(US Adopted Name, rINN)
Pharmacopoeias. In US.
The United States Pharmacopeia 31, 2008 (Dronabinol). Store at a temperature between 8° and 15° in airtight glass containers in an inert atmosphere. Protect from light.
Adverse Effects and Precautions
As for Nabilone. The most frequent adverse effects of dronabinol include abdominal pain, nausea and vomiting, dizziness, euphoria, paranoid reactions, and somnolence. Seizures and seizure-like activity have been reported dronabinol should be used with caution in those with a history of seizure disorders, and therapy should be stopped if seizures occur.
The abuse liability of dronabinol was rated as being substantially lower than that of cannabis.
US licensed product information states that dronabinol is concentrated in breast milk and recommends that it should not be used in breast-feeding mothers.
After oral doses dronabinol is slowly and erratically absorbed from the gastrointestinal tract the bioavailability of an oral dose is about 10 to 20%, due to extensive first-pass metabolism. Peak plasma concentrations of dronabinol and its 11-hydroxy metabolite are achieved about 2 to 4 hours after a dose by mouth. It is widely distributed and is extensively protein bound, with a volume of distribution of about 10 litres/kg. Elimination is biphasic, with an initial half-life of about 4 hours, and a terminal half-life of about 25 to 36 hours.
Dronabinol is extensively metabolised, mainly in the liver by cytochrome P450 isoenzymes the primary metabolite, 11 -hydroxydronabinol is also active. The 11-hydroxy metabolite is converted to other, more polar and acidic compounds which are excreted in faeces via the bile, and in the urine. About 50% of an oral dose is recovered in faeces within 72 hours and 10 to 15% in urine. Many of the metabolites have relatively prolonged half-lives, and accumulation may occur with repeated dosage. Dronabinol is distributed into breast milk and crosses the placenta.
Uses and Administration
Dronabinol, the major psychoactive constituent of cannabis, has antiemetic properties and is used for the control of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetics.
The usual initial oral dose of dronabinol is 5 mg/m given 1 to 3 hours before the first dose of the antineoplastic drug with subsequent doses being given every 2 to 4 hours after chemotherapy to a maximum of 4 to 6 doses daily. If necessary, the dose may be increased by increments of 2.5 mg/m to a maximum dose of 15 mg/m, if adverse effects permit.
Dronabinol also has appetite-stimulant effects and is used in the treatment of anorexia associated with weight loss in patients with AIDS. For this purpose 2.5 mg may be taken twice daily, before lunch and supper, reduced to a single 2.5-mg dose in the evening in patients who tolerate the drug poorly. If necessary, and if adverse effects permit, doses may also be increased up to 20 mg daily in divided doses.
Dronabinol is used with cannabidiol, another cannabinoid, in a buccal spray preparation as adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis in adults this combination is also used as adjunctive analgesic treatment in adult patients with advanced cancer and is under investigation for a number of other conditions (see under Cannabis).
There is some suggestion that dronabinol may decrease agitation in patients with Alzheimer’s disease.
Dronabinol is used for the management of anorexia in patients with HIV-associated wasting. However, although dronabinol may stimulate appetite and prevent weight loss, it does not appear to produce significant weight gain, and may produce less benefit than megestrol acetate. Benefits were also less than those of megestrol in patients with anorexia associated with malignant disease.
Anecdotal evidence has suggested that cannabinoids might improve symptoms in patients with multiple sclerosis a review considered evidence of effectiveness to be lacking. In a large placebo-controlled study, treatment with dronabinol or oral cannabis extract had no benefit on objective assessment of spasticity however, there were improvements in walking time, and subjective improvements in both spasticity and pain. A subsequent small controlled study found dronabinol to have a modest but clinically relevant effect on central neuropathic pain in patients with multiple sclerosis. Dronabinol is used with cannabidiol, another cannabinoid, in a buccal spray preparation for the symptomatic relief of neuropathic pain in multiple sclerosis in adults.
Preliminary studies indicate that dronabinol may reduce tic severity in Tourette’s syndrome (see Tics).
The United States Pharmacopeia 31, 2008: Dronabinol Capsules.
South Africa: Elevat