Consumer medicine information

Megace tablets

Megestrol acetate

BRAND INFORMATION

Brand name

Megace Tablets

Active ingredient

Megestrol acetate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Megace tablets.

What is in this leaflet

This leaflet answers some common questions about Megace. It does not contain all of the available information. It does not take the place of talking with your doctor or pharmacist.

You should read this leaflet carefully before starting Megace.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep the leaflet with the medicine.

You may need to read it again.

What Megace is used for

Megace contains megestrol acetate a synthetic steroid which is similar to the naturally occurring hormone progesterone. Megestrol acetate competes with naturally occurring hormones for receptor sites in breast tissue, in this way preventing the naturally occurring hormones from stimulating breast cancer cells.

Megace is used to treat the symptoms of breast cancer.

Before you take it

When you must not take it

You must not take Megace if you have an allergy to megestrol acetate or to any of the ingredients listed at the end of this leaflet.

You must not take Megace as a test to see if you are pregnant.

Do not take Megace after the expiry date printed on the pack.

If you take this medicine after the expiry date has passed, it may not work as well.

Do not take this medicine if the packaging shows signs of tampering.

If you are not sure whether you should start taking it, talk to your doctor or pharmacist.

Before you start to take it

You must tell your doctor if:

  • you are or may be pregnant; your doctor will discuss the possible risks and benefits of taking Megace during pregnancy.
  • you are breast feeding; your doctor will discuss the possible risks and benefits of taking Megace during breast feeding.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • diabetes
  • swelling and clotting in a vein

If you have not told your doctor about any of the above, tell them before you start to take Megace.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

How to take it

How much to take

Your doctor or pharmacist will tell you how many Megace tablets you will need to take each day. Usually patients with breast cancer take 160mg (four 40mg tablets or one 160mg tablet each day).

How to take it

Swallow Megace with a glass of water.

When to take it

Take Megace tablets at about the same time each day.

Taking your tablet(s) at the same time each day will have the best effect. It will also help you to remember when to take the tablet(s).

It doesn't matter if you take Megace before or after food.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant too.

Otherwise take it as soon as you remember, and then go back to taking it as you would normally.

Do not take a double dose to make up for the dose you missed.

How long to take it

Megace is taken continuously (every day) and your doctor will tell you when to stop taking it.

If you take too much (Overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) or go Accident and Emergency at the nearest hospital if you think that you or anyone one else may have taken too much Megace. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

While you are taking it

Things you must do

If you become pregnant while taking Megace, tell your doctor immediately.

If you are about to be started on any new medicine, tell your doctor or pharmacist that you are taking Megace.

Things you must not do

Do not give Megace to anyone else, even if they have the same condition as you.

Do not take this medicine for any other complaints unless your doctor tells you to.

Do not stop taking Megace, or lower the dosage, without checking with your doctor or pharmacist.

Things to be careful of

Be careful driving or operating machinery until you know how Megace affects you.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while taking Megace.

Megace will help most people with breast cancer but it may have unwanted side effects in a few people. All medicines can have side effects, sometimes they are serious, most of the time they are not.

Tell your doctor or pharmacist if you notice any of the following and they worry you:
Weight gain (this is a frequent side effect of Megace), nausea, vomiting, and fluid retention. In women vaginal bleeding may occur while taking, or after stopping taking Megace. These are the more common side effects of Megace.

Shortness of breath, hot flushes, mood changes, unusual hair loss or thinning, rash, pain and/or swelling at the wrists, high blood pressure, high levels of sugar in the blood (hyperglycemia) and moon face appearance may also occur very rarely.

If any of the following happen, tell your doctor immediately, or go to Accident and Emergency at your nearest hospital:
Swelling and redness along a vein which is extremely tender when touched; difficulty breathing with swelling of legs or feet due to fluid build up; sudden collapse.

These are very serious side effects. You may need urgent medical attention.

Some patients have experienced adrenal insufficiency after stopping taking Megace. If this happens you may feel weak, tired, loose weight and feel a bit dizzy from time to time. If this happens contact your doctor immediately.

Other side effects not listed above may occur in some patients.

Tell your doctor if you notice anything that is making you feel unwell.

After using it

Storage

Keep Megace tablets in a cool dry place where the temperature stays below 30 degrees C.

Product description

What it looks like

Megace 160mg tablets are white, scored, oval tablets, marked with 160, and are in bottles of 30 tablets.

Ingredients

Megace tablets contain:

Active ingredients:
160mg megestrol acetate.

Inactive ingredients:

  • acacia,
  • lactose,
  • calcium hydrogen phosphate,
  • maize starch,
  • magnesium stearate,
  • silicon dioxide,
  • microcrystalline cellulose and
  • povidone.

BRAND INFORMATION

Brand name

Megace Tablets

Active ingredient

Megestrol acetate

Schedule

S4

 

Name of the medicine

Megestrol acetate.

Excipients.

Lactose, sodium starch glycolate, magnesium stearate, silicon dioxide, microcrystalline cellulose and povidone.

Description

Chemical name: 17α-acetoxy-6-methylpregna -4,6-diene-3,20-dione. Molecular formula: C24H32O4. MW: 384.5. Megestrol acetate is a white, crystalline solid. Megestrol acetate is chemically related to progesterone. It differs by the addition of a 17-acetoxy group, a double bond at position 6 and the presence of a methyl group. Megestrol acetate is practically insoluble in water; soluble in alcohol (1 in 55), chloroform (1 in 8.0), ether (1 in 130), acetone and benzyl alcohol; slightly soluble in fixed oils.

Pharmacology

Megestrol acetate exhibits classical progestational activity. It possesses little or no oestrogenic, androgenic or adrenocorticoid action.
The antineoplastic action of Megace (megestrol acetate) on carcinoma of the breast is unclear. However, it is known to compete for progesterone, androgen and glucocorticoid receptors, and affect pituitary functions.

Pharmacokinetics.

Absorption.

Estimates of plasma levels of megestrol acetate are dependent on the measurement method used. Peak plasma concentrations occur two to three hours after a single oral dose 160 mg tablets.

Distribution.

Similar peak plasma concentrations (90 to 110 nanogram/mL) occur after the administration of one 160 mg tablet or four 40 mg tablets given over 24 hours. The extent of absorption (AUC) was also not different between the two dosage forms. The plasma half-life was 33 to 38 hours.

Metabolism.

The metabolites are three glucuronide conjugates with hydroxylation occurring at either the 2-alpha, or the 6-methyl position or at both positions. Other metabolites occur but account for only 5 to 8% of the dose.

Excretion.

Approximately 66% of an administered dose is excreted in the urine and approximately 20% in the faeces.
Respiratory excretion and fat storage may account for the fraction of an administered dose not found in urine or faeces.

Clinical implications of pharmacokinetic data.

As megestrol acetate is primarily excreted in the urine and has a reasonably long half-life, a potential for accumulation does exist. However, because megestrol acetate is relatively non-toxic, there are no recommendations at present for routine dosage adjustment.

Pharmacodynamics.

Mechanism of Action.

The antitumour action of Megace (megestrol acetate) on carcinoma of the breast is unclear. However, it is known to compete for progesterone, androgen and glucocorticoid receptors, and affect pituitary functions.

Indications

Palliative treatment of recurrent, inoperable or metastatic carcinoma of the breast (see Dosage and Administration). It should not be used in lieu of currently accepted procedures such as surgery, radiation or chemotherapy.

Contraindications

Allergy to megestrol acetate or any of the excipients. As a diagnostic test for pregnancy.
Women of childbearing potential should be advised to avoid becoming pregnant.

Warnings

Progestational agents have been used beginning with the first trimester of pregnancy in an attempt to prevent habitual abortion or treat threatened abortion.
There is no adequate evidence that such use is effective and there is evidence of potential harm to the fetus when such drugs are given during the first four months of pregnancy.
Furthermore, in the vast majority of women, the cause of abortion is a defective ovum, which progestational agents could not be expected to influence. In addition, the uterine relaxant properties of progesterone agents in patients with fertilised defective ova may cause a delay in spontaneous abortion. Therefore, the use of such drugs during the first four months of pregnancy is not recommended.
Several reports suggest an association between intrauterine exposure to female sex hormones and congenital heart defects and limb reduction defects. One study estimated a 4.7-fold increased risk of limb reduction defects in infants exposed to sex hormones (oral contraceptives, hormone withdrawal tests for pregnancy, or attempted treatment for threatened abortion).
Some of these exposures were very short and involved only a few days treatment. The data suggest that the risk of limb reduction defects in exposed fetuses is somewhat less than 1 in 1,000.
Several reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and genital abnormalities in male and female fetuses. The risk of hypospadias, 5 to 8/1,000 male births in the general population, may be approximately doubled with exposure to these drugs. There are insufficient data to quantify the risk to exposed female fetuses, but insofar as some of these drugs induce mild virilisation of the external genitalia of the female fetus, and because of the increased association of hypospadias in the male fetus, it is prudent to avoid the use of these drugs during the first trimester of pregnancy.
If the patient is exposed to megestrol acetate during the first four months of pregnancy, or if she becomes pregnant while taking this drug, she should be apprised of the potential risks to the fetus.

Tumorigenicity.

Administration of megestrol acetate in doses up to 0.25 mg/kg/day for periods up to seven years to female beagle dogs is associated with increased incidence of both benign and malignant tumours of the breast. Studies in rats using doses of 10 mg/kg/day for two years and in monkeys using doses up to 0.5 mg/kg/day for ten years have not been associated with any increased incidence of tumours. The relationship of the dog tumours to humans is unknown but should be considered in assessing the benefit-to-risk ratio when prescribing megestrol acetate and in surveillance of patients on therapy.

Precautions

In rats and beagle dogs, megestrol acetate increased blood glucose. In beagle dogs this was accompanied by changes in the eyes, pancreas and kidneys that were indicative of diabetes mellitus. Close, customary surveillance is indicated for any patient being treated for recurrent or metastatic cancer.
Use with caution in patients with a history of thromboembolic disease or diabetes mellitus.

Use in pregnancy.

(Category D)
The use of progestational agents during the first four months of pregnancy is not recommended (see Warnings).
Animal studies have shown that high doses of progestogens can cause masculinisation of the female fetus.

Use in lactation.

Very small amounts (approximately 0.1%) are excreted in mother's milk. It is however, not known whether these amounts exert any harmful effect on the newborn. Because of the potential for adverse effects on the new born, nursing should be discontinued during treatment with Megace.

Renal impairment.

No information available.

Hepatic impairment.

No information available.

Paediatric use.

Safety and effectiveness have not been established.

Use in the 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 difference 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.

Interactions

No information is available regarding interactions with food, alcohol or other drugs.

Adverse Effects

Weight gain.

Weight gain is a frequent side effect of Megace. This gain has been associated with increased appetite. Weight gain is caused by an increase in fat and body cell mass.

Thromboembolic phenomena.

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

Other adverse reactions.

Nausea, vomiting, oedema and breakthrough uterine bleeding occur in approximately 1 to 2% of patients. Dyspnoea, pain, heart failure, hypertension, hot flushes, sweating, mood changes, cushingoid facies, tumour flare (with or without hypercalcaemia), hyperglycaemia, alopecia, carpal tunnel syndrome, asthenia, malaise, lethargy, rash, flatulence, diarrhoea and impotence have been reported.
Constipation and urinary frequency have 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 glucocorticoid activity of Megace has not been fully evaluated. Clinical cases of glucose intolerance, 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 Megace. In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic Megace therapy in the stressed and non-stressed state. Furthermore, adrenocorticotropin (ACTH) stimulation testing has revealed the frequent occurrence of asymptomatic pituitary/ adrenal suppression in patients treated with chronic Megace therapy. Therefore, the possibility of adrenal insufficiency should be considered in any patient receiving or being withdrawn from chronic Megace therapy who presents with symptoms and/or signs suggestive of hypoadrenalism (e.g. hypotension, nausea, vomiting, dizziness or weakness) in either the stressed or nonstressed 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 recognise inhibition of the hypothalamic/ pituitary/ adrenal axis may result in death. Finally, in patients who are receiving or being withdrawn from chronic Megace therapy, consideration should be given to the use of empirical therapy with stress doses of a rapidly acting glucocorticoid in conditions of stress or serious intercurrent illness (e.g. surgery, infection).

Dosage and Administration

Adults.

Carcinoma of the breast.

The recommended dose is 160 mg/day in single or divided doses. At least two months of continuous treatment is considered an adequate period for determining the efficacy of megestrol acetate.
Best results are obtained in previously untreated receptor positive cases who are more than five years postmenopausal (approximately 40% response rate). In patients with less favourable characteristics, the response rate could be 15% or less.
The oral suspension should not be substituted for the tablets or vice versa.

Overdosage

No serious side effects have resulted from studies involving Megace (megestrol acetate) administered in dosages as high as 1,600 mg/day. Oral administration of large single doses of megestrol acetate (5 g/kg) did not produce toxic effects in mice.
Due to the low solubility of megestrol acetate it is unlikely that dialysis would be an effective means of treating overdosage.

Presentation

Tablets, 160 mg (white, scored, oval, marked 160): 30's.

Storage

Store below 30°C. Shelf life: 3 years.

Poison Schedule

S4.