This preparation tablet is indicated for the treatment of women with severe acne, unresponsive to oral antibiotic and other available treatments, with associated symptoms of androgenization, including seborrhea and mild hirsutism.

This tablet is supplied in blister pack units consisting of 21 tablets; each tablet containing Cyproterone acetate 2 mg and Ethinylestradiol 0.035 mg. Each cycle consists of 21 days on medication and a 7-day interval without medication (3 weeks on, 1 week off).

Cyproterone is a steroid compound with potent antiandrogenic, progestogenic and antigonadotrophic activity. It exerts its antiandrogenic effect by blocking androgen receptors. It also reduces androgen synthesis by a negative feedback effect on the hypothalamo-pituitary-ovarian systems. The estrogen component (Ethinylestradiol) increases levels of sex hormone binding globulin (SHBG) and thus reduces the free circulating plasma levels of androgens. Cyproterone has no tendency to reduce SHBG levels.

If used alone in women,Cyproterone leads to menstrual cycle disturbances which are avoided when combined with Ethinylestradiol. When this tablet is administered in a cyclic manner, it has the added effect of preventing ovulation and possible conception.

The components of this tablet are rapidly absorbed after oral administration. Due to the long terminal half-life of Cyproterone, a 4-fold increase in plasma levels occurs after 6 to 12 days of daily dosing. Long-term therapy (36 months) with this product did not have a significant influence on lipid metabolism. A trend to increase plasma cholesterol and triglyceride levels was observed. There was a slight decrease in low density lipoprotein (LDL) with a simultaneous increase in high density lipoprotein (HDL).

This tablet should not be prescribed solely for its contraceptive properties. If patient compliance is uncertain and contraception is necessary, then a supplementary nonhormonal contraceptive method should be considered.

First Treatment Course: The patient is instructed to take 1 tablet daily for 21 consecutive days beginning on day 1 of her menstrual cycle. (For the first cycle only the first day of menstrual flow is considered Day 1). The tablets are then discontinued for 7 days (1 week). Withdrawal bleeding should usually occur during the period that the patient is off the tablets.The first cycle will be somewhat shorter than usual, whereas all following cycles will last 4 weeks. The patient should be instructed to take the first tablet from the blister pack out of the section marked with the corresponding day (for example "Mon" for Monday) of the week and swallow it with some liquid. The patient should be instructed to take the tablet at the same time each day.

Subsequent Courses: The patient begins her next and all subsequent 21-day course of tablets (following the same 21 days on, 7 days off) on the same day of the week that she began her first course. She begins taking her tablets 7 days after discontinuation,regardless of whether or not withdrawal bleeding is still in progress.

Treatment should be continued for several months,since improvement may not be observed for at least 3 months. The need to continue treatment with This tablet should be evaluated periodically by the treating physician. This drug should be discontinued 3 to 4 cycles after signs have completely resolved.

Pregnancy should be ruled out before continuing treatment with This tablet in patients who have missed a menstrual period, if pregnancy is suspected, medication should be discontinued.

Missed dose: If the patient forgets to take a tablet at the usual time, the tablet may be taken within the next 12 hours. If more than 12 hours have elapsed from the time of usual administration, the patient must discard the missed tablet and continue to take the remaining tablets in the pack at the usual time in order to avoid premature withdrawal bleeding during this cycle. A supplementary nonhormonal method of contraception must be employed until the pack is empty to prevent pregnancy which would necessitate immediate discontinuation of this treatment.

Concurrent use of the following drugs may result in reduced efficacy of this tablet and increased incidence of breakthrough bleeding: Ampicillin, Analgesics, Antihistamines, Antimigraine preparations, Chloramphenicol, Griseofulvin, Isoniazid, Neomycin, Nitrofurantain, Penicillin V, Phenylbutazone, Sulfonamides and Tetracycline.

Concurrent use of anticoagulants with estrogen/progestogen combinations may reduce the anticoagulant effect. Effectiveness of the following drugs may be altered when used concurrently: Antihypertensive, Benzodiazepines (those that undergo oxidative degradation), Beta-adrenergic blockers,Caffeine, Corticosteroids, Hypoglycemic, Phenothiazine, Theophylline, Tricyclic antidepressants and Vitamins.

Concurrent use of the following drugs may reduce the efficacy of this tablet because of accelerated estrogen metabolism caused by the induction of hepatic enzymes: Carbamazepine, Phenobarbital, Phenytoin, Pyrimidine and Rifampicin.

Diabetics using estrogen/progestogen combinations may require adjustment of their antidiabetic medication. Concurrent administration of vitamin C (ascorbic acid) with estrogen/ progestogen combinations has been reported to result in a significant rise in plasma Ethinylestradiol levels.

Rule out pregnancy before treatment is begun. Because of the antiandrogenic action of this tablet,feminization of male fetuses has occurred in animal studies and may possibly occur in humans.

Common side effects are Bleeding, Dizziness, Depression, Weight gain, Headache, Edema, Breast pain, Lactation, Blood clot, Gallstones.
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Fetal abnormalities have been reported to occur in the offspring of women who have taken estrogen/progestogen combinations in early pregnancy. Rule out pregnancy as soon as it is suspected. The use of estrogen/progestogen combinations during the period a mother is breast-feeding her infant may not be advisable. The hormonal components are excreted in breast milk and may reduce its quantity and quality. The long-term effects on the developing child are not known. This drug may cause fluid retention, conditions such as epilepsy.

Predisposing Factors for Coronary Artery Diseases: In women with predisposing factors for coronary artery disease (such as cigarette smoking, hypertension; hypercholesterolemia, obesity, diabetes and increasing age), the use of estrogen or progestogen combinations have been reported as an additional risk factor. After the age of 35 years, estrogen or progestogen combinations should be considered only in exceptional circumstances and when the risk/benefit ratio has been carefully weighed by both the patient and the physician. Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels from the use of this class of medication. This risk increases with age and heavy smoking (15 or more cigarettes per day) and is more marked in women over 35 years of age. Women who use such medication should not smoke. Estrogen/progestogen combinations may cause an increase in plasma lipoproteins and should be administered with caution to women known to have pre-existent hyperlipoproteinemia. Lipid profiles should be determined regularly in these patients. The combination of obesity, hypertension and diabetes is particularly hazardous to women who are taking this class of medication. To avoid this triad of conditions develop, the patient should be placed on an alternate form of therapy.

Discontinue medication at the earliest manifestation of: Thromboembolic and cardiovascular disorders such as: thrombophlebitis, pulmonary embolism, cerebrovascular disorders, myocardial ischemia, mesenteric thrombosis and retinal thrombosis. The use of estrogen/progestogen-combination products should be avoided in conditions which predispose to venous stasis and to vascular thrombosis, e.g. immobilization after accidents or confinement to bed during long-term illness. Under such conditions other nonhormonal methods of treatment should be considered. For use when surgery is contemplated, see Precautions.

• Visual defects, partial or complete.
• Papilledema, or ophthalmic vascular lesions.
• Severe headache of unknown etiology, or worsening of pre-existing migraine headache.
• Onset of jaundice or hepatitis.
• Itching of the whole body.

Hypertension: Patients with essential hypertension whose blood pressure is wellcontrolled may be given the drug but only under close supervision. If a significant elevation of blood pressure in previously normotensive or hypertensive subjects occurs at any time during the administration of the drug, cessation of medication is necessary.

Migraine and Headache: The onset or exacerbation of migraine or the development of headache of a new pattern which is recurrent persistent or severe, requires discontinuation of medication and evaluation of the cause.

Diabetes: Diabetic patients, or those with a family history of diabetes, should be observed closely to detect any alterations in carbohydrate metabolism. Patients predisposed to diabetes who can be kept under close supervision may be given estrogen/progestogen combinations under strict medical supervision. Young diabetic patients whose disease is of recent origin, well-controlled, and not associated with hypertension or other signs of vascular disease such as ocular fundal changes should be closely observed.

Symptoms and Treatment:There have been no reports of overdose with this tablet. There are no specific antidotes and treatment should be symptomatic, based on the knowledge of the pharmacological action of the constituents.

Store below 30°C and in dry place. Protect from light. Keep out of the reach of children.