Marinol (Dronabinol) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Drug Interactions: In studies involving patients with AIDS and/or cancer, MARINOL Capsules has been co-administered with a variety of medications (e.g., cytotoxic agents, anti-infective agents, sedatives, or opioid analgesics) without resulting in any clinically significant drug/drug interactions. Although no drug/drug interactions were discovered during the clinical trials of MARINOL Capsules, cannabinoids may interact with other medications through both metabolic and pharmacodynamic mechanisms. Dronabinol is highly protein bound to plasma proteins, and therefore, might displace other protein-bound drugs. Although this displacement has not been confirmed in vivo, practitioners should monitor patients for a change in dosage requirements when administering dronabinol to patients receiving other highly protein-bound drugs. Published reports of drug/drug interactions involving cannabinoids are summarized in the following table.

CONCOMITANT DRUG	CLINICAL EFFECT(S)
Amphetamines, cocaine, other sympathomimetic agents	Additive hypertension, tachycardia, possibly cardiotoxicity
Atropine, scopolamine, antihistamines, other anticholinergic agents	Additive or super-additive tachycardia, drowsiness
Amitriptyline, amoxapine, desipramine, other tricyclic antidepressants	Additive tachycardia, hypertension, drowsiness
Barbiturates, benzodiazepines, ethanol, lithium, opioids, buspirone, antihistamines, muscle relaxants, other CNS depressants	Additive drowsiness and CNS depression
Disulfiram	A reversible hypomanic reaction was reported in a 28 y/o man who smoked marijuana; confirmed by dechallenge and rechallenge
Fluoxetine	A 21 y/o female with depression and bulimia receiving 20 mg/day fluoxetine X 4 wks became hypomanic after smoking marijuana; symptoms resolved after 4 days
Antipyrine, barbiturates	Decreased clearance of these agents, presumably via competitive inhibition of metabolism
Theophylline	Increased theophylline metabolism reported with smoking of marijuana; effect similar to that following smoking tobacco

OVERDOSAGE

Signs and symptoms following MILD MARINOL Capsules intoxication include drowsiness, euphoria, heightened sensory awareness, altered time perception, reddened conjunctiva, dry mouth and tachycardia; following MODERATE intoxication include memory impairment, depersonalization, mood alteration, urinary retention, and reduced bowel motility; and following SEVERE intoxication include decreased motor coordination, lethargy, slurred speech, and postural hypotension. Apprehensive patients may experience panic reactions and seizures may occur in patients with existing seizure disorders.

The estimated lethal human dose of intravenous dronabinol is 30 mg/kg (2100 mg/ 70 kg). Significant CNS symptoms in antiemetic studies followed oral doses of 0.4 mg/kg (28 mg/70 kg) of MARINOL Capsules.

Management: A potentially serious oral ingestion, if recent, should be managed with gut decontamination. In unconscious patients with a secure airway, instill activated charcoal (30 to 100 g in adults, 1 to 2 g/kg in infants) via a nasogastric tube. A saline cathartic or sorbitol may be added to the first dose of activated charcoal. Patients experiencing depressive, hallucinatory or psychotic reactions should be placed in a quiet area and offered reassurance. Benzodiazepines (5 to 10 mg diazepam po) may be used for treatment of extreme agitation. Hypotension usually responds to Trendelenburg position and IV fluids. Pressors are rarely required.

CONTRAINDICATIONS

MARINOL Capsules is contraindicated in any patient who has a known sensitivity to MARINOL Capsules or any of its ingredients. It contains cannabinoid and sesame oil and should never be used by patients allergic to these substances.