Drug Interactions between apomorphine and Meprozine

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.

GENERALLY AVOID: Central nervous system (CNS) depressant effects may be additively or synergistically increased in patients using apomorphine in combination with other drugs that can also cause these effects. Apomorphine alone has been frequently associated with somnolence and dizziness. Patients may suddenly fall asleep during activities of daily living.

MANAGEMENT: The use of other sedating drugs should generally be avoided during apomorphine treatment. Patients prescribed these agents concurrently should be monitored for potentially excessive or prolonged CNS depression, especially if they are elderly or debilitated. Ambulatory patients should be made aware of the possibility of additive CNS effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them. If patients experience increased episodes of falling asleep during normal daily activities, they should avoid driving and other potentially hazardous activities until they have contacted their physician.

GENERALLY AVOID: Coadministration with dopamine antagonists (e.g., neuroleptic agents, metoclopramide) or other drugs that interfere with central amine mechanisms may decrease the effectiveness of apomorphine, which is a dopaminergic agent. In addition, some of these agents as well as apomorphine have been associated with sedation, hypotension, and QT interval prolongation. Additive pharmacodynamic effects may occur when used in combination. Excessive prolongation of the QT interval can increase the risk of ventricular arrhythmias including torsade de pointes and sudden death in susceptible patients. Apomorphine doses greater than 6 mg have been associated with minimal increases of the QT interval. The average QTc prolongation was 1 msec at 6 mg and 7 msec at 8 mg. Two patients experienced large increases of more than 60 msec with 2 mg and 6 mg doses. Torsade de pointes has not been reported with apomorphine alone at recommended doses. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: The use of apomorphine in combination with dopamine antagonists should generally be avoided unless the potential benefits outweigh the risks. The UK product labeling recommends considering a gradual reduction of apomorphine dosage when this is administered by minipump and/or syringe-driver. Monitoring for altered efficacy of apomorphine and increased side effects such as sedation or hypotension is recommended if concomitant use is required. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Also, they should avoid activities requiring mental alertness until they know how these agents affect them. Patients who experience increased episodes of falling asleep during normal daily activities should avoid driving and other potentially hazardous activities until they have been evaluated by their physician.