Download nabilone - Valeant

DRUGDEX® Evaluations
NABILONE
0.0 Overview
1) Class
a) This drug is a member of the following class(es):
Antiemetic
Cannabinoid
2) Dosing Information
a) Adult
1) Chemotherapy-induced nausea and vomiting, in patients who fail to respond adequately to other antiemetic agents
a) 1 to 2 mg ORALLY twice daily; first dose should be given 1 to 3 hours before chemotherapy; start with 1 mg to minimize side effects
and increase dose as necessary; may also be helpful to administer 1 or 2 mg the night prior to chemotherapy; may be administered 2 or
3 times daily during the entire course of each cycle of chemotherapy; if required, continue up to 48 hours after the last dose of
[1]
chemotherapy; MAX 6 mg a day in 3 divided doses
b) Pediatric
[1]
1) safety and efficacy not established in children younger than 18 years of age
3) Contraindications
[1]
a) hypersensitivity to marijuana or other cannabinoids
4) Serious Adverse Effects
a) Psychotic disorder
5) Clinical Applications
a) FDA Approved Indications
1) Chemotherapy-induced nausea and vomiting, in patients who fail to respond adequately to other antiemetic agents
1.0 Dosing Information
Drug Properties
Storage and Stability
Adult Dosage
Pediatric Dosage
1.1 Drug Properties
A) Information on specific products and dosage forms can be obtained by referring to the Tradename List (Product Index)
B) Synonyms
Nabilone
C) Physicochemical Properties
1) Molecular Weight
[1]
a) 372.55
2) Solubility
[1]
a) In an aqeuous media at a pH range of 1.2 to 7, the solubility of nabilone is less than 0.5 mg/L .
1.2 Storage and Stability
A) Oral route
1) Capsule
a) Store at 25 degrees Celsius (77 degrees Fahrenheit); excursions permitted between 15 and 30 degrees Celsius (59 and 86 degrees
[1]
Fahrenheit) .
1.3 Adult Dosage
Normal Dosage
Dosage in Geriatric Patients
1.3.1 Normal Dosage
Important Note
Intravenous route
Oral route
Chemotherapy-induced nausea and vomiting; Treatment and Prophylaxis
1.3.1.A Important Note
Due to the high potential of altered mental state with use of nabilone, use under close supervision of the patient by a responsible
[1]
individual particularly during initial use of nabilone and during dose adjustments .
1.3.1.B Intravenous route
1.3.1.B.1 Anxiety
a) Nabilone has been given by the intravenous route (0.5 milligram) for the management of anxiety
[4]
.
1.3.1.C Oral route
Anxiety
Chemotherapy-induced nausea and vomiting, in patients who fail to respond adequately to other antiemetic agents
1.3.1.C.1 Anxiety
a) Two to 8 milligrams orally daily have been shown to be superior to placebo
[2][3]
.
1.3.1.C.2 Chemotherapy-induced nausea and vomiting, in patients who fail to respond adequately to other antiemetic agents
a) The usual recommended dose of nabilone is 1 to 2 milligrams (mg) orally twice daily. The first dose should be given 1 to 3 hours
before chemotherapy. Start with the lower dose (1 mg) to minimize side effects and increase the dose as necessary. It may also be
helpful to administer a dose of 1 or 2 milligrams the night prior to chemotherapy. Nabilone may be administered 2 or 3 times daily
during the entire course of each cycle of chemotherapy. If required, nabilone can be continued up to 48 hours after the last dose of
[1]
chemotherapy. The maximum recommended dose is 6 mg a day in three divided doses .
1.3.1.D Chemotherapy-induced nausea and vomiting; Treatment and Prophylaxis
See Drug Consult reference: CHEMOTHERAPY AND RADIOTHERAPY TREATMENT GUIDELINES FOR NAUSEA AND VOMITING
1.3.4 Dosage in Geriatric Patients
A) Start at the low end of the dosing range in elderly subjects due to a greater likelihood of decreased hepatic, renal, or cardiac
[1]
function, and of concomitant disease or other drug therapy .
1.4 Pediatric Dosage
1.4.1 Normal Dosage
Important Note
Oral route
1.4.1.A Important Note
Due to the high potential of altered mental state with use of nabilone, use under close supervision of the patient by a responsible
[1]
individual particularly during initial use of nabilone and during dose adjustments .
1.4.1.B Oral route
1.4.1.B.1 Chemotherapy-induced nausea and vomiting, in patients who fail to respond adequately to other antiemetic agents
a) SUMMARY
1) Safety and efficacy not established in children younger than 18 years of age. Psychoactive effects are a concern when using
[1]
nabilone in children .
b) The following dosages, based on body weight, were used in 30 children (3.5 to 17.8 years of age) receiving emetogenic
[14]
chemotherapy other than cisplatin : a) less than 18 kilograms, 0.5 milligram orally twice daily; b) 18 to 30 kilograms, 1 milligram orally
twice daily; c) greater than 30 kilograms, 1 milligram orally 3 times daily.
c) Similar doses of nabilone were used in 23 children aged 10 months to 17 years receiving a variety of emetogenic chemotherapy
regimens, some including cisplatin. Children less than 18 kilograms received 0.5 milligram orally twice daily, 18 to 36 kilograms
[15]
received 1 milligram orally twice daily, and greater than 36 kilograms received 1 milligram orally 3 times daily .
2.0 Pharmacokinetics
Onset and Duration
Drug Concentration Levels
ADME
2.1 Onset and Duration
A) Onset
1) Initial Response
[37]
a) Emesis, oral: 60 to 90 minutes .
B) Duration
1) Single Dose
[38]
Emesis, oral: 8 to 12 hours .1) The long duration of action of the drug, and the rapid metabolism of the parent compound in the body,
[39]
suggest that the pharmacologic effects are at least partially due to 1 or more active metabolites .
2.2 Drug Concentration Levels
A) Time to Peak Concentration
[1]
Oral, capsule: 2 hours .a) Following an oral dose of nabilone 2 mg, peak serum levels of 2 nanograms/mL are achieved
2.3 ADME
Absorption
Distribution
Metabolism
Excretion
Elimination Half-life
2.3.1 Absorption
A) Bioavailability
[1][39]
[1]
Oral, capsule: 95.6% to 100%
.a) Oral nabilone is completely absorbed . Site of absorption is the small intestine
[39]
b) Following oral administration as a polyvinyl pyrrolidone, the drug was readily absorbed .
B) Effects of Food
[1]
[1]
No affect on systemic availability .a) Neither the rate nor the extent of absorption is affected by food .
2.3.2 Distribution
A) Distribution Sites
[38]
.
[1]
.
1) OTHER DISTRIBUTION SITES
[39]
[39]
TISSUES, extensive .1) Extensive and rapid tissue distribution and rapid metabolism occurs .
B) Distribution Kinetics
1) Volume of Distribution
[1]
[1]
12.5 L/kg 1) The volume of distribution for nabilone is 12.5 L/kg .
2.3.3 Metabolism
A) Metabolism Sites and Kinetics
[1]
LIVER, extensive .a) There are numerous metabolic pathways with extensive metabolism via the cytochrome P450 isoenzymes.
Nabilone is unlikely to interfere with the CYP450 isoenzyme degradation of other drugs, despite in vitro data demonstrating a weak
inhibitory effect on CYP2E1 and 3A4 and a moderate inhibitory effect on CYP2C8 and 2C9. In vitro data demonstrate no inhibition of
[1]
CYP1A2, 2A6, 2C19, 2D6, and 3A4 .
b) Two major enzymatic pathways has been identified: direct enzymatic oxidation and stereo-specific reduction. Direct enzymatic
[40]
oxidation appears to be more important in man .
[39]
c) Rapidly metabolized to 1 or more active metabolites .
B) Metabolites
[1][39]
[1][39]
Isomeric carbinols, active
.a) Circulating metabolites include isomeric carbinols formed by ketone reduction in the 9-position
.
[1]
Diol a) A metabolite, found in the feces, identified as a diol formed by ketone reduction in the 9-position plus oxidation at the
[1]
penultimate carbon of the diemethylheptyl side chain .
2.3.4 Excretion
A) Kidney
1) Renal Excretion (%)
[1][40][39]
[1]
20% to 24%
.1) After an oral dose of nabilone, 24% of nabilone and its metabolites are excreted in the urine .
B) Other
1) OTHER EXCRETION
[1][40][39]
FECES, 60% to 65%
.1) After an oral dose of nabilone, 60% of nabilone and its metabolites are excreted in the feces. Major
[1][40]
excretory pathway is the bile
.
2.3.5 Elimination Half-life
A) Parent Compound
[1][40][39]
[1]
2 hours
.a) The half-life is 2 hours for nabilone .
B) Metabolites
[1][40]
1) Metabolites, 35 hours
.
3.0 Cautions
Contraindications
Precautions
Adverse Reactions
Teratogenicity/Effects in Pregnancy/Breastfeeding
3.1 Contraindications
A) hypersensitivity to marijuana or other cannabinoids
[1]
3.2 Precautions
[1]
A) central nervous system effects can occur; may be persistent (up to 72 hours) and unpredictable
B) concomitant use of central nervous system depressants or other psychoactive drugs; additive or synergistic effects may occur
[1]
C) elderly patients; increased risk of postural hypotension
[1]
D) heart disease; increased risk of postural hypotension
[1]
E) hepatic dysfunction
[1]
F) hypertension; increased risk of postural hypotension
[1]
G) orthostatic hypotension may occur
H) potential for abuse or dependence; prescriptions should be limited to the smallest amount needed for a single course of
[1]
chemotherapy
I) psychiatric disorders, current or history; use may unmask symptoms of disorders such as manic depression, depression, and
[1]
schizophrenia
[1]
J) substance abuse, history
[1]
K) tachycardia may occur
[1]
3.3 Adverse Reactions
Cardiovascular Effects
Gastrointestinal Effects
Neurologic Effects
Ophthalmic Effects
Psychiatric Effects
Respiratory Effects
Other
3.3.1 Cardiovascular Effects
Hypotension
Orthostatic hypotension
Tachyarrhythmia
3.3.1.A Hypotension
1) Incidence: 8%
Hypotension occurred more frequently in nabilone-treated patients than prochlorperazine-treated patients during controlled clinical
[1]
trials .
Active-Controlled Studies
Adverse Event Nabilone (n=250) Prochlorperazine (n=232)
Hypotension 8%
1%
3.3.1.B Orthostatic hypotension
1) Incidence: 5% to 42%
2) Nabilone may cause postural hypotension and therefore should be used with caution in the elderly and in patients with hypertension
[1]
or heart disease . Postural hypotension is one of the most troublesome side effects seen with nabilone therapy and has been
[26][27][28][29]
reported to occur in 5% to 42% of patients
.
[27]
3) Postural hypotension was reported in 16.9% of 53 patients receiving nabilone 2 mg every 12 hours .
4) Orthostatic hypotension appeared about 2 hours after nabilone ingestion and remained prominent until 6 hours post ingestion when
[30]
monitoring was discontinued .
[31]
5) The orthostatic effect seen with nabilone becomes less marked upon repeat administration .
3.3.1.C Tachyarrhythmia
[1]
1) Nabilone can cause tachycardia .
3.3.4 Gastrointestinal Effects
Loss of appetite
Xerostomia
3.3.4.A Loss of appetite
1) Incidence: 8%
Anorexia occurred in nabilone-treated patients and prochlorperazine-treated patients at approximately the same frequency during
[1]
controlled clinical trials .
Active-Controlled Studies
Adverse Event Nabilone (n=250) Prochlorperazine (n=232)
Anorexia
8%
9%
3.3.4.B Xerostomia
1) Incidence: 22% to 36%
Dry mouth occurred more frequently in nabilone-treated patients than placebo and prochlorperazine-treated patients during controlled
[1]
clinical trials .
Placebo-Controlled Studies
Adverse Event Nabilone (n=132) Placebo (n=119)
Dry mouth
36%
2%
Active-Controlled Studies
Adverse Event Nabilone (n=250) Prochlorperazine (n=232)
Dry mouth
22%
5%
[32]
3) Accumulated data from 436 patients who received nabilone indicate dry mouth occurred in 29% .
3.3.9 Neurologic Effects
Asthenia
Ataxia
Dizziness
Dyssomnia
Headache
Insomnia
Paresthesia
Poor concentration
Somnolence
Vertigo
3.3.9.A Asthenia
1) Incidence: 8%
Asthenia occurred more frequently in nabilone-treated patients than prochlorperazine-treated patients during controlled clinical trials
Active-Controlled Studies
Adverse Event Nabilone (n=250) Prochlorperazine (n=232)
Asthenia
8%
4%
3.3.9.B Ataxia
1) Incidence: 13% to 14%
Ataxia occurred more frequently in nabilone-treated patients than placebo and prochlorperazine-treated patients during controlled
[1]
clinical trials .
[1]
.
Placebo-Controlled Studies
Adverse Event Nabilone (n=132) Placebo (n=119)
Ataxia
14%
0%
Active-Controlled Studies
Adverse Event Nabilone (n=250) Prochlorperazine (n=232)
Ataxia
13%
2%
3.3.9.C Dizziness
1) A 36% incidence of dizziness among 53 patients receiving nabilone 2 mg every 12 hours was reported. Four patients withdrew from
the study after the first 2-mg dose because of intolerable adverse effects. These included severe dizziness, decreased ability to
[27]
concentrate, lack of coordination and dysphoria .
[29]
2) DIZZINESS has been reported in many of the patients receiving nabilone .
3.3.9.D Dyssomnia
1) Incidence: 11%
Sleep disturbance occurred more frequently in nabilone-treated patients than placebo-treated patients during controlled clinical trials
Placebo-Controlled Studies
Nabilone (n=132) Placebo (n=119)
Adverse Event
Sleep disturbance 11%
1%
[1]
.
3.3.9.E Headache
1) Incidence: 6% to 7%
Headache occurred more frequently in nabilone-treated patients than placebo and prochlorperazine-treated patients during controlled
[1]
clinical trials .
Placebo-Controlled Studies
Adverse Event Nabilone (n=132) Placebo (n=119)
Headache
6%
0%
Active-Controlled Studies
Adverse Event Nabilone (n=250) Prochlorperazine (n=232)
Headache
7%
6%
3.3.9.F Insomnia
[33]
1) A side effect reported less frequently in patients receiving nabilone 1 mg three times a day include insomnia .
3.3.9.G Paresthesia
1) A side effect reported less frequently in patients receiving nabilone 1 mg three times a day include tingling in the toes
[33]
.
3.3.9.H Poor concentration
1) Incidence: 12%
Concentration difficulties occurred more frequently in nabilone-treated patients than prochlorperazine-treated patients during controlled
[1]
clinical trials .
Active-Controlled Studies
Nabilone (n=250) Prochlorperazine (n=232)
Adverse Event
Concentration difficulties 12%
1%
3.3.9.I Somnolence
1) Incidence: 52% to 66%
Drowsiness occurred more frequently in nabilone-treated patients than placebo and prochlorperazine-treated patients during controlled
clinical trials. Concomitant use of nabilone with alcohol or other drugs with central nervous system effects may exacerbate the
[1]
drowsiness. Tolerance to drowsiness develops rapidly and is readily reversible .
Placebo-Controlled Studies
Adverse Event Nabilone (n=132) Placebo (n=119)
Drowsiness 52%
5%
Active-Controlled Studies
Adverse Event Nabilone (n=250) Prochlorperazine (n=232)
Drowsiness 66%
47%
[32]
3) Accumulated data from 436 patients who received nabilone indicate that 65% of patients experienced drowsiness .
4) A 47% incidence of DROWSINESS and 36% incidence of dizziness was reported among 53 patients receiving nabilone 2 mg every
12 hours. Four patients withdrew from the study after the first 2-mg dose because of intolerable adverse effects. These included severe
[27]
dizziness, decreased ability to concentrate, lack of coordination and dysphoria .
3.3.9.J Vertigo
1) Incidence: 52% to 59%
Vertigo occurred more frequently in nabilone-treated patients than placebo and prochlorperazine-treated patients during controlled
[1]
clinical trials .
Placebo-Controlled Studies
Adverse Event Nabilone (n=132) Placebo (n=119)
Vertigo
52%
3%
Active-Controlled Studies
Adverse Event Nabilone (n=250) Prochlorperazine (n=232)
Vertigo
59%
23%
[32]
3) Accumulated data from 436 patients who received nabilone indicate that 65% of patients experienced vertigo .
3.3.10 Ophthalmic Effects
3.3.10.A Visual disturbance
1) Incidence: 13%
Visual disturbance occurred more frequently in nabilone-treated patients than prochlorperazine-treated patients during controlled
[1]
clinical trials .
Active-Controlled Studies
Nabilone (n=250) Prochlorperazine (n=232)
Adverse Event
Visual disturbance 13%
4%
3.3.12 Psychiatric Effects
Anxiety
Delusional disorder
Depersonalization
Depression
Derealization
Dysphoric mood
Hallucinations
Impaired cognition
Impulse control disorder
Memory impairment
Panic
Psychotic disorder
3.3.12.A Anxiety
1) Anxiety may occur, especially with larger doses of nabilone. Tolerance develops rapidly and is readily reversible
[1]
3.3.12.B Delusional disorder
1) Paranoia may occur, especially with larger doses of nabilone. Tolerance develops rapidly and is readily reversible
[1]
3.3.12.C Depersonalization
1) Incidence: 2%
2) Depersonalization occurred in 2% of patients treated nabilone compared with 1% of placebo-treated patients. Effect appear to be
[1]
more common when larger doses are utilized. Tolerance develops rapidly and is readily reversible .
3.3.12.D Depression
1) Incidence: 14%
Depression occurred more frequently in prochlorperazine-treated patients than nabilone-treated patients during controlled clinical trials
[1]
.
Active-Controlled Studies
Adverse Event Nabilone (n=250) Prochlorperazine (n=232)
Depression
14%
16%
3.3.12.E Derealization
1) Alterations in the experience of reality (distortions in the perception of objects and the sense of time) may occur, especially with
[1]
larger doses of nabilone. Tolerance develops rapidly and is readily reversible
3.3.12.F Dysphoric mood
1) Incidence: 9%
Dysphoria occurred more frequently in nabilone-treated patients than placebo-treated patients during controlled clinical trials
Placebo-Controlled Studies
Adverse Event Nabilone (n=132) Placebo (n=119)
Dysphoria
9%
0%
3.3.12.G Hallucinations
1) Hallucinations may occur, especially with larger doses of nabilone. Tolerance develops rapidly and is readily reversible
[1]
.
[1]
3.3.12.H Impaired cognition
1) Decrements in cognitive performance may occur, especially with larger doses of nabilone. Tolerance develops rapidly and is readily
[1]
reversible
3.3.12.I Impulse control disorder
1) A decreased ability to control drives and impulses may occur, especially with larger doses of nabilone. Tolerance develops rapidly
[1]
and is readily reversible
3.3.12.J Memory impairment
1) Decrements in memory may occur, especially with larger doses of nabilone. Tolerance develops rapidly and is readily reversible
3.3.12.K Panic
1) Panic may occur, especially with larger doses of nabilone. Tolerance develops rapidly and is readily reversible
[1]
3.3.12.L Psychotic disorder
1) Psychosis (psychotic organic brain syndrome) may occur, even at doses at the lower end of the therapeutic range. Tolerance to
[1]
psychosis develops rapidly and is readily reversible .
3.3.15 Respiratory Effects
[1]
3.3.15.A Summary
1) In a comparative study, nabilone 2 mg, terbutaline 5 mg and placebo were administered to six stable asthmatics and six volunteers.
No significant changes in respiratory rate, forced vital capacity or forced expiratory volume was demonstrated with either drug in healthy
subjects. Specific airways conductance was increased with both terbutaline and to a lesser extent nabilone as compared to placebo. In
the asthmatic subjects, only terbutaline produced significant increases in forced vital capacity (FVC), forced expiratory volume (FEV) or
[34]
specific airway conductance .
3.3.16 Other
Summary
Drug tolerance - finding
Euphoria
3.3.16.A Summary
1) Due to similar qualitative and quantitative cannabis-like effects with delta-9-tetrahydrocannabinol (THC) (marijuana), nabilone has
potential for abuse. No patients experienced withdrawal symptoms after stopping nabilone during clinical trials of up to 5 days'
duration. The frequency of psychological or physical dependence of individuals exposed chronically to nabilone is unknown. Disorders
of motivation, judgment, and cognition has been associated with long term use to delta-9-THC compounds. However, it is unknown if
these effects are due to a manifestation of the underlying personalities of chronic users of this class of drugs or if it is a direct effect of
cannabinoids. Patients at a possible risk for substance abuse include those with a personal or family history of substance abuse
[1]
(including drug or alcohol abuse) or mental illness . Tolerance to adverse but not therapeutic effects occurred in a single-blind study
[31]
.
3.3.16.B Drug tolerance - finding
1) Tolerance to adverse but not therapeutic effects occurred in a single-blind study. Repeated administration of 1 to 2 mg twice a day
resulted in adverse symptoms which varied with dose, during the first 2 days. These effects decreased until they were virtually absent
at 6 and 7 days. There was not a concomitant reduction in degree of relaxation. These results were confirmed when patients were
challenged with single doses of nabilone 5 mg. There was a much reduced incidence of adverse effects compared with patients who
[31]
had received placebo .
3.3.16.C Euphoria
1) Incidence: 11% to 38%
Euphoria occurred more frequently in nabilone-treated patients than placebo and prochlorperazine-treated patients during controlled
clinical trials. Due to similar qualitative and quantitative cannabis-like effects with delta-9-tetrahydrocannabinol (THC) (marijuana),
nabilone has potential for abuse. The euphoria or marijuana-like "high" occurs at therapeutic doses. Tolerance to euphoria develops
[1]
rapidly and is readily reversible .
Placebo-Controlled Studies
Adverse Event Nabilone (n=132) Placebo (n=119)
Euphoria
11%
1%
Active-Controlled Studies
Adverse Event Nabilone (n=250) Prochlorperazine (n=232)
Euphoria
38%
5%
3) Like delta-9-tetrahydrocannabinol, nabilone has been shown to have abuse potential of the cannabis-type (producing euphoria or a
[35]
"high"). Although one study
demonstrated intravenous (0.25 mg) and oral (2 mg) nabilone produced a lower degree of "high" than
intravenous (2.2 mg) and oral (17.5 mg) delta-9-tetrahydrocannabinol according to the Cornell Medical Index rating. Nabilone 2, 4 and
8 mg and delta-9-tetrahydrocannabinol 5, 10 and 20 mg produced similar dose-related increases in symptoms such as euphoria,
sedation and liking the drug. It has also been reported that nabilone is 7 times more potent on a weight for weight basis than is delta-9[36]
tetrahydrocannabinol .
[32]
4) Accumulated data from 436 patients who received nabilone indicate that 27% of patients reported a "high" .
3.4 Teratogenicity/Effects in Pregnancy/Breastfeeding
A) Teratogenicity/Effects in Pregnancy
1) U.S. Food and Drug Administration's Pregnancy Category: Category C (All Trimesters)
a) Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no
controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit
justifies the potential risk to the fetus.
See Drug Consult reference: PREGNANCY RISK CATEGORIES
2) Crosses Placenta: Unknown
3) Clinical Management
a) There is no data on the use of nabilone in pregnant women. The effects, if any, on the developing fetus are unknown. Until more
information is available, nabilone should only be used during pregnancy if the maternal condition justifies the potential risk to the fetus.
4) Literature Reports
a) No studies examining the use of nabilone during human pregnancy are available at this time. Studies conducted in rats and rabbits
using doses 16 and 9 times the human dose, respectively, based on body surface area did not reveal evidence for teratogenicity with
nabilone. However, maternal toxicity was demonstrated (increases in embryo lethality, fetal resorptions, decreased fetal weights, and
[1]
pregnancy disruptions). Postnatal developmental toxicity was observed in rats .
B) Breastfeeding
1) Thomson Lactation Rating: Infant risk cannot be ruled out.
a) Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during
breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during breastfeeding.
2) Clinical Management
a) No reports describing the use of nabilone during human lactation are available and the effects on the nursing infant from exposure
to the drug in milk are unknown. It is not known if nabilone affects the quantity and composition of breastmilk. Because some
cannabinoids are excreted into breastmilk, the use of nabilone is not recommended in women who choose to breastfeed their infants
[1]
.
3) Literature Reports
a) No reports describing the use of nabilone during human lactation or measuring the amount, if any, of the drug excreted into milk
[1]
have been located .
4.0 Clinical Applications
Monitoring Parameters
Patient Instructions
Place In Therapy
Mechanism of Action / Pharmacology
Therapeutic Uses
Comparative Efficacy / Evaluation With Other Therapies
4.1 Monitoring Parameters
A) Toxic
1) Physical Findings
a) Monitor for signs of excessive use, abuse, and misuse. Those with a personal or family history of substance abuse (including drug
[1]
or alcohol abuse) or mental illness are at greatest risk .
4.2 Patient Instructions
A) Nabilone (By mouth)
Nabilone
Treats or prevents nausea and vomiting caused by cancer medicines. This medicine is used when other medicines for nausea and
vomiting do not work.
When This Medicine Should Not Be Used:
You should not use this medicine if you have had an allergic reaction to nabilone or any marijuana products.
How to Use This Medicine:
Capsule
Your doctor will tell you how much of this medicine to use and how often. Do not use more medicine or use it more often than your
doctor tells you to.
You may take this medicine with or without food.
If a Dose is Missed:
If you miss a dose or forget to use your medicine, use it as soon as you can. If it is almost time for your next dose, wait until then to use
the medicine and skip the missed dose. Do not use extra medicine to make up for a missed dose.
How to Store and Dispose of This Medicine:
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light.
Ask your pharmacist, doctor, or health caregiver about the best way to dispose of any leftover medicine after you have finished your
treatment. You will also need to throw away old medicine after the expiration date has passed.
Keep all medicine away from children and never share your medicine with anyone.
Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.
Make sure your doctor knows if you are using stimulants (such as amphetamines or cocaine) or anticholinergic medicines (such as
atropine or scopolamine). Tell your doctor if you are taking any drugs for depression (such as amitriptyline, amoxapine, desipramine,
Asendin®, Elavil®, or Norpramin®). Make sure your doctor knows if you are also using disulfiram (Antabuse®), lithium (Eskalith®),
naltrexone (Revia®), or theophylline (Theo-Dur®).
Tell your doctor if you are using any medicines that make you sleepy. These include sleeping pills, cold and allergy medicine, narcotic
pain relievers, and sedatives.
Do not drink alcohol while you are using this medicine.
Warnings While Using This Medicine:
Make sure your doctor knows if you are pregnant or breastfeeding, if you have high blood pressure or heart disease, or if you have a
history of any mental illness, substance abuse, or alcohol abuse.
This medicine may make you dizzy or drowsy. Avoid driving, using machines, or doing anything else that could be dangerous if you are
not alert.
This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose.
Call your doctor for instructions.
If your symptoms do not improve or if they get worse, call your doctor.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble
breathing
Change in how much or how often you urinate.
Changes in vision, or red, itchy, swollen, or dry eye.
Chest pain.
Fast, pounding, or uneven heart beat.
Fever, chills, cough, runny or stuffy nose, sore throat.
Lightheadedness, dizziness, or fainting.
Numbness or weakness in your arm or leg, or on one side of your body.
Numbness, tingling, or burning pain in your hands, arms, legs, feet, or around the mouth.
Problems with hearing, balance, or speech.
Seeing or hearing things which are not really there.
Seizures, tremors, or muscle twitching.
Trouble breathing.
Unusual bleeding, bruising, or weakness.
If you notice these less serious side effects, talk with your doctor:
Changes in taste or appetite.
Clumsiness, tiredness, or problems with muscle movement.
Decreased or increased sweating, or increased thirst.
Depression or feeling "high".
Drowsiness.
Dry mouth, throat, or nose.
Headache.
Mood changes, memory problems, or confusion.
Muscle pain, back pain, joint pain, or body aches.
Nausea, vomiting, diarrhea, constipation, upset stomach, or stomach pain.
Nosebleed.
Skin rash or itching.
Sores or white patches on your lips, mouth, or throat.
Swelling on your face.
Trouble sleeping, restlessness, or nervousness.
Warmth or redness in your face, neck, arms, or upper chest.
If you notice other side effects that you think are caused by this medicine, tell your doctor.
4.3 Place In Therapy
A) Clinical trials have clearly demonstrated nabilone effective in reducing nausea and vomiting associated with chemotherapy, even in
some patients who were unresponsive to therapy with phenothiazines, dopamine antagonists and antihistamines. However, some of
these studies are difficult to interpret because of the widely varying doses of both drugs.
B) Nabilone appears to be at least as effective as alizapride, chlorpromazine, domperidone, or prochlorperazine in managing
chemotherapy-induced nausea and vomiting.
C) The adverse effects associated with nabilone may be more bothersome than those with other therapeutic regimens. At this point,
nabilone should be made available as an alternative for patients who experience nausea and vomiting during chemotherapy, which is
refractory to other more conventional modalities, providing that the expected side effects of nabilone will not decrease the benefits
perceived by the patient.
See Drug Consult reference: CHEMOTHERAPY AND RADIOTHERAPY TREATMENT GUIDELINES FOR NAUSEA AND VOMITING
4.4 Mechanism of Action / Pharmacology
A) MECHANISM OF ACTION
1) Nabilone is a synthetic cannabinoid utilized as an anti-emetic drug in the control of nausea and vomiting in patients receiving cancer
chemotherapy. Like delta-9-tetrahydrocannabinol (the active principal of marijuana), nabilone is a dibenzo(b,d)pyrans. A ketone group
at position 9 of the dibenzopyran nucleus and a dimethyl heptyl side chain are believed to be responsible for the differing
[41]
[42]
pharmacologic profiles of nabilone and delta-9-tetrahydrocannabinol . Animal studies
suggest that the anti-emetic action of
nabilone occurs at a CNS site which is not mediated by a dopaminergic pathway. However, some activity may occur at the
chemoreceptor trigger zone.
[43][44][45][46][47][48]
2) In both animal and human studies, nabilone has demonstrated an anxiolytic activity
. However, the anxiolytic effects
[49]
of nabilone 2 mg were only mild as compared to those produced with diazepam 5 mg .
[50][51]
3) Like delta-9-tetrahydrocannabinol
oral nabilone 0.5 to 2 mg reduced intraocular pressure (IOP) by an average of 40% in
[52]
patients with open angle glaucoma or raised IOP in a single-dose study . The peak effect was seen 2 to 6 hours following a dose.
Animal studies indicate tolerance to these effects occurred after 6 days.
4.5 Therapeutic Uses
AIDS - Nausea and vomiting
Anxiety
Chemotherapy-induced nausea and vomiting, in patients who fail to respond adequately to other antiemetic agents
Chemotherapy-induced nausea and vomiting; Treatment and Prophylaxis
Dystonia
Glaucoma
Postoperative nausea and vomiting; Prophylaxis
4.5.A AIDS - Nausea and vomiting
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category C
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
A case report describes the effective use of nabilone to treat refractory nausea and vomiting in a patient with ACQUIRED
IMMUNODEFICIENCY SYNDROME (Green et al, 1989)
3) Adult:
a) The administration of nabilone 1 milligram twice daily eliminated the intractable nausea and vomiting associated with
cryptosporidiosis in a patient with acquired immunodeficiency syndrome (AIDS). Drowsiness, which was acceptable to the patient, was
the only side effect encountered. The patient was maintained on nabilone for 4 days. Subsequently, the patient died. Previous therapy
[18]
with prochlorperazine, cyclizine, domperidone, and high-dose metoclopramide failed to control these gastrointestinal symptoms .
4.5.B Anxiety
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category C
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Nabilone was effective for the treatment of anxiety in a small study (Fabre et al, 1978)
3) Adult:
a) Five patients treated with nabilone (2 to 8 mg daily for 28 days) demonstrated significant improvement in their symptoms of anxiety
[2]
. Improvement was significantly superior with nabilone (3 mg daily) as compared with placebo. Alleviation of anxiety with nabilone
occurred within 3 days.
4.5.C Chemotherapy-induced nausea and vomiting, in patients who fail to respond adequately to other antiemetic agents
FDA Labeled Indication
1) Overview
FDA Approval: Adult, yes; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Indicated for the treatment of cancer chemotherapy-induced nausea and vomiting
[1]
Restricted to patients who have failed to respond adequately to conventional antiemetic treatments because of a significant risk of
disturbing psychomimetic reactions experienced with nabilone
[1]
In both open and placebo cross-over trials, nabilone 1 to 2 milligrams/day was effective in providing relief of nausea and vomiting in
patients utilizing a variety of emetogenic drugs (Herman et al, 1977; Niamatali et al, 1984; Wada et al, 1982; Levitt, 1982; Einhorn,
1982; Jones et al, 1982)
3) Adult:
a) Nabilone has effectively treated nausea and vomiting induced by cancer chemotherapy in a wide variety of chemotherapy
regimens. Regimens have included low-dose cisplatin (20 milligrams/square meter) in both placebo-controlled and prochlorperazine
[1]
trials .
[5]
b) The combination of nabilone and metoclopramide (dose not stated) was more effective than metoclopramide alone . Nabilone 2
milligrams (mg) twice a day combined with prochlorperazine 5 mg twice a day was effective in controlling emesis induced by cytotoxic
[6]
drugs . Coadministration of nabilone with prochlorperazine also appeared to diminish the incidence of central nervous system
adverse effects.
c) In an open trial, 13 cancer patients whose gastrointestinal symptoms could not be controlled by standard antiemetics received
nabilone 1 or 2 milligrams (mg) orally every 8 hours for 5 days produced clinically useful reduction in chemotherapy-induced nausea
and vomiting in 10 (77%) of the patients. The response was best in those patients who received 2 mg several hours before their cancer
[7]
chemotherapy . Good to excellent responses were reported in 85% of 20 patients who had experienced inadequate relief from nausea
[8]
and vomiting following prochlorperazine 4 mg four times a day .
[9][10][11][12]
d) Nabilone 2 milligrams (mg) twice a day was superior to placebo in 4 double-blind, randomized, cross-over trials
in
reducing the frequency of vomiting and nausea, as well as in patient-preference. In each of these trials, patients received nabilone or
[13]
placebo according to a protocol designed independently . According to this protocol, each patient received 2 identical cycles of
chemotherapy. The first dose of nabilone or placebo was given the evening prior to chemotherapy. Second doses were given 1 to 3
hours before chemotherapy; all patients received at least 3 doses of nabilone. Patients preferred nabilone to placebo and, in one
[9]
[11][12]
study , 64% of patients elected to continue nabilone therapy on an open-trial basis. However, in other studies
only 19% chose
to continue nabilone therapy.
4.5.D Chemotherapy-induced nausea and vomiting; Treatment and Prophylaxis
See Drug Consult reference: CHEMOTHERAPY AND RADIOTHERAPY TREATMENT GUIDELINES FOR NAUSEA AND VOMITING
4.5.E Dystonia
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Ineffective
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category C
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Apparently ineffective in primary dystonia, based on a small, cross-over study
3) Adult:
a) A single-dose of oral NABILONE failed to show efficacy for reduction of dystonic movement in patients with dystonia, based on a
Phase IIa double-blind, cross-over trial (n=15). Enrollees had PRIMARY TORSION DYSTONIA, including 9 cases of generalized
dystonia and 6 cases of segmental; excluded were patients with secondary dystonia (dopa-responsive dystonia, Wilson's disease,
Huntington's disease, or tardive dystonia). On the day of testing, subjects were randomized to placebo or NABILONE 0.03
milligram/kilogram as a single dose. A baseline measure of dystonia movement was made before treatment, then at 60, 120, and 180
minutes following administration of study medication. Total median dystonic movement scores accumulated over 180 minutes were
70.5 after nabilone treatment and 81 after placebo treatment (p greater than 0.05). There were no significant differences in dystonia
movement scale scores comparing baseline with 60, 120, and 180 minutes after nabilone dosing (p greater than 0.05). No significant
differences occurred between placebo and nabilone treatment when subjects were stratified according to generalized or segmental
[16]
dystonia (p greater than 0.05). Two patients had adverse effects attributable to nabilone (postural hypotension and sedation) .
4.5.F Glaucoma
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category C
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Nabilone was effective in lowering intraocular pressure in a small study (Newell et al, 1979)
3) Adult:
a) Nabilone 0.5 milligram orally produced an average decrease in intraocular pressure of 27.9% in 18 patients with OPEN ANGLE
[17]
GLAUCOMA. The maximum decrease in intraocular pressure occurred from 2 to 6 hours following administration .
4.5.G Postoperative nausea and vomiting; Prophylaxis
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Ineffective
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Limited data indicate that nabilone has no efficacy in the treatment of postoperative nausea and vomiting (Lewis et al, 1996)
3) Adult:
a) According to 1 clinical trial, nabilone is not effective in reducing postoperative nausea and vomiting (PONV). Patients (n=53)
undergoing total abdominal hysterectomy (TAH) were randomized to either nabilone 2 milligrams (mg) or metoclopramide 10 mg 90
minutes prior to surgery. At the study site, the baseline incidence (ie, without treatment) of PONV associated with TAH was 70%. At the
conclusion of the study, the incidence of PONV was 70% and 67% (p greater than 0.05) for the nabilone and metoclopramide groups,
[19]
respectively .
4.6 Comparative Efficacy / Evaluation With Other Therapies
Alizapride
Chlorpromazine
Diazepam
Domperidone
Metoclopramide
Prochlorperazine
4.6.A Alizapride
Chemotherapy-induced nausea and vomiting
Vomiting
4.6.A.1 Chemotherapy-induced nausea and vomiting
a) Nabilone has been reported more effective than alizapride in providing relief from nausea, and shortening the duration of nausea in
[59]
patients receiving cisplatin for treatment of nonseminomatous testicular cancer . Twenty patients (19 to 45 years) received
chemotherapy consisting of low-dose cisplatin and doxorubicin therapy. Cisplatin 20 milligrams/square meter (mg/m(2)) was
administered as a 1-hour infusion on days 1 and 5 with doxorubicin 60 mg/m(2) administered on day 6. None of the patients had
received prior treatment with emetogenic chemotherapy. Patients were randomized to receive either nabilone 2 mg or alizapride 150
mg the night before cisplatin therapy and 2 hours before each cisplatin dose. In addition, alizapride 150 mg was also administered at 2
and 8 hours following each cisplatin dose, and nabilone 2 mg at 8 hours following cisplatin. After their first cycle of chemotherapy,
patients were crossed over to the opposite antiemetic therapy. Patients on nabilone had significantly fewer episodes of vomiting than
those on alizapride (p less than 0.01) and had more complete relief from nausea (p less than 0.01). The duration of nausea was also
significantly shorter with nabilone. These advantages were, in part, outweighed by more frequent side effects with nabilone;
drowsiness, the most common adverse effect was seen in 80% of patients given nabilone as compared with only 20% of patients given
alizapride.
4.6.A.2 Vomiting
a) Control of emetic activity with nabilone was demonstrated in patients formerly not controlled with chlorperazine. In 13 cancer
patients whose gastrointestinal symptoms could not be controlled by chlorperazine, nabilone 1 to 2 milligrams orally every 8 hours for 5
[29]
days produced a reduction in nausea and vomiting in 10 (77%) of the patients .
4.6.B Chlorpromazine
4.6.B.1 Chemotherapy-induced nausea and vomiting
a) Although chlorpromazine has been effective in treating cisplatin-induced emesis, for highly emetogenic chemotherapy (eg, cisplatin),
selective serotonin 5-HT3 receptor antagonists remain the drugs of choice.
b) Nabilone 3 milligrams three times a day commencing the day prior to chemotherapy was not significantly different than
intramuscular chlorpromazine 0.5 milligram given 15 minutes prior to chemotherapy in a randomized, double-blind trial of 20 patients
with advanced gynecologic cancer who were receiving cisplatin-based chemotherapy. The frequency of vomiting was 9.5 episodes for
[55]
nabilone patients and 11.4 episodes for chlorpromazine patients. Subjectively, patients preferred nabilone .
4.6.C Diazepam
4.6.C.1 Anxiety
a) The antianxiety effect of nabilone (2 milligrams (mg)) and diazepam (5 mg) in a single-dose double-masked study. Anxiety induced
[58]
by an experimental procedure was more effectively alleviated by diazepam than by nabilone .
4.6.D Domperidone
4.6.D.1 Chemotherapy-induced nausea and vomiting
a) The efficacy of nabilone was compared with oral domperidone in the management of chemotherapy-induced emesis. In this
prospective, randomized, double-blind cross-over trial, 18 children (10 months to 17 years of age) received either nabilone or
domperidone 2 or 3 times daily, beginning the night before chemotherapy and continuing for 24 hours after the last chemotherapy dose.
Dosages of nabilone or domperidone were based on patient weight and ranged from 0.5 milligram (mg) twice daily to 1 mg three times
daily for nabilone and 5 mg three times a day to 15 mg three times a day for domperidone. Patients taking nabilone experienced
significantly fewer episodes of vomiting (p less than 0.01) and less nausea (p equals 0.01). Sixty-seven percent of patients perferred
[15]
nabilone over domperidone. Adverse effects were more common with nabilone, although they were generally felt to be acceptable .
b) Nabilone was superior to domperidone in reducing the number of vomiting episodes in patients receiving emetogenic
[57]
chemotherapy. Seventy percent of patients in this trial received cisplatin .
4.6.E Metoclopramide
Postoperative nausea and vomiting
Radiation-induced nausea and vomiting
4.6.E.1 Postoperative nausea and vomiting
a) Both nabilone and metoclopramide were equally INEFFECTIVE in the treatment of postoperative nausea and vomiting (PONV). In
1 clinical trial, patients (n=53) undergoing total abdominal hysterectomy (TAH) were randomized to either nabilone 2 milligrams (mg) or
metoclopramide 10 mg 90 minutes before the operation. At the study site, the baseline incidence (ie, without treatment) of PONV
associated with TAH is 70%. At the conclusion of the study, the incidence of PONV was 70% and 67% (p greater than 0.05) for the
[53]
nabilone and metoclopramide groups, respectively .
4.6.E.2 Radiation-induced nausea and vomiting
a) Nabilone 1 milligram (mg) two times a day was reported to be as effective as metoclopramide 10 mg three times a day in controlling
radiation-induced nausea and vomiting in a controlled study involving 40 patients. The interval between initiation of radiotherapy and
antiemetic therapy was 9.5 days and 8.36 days for nabilone and metoclopramide, respectively. However, metoclopramide was
associated with a lower incidence of adverse effects as compared to nabilone; vertigo, dry mouth, disorientation and fatigue occurred
to a greater degree in nabilone-treated patients. Euphoria, change in personality and anorexia occurred in one patient each receiving
nabilone but in none receiving metoclopramide. Metoclopramide would appear to be a more appropriate first-line agent for the
treatment of nausea and vomiting secondary to radiotherapy. Nabilone is recommended in patients unable to tolerate, or unresponsive
[54]
to, metoclopramide .
4.6.F Prochlorperazine
4.6.F.1 Chemotherapy-induced nausea and vomiting
a) SUMMARY: Nabilone appears to be more effective than prochlorperazine; however, summarizing this data is difficult because of
the inconsistency of dosage regimens, patient populations and chemotherapy regimens. In some of these studies, doses of
[56]
prochlorperazine that were utilized are now considered to be subtherapeutic .
6.0 References
1. Product Information: CESAMET(TM) oral capsules, nabilone oral capsules. Valeant Pharmaceuticals,Inc, Costa Mesa, CA, 2006.
2. Fabre LF, McClendon DM, & Stark PD: Nabilone, and cannabinoid, in the treatment of anxiety: an open-label and double-blind
study. Curr Ther Res 1978; 24:161-169.
3. Ilaria RL, Thornby JI, & Fann WE: Nabilone, a cannabinol derivative in the treatment of anxiety neurosis. Curr Ther Res 1981;
29:943-949.
4. Rubin A, Lemberger L, Warrick P, et al: Physiologic disposition of nabilone, a cannabinol derivative, in man. Clin Pharmacol Ther
1977; 22:85-91.
5. Meyer BR, Reidenberg MM, Drayer DE, et al: Initial trial of metclopramide and nabilone combination anti-emetic therapy. Clin Res
1984; 32:688A.
6. Cunningham D, Forrest GJ, Soukop M, et al: Nabilone and prochlorperazine: a useful combination for emesis induced by cytotoxic
drugs. Br Med J 1985; 291:864-865.
7. Herman TS, Jones SE, Dean J, et al: Nabilone: a potent anti-emetic cannabinol with minimal euphoria. Biomedicine 1977; 27:331334.
8. Niamatali C, Fallon SD, & Egan EL: Nabilone in the management of prochlorperazine resistant cancer chemotherapy induced
emesis. Irish Med J 1984; 77:276-277.
9. Einhorn L: Nabilone: an effective antiemetic agent in patients receiving cancer chemotherapy. Cancer Treat Rev 1982; 9:55-61.
10. Jones SE, Durant JR, Greco FA, et al: A multi-institutional phase III study of nabilone vs chemotherapy-induced nausea and
vomiting. Cancer Treat Rev 1982; 9:45-48.
11. Levitt M: Nabilone vs placebo in the treatment of chemotherapy-induced nausea and vomiting in cancer patients. Cancer Treat Rev
1982; 9(Suppl B):49-53.
12. Wada JK, Bogbon DL, Gunnel JC, et al: Double-blind, randomized, crossover trial of nabilone vs placebo in cancer chemotherapy.
Cancer Treat Rev 1982; 9:39-44.
13. Stark P: Study design for the evaluation of the efficacy and safety of nabilone. Cancer Treat Rev 1982b; 9:35-37.
14. Chan HSL, Correia JA, & MacLeod SM: Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in
children: a double-blind, crossover trial. Pediatrics 1987; 79:946-952.
15. Dalzell AM, Bartlett H, & Lilleyman JS: Nabilone: an alternative antiemetic for cancer chemotherapy. Arch Dis Child 1986; 61:502505.
16. Fox SH, Kellett M, Moore AP, et al: Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid
receptor stimulation in the treatment of dystonia. Movement Disord 2002; 17(1):145-149.
17. Newell FW, Stark P, Jay WM, et al: Nabilone: a pressure-reducing synthetic benzoppyran in open-angle glaucoma. Ophthalmol
1979; 86:156-160.
18. Green ST, Nathwani D, Goldberg DJ, et al: Nabilone as effective therapy for intractable nausea and vomiting in AIDS (letter). Br J
Clin Pharmacol 1989; 28:494-495.
19. Lewis IH, Campbell DN, & Barrowcliffe MP: Effect of nabilone on nausea and vomiting after total abdominal hysterctomy. Br J
Anaesth 1994; 73:244-246.
20. .. Package inserts for Cesamet., .
21. Cesamet product monograph. In: Gillis MC, Editor. CPS Compendium of pharmaceuticals and specialities. 33rd ed. Ottawa:
Canadian Pharmacists Association; 1998.. p. 303., 1998.
22. 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; 10(4):325-9.
23. Reviewer comment.. ., 6/28/93.
24. Reviewers" consensus.. ., 1993.
25. CPS 1987: 148.. ., .
26. Einhorn L: Nabilone: an effective antiemetic agent in patients receiving cancer chemotherapy. Cancer Treat Rev 1982; 9:55-61.
27. Steele N, Gralla RJ, Braun DW, et al: Double-blind comparison of the anti-emetic effects of nabilone and prochlorperazine on
chemotherapy-induced emesis. Cancer Treat Rep 1980; 64:219-224.
28. Johansson R, Kikku P, & Groenroos M: A double-blind, controlled study of nabilone vs prochlorperazine for refractory emesis
induced by cancer chemotherapy. Cancer Treat Res 1982; 9:25-33.
29. Herman TS, Jones SE, Dean J, et al: Nabilone: a potent anti-emetic cannabinol with minimal euphoria. Biomedicine 1977; 27:331334.
30. Glass RM, Uhlenhuth EH, Hartel EW, et al: A single dose study of nabilone, a synthetic cannabinoid. Psychopharmacology 1980;
71:137-142.
31. Lemberger L & Rowe H: Clinical pharmacology of nabilone, a cannabinol derivative. Clin Pharmacol Ther 1975; 18:720-726.
32. Ward A & Holmes B: Nabilone a preliminary review of its pharmacological properties and therapeutic use. Drugs 1985; 30:127-144.
33. Fabre LF, McClendon DM, & Stark PD: Nabilone, and cannabinoid, in the treatment of anxiety: an open-label and double-blind
study. Curr Ther Res 1978; 24:161-169.
34. Gong H, Tashkin DP, & Calvarese B: Comparison of bronchial effects of nabilone and terbutaline in healthy and asthmatic subject.
J Clin Pharmacol 1983; 23:127-133.
35. Lemberger L, Rubin A, Wolen R, et al: Pharmacokinetics, metabolism and drug-abuse potential of nabilone. Cancer Treat Rev
1982; 9:17-23.
36. Johnson RE, Jasinski DR, Boren JJ, et al: Abuse potential of nabilone, Proceedings of the 2nd World Conference on Clinical
Pharmacology and Therapeutics, Washington, DC, 1983.
37. Einhorn LH, Nagy C, Furnas B, et al: Nabilone: an effective antiemetic in patients receiving cancer chemotherapy. J Clin
Pharmacol 1981; 21:64S-69S.
38. Product Information: Cesamet(R), nabilone. Eli Lilly, Canada Inc, Toronto, Ontario, 1981.
39. Rubin A, Lemberger L, Warrick P, et al: Physiologic disposition of nabilone, a cannabinol derivative, in man. Clin Pharmacol Ther
1977; 22:85-91.
40. Krogh CMEKrogh CME (Ed): Compendium of Pharmaceuticals and Specialties, 30th. Canadian Pharmaceutical Association,
Ottawa, Ontario, Canada, 1995.
41. Ward A & Holmes B: Nabilone a preliminary review of its pharmacological properties and therapeutic use. Drugs 1985; 30:127-144.
42. Stark P: The pharmacologic profile of nabilone: a new anti-emetic agent. Cancer Treat Rev 1982a; 9:11-16.
43. Stark P & Henderson JK: Increased reactivity in rats caused by septal lesions. Intl J Neuropharmacol 1966; 5:379-383.
44. McCarthy LE & Borison HL: Antiemetic activity of N-methyllevonantradol, and nabilone in cisplatin-treated cats. J Clin Pharmacol
1981; 21:30S-37S.
45. London SW, McCarthy LE, & Borison HL: Suppression of cancer chemotherapy-induced vomiting in the cat by nabilone, a
synthetic cannabinoid. Proceedings of the Society for Experimental Biology and Medicine 1979; 160:437-440.
46. Fabre LF & McClendon D: The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety. J Clin
Pharmacol 1981; 21:377S-382S.
47. Ilaria RL, Thornby JI, & Fann WE: Nabilone, a cannabinol derivative in the treatment of anxiety neurosis. Curr Ther Res 1981;
29:943-949.
48. Fabre LF, McClendon DM, & Stark PD: Nabilone, and cannabinoid, in the treatment of anxiety: an open-label and double-blind
study. Curr Ther Res 1978; 24:161-169.
49. Nakano S, Gillespie HK, & Hollister LE: A model for evaluation of antianxiety drugs with the use of experimentally induced stress:
comparison of nabilone and diazepam. Clin Pharmacol Ther 1978; 23:54-62.
50. Hepler RS, Frank IM, & Ungerleider JT: Pupillary constriction after marijuana smoking. Am J Ophthamol 1972; 74:1185-1190.
51. Green J, Bigger JF, Kim K, et al: Canabinoid action on the eye as mediated through the central nervous system and local
adrenergic activity. Exp Eye Res 1977; 24:189-196.
52. Newell FW, Stark P, Jay WM, et al: Nabilone: a pressure-reducing synthetic benzoppyran in open-angle glaucoma. Ophthalmol
1979; 86:156-160.
53. Lewis IH, Campbell DN, & Barrowcliffe MP: Effect of nabilone on nausea and vomiting after total abdominal hysterectomy. Br J
Anaesth 1994; 73:244-246.
54. Priestman SG, Priestman TJ, & Canney PA: A double-blind randomised cross-over comparison of nabilone and metoclopramide in
the control of radiation-induced nausea. Clin Radiol 1987; 38:543-544.
55. George M, Pejovic MH, Thuaire M, et al: Comparatif randomise d'un nouvel anti-emetique: la nabilone, chez des maladies
cancereuses traitees par le cisplatinum. Biomed Pharmacother 1983; 37:24-27.
56. Ward A & Holmes B: Nabilone a preliminary review of its pharmacological properties and therapeutic use. Drugs 1985; 30:127-144.
57. 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; 17:285-288.
58. Nakano S, Gillespie HK, & Hollister LE: A model for evaluation of antianxiety drugs with the use of experimentally induced stress:
comparison of nabilone and diazepam. Clin Pharmacol Ther 1978; 23:54-62.
59. Niederle N, Schutte J, & Schmidt CG: Crossover comparison of the antiemetic efficacy of nabilone and alizapride in patients with
nonseminomatous testicular cancer receiving cisplatin therapy. Klin Wochenschr 1986; 64:362-365.
60. Gralla RJ, Osoba D, Kris MG, et al: Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines.
American Society of Clinical Oncology. J Clin Oncol 1999; 17(9):2971-2994.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...PubMed
Article: http://www.ncbi.nlm.nih.gov/...
61. Kris MG, Hesketh PJ, Somerfield MR, et al: American Society of Clinical Oncology guideline for antiemetics in oncology: update
2006. J Clin Oncol 2006; 24(18):2932-2947.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...PubMed Article:
http://www.ncbi.nlm.nih.gov/...
62. Anon: ASHP Therapeutic guidelines on the pharmacologic management of nausea and vomiting in adult and pediatric patients
receiving chemotherapy or radiation therapy or undergoing surgery. Am J Health-Syst Pharm 1999; 56:729-764.
63. U.S. Food and Drug Administration: FDA drug safety communication: Abnormal heart rhythms associated with use of Anzemet
(dolasetron mesylate). U.S. Food and Drug Administration. Silver Spring, MD. 2010. Available from URL: . As accessed 2010-12-17.
Last Modified: October 25, 2011
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