Sertraline.
Hypnotics: for reference to visual hallucinations in patients receiving an SSRI concomitantly with Zolpidem.
Muscle relaxant: Report of QT prolongation in patients taking Fluoxetine and Cyclobenzaprine.
NSAIDs: An increased risk of upper gastrointestinal bleeding in patients taking SSRIs and NSAIDs together.
Opioid analgesics: There have also been occasional reports of the syndrome in patients given Tramadol with Citalopram, Fluoxetine or Paroxetine. Other reports of serotonin syndrome were associated with use of Pethidine and Fluoxetine.
Sibutramine: There is a risk of CNS toxicity due to synergistic serotonergic actions when an SSRI is given with Sibutramine.