Marinol Warnings, Precautions, Pregnancy, Nursing, Abuse - Dronabinol

Marinol Warnings, Precautions, Pregnancy, Nursing, Abuse - Dronabinol

WARNINGS

Patients receiving treatment with MARINOL^® 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.

The risk/benefit ratio of MARINOL^® (Dronabinol) Capsules use should be carefully evaluated in patients with the following medical conditions because of individual variation in response and tolerance to the effects of MARINOL^® Capsules.

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

MARINOL^® 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 MARINOL^® Capsules as well. Multiple substance abuse is common and marijuana, which contains the same active compound, is a frequently abused substance.

MARINOL^® Capsules should be used with caution and careful psychiatric monitoring in patients with mania, depression, or schizophrenia because MARINOL^® Capsules may exacerbate these illnesses.

MARINOL^® 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.

MARINOL^® 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 MARINOL^® (Dronabinol) Capsules should be alerted to the potential for additive central nervous system depression if MARINOL^® Capsules is used concomitantly with alcohol or other CNS depressants such as benzodiazepines and barbiturates.

Patients receiving treatment with MARINOL^® 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 MARINOL^® 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 MARINOL^® Capsules and following dosage adjustments.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenicity studies in mice and rats have been conducted under the US 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 90mg/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.

Nursing Mothers

Use of MARINOL^® Capsules is not recommended in nursing mothers since, in addition to the secretion of HIV virus in breast milk, dronabinol is concentrated in and secreted in human breast milk and is absorbed by the nursing baby.

Geriatric Use

Clinical studies of MARINOL^® (Dronabinol) Capsules in AIDS and cancer patients did not include the sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, increased sensitivity to psychoactive effects and of concomitant disease or other drug therapy.