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Monoamine oxidase inhibitors: Fluvoxamine should not be used in combination with MAOIs, including linezolid, due to risk of serotonin syndrome (see Contraindications).
Effect of fluvoxamine on the oxidative metabolism of other drugs: Fluvoxamine can inhibit the metabolism of drugs metabolized by certain cytochrome P450 isoenzymes (CYPs). A strong inhibition of CYP1A2 and CYP2C19 is demonstrated in in vitro and in vivo studies. CYP2C9, CYP2D6 and CYP3A4 are inhibited to a lesser extent.
Drugs which are largely metabolised via these isoenzymes may have higher/lower (e.g. in case of prodrugs like Clopidogrel) plasma concentrations of the active substance/metabolite when co-administered with Fluvoxamine. Concomitant therapy of fluvoxamine and these drugs should be initiated at or adjusted to the low vs high end of their dose range. Plasma concentrations, effects or adverse effects of co-administered drugs should be monitored and their dosage should be reduced/increased if necessary. This is particularly relevant for drugs with a narrow therapeutic index.
Ramelteon: When immediate-release fluvoxamine maleate tablets 100 mg twice daily was administered for 3 days prior to single-dose co-administration of ramelteon 16 mg and immediate-release fluvoxamine maleate tablets, the AUC for ramelteon increased approximately 190-fold and the Cmax increased approximately 70-fold compared to ramelteon administered alone.
Compounds with narrow therapeutic index: Co-administration of fluvoxamine and drugs with a narrow therapeutic index (such as tacrine, theophylline, methadone, mexiletine, phenytoin, carbamazepine and cyclosporine) should be carefully monitored when these drugs are metabolized exclusively or by a combination of CYPs inhibited by fluvoxamine.
If necessary, dose adjustment of these drugs is recommended.
Due to the narrow therapeutic index of pimozide and its known ability to prolong QT interval, concomitant use of pimozide and fluvoxamine is contraindicated see Contraindications.
Tricyclic antidepressants and neuroleptics: An increase in previously stable plasma levels of those tricyclic antidepressants (e.g., clomipramine, imipramine, amitriptyline) and neuroleptics (e.g., clozapine, olanzapine, quetiapine) which are largely metabolised through cytochrome P450 1A2 when given together with fluvoxamine, has been reported. A decrease in the dose of these products should be considered if treatment with fluvoxamine is initiated.
Benzodiazepines: The plasma levels of oxidatively metabolised benzodiazepines (e.g. triazolam, midazolam, alprazolam, and diazepam) are likely to be increased when co-administered with fluvoxamine. The dosage of these benzodiazepines should be reduced during co-administration with fluvoxamine.
Cases of increased plasma concentration: As plasma concentrations of ropinirol may be increased in combination with fluvoxamine thus increasing the risk of overdose, surveillance and reduction in the posology of ropinirol during fluvoxamine treatment and after its withdrawal may be required.
As plasma concentrations of propranolol are increased in combination with fluvoxamine, the propranolol dose may need to be lowered.
When given with fluvoxamine, warfarin plasma concentrations were significantly increased and prothrombin times prolonged.
Cases of increased side effects: Isolated cases of cardiac toxicity have been reported when fluvoxamine was combined with thioridazine.
Caffeine plasma levels are likely to be increased during co-administration with fluvoxamine. Thus, patients who consume high quantities of caffeine-containing beverages should lower their intake when fluvoxamine is administered and adverse caffeine effects (like tremor, palpitations, nausea, restlessness, insomnia) are observed.
Terfenadine, astemizole, cisapride, sildenafil: see Precautions.
Glucuronidation: Fluvoxamine does not influence plasma concentrations of digoxin.
Renal excretion: Fluvoxamine does not influence plasma concentrations of atenolol.
Pharmacodynamic interactions: The serotonergic effects of fluvoxamine may be enhanced when used in combination with other serotonergic agents (including triptans, tramadol, SSRIs and St. John's Wort preparations) (see Precautions).
Fluvoxamine has been used in combination with lithium in the treatment of severely ill, drug-resistant patients. However, lithium (and possibly also tryptophan) enhances the serotonergic effects of fluvoxamine. The combination should be used with caution in patients with severe, drug-resistant depression.
In patients on oral anticoagulants and fluvoxamine, the risk for haemorrhage may increase and these patients should therefore be closely monitored.
As with other psychotropic drugs patients should be advised to avoid alcohol use while taking fluvoxamine.
