Interactions between rabeprazole and Luvox cr (fluvoxamine)
fluvoxamine and rabeprazole (Moderate Drug-Drug)
MONITOR: Coadministration with fluvoxamine may increase the plasma concentrations of omeprazole and other proton pump inhibitors in a dose-dependent manner. The mechanism is fluvoxamine inhibition of the CYP450 2C19 metabolism of proton pump inhibitors. In 12 healthy volunteers, pretreatment with fluvoxamine for 7 days (10 mg once or twice a day) resulted in a 174% increase in the mean 8-hour area under the plasma concentration-time curve (AUC) of a single 20 mg oral dose of omeprazole compared to administration of omeprazole alone. When the dosage of fluvoxamine was increased (25 mg once or twice a day for 7 days), the mean 8-hour AUC of single-dose omeprazole increased 330%. The interaction apparently does not occur in poor metabolizers (PMs) of CYP450 2C19, which comprise approximately 3% to 5% of the Caucasian and 17% to 20% of the Asian population. In 18 healthy volunteers--six each of homozygous extensive metabolizers (EMs), heterozygous EMs, and PMs of CYP450 2C19--fluvoxamine (25 mg orally twice a day for 6 days) increased the Cmax, AUC, and elimination half-life (T1/2) of a single 40 mg oral dose of omeprazole by 3.7-, 6.2-, and 2.6-fold, respectively, in homozygous EMs and by 2.0-, 2.5, and 1.4-fold, respectively, in heterozygous EMs compared to placebo. The AUC ratio of 5-hydroxyomeprazole to omeprazole, which is considered an index of CYP450 2C19 activity, was decreased during fluvoxamine treatment to 17% in homozygous EMs and 49% in heterozygous EMs. In contrast, no changes in omeprazole pharmacokinetics or AUC ratio of 5-hydroxyomeprazole to omeprazole were observed in PMs. No adverse effects were attributed to the increased omeprazole exposure in the study.
MANAGEMENT: Although proton pump inhibitors are generally well tolerated, caution is advised if they are prescribed with fluvoxamine. Dosage adjustment should be considered in patients who experience excessive adverse effects such as drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, and dry mouth.
