Apetiz Tablet

Apetiz tablet is indicated for the palliative treatment of advanced carcinoma of the breast or endometrium (i.e., recurrent, inoperable or metastatic disease). It should not be used instead of currently accepted procedures such as surgery, radiation or chemotherapy.

Apetiz oral suspension is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of Acquired Immunodeficiency Syndrome (AIDS) & cancer.

Megestrol Acetate is a synthetic, antineoplastic and progestational drug. While the precise mechanism by which Megestrol Acetate produces its antineoplastic effects against endometrial carcinoma is unknown at the present time, inhibition of pituitary gonadotrophin production and resultant decrease in estrogen secretion may be factors. The antineoplastic action of megestrol acetate on carcinoma of the breast is effected by modifying the action of other steroid hormones and by exerting a direct cytotoxic effect on tumor cells. In metastatic cancer, hormone receptors may be present in some tissues but not others. The receptor mechanism is a cyclic process whereby estrogen produced by the ovaries enters the target cell, forms a complex with cytoplasmic receptor and is transported into the cell nucleus. There it induces gene transcription and leads to the alteration of normal cell functions. Pharmacologic doses of megestrol acetate not only decrease the number of hormone-dependent human breast cancer cells but also are capable of modifying and abolishing the stimulatory effects of estrogen on these cells.

Estimates of plasma levels of Megestrol Acetate are dependent on the measurement method used. Peak plasma concentrations occur 2 to 3 hours after a single oral dose 160 mg tablets. The plasma half-life of Megestrol Acetate is 33 to 38 hours. Approximately 66% of an administered dose is excreted in the urine and approximately 20% in the faeces.

Tablet:

• Breast cancer: 160 mg/day
• Endometrial carcinoma: 40-320 mg/day in divided doses.
• At least 2 months of continuous treatment is considered an adequate period for determining the efficacy of Megestrol.

Oral Suspension: The recommended adult initial dosage of Megestrol Oral Suspension is 800 mg/day (20 ml/day).

With medicine: Possible interactions of Apetiz with concomitant medications have not been investigated.

With food and others: Estrogens and Progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid.

History of hypersensitivity to Megestrol Acetate or any component of the formulation. Known or suspected pregnancy.

Weight gain is a frequent side effect of Apetiz when it is used in patients with cancer of the breast or endometrium. This gain is associated with increased appetite. It is this effect which forms the basis for use of Apetiz in patients with anorexia, cachexia or weight loss. Weight gain is associated with an increase in fat and body cell mass.

Untoward reactions that have been reported to occur in patients receiving Apetiz include nausea, vomiting, edema and breakthrough uterine bleeding and occur in approximately 1% to 2% of patients. Gynecomastia and loss of hearing have also been reported. Dyspnea, heart failure, hypertension, hot flashes, mood changes, Cushingoid facies, tumor flare (with or without hypercalcemia), hyperglycemia, alopecia, carpal tunnel syndrome and rash have also occurred.

Thromboembolic phenomenon including thrombophlebitis and pulmonary embolism (in some cases fatal) have also been reported.

Megestrol is not recommended for women who are pregnant. Several reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and genital abnormalities in male and female foetuses. There are insufficient data to quantify the risk to exposed female foetuses, however some of these drugs induce mild virilisation of the external genitalia of the female foetuses. If a patient is exposed to Megestrol Acetate during the first four months of pregnancy or if she becomes pregnant whilst taking Megestrol, she should be apprised of the potential risks to the foetus. Women of child bearing potential should be advised to avoid becoming pregnant. Because of the potential for adverse effects, nursing should be discontinued during treatment with Megestrol.

Apetiz should be used with caution in patients with a history of thrombophlebitis and in patients with severe impaired liver function.

Apetiz should be used under the supervision of a specialist and the patients kept under regular surveillance. Apetiz can exert adrenocortical effects. This should be borne in mind in patient surveillance.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Insufficient data from clinical studies of megesterol acetate are available for patients 65 years of age 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, use in elderly patients should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Apetiz is known to be substantially excreted by the kidney, and the risk of toxic reactions to Apetiz may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken during treatment with Apetiz, and it may be useful to monitor renal function.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Insufficient data from clinical studies of Apetiz tablets are available for patients 65 years of age and older to determine whether they respond differently than younger patients.

No acute toxicological effects have resulted from studies involving Apetiz administered in dosages as high as 1600 mg/day for six months or more. Reports of overdose have also been received in the postmarketing setting. Signs and symptoms reported in the context of overdose included diarrhoea, nausea, abdominal pain, shortness of breath, cough, unsteady gait, listiessness, and chest pain. There is no specific antidote for overdose with Apetiz. In case of overdose, appropriate supportive measures should be taken.

Store in a cool (below 30°C) and dry place, away from light & moisture. Keep all medicines out of reach of children.