CYPROTERONE ACETATE AND ETHINYL ESTRADIOL TABLET

NAME OF THE MEDICINAL PRODUCT

Cyproterone Acetate And Ethinyl Estradiol 2 mg/0.035 mg Tablet

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains:

Actives:
Cyproterone acetate

 

Ethinylestradiol

2.00 mg

 

35 micrograms

Excipients:
Lactose monohydrate

Sucrose

31.115 mg

19.371 mg

 

 

 

 

 

 

 

PHARMACEUTICAL FORM
Sugar-coated tablets.
Beige, round tablet, with convex faces.

CLINICAL PARTICULARS

Therapeutic indications
Treatment of moderate to severe acne related to androgen-sensitivity (with or without seborrhoea) and/or hirsutism, in women of reproductive age.

For the treatment of acne, Cyproterone acetate/ EE should only be used after topical therapy or systemic antibiotic treatments have failed.

Since Cyproterone acetate/ EE is also a hormonal contraceptive, it should not be used in combination with other hormonal contraceptives

Posology and method of administration

Method of Administration
Oral use

Dosage regimen
Cyproterone acetate/ EE inhibits ovulation and thereby prevents conception. Patients who are using Cyproterone acetate/ EE should not therefore use an additional hormonal contraceptive, as this will expose the patient to an excessive dose of hormones and is not necessary for effective contraception.

First treatment course: One tablet daily for 21 days, starting on the first day of the menstrual cycle (the first day of menstruation counting as Day 1).

Subsequent courses: Each subsequent course is started after 7 tablet-free days have followed the preceding course.

When the contraceptive action of Cyproterone acetate/ EE is also to be employed, it is essential that the above instructions be rigidly adhered to. Should bleeding fail to occur during the tablet-free interval, the possibility of pregnancy must be excluded before the next pack is started.

When changing from an oral contraceptive and relying on the contraceptive action of Cyproterone acetate/ EE, follow the instructions given below:

Changing from 21-day combined oral contraceptives: The first tablet of Cyproterone acetate/ EE should be taken on the first day immediately after the end of the previous oral contraceptive course. Additional contraceptive precautions are not required.

Changing from a combined Every Day pill (28 day tablets):
Cyproterone acetate/ EE should be started after taking the last hormone containing tablet from the Every Day Pill pack. The first Cyproterone acetate/ EE tablet is taken the next day. Additional contraceptive precautions are not then required.

Changing from a progestogen-only pill (POP):
The first tablet of Cyproterone acetate/ EE should be taken on the first day of bleeding, even if a POP has already been taken on that day. Additional contraceptive precautions are not then required. The remaining progestogen-only pills should be discarded.

Post-partum and post-abortum use:
After pregnancy, Cyproterone acetate/ EE can be started 21 days after a vaginal delivery, provided that the patient is fully ambulant and there are no puerperal complications. Additional contraceptive precautions will be required for the first 7 days of pill taking. Since the first post-partum ovulation may precede the first bleeding, another method of contraception should be used in the interval between childbirth and the first course of tablets. Lactation is contra-indicated with Cyproterone acetate/ EE. After a first-trimester abortion, Cyproterone acetate/ EE may be started immediately in which case no additional contraceptive precautions are required.

Duration of Use
Time to relief of symptoms is at least three months. The need to continue treatment should be evaluated periodically by the treating physician.

Special circumstances requiring additional contraception

Incorrect administration: A single delayed tablet should be taken as soon as possible, and if this can be done within 12 hours of the correct time, contraceptive protection is maintained. With longer delays, additional contraception is needed. Only the most recently delayed tablet should be taken, earlier missed tablets being omitted, and additional non-hormonal methods of contraception (except the rhythm or temperature methods) should be used for the next 7 days, while the next 7 tablets are being taken. Additionally, therefore, if tablet(s) have been missed during the last 7 days of a pack, there should be no break before the next pack is started. In this situation, a withdrawal bleed should not be expected until the end of the second pack. Some breakthrough bleeding may occur on tablet taking days but this is not clinically significant. If the patient does not have a withdrawal bleed during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before starting the next pack.

Gastro-intestinal upset: Vomiting or diarrhoea may reduce the efficacy of oral contraceptives by preventing full absorption. Tablet-taking from the current pack should be continued. Additional non-hormonal methods of contraception (except the rhythm or temperature methods) should be used during the gastro-intestinal upset and for 7 days following the upset. If these 7 days overrun the end of a pack, the next pack should be started without a break. In this situation, a withdrawal bleed should not be expected until the end of the second pack. If the patient does not have a withdrawal bleed during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before starting the next pack. Other methods of contraception should be considered if the gastro-intestinal disorder is likely to be prolonged.

Additional information on special populations

Children and adolescents

Cyproterone acetate/ EE is only indicated after menarche.

Geriatric patients

Not applicable. Cyproterone acetate/ EE is not indicated after menopause.

Patients with hepatic impairment

Cyproterone acetate/ EE is contraindicated in women with severe hepatic disease as long as liver function values have not returned to normal.

Patients with renal impairment

Cyproterone acetate/ EE has not been specifically studied in renally impaired patients. Available data do not suggest a change in treatment in this patient population.

CONTRAINDICATION
Preparations containing oestrogen /progestogen combinations should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first time during their use, the product should be stopped immediately.
• Concomitant use with another hormonal contraceptive
• Venous thrombosis present or in history (deep venous thrombosis, pulmonary embolism)
• Arterial thrombosis present or in history (e.g. myocardial infarction) or prodromal conditions (e.g. angina pectoris and transient ischaemic attack).
• Presence or history of cerebrovascular accident

  • The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis such as:

o diabetes mellitus with vascular symptoms
o severe hypertension
o severe dyslipoproteinaemia

  • Hereditary or acquired predisposition for venous or arterial thrombosis, such as activated protein C (APC) resistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant)
    • History of migraine with focal neurological symptoms.
    • Presence or history of severe hepatic disease e.g. active viral hepatitis and severe cirrhosis, as long as liver function values have not returned to normal.
    • Presence or history of liver tumours (benign or malignant).
    • Current or history of breast cancer.
  • Known or suspected pregnancy.
    • Breast-feeding
    • Hypersensitivity to the active substances or to any of the excipients.

Cyproterone acetate/ EE is contraindicated for concomitant use with the medicinal products containing ombitasvir / paritaprevir / ritonavir or dasabuvir

Relevant UK clinical guidance on COCs should also be consulted.

Cyproterone acetate/ EE is not for use in men.

SPECIAL PRECAUTIONS & WARNINGS

Medical Examination

Assessment of women prior to starting oral contraceptives (and at regular intervals thereafter) should include a personal and family medical history of each woman. Physical examination should be guided by this and by the contraindications and warnings for this product. The frequency and nature of these assessments should be based upon relevant guidelines and should be adapted to the individual woman, but should include measurement of blood pressure and, if judged appropriate by the clinician, breast, abdominal and pelvic examination including cervical cytology.

Exclude the likelihood of pregnancy before starting treatment.

Undiagnosed vaginal bleeding that is suspicious for underlying conditions should be investigated.

Warnings:
Cyproterone acetate/ EE is composed of the progestogen cyproterone acetate and the oestrogen ethinylestradiol and is administered for 21 days of a monthly cycle. It has a similar composition to that of a combined oral contraceptive (COC).

 Duration of Use

Time to relief of symptoms is at least three months. The need to continue treatment should be evaluated periodically by the treating physician.

Women should be advised that Cyproterone acetate/ EE does not protect against HIV infections (AIDS) and other sexually transmitted diseases.

Conditions which require strict medical supervision

If any of the conditions/risk factors mentioned below is present, the benefits of the use of Cyproterone acetate/ EE should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start using Cyproterone acetate/ EE. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her physician. The physician should then decide on whether the use of Cyproterone acetate/ EE should be discontinued.

  • Diabetes mellitus, with mild vascular disease or mild nephropathy, retinopathy or neuropathy
  • Hypertension that is adequately controlled, i.e. systolic >140 to159 mm Hg or diastolic > 90 to 94mmHg (see also Section 4.4 ‘Reasons for stopping Cyproterone acetate/ EE immediately’
  • porphyria
    • clinical depression
    • obesity
    • migraine
    • cardiovascular diseases
    • chloasma

Patients with a history of depression or any condition mentioned above should be monitored during treatment with Cyproterone acetate/ EE.

 Reasons for stopping Cyproterone acetate/ EE immediately:

When stopping oral contraception non-hormonal contraception should be used to ensure contraceptive protection is maintained, if needed.
1. Occurrence for the first time, or exacerbation, of migrainous headaches or unusually frequent or unusually severe headaches.
2. Sudden disturbances of vision or hearing or other perceptual disorders.
3. First signs of thrombosis or blood clots (e.g. unusual pains in or swelling of the leg(s), stabbing pains on breathing or coughing for no apparent reason). Feeling of pain and tightness in the chest.
4. Six weeks before an elective major operation (e.g. abdominal, orthopaedic), any surgery to the legs, medical treatment for varicose veins or prolonged immobilisation, e.g. after accidents or surgery. Do not restart until 2 weeks after full ambulation. In case of emergency surgery, thrombotic prophylaxis is usually indicated e.g. subcutaneous heparin.
5. Onset of jaundice, hepatitis, itching of the whole body.
6. Significant rise in blood pressure
7. Onset of severe depression.
8. Severe upper abdominal pain or liver enlargement.
9. Clear worsening of conditions known to deteriorate during use of hormonal contraception or during pregnancy
10. Pregnancy is a reason for stopping immediately

Circulatory disorders

  • The use of Cyproterone acetate/ EE carries an increased risk of venous thromboembolism (VTE) compared with no use. The excess risk of VTE is highest during the first year a woman starts Cyproterone acetate/ EE or when restarting or switching after a pill-free interval of at least a month. Venous thromboembolism can be fatal in 1-2% of cases.
    • Epidemiological studies have shown that the incidence of VTE is 1.5 to 2 times higher in users of Cyproterone acetate/ EE than in users of levonorgestrel-containing combined oral contraceptives (COCs) and may be similar to the risk for desogestrel / gestodene / drospirenone-containing COCs.
    • The user group of Cyproterone acetate/ EE is likely to include patients that may have an inherently increased cardiovascular risk such as that associated with polycystic ovarian syndrome.
    • Epidemiological studies have also associated the use of hormonal contraceptive with an increased risk for arterial (myocardial infarction, transient ischaemic attack) thromboembolism.
    • Extremely rarely, thrombosis has been reported to occur in other blood vessels, e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in hormonal contraceptive users.
    • Symptoms of venous or arterial thrombosis or of a cerebrovascular accident can include: unusual unilateral leg pain and / or swelling; sudden severe pain in the chest, whether or not it radiates to the left arm; sudden breathlessness; sudden onset of coughing; any unusual, severe, prolonged headache; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; vertigo; collapse with or without focal seizure; weakness or very marked numbness suddenly affecting one side or one part of the body; motor disturbances; ‘acute’ abdomen.
    • The risk of venous thromboembolic events increases with:
    – increasing age;
    – smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age. Women over 35 years of age should be strongly advised not to smoke if they wish to use Cyproterone acetate/ EE);
    – a positive family history (i.e. venous thromboembolism ever in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any hormonal contraceptive use;
    – prolonged immobilisation, major surgery, any surgery to the legs, or major trauma. In these situations it is advisable to discontinue use (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilisation. Antithrombotic treatment should be considered if the use of Cyproterone acetate/ EE has not been discontinued in advance.
    – obesity (body mass index over 30 kg/m2).

There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.

  • The risk of arterial thromboembolic complications or of a cerebrovascular accident increases with:
    – increasing age;
    – smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age. Women over 35 years of age should be strongly advised not to smoke if they wish to use Cyproterone acetate/ EE);
    – dyslipoproteinemia;
    – obesity (body mass index over 30 kg/m2);
    – hypertension;
    – migraine;
    – valvular heart disease;
    – atrial fibrillation;
    – a positive family history (arterial thrombosis ever in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any hormonal contraceptive use.

Other medical conditions, which have been associated with adverse circulatory events, include diabetes mellitus, systemic lupus erythematosus, hemolytic uraemic syndrome, chronic inflammatory bowel disease (e.g. Crohn’s disease or ulcerative colitis) and sickle cell disease.

The increased risk of thromboembolism in the puerperium must be considered (for information on ‘Pregnancy and lactation’.

An increase in frequency or severity of migraine during use of Cyproterone acetate/ EE (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of Cyproterone acetate/ EE.

Women using Cyproterone acetate/ EE should be specifically pointed out to contact their physician in case of possible symptoms of thrombosis. In case of suspected or confirmed thrombosis, Cyproterone acetate/ EE use should be discontinued. Adequate contraception should be initiated because of the teratogenicity of anti-coagulant therapy (coumarins).

  • Other factors affecting circulatory events

The user group of Cyproterone acetate/ EE as a treatment for acne or moderately severe hirsutism is likely to include patients that may have an inherently increased cardiovascular risk such as that associated with polycystic ovarian syndrome.

Biochemical factors that may be indicative of hereditary or acquired predisposition for venous or arterial thrombosis include Activated Protein C (APC) resistance, hyperhomocysteinaemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

When considering risk/benefit, the physician should take into account that adequate treatment of a condition may reduce the associated risk of thrombosis and that the risk associated with pregnancy is higher than that associated with COC or Cyproterone acetate/ EE use.

Tumours
Like many other steroids, Cyproterone acetate/ EE, when given in very high doses and for the majority of the animal’s life-span, has been found to cause an increase in the incidence of tumours, including carcinoma, in the liver of rats. The relevance of this finding to humans is unknown.
Numerous epidemiological studies have been reported on the risks of ovarian, endometrial, cervical and breast cancer in women using combined oral contraceptives. The evidence is clear that high dose combined oral contraceptives offer substantial protection against both ovarian and endometrial cancer. However, it is not clear whether low dose COCs or Cyproterone acetate/ EE confer protective effects to the same level.

  • Breast cancer
    A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using combined oral contraceptives (COCs). The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs or a combination of both. The additional breast cancers diagnosed in current users of COCs or in women who have used COCs in the last ten years are more likely to be localised to the breast than those in women who never used COCs.
    Breast cancer is rare among women under 40 years of age whether or not they take COCs. Whilst this background risk increases with age, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer

The most important risk factor for breast cancer in COC users is the age women discontinue the COC; the older the age at stopping, the more breast cancers are diagnosed. Duration of use is less important and the excess risk gradually disappears during the course of the 10 years after stopping COC use such that by 10 years there appears to be no excess.

The possible increase in risk of breast cancer should be discussed with the user and weighed against the benefits of COCs taking into account the evidence that they offer substantial protection against the risk of developing certain other cancers (e.g. ovarian and endometrial cancer).

  • Cervical Cancer
    The most important risk factor for cervical cancer is persistent HPV infection. Some epidemiological studies have indicated that long-term use of COCs may further contribute to this increased risk but there continues to be controversy about the extent to which this finding is attributable to confounding effects, e.g., cervical screening and sexual behaviour including use of barrier contraceptives.
  • Liver Cancer
    In rare cases benign and in even rarer cases malignant liver tumours leading in isolated cases to life-threatening intra-abdominal haemorrhage have been observed after the use of hormonal substances such as those contained in Cyproterone acetate/ EE. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, a liver tumour should be included in the differential diagnosis.

Other conditions
The possibility cannot be ruled out that certain chronic diseases may occasionally deteriorate during the use of Cyproterone acetate/ EE.

  • Known hyperlipidaemias
    Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs or Cyproterone acetate/ EE.

Women with hyperlipidaemias are at an increased risk of arterial disease. However routine screening of women on COCs or Cyproterone acetate/ EE is not appropriate.

  • Blood pressure
    Hypertension is a risk factor for stroke and myocardial infarction (see section 4.4 ‘Arterial thromboembolic-related conditions’). Although small increases in blood pressure have been reported in many women taking COCs or oestrogen/progestogen combinations like Cyproterone acetate/ EE, clinically relevant increases are rare. However, if sustained hypertension develops during the use of Cyproterone acetate/ EE, antihypertensive treatment should normally be instigated at a level of 160/100 mm Hg in uncomplicated patients or at 140/90 mm Hg in those with target organ damage, established cardiovascular disease, diabetes or with increased cardiovascular risk factors. Decisions about the continued use of Cyproterone acetate/ EE, should be made at lower BP levels, and alternative contraception may be advised.
  • Conditions which deteriorate with pregnancy or during previous COC or Cyproterone acetate/ EE use:

The following conditions have been reported to occur or deteriorate with both pregnancy and use of a COC or oestrogen/progestogen combinations like Cyproterone acetate/ EE. Consideration should be given to stopping Cyproterone acetate/ EE if any of the following occur during use:

• jaundice and/or pruritus related to cholestasis

• COCs or Cyproterone acetate/ EE may increase the risk of gallstone formation and may worsen existing disease

• systemic lupus erythematosus

• herpes gestationis

• otosclerosis-related hearing loss

• sickle cell anaemia

• renal dysfunction

• hereditary angioedema

• epilepsy

• any other condition an individual woman has experienced worsening of during pregnancy or previous use of COCs or Cyproterone acetate/ EE.

  • Disturbances of liver function
    Acute or chronic disturbances of liver function may necessitate the discontinuation of COC or Cyproterone acetate/ EE use until markers of liver function return to normal.
  • Diabetes (without vascular involvement)
    Insulin-dependent diabetics without vascular disease can use Cyproterone acetate/ EE. However it should be remembered that all diabetics are at an increased risk of arterial disease and this should be considered when prescribing COCs or Cyproterone acetate/ EE. Diabetics with existing vascular disease are contraindicated from using Cyproterone acetate/ EE (see section 4.3 Contraindications).
    Although COCs or oestrogen/progestogen combinations like Cyproterone acetate/ EE may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for a need to alter the therapeutic regimen in diabetics using low-dose COCs (containing < 0.05 mg ethinylestradiol). However, diabetic women should be carefully observed while taking COCs or Cyproterone acetate/ EE.
  • Chloasma
    Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking Cyproterone acetate/ EE
  • Menstrual Changes
    Reduction of menstrual flow:This is not abnormal and it is to be expected in some patients. Indeed, it may be beneficial where heavy periods were previously experienced.

Missed menstruation: Occasionally, withdrawal bleeding may not occur at all. If the tablets have been taken correctly, pregnancy is unlikely. Should bleeding fail to occur during the tablet-free interval the possibility of pregnancy must be excluded before the next pack is started.

Intermenstrual bleeding: Irregular bleeding (spotting or breakthrough bleeding) may occur especially during the first months of use. Therefore, the evaluation of any irregular bleeding is only meaningful after an adaptation interval of about three cycles. If bleeding irregularities persist or occur after previously regular cycles, then non-hormonal causes should be considered and adequate diagnostic measures are indicated to exclude malignancy or pregnancy. This may include curettage.

Some women may experience amenorrhoea or oligomenorrhoea after discontinuation of Cyproterone acetate/ EE, especially when these conditions existed prior to use. Women should be informed of this possibility.

  • Lactose and Sucrose Intolerance
    Each tablet of this medicinal product contains 31.115 mg lactose and 19.371 mg sucrose per tablet. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, fructose intolerance or glucose-galactose malabsorption or sucrase-isomaltase should not take this medicine
  • ALT elevations
    During clinical trials with patients treated for hepatitis C virus infections (HCV) with the medicinal products containing ombitasvir / paritaprevir / ritonavir and dasabuvir with or without ribavirin, transaminase (ALT) elevations higher than 5 times the upper limit of normal (ULN) occurred significantly more frequently in women using ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs)

Interaction with other medicinal products and other forms of interaction

Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.

Enzyme inducers

Interactions can occur with drugs that induce microsomal enzymes (especially cytochrome P450 3A4) which can result in increased clearance of sex hormones and which may lead to breakthrough bleeding and/or contraceptive failure.

Enzyme induction can already be observed after a few days of treatment. Maximal enzyme induction is generally seen within a few weeks. After the cessation of drug therapy enzyme induction may be sustained for about 4 weeks.

Women on short term treatment with any of these drugs should temporarily use a barrier method in addition to the COC or choose another method of contraception. The barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation. If the period during which the barrier method is used runs beyond the end of a pack, the next pack should be started without a break. In this situation, a withdrawal bleed should not be expected until the end of the second pack. If the patient does not have a withdrawal bleed during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before resuming with the next pack.

For women receiving long-term therapy with enzyme inducers, another method of contraception should be used.

The following have been shown to have clinically important interactions with Cyproterone acetate/ EE:

Anticonvulsants: barbiturates (including phenobarbitone), primidone, phenytoin, carbamazepine, oxcarbazepine, topiramate.

Antibiotics/antifungals: griseofulvin, rifampicin.

Herbal remedies: St John’s wort (Hypericum perforatum).

Antiretroviral agents:ritonavir, nelfinavir, nevirapine.

Note: There are other antiretroviral agents that may increase plasma concentration of sex hormones.

Substances decreasing the clearance of CHC (enzyme inhibitors)

The clinical relevance of potential interactions with enzyme inhibitors remains unknown.

Concomitant administration of strong CYP3A4 inhibitors can increase plasma concentrations of the oestrogen or the progestin or both.

Etoricoxib doses of 60 to 120 mg/day have been shown to increase plasma concentrations of ethinylestradiol 1.4 to 1.6-fold, respectively when taken concomitantly with a combined hormonal contraceptive containing 0.035 mg ethinylestradiol.

Effects of oestrogen/progestogen combinations on other medicinal products

Oral contraceptives and oestrogen/progestogen combinations like Cyproterone acetate/ EE may affect the metabolism of certain other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine).

Pharmacodynamic interactions
Concomitant use with the medicinal products containing ombitasvir / paritaprevir / ritonavir and dasabuvir, with or without ribavirin may increase the risk of ALT elevations

Therefore, Cyproterone acetate/ EE-users must switch to an alternative method of contraception (e.g., progestagen-only contraception or non-hormonal methods) prior to starting therapy with this combination drug regimen. Cyproterone acetate/ EE can be restarted 2 weeks following completion of treatment with this combination drug regimen.

Clinical data suggest that ethinylestradiol is inhibiting the clearance of CYP1A2 substrates leading to a weak (e.g. theophylline) or moderate (e.g. tizanidine) increase in their plasma concentration.

Other forms of interactions

Laboratory tests
The use of oral contraceptives may influence the results of certain laboratory tests including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of carrier proteins and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Laboratory staff should therefore be informed about oral contraceptive use when laboratory tests are requested.

Fertility, pregnancy and lactation

Cyproterone acetate/ EE is not indicated during pregnancy. If pregnancy occurs during treatment with Cyproterone acetate/ EE, further intake must be stopped.

Animal studies have revealed that feminisation of male foetuses may occur if cyproterone acetate is administered during the phase of embryogenesis at which differentiation of the external genitalia occurs. Although the results of these tests are not necessarily relevant to man, the possibility must be considered that administration of Cyproterone acetate/ EE to women after the 45th day of pregnancy could cause feminisation of male foetuses. It follows from this that pregnancy is an absolute contraindication for treatment with Cyproterone acetate/ EE, and must be excluded before such treatment is begun.

The use of Cyproterone acetate/ EE during lactation may lead to a reduction in the volume of milk produced and to a change in its composition. Minute amounts of the active substances are excreted with the milk. These amounts may affect the child particularly in the first 6 weeks post-partum. Mothers who are breast-feeding should be advised not to take Cyproterone acetate/ EE until the nursing mother has weaned her child off breast milk.

Effects on ability to drive and use machines
None known.

System Organ Class Adverse events reported in clinical trials Adverse events reported post marketing
Common

(≥ 1/100 to <1/10)

Uncommon

(≥ 1/1000 to <1/100)

Rare

(≥1/10,000 to < 1/1000)

Eye disorders contact lens intolerance
Gastrointestinal disorders nausea, abdominal pain vomiting, diarrhea
Immune system disorders hypersensitivity exacerbation of hereditary angioedema
Investigations weight increased weight decreased
Metabolism and nutrition disorders fluid retention hypertriglyceridemia
Nervous system disorders headache migraine exacerbation of chorea
Gastrointestinal disorders Crohn’s disease, ulcerative colitis
Hepatobiliary disorders liver function disturbances
Psychiatric disorders depressed mood, mood altered libido decreased libido increased
Reproductive system and breast disorders breast pain, breast tenderness breast hypertrophy vaginal discharge, breast discharge reduced menstrual flow, spotting, breakthrough bleeding and missed withdrawal bleeding, post pill amenorrhoea
Skin and subcutaneous tissue disorders rash, urticaria erythema nodosum, erythema multiforme chloasma
Vascular Disorders Thromboembolism increase in blood pressure

UNDESIRABLE EFFECTS
Summary of safety profile

The most commonly reported adverse reactions with Cyproterone acetate/ EE are nausea, abdominal pain, increased weight, headache, depressed mood, altered mood, breast pain, breast tenderness. They occur in ≥ 1 % of users.

There is an increased risk of thromboembolism for all women who use Cyproterone acetate/ EE
Tabulated list of adverse events:

Description of selected adverse reactions
Post-marketing reports of severe depression (including very rare reports of suicidal ideation or behaviour) in patients using Cyproterone acetate/ EE have been received. However, a causal relationship between clinical depression and Cyproterone acetate/ EE has not been established.
An increased risk of arterial and venous thrombotic and thrombo-embolic events, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism has been observed in women using CHCs, which are discussed in more detail in.

The following serious adverse events have been reported in women using CHCs, which are discussed in section 4.4 Special warnings and precautions for use:
– Venous thromboembolic disorders;
– Arterial thromboembolic disorders;
– Hypertension;
– Liver tumours;
– Occurrence or deterioration of conditions for which association with COC use is not conclusive: Crohn’s disease, ulcerative colitis, epilepsy, uterine myoma, porphyria, systemic lupus erythematosus, herpes gestationis, Sydenham’s chorea, haemolytic uremic syndrome, cholestatic jaundice;
– Chloasma;
– Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal.
– In women with hereditary angioedema exogenous oestrogens may induce or exacerbate symptoms of angioedema.

The frequency of diagnosis of breast cancer is very slightly increased among COC users. As breast cancer is rare in women under 40 years of age the excess number is small in relation to the overall risk of breast cancer. Causation with COC use is unknown. For further information

Overdose
Interactions

Breakthrough bleeding and/or contraceptive failure may result from interactions of other drugs (enzyme inducers) with oral contraceptives

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 at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Pharmacological properties

Pharmacodynamic properties

Cyproterone acetate/ EE blocks androgen-receptors. It also reduces androgen synthesis both by negative feedback effect on the hypothalamo-pituitiary-ovarian systems and by the inhibition of androgen-synthesising enzymes.

Although Cyproterone acetate/ EE also acts as an oral contraceptive, it is not recommended in women solely for contraception, but should be reserved for those women requiring treatment for the androgen-dependent skin conditions described.

Pharmacokinetic properties

Cyproterone acetate: Following oral administration cyproterone acetate is completely absorbed in a wide dose range. The ingestion of Cyproterone acetate/ EE effects a maximum serum level of 15ng cyproterone acetate/ml at 1.6 hours. Thereafter drug serum levels decrease in two disposition phases characterised by half-lives of 0.8 hours and 2.3 days. The total clearance of cyproterone acetate from serum was determined to be 3.6 ml/min/kg. Cyproterone acetate is metabolised by various pathways including hydroxylations and conjugations. The main metabolite in human plasma is the 15β-hydroxy derivative.
Some dose parts are excreted unchanged with the bile fluid. Most of the dose is excreted in form of metabolites at a urinary to biliary ratio of 3:7. The renal and biliary excretion was determined to proceed with half-life of 1.9 days. Metabolites from plasma were eliminated at a similar rate (half-life of 1.7 days). Cyproterone acetate is almost exclusively bound to plasma albumin. About 3.5 – 4.0% of total drug levels are present unbound. Because protein binding is non-specific changes in sex hormone binding globulin (SHBG) levels do not affect cyproterone acetate pharmacokinetics.
According to the long half-life of the terminal disposition phase from plasma (serum) and the daily intake cyproterone acetate accumulates during one treatment cycle. Mean maximum drug serum levels increased from 15ng/ml (day 1) to 21ng/ml and 24ng/ml at the end of the treatment cycles 1 and 3 respectively. The area under the concentration versus time profile increased 2.2 fold (end of cycle 1) and 2.4 fold (end of cycle 3). Steady state conditions were reached after about 16 days. During long term treatment cyproterone acetate accumulates over treatment cycles by a factor of 2.
The absolute bioavailability of cyproterone acetate is almost complete (88% of dose). The relative bioavailability of cyproterone acetate from Cyproterone acetate/ EE was 109% when compared to an aqueous microcrystalline suspension.

Ethinylestradiol: Orally administered ethinylestradiol is rapidly and completely absorbed. Following ingestion of Cyproterone acetate/ EE maximum drug serum levels of about 80pg/ml are reached at 1.7 hours. Thereafter ethinylestradiol plasma levels decrease in two phases characterised by half-lives of 1 – 2 hours and about 20 hours. For analytical reasons these parameters can only be calculated for higher dosages.
For ethinylestradiol an apparent volume of distribution of about 5 l/kg and a metabolic clearance rate from plasma of about 5 ml/min/kg were determined.
Ethinylestradiol is highly but non-specifically bound to serum albumin. 2% of the drug levels are present unbound. During absorption and first liver passage ethinylestradiol is metabolised resulting in a reduced absolute and variable oral bioavailability. Unchanged drug is not excreted. Ethinylestradiol metabolites are excreted at a urinary to biliary ratio of 4:6 with a half-life of about 1 day.
According to the half-life of the terminal disposition phase from plasma and the daily ingestion steady state plasma levels are reached after 3 – 4 days and are higher by 30 – 40% as compared to a single dose. The relative bioavailability (reference: aqueous microcrystalline suspension) of ethinylestradiol was almost complete.

The systemic bioavailability of ethinylestradiol might be influenced in both directions by other drugs. There is, however, no interaction with high doses of vitamin C.
Ethinylestradiol induces the hepatic synthesis of SHBG and corticosteroid binding globulin (CBG) during continuous use. The extent of SHBG induction, however, is dependent upon the chemical structure and dose of the co-administered progestin. During treatment with Cyproterone acetate/ EE SHBG concentrations in serum increased from about 100nmol/l to 300nmol/l and the serum concentrations of CBG were increased from about 50μg/ml to 95μg/ml.
In vitro, ethinylestradiol is a reversible inhibitor of CYP2C19, CYP1A1 and CYP1A2 as well as a mechanism based inhibitor of CYP3A4/5, CYP2C8 and CYP2J2.

Preclinical safety data

There are no preclinical safety data which could be of relevance to the prescriber and which are not already included in other relevant sections of the SPC.

Pharmaceutical particulars

List of excipients
Lactose, maize starch,
povidone,
talc,
magnesium stearate (E 572),
sucrose, polyethylene glycol 6,000,
calcium carbonate (E 170),
titanium dioxide (E 171),
glycerol 85%,
montan glycol wax,
yellow ferric oxide pigment (E 172).

 Incompatibilities

Not applicable.

 Shelf life

3 years.

.Special precautions for storage
Do not store above 25°C.

Nature and contents of container

Outer carton contains aluminium foil and PVC blister memo packs each containing 21 tablets. Each carton contains either 1 or 3 blister memo packs.

 Special precautions for disposal and other handling

No special requirements.

MARKETING AUTHORISATION HOLDER

TAJ PHARMA CIS LTD.
Marksistsky lane 6, office 221, Moscow, 109147, Russia

MANUFACTURER:

Manufactured in India by:
TAJ PHARMACEUTICALS LTD,
220, Mahagujarat Ind. Estate,  Moraiya,

Tal. Sanand , Dist. Ahmedabad,

Gujarat, INDIA.

Package leaflet:

Information for the patient

Cyproterone Acetate and Ethinyl estradiol 2mg/0.03mg tablets

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. See section 4.

What is in this leaflet

  1. What Cyproterone Acetate / Ethinylestradiol is and what is it used for
    2. What do you need to know Before you take Cyproterone Acetate / Ethinylestradiol
    3. How to take Cyproterone Acetate / Ethinylestradiol
    4. Possible side effects
    5. How to store Cyproterone Acetate / Ethinylestradiol
    6. Contents of the pack and other information

 

1.What  Cyproterone Acetate / Ethinylestradiol is and what is it used for

Cyproterone Acetate / Ethinylestradiol is used to treat skin conditions such as acne, very oily skin and excessive hair growth in women of reproductive age. Due to its contraceptive properties it should only be prescribed for you if your doctor considers that treatment with a hormonal contraceptive is appropriate.
You should only take Cyproterone Acetate / Ethinylestradiol if your skin condition has not improved after use of other anti-acne treatments, including topical treatments and antibiotics.

  1. What do you need to know Before you take Cyproterone Acetate/Ethinylestradiol

Before you take Cyproterone Acetate / Ethinylestradiol
It’s important that you understand the benefits and risks of taking Cyproterone Acetate / Ethinylestradiol before you start taking it, or when deciding whether to carry on taking it. Although Cyproterone Acetate / Ethinylestradiol is suitable for most healthy women it isn’t suitable for everyone.
Warnings and precautions
Talk to your doctor or pharmacist before taking Cyproterone Acetate / Ethinylestradiol or if you have any of the illnesses or risk factors mentioned in this leaflet.
Before you start taking Cyproterone Acetate / Ethinylestradiol
–Your doctor will ask about you and your family’s medical problems and check your bloodØ pressure and exclude the likelihood of you being pregnant. You may also need other checks, such as a breast examination, but only if these examinations are necessary for you or if you have any special concerns.
–Cyproterone Acetate / Ethinylestradiol also works as an oral contraceptive. You and yourØ doctor will have to consider all the things that would normally apply to the safe use of oral hormonal contraceptives.
When should you contact your doctor?
Stop taking the tablets and contact your doctor immediately if you notice possible signs of a blood clot.
While you’re on Cyproterone Acetate / Ethinylestradiol
–You will need regular check-ups with your doctor, usually when you need another prescription of Cyproterone Acetate / Ethinylestradiol.
You should go for regular cervical smear tests.
Ø  Check your breasts and nipples every month for changes – tell your doctor if you can see or
Ø feel anything odd, such as lumps or dimpling of the skin.
If you need a blood test tell your doctor that you are taking Cyproterone Acetate /Ø Ethinylestradiol, because this type of medicine can affect the results of some tests.
–If you’re going to have an operation, make sure your doctor knows about it. You may needØ to stop taking Cyproterone Acetate / Ethinylestradiol about 4–6 weeks before the operation. This is to reduce the risk of a blood clot (see section below). Your doctor will tell you when you can start taking Cyproterone Acetate / Ethinylestradiol again.
–If you need to stop taking Cyproterone Acetate / Ethinylestradiol, remember to useØ another contraceptive (e.g. condoms) if you are relying on Cyproterone Acetate / Ethinylestradiol for contraception.

Cyproterone Acetate / Ethinylestradiol and blood clots
Taking Cyproterone Acetate / Ethinylestradiol may slightly increase your risk of having a blood clot (called a thrombosis), especially in the first year of taking it.
A clot in a leg vein – a deep vein thrombosis (or DVT) – is not always serious. However, if it moves up the veins and blocks an artery in the lungs, it can cause chest pain, breathlessness or collapse. A full recovery is not always made and in 1-2% of cases, can be fatal. This is called a pulmonary embolism and is very rare.
Your chances of having a blood clot are only increased slightly by taking Cyproterone Acetate / Ethinylestradiol compared with women who do not take Cyproterone Acetate / Ethinylestradiol or any contraceptive pill.
–Of 100,000 women who are not taking Cyproterone Acetate / Ethinylestradiol, not on theØ Pill and not pregnant, about 5 to 10 will have a blood clot in a year.
–Of 100,000 women who take Cyproterone Acetate / Ethinylestradiol or the Pill, up to 40Ø will have a blood clot in a year.
–Of 100,000 women who are pregnant, around 60 will have a blood clot in a year.
Ø Very rarely, blood clots can also form in the blood vessels of the heart (causing a heart attack) or the brain (causing a stroke). In healthy young women the chance of having a heart attack or stroke is extremely small.
Blood clots in a vein
A blood clot in a vein (known as a ‘venous thrombosis’) can block the vein. This can happen in veins of the leg, the lung (a lung embolus), or any other organ.
Using a combined pill increases a woman’s risk of developing such clots compared with a woman not taking any combined pill. The risk of developing a blood clot in a vein is highest during the first year a woman uses the pill. The risk is not as high as the risk of developing a blood clot during pregnancy.
The risk of blood clots in a vein in users of a combined pill increases further:
–If you have polycystic ovary syndrome
Ø  as you get older
Ø  if you smokeØ
o When using a hormonal contraceptive like Cyproterone Acetate / Ethinylestradiol you are strongly advised to stop smoking, especially if you are older than 35 years
–if you or any of your close family have had blood clots in the leg, lung or other organ at a
Ø young age  if you are overweight
Ø  if you have very rare blood disorders
Ø  if you have recently had a baby
Ø  if you have diabetes
Ø  if you have certain rare medical conditions such as systemic lupus erythematosus, Crohn’s
disease or ulcerative colitis
–if you have sickle cell disease
Symptoms of blood clots
Stop taking the tablets and see your doctor immediately if you notice possible signs of a blood clot such as:
–a migraine for the first time, a migraine that is worse than normal, unusual, or are frequent, or
severe or long-lasting headaches
Øany sudden changes to your eyesight (such as partial or complete loss of vision, double  vision, or blurred vision)
Øany sudden changes to your hearing, speech (such as slurring or speech disability), sense of smell, taste or touch
Øsevere pain in your abdomen
Ø  severe pain or swelling in either of your legs
Ø  breathlessness or stabbing pain when you breathe
Øunusual sudden coughing for no apparent reason
Ø  severe pain and tightness in the chest which may reach the left arm
Ø  sudden weakness or numbness in one side or any part of your body
Ø  dizziness or fainting.
See a doctor as soon as possible. Do not take any more Cyproterone Acetate / Ethinylestradiol until your doctor says you can. If needed, use another method of contraception, such as condoms, in the meantime.
Following a blood clot, recovery is not always complete. Rarely serious permanent disabilities may occur or the blood clot may even be fatal.
Directly after giving birth, women are at an increased risk of blood clots so you should ask your doctor how soon after delivery you can start taking Cyproterone Acetate / Ethinylestradiol.

Cyproterone Acetate / Ethinylestradiol and cancer
While high dose COCs reduce your risk of cancer of the ovary and womb if used in the long term, it is not clear whether lower dose oestrogen-progestogen containing Pills like Cyproterone Acetate / Ethinylestradiol also provide the same protective effects. However, it also seems that taking Cyproterone Acetate / Ethinylestradiol slightly increases your risk of cancer of the cervix – although this may be due to having sex without a condom, rather than Cyproterone Acetate / Ethinylestradiol. All women should have regular smear tests.
If you have breast cancer, or have had it in the past, you should not take Cyproterone Acetate / Ethinylestradiol or other oral contraceptives, as they slightly increase your risk of breast cancer. This risk goes up the longer you’re on Cyproterone Acetate / Ethinylestradiol, but returns to normal within about 10 years of stopping it. Because breast cancer is rare in women under the age of 40, the extra cases of breast cancer in current and recent Cyproterone Acetate / Ethinylestradiol users is small. For example:
–Of 10,000 women who have never taken Cyproterone Acetate / Ethinylestradiol or theØ Pill, about 16 may have breast cancer by the time they are 35 years old.
–Of 10,000 women who take Cyproterone Acetate / Ethinylestradiol or the Pill for 5 yearsØ in their early twenties, about 17–18 may have breast cancer by the time they are 35 years old.
— Of 10,000 women who have never taken Cyproterone Acetate / Ethinylestradiol or theØ Pill, about 100 may have breast cancer by the time they are 45 years old.
–Of 10,000 women who take Cyproterone Acetate / Ethinylestradiol or the Pill for 5 yearsØ in their early thirties, about 110 may have breast cancer by the time they are 45 years old.
Your risk of breast cancer is higher:
–if you have a close relative (mother, sister or grandmother) who has had breast cancer
Ø  if you are seriously overweight
See a doctor as soon as possible if you notice any changes in your breasts, such as dimpling of the skin, changes in the nipple or any lumps you can see or feel.
-Taking Cyproterone Acetate / Ethinylestradiol has also been linked to liver diseases, such asØ jaundice and noncancer liver tumours, but this is rare. Very rarely, Cyproterone Acetate / Ethinylestradiol has also been linked with some forms of liver cancer in women who have taken it for a long time.
See a doctor as soon as possible if you get severe pain in your stomach, or yellow skin or eyes (jaundice). You may need to stop taking Cyproterone Acetate / Ethinylestradiol.
Make sure Cyproterone Acetate / Ethinylestradiol is OK for you
Cyproterone Acetate / Ethinylestradiol should not be taken by some women

Tell your doctor if you have any medical problems or illnesses.
Do not take Cyproterone Acetate / Ethinylestradiol
Tell your doctor if any of the following conditions applies to you before starting to use Cyproterone Acetate / Ethinylestradiol. Taking Cyproterone Acetate / Ethinylestradiol would put your health at risk. Your doctor may then advise you to use a different treatment:
–If you are using another hormonal contraceptive
Ø  If you are pregnant or might be pregnant
Ø  If you are breast-feeding
Ø  If you have or have ever had breast cancer
Ø  If you have (or have ever had) a problem with your blood circulation. This includes aØ blood clot in the legs (deep vein thrombosis) or the lungs (pulmonary embolism) or any other part of the body
— If you have (or have ever had), or your close family have ever had, a heart attack or stroke.
Ø  If you have any condition which makes you more at risk of a blood clot (thrombosis – seeØ section above, Cyproterone Acetate / Ethinylestradiol and blood clots) or a blood clot in your arteries. This applies to the following conditions:
o diabetes affecting your blood vessels
o very high blood pressure
o a very high level of fat in your blood (cholesterol or triglycerides)
— If you have (or have ever had) any symptoms of a blood clot or of a disease that may beØ an indicator of a heart attack in the future, such as severe chest pain (angina pectoris) or ‘mini-stroke’ (transient ischaemic attack)
–If you have problems with blood clotting (e.g. protein C deficiency)
Ø  If you have uncontrolled blood pressure
Ø  If you have (or have ever) suffered from migraine, with visual disturbances
Ø  If you have ever had a severe liver disease, and you have been told by your doctor thatØ your liver test results are not yet back to normal
— If you have hepatitis C and are taking the medicinal products containingØ ombitasvir/paritaprevir/ritonavir and dasabuvir (see also in section Other medicines and Cyproterone Acetate/Ethinylestradiol).
— If you have ever had liver tumours
Ø  If you are allergic to cyproterone acetate, ethinylestradiol or any of the other ingredientsØ of this medicine .
If you suffer from any of these, or get them for the first time while taking Cyproterone Acetate / Ethinylestradiol, contact your doctor as soon as possible. Do not take Cyproterone Acetate / Ethinylestradiol. If needed, use another form of contraception. Cyproterone Acetate / Ethinylestradiol can make some illnesses worse
Some of the conditions listed below can be made worse by taking Cyproterone Acetate / Ethinylestradiol. Or they may mean it is less suitable for you. You may still be able to take Cyproterone Acetate / Ethinylestradiol but you need to take special care and have check-ups more often.
— If you or your close family have ever had problems with your heart or circulation, such asØ high blood pressure  If you or your close family have ever had problems with blood clotting
Ø  If you have had migraines
Ø  If you are currently suffering from depression or have done so in the past
Ø  If you are overweight (obese)
Ø  If you have the inherited disease called porphyria
Ø  If you have diabetes with blood disorders or disorder of the eye, kidneys or nerves
Ø  If you have inflammation of the pancreas (pancreatitis), or a history or family historyØ of high levels of fat in your blood (hypertriglyceridemia),as you may be at risk of developing pancreatitis
–If you have brown patches on your face or body (chloasma) (see below ‘CyproteroneØ Acetate / Ethinylestradiol and sun-beds or sun-lamps’)
— If you have any illness that worsened during pregnancy or previous use of the Pill orØ  Cyproterone Acetate / Ethinylestradiol .
–If you have hereditary angioedema. Consult your doctor immediately if you experienceØ symptoms of angioedema such as swollen face, tongue or throat, and/or difficulty swallowing, or hives, together with difficulty breathing. Products containing oestrogens may induce or worsen symptoms of angioedema.
Tell your doctor if any apply to you.
Also tell them if you get any of these for the first time while taking Cyproterone Acetate / Ethinylestradiol, or if any get worse or come back, because you may need to stop taking it. Cyproterone Acetate / Ethinylestradiol will not protect you against sexually transmitted infections, such as Chlamydia or HIV. Only condoms can help to do this.
Other medicines and Cyproterone Acetate / Ethinylestradiol
Also check the leaflets that come with all your medicines to see if they can be taken with hormonal contraceptives. Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
If you are taking Cyproterone Acetate / Ethinylestradiol for skin treatment, you must not take any other hormonal contraceptive at the same time.
Some medicines can stop Cyproterone Acetate / Ethinylestradiol from working properly – for example:
— some medicines used to treat epilepsy (such as primidone, phenytoin,
Ø carbamazepine, oxcarbazepine, topiramate, felbamate)  some medicines used to treat HIV and Hepatitis C Virus infection (so-called proteaseØ inhibitors and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nelfinavir and nevirapine)
–griseofulvin and rifampicin (anti-fungal medicines)
Ø  certain sedatives (called barbiturates)
Ø  St. John’s wort (a herbal remedy).
If you do need to take one of these medicines, Cyproterone Acetate / Ethinylestradiol may not be suitable for you or you may need to use extra contraception for a while. Your doctor, pharmacist or dentist can tell you if this is necessary and for how long.
Do not use Cyproterone Acetate/Ethinylestradiol if you have Hepatitis C and are taking the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir as this may cause increases in liver function blood test results (increase in ALT liver enzyme).
Your doctor will prescribe another type of contraceptive prior to start of the treatment with these medicinal products.
Cyproterome Acetate/Ethinylestradiol can be restarted approximately 2 weeks after completion of this treatment.
Cyproterone Acetate / Ethinylestradiol can also affect how well other medicines work. Cyproterone Acetate / Ethinylestradiol may increase or decrease the amount of certain medicines (such as ciclosporin and lamotrigine) in your blood. Your doctor may need to adjust the dose of your other medicine.
In addition, Cyproterone Acetate / Ethinylestradiol can also interfere with the results of some blood tests, so always tell your doctor that you are taking Cyproterone Acetate / Ethinylestradiol if you have a blood test.
Pregnancy and breast-feeding
Do not use Cyproterone Acetate / Ethinylestradiol if you are pregnant or are breast-feeding.
If you think you might be pregnant, do a pregnancy test to confirm that you are before you stop taking Cyproterone Acetate / Ethinylestradiol.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
 Cyproterone Acetate / Ethinylestradiol has no known effect on the ability to drive or use machines.
Cyproterone Acetate / Ethinylestradiol and sun-beds or sun-lamps
 Sun-lamps are used by some women for acne as well as to tan the skin. This is not a very useful treatment for acne. Do not use sun-beds or sun-lamps and avoid prolonged sunbathing if you are taking Cyproterone Acetate / Ethinylestradiol. Their use increases the chance of chloasma, a patchy discolouration of the skin (as it does with ordinary oral contraceptives). Cyproterone Acetate / Ethinylestradiol contains lactose and sucrose
 If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

  1. How to take Cyproterone Acetate / Ethinylestradiol

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Your doctor has chosen Cyproterone Acetate / Ethinylestradiol as a treatment for your severe acne or excessive hair growth on your face and body. However, Cyproterone Acetate / Ethinylestradiol also has a contraceptive effect, so it is important to follow the advice below if you are relying on Cyproterone Acetate / Ethinylestradiol for contraception.

If you are only using Cyproterone Acetate / Ethinylestradiol for your acne or excessive hair growth, you can still follow this advice, but ask your doctor if you are unsure.
Duration of use
Your doctor will tell you how long you need to keep taking Cyproterone Acetate / Ethinylestradiol.
 How to take it
Take Cyproterone Acetate / Ethinylestradiol every day for 21 days
Cyproterone Acetate / Ethinylestradiol comes in strips of 21 pills, each marked with a day of the week.
ØTake your pill at the same time every day.
Ø  Start by taking a pill marked with the correct day of the week.
Ø  Follow the direction of the arrows on the strip. Take one pill each day, until you have
finished all 21 pills.
Ø Swallow each pill whole, with water if necessary. Do not chew the pill.
Then have seven pill-free days
After you have taken all 21 pills in the strip, you have seven days when you take no pills. Within a few days of taking the last pill from the strip, you should have a withdrawal bleed like a period. This bleed may not have finished when it is time to start your next strip of pills. If you are relying on this medicine to prevent pregnancy, always take Cyproterone Acetate / Ethinylestradiol as described here. You don’t need to use extra contraception during the seven pill- free days – as long as you have taken your pills correctly and start the next strip of pills on time. Check with your doctor if you are not sure.
Start your next strip on day eight
 Start taking your next strip of Cyproterone Acetate / Ethinylestradiol after the seven pill-free days (on day eight) – even if you are still bleeding. So if you take the last pill of one pack on a Friday, you willtake the first pill of your next pack on the Saturday of the following week. Always start the new strip on time.
As long as you take Cyproterone Acetate / Ethinylestradiol correctly, you will always start each new strip on the same day of the week. Starting Cyproterone Acetate / Ethinylestradiol

New users or starting Cyproterone Acetate / Ethinylestradiol after a break
It is best to take your first Cyproterone Acetate / Ethinylestradiol pill on the first day of your next period. By starting in this way, you will have contraceptive protection with your first pill.
Changing to Cyproterone Acetate / Ethinylestradiol from another contraceptive Pill
If you are currently taking a 21-day Pill: start Cyproterone Acetate / EthinylestradiolØ the next day after the end of the previous strip. You will have contraceptive protection with your first pill. You will not have a bleed until after your first strip of Cyproterone Acetate / Ethinylestradiol.
If you are taking a 28-day Pill: start taking Cyproterone Acetate / Ethinylestradiol theØ day after your last active pill. You will have contraceptive protection with your first pill. You will not have a bleed until after your first strip of Cyproterone Acetate / Ethinylestradiol.
If you are taking a progestogen-only Pill (POP or ‘mini Pill’):  start Cyproterone AcetateØ / Ethinylestradiol on the first day of bleeding, even if you have already taken the progestogen- only Pill for that day. You will have contraceptive protection straight away.
Starting Cyproterone Acetate / Ethinylestradiol after a miscarriage or abortion
If you have had a miscarriage or an abortion during the first three months of pregnancy, your doctor may tell you to start taking Cyproterone Acetate / Ethinylestradiol straight away. This means that you will have contraceptive protection with your first pill. If you have had a miscarriage or an abortion after the third month of pregnancy, ask your doctor for advice. You may need to use extra contraception, such as condoms, for a short time.
Contraception after having a baby
If you have just had a baby, your doctor may advise you that Cyproterone Acetate / Ethinylestradiol should be started 21 days after delivery provided that you are fully mobile. You do not have to wait for a period. You will need to use another method of contraception, such as a condom, until you start Cyproterone Acetate / Ethinylestradiol and for the first 7 days of pill taking.
A missed pill
If you are less than 12 hours late with a pill, take it straight away. Keep taking your pills at the usual time. This may mean taking two pills in one day. Don’t worry – your contraceptive protection should not be reduced.
If you are more than 12 hours late with a pill, or you have missed more than one pill, your contraceptive protection may be reduced.
ØTake the most recently missed pill as soon as you remember, even if it means taking two
at once. Leave any earlier missed pills in the pack.
ØContinue to take a pill every day for the next seven days at your usual time.
Ø  If you come to the end of a strip of pills during these seven days, start the next stripØ without taking the usual seven day break. You probably won’t have a bleed until after you finish the second strip of pills, but don’t worry. If you finish the second strip of pills and don’t have a bleed, do a pregnancy test before starting another strip.
ØUse extra contraception for seven days after missing a pill, such as condoms.
Ø  If you have missed one or more pills from the first week of your strip (days 1 to 7) andØyou 9 had sex in that week, you could become pregnant. Contact your doctor or pharmacist for advice as soon as possible. They may recommend you use emergency contraception. If you have missed any of the pills in a strip, and you do not bleed in the first pill free break, you may be pregnant. Contact your doctor or do a pregnancy test yourself.
If you start a new strip of pills late, or make your ‘week off’ longer than seven days, you may not be protected from pregnancy. If you had sex in the last seven days, ask your doctor or pharmacist for advice. You may need to consider emergency contraception. You should also use extra contraception, such as a condom, for seven days.
A lost pill
If you lose a pill,
Either take the last pill of the strip in place of the lost pill. Then take all the other pills on their proper days. Your cycle will be one day shorter than normal, but your contraceptive protection won’t be affected. After your seven pill-free days you will have a new starting day, one day earlier than before.
Or if you do not want to change the starting day of your cycle, take a pill from a spare strip if you have one. Then take all the other pills from your current strip as usual. You can then keep the opened spare strip in case you lose any more pills.
If you are sick or have diarrhoea
If you are sick (vomit) or have very bad diarrhoea, your body may not get its usual dose of hormones from that pill. If you are better within 12 hours of taking Cyproterone Acetate / Ethinylestradiol, follow the instructions in section above, A lost pill, which describes how to take another pill.
If you are still sick or have diarrhoea more than 12 hours after taking Cyproterone Acetate / Ethinylestradiol, see section above, A missed pill.
Talk to your doctor if your stomach upset carries on or gets worse. He or she may recommend another form of contraception. Missed a period – could you be pregnant? Occasionally, you may miss a withdrawal bleed. This could mean that you are pregnant, but that is very unlikely if you have taken your pills correctly. Start your next strip at the normal time. If you think that you might have put yourself at risk of pregnancy (for example, by missing pills or taking other medicines), or if you miss a second bleed, you should do a pregnancy test. You can buy these from the chemist or get a free test at your doctors surgery. If you are pregnant, stop taking Cyproterone Acetate / Ethinylestradiol and see your doctor.
Taking more than one pill should not cause harm
It is unlikely that taking more than one pill will do you any harm, but you may feel sick, vomit or have some vaginal bleeding. Talk to your doctor if you have any of these symptoms. When you want to get pregnant
If you are planning a baby, it’s best to use another method of contraception after stopping Cyproterone Acetate / Ethinylestradiol until you have had a proper period. Your doctor or midwife relies on the date of your last natural period to tell you when your baby is due. However, it will not cause you or the baby any harm if you get pregnant straight away.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If any of the following side effects happen, you may need urgent medical attention. Stop taking Cyproterone Acetate / Ethinylestradiol and contact a doctor or go to the nearest hospital immediately.
Uncommon (may affect up to 1 in 100 people)
  –if you get migraines or if you get more frequent headaches
Rare (may affect up to 1 in 1,000 people)
–Signs of a severe allergic reaction or worsening of hereditary angioedema:  a red bumpy rash (hives) and itching, swelling of the hands, face, lips, mouth, tongueØ or throat. A swollen tongue/throat may lead to difficulty swallowing and breathing

Venous or arterial blood clot which include signs such as:
–a migraine for the first time, a migraine that is worse than normal or unusually frequentØ or severe headaches
— any sudden changes to your eyesight (such as loss of vision or blurred vision)
Ø  any sudden changes to your hearing, speech, sense of smell, taste or touch
Ø  pain or swelling in your leg
Ø  stabbing pain when you breathe
Ø  coughing for no apparent reason
Ø  pain and tightness in the chest
Ø  sudden weakness or numbness in one side or part of your body
Ø  dizziness or fainting.
Not known (frequency cannot be estimated from the available data)
Severe depression:
Although, it is not considered a direct side effect of Cyproterone Acetate / Ethinylestradiol, some women have reported feeling depressed whilst taking Cyproterone Acetate / Ethinylestradiol. In very rare cases this has been associated with thoughts of ending their lives. If you develop severe depression, you should stop Cyproterone Acetate / Ethinylestradiol as a precaution, and see your doctor straight away.  –inflammation of the colon or other parts of the intestine (Crohn’s disease orØ ulcerative colitis)
–severe increase in blood pressure

breast cancer, which include signs such as:
–dimpling of the skin
Ø  changes in the nipple
Ø  any lumps you can see or feel.
 cancer of the cervix, which include signs such as:
vaginal discharge that smells and/or contains blood
Ø  unusual vaginal bleeding
Ø  pelvic pain
Ø  painful sex.
 severe liver problems, which include signs such as:
–severe pain in your stomach
Ø  yellow skin or eyes (jaundice)
Ø  inflammation of the liver (hepatitis)
Ø  your whole body starts itching.
Other conditions that may happen or worsen during pregnancy or use of the Pill such as:
– yellowing of the skin (jaundice)
– persistent itching (pruritus)
– kidney or liver problems
– gall stones
– certain rare medical conditions such as systemic lupus erythematosus
– blister-like rash (herpes gestationis) whilst pregnant
– an inherited form of deafness (otosclerosis)
– a personal or family history or a form of sickle cell disease
– an inherited disease called porphyria
– cancer of the cervix
– movement disorder chorea
If you have hereditary angioedema medicines containing certain female sex hormones (oestrogens) may induce or worsen the symptoms of angioedema

Other possible side effects:
Common (may affect up to 1 in 10 people)  ——feeling sick
Ø  stomach ache
Ø  putting on weight
Ø  headaches
Ø  depressive moods or mood swings
Ø  sore or tender breasts
Uncommon (may affect up to 1 in 100 people)  –being sick, diarrhea
Ø  fluid retention
Ø  reduced sex drive
Ø  breast enlargement
Ø  skin rash, which may be itchy
Rare (may affect up to 1 in 1,000 people)
  poor tolerance of contact lenses
Ø  losing weight
Ø  increased sex drive
Ø  vaginal or breast discharge
Ø  painful reddish nodules in the skin ( erythema nodosum ) , skin rash with irregular red
Ø patches ( erythema multiforme )
Not known (frequency cannot be estimated from the available data)
–changes in the amount of fat in the blood or in liver function which may be seen in blood
Ø tests  change in menstrual periods including absence of menstruation. elevated blood glucose( glucose intolerance)
Ø bleeding and spotting between your periods can sometimes occur for the first few monthsØ but this usually stops once your body has adjusted to Cyproterone Acetate / Ethinylestradiol. If it continues, becomes heavy or starts again, contact your doctor chloasma (yellow brown patches on the skin). This may happen even if you have been using Cyproterone Acetate / Ethinylestradiol for a number of months. Chloasma may be reduced by avoiding too much sunlight and/or UV lamps  –increase in blood pressure
Bleeding between periods should not last long A few women have a little unexpected bleeding or spotting while they are taking Cyproterone Acetate / Ethinylestradiol, especially during the first few months. Normally, this bleeding is nothing to worry about and will stop after a day or two. Keep taking Cyproterone Acetate / Ethinylestradiol as usual. The problem should disappear after the first few strips.
You may also have unexpected bleeding if you are not taking your pills regularly, so try to take your pill at the same time every day. Also, unexpected bleeding can sometimes be caused by other medicines.
Make an appointment to see your doctor if you get breakthrough bleeding or spotting that:  –carries on for more than the first few months
Ø  starts after you’ve been taking Cyproterone Acetate / Ethinylestradiol for a while
Ø  carries on even after you’ve stopped taking Cyproterone Acetate / Ethinylestradiol. Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.yellow.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

  1. How to store Cyproterone Acetate / Ethinylestradiol

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton/strip after EXP. The expiry date refers to the last day of that month.
Keep the blister strips in the outer carton in order to protect from light. Do not store above 25degrees.
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.

  1. Contents of the pack and other information


What  Cyproterone Acetate / Ethinylestradiol contain

The active substances are cyproterone acetate and ethinylestradiol. Each coated tablet contains cyproterone acetate 2 mg and ethinylestradiol 35 micrograms.
The tablet also contains: Lactose monohydrate, Maize starch, Povidone, Talc, Magnesium stearate, Sucrose, Macrogol, Calcium carbonate, Glycerol 85%, Titanium dioxide, Iron oxide yellow, Montanglycol wax

What  Cyproterone Acetate / Ethinylestradiol looks like and contents of the pack
Cyproterone Acetate / Ethinylestradiol tablets are round, beige, coated tablets with no markings.
These tablets are available in blister packs of 21, 42, 63, 84, 105, 126, 147, 168, 189, 210, 231, 252 tablets*. Your pharmacist will dispense the number of tablets prescribed by your doctor.
*Not all pack sizes may be marketed.

Manufactured by:
Taj Pharmaceuticals Limited
220, Mahagujarat Ind. Estate, Moraiya, Tal. Sanand, Dist. Ahmedabad, Gujarat, INDIA

Marketing Authorization Holder:
Regal sun co., Ltd.Myanmar

Package leaflet:

Information for the patient

Cyproterone Acetate and Ethinyl estradiol 2mg/0.03mg tablets

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. See section 4.

What is in this leaflet

  1. What Cyproterone Acetate / Ethinylestradiol is and what is it used for
    2. What do you need to know Before you take Cyproterone Acetate / Ethinylestradiol
    3. How to take Cyproterone Acetate / Ethinylestradiol
    4. Possible side effects
    5. How to store Cyproterone Acetate / Ethinylestradiol
    6. Contents of the pack and other information

 

1.What  Cyproterone Acetate / Ethinylestradiol is and what is it used for

Cyproterone Acetate / Ethinylestradiol is used to treat skin conditions such as acne, very oily skin and excessive hair growth in women of reproductive age. Due to its contraceptive properties it should only be prescribed for you if your doctor considers that treatment with a hormonal contraceptive is appropriate.
You should only take Cyproterone Acetate / Ethinylestradiol if your skin condition has not improved after use of other anti-acne treatments, including topical treatments and antibiotics.

  1. What do you need to know Before you take Cyproterone Acetate/Ethinylestradiol

Before you take Cyproterone Acetate / Ethinylestradiol
It’s important that you understand the benefits and risks of taking Cyproterone Acetate / Ethinylestradiol before you start taking it, or when deciding whether to carry on taking it. Although Cyproterone Acetate / Ethinylestradiol is suitable for most healthy women it isn’t suitable for everyone.

Warnings and precautions
Talk to your doctor or pharmacist before taking Cyproterone Acetate / Ethinylestradiol or if you have any of the illnesses or risk factors mentioned in this leaflet.

Before you start taking Cyproterone Acetate / Ethinylestradiol
–Your doctor will ask about you and your family’s medical problems and check your bloodØ pressure and exclude the likelihood of you being pregnant. You may also need other checks, such as a breast examination, but only if these examinations are necessary for you or if you have any special concerns.
–Cyproterone Acetate / Ethinylestradiol also works as an oral contraceptive. You and yourØ doctor will have to consider all the things that would normally apply to the safe use of oral hormonal contraceptives.

When should you contact your doctor?
Stop taking the tablets and contact your doctor immediately if you notice possible signs of a blood clot.

While you’re on Cyproterone Acetate / Ethinylestradiol
–You will need regular check-ups with your doctor, usually when you need another prescription of Cyproterone Acetate / Ethinylestradiol.
You should go for regular cervical smear tests.
Ø  Check your breasts and nipples every month for changes – tell your doctor if you can see or
Ø feel anything odd, such as lumps or dimpling of the skin.
If you need a blood test tell your doctor that you are taking Cyproterone Acetate /Ø Ethinylestradiol, because this type of medicine can affect the results of some tests.
–If you’re going to have an operation, make sure your doctor knows about it. You may needØ to stop taking Cyproterone Acetate / Ethinylestradiol about 4–6 weeks before the operation. This is to reduce the risk of a blood clot (see section below). Your doctor will tell you when you can start taking Cyproterone Acetate / Ethinylestradiol again.
–If you need to stop taking Cyproterone Acetate / Ethinylestradiol, remember to useØ another contraceptive (e.g. condoms) if you are relying on Cyproterone Acetate / Ethinylestradiol for contraception.

Cyproterone Acetate / Ethinylestradiol and blood clots
Taking Cyproterone Acetate / Ethinylestradiol may slightly increase your risk of having a blood clot (called a thrombosis), especially in the first year of taking it.
A clot in a leg vein – a deep vein thrombosis (or DVT) – is not always serious. However, if it moves up the veins and blocks an artery in the lungs, it can cause chest pain, breathlessness or collapse. A full recovery is not always made and in 1-2% of cases, can be fatal. This is called a pulmonary embolism and is very rare.

Your chances of having a blood clot are only increased slightly by taking Cyproterone Acetate / Ethinylestradiol compared with women who do not take Cyproterone Acetate / Ethinylestradiol or any contraceptive pill.
–Of 100,000 women who are not taking Cyproterone Acetate / Ethinylestradiol, not on theØ Pill and not pregnant, about 5 to 10 will have a blood clot in a year.
–Of 100,000 women who take Cyproterone Acetate / Ethinylestradiol or the Pill, up to 40Ø will have a blood clot in a year.
–Of 100,000 women who are pregnant, around 60 will have a blood clot in a year.
Ø Very rarely, blood clots can also form in the blood vessels of the heart (causing a heart attack) or the brain (causing a stroke). In healthy young women the chance of having a heart attack or stroke is extremely small.

Blood clots in a vein
A blood clot in a vein (known as a ‘venous thrombosis’) can block the vein. This can happen in veins of the leg, the lung (a lung embolus), or any other organ.
Using a combined pill increases a woman’s risk of developing such clots compared with a woman not taking any combined pill. The risk of developing a blood clot in a vein is highest during the first year a woman uses the pill. The risk is not as high as the risk of developing a blood clot during pregnancy.

The risk of blood clots in a vein in users of a combined pill increases further:
–If you have polycystic ovary syndrome
Ø  as you get older
Ø  if you smokeØ

o When using a hormonal contraceptive like Cyproterone Acetate / Ethinylestradiol you are strongly advised to stop smoking, especially if you are older than 35 years
–if you or any of your close family have had blood clots in the leg, lung or other organ at a
Ø young age  if you are overweight
Ø  if you have very rare blood disorders
Ø  if you have recently had a baby
Ø  if you have diabetes
Ø  if you have certain rare medical conditions such as systemic lupus erythematosus, Crohn’s
disease or ulcerative colitis
–if you have sickle cell disease

Symptoms of blood clots
Stop taking the tablets and see your doctor immediately if you notice possible signs of a blood clot such as:
–a migraine for the first time, a migraine that is worse than normal, unusual, or are frequent, or
severe or long-lasting headaches
Øany sudden changes to your eyesight (such as partial or complete loss of vision, double  vision, or blurred vision)
Øany sudden changes to your hearing, speech (such as slurring or speech disability), sense of smell, taste or touch
Øsevere pain in your abdomen
Ø  severe pain or swelling in either of your legs
Ø  breathlessness or stabbing pain when you breathe
Øunusual sudden coughing for no apparent reason
Ø  severe pain and tightness in the chest which may reach the left arm
Ø  sudden weakness or numbness in one side or any part of your body
Ø  dizziness or fainting.

See a doctor as soon as possible. Do not take any more Cyproterone Acetate / Ethinylestradiol until your doctor says you can. If needed, use another method of contraception, such as condoms, in the meantime.
Following a blood clot, recovery is not always complete. Rarely serious permanent disabilities may occur or the blood clot may even be fatal.
Directly after giving birth, women are at an increased risk of blood clots so you should ask your doctor how soon after delivery you can start taking Cyproterone Acetate / Ethinylestradiol.

Cyproterone Acetate / Ethinylestradiol and cancer
While high dose COCs reduce your risk of cancer of the ovary and womb if used in the long term, it is not clear whether lower dose oestrogen-progestogen containing Pills like Cyproterone Acetate / Ethinylestradiol also provide the same protective effects. However, it also seems that taking Cyproterone Acetate / Ethinylestradiol slightly increases your risk of cancer of the cervix – although this may be due to having sex without a condom, rather than Cyproterone Acetate / Ethinylestradiol. All women should have regular smear tests.
If you have breast cancer, or have had it in the past, you should not take Cyproterone Acetate / Ethinylestradiol or other oral contraceptives, as they slightly increase your risk of breast cancer. This risk goes up the longer you’re on Cyproterone Acetate / Ethinylestradiol, but returns to normal within about 10 years of stopping it. Because breast cancer is rare in women under the age of 40, the extra cases of breast cancer in current and recent Cyproterone Acetate / Ethinylestradiol users is small. For example:
–Of 10,000 women who have never taken Cyproterone Acetate / Ethinylestradiol or theØ Pill, about 16 may have breast cancer by the time they are 35 years old.
–Of 10,000 women who take Cyproterone Acetate / Ethinylestradiol or the Pill for 5 yearsØ in their early twenties, about 17–18 may have breast cancer by the time they are 35 years old.
— Of 10,000 women who have never taken Cyproterone Acetate / Ethinylestradiol or theØ Pill, about 100 may have breast cancer by the time they are 45 years old.
–Of 10,000 women who take Cyproterone Acetate / Ethinylestradiol or the Pill for 5 yearsØ in their early thirties, about 110 may have breast cancer by the time they are 45 years old.

Your risk of breast cancer is higher:
–if you have a close relative (mother, sister or grandmother) who has had breast cancer
Ø  if you are seriously overweight

See a doctor as soon as possible if you notice any changes in your breasts, such as dimpling of the skin, changes in the nipple or any lumps you can see or feel.
-Taking Cyproterone Acetate / Ethinylestradiol has also been linked to liver diseases, such asØ jaundice and noncancer liver tumours, but this is rare. Very rarely, Cyproterone Acetate / Ethinylestradiol has also been linked with some forms of liver cancer in women who have taken it for a long time.

See a doctor as soon as possible if you get severe pain in your stomach, or yellow skin or eyes (jaundice). You may need to stop taking Cyproterone Acetate / Ethinylestradiol.

Make sure Cyproterone Acetate / Ethinylestradiol is OK for you
Cyproterone Acetate / Ethinylestradiol should not be taken by some women

Tell your doctor if you have any medical problems or illnesses.
Do not take Cyproterone Acetate / Ethinylestradiol
Tell your doctor if any of the following conditions applies to you before starting to use Cyproterone Acetate / Ethinylestradiol. Taking Cyproterone Acetate / Ethinylestradiol would put your health at risk. Your doctor may then advise you to use a different treatment:
–If you are using another hormonal contraceptive
Ø  If you are pregnant or might be pregnant
Ø  If you are breast-feeding
Ø  If you have or have ever had breast cancer
Ø  If you have (or have ever had) a problem with your blood circulation. This includes aØ blood clot in the legs (deep vein thrombosis) or the lungs (pulmonary embolism) or any other part of the body
— If you have (or have ever had), or your close family have ever had, a heart attack or stroke.
Ø  If you have any condition which makes you more at risk of a blood clot (thrombosis – seeØ section above, Cyproterone Acetate / Ethinylestradiol and blood clots) or a blood clot in your arteries. This applies to the following conditions:
o diabetes affecting your blood vessels
o very high blood pressure
o a very high level of fat in your blood (cholesterol or triglycerides)
— If you have (or have ever had) any symptoms of a blood clot or of a disease that may beØ an indicator of a heart attack in the future, such as severe chest pain (angina pectoris) or ‘mini-stroke’ (transient ischaemic attack)
–If you have problems with blood clotting (e.g. protein C deficiency)
Ø  If you have uncontrolled blood pressure
Ø  If you have (or have ever) suffered from migraine, with visual disturbances
Ø  If you have ever had a severe liver disease, and you have been told by your doctor thatØ your liver test results are not yet back to normal
— If you have hepatitis C and are taking the medicinal products containingØ ombitasvir/paritaprevir/ritonavir and dasabuvir (see also in section Other medicines and Cyproterone Acetate/Ethinylestradiol).
— If you have ever had liver tumours
Ø  If you are allergic to cyproterone acetate, ethinylestradiol or any of the other ingredientsØ of this medicine .

If you suffer from any of these, or get them for the first time while taking Cyproterone Acetate / Ethinylestradiol, contact your doctor as soon as possible. Do not take Cyproterone Acetate / Ethinylestradiol. If needed, use another form of contraception.

Cyproterone Acetate / Ethinylestradiol can make some illnesses worse
Some of the conditions listed below can be made worse by taking Cyproterone Acetate / Ethinylestradiol. Or they may mean it is less suitable for you. You may still be able to take Cyproterone Acetate / Ethinylestradiol but you need to take special care and have check-ups more often.
— If you or your close family have ever had problems with your heart or circulation, such asØ high blood pressure  If you or your close family have ever had problems with blood clotting
Ø  If you have had migraines
Ø  If you are currently suffering from depression or have done so in the past
Ø  If you are overweight (obese)
Ø  If you have the inherited disease called porphyria
Ø  If you have diabetes with blood disorders or disorder of the eye, kidneys or nerves
Ø  If you have inflammation of the pancreas (pancreatitis), or a history or family historyØ of high levels of fat in your blood (hypertriglyceridemia),as you may be at risk of developing pancreatitis
–If you have brown patches on your face or body (chloasma) (see below ‘CyproteroneØ Acetate / Ethinylestradiol and sun-beds or sun-lamps’)
— If you have any illness that worsened during pregnancy or previous use of the Pill orØ  Cyproterone Acetate / Ethinylestradiol .
–If you have hereditary angioedema. Consult your doctor immediately if you experienceØ symptoms of angioedema such as swollen face, tongue or throat, and/or difficulty swallowing, or hives, together with difficulty breathing. Products containing oestrogens may induce or worsen symptoms of angioedema.

Tell your doctor if any apply to you.
Also tell them if you get any of these for the first time while taking Cyproterone Acetate / Ethinylestradiol, or if any get worse or come back, because you may need to stop taking it. Cyproterone Acetate / Ethinylestradiol will not protect you against sexually transmitted infections, such as Chlamydia or HIV. Only condoms can help to do this.

Other medicines and Cyproterone Acetate / Ethinylestradiol
Also check the leaflets that come with all your medicines to see if they can be taken with hormonal contraceptives. Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
If you are taking Cyproterone Acetate / Ethinylestradiol for skin treatment, you must not take any other hormonal contraceptive at the same time.

Some medicines can stop Cyproterone Acetate / Ethinylestradiol from working properly – for example:
— some medicines used to treat epilepsy (such as primidone, phenytoin,
Ø carbamazepine, oxcarbazepine, topiramate, felbamate)  some medicines used to treat HIV and Hepatitis C Virus infection (so-called proteaseØ inhibitors and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nelfinavir and nevirapine)
–griseofulvin and rifampicin (anti-fungal medicines)
Ø  certain sedatives (called barbiturates)
Ø  St. John’s wort (a herbal remedy).
If you do need to take one of these medicines, Cyproterone Acetate / Ethinylestradiol may not be suitable for you or you may need to use extra contraception for a while. Your doctor, pharmacist or dentist can tell you if this is necessary and for how long.
Do not use Cyproterone Acetate/Ethinylestradiol if you have Hepatitis C and are taking the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir as this may cause increases in liver function blood test results (increase in ALT liver enzyme).
Your doctor will prescribe another type of contraceptive prior to start of the treatment with these medicinal products.
Cyproterome Acetate/Ethinylestradiol can be restarted approximately 2 weeks after completion of this treatment.

Cyproterone Acetate / Ethinylestradiol can also affect how well other medicines work. Cyproterone Acetate / Ethinylestradiol may increase or decrease the amount of certain medicines (such as ciclosporin and lamotrigine) in your blood. Your doctor may need to adjust the dose of your other medicine.
In addition, Cyproterone Acetate / Ethinylestradiol can also interfere with the results of some blood tests, so always tell your doctor that you are taking Cyproterone Acetate / Ethinylestradiol if you have a blood test.

Pregnancy and breast-feeding
Do not use Cyproterone Acetate / Ethinylestradiol if you are pregnant or are breast-feeding.
If you think you might be pregnant, do a pregnancy test to confirm that you are before you stop taking Cyproterone Acetate / Ethinylestradiol.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines
 Cyproterone Acetate / Ethinylestradiol has no known effect on the ability to drive or use machines.

Cyproterone Acetate / Ethinylestradiol and sun-beds or sun-lamps
 Sun-lamps are used by some women for acne as well as to tan the skin. This is not a very useful treatment for acne. Do not use sun-beds or sun-lamps and avoid prolonged sunbathing if you are taking Cyproterone Acetate / Ethinylestradiol. Their use increases the chance of chloasma, a patchy discolouration of the skin (as it does with ordinary oral contraceptives). Cyproterone Acetate / Ethinylestradiol contains lactose and sucrose
 If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

  1. How to take Cyproterone Acetate / Ethinylestradiol

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Your doctor has chosen Cyproterone Acetate / Ethinylestradiol as a treatment for your severe acne or excessive hair growth on your face and body. However, Cyproterone Acetate / Ethinylestradiol also has a contraceptive effect, so it is important to follow the advice below if you are relying on Cyproterone Acetate / Ethinylestradiol for contraception.

If you are only using Cyproterone Acetate / Ethinylestradiol for your acne or excessive hair growth, you can still follow this advice, but ask your doctor if you are unsure.

Duration of use
Your doctor will tell you how long you need to keep taking Cyproterone Acetate / Ethinylestradiol.
 How to take it

Take Cyproterone Acetate / Ethinylestradiol every day for 21 days
Cyproterone Acetate / Ethinylestradiol comes in strips of 21 pills, each marked with a day of the week.
ØTake your pill at the same time every day.
Ø  Start by taking a pill marked with the correct day of the week.
Ø  Follow the direction of the arrows on the strip. Take one pill each day, until you have
finished all 21 pills.
Ø Swallow each pill whole, with water if necessary. Do not chew the pill.

Then have seven pill-free days
After you have taken all 21 pills in the strip, you have seven days when you take no pills. Within a few days of taking the last pill from the strip, you should have a withdrawal bleed like a period. This bleed may not have finished when it is time to start your next strip of pills. If you are relying on this medicine to prevent pregnancy, always take Cyproterone Acetate / Ethinylestradiol as described here. You don’t need to use extra contraception during the seven pill- free days – as long as you have taken your pills correctly and start the next strip of pills on time. Check with your doctor if you are not sure.

Start your next strip on day eight
 Start taking your next strip of Cyproterone Acetate / Ethinylestradiol after the seven pill-free days (on day eight) – even if you are still bleeding. So if you take the last pill of one pack on a Friday, you willtake the first pill of your next pack on the Saturday of the following week. Always start the new strip on time.
As long as you take Cyproterone Acetate / Ethinylestradiol correctly, you will always start each new strip on the same day of the week. Starting Cyproterone Acetate / Ethinylestradiol

New users or starting Cyproterone Acetate / Ethinylestradiol after a break
It is best to take your first Cyproterone Acetate / Ethinylestradiol pill on the first day of your next period. By starting in this way, you will have contraceptive protection with your first pill.

Changing to Cyproterone Acetate / Ethinylestradiol from another contraceptive Pill
If you are currently taking a 21-day Pill: start Cyproterone Acetate / EthinylestradiolØ the next day after the end of the previous strip. You will have contraceptive protection with your first pill. You will not have a bleed until after your first strip of Cyproterone Acetate / Ethinylestradiol.
If you are taking a 28-day Pill: start taking Cyproterone Acetate / Ethinylestradiol theØ day after your last active pill. You will have contraceptive protection with your first pill. You will not have a bleed until after your first strip of Cyproterone Acetate / Ethinylestradiol.
If you are taking a progestogen-only Pill (POP or ‘mini Pill’):  start Cyproterone AcetateØ / Ethinylestradiol on the first day of bleeding, even if you have already taken the progestogen- only Pill for that day. You will have contraceptive protection straight away.
Starting Cyproterone Acetate / Ethinylestradiol after a miscarriage or abortion
If you have had a miscarriage or an abortion during the first three months of pregnan

cy, your doctor may tell you to start taking Cyproterone Acetate / Ethinylestradiol straight away. This means that you will have contraceptive protection with your first pill. If you have had a miscarriage or an abortion after the third month of pregnancy, ask your doctor for advice. You may need to use extra contraception, such as condoms, for a short time.

Contraception after having a baby
If you have just had a baby, your doctor may advise you that Cyproterone Acetate / Ethinylestradiol should be started 21 days after delivery provided that you are fully mobile. You do not have to wait for a period. You will need to use another method of contraception, such as a condom, until you start Cyproterone Acetate / Ethinylestradiol and for the first 7 days of pill taking.

A missed pill
If you are less than 12 hours late with a pill, take it straight away. Keep taking your pills at the usual time. This may mean taking two pills in one day. Don’t worry – your contraceptive protection should not be reduced.

If you are more than 12 hours late with a pill, or you have missed more than one pill, your contraceptive protection may be reduced.
ØTake the most recently missed pill as soon as you remember, even if it means taking two
at once. Leave any earlier missed pills in the pack.
ØContinue to take a pill every day for the next seven days at your usual time.
Ø  If you come to the end of a strip of pills during these seven days, start the next stripØ without taking the usual seven day break. You probably won’t have a bleed until after you finish the second strip of pills, but don’t worry. If you finish the second strip of pills and don’t have a bleed, do a pregnancy test before starting another strip.
ØUse extra contraception for seven days after missing a pill, such as condoms.
Ø  If you have missed one or more pills from the first week of your strip (days 1 to 7) andØyou 9 had sex in that week, you could become pregnant. Contact your doctor or pharmacist for advice as soon as possible. They may recommend you use emergency contraception.

If you have missed any of the pills in a strip, and you do not bleed in the first pill free break, you may be pregnant. Contact your doctor or do a pregnancy test yourself.

If you start a new strip of pills late, or make your ‘week off’ longer than seven days, you may not be protected from pregnancy. If you had sex in the last seven days, ask your doctor or pharmacist for advice. You may need to consider emergency contraception. You should also use extra contraception, such as a condom, for seven days.

A lost pill
If you lose a pill,
Either take the last pill of the strip in place of the lost pill. Then take all the other pills on their proper days. Your cycle will be one day shorter than normal, but your contraceptive protection won’t be affected. After your seven pill-free days you will have a new starting day, one day earlier than before.
Or if you do not want to change the starting day of your cycle, take a pill from a spare strip if you have one. Then take all the other pills from your current strip as usual. You can then keep the opened spare strip in case you lose any more pills.

If you are sick or have diarrhoea
If you are sick (vomit) or have very bad diarrhoea, your body may not get its usual dose of hormones from that pill. If you are better within 12 hours of taking Cyproterone Acetate / Ethinylestradiol, follow the instructions in section above, A lost pill, which describes how to take another pill.
If you are still sick or have diarrhoea more than 12 hours after taking Cyproterone Acetate / Ethinylestradiol, see section above, A missed pill.

Talk to your doctor if your stomach upset carries on or gets worse. He or she may recommend another form of contraception. Missed a period – could you be pregnant? Occasionally, you may miss a withdrawal bleed. This could mean that you are pregnant, but that is very unlikely if you have taken your pills correctly. Start your next strip at the normal time. If you think that you might have put yourself at risk of pregnancy (for example, by missing pills or taking other medicines), or if you miss a second bleed, you should do a pregnancy test. You can buy these from the chemist or get a free test at your doctors surgery. If you are pregnant, stop taking Cyproterone Acetate / Ethinylestradiol and see your doctor.

Taking more than one pill should not cause harm
It is unlikely that taking more than one pill will do you any harm, but you may feel sick, vomit or have some vaginal bleeding. Talk to your doctor if you have any of these symptoms.

When you want to get pregnant
If you are planning a baby, it’s best to use another method of contraception after stopping Cyproterone Acetate / Ethinylestradiol until you have had a proper period. Your doctor or midwife relies on the date of your last natural period to tell you when your baby is due. However, it will not cause you or the baby any harm if you get pregnant straight away.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If any of the following side effects happen, you may need urgent medical attention. Stop taking Cyproterone Acetate / Ethinylestradiol and contact a doctor or go to the nearest hospital immediately.
Uncommon (may affect up to 1 in 100 people)
  –if you get migraines or if you get more frequent headaches
Rare (may affect up to 1 in 1,000 people)
–Signs of a severe allergic reaction or worsening of hereditary angioedema:  a red bumpy rash (hives) and itching, swelling of the hands, face, lips, mouth, tongueØ or throat. A swollen tongue/throat may lead to difficulty swallowing and breathing

Venous or arterial blood clot which include signs such as:
–a migraine for the first time, a migraine that is worse than normal or unusually frequentØ or severe headaches
— any sudden changes to your eyesight (such as loss of vision or blurred vision)
Ø  any sudden changes to your hearing, speech, sense of smell, taste or touch
Ø  pain or swelling in your leg
Ø  stabbing pain when you breathe
Ø  coughing for no apparent reason
Ø  pain and tightness in the chest
Ø  sudden weakness or numbness in one side or part of your body
Ø  dizziness or fainting.

Not known (frequency cannot be estimated from the available data)
Severe depression:
Although, it is not considered a direct side effect of Cyproterone Acetate / Ethinylestradiol, some women have reported feeling depressed whilst taking Cyproterone Acetate / Ethinylestradiol. In very rare cases this has been associated with thoughts of ending their lives. If you develop severe depression, you should stop Cyprotero

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