Megestrol Acetate

History of hypersensitivity to megestrol acetate or any component of the formulation. Known or suspected pregnancy.

• Megestrol acetate may cause fetal harm when administered to a pregnant woman.
• For animal data on fetal effects, (see PRECAUTIONS:
• Carcinogenesis, Mutagenesis, Impairment of Fertility:
• Impairment of Fertility ).
• There are no adequate and well-controlled studies in pregnant women.
• If this drug is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this drug, the patient should be apprised of the potential hazard to the fetus.
• Women of childbearing potential should be advised to avoid becoming pregnant.
• Megestrol acetate is not intended for prophylactic use to avoid weight loss.
• (See also PRECAUTIONS:
• Carcinogenesis, Mutagenesis, and Impairment of Fertility section.) The glucocorticoid activity of megestrol acetate oral suspension has not been fully evaluated.
• Clinical cases of new onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and overt Cushing's Syndrome have been reported in association with the chronic use of megestrol acetate.
• In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic megestrol acetate therapy in the stressed and non-stressed state.
• Furthermore, adrenocorticotropin (ACTH) stimulation testing has revealedthe frequent occurrence of asymptomatic pituitary-adrenal suppression in patients treated with chronic megestrol acetate therapy.
• Therefore, the possibility of adrenal insufficiency should be considered in any patient receiving or being withdrawn from chronic megestrol acetate therapy who presents with symptoms and/or signs suggestive of hypoadrenalism (e.g., hypotension, nausea, vomiting, dizziness, or weakness) in either the stressed or non-stressed state.
• Laboratory evaluation for adrenal insufficiency and consideration of replacement or stress doses of a rapidly acting glucocorticoid are strongly recommended in such patients.
• Failure to recognize inhibition of the hypothalamic-pituitary-adrenal axis may result in death.
• Finally, in patients who are receiving or being withdrawn from chronic megestrol acetate therapy, consideration should be given to the use of empiric therapy with stress doses of a rapidly acting glucocorticoid in conditions of stress or serious intercurrent illness (e.g., surgery, infection).
• General:
• Therapy with megestrol acetate oral suspension for weight loss should only be instituted after treatable causes of weight loss are sought and addressed.
• These treatable causes include possible malignancies, systemic infections, gastrointestinal disorders affecting absorption, endocrine disease and renal or psychiatric diseases.
• Effects on HIV viral replication have not been determined.
• Use with caution in patients with a history of thromboembolic disease.
• Use in Diabetics:
• Exacerbation of pre-existing diabetes with increased insulin requirements has been reported in association with the use of megestrol acetate.
• Information for Patients:
• Patients using megestrol acetate should receive the following instructions:
• This medication is to be used as directed by the physician.
• Report any adverse reaction experiences while taking this medication.
• Use contraception while taking this medication
• if you are a woman capable of becoming pregnant.
• Notify your physician if you become pregnant while taking this medication.
• Drug Interactions:
• Pharmacokinetic studies show that there are no significant alterations in pharmacokinetic parameters of zidovudine or rifabutin to warrant dosage adjustment when megestrol acetate is administered with these drugs.
• The effects of zidovudine or rifabutin on the pharmacokinetics of megestrol acetate were not studied.
• Megestrol acetate may interact with warfarin and increase International Normalized Ratio (INR).
• Closely monitor INR in patients taking megestrol acetate and warfarin.
• Animal Toxicology:
• Long-term treatment with megestrol acetate may increase the risk of respiratory infections.
• A trend toward increased frequency of respiratory infections, decreased lymphocyte counts, and increased neutrophil counts was observed in a two-year chronic toxicity/carcinogenicity study of megestrol acetate conducted in rats.
• Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis - Data on carcinogenesis were obtained from studies conducted in dogs, monkeys and rats treated with megestrol acetate at doses 53.2, 26.6 and 1.3 times lower than the proposed dose (13.3 mg/kg/day) for humans.
• No males were used in the dog and monkey studies.
• In female beagles, megestrol acetate (0.01, 0.1 or 0.25 mg/kg/day) administered for up to 7 years induced both benign and malignant tumors of the breast.
• In female monkeys, no tumors were found following 10 years of treatment with 0.01, 0.1 or 0.5 mg/kg/day megestrol acetate.
• Pituitary tumors were observed in female rats treated with 3.9 or 10 mg/kg/day of megestrol acetate for 2 years.
• The relationship of these tumors in rats and dogs to humans is unknown but should be considered in assessing the risk-to-benefit ratio when prescribing megestrol acetate oral suspension and in surveillance of patients on therapy.
• (See WARNINGS .) Mutagenesis - No mutagenesis data are currently available.
• Impairment of Fertility - Perinatal/postnatal (segment III) toxicity studies were performed in rats at doses (0.05 to 12.5 mg/kg) less than that indicated for humans (13.3 mg/kg); in these low dose studies, the reproductive capability of male offspring of megestrol acetate-treated females was impaired.
• Similar results were obtained in dogs.
• Pregnant rats treated with megestrol acetate showed a reduction in fetal weight and number of live births, and feminization of male fetuses.
• No toxicity data are currently available on male reproduction (spermatogenesis).
• Pregnancy:
• No adequate animal teratology information is available at clinically relevant doses.
• (See WARNINGS and PRECAUTIONS:
• Carcinogenesis, Mutagenesis, Impairment of Fertility:
• Impairment of Fertility. ) Nursing Mothers:
• Because of the potential for adverse effects on the newborn, nursing should be discontinued if megestrol acetate oral suspension is required.
• Use in Women:
• Breakthrough bleeding was observed in all 10 female patients participating in the clinical trials.
• Megestrol acetate oral suspension is a progesterone derivative, which may induce vaginal bleeding in women.
• Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
• Geriatric Use:
• Clinical studies of megestrol acetate oral suspension in the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with AIDS did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients.
• Other reported clinical experience has not identified differences in responses between 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, and of concomitant disease of other drug therapy.
• Megestrol acetate is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.
• Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

• No serious unexpected side effects have resulted from studies involving megestrol acetate oral suspension administered in dosages as high as 1200 mg/day.
• In post-marketing experience, limited reports of overdose have been received.
• Signs and symptoms reported in the context of overdose included diarrhea, nausea, abdominal pain, shortness of breath, cough, unsteady gait, listlessness, and chest pain.
• There is no specific antidote for overdose with megestrol acetate oral suspension.
• In case of overdose, appropriate supportive measures should be taken.
• Megestrol acetate has not been tested for dialyzability, however, due to its low solubility it is postulated that dialysis would not be an effective means of treating overdose