Drug Interactions between levomethadyl acetate and Rezulin

GENERALLY AVOID: The concurrent use of levomethadyl acetate and alcohol may result in additive CNS and respiratory depression, hypotension, sedation, or coma. Grapefruit juice may increase the plasma concentrations of orally administered drugs which are substrates of the CYP450 3A4 isoenzyme, such as levomethadyl acetate. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who are known to abuse alcohol should be warned of the risk of potentially fatal overdose if these substances are taken concurrently. Patients who regularly consume grapefruits and grapefruit juice should be monitored for adverse effects and altered plasma concentrations of levomethadyl acetate. A 12-lead ECG should be performed before initiating therapy, 12 to 14 days after initiating therapy, and periodically thereafter. Patients should be advised to immediately seek medical attention if they experience palpitations, dizziness, lightheadedness, fainting, or seizures. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.