Drug Interactions between mirtazapine and Omeclamox-Pak

MONITOR: Coadministration of mirtazapine with drugs that inhibit one or more of its metabolic pathways may result in increased plasma concentrations of mirtazapine. In vitro data from human liver microsomes indicate that CYP450 2D6 and 1A2 are involved in the formation of the 8-hydroxy metabolite, while CYP450 3A4 is primarily responsible for the formation of the N-desmethyl and N-oxide metabolites. When cimetidine, a weak inhibitor of CYP450 1A2, 2D6 and 3A4, was given at 800 mg twice daily for 14 days to twelve healthy male subjects in combination with mirtazapine 30 mg once daily on days 6 to 12, mean steady-state mirtazapine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 22% and 54%, respectively. Mirtazapine had no effect on the pharmacokinetics of cimetidine. In another study with 24 healthy male Caucasian subjects, administration of the potent CYP450 3A4 inhibitor ketoconazole at 200 mg twice daily for 6.5 days increased Cmax and AUC of a single 30 mg dose of mirtazapine by approximately 40% and 50%, respectively. A case report described increases in serum mirtazapine concentrations of three- to fourfold in two patients following the addition of fluvoxamine, a potent CYP450 1A2 and weak CYP450 2D6/3A4 inhibitor. One patient reported feeling more anxious with the combination.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of mirtazapine should be considered during coadministration of drugs that inhibit CYP450 1A2, 2D6 and/or 3A4. Therapeutic response to mirtazapine should be monitored more closely following initiation, discontinuation, or dosing change of CYP450 inhibitors, and the mirtazapine dosage adjusted as necessary. A prolonged duration of monitoring for adverse effects may be required depending on the elimination half-life of the concomitant drug. For example, it should be noted that rolapitant, a moderate CYP450 2D6 inhibitor, can increase plasma concentrations and the risk of adverse effects of mirtazapine for at least 28 days after administration of rolapitant.

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Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

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Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.

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