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 |
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
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 marijuana-like "high" at therapeutic
doses. Cesamet was shown to be qualitatively and quantitatively similar to approved
oral delta-9-THC in the production of cannabis-like effects, thus demonstrating
its potential for abuse.
Preclinical studies performed in both dogs and monkeys demonstrated that Cesamet
was cannabinoid-like. 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.