Drug Interactions between dronabinol 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: Alcohol may potentiate some of the effects of CNS-active and/or CNS-toxic agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations and effects of drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4 mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit the consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. It may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with drugs that undergo metabolism by CYP450 3A4. Orange juice is not expected to interact with these drugs.