Drug Interactions between Mepergan and Viekira XR

ADJUST DOSE: The central nervous system and respiratory depressant effects of meperidine may be potentiated by concomitant use of other agents with CNS depressant effects. An increased risk of serious adverse reactions such as respiratory depression, hypotension, profound sedation, syncope, coma, and even death should be considered, particularly in elderly or debilitated patients.

MANAGEMENT: Caution and dosage adjustments are advisable when meperidine is used in combination with other narcotic analgesics, general anesthetics, phenothiazines, sedative-hypnotics, tranquilizers, tricyclic antidepressants, or other CNS depressants such as alcohol. A lower dosage of meperidine should be considered initially, then titrated carefully according to pain level and clinical response. Meperidine dosage reductions of 25% to 50% have been recommended for patients receiving phenothiazines and other tranquilizers. Patients should be advised to avoid rising abruptly from a sitting or recumbent position, and to notify their physician if they experience dizziness, lightheadedness, orthostasis, syncope, tachycardia, or excessive CNS effects that interfere with their normal activities. Patients should also avoid driving or operating hazardous machinery until they know how these medications affect them.

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GENERALLY AVOID: Ritonavir may induce the metabolism of meperidine to its pharmacologically active metabolite, normeperidine. In eight healthy, HIV-negative volunteers, ritonavir (500 mg twice a day for 10 days) decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of meperidine (50 mg single oral dose) by 60% and 67%, respectively, compared to administration of meperidine alone. In contrast, normeperidine Cmax and AUC increased by 87% and 47%, suggesting induction of hepatic metabolism. The net effect of this interaction is unknown. Normeperidine has been associated with adverse effects such as lethargy, agitation, and seizures.

MANAGEMENT: Meperidine product labeling recommends that the combination of meperidine and ritonavir be avoided. If concomitant administration is necessary, it is best that meperidine be limited to short-term use at lower dosages.

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MONITOR: Coadministration with ritonavir may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to competitive inhibition of CYP450 2D6 activity by ritonavir. The systemic exposure (AUC) of some coadministered drugs has been reported to increase by up to twofold.

MANAGEMENT: Caution is advised if ritonavir must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ritonavir is added to or withdrawn from therapy.

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