Cesamet

Cannabinoid Antiemetics

May be administered without regard to meals.
Because of the potential for adverse CNS effects, patients should remain under the supervision of a responsible adult during the initial use of nabilone and following dosage adjustments.

seizures / Delayed / Incidence not known

euphoria / Early / 11.0-38.0
depression / Delayed / 14.0-16.0
ataxia / Delayed / 13.0-14.0
dysphoria / Early / 12.0-12.0
hypotension / Rapid / 8.0-8.0
hallucinations / Early / Incidence not known
impaired cognition / Early / Incidence not known
psychosis / Early / Incidence not known
akathisia / Delayed / Incidence not known
confusion / Early / Incidence not known
hypertension / Early / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
chest pain (unspecified) / Early / Incidence not known
palpitations / Early / Incidence not known
wheezing / Rapid / Incidence not known
dyspnea / Early / Incidence not known
photophobia / Early / Incidence not known
amblyopia / Delayed / Incidence not known
constipation / Delayed / Incidence not known
oral ulceration / Delayed / Incidence not known
gastritis / Delayed / Incidence not known
hot flashes / Early / Incidence not known
urinary retention / Early / Incidence not known
leukopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
hypotonia / Delayed / Incidence not known
anhidrosis / Delayed / Incidence not known

drowsiness / Early / 52.0-66.0
vertigo / Early / 52.0-59.0
dizziness / Early / 59.0-59.0
asthenia / Delayed / 8.0-8.0
headache / Early / 6.0-7.0
paranoia / Early / Incidence not known
malaise / Early / Incidence not known
hyperactivity / Early / Incidence not known
emotional lability / Early / Incidence not known
insomnia / Early / Incidence not known
fatigue / Early / Incidence not known
anxiety / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
irritability / Delayed / Incidence not known
tremor / Early / Incidence not known
syncope / Early / Incidence not known
flushing / Rapid / Incidence not known
cough / Delayed / Incidence not known
pharyngitis / Delayed / Incidence not known
nasal congestion / Early / Incidence not known
epistaxis / Delayed / Incidence not known
ocular irritation / Rapid / Incidence not known
xerophthalmia / Early / Incidence not known
mydriasis / Early / Incidence not known
tinnitus / Delayed / Incidence not known
nausea / Early / Incidence not known
abdominal pain / Early / Incidence not known
diarrhea / Early / Incidence not known
vomiting / Early / Incidence not known
dyspepsia / Early / Incidence not known
appetite stimulation / Delayed / Incidence not known
anorexia / Delayed / Incidence not known
xerostomia / Early / Incidence not known
increased urinary frequency / Early / Incidence not known
back pain / Delayed / Incidence not known
hyperhidrosis / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known
fever / Early / Incidence not known
rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
infection / Delayed / Incidence not known

Cesamet

Rx, schedule II

Oral synthetic cannabinoid that provides standardized THC concentrations.
Approved use for refractory chemotherapy-induced emesis; a second-line agent in ASCO guidelines.
DEA Schedule C-II controlled substance.

1 or 2 mg PO twice daily. The initial dose should be given 1 to 3 hours before the chemotherapeutic agent is administered. A dose of 1 or 2 mg the night before chemotherapy administration may be useful. Nabilone may be administered 2 or 3 times daily during the entire course of each cycle of chemotherapy and, if needed, for 48 hours after the last dose of each cycle of chemotherapy. The manufacturer states that nabilone is not indicated as first-line antiemetic therapy because of the substantial frequency of disturbing psychotomimetic reactions, which is not observed with conventional antiemetic agents. Because of the potential for adverse CNS effects, patients should be supervised by a responsible adult during the initial use of nabilone and following dosage adjustments.

The following dosage regimens have been studied: 1 mg PO every 8 to 12 hours for adolescents and children > 30 kg, 1 mg PO twice daily for children 18 to 30 kg, and 0.5 mg PO twice daily for children < 18 kg. In a randomized trial comparing nabilone to prochlorperazine in pediatric patients aged 3.5 to 17.8 years, the overall rate of improvement of retching and emesis was 70% during nabilone treatment and 30% during prochlorperazine treatment for the 30 patients evaluated. After completing the trial, 66% of children stated a preference for nabilone. Dose-related CNS side effects occurred including dizziness, drowsiness, and mood alteration. CNS adverse events appeared to be more frequent when dosage exceeded 60 mcg/kg/day; however, individual tolerance to nabilone was variable. Lower doses may have comparable efficacy and less side effects. A similar dosing regimen was used in a separate cross-over study comparing the effectiveness of nabilone to oral domperidone in children aged 0.8 to 17 years. Among 18 patients evaluated, a mean of 5.94 vomiting episodes was reported in the nabilone group compared to a mean of 16.72 episodes in the domperidone group. Additionally, the severity of nausea was assessed on a scale from 0 to 3, where a score of 3 represented severe nausea. The mean severity of nausea score was lower in the nabilone group compared to the domperidone group (1.5 vs. 2.5). Overall, two-thirds of participants expressed a preference for nabilone. According to the manufacturer, safe and effective use of Cesamet (nabilone) has not been established in patients younger than 18 years.

1 to 2 mg/day PO has been used. Closely monitor patients for adverse CNS effects, particularly during initiation and dose adjustments. Moderate decreases in Huntington's chorea were demonstrated in a placebo-controlled, crossover trial that randomized subjects (n = 44) to 5 weeks of treatment with nabilone titrated to 1 mg or 2 mg PO daily or placebo. The Unified Huntington's Disease Rating Scale was used to assess subject chorea severity at baseline and at the end of treatment intervals. Chorea scores only decreased by 1.68 (95% CI 0.44—2.92, p = 0.009). The long-term efficacy and safety (including abuse potential) of nabilone for the treatment Huntington's chorea is unknown. The American Academy of Neurology suggests that nabilone may be prescribed for modest decreases in Huntington's chorea.

†Indicates off-label use

No specific guidelines are available. Since nabilone is extensively metabolized by the liver, use caution when initiating or adjusting nabilone dosage. Nabilone has not been studied in patients with hepatic impairment.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression.
Acetaminophen; Tramadol: (Moderate) Concomitant use of nabilone with other CNS depressants, including tramadol, can potentiate the effects of nabilone on respiratory depression.
Amitriptyline: (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Amitriptyline; Chlordiazepoxide: (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Amoxapine: (Moderate) Nabilone or other CNS depressants should be combined cautiously with heterocyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Anticholinergics: (Moderate) Concurrent use of nabilone with anticholinergics may result in pronounced tachycardia and drowsiness.
Apomorphine: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with nabilone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Atropine; Diphenoxylate: (Moderate) Concurrent administration of diphenoxylate/difenoxin with nabilone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
atypical antipsychotic: (Moderate) Drugs that can cause CNS depression, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Barbiturates: (Moderate) Concomitant use of nabilone with other CNS depressants, like barbiturates, can potentiate the effects of nabilone on respiratory depression.
Benzodiazepines: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression.
Bupropion; Naltrexone: (Moderate) Concomitant administration of naltrexone and nabilone enhances the 'positive' subjective effects of nabilone. Data from separate investigations demonstrate that pretreatment with an opioid receptor blocker such as naltrexone significantly increases many of the euphoric effects of oral THC in heavy marijuana smokers.
Buspirone: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression.
Butyrophenone: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression.
Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of nabilone with other CNS depressants like entacapone can potentiate the effects of nabilone on respiratory depression.
Cetirizine: (Moderate) Additive drowsiness may occur if cetirizine or levocetirizine is administered with other drugs that depress the CNS, such as nabilone.
Cetirizine; Pseudoephedrine: (Moderate) Additive drowsiness may occur if cetirizine or levocetirizine is administered with other drugs that depress the CNS, such as nabilone.
Chlorpromazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Clobazam: (Moderate) Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects. Potentiation of CNS effects (i.e., increased sedation or respiratory depression) may occur when clobazam is combined with other CNS depressants such as nabilone.
Clomipramine: (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Cocaine: (Major) Concurrent use of nabilone with sympathomimetics like amphetamine or cocaine may result in additive hypertension, tachycardia, and possibly cardiotoxicity.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Codeine; Promethazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Coadministration of ritonavir and oral THC results in increased THC concentrations. A decreased dose of nabilone may be needed if these drugs are coadministered with ritonavir.
Desipramine: (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Dextromethorphan; Promethazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Disulfiram: (Minor) A reversible hypomanic reaction was reported in a 28 year old male who smoked marijuana while taking disulfiram. This reaction was confirmed by dechallenge and rechallenge. Because nabilone is a synthetic analog similar to a naturally occurring substance found in marijuana, this interaction may also occur with nabilone.
Doxepin: (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Dronabinol: (Severe) Avoid use together. While a patient is taking dronabinol or is taking nabilone, the patient should not be treated with other oral or inhaled cannabinoids. Combining 2 cannabinoids will lead to an increase in psychotoxic effects, and would not represent any therapeutic benefit to the patient.
Entacapone: (Moderate) Concomitant use of nabilone with other CNS depressants like entacapone can potentiate the effects of nabilone on respiratory depression.
Eszopiclone: (Moderate) A reduction in the dose of eszopiclone and concomitantly administered CNS depressants, such as nabilone, should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethanol: (Major) Patients receiving nabilone should avoid ethanol due to the increased incidence of CNS effects.
Ezogabine: (Moderate) Due to the CNS effects of ezogabine, an enhanced CNS depressant effect may occur during concurrent use of other centrally-acting medications such as nabilone. Patients should be monitored for excessive somnolence during concurrent therapy with this agent.
Flibanserin: (Severe) The concomitant use of flibanserin with CNS depressants, such as nabilone, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Fluoxetine: (Minor) A hypomanic episode was reported in a 21 year old female with depression and bulimia receiving fluoxetine 20 mg/day for 4 weeks after smoking marijuana. Her symptoms resolved in 4 days. This interaction may also occur with nabilone which is a synthetic analog of a naturally occurring substance found in marijuana.
Fluoxetine; Olanzapine: (Minor) A hypomanic episode was reported in a 21 year old female with depression and bulimia receiving fluoxetine 20 mg/day for 4 weeks after smoking marijuana. Her symptoms resolved in 4 days. This interaction may also occur with nabilone which is a synthetic analog of a naturally occurring substance found in marijuana.
Fluphenazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Food: (Severe) Avoid use together. While a patient is taking nabilone, the patient should not be treated with other oral or inhaled cannabinoids, and should not use Marijuana in any form. Combining 2 cannabinoids will lead to an increase in psychotoxic effects, and would not represent any therapeutic benefit to the patient.
General anesthetics: (Moderate) Concomitant use of nabilone with other CNS depressants like general anesthetics can potentiate the effects of nabilone on respiratory depression.
Heterocyclic antidepressants: (Moderate) Nabilone or other CNS depressants should be combined cautiously with heterocyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Imipramine: (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Levocetirizine: (Moderate) Additive drowsiness may occur if cetirizine or levocetirizine is administered with other drugs that depress the CNS, such as nabilone.
Lithium: (Moderate) Concomitant use of nabilone with lithium can potentiate the effects of cannabinoids on drowsiness and CNS depression.
Lopinavir; Ritonavir: (Moderate) Coadministration of ritonavir and oral THC results in increased THC concentrations. A decreased dose of nabilone may be needed if these drugs are coadministered with ritonavir.
Maprotiline: (Moderate) Nabilone or other CNS depressants should be combined cautiously with heterocyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Meperidine; Promethazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Meprobamate: (Moderate) Additive CNS and respiratory depressant effects may occur with concurrent use of nabilone and meprobamate.
Mesoridazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Methocarbamol: (Moderate) Concomitant use of nabilone with other CNS depressants like methocarbamol can potentiate the effects of nabilone on respiratory depression.
Metyrapone: (Moderate) Metyrapone may cause drowsiness or dizziness. Use caution if coadministration of nabilone with metyrapone is necessary, and monitor for additive CNS effects, such as drowsiness or dizziness.
Mirtazapine: (Moderate) Nabilone or other CNS depressants should be combined cautiously with heterocyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Molindone: (Moderate) Concomitant use of nabilone with other CNS depressants like molindone can potentiate the effects of nabilone on respiratory depression.
Monoamine oxidase inhibitors: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including nabilone.
Naltrexone: (Moderate) Concomitant administration of naltrexone and nabilone enhances the 'positive' subjective effects of nabilone. Data from separate investigations demonstrate that pretreatment with an opioid receptor blocker such as naltrexone significantly increases many of the euphoric effects of oral THC in heavy marijuana smokers.
Nefazodone: (Moderate) Concomitant use of nabilone with nefazodone can potentiate the effects of cannabinoids on drowsiness and CNS depression.
Neuromuscular blockers: (Moderate) Concomitant use of nabilone with other CNS depressants like neuromuscular blockers can potentiate the effects of nabilone on respiratory depression.
Nortriptyline: (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Coadministration of ritonavir and oral THC results in increased THC concentrations. A decreased dose of nabilone may be needed if these drugs are coadministered with ritonavir.
Opiate Agonists: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants, such as nabilone, can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of an opiate in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Opiate Agonists-Antagonists: (Moderate) Concomitant use of mixed opiate agonists-antagonists with nabilone can potentiate the effects of nabilone and may lead to additive CNS or respiratory depression. Prior to concurrent use of nabilone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, a reduced dosage nabilone and/or the opiate agonist-antagonist may be necessary. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as nabilone.
Perphenazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Perphenazine; Amitriptyline: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression. (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Phenothiazines: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Phenylephrine; Promethazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Pimozide: (Moderate) Concomitant use of nabilone with other CNS depressants like pimozide can potentiate the effects of nabilone on respiratory depression.
Pramipexole: (Moderate) Concomitant use of nabilone with other CNS depressants, like pramipexole, can potentiate the effects of nabilone on respiratory depression.
Pregabalin: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression. Pregabalin can cause considerable somnolence and the combined use of ethanol or other CNS depressants with pregabalin may lead to an additive drowsy effect.
Prochlorperazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Promethazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Protriptyline: (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Ramelteon: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression.
Rasagiline: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including nabilone. Use these drugs cautiously with MAOIs; warn patients to not drive or perform other hazardous activities until they know how a particular drug combination affects them. In some cases, the dosages of the CNS depressants may need to be reduced.
Ritonavir: (Moderate) Coadministration of ritonavir and oral THC results in increased THC concentrations. A decreased dose of nabilone may be needed if these drugs are coadministered with ritonavir.
Ropinirole: (Moderate) Concomitant use of ropinirole with other CNS depressants like nabilone can potentiate the sedation effects of ropinirole.
Rotigotine: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as nabilone, can potentiate the sedation effects of rotigotine.
Sedating H1-blockers: (Moderate) Concomitant use of nabilone with other CNS depressants, such as sedating H1-blockers, can potentiate the effects of nabilone on respiratory depression.
Skeletal Muscle Relaxants: (Moderate) Concomitant use of nabilone with other CNS depressants like skeletal muscle relaxants can potentiate the effects of nabilone on respiratory depression, sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness.
Sodium Oxybate: (Moderate) Concomitant use of nabilone with other CNS depressants like sodium oxybate can potentiate the effects of nabilone on respiratory depression.
Solifenacin: (Moderate) Concurrent use of nabilone with anticholinergics may result in additive tachycardia and drowsiness, which may be pronounced.
Suvorexant: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
Sympathomimetics: (Moderate) Concurrent use of nabilone with sympathomimetics (e.g., amphetamine or cocaine) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 to 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm.
Tapentadol: (Moderate) Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants. Severe hypotension, profound sedation, coma, or respiratory depression may occur. Prior to concurrent use of tapentadol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with tapentadol, a reduced dosage of tapentadol and/or the CNS depressant is recommended. If the extended-release tapentadol tablets are used concurrently with a CNS depressant, it is recommended to use an initial tapentadol dose of 50 mg PO every 12 hours. Monitor patients for sedation and respiratory depression.
Tetrabenazine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as nabilone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
Theophylline, Aminophylline: (Minor) Increased theophylline metabolism has been reported with smoking of marijuana. This interaction may also occur with nabilone which is a synthetic analog of a naturally occurring substance found in marijuana. (Minor) Increased theophylline metabolism has been reported with smoking of marijuana. This interaction may also occur with nabilone which is a synthetic analog of a naturally occurring substance found in marijuana.
Thiethylperazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Thioridazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Thiothixene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as nabilone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Tizanidine: (Moderate) Concomitant use of nabilone with other CNS depressants, like tizanidine, can potentiate the effects of nabilone on CNS and respiratory depression.
Tramadol: (Moderate) Concomitant use of nabilone with other CNS depressants, including tramadol, can potentiate the effects of nabilone on respiratory depression.
Trazodone: (Moderate) Nabilone or other CNS depressants should be combined cautiously with heterocyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Tricyclic antidepressants: (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Trifluoperazine: (Moderate) Concomitant use of nabilone with other CNS depressants, including phenothiazines, can potentiate the effects of nabilone on respiratory depression.
Trimethobenzamide: (Moderate) Trimethobenzamide has CNS depressant effects and may cause drowsiness. The concurrent use of trimethobenzamide with other medications that cause CNS depression like nabilone may potentiate the effects of either medication.
Trimipramine: (Moderate) Nabilone or other CNS depressants should be combined cautiously with tricyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Trospium: (Moderate) Concurrent use of oral cannabinoids, such as nabilone, with anticholinergics such as trospium may result in pronounced tachycardia and drowsiness.
Vigabatrin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with nabilone.
Vilazodone: (Moderate) Due to the CNS effects of vilazodone, caution should be used when vilazodone is given in combination with other centrally acting medications such as nabilone.
Zaleplon: (Moderate) Additive respiratory and CNS depressant effects are possible during concurrent use of nabilone and zaleplon. In premarketing studies, zaleplon potentiated the CNS effects of ethanol, imipramine, and thioridazine for at least 2 to 4 hours. Similar interactions may occur with other CNS depressants including nabilone. If concurrent use is necessary, monitor for additive side effects. A reduction in the dose of one or both drugs may be needed.
Zolpidem: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression. Sleep-related behaviors, such as sleep-driving, are also more likely to occur during concurrent use of zolpidem and ethanol or other CNS depressants than with zolpidem alone. A reduction in the dose, should be considered to minimize additive sedative effects; for Intermezzo brand of sublingual zolpidem tablets, reduce the dose to 1.75 mg/night.

Cesamet Oral Cap: 1mg

6 mg/day PO.

6 mg/day PO.

3 mg/day PO has been studied.

> 30 kg: 3 mg/day PO has been studied.
18—30 kg: 2 mg/day PO has been studied.
< 18 kg: 1 mg/day PO has been studied.

Mechanism of Action: Nabilone is a synthetic cannabinoid which acts as an agonist at endogenous cannabinoid receptors. At least two endogenous cannabinoid receptors, CB1 and CB2, have been identified, and an endogenous cannabinoid ligand (e.g., anandamide) has also been isolated. Cannabinoid receptors exert signal transduction effects through G-protein-coupled receptors, resulting in decreased excitability of neurons; however, some reports have suggested that cannabinoids can stimulate adenylyl cyclase. The CB2 receptor is generally only found peripherally and has been shown to affect the immune system. The CB1 receptor is highly distributed throughout the brain and can also be found in several peripheral tissues.Cannabinoids exert a wide range of CNS effects including short-term memory deficits, sense of time dilation, enhanced sensation, and higher-order cognitive impairment. Cannabinoids also produce both euphoria and dysphoria, depending upon the prior experience of the individual and the dose administered. The brain distribution of CB1 receptors and receptor-activated G-proteins correlates with the behavioral effects of these compounds. Cannabinoids also exhibit CNS-mediated effects on thermoregulation, feeding behavior, nausea, and reward mechanisms. Cannabinoids were thought to produce antiemetic effects by affecting sites in the upper cortex, which then influence the vomiting center in the medulla; however, it is now hypothesized that the antiemetic effects are mediated by cannabinoid (CB1) receptors in the vomiting center of the medulla, the area subpostrema of the nucleus tractus solitarii (ASNTS). Cannabinoids may act in the vomiting center to oppose the effects of serotonin (5-HT3) to block the release of neurotransmitters from vagal afferent terminals, which help to produce emesis.

Nabilone is administered orally. 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2E1, CYP2C8, CYP2C9
Nabilone is extensively metabolized via multiple cytochrome P450 isoforms. In vitro cytochrome P450 inhibition studies using human liver microsomes have shown that nabilone does not significantly inhibit CYP1A2, CYP2A6, CYP2C19, or CYP2D6. However, nabilone demonstrates a weak inhibitory effect on CYP2E1 and CYP3A4 and a moderate inhibitory effect on CYP2C8 and CYP2C9. Due to significant tissue distribution and rapid metabolism, absorbed nabilone disappears from plasma rapidly. The plasma half-life is approximately 2 hours. At recommended doses, the low plasma concentrations achieved are considered unlikely to interfere with P450-mediated degradation of coadministered drugs.
 
At least two metabolites have been identified. The relative activities of the metabolites have not been established. One or more active metabolites may contribute to the long duration of action. The metabolites remain in plasma for prolonged periods (half-life of total radioactivity is about 35 hours). During repeated use, the metabolites may accumulate to concentrations in excess of the parent drug. Following oral administration, about 60% of nabilone and its metabolites are recovered in the feces and about 24% are recovered in urine. It appears that the major excretory pathway is the biliary system.

Nabilone is completely absorbed from the gastrointestinal tract after a single dose. Following administration of a 2 mg dose, peak plasma concentrations are reached within 2 hours. Clinical data suggest that the intake of food does not significantly change the rate or extent of absorption.

Nabilone is classified as FDA pregnancy risk category C. There are no adequate and well-controlled studies of nabilone in pregnant women. Two animal studies have shown dose-related developmental toxicities which include growth retardation and death. It is unknown if nabilone crosses the placenta to the fetus, however its molecular weight (about 373) and lipid solubility suggests it would. Although the plasma half-life of nabilone is short (2 hours), its metabolites have a prolonged plasma half-life of around 35 hours. Nabilone is derived from cannabinol, a chemical constituent of marijuana, from which active delta-9-tetrahydrocannabinol (delta-9-THC) forms. Chemically, nabilone is similar to delta-9-THC. Marijuana use in pregnancy is associated with developmental toxicity including growth restriction and long-term neurobehavioral deficits. Due to the scarcity of pregnancy exposure data with nabilone and the possibility of serious risk of adverse effects to the developing fetus, it is advisable that nabilone be avoided during pregnancy. The use of nabilone should only be considered in the most refractory of pregnant patients who do not response to or cannot tolerate alternate antiemetics.

Because of the potential for serious adverse reactions from nabilone in breast-fed infants, nabilone and other cannabinoids should be avoided in breast-feeding women. It is not known whether nabilone is excreted in breast milk. Delta-9-THC, another cannabinoid and chemically similar compound, is known to be excreted in breast milk. Although the plasma half-life of nabilone is short, its metabolites have a prolonged plasma half-life of around 35 hours. The relative activities of the metabolites have not been established; however, one or more active metabolites may contribute to the long duration of action. Moreover, it is unknown if these metabolites are excreted in breast milk. A decision should be made whether to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother.