Fluvoxamine. A review of global drug-drug interaction data

The overall reporting rate of drug-drug interactions with fluvoxamine is very low: only 73 cases have been identified from an estimated exposure of over 8 million patients worldwide. The reporting rate is similar in men and women, and most events relate to the use of fluvoxamine in conjunction with psychotropic compounds and anticoagulants. Two deaths have been documented. One involved a female patient who was given concomitant tryptophan and reportedly developed neuroleptic malignant syndrome. The causative role of fluvoxamine/tryptophan interaction in this case is unknown. The other reported death was considered to be unrelated to fluvoxamine. Fluvoxamine interactions with anti-epileptic or antidepressant drugs resulted in elevated plasma concentrations of the target drug and/or clinical symptoms, while interactions with neuroleptic or anticoagulant agents mostly resulted in clinical symptoms. Fluvoxamine increased plasma concentrations of tricyclic antidepressants by varying extents, particularly those of clomipramine (maximum reported increase 8-fold). Generally, clinical symptoms were infrequent and varied widely; no symptom clusters were identified. Those agents metabolised by cytochrome P450 1A2 isoenzyme appear most likely to be involved in drug-drug interactions with fluvoxamine.