Nabilone (Monograph)

Brand name: Cesamet
Drug class: Cannabinoids

Medically reviewed by Drugs.com on Aug 10, 2024. Written by ASHP.

Introduction

Antiemetic; a synthetic cannabinoid.

Uses for Nabilone

Cancer Chemotherapy-induced Nausea and Vomiting

Treatment of nausea and vomiting associated with chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.

ASCO does not consider cannabinoids (e.g., nabilone, dronabinol) appropriate first-line antiemetics for patients receiving chemotherapy of low, moderate, or high emetic risk; however, cannabinoids may be used in addition to first-line antiemetic therapies for patients experiencing refractory nausea and vomiting despite optimal therapy. For patients in whom a cannabinoid is chosen for treatment of nausea and vomiting caused by chemotherapy or radiation therapy, ASCO recommends nabilone or dronabinol over medical marijuana.

Nabilone Dosage and Administration

General

Patient Monitoring

Monitor for CNS effects (i.e., dizziness, drowsiness, euphoria, ataxia, anxiety, disorientation, depression, hallucinations, and psychosis), particularly during treatment initiation and dosage adjustments.
Monitor patients for signs of excessive use, abuse, and misuse.
Monitor patients for adverse psychiatric reactions during treatment and for up to 72 hours following discontinuance of the drug.
Monitor patients for development of tachycardia and orthostatic hypotension during treatment.

Administration

Oral Administration

Administer orally without regard to meals.

Dosage

Adults

Chemotherapy-induced Nausea and Vomiting

Oral

Usual dosage: 1 or 2 mg twice daily; administer initial dose 1–3 hours before chemotherapy. May be administered 2 or 3 times daily during entire chemotherapy cycle and, if needed, for 48 hours after last dose of chemotherapy in each cycle.

Initiate with lower dosage (i.e., 1 mg twice daily) to minimize adverse effects, then increase dosage as necessary up to a maximum of 2 mg three times daily.

May administer a dose of 1 or 2 mg the night prior to chemotherapy.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time. Select dosage with caution, usually initiating at the lower end of the recommended dosage range.

Cautions for Nabilone

Contraindications

History of hypersensitivity to any cannabinoid.

Warnings/Precautions

CNS Effects

CNS effects including dizziness, drowsiness or sedation, euphoria (i.e., “high”), ataxia, anxiety, disorientation, depression, hallucinations, and psychosis reported. Adverse psychiatric reactions can persist for 48–72 hours following discontinuance of nabilone.

Individual response and tolerance may vary; a responsible adult should supervise patients, particularly during initial administration and dosage adjustments.

Cardiovascular Effects

May cause tachycardia and orthostatic hypotension. Elevations in supine and standing heart rates also reported.

Carefully evaluate potential risks and benefits of the drug; use with caution in geriatric patients and in patients with hypertension and/or cardiovascular disease.

Psychiatric Disorders

Use with caution in patients with current or history of psychiatric disorders (e.g., bipolar disorder, depression, schizophrenia); cannabinoid use may unmask the symptoms of these diseases.

Abuse Potential

Marijuana contains an active compound similar to nabilone. Use nabilone with caution in patients with history of substance abuse, including alcohol abuse or dependence and marijuana use. Increased risk of substance abuse in patients with personal or family history of substance abuse or mental illness. Monitor patients receiving nabilone for signs of excessive use, abuse, and misuse.

High potential for abuse. Limit prescriptions to quantity necessary for a single cycle of chemotherapy (i.e., a few days); not intended for use on an as-needed basis or as the initial antiemetic therapy.

Specific Populations

Pregnancy

No adequate and well controlled studies in pregnant patients; developmental toxicity observed in animal studies. Use during pregnancy if potential benefit justifies potential risk to fetus.

Lactation

Not known whether nabilone is distributed into human milk. Avoid use in nursing women.

Pediatric Use

Safety and effectiveness not established. Caution is advised because of psychoactive effects.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults. Use with caution because of increased sensitivity to psychoactive effects, risk of elevated supine and standing heart rates, and postural hypotension.

Hepatic Impairment

Not studied in patients with hepatic impairment.

Renal Impairment

Not studied in patients with renal impairment.

Common Adverse Effects

Most frequent adverse effects are drowsiness, vertigo, dry mouth, euphoria.

Drug Interactions

Nabilone is a synthetic cannabinoid; interactions reported with Cannabis sativa L. (marijuana) also may occur with nabilone.

Extensively metabolized by multiple CYP isoenzymes.

Does not substantially inhibit CYP isoenzymes 1A2, 2A6, 2C19, 2D6, and 3A4; weak inhibitor of CYP2E1 and 3A4 isoenzymes and a moderate inhibitor of CYP2C8 and 2C9 isoenzymes.

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interaction with drugs metabolized by CYP isoenzymes unlikely because very low plasma nabilone concentrations are achieved with clinical use.

Protein-bound Drugs

Possible displacement of other protein-bound drugs. Monitor patients and adjust dosages as necessary.

Specific Drugs

Drug	Interaction	Comments
Alcohol	Possible additive drowsiness and CNS depression; increase in the positive subjective mood effects reported with smoked marijuana	Avoid alcohol during therapy
Anticholinergic agents (e.g., antihistamines, atropine, scopolamine)	Possible additive or super-additive anticholinergic effects (e.g., tachycardia, drowsiness)
Antidepressants, tricyclic (e.g., amitriptyline, desipramine)	Possible additive tachycardia, hypertension, or drowsiness
Antipyrine	Possible decreased antipyrine clearance
CNS depressants (e.g., antihistamines, barbiturates, benzodiazepines, buspirone, hypnotics, lithium, muscle relaxants, sedatives)	Possible additive drowsiness and CNS depression Possible decreased barbiturate clearance	Administer with caution
Disulfiram	Reversible hypomanic reaction reported in a disulfiram-treated patient who smoked marijuana
Fluoxetine	Hypomanic reaction reported in a fluoxetine-treated patient after smoking marijuana; symptoms resolved within 4 days
Naltrexone	Possible enhanced effects of oral delta-9-tetrahydrocannabinol observed during opiate receptor blockade
Opiate agonists (e.g., meperidine, methadone, morphine)	Possible additive drowsiness and CNS depression; possible cross-tolerance and potentiation of other pharmacologic effects
Sympathomimetic agents (e.g., amphetamines, cocaine)	Possible additive hypertension, tachycardia, or cardiotoxicity
Theophylline	Increased theophylline metabolism reported with marijuana smoking; similar to that reported following tobacco smoking

Nabilone Pharmacokinetics

Absorption

Bioavailability

Exhibits linear pharmacokinetics across therapeutic dosing range.

Appears to be completely absorbed from the GI tract after oral administration; peak plasma concentrations achieved within 2 hours.

Food

Food does not appear to significantly affect the rate or extent of absorption.

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Metabolism

Extensively metabolized, including metabolism via multiple CYP isoenzymes, to several metabolites; relative pharmacologic activities of the metabolites and the parent drug not established.

Elimination Route

Following IV administration, nabilone and its metabolites are eliminated principally in feces (approximately 67%) and to a lesser extent in urine (approximately 22%) within 7 days.

Following oral administration, about 60% of nabilone and its metabolites were recovered in feces and about 24% in urine. The principal excretory pathway appears to be the biliary system.

No substantial accumulation observed after chronic oral administration, but metabolites may accumulate at concentrations in excess of the parent drug with repeated administration.

Half-life

Metabolite(s) have a terminal elimination half-life exceeding that of nabilone; plasma half-life is about 2 hours for nabilone and 35 hours for metabolites.

Special Populations

Not known whether age, gender, or renal/hepatic impairment impact pharmacokinetics of nabilone.

Stability

Storage

Oral

Capsules

25°C (excursions permitted to 15–30°C).

Actions

Exerts complex effects on CNS.
Antiemetic effect may be caused by interaction with the cannabinoid receptor system, including the cannabinoid 1 (CB₁) receptors in the central and peripheral nervous systems.
Binds to cannabinoid 2 (CB₂) receptors in the spleen and other peripheral tissues, which may play a role in the immunosuppressive effects of cannabinoids.
Like other cannabinoids, may possess analgesic, antispasmodic, and muscle relaxant activity; however, further evaluation is necessary.

Advice to Patients

Advise patients that they should be under the supervision of a responsible adult during nabilone therapy.
Risk of additive or synergistic CNS depression during concurrent use with alcohol or other CNS depressants, including benzodiazepines and barbiturates. Advise patients to avoid alcohol and other CNS depressants during nabilone therapy.
Advise patients to avoid driving, operating machinery, or performing hazardous tasks during nabilone therapy.
Inform patients about possible changes in mood and other adverse behavioral effects of nabilone.
Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.
Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.