Bristol-Myers Squibb Holdings Limited

Megace 40 mg/ml Oral Suspension

Megestrol acetate 40mg/ml

Also contains Sucrose 50 mg/ml and Sodium (<1mmol/ml)

For a full list of excipients, see section 6.1

Oral suspension

White to cream coloured, milky suspension

Megace Suspension is indicated in male and female patients for the treatment of anorexia or weight loss secondary to cancer or AIDS.

Adults:

400-800mg given as a single daily dose.

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

Children:

Megace is not recommended for use in children.

Elderly:

Insufficient data from clinical studies of megestrol 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, 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 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 in dose selection, and it may be useful to monitor renal function.

Megace is contraindicated in patients who have demonstrated hypersensitivity to any of the components of the formulations. Megace is also contraindicated in patients with thromboembolic disorders.

Megace should be used with caution in patients with a history of thrombophlebitis.

Megace Oral Suspension contains sucrose which may be harmful to the teeth.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Progesterone and certain progesterones have shown to produce reversible virilisation in some female offspring of women treated with such substances during pregnancy.

At present, no data are known regarding these effects.

Megace should not be administered to women who are pregnant or to mothers who are breast feeding.

Fertility and reproduction studies with high doses of megestrol acetate have shown a reversible feminising effect on some male rat foetuses.

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 in male foetuses may be approximately doubled with the exposure to progestational drugs.

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.

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

None known.

Occasionally noted side effects are nausea, vomiting, oedema and breakthrough uterine bleeding.

Rare reports have been received of patients developing dyspnoea, heart failure, hypertension, hot flushes, mood changes, cushingoid facies, tumour flare (with or without hypercalcaemia), hyperglycaemia, alopecia and carpal tunnel syndrome while taking megestrol acetate. Thromboembolic phenomena including thrombophlebitis and pulmonary embolism (in some cases fatal) have been reported. 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.

Similarly in patients with advanced non-endocrine sensitive cancer who received megestrol acetate for anorexia and weight loss, dyspnoea, nausea, oedema, pain, lethargy and diarrhoea were commonly observed.

In clinical trials in patients with AIDS there was no significant difference between active and placebo treatment in patients reporting at least one adverse event. Events reported included diarrhoea, impotence, rash, flatulence, asthenia, and pain. Aside from impotence, all occurred more commonly in patients receiving placebo.

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

Pituitary adrenal axis abnormalities including glucose intolerance 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.

Patients should be observed when Megace is abruptly withdrawn.

No serious side effects have resulted from studies involving Megace (megestrol acetate) administered in dosages as high as 1600 mg/day.

Reports of overdose have 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.

The major 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/food intake and an increase in fat and body cell mass. It is this effect which forms the basis for use of megestrol acetate in patients with anorexia or weight loss. The mechanism by which Megace produces its effects in anorexia and cachexia are unclear.

Estimates of plasma levels of megestrol acetate are dependent on the measurement method used. Plasma levels depend on intestinal and hepatic inactivation of the drug, which may be affected by intestinal tract motility, intestinal bacteria, concomitant antibiotic administration, body weight, diet and hepatic function.

Metabolites have accounted for only 5% to 8% of an administered dose of megestrol acetate. The major route of drug elimination in humans is urinary excretion averaging approximately 66% and faecal excretion averaging approximately 20% of the administered dose. Respiratory excretion and fat storage may account for the fraction of an administered dose not found in urine or faeces.

There are no alterations in pharmacokinetic parameters when megestrol acetate is administered with zidovudine or rifabutin.

There are no findings in the preclinical animal studies which are relevant to the therapeutic indications.

Citric acid anhydrous

Lemon-lime flavour

Polyethylene glycol

Polysorbate 80

Sodium benzoate

Sodium citrate

Sucrose

Water

Xanthan gum.

Not applicable

3 years

Do not store above 25°C.

High density polyethylene bottles with a child-resistant closure available in 240ml pack size.

No special requirements

Bristol-Myers Squibb Holdings Limited

t/a Bristol-Myers Pharmaceuticals,

Swords,

County Dublin

PA 48/27/3

Date of first authorisation: 10 December 1998

Date of last renewal: 10 December 2008

07 April 2011

POM