Drug Interactions between imipramine and sodium oxybate

CONTRAINDICATED: Alcohol may potentiate the central nervous system and respiratory depressant effects of sodium oxybate, which is the sodium salt of gamma hydroxybutyrate (GHB). An increased risk of serious adverse reactions such as respiratory depression, hypotension, profound sedation, syncope, coma, and even death should be anticipated.

ADJUST DOSING INTERVAL: Food may delay the absorption and significantly decrease the bioavailability of sodium oxybate. When sodium oxybate was administered immediately after a high-fat meal, the time to reach peak plasma concentration (Tmax) increased from 0.75 hour to 2 hours, the peak plasma concentration (Cmax) decreased by a mean of 59%, and the systemic exposure (AUC) decreased by a mean of 37%.

MANAGEMENT: The concomitant use of sodium oxybate with alcohol is considered contraindicated. The first dose of sodium oxybate should be taken at least 2 hours after a meal to ensure maximal absorption.

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.