Nabilone (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- CESAMET
Indications and Usage
Cesamet capsules are indicated for the treatment of the nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. This restriction is required because a substantial proportion of any group of patients treated with Cesamet can be expected to experience disturbing psychotomimetic reactions not observed with other antiemetic agents. Because of its potential to alter the mental state, Cesamet is intended for use under circumstances that permit close supervision of the patient by a responsible individual particularly during initial use of Cesamet and during dose adjustments. Cesamet contains nabilone, which is controlled in Schedule II of the Controlled Substances Act. Schedule II substances have a high potential for abuse. Prescriptions for Cesamet should be limited to the amount necessary for a single cycle of chemotherapy (i.e., a few days). Cesamet capsules are not intended to be used on as needed basis or as a first antiemetic product prescribed for a patient. As with all controlled drugs, prescribers should monitor patients receiving nabilone for signs of excessive use, abuse and misuse. Patients who may be at increased risk for substance abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse) or mental illness.
Dosage and Administration
The usual adult dosage is 1 or 2 mg 2 times a day. On the day of chemotherapy, the initial dose should be given 1 to 3 hours before the chemotherapeutic agent is administered. To minimize side effects, it is recommended that the lower starting dose be used and that the dose be increased as necessary. A dose of 1 or 2 mg the night before may be useful. The maximum recommended daily dose is 6 mg given in divided doses 3 times a day. Cesamet may be administered 2 or 3 times a day during the entire course of each cycle of chemotherapy and, if needed, for 48 hours after the last dose of each cycle of chemotherapy.
Contraindications
Cesamet is contraindicated in any patient who has a history of hypersensitivity to any cannabinoid.
Adverse Reactions
Commonly Encountered Reactions: During controlled clinical trials of Cesamet, virtually all patients experienced at least one adverse reaction. The most commonly encountered events were drowsiness, vertigo, dry mouth, euphoria (feeling “high”), ataxia, headache, and concentration difficulties. Comparative Incidence of Reactions: Accurate estimates of the incidence of adverse events associated with the use of any drug are difficult to obtain. Estimates are influenced by factors such as drug dose, detection technique, setting, and physician judgments, among others. Consequently, the tables presented below are presented solely to indicate the relative frequency of adverse events reported in representative controlled clinical studies conducted to evaluate the safety and efficacy of Cesamet under relatively similar conditions of use. The figures cited cannot be used to predict precisely the incidence of untoward events in the course of usual medical practice, in which patient characteristics and other factors may differ from those that prevailed in the clinical trials. These incidence figures also cannot be compared with those obtained from other clinical studies involving related drug products because each group of drug trials is conducted under a different set of conditions. Finally, it is important to emphasize that these tabulations do not reflect the relative severity and/or clinical importance of the adverse events. A better perspective on the serious adverse events associated with the use of Cesamet is provided in the WARNINGS and PRECAUTIONS sections. The following tables list in order of decreasing frequency the adverse reactions encountered by a substantial proportion of patients treated with Cesamet participating in representative controlled clinical trials. Incidence of Adverse Reactions in Placebo-Controlled Studies Nabilone (n=132) Placebo (n=119) Adverse Event Patients Percent Patients Percent Vertigo 69 52 3 3 Drowsiness 69 52 6 5 Dry Mouth 47 36 2 2 Atax
Drug Interactions
Potential interactions between Cesamet 2 mg, and diazepam 5 mg; sodium secobarbital 100 mg; alcohol 45 mL (absolute laboratory alcohol); or codeine 65 mg, were evaluated in 15 subjects. Only a single combination was utilized at any one time. The subjects were evaluated according to physiologic (i.e., heart rate and blood pressure), psychometric, psychomotor, and subjective parameters. In this study, as expected, the depressant effects of the combinations were additive. Psychomotor function was particularly impaired with concurrent use of diazepam. Caution must thus be used when administering nabilone in combination with any CNS depressant. Nabilone is purportedly highly bound to plasma proteins, and therefore, might displace other protein-bound drugs. Therefore, practitioners should monitor patients for a change in dosage requirements when administering nabilone 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 sympathomimeticagents Additive hypertension, tachycardia, possibly cardiotoxicity Atropine, scopolamine, antihistamines, otheranticholinergic agents Additive or super-additive tachycardia, drowsiness Amitriptyline, amoxapine, desipramine, othertricyclic 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/oman who smoked marijuana; confirmed by dechallenge andrechallenge Fluoxetine A 21 y/o female with depression and bulimia receiving 20mg/day fluoxetine X 4 wks became hypomanic aftersmoking marijuana; symptoms resolved after 4 days Antipyrine, barbiturates Decreased clearance of these agents, presumably viacompetitive inhibition of metabolism Theophyl
Overdosage
Signs and Symptoms—Signs and symptoms of overdosage are an extension of the psychotomimetic and physiologic effects of Cesamet. Treatment—To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient. Overdosage 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. In controlled clinical trials, alterations in mental status related to the use of Cesamet resolved within 72 hours without specific medical therapy. In overdose settings, attention should be paid to vital signs, since both hypertension and hypotension have been known to occur; tachycardia and orthostatic hypotension were most commonly reported. No cases of overdosage with more than 10 mg/day of nabilone were reported during clinical trials. Signs and symptoms that would be expected to occur in large overdose situations are psychotic episodes, including hallucinations, anxiety reactions, respiratory depression, and coma. 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