| CESAMET® |
|Action And Clinical Pharmacology: Nabilone is a synthetic cannabinoid with antiemetic properties which have been found to be of value in the management of some patients with nausea and vomiting associated with cancer chemotherapy. It also has sedative and psychotropic effects.
After oral administration, comparable peak plasma levels of nabilone and of its carbinol metabolite were attained within 2 hours. The combined plasma concentrations of nabilone and of its carbinol metabolite accounted for, at most, 10 to 20% of the total radio-carbon concentration in plasma. The plasma half life of nabilone was approximately 2 hours, while that of the total radiocarbon was of the order of 35 hours.
Of the 2 major possible metabolic pathways, stereo-specific enzymatic reduction and direct enzymatic oxidation, the latter appears to be the more important in man.
The drug and its metabolites are eliminated mainly in the feces (approximately 65%) and to a lesser extent in the urine (approximately 20%). The major excretory pathway is the biliary system.
Indications And Clinical Uses: For the management of severe nausea and vomiting associated with cancer chemotherapy.
Contra-Indications: Sensitivity to marijuana or other cannabinoid agents, and in patients with a history of psychotic reactions. tag_WarningWarnings
Manufacturers' Warnings In Clinical States: Nabilone should be used with extreme caution in patients with severe liver dysfunction and in those with a history of non-psychotic emotional disorders.
Nabilone should not be taken with alcohol, sedatives, hypnotics, or other psychotomimetic substances.
Pregnancy, Lactation and Children: Nabilone should not be used during pregnancy, in nursing mothers or in pediatric patients, since its safety under these conditions has not been established.
Precautions: Occupational Hazards: Since nabilone will often impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car and operating machinery, the patient should be warned accordingly and should not be permitted to drive or engage in dangerous tasks until the effects of nabilone are no longer present.
Adverse psychiatric reactions can persist for 48 to 72 hours following cessation of treatment.
Since nabilone elevates supine and standing heart rates and causes postural hypotension, it should be used with caution in the elderly and in patients with hypertension or heart disease.
Drug Interactions: Potential interactions between nabilone, and diazepam; sodium secobarbital; alcohol or codeine were evaluated. The depressant effects of the combinations were additive. Psychomotor function was particularly impaired with concurrent use of diazepam.
Adverse Reactions: The most frequently observed adverse reactions to nabilone and their incidences reported in the course of clinical trials were as follows: drowsiness (66.0%), vertigo (58.8%), psychological high (38.8%), dry mouth (21.6%), depression (14.0%), ataxia (12.8%), blurred vision (12.8%), sensation disturbance (12.4%), anorexia (7.6%), asthenia (7.6%), headache (7.2%), orthostatic hypotension (5.2%), euphoria (4.0%) and hallucinations (2.0%).
The following adverse reactions were observed in less than 1% of the patients who were administered nabilone in the course of the clinical trials: tachycardia, tremors, syncope, nightmares, distortion in the perception of time, confusion, dissociation, dysphoria, psychotic reactions and seizures.
Spontaneously Reported Adverse Events: The following adverse reactions listed in order of decreasing frequency by body system have been reported since nabilone has been marketed. All events are listed regardless of causality assessment.
Blood and Hematopoietic: leukopenia.
Cardiovascular: hypotension and tachycardia.
Eye and Ear: visual disturbances.
Gastrointestinal: dry mouth, nausea, vomiting and constipation.
CNS: hallucinations, CNS depression, CNS stimulation, ataxia, stupor, vertigo, convulsion and circumoral paresthesia.
Psychiatric: somnolence, confusion, euphoria, depression. dysphoria, depersonalization, anxiety, psychosis and emotional lability.
Miscellaneous and Ill-Defined Conditions: dizziness, headache, insomnia, abnormal thinking, chest pain, lack of effect, and face edema.
Symptoms And Treatment Of Overdose: Symptoms: Signs and symptoms which might be expected to occur are psychotic episodes including hallucinations, anxiety reactions, respiratory depression and coma (experience with cases of overdosage of more than 10 mg/day has not yet been reported). tag_Treatment
Treatment: Overdose may be considered to have occurred, even at prescribed dosages, if disturbing psychiatric symptoms are present. In these cases, the patient should be observed in a quiet environment and supportive measures, including reassurance, should be used. Subsequent doses should be withheld until patients have returned to their baseline mental status; routine dosing may then be resumed if clinically indicated. In such instances, a lower initiating dose is suggested.
If psychotic episodes occur, the patient should be managed conservatively, if possible. For moderate psychotic episodes and anxiety reactions, verbal support and comforting may be sufficient. In more severe cases, antipsychotic drugs may be useful; however, the utility of antipsychotic drugs in cannabinoid psychosis has not been systematically evaluated. Support for their use is drawn from limited experience using anti-psychotic agents to manage cannabis overdoses. Because of the potential for drug-drug interactions (e.g., additive CNS depressant effects due to nabilone and chlorpromazine), such patients should be closely monitored.
Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal.
The use of forced diuresis, peritoneal dialysis, hemodialysis, charcoal hemoperfusion or cholestyramine has not been reported. In the presence of normal renal function, most of a dose of nabilone is eliminated through the biliary system.
Treatment for respiratory depression and comatose state consists of symptomatic and supportive therapy. Particular attention should be paid to the occurrence of hypothermia. If the patient becomes hypotensive, consider fluids, inotropes and/or vasopressors.
Dosage: Adults: 1 mg or 2 mg twice a day. The first dose should be given the night before initiating administration of the chemotherapeutic medication. The second dose is usually administered 1 to 3 hours before chemotherapy. If required, administration of nabilone can be continued up to 24 hours after the chemotherapeutic agent is given. The maximum recommended daily dose is 6 mg in divided doses.
Availability And Storage: Each No. 2, opaque, blue and white pulvule, Indenti-Code 3101, contains: nabilone 1 mg. Nonmedicinal ingredients: povidone and starch flowable; capsule shell and printing ink: gelatin, indigo carmine, red iron oxide, sodium lauryl sulfate and titanium dioxide; Colorcon S-1-8159 (antifoam DC 1510, black iron oxide E172, N-butyl alcohol, IMS 74 OP BP, purified water, shellac and soya lecithin) or Tek SW-9008 (ammonium hydroxide, black iron oxide E172, N-butyl alcohol, ethyl alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water and shellac). Bottles of 20.