Megestrol Acetate Tablets USP 160mg TajPharma

1. Name of the medicinal product
a) Megestrol Acetate Tablets USP 20mg TajPharma
b) Megestrol Acetate Tablets USP 40mg TajPharma
c) Megestrol Acetate Tablets USP 160mg TajPharma

2. Qualitative and quantitative composition
a) Each tablet contains
Megestrol Acetate USP 20 mg
Excipients         q.s.

b) Each tablet contains
Megestrol Acetate USP 40 mg
Excipients           q.s.

c) Each tablet contains
Megestrol Acetate USP 160 mg
Excipients            q.s.

3. Pharmaceutical form
Tablets
Off-white, oval, biconvex tablets with a break line.
The break line is only to facilitate breaking for ease of swallowing and not to divide into equal doses

4. Clinical particulars

4.1 Therapeutic indications
Megestrol acetate 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 Megestrol Acetate.

Children:
Safety and effectiveness in paediatric patients have not been established.
Megestrol Acetate 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.

4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients present in the drug

4.4 Special warnings and precautions for use
Precautions:
Megestrol Acetate 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, 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. 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
None stated.

4.6 Fertility, pregnancy and lactation
Megestrol Acetate 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 Megestrol Acetate during the first four months of pregnancy or if she becomes pregnant whilst taking Megestrol Acetate, 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 Megestrol Acetate.

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).

4.9 Overdose
No acute toxicological effects have resulted from studies involving Megestrol Acetate (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 Megestrol Acetate. In case of overdose, appropriate supportive measures should be taken.

5. Pharmacological properties

5.1 Pharmacodynamic properties
Megestrol acetate possesses pharmacological properties similar to those of natural progesterone. Its progestational activity is slightly greater than that of medroxyprogesterone acetate, norethindrone, norethindrone acetate and norethynodrel; slightly less than that of chlormadinone acetate; and substantially less than that of norgestrel.

Megestrol acetate is a potent progestogen that exerts significant anti-oestrogenic effects. It has no androgenic or oestrogenic properties. It has anti-gonadotropic, anti-uterotropic and anti-androgenic/anti-myotropic actions. It has a slight but significant glucocorticoid effect and a very slight mineralocorticoid effect.

5.2 Pharmacokinetic properties
Orally Peak plasma levels of tritiated megestrol acetate and metabolites occur one to three hours after oral administration. When 4 to 91mg of c-labelled megestrol acetate were administered orally to women, the major route of drug elimination was in the urine. The urinary and fecal recovery of total radioactivity within 10 days ranged from 56.6% to 78.4% (mean 66.4%) and 7.7% to 30.3% (mean 19.8%), respectively. The total recovered radioactivity varied between 83.1% and 94.7% (mean 86.2%).

Megestrol acetate metabolites, which were identified in the urine as glucuronide conjugates, were 17-alpha-acetoxy-2-alpha hydroxy-6-methylpregna-4, 6-diene-3, 20-dione; 17-alpha-acetoxy-6-hydroxymethylpregna-4, 6-diene-3, 20-dione; and 17-alpha-acetoxy-2 alpha-hydroxy-6-hydromethylpregna-4, 6-diene-3, 20-dione; these identified metabolites accounted for only 5-8% of the administered dose.

Serum concentrations were measured after the administration of single and multiple oral doses of megestrol acetate. Adult male and post-menopausal female volunteers, no more than 65 years of age participated in the study.

Megestrol acetate is readily absorbed following oral administration of 20, 40, 80 and 200 mg doses. Megestrol serum concentrations increase with increasing doses, the relationship between increasing dosage and increasing serum levels not being arithmetically proportional. Average peak serum concentrations for the four doses tested were 89, 190, 209 and 465 ng/ml.

Mean peak serum concentrations are found three hours after single-dose administration for all dosage levels studied. The serum concentration curve appears biphasic, and the beta-phase half-life is 15 to 20 hours long.

After multiple doses over a three-day period, serum levels increase each day and are estimated to reach 80% to 90% predicted steady-state levels on the third day.

5.3 Preclinical safety data
Administration of megestrol acetate to female dogs for up to 7 years was associated with an increased incidence of both benign and malignant tumors of the breast. Comparable studies in rats and studies in monkeys were not associated with an increased incidence of tumors. The relationship of megestrol acetate-associated dog tumors 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

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

6. Pharmaceutical particulars

 6.1 List of excipients
Colloidal anhydrous silica
Lactose monohydrate
Magnesium stearate
Microcrystalline cellulose
Povidone
Sodium starch glycollate

6.2 Incompatibilities
Not applicable.

6.3 Shelf life
36 months – Blister packs
36 months – Amber glass bottles

6.4 Special precautions for storage
Do not store Megestrol Acetate Tablets above 25°C. Store in the original package in order to protect from moisture.

6.5 Nature and contents of container
Amber glass bottles of 30, 60 or 100
Blister packs of 30 tablets
Pack sizes: 30 and 100 tablets.

6.6 Special precautions for disposal and other handling
None.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Megestrol Acetate Tablets USP 160mg TajPharma

Package leaflet: Information for the patient

a) Megestrol Acetate Tablets USP 20mg TajPharma
b) Megestrol Acetate Tablets USP 40mg TajPharma
c) Megestrol Acetate Tablets USP 160mg TajPharma

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
– Keep this leaflet. You may need to read it again.
– If you have any further questions, ask your doctor or pharmacist.
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
– If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

What is in this leaflet
1. What Megestrol Acetate Tablets are and what they are used for
2. What you need to know before you take Megestrol Acetate Tablets
3. How to take Megestrol Acetate Tablets
4. Possible side effects
5. How to store Megestrol Acetate Tablets
6. Contents of the pack and other information

1. WHAT MEGESTROL ACETATE TABLETS ARE AND WHAT THEY ARE USED FOR
The active ingredient  is megestrol acetate. Megestrol acetate belongs to a group of medicines called progestogens and is used to treat certain types of cancer known as hormone-dependent cancer, which include cancer of the breast.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE MEGESTROL ACETATE TABLETS
Do not take Megestrol Acetate tablets if you:
– are allergic to megestrol acetate or any of the other ingredients of this medicine .
Warnings and precautions
Tell you doctor if you:
– have severe liver problems
– currently suffer from, or have a history of suffering from blood clots (thrombophlebitis)
– have diabetes, as Megestrol Acetate tablets can increase your blood sugar levels
If you are over 65 years of age your doctor may want to monitor your kidney function from time to time, as this can sometimes decrease with age.
Other medicines and Megestrol Acetate tablets
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Pregnancy and breast-feeding
Do not take Megestrol Acetate tablets if you are pregnant, think you may be pregnant, or if you are breast-feeding.
Driving and using machines
Megestrol Acetate Tablets do not usually affect your ability to drive.
Megestrol Acetate tablets contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. HOW TO TAKE MEGESTROL ACETATE TABLETS
Always take Megestrol Acetate tablets exactly as your doctor has told you. You should check with your doctor if you are not sure.
The usual dosage is 160 mg megestrol acetate per day.
Tablets should be swallowed with a glass of water.
This medicine is not recommended for children. Megestrol Acetate tablets should be taken for at least two months to see if they are effective.
Some patients take them for many years.
Do not stop taking them, unless advised to do so by your doctor.
If you take more Megestrol Acetate tablets than you should
If you take more Megestrol Acetate than you should, go to your nearest hospital emergency department or contact your doctor immediately.
Take the empty container and any remaining medicine with you.
If you forget to take Megestrol Acetate tablets
If you miss a dose, do not worry. If you remember within a few hours of the missed dose take it as soon as possible, but if it is almost time for your next dose then skip the forgotten one and continue as before. Do not take a double dose to make up for the one you missed.

4. POSSIBLE SIDE EFFECTS
As with all medicines, Megestrol Acetate can cause side effects although not everybody gets them.
If you notice any of the following, stop taking Megestrol Acetate and contact your doctor immediately:
– swelling of the face, lips, or tongue
– skin rash
– difficulty breathing
As these may be signs of an allergic reaction. Other side effects which may occur with Megestrol Acetate tablets are:
Very Common (affects more than 1 in 10 people)
– increase in appetite and weight gain (not associated with water retention)
– shortness of breath
– hot flushes, reddening of the face and neck – high blood pressure
– increased blood sugar levels
– rounded face, sometimes called ‘moon’ face
– constipation
– swelling of a vein due to a blood clot
– blood clot in the lungs

Signs of a blood clot can include loss of co-ordination, slurred speech, pains in your groin, pains or numbness in your arm or leg (especially in calf of leg), shortness of breath, weakness, headache, and fainting. If you experience any of these signs tell your doctor immediately.  Common (affects between 1 in 10 to 1 in 100 people) –
temporary increase in the signs and symptoms of your disease.
– changes in mood
– numbness, pain or tingling in fingers or thumb – heart attack
– hair loss
– diarrhoea
– tiredness
– feeling weak
– impotence
– passing wind
– needing to urinate more often
– feeling sick and being sick
– changes in vaginal bleeding (breakthrough bleeding, spotting)
–  build up of fluid which causes swelling (mainly in the ankles)
–  pain
–  rash, including hives or nettle rash(urticaria)

Reporting of side effects
 If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

5. HOW TO STORE MEGESTROL ACETATE TABLETS
Do not store above 25°C. Store in the original package in order to protect from moisture. They should not get too hot or damp; so do not leave your tablets near a radiator, on a window sill or in the bathroom.
Please check the expiry date of the product, shown on the carton and blister of Megestrol Acetate tablets. Do not use after the month stated. Keep this medicine out of the sight and reach of children.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Further Information

What Megestrol Acetate Soluble Tablets contain
The active ingredient is megestrol acetate.
a) Each tablet contains: Megestrol Acetate USP 20mg
b) Each tablet contains: Megestrol Acetate USP 40mg
c) Each tablet contains: Megestrol Acetate USP 160mg
The other ingredients are: microcrystalline cellulose, lactose monohydrate, magnesium stearate, povidone, colloidal anhydrous silica, and sodium starch glycolate.

What Megestrol Acetate Tablets look like and contents of the pack
Megestrol acetate tablets (160 mg) are oval shaped biconvex tablets. Tablets are available in blister packs of 30 tablets.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com