Dronabinol (Page 2 of 4)

INDICATIONS AND USAGE

Dronabinol capsules are indicated for the treatment of:

  1. anorexia associated with weight loss in patients with AIDS; and
  2. nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.

CONTRAINDICATIONS

Dronabinol capsules are contraindicated in any patient who has a known sensitivity to dronabinol or any of its ingredients. It contains cannabinoid and sesame oil and should never be used by patients allergic to these substances.

WARNINGS

Patients receiving treatment with dronabinol capsules should be specifically warned not to drive, operate machinery, or engage in any hazardous activity until it is established that they are able to tolerate the drug and to perform such tasks safely.

PRECAUTIONS

General:

The risk/benefit ratio of dronabinol use should be carefully evaluated in patients with the following medical conditions because of individual variation in response and tolerance to the effects of dronabinol.

Seizure and seizure-like activity have been reported in patients receiving dronabinol capsules during marketed use of the drug and in clinical trials. (See ADVERSE REACTIONS and OVERDOSAGE.) Dronabinol capsules should be used with caution in patients with a history of seizure disorder because dronabinol capsules may lower the seizure threshold. A causal relationship between dronabinol capsules and these events has not been established. Dronabinol capsules should be discontinued immediately in patients who develop seizures and medical attention should be sought immediately.

Dronabinol capsules should be used with caution in patients with cardiac disorders because of occasional hypotension, possible hypertension, syncope, or tachycardia (see CLINICAL PHARMACOLOGY).

Dronabinol capsules should be used with caution in patients with a history of substance abuse, including alcohol abuse or dependence, because they may be more prone to abuse dronabinol capsules as well. Multiple substance abuse is common and marijuana, which contains the same active compound, is a frequently abused substance.

Dronabinol capsules should be used with caution and careful psychiatric monitoring in patients with mania, depression, or schizophrenia because dronabinol capsules may exacerbate these illnesses.

Dronabinol capsules should be used with caution in patients receiving concomitant therapy with sedatives, hypnotics or other psychoactive drugs because of the potential for additive or synergistic CNS effects.

Dronabinol capsules should be used with caution in elderly patients because they may be more sensitive to the neurological, psychoactive, and postural hypotensive effects of the drug. (see INDIVIDUALIZATION OF DOSAGES.)

Dronabinol capsules should be used with caution in pregnant patients, nursing mothers, or pediatric patients because it has not been studied in these patient populations.

Information for Patients:

Patients receiving treatment with dronabinol capsules should be alerted to the potential for additive central nervous system depression if dronabinol capsules is used concomitantly with alcohol or other CNS depressants such as benzodiazepines and barbiturates.

Patients receiving treatment with dronabinol capsules should be specifically warned not to drive, operate machinery, or engage in any hazardous activity until it is established that they are able to tolerate the drug and to perform such tasks safely.

Patients using dronabinol capsules should be advised of possible changes in mood and other adverse behavioral effects of the drug so as to avoid panic in the event of such manifestations. Patients should remain under the supervision of a responsible adult during initial use of dronabinol capsules and following dosage adjustments.

Drug Interactions:

In studies involving patients with AIDS and/or cancer, dronabinol capsules have been co-administered with a variety of medications (e.g., cytotoxic agents, anti-infective agents, sedatives, or opioid analgesics) without resulting in any clinically significant drug/drug interactions. Although no drug/drug interactions were discovered during the clinical trials of dronabinol capsules, cannabinoids may interact with other medications through both metabolic and pharmacodynamic mechanisms. Dronabinol is highly protein bound to plasma proteins, and therefore, might displace other protein-bound drugs. Although this displacement has not been confirmed in vivo , practitioners should monitor patients for a change in dosage requirements when administering dronabinol to patients receiving other highly protein-bound drugs. Published reports of drug/drug interactions involving cannabinoids are summarized in the following table.

CONCOMITANT DRUG CLINICAL EFFECT(S)
Amphetamines, cocaine, other sympathomimetic agents Additive hypertension, tachycardia, possibly cardiotoxicity
Atropine, scopolamine, antihistamines, other anticholinergic agents Additive or super-additive tachycardia, drowsiness
Amitriptyline, amoxapine, desipramine, other tricyclic antidepressants Additive tachycardia, hypertension, drowsiness
Barbiturates, benzodiazepines, ethanol, lithium, opioids, buspirone, antihistamines, muscle relaxants, other CNS depressants 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

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Carcinogenicity studies in mice and rats have been conducted under the U.S. National Toxicology Program (NTP). In the 2-year carcinogenicity study in rats, there was no evidence of carcinogenicity at doses up to 50 mg/kg/day, about 20 times the maximum recommended human dose on a body surface area basis. In the 2-year carcinogenicity study in mice, treatment with dronabinol at 125 mg/kg/day, about 25 times the maximum recommended human dose on a body surface area basis, produced thyroid follicular cell adenoma in both male and female mice but not at 250 or 500 mg/kg/day.

Dronabinol was not genotoxic in the Ames tests, the in vitro chromosomal aberration test in Chinese hamster ovary cells, and the in vivo mouse micronucleus test. It, however, produced a weak positive response in a sister chromatid exchange test in Chinese hamster ovary cells.

In a long-term study (77 days) in rats, oral administration of dronabinol at doses of 30 to 150 mg/m2 , equivalent to 0.3 to 1.5 times maximum recommended human dose (MRHD) of 90 mg/m2 /day in cancer patients or 2 to 10 times MRHD of 15 mg/m2 /day in AIDS patients, reduced ventral prostate, seminal vesicle and epididymal weights and caused a decrease in seminal fluid volume. Decreases in spermatogenesis, number of developing germ cells, and number of Leydig cells in the testis were also observed. However, sperm count, mating success and testosterone levels were not affected. The significance of these animal findings in humans is not known.

Pregnancy:

Pregnancy Category C. Reproduction studies with dronabinol have been performed in mice at 15 to 450 mg/m2 , equivalent to 0.2 to 5 times maximum recommended human dose (MRHD) of 90 mg/m2 /day in cancer patients or 1 to 30 times MRHD of 15 mg/m2 /day in AIDS patients, and in rats at 74 to 295 mg/m2 (equivalent to 0.8 to 3 times MRHD of 90 mg/m2 in cancer patients or 5 to 20 times MRHD of 15 mg/m2 /day in AIDS patients). These studies have revealed no evidence of teratogenicity due to dronabinol. At these dosages in mice and rats, dronabinol decreased maternal weight gain and number of viable pups and increased fetal mortality and early resorptions. Such effects were dose dependent and less apparent at lower doses which produced less maternal toxicity. There are no adequate and well-controlled studies in pregnant women. Dronabinol should be used only if the potential benefit justifies the potential risk to the fetus.

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