Nabilone

Teratogenic Effects

Teratology studies conducted in pregnant rats at doses up to 12 mg/kg/day (about 16 times the human dose on a body surface area basis) and in pregnant rabbits at doses up to 3.3 mg/kg/day (about 9 times the human dose on a body surface area basis) did not disclose any evidence for a teratogenic potential of nabilone. However, there was dose related developmental toxicity in both species as evidenced by increases in embryo lethality, fetal resorptions, decreased fetal weights and pregnancy disruptions. In rats, postnatal developmental toxicity was also observed. There are no adequate and well-controlled studies in pregnant women. Because animal studies cannot rule out the possibility of harm, nabilone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether this drug is excreted in breast milk. Because many drugs including some cannabinoids are excreted in breast milk it is not recommended that nabilone be given to nursing mothers.

No long-term studies in animals have been performed to evaluate the carcinogenic potential of nabilone.

Nabilone was not genotoxic in the Ames test, the rat hepatocyte unscheduled DNA synthesis (UDS) test, the Chinese hamster bone marrow cell sister chromatid exchange (SCE) test, the male rat dominant lethal tests nor the rat micronucleus test.

Dietary administration of nabilone up to 4 mg/kg/day (about 6 times the recommended maximum human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

Commonly Encountered Reactions: During controlled clinical trials of nabilone, virtually all patients experienced at least one adverse reaction. The most commonly encountered events were drowsiness, vertigo, dry mouth, euphoria (feeling “high”), ataxia, headache, and concentration difficulties.

Comparative Incidence of Reactions: Accurate estimates of the incidence of adverse events associated with the use of any drug are difficult to obtain. Estimates are influenced by factors such as drug dose, detection technique, setting, and physician judgments, among others. Consequently, the tables presented below are presented solely to indicate the relative frequency of adverse events reported in representative controlled clinical studies conducted to evaluate the safety and efficacy of nabilone under relatively similar conditions of use. The figures cited cannot be used to predict precisely the incidence of untoward events in the course of usual medical practice, in which patient characteristics and other factors may differ from those that prevailed in the clinical trials. These incidence figures also cannot be compared with those obtained from other clinical studies involving related drug products because each group of drug trials is conducted under a different set of conditions.

Finally, it is important to emphasize that these tabulations do not reflect the relative severity and/or clinical importance of the adverse events. A better perspective on the serious adverse events associated with the use of nabilone is provided in the WARNINGS and PRECAUTIONS sections.

The following tables list in order of decreasing frequency the adverse reactions encountered by a substantial proportion of patients treated with nabilone participating in representative controlled clinical trials.

Adverse Reactions by Body System:

The following list of adverse events is organized by decreasing frequency within body systems for patients treated with nabilone in controlled clinical trials. All events are listed regardless of causality assessment.

Blood and Hematopoietic: Anemia

Cardiovascular: Orthostatic hypotension, hypotension, tachycardia, syncope, palpitation, flushing, hypertension, arrhythmia, and cerebral vascular accident.

Eye and Ear: Vision disturbance, ear tightness, eye irritation, eye dryness, equilibrium dysfunction, tinnitus, eye disorder, amblyopia, eye swelling, eyelid diseases, pupil dilation, photophobia, and visual field defect.

Gastrointestinal: Dry mouth, nausea, anorexia, vomiting, diarrhea, abdominal pain, constipation, aphthous ulcer, mouth irritation, gastritis, and dyspepsia.

Genitourinary: Increased urination, decreased urination, hot flashes, urinary retention, and frequency of micturition.

Infection: Bacterial infection

Metabolic and Endocrine: Thirst

Musculoskeletal: Muscle pain, back pain, neck pain, joint pain, and unspecified pain.

Nervous System: Drowsiness, vertigo, ataxia, decreased concentration, sedation, hallucinations, paresthesia, tremor, memory disturbance, perception disturbance, convulsions, dystonia, numbness, and akathisia.

Psychiatric: Euphoria (feeling “high”), sleep disturbance, depression, confusion, disorientation, anxiety, depersonalization syndrome, speech disorder, abnormal dreams, insomnia, mood swings, inebriated feeling, toxic psychosis, paranoia, apathy, thought disorder, withdrawal, panic disorder, phobic neurosis, emotional disorder, and hyperactivity.

Respiratory: Dyspnea, pharyngitis, nasal congestion, sinus headache, thick tongue, dry throat, dry nose, wheezing, nosebleed, cough, voice change, and chest pain.

Skin and Appendages: Anhidrosis, photosensitivity, pruritus, rash, and allergic reactions.

Miscellaneous and Ill-Defined Conditions: Headache, fatigue, lightheadedness, coordination disturbance, asthesia, dysphoria, dizziness, taste change, excessive appetite, chills, excessive sweating, nervousness, malaise, postural dizziness, twitch, irritability, fever, inhibited walking, unconsciousness, hypotonia, and impaired urination.

Postmarketing Adverse Reactions: Nabilone has been marketed internationally since 1982. The following adverse reactions listed in order of decreasing frequency by body system have been reported since nabilone has been marketed. All events are listed regardless of causality assessment.

Blood and Hematopoietic: Leukopenia

Cardiovascular: Hypotension and tachycardia

Eye and Ear: Visual disturbances

Gastrointestinal: Dry mouth, nausea, vomiting, and constipation

Nervous System: Hallucinations, CNS depression, CNS stimulation, ataxia, stupor, vertigo, convulsion, and circumoral paresthesia

Psychiatric: Somnolence, confusion, euphoria, depression, dysphoria, depersonalization, anxiety, psychosis, and emotional lability

Miscellaneous and Ill-Defined Conditions: Dizziness, headache, insomnia, abnormal thinking, chest pain, lack of effect, and face edema