Cesamet Side Effects Center

SIDE EFFECTS

Commonly Encountered Reactions

During controlled clinical trials of Cesamet, 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 Cesamet 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 Cesamet 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 Cesamet participating in representative controlled clinical trials.

Incidence of Adverse Reactions in Placebo-Controlled Studies

Adverse Event	Nabilone (n=132)		Placebo (n=119)
	Patients	Percent	Patients	Percent
Vertigo	69	52	3	3
Drowsiness	69	52	6	5
Dry Mouth	47	36	2	2
Ataxia	19	14	0	0
Euphoria	14	11	1	1
Sleep Disturbance	14	11	1	1
Dysphoria	12	9	0	0
Headache	8	6	0	0
Nausea	5	4	0	0
Disorientation	3	2	0	0
Depersonalization	2	2	1	1

Incidence of Adverse Reactions in Active-Controlled Studies

Adverse Event	Nabilone (n=250)		Prochlorperazine (n=232)
	Patients	Percent	Patients	Percent
Drowsiness	165	66	108	47
Vertigo/Dizziness	147	59	53	23
Euphoria	95	38	12	5
Dry Mouth	54	22	11	5
Depression	35	14	37	16
Ataxia	32	13	4	2
Visual Disturbance	32	13	9	4
Concentration Difficulties	31	12	3	1
Hypotension	20	8	3	1
Asthenia	19	8	10	4
Anorexia	19	8	22	9
Headache	18	7	14	6
Sedation	7	3	2	1
Increased Appetite	6	2	2	1

Incidence of Adverse Reactions in Placebo-Controlled Studies

Adverse Reactions by Body System - The following list of adverse events is organized by decreasing frequency within body systems for patients treated with Cesamet 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 - Cesamet has been marketed internationally since 1982. The following adverse reactions listed in order of decreasing frequency by body system have been reported since Cesamet 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

To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321- 4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Potential interactions between Cesamet 2 mg, and diazepam 5 mg; sodium secobarbital 100 mg; alcohol 45 mL (absolute laboratory alcohol); or codeine 65 mg, were evaluated in 15 subjects. Only a single combination was utilized at any one time. The subjects were evaluated according to physiologic (i.e., heart rate and blood pressure), psychometric, psychomotor, and subjective parameters. In this study, as expected, the depressant effects of the combinations were additive. Psychomotor function was particularly impaired with concurrent use of diazepam. Caution must thus be used when administering nabilone in combination with any CNS depressant.

Nabilone is purportedly highly bound to plasma proteins, and therefore, might displace other proteinbound drugs. Therefore, practitioners should monitor patients for a change in dosage requirements when administering nabilone to patients receiving other highly protein-bound drugs. Published reports of drugdrug interactions involving cannabinoids are summarized in the following table.

CONCOMITANT DRUG	CLINICAL EFFECT(S)
Amphetamines, cocaine, other sympathomimetic agents Atropine, scopolamine, antihistamines, other anticholinergic agents Amitriptyline, amoxapine, desipramine, other tricyclic antidepressants Barbiturates, benzodiazepines, ethanol, lithium, opioids, buspirone, antihistamines, muscle relaxants, other CNS depressants	Additive hypertension, tachycardia, possibly cardiotoxicity Additive or super-additive tachycardia, drowsiness Additive tachycardia, hypertension, drowsiness Additive drowsiness and CNS depression
Disulfiram	A reversible hypomanic reaction was reported in a 28 y/o man who smoked marijuana; confirmed by dechallenge and rechallenge
Fluoxetine	A 21 y/o female with depression and bulimia receiving 20 mg/day fluoxetine X 4 wks became hypomanic after smoking marijuana; symptoms resolved after 4 days
Antipyrine, barbiturates	Decreased clearance of these agents, presumably via competitive inhibition of metabolism
Theophylline	Increased theophylline metabolism reported with smoking of marijuana; effect similar to that following smoking tobacco
Opioids Naltrexone	Cross-tolerance and mutual potentiation Oral THC effects were enhanced by opioid receptorblockade.
Alcohol	Increase in the positive subjective mood effects of smoked marijuana

Drug Abuse And Dependence

Controlled Substance

Cesamet, a synthetic cannabinoid pharmacologically related to Cannabis sativa L. (Marijuana; (delta-9-THC) is a highly abusable substance. Cesamet is controlled under Schedule II (CII) of the Controlled Substances Act. Prescriptions for Cesamet should be limited to the amount necessary for a single cycle of chemotherapy (i.e., a few days). Cesamet may produce subjective side effects which may be interpreted as a euphoria or marijuana-like “high” at therapeutic doses.

It is not known what proportion of individuals exposed chronically to Cesamet or other cannabinoids will develop either psychological or physical dependence. Long term use of these compounds has, however, been associated with disorders of motivation, judgment, and cognition. It is not clear, though, if this is a manifestation of the underlying personalities of chronic users of this class of drugs or if cannabinoids are directly responsible for these effects. An abstinence syndrome has been reported following discontinuation of delta-9-THC at high doses of 200 mg per day for 12 to 16 consecutive days. The acute phase was characterized by psychic distress, insomnia, and signs of autonomic hyperactivity (sweating, rhinorrhea, loose stools, hiccups). A protracted abstinence phase may have occurred in subjects who reported sleep disturbances for several weeks after delta-9-THC discontinuation.

Abuse

Cesamet may produce subjective side effects that may be interpreted as a euphoria or marijuanalike “high” at therapeutic doses. Cesamet was shown to be qualitatively and quantitatively similar to delta-9-THC in the production of cannabis-like effects, thus demonstrating that Cesamet has a high potential for abuse.

Preclinical studies performed in both dogs and monkeys demonstrated that Cesamet was cannabinoidlike. As with delta-9-THC, tolerance develops rapidly to the pharmacological effects in both the dog and the monkey. Cross-tolerance between Cesamet and delta-9-THC was demonstrated in the monkey.

Dependence

The physical dependence capacity of Cesamet is unknown at this time. Patients who participated in clinical trials of up to 5 days’ duration evidenced no withdrawal symptoms on cessation of dosing.

Read the entire FDA prescribing information for Cesamet (Nabilone Capsules)