Professional Drug Information > Nabilone

Nabilone (Systemic)

VA CLASSIFICATION
Primary: GA609

Note: Controlled substance classification—

Note: Controlled substance classification


Canada—N
Commonly used brand name(s): Cesamet.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

^*Not commercially available in the U.S.

Category:


Antiemetic—

Indications

Accepted

Nausea and vomiting, cancer chemotherapy–induced (prophylaxis)—Nabilone is indicated in selected patients for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy when other antiemetic medications are not effective. ^{{01} {06} {10} {12}}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Synthetic 9-ketocannabinoid ^{01}; resembles the cannabinols but is not a tetrahydrocannabinol ^{17}
Molecular weight—
    372.55 ^{20}

Mechanism of action/Effect:

The exact mechanism of nabilone's antiemetic action is not known. However, animal studies with other cannabinoids suggest it may be due to inhibition of the vomiting control mechanism in the medulla oblongata. ^{{03} {04} {14} {16}}


Other actions/effects:

Central nervous system (CNS) depression and stimulation; may increase supine and standing heart rates (dose-dependent); may inhibit prolactin release. ^{{01} {05} {15}}

Absorption:

Rapidly absorbed from the gastrointestinal tract after oral administration. ^{01}

Biotransformation:

Hepatic. ^{01}

Half-life:


Elimination:


Terminal phase—

Nabilone—2 hours.

Other metabolites—35 hours. ^{{01} {09}}



Time to peak concentration:

2 hours. ^{01}

Elimination:
    Primarily fecal (biliary); approximately 65% of an oral dose appears in the feces and 20% in the urine. ^{{01} {09}}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other marijuana products may be sensitive to this preparation also. ^{{01} {22}}

Carcinogenicity

Studies to evaluate the carcinogenic potential of nabilone have not been performed. ^{01}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. ^{{01} {22}}

Studies in rats and rabbits at doses 150 and 40 times, respectively, the usual human adult dose have shown that nabilone decreases litter size and increases the incidence of fetal resorptions and stillborn pups. ^{01}

Breast-feeding

It is not known whether nabilone is distributed into breast milk. However, use of nabilone in nursing mothers is not recommended since dronabinol, another synthetic cannabinoid closely related to nabilone, is concentrated and distributed into breast milk. ^{{01} {21}}

Pediatrics

Appropriate studies on the relationship of age to the effects of nabilone have not been performed in children up to 18 years of age. Safety and efficacy have not been established. ^{{01} {22}}


Geriatrics


Although appropriate studies on the relationship of age to the effects of nabilone have not been performed in the geriatric population, the elderly may be more sensitive to the cardiac effects and orthostatic hypotension produced by nabilone. ^{{01} {11} {22}}

Also, because of this medication's psychoactive effects and potential for dependence and withdrawal effects ^{19}, therapy could be more troublesome in the elderly and should be used with caution, after less toxic alternatives have been considered and found ineffective. Recommended doses should not be exceeded, and the elderly patient should be carefully monitored during therapy. ^{03}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Alcohol or
» CNS depression–producing medications, other (see Appendix II )    (concurrent use may potentiate the CNS-depressant effects of either these medications or nabilone ^{{01} {22}})


Apomorphine    (prior administration of nabilone may decrease the emetic response to apomorphine; also, concurrent use may potentiate the CNS-depressant effects of either apomorphine or nabilone ^{03})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Cardiac disorders^{22}    (nabilone may elevate supine and standing heart rates)


Drug abuse or dependence, history of, including active or treated alcoholism^{03}    (increased risk of nabilone abuse and dependence)


Emotional disorders, nonpsychotic^{22}    (symptoms may be exacerbated)


Hepatic function impairment, severe^{02}{22}    (increased risk of toxic effects because of decreased metabolism of nabilone)


Hypotension^{22}    (hypotensive effects of nabilone may further decrease blood pressure)


» Manic or depressive states or
» Psychotic reactions, history of or
» Schizophrenia    (symptoms may be exacerbated ^{{01} {22}})


Sensitivity to nabilone or other marijuana products^{01}{22}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood pressure determinations and
Cardiac function monitoring    (recommended for early detection of tachycardia and changes in blood pressure, especially in patients with hypotension or cardiac disease ^{03})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
    
Asthenia^{22} (unusual tiredness or weakness, severe)
    
hypotension^{22} ( dizziness or fainting)
    
psychiatric effects^{22} (changes in mood; confusion; delusions; hallucinations; mental depression; nervousness or anxiety)
    
seizures
    
tachycardia^{22} (fast or pounding heartbeat)

Note: Psychiatric effects usually resolve by themselves within 48 to 72 hours after discontinuation of nabilone. ^{{01} {22}}




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Ataxia^{{22} {22}} (clumsiness or unsteadiness)
    
dizziness^{22}
    
drowsiness^{22}
    
dryness of mouth^{22}
    
euphoria^{22} (false sense of well-being)
    
headache^{22}

Incidence less frequent or rare
    
Anorexia^{22} (loss of appetite)
    
blurred vision or any changes in vision^{22}
    
orthostatic hypotension^{22} (dizziness or lightheadedness, especially when getting up from a lying or sitting position)—more frequent with high doses





Overdose

Note: Overdose may occur either with therapeutic doses or at higher, non-therapeutic doses.

For specific information on the agents used in the management of nabilone overdose, see:    • Charcoal, Activated (Oral-Local) monograph.


For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects ^{{01} {05} {06} {07} {08} {14} {16}} have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)–not necessarily inclusive:
    
Severe anxiety reactions^{22} (severe nervousness or anxiety)
    
coma^{22}
    
psychotic episodes^{22} (severe mental changes; hallucinations [seeing, hearing, or feeling things that are not there])
    
respiratory depression^{22} (difficulty in breathing)


Treatment of overdose
To decrease absorption—Activated charcoal may decrease absorption from the gastrointestinal tract; may be used instead of or in addition to induction of emesis or gastric lavage ^{22}.

Specific treatment—Observation of patient in a quiet environment. Verbal support and comforting if psychotic episodes occur; in severe cases, antipsychotic drugs may be used with careful attention being paid to possible additive CNS-depressant effects. Treatment of hypertension or hypotension, if necessary. ^{{01} {22}}

Monitoring—Continuous blood pressure monitoring ^{01}; cardiac monitoring ^{01}; monitoring of (and maintenance of) vital signs, blood gases, and serum electrolytes; observing for hypothermia.

Supportive care—Supportive therapy. ^{{01} {22}} Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Nabilone (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to nabilone or other marijuana products

Pregnancy—No studies have been done in humans; fetal resorptions and stillbirths were seen in animal studies with doses many times the usual human dose





Breast-feeding—Use not recommended; although not known if distributed into breast milk, potential for serious adverse effects in nursing infant





Use in the elderly—Increased sensitivity to cardiac effects and orthostatic hypotension; caution recommended because of psychoactive effects and potential for dependence and withdrawal symptoms
Other medications, especially alcohol and CNS depressants
Other medical problems, especially manic or depressive states, history of psychotic reactions, and schizophrenia

Proper use of this medication
» Importance of not taking more medication than the amount prescribed because of danger of overdose

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
» Avoiding use of alcohol or other CNS depressants during therapy

» Suspected overdose: Getting emergency help at once

» Caution if dizziness, drowsiness, lightheadedness, or false sense of well-being occurs

Caution when getting up suddenly from a lying or sitting position

Possible dryness of mouth; using sugarless candy or gum, ice, or saliva substitute for relief


Side/adverse effects
Signs of potential side effects, especially asthenia, hypotension, psychiatric effects, seizures, and tachycardia


General Dosing Information
Amount of nabilone dispensed should be limited to the amount necessary for a single cycle of chemotherapy. ^{03}

Patients on nabilone therapy should be closely observed, if possible within an inpatient setting. Since response and tolerance to the effects of nabilone vary with each patient, the period of patient supervision required should be determined by the physician on an individual basis. ^{{03} {13}}

Adequate and well-controlled studies have not been done to determine whether psychological and physical dependence will develop with chronic administration of nabilone. However, like other similar cannabinoids, nabilone has a high potential for abuse and for production of psychological dependence. ^{01}


Oral Dosage Forms

NABILONE CAPSULES

Usual adult and adolescent dose
Antiemetic
Oral, 1 or 2 mg two times a day. A dose of 1 or 2 mg may be given the night before chemotherapy is initiated. On the day of chemotherapy, the initial dose of nabilone should be given one to three hours before the chemotherapeutic agent. The dose of nabilone may be administered two or three times a day during the course of chemotherapy and, if needed, for forty-eight hours after the last dose of the chemotherapeutic cycle. ^{{01} {02} {22}}


Note: The lower starting dose should be used to minimize side effects. Dosage may be increased as necessary if side effects are not significant. ^{01}


Usual adult prescribing limits
6 mg daily, in divided doses three times a day. ^{{01} {22}}

Usual pediatric dose
Safety and efficacy have not been established. ^{01}

Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


1 mg (Rx) [Cesamet]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. ^{01}

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.

Note: Controlled substance in Canada.

Revised: 01/29/1999

References

1. Package inserts for Cesamet.
   

2. CPS 1987: 148.
   

3. Reviewers' consensus, 1993.
   

4. Medical Sciences Bulletin 1986 Jun; 8(10).
   

5. Lemberger L. Commentary. From ``grass'' roots to clinical utility. Clin Pharmacol Ther 1986 Jan; 39(1): 1-4.
   

6. Lemberger L, Rowe H. Clinical pharmacology of nabilone, a cannabinol derivative. Clin Pharmacol Ther 1975 Dec; 18(6): 720-6.
   

7. Herman TS, Einhorn LH, Jone SE, et al. N Engl J Med 1979 Jun 7; 300(23): 1295-7.
   

8. Herman TS, Jones SE, Dean J, et al. Nabilone: a potent antiemetic cannabinol with minimal euphoria. Biomedicine 1977 Dec; 27(9-10): 331-4.
   

9. Rubin A, Lemberger L, Warrick P, et al. Physiologic disposition of nabilone, a cannabinol derivative, in man. Clin Pharmacol Ther 1977 Jul; 22(1): 85-91.
   

10. Steele N, Gralla RJ, Braun DW Jr, et al. Double-blind comparison of the antiemetic effects of nabilone and prochlorperazine on chemotherapy-induced emesis. Cancer Treat Rep 1980 Feb-Mar; 64(2-3): 219-24.
    

11. Niiranen A, Mattson K. Antiemetic efficacy of nabilone and dexamethasone: a randomized study of patients with lung cancer receiving chemotherapy. Am J Clin Oncol 1987 Aug; 10(4): 325-9.
    

12. Pomeroy M, Fennelly JJ, Towers M. Prospective randomized double-blind trial of nabilone versus domperidone in the treatment of cytotoxic-induced emesis. Cancer Chemother Pharmacol 1986; 17(3): 285-8.
    

13. Niiranen A, Mattson K. A cross-over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy. Am J Clin Oncol 1985 Aug; 8(4): 336-40.
    

14. Ward A, Holmes B. Nabilone: a preliminary review of its pharmacological properties and therapeutic use. Drugs 1985 Aug; 30(2): 127-44.
    

15. Kumar S, Mansel RE. Prolactin and antiemetics for adjuvant chemotherapy of breast cancer. Br Med J 1984 Mar 10; 228: 760.
    

16. London SW, McCarthy LE, Borison HL. Suppression of cancer chemotherapy-induced vomiting in the cat by nabilone, a synthetic cannabinoid. Proc Soc Exp Biol Med 1979; 160: 437-40.
    

17. Newell FW, Stark P, Jay WM, Schanzlin DJ. Nabilone: a pressure-reducing synthetic benzopyran in open-angle glaucoma. Ophthalmology 1979 Jan; 86(1): 156-60.
    

18. Rubin A, Lemberger L, Warrick P, Crabtree RE, Sullivan H, Rowe H, et al. Physiologic disposition of nabilone, a cannabinol derivative, in man. Clin Pharmacol Ther 1977; 22(1): 85-91.
    

19. Reviewer comment, 6/28/93.
    

20. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 492-3.
    

21. Dronabinol package insert (Marinol, Roxane—US), Rev 12/92, Rec 1/21/93.
    

22. Cesamet product monograph. In: Gillis MC, Editor. CPS Compendium of pharmaceuticals and specialities. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 303.
    

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