Drug Interactions between Meprozine and timolol ophthalmic

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.

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the systemic effects of topically administered timolol, which is metabolized by the isoenzyme. Following ocular administration, timolol is systemically absorbed and can reach plasma levels associated with adverse beta-adrenergic blocking effects such as bronchospasm, depression, bradycardia, and hypotension. The risk may be increased if clearance of the drug is significantly diminished by concomitant CYP450 2D6 inhibitors. In one case report, a 70-year-old man experienced dizziness secondary to sinus bradycardia after 12 weeks of treatment with a 0.5% timolol eye drop while also taking quinidine sulfate 500 mg three times a day. The symptoms subsided and sinus rhythm returned to normal a day after discontinuation of both drugs. However, symptoms returned within 30 hours after restarting both drugs a month later. Quinidine was discontinued, and the patient did not experience further problems. In a study of 13 healthy volunteers, extensive metabolizers of CYP450 2D6 administered quinidine (50 mg single oral dose) 30 minutes before 0.5% timolol eye drop (2 drops in each nostril) demonstrated significantly greater reductions in exercise heart rate and had higher plasma timolol concentrations than when given timolol alone. The changes resulted in values that were similar to those observed in poor metabolizers given the timolol eye drop without quinidine. In another study, 12 healthy volunteers given cimetidine (400 mg orally twice a day for 7 doses) and 0.5% timolol eye drop (0.05 mL in each eye 30 minutes after last dose of cimetidine) demonstrated additional reductions in resting heart rate and intraocular pressure relative to administration of the timolol eye drop alone, although there were no additional reductions of exercise heart rate or systolic blood pressure (at rest or after exercise) compared to timolol alone.

MANAGEMENT: Patients should be monitored for systemic beta-adrenergic blocking effects of topical timolol during coadministration with CYP450 2D6 inhibitors such as cimetidine, quinidine, and certain selective serotonin reuptake inhibitors. Particular caution is warranted in elderly patients, since they are generally more susceptible to adverse effects of topically administered beta blockers.