Nabilone capsules

You will have been prescribed nabilone to prevent (or treat) feelings of sickness caused by your anticancer medicines. It is not clear how the medicine works, but it can be helpful even if other anti-sickness medicines have not been effective. It is usually prescribed by a hospital doctor. It is a man-made cannabinoid. This means that it has effects similar to extracts from the cannabis plant.

• Before you start the treatment, read the manufacturer's printed information leaflet from inside the pack and any additional information your doctor has given to you. These will give you more information about nabilone, and will also provide you with a full list of side-effects which you could experience from taking it.
• Take the capsules exactly as your doctor tells you to. It is likely that you will be prescribed one (1 mg) capsule twice-daily throughout each cycle of your chemotherapy and for up to two days afterwards. Swallow the capsule with a drink of water. You may be advised to take your first dose the night before you start chemotherapy and then another dose one to three hours before your treatment begins. If it is considered necessary, your doctor can increase your dose to a maximum of two 1 mg capsules three times a day.
• Take nabilone at the same time of day each day if possible - this will help you to take your doses regularly. Try to take the correct number of doses each day, but never take two doses at the same time to make up for a missed dose.

Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains the most common ones associated with nabilone. You will find a full list in the manufacturer's information leaflet supplied with your medicine. Some of the side-effects listed below may last for two or three days after you've stopped taking nabilone.

If you experience other symptoms which you think may be due to the capsules, speak with your doctor or pharmacist for further advice.

• Keep all medicines out of the sight and reach of children.
• Store in a cool, dry place, away from direct heat and light.

Cesamet® (nabilone) is a synthetic cannabinoid for oral administration. Nabilone as a raw material occurs as a white to off-white polymorphic crystalline powder. In aqueous media, the solubility of nabilone is less than 0.5 mg/L, with pH values ranging from 1.2 to 7.0.

Chemically, nabilone is similar to the active ingredient found in naturally occurring Cannabis sativa L. [Marijuana; delta-9-tetrahydrocannabinol (delta-9-THC)]. Nabilone is (±)-trans-3-(l,l-dimethylheptyl)- 6,6a,7,8,10,10a-hexahydro-l-hydroxy-6-6-dimethyl-9H-dibenzo[b,d]pyran-9-one and has the empirical formula C24H36O3. It has a molecular weight of 372.55. The structural formula is as follows:

Each 1 mg Cesamet capsule contains 1 mg of nabilone and the following inactive ingredients: povidone and corn starch. The capsule shells contain the following inactive ingredients: FD&C Blue No. 2 (indigo carmine), red iron oxide, gelatin, and titanium dioxide.

To report SUSPECTED ADVERSE REACTIONS, contact Meda Pharmaceuticals Inc. at 1-800-723-1400 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

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

Incidence of Adverse Reactions in Active-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

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 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 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.

Nabilone may be habit-forming and should be used only by the person it was prescribed for. Nabilone should never be given to another person, especially someone who has a history of drug abuse or habitual marijuana use. Keep the medication in a secure place where others cannot get to it.

Do not use nabilone if you have ever had an allergic reaction to natural or man-made marijuana.

Before taking nabilone, tell your doctor if you have high blood pressure, heart disease, a history of mental illness or drug addiction, or if you are also using other medicines that can affect your central nervous system, such as a tranquilizer, sleep medicine, or anti-psychotic medications.

Use this medication exactly as it was prescribed for you. Do not use it in larger amounts or for longer than recommended by your doctor.

Avoid using other medicines that affect the central nervous system (such as stimulants, diet pills, cold medicine, pain medication, muscle relaxers, and medicine for seizures, depression, anxiety, mental illness, or Parkinson's disease). These other drugs can add to the effects of nabilone.

Nabilone causes effects that will impair your thinking or reactions. Do not drive or do anything that requires you to be awake and alert until the effects of nabilone wear off.

There are many other medicines that can add to the side effects of nabilone. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Avoid using other medicines that affect the central nervous system (such as stimulants, diet pills, cold medicine, pain medication, muscle relaxers, and medicine for seizures, depression, anxiety, mental illness, or Parkinson's disease). These other drugs can add to the effects of nabilone.

Nabilone causes effects that will impair your thinking or reactions. Do not drive or do anything that requires you to be awake and alert until the effects of nabilone wear off.