Adverse experiences information summarized in the tables below was derived from well-controlled clinical trials conducted in the US and US territories involving 474 patients exposed to MARINOL (dronabinol) Capsules. Studies of AIDS-related weight loss included 157 patients receiving dronabinol at a dose of 2.5 mg twice daily and 67 receiving placebo. Studies of different durations were combined by considering the first occurrence of events during the first 28 days. Studies of nausea and vomiting related to cancer chemotherapy included 317 patients receiving dronabinol and 68 receiving placebo.
A cannabinoid dose-related "high" (easy laughing, elation and heightened awareness) has been reported by patients receiving MARINOL (dronabinol) Capsules in both the antiemetic (24%) and the lower dose appetite stimulant clinical trials (8%). (See Clinical Trials.)
The most frequently reported adverse experiences in patients with AIDS during placebo-controlled clinical trials involved the CNS and were reported by 33% of patients receiving MARINOL (dronabinol) Capsules. About 25% of patients reported a minor CNS adverse event during the first 2 weeks and about 4% reported such an event each week for the next 6 weeks thereafter.
PROBABLY CAUSALLY RELATED: Incidence greater than 1%.
Rates derived from clinical trials in AIDS-related anorexia (N=157) and chemotherapy-related nausea (N=317). Rates were generally higher in the anti-emetic use (given in parentheses).
Body as a whole: Asthenia.
Cardiovascular: Palpitations, tachycardia, vasodilation/facial flush.
Digestive: Abdominal pain*, nausea*, vomiting*.
Nervous system: (Amnesia), anxiety/nervousness, (ataxia), confusion, depersonalization, dizziness*, euphoria*, (hallucination), paranoid reaction*, somnolence*, thinking abnormal*.
*Incidence of events 3% to 10%
PROBABLY CAUSALLY RELATED: Incidence less than 1%.
Event rates derived from clinical trials in AIDS-related anorexia (N=157) and chemotherapy-related nausea (N=317).
Cardiovascular: Conjunctivitis*, hypotension*.
Digestive: Diarrhea*, fecal incontinence.
Nervous system: Depression, nightmares, speech difficulties, tinnitus.
Skin and Appendages: Flushing*.
Special senses: Vision difficulties.
*Incidence of events 0.3% to 1%
CAUSAL RELATIONSHIP UNKNOWN: Incidence less than 1%.
The clinical significance of the association of these events with MARINOL (dronabinol) Capsules treatment is unknown, but they are reported as alerting information for the clinician.
Body as a whole: Chills, headache, malaise.
Digestive: Anorexia, hepatic enzyme elevation.
Respiratory: Cough, rhinitis, sinusitis.
Skin and Appendages: Sweating.
Seizure and seizure-like activity have been reported in patients receiving MARINOL (dronabinol) Capsules during marketed use of the drug and in clinical trials. (See PRECAUTIONS and OVERDOSAGE.) Reports of fatigue have also been received. A causal relationship between MARINOL (dronabinol) Capsules and these events has not been established.
Drug Abuse And Dependence
MARINOL (dronabinol) Capsules is one of the psychoactive compounds present in cannabis, and is abusable and controlled [Schedule III (CIII)] under the Controlled Substances Act. Both psychological and physiological dependence have been noted in healthy individuals receiving dronabinol, but addiction is uncommon and has only been seen after prolonged high dose administration.
Chronic abuse of cannabis has been associated with decrements in motivation, cognition, judgement, and perception. The etiology of these impairments is unknown, but may be associated with the complex process of addiction rather than an isolated effect of the drug. No such decrements in psychological, social or neurological status have been associated with the administration of MARINOL (dronabinol) Capsules for therapeutic purposes.
In an open-label study in patients with AIDS who received MARINOL (dronabinol) Capsules for up to five months, no abuse, diversion or systematic change in personality or social functioning were observed despite the inclusion of a substantial number of patients with a past history of drug abuse.
An abstinence syndrome has been reported after the abrupt discontinuation of dronabinol in volunteers receiving dosages of 210 mg/day for 12 to 16 consecutive days. Within 12 hours after discontinuation, these volunteers manifested symptoms such as irritability, insomnia, and restlessness. By approximately 24 hours post-dronabinol discontinuation, withdrawal symptoms intensified to include "hot flashes", sweating, rhinorrhea, loose stools, hiccoughs and anorexia.
These withdrawal symptoms gradually dissipated over the next 48 hours. Electroencephalographic changes consistent with the effects of drug withdrawal (hyperexcitation) were recorded in patients after abrupt dechallenge. Patients also complained of disturbed sleep for several weeks after discontinuing therapy with high dosages of dronabinol.