4.1. Therapeutic indications

Megace is a progestational agent, indicated for the treatment of certain hormone dependent neoplasms, such as breast cancer.

4.2. Posology and method of administration

Breast cancer:

160 mg/day taken once daily.

At least two months of continuous treatment is considered an adequate period for determining the efficacy of Megace.

Children:

Safety and effectiveness in paediatric patients have not been established.

Megace is not recommended for use in children.

Elderly:

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. See section 4.4.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Precautions:

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

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

Patients with rare hereditary problems of galactose intolerance, total 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. 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 during treatment with megestrol acetate, and it may be useful to monitor renal function.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6. Fertility, pregnancy and lactation

Megace is not recommended for women who are pregnant or who are breast feeding.

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. The risk of hypospadias, 5 to 8 per 1,000 male births in the general population, may be approximately doubled with the exposure to progestational drugs. 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 Megace during the first four months of pregnancy or if she becomes pregnant whilst taking Megace, she should be apprised of the potential risks to the foetus.

Women of child bearing potential should be advised to avoid becoming pregnant.

Breastfeeding

Because of the potential for adverse effects, nursing should be discontinued during treatment with Megace.

4.7. Effects on ability to drive and use machines

There are no known effects of megestrol acetate on the ability to drive or operate machinery.

4.8. Undesirable effects

The main side-effect experienced by patients while taking megestrol acetate, particularly at high doses, is weight gain, which is usually not associated with water retention, but which is secondary to an increased appetite and food intake. Weight gain is associated with an increase in fat and body cell mass.

Constipation and urinary frequency have also been reported in patients who received high doses of megestrol acetate in clinical trials.

A rarely encountered side effect of prolonged administration of megestrol acetate is urticaria, presumably an idiosyncratic reaction to the drug. The drug is devoid of the myelosuppressive activity characteristic of many cytotoxic drugs and it causes no significant changes in haematology, blood chemistry or urinalysis.

Pituitary adrenal axis abnormalities including glucose intolerance, new onset diabetes, exacerbation of pre-existing diabetes with decreased glucose tolerance and Cushing's syndrome have been reported with the use of megestrol acetate. Clinically apparent adrenal insufficiency has been rarely reported in patients shortly after discontinuing megestrol acetate. The possibility of adrenal suppression should be considered in all patients taking or withdrawing from chronic megestrol acetate therapy. Replacement stress doses of glucocorticoids may be indicated.

The list is presented by system organ class, MedDRA preferred term, and frequency using the following frequency categories: very common (≥1/10), common (≥1/100, < 1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (< 1/10000), and not known (cannot be estimated from the available data).

System Organ Class

Frequency

MedDRA Term

Neoplasms benign, malignant, and unspecified (including cysts and polyps)

Common

Tumour flare #

Endocrine disorders

Very common

Adrenal insufficiency, cushingoid, Cushing's syndrome

Metabolism and nutrition disorders

Very common

Diabetes mellitus, glucose tolerance impaired, hyperglycaemia, increased appetite

Psychiatric disorders

Common

Mood altered

Nervous system disorders

Common

Carpal tunnel syndrome, lethargy

Cardiac disorders

Common

Cardiac failure

Vascular disorders

Very common

Thrombophlebitis, pulmonary embolism*, hypertension, hot flush

Respiratory, thoracic and mediastinal disorders

Very common

Dyspnoea

Gastrointestinal disorders

Common

Nausea, vomiting, diarrhoea, flatulence

Very common

Constipation

Skin and subcutaneous tissue disorders

Common

Rash, alopecia

Renal and urinary disorders

Common

Pollakiuria

Reproductive system and breast disorders

Common

Menrorrhagia, erectile dysfunction

General disorders and administration site condition

Common

Asthenia, pain, oedema

Investigations

Very common

Weight increased

† Source of frequencies: Megestrol Acetate Oral, Corporate Product Labeling Profile (CPLP) dated 12 November 1996.

#with or without hypercalcemia

* Pulmonary embolism (in some cases fatal)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

No acute toxicological effects have resulted from studies involving Megace (megestrol acetate) 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, listlessness, and chest pain. There is no specific antidote for overdose with Megace. In case of overdose, appropriate supportive measures should be taken.