Ethinyl Estradiol/Gestodene 30mcg/75mcg & 20mcg/75mcg Film-coated Tablets Taj Pharma
1.Name of the medicinal product

a) Ethinyl Estradiol/Gestodene 30mcg/75mcg Film-coated Tablets

b) Ethinyl Estradiol/Gestodene 20mcg/75mcg Film-coated Tablets

2.Qualitative and quantitative composition
a) Ethinyl Estradiol/Gestodene 30mcg/75mcg Film-coated Tablets
Each tablet contains:

Actives:
Gestodene75 micrograms
Ethinylestradiol30 micrograms

b) Ethinyl Estradiol/Gestodene 20mcg/75mcg Film-coated Tablets
Each tablet contains:

Actives:
Gestodene75 micrograms
Ethinylestradiol20 micrograms

For full list of excipients, see section 6.1

3.Pharmaceutical form

Sugar-coated tablets

4. Clinical particulars

4.1 Therapeutic indications

Oral contraception and the recognised gynaecological indications for such oestrogen-progestogen combinations.

The decision to prescribe Femodene should take into consideration the individual woman’s current risk factors, particularly those for venous thromboembolism (VTE), and how the risk of VTE with Femodene compares with other combined hormonal contraceptives (CHCs) (see sections 4.3 and 4.4).

4.2 Posology and method of administration

First treatment cycle: 1 tablet daily for 21 days, starting on the first day of the menstrual cycle. Contraceptive protection begins immediately.

Subsequent cycles: Tablet taking from the next pack of Femodene is continued after a 7-day interval, beginning on the same day of the week as the first pack.

Changing from 21-day combined oral contraceptives: The first tablet of Femodene 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):

Femodene should be started after taking the last active tablet from the Every Day Pill pack. The first Femodene tablet is taken the next day. Additional contraceptive precautions are not then required.

Changing from a progestogen-only pill (POP):

The first tablet of Femodene 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, oral contraception 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 tablet 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. After a first-trimester abortion, oral contraception may be started immediately in which case no additional contraceptive precautions are required.

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. If vomiting or diarrhoea occurs within 4 hours of taking Femodene 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.

Children: Not applicable.

Elderly: Not applicable.

4.3 Contraindications

Combined hormonal contraceptives (CHCs) should not be used in the following conditions. Should any of the conditions appear for the first time during CHC use, the product should be stopped immediately.

  • Presence or risk of venous thromboembolism (VTE)

o Venous thromboembolism – current VTE (on anticoagulants) or history of (e.g. deep venous thrombosis [DVT] or pulmonary embolism [PE])

o Known hereditary or acquired predisposition for venous thromboembolism, such as APC-resistance, (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency

o Major surgery with prolonged immobilisation (see section 4.4)

o A high risk of venous thromboembolism due to the presence of multiple risk factors (see section 4.4)

  • Presence or risk of arterial thromboembolism (ATE)

o Arterial thromboembolism – current arterial thromboembolism, history of arterial thromboembolism (e.g. myocardial infarction) or prodromal condition (e.g. angina pectoris)

o Cerebrovascular disease – current stroke, history of stroke or prodromal condition (e.g. transient ischaemic attack, TIA)

o Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and anti-phospholipid antibodies (anticardiolipin-antibodies, lupus anticoagulant)

o History of migraine with focal neurological symptoms

o A high risk of arterial thromboembolism due to multiple risk factors (see section 4.4) or to the presence of one serious risk factor such as:

• diabetes mellitus with vascular symptoms

• severe hypertension

• severe dyslipoproteinaemia

  • 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.
  • Hypersensitivity to the active substance(s) or to any of the excipients.

Femodene is contraindicated for concomitant use with the medicinal products containing ombitasvir / paritaprevir / ritonavir or dasabuvir (see sections 4.4 and 4.5).

Relevant UK clinical guidance should also be consulted.

4.4 Special warnings and precautions for use

Warnings

  • If any of the conditions or risk factors mentioned below is present, the suitability of Femodene should be discussed with the woman.
  • In the event of aggravation, or first appearance of any of these conditions or risk factors, the woman should be advised to contact her doctor to determine whether the use of Femodene should be discontinued.

Risk of venous thromboembolism (VTE)

The use of any combined hormonal contraceptive (CHC) increases the risk of venous thromboembolism (VTE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with the lowest risk of VTE. Other products such as Femodene may have up to twice this level of risk. The decision to use any product other than one with the lowest VTE risk should be taken only after a discussion with the woman to ensure she understands the risk of VTE with Femodene, how her current risk factors influence this risk, and that her VTE risk is highest in the first ever year of use. There is also some evidence that the risk is increased when a CHC is re-started after a break in use of 4 weeks or more.

In women who do not use a CHC and are not pregnant, about 2 out of 10,000 will develop a VTE over the period of one year. However, in any individual woman the risk may be far higher, depending on her underlying risk factors (see below).

It is estimated1 that out of 10,000 women who use a CHC containing gestodene between 9 and 12 women will develop a VTE in one year; this compares with about 62 in women who use a levonorgestrel-containing CHC.

In both cases, the number of VTEs per year is fewer than the number expected during pregnancy or in the postpartum period.

VTE may be fatal in 1-2% of cases.

Number of VTE events per 10,000 women in one year

Extremely rarely, thrombosis has been reported to occur in CHC users in other blood vessels, e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries.

Risk factors for VTE

The risk for venous thromboembolic complications in CHC users may increase substantially in a woman with additional risk factors, particularly if there are multiple risk factors (see table).

Femodene is contraindicated if a woman has multiple risk factors that put her at high risk of venous thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors – in this case her total risk of VTE should be considered. If the balance of benefits and risks is considered to be negative a CHC should not be prescribed (see section 4.3).

Table: Risk factors for VTE

Risk factorComment
Obesity (body mass index over 30 kg/m²)Risk increases substantially as BMI rises.

Particularly important to consider if other risk factors also present.

Prolonged immobilisation, major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma

Note: temporary immobilisation including air travel >4 hours can also be a risk factor for VTE, particularly in women with other risk factors

In these situations it is advisable to discontinue use of the pill (in the case of elective surgery at least four weeks in advance) and not resume until two weeks after complete remobilisation. Another method of contraception should be used to avoid unintentional pregnancy.

Antithrombotic treatment should be considered if Femodene has not been discontinued in advance.

Positive family history (venous thromboembolism ever in a sibling or parent especially at a relatively early age e.g. before 50).If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any CHC use.
Other medical conditions associated with VTECancer, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis) and sickle cell disease.
Increasing ageParticularly above 35 years.

There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in the onset or progression of venous thrombosis.

The increased risk of thromboembolism in pregnancy, and particularly the 6 week period of the puerperium, must be considered (for information on “Pregnancy and lactation” see Section 4.6).

Symptoms of VTE (deep vein thrombosis and pulmonary embolism)

In the event of symptoms women should be advised to seek urgent medical attention and to inform the healthcare professional that she is taking a CHC.

Symptoms of deep vein thrombosis (DVT) can include:

– unilateral swelling of the leg and/or foot or along a vein in the leg;

– pain or tenderness in the leg which may be felt only when standing or walking,

– increased warmth in the affected leg; red or discoloured skin on the leg.

Symptoms of pulmonary embolism (PE) can include:

– sudden onset of unexplained shortness of breath or rapid breathing;

– sudden coughing which may be associated with haemoptysis;

– sharp chest pain;

– severe light headedness or dizziness;

– rapid or irregular heartbeat.

Some of these symptoms (e.g. “shortness of breath”, “coughing”) are non-specific and might be misinterpreted as more common or less severe events (e.g. respiratory tract infections).

Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of an extremity.

If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can progress to loss of vision. Sometimes loss of vision can occur almost immediately.

Risk of arterial thromboembolism (ATE)

Epidemiological studies have associated the use of CHCs with an increased risk for arterial thromboembolism (myocardial infarction) or for cerebrovascular accident (e.g. transient ischaemic attack, stroke). Arterial thromboembolic events may be fatal.

Risk factors for ATE

The risk of arterial thromboembolic complications or of a cerebrovascular accident in CHC users increases in women with risk factors (see table). Femodene is contraindicated if a woman has one serious or multiple risk factors for ATE that puts her at high risk of arterial thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors – in this case her total risk should be considered. If the balance of benefits and risks is considered to be negative a CHC should not be prescribed (see section 4.3).

Table: Risk factors for ATE

Risk factorComment
Increasing ageParticularly above 35 years
SmokingWomen should be advised not to smoke if they wish to use a CHC. Women over 35 who continue to smoke should be strongly advised to use a different method of contraception.
Hypertension
Obesity (body mass index over 30 kg/m2)Risk increases substantially as BMI increases.

Particularly important in women with additional risk factors

Positive family history (arterial thromboembolism ever in a sibling or parent especially at relatively early age e.g. below 50).If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any CHC use
MigraineAn increase in frequency or severity of migraine during CHC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation
Other medical conditions associated with adverse vascular eventsDiabetes mellitus, hyperhomocysteinaemia, valvular heart disease and atrial fibrillation, dyslipoproteinaemia and systemic lupus erythematosus.

Symptoms of ATE

In the event of symptoms women should be advised to seek urgent medical attention and to inform the healthcare professional that she is taking a CHC.

Symptoms of a cerebrovascular accident can include:

– sudden numbness or weakness of the face, arm or leg, especially on one side of the body;

– sudden trouble walking, dizziness, loss of balance or coordination;

– sudden confusion, trouble speaking or understanding;

– sudden trouble seeing in one or both eyes;

– sudden, severe or prolonged headache with no known cause;

– loss of consciousness or fainting with or without seizure.

Temporary symptoms suggest the event is a transient ischaemic attack (TIA).

Symptoms of myocardial infarction (MI) can include:

– pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm, or below the breastbone;

– discomfort radiating to the back, jaw, throat, arm, stomach;

– feeling of being full, having indigestion or choking;

– sweating, nausea, vomiting or dizziness;

– extreme weakness, anxiety, or shortness of breath;

– rapid or irregular heartbeats.

Medical Examination/Consultation

Prior to the initiation or reinstitution of Femodene a complete medical history (including family history) should be taken and pregnancy must be ruled out. Blood pressure should be measured and a physical examination should be performed, guided by the contra-indications (see section 4.3) and warnings (see section 4.4). It is important to draw a woman’s attention to the information on venous and arterial thrombosis, including the risk of Femodene compared with other CHCs, the symptoms of VTE and ATE, the known risk factors and what to do in the event of a suspected thrombosis.

The woman should also be instructed to carefully read the user leaflet and to adhere to the advice given. The frequency and nature of examinations should be based on established practice guidelines and be adapted to the individual woman.

Women should be advised that hormonal contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases.

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

Conditions which require strict medical supervision

The decision to prescribe the COC must be made using clinical judgement and in consultation with the woman. Exacerbation or first appearance of any of these conditions may indicate that use of the oral contraceptive 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 oral contraception immediately’)
  • porphyria
  • obesity
  • migraine
  • cardiovascular diseases

Reasons for stopping oral contraception immediately:

When stopping oral contraception non-hormonal contraception should be used to ensure contraceptive protection is maintained.

  1. Occurrence for the first time, or exacerbation, of migrainous headaches or unusually frequent or unusually severe headaches
  2. Sudden disturbances of vision, of 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. At least four 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. Severe upper abdominal pain or liver enlargement
  8. Clear exacerbation of conditions known to be capable of deteriorating during oral contraception or pregnancy (see section 4.4 ‘Conditions which deteriorate in pregnancy or during previous COC use’ under ‘Other conditions’)

Tumours

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 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 (see bar chart).

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 Femodene. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, the possibility of 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 combined oral contraceptives.

  • Known hyperlipidaemia

Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.

Women with hyperlipidaemias are at an increased risk of arterial disease (see section 4.4 ‘Circulatory disorders’). However routine screening of women on COCs 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, clinically relevant increases are rare. However, if sustained hypertension develops during the use of a COC, 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 the COC should be made at lower BP levels, and alternative contraception may be advised.

  • Conditions which deteriorate in pregnancy or during previous COC use

The following conditions have been reported to occur or deteriorate with both pregnancy and COC use. Consideration should be given to stopping Femodene if any of the following occur during use:

• jaundice and/or pruritus related to cholestasis

• COCs 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

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

  • Disturbances of liver function

Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal.

  • Diabetes (without vascular involvement)

Insulin-dependent diabetics without vascular disease can use COCs. However it should be remembered that all diabetics are at an increased risk of arterial disease and this should be considered when prescribing COCs. Diabetics with existing vascular disease are contraindicated from using COCs (see section 4.3 Contraindications).

Although COCs 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.

  • Psychiatric Disorders

Depressed mood and depression are well-known undesirable effects of hormonal contraceptive use (see section 4.8). Depression can be serious and is a well-known risk factor for suicidal behaviour and suicide. Women should be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment.

  • 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 COCs.

  • 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 very unlikely. If withdrawal bleeding fails to occur at the end of a second pack, the possibility of pregnancy must be ruled out before resuming with the next pack.

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 oral contraceptives, 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 37.43 mg lactose and 19.660 mg sucrose per tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp 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) (see section 4.3 and 4.5).

1 These incidences were estimated from the totality of the epidemiological study data, using relative risks for the different products compared with levonorgestrel-containing CHCs.

2 Mid-point of range of 5-7 per 10,000 WY, based on a relative risk for CHCs containing levonorgestrel versus non-use of approximately 2.3 to 3.6.

4.5 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 COCs:

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

Antibiotics/antifungals: griseofulvin, rifampacin.

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 COCs (enzyme inhibitors)

Strong and moderate CYP3A4 inhibitors such as azole antifungals (e.g. itraconazole, voriconazole, fluconazole) and macrolides (e.g. erythromycin) 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 on other drugs

Oral contraceptives may affect the metabolism of certain other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin, tizanidine, theophylline) 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 (see sections 4.3 and 4.4).

Therefore, Femodene-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. Femodene can be restarted 2 weeks following completion of treatment with this combination drug regimen.

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.

4.6 Pregnancy and lactation

Femodene is not indicated during pregnancy. If pregnancy occurs during treatment with Femodene, further intake must be stopped. However, extensive epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used COCs prior to pregnancy, nor a teratogenic effect when COCs were taken inadvertently during early pregnancy.

The increased risk of VTE during the postpartum period should be considered when re-starting Femodene (see section 4.2 and 4.4).

The use of Femodene 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 may be advised instead to use another method of contraception.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

Summary of the safety profile

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

Serious adverse reactions are arterial and venous thromboembolism.

System Organ ClassAdverse events reported in clinical trialsAdverse events reported post marketing
Common

(≥ 1/100)

Uncommon

(≥ 1/1000, <1/100)

Rare

(< 1/1000)

Eye disorderscontact lens intolerance
Gastrointestinal disordersnausea, abdominal painvomiting, diarrheaulcerative colitis
Immune system disordershypersensitivityexacerbation of hereditary angioedema
Investigationsweight increasedweight decreased
Metabolism and nutrition disordersfluid retention
Nervous system disordersheadachemigraineexacerbation of chorea
Vascular systemVenous thromboembolism (VTE), Arterial thromboembolism (ATE)
Hepatobiliary disordersliver function disturbances
Psychiatric disordersdepressed mood, mood alteredlibido decreasedlibido increased
Reproductive system and breast disordersbreast pain, breast tendernessbreast hypertrophyvaginal discharge, breast dischargereduced menstrual flow, spotting, breakthrough bleeding and missed withdrawal bleeding, post pill amenorrhoea
Skin and subcutaneous tissue disordersrash, urticariaerythema nodosum, erythema multiformechloasma

Description of selected adverse reactions

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 section 4.4.

The following serious adverse events have been reported in women using COCs, which are discussed in section 4.4 ‘Special warnings and precautions for use’:

  • Venous thromboembolic disorders
  • Arterial thromboembolic disorders
  • Strokes (e.g. transient ischemic attack, ischemic stroke, haemorrhagic stroke)
  • Hypertension
  • Hypertriglyceridemia
  • Liver tumours (benign and malignant)

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, see sections 4.3 ‘Contraindications’ and 4.4 ‘Special warnings and precautions for use’.

Conditions reported to deteriorate with pregnancy or previous COC use

Jaundice and/or pruritus related to cholestasis; gallstone formation; systemic lupus erythematosus; herpes gestationis; otosclerosis-related hearing loss; Crohn’s disease, sickle cell anaemia; renal dysfunction; hereditary angioedema; porphyria; cervical cancer.

Changes in glucose tolerance or effect on peripheral insulin resistance have been reported in women using COCs (see section 4.4).

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.

4.9 Overdose

Overdosage may cause nausea, vomiting and, in females, withdrawal bleeding. Withdrawal bleeding may even occur in girls before their menarche, if they accidentally take the medicinal product.

There are no specific antidotes and treatment should be symptomatic.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, progestogens and oestrogens, fixed combinations.

This oestrogen-progestogen combination acts by inhibiting ovulation by suppression of the mid-cycle surge of luteinising hormone, the inspissation of cervical mucus so as to constitute a barrier to sperm, and the rendering of the endometrium unreceptive to implantation.

5.2 Pharmacokinetic properties

Gestodene

Orally administered gestodene is rapidly and completely absorbed. Following single ingestion of Femodene, maximum drug serum levels of 4ng/ml are reached at about 1.0 hour. Thereafter, gestodene serum levels decrease in two phases. The terminal disposition phase is characterized by a half-life of 12 – 15 hours. For gestodene, an apparent volume of distribution of 0.7 l/kg and a metabolic clearance rate from serum of about 0.8 ml/min/kg were determined. Gestodene is not excreted in unchanged form but as metabolites, which are eliminated with a half-life of about 1 day. Gestodene metabolites are excreted at a urinary to biliary ratio of about 6:4. The biotransformation follows the known pathways of steroid metabolism. No pharmacologically active metabolites are known.

Gestodene is bound to serum albumin and to SHBG (sex hormone binding globulin). Only 1 – 2% of the total serum drug levels are present as free steroid, about 50 – 70% are specifically bound to SHBG. The relative distribution (free, albumin-bound, SHBG-bound) depends on the SHBG concentrations in the serum. Following induction of the binding protein, the SHBG-bound fraction increases while the unbound and the albumin-bound fractions decrease.

Following daily repeated administration of Femodene, gestodene concentrations in the serum increase by a factor of 2.8. Mean serum levels are fourfold higher at steady-state conditions which are reached during the second half of a treatment cycle. The pharmacokinetics of gestodene is influenced by SHBG serum levels. Under treatment with Femodene, a threefold increase in the serum SHBG levels has been observed for the first treatment cycle. Due to the specific binding of gestodene to SHBG, the increase in SHBG levels is accompanied by an almost parallel increase in gestodene serum levels. After three treatment cycles the extent of SHBG induction per cycle does not change any more. The absolute bioavailability of gestodene was determined to be 99% of the dose administered.

Ethinylestradiol

Orally administered ethinylestradiol is rapidly and completely absorbed. Following ingestion of Femodene, maximum drug serum levels of 82pg/ml are reached at 1.4 hours. Thereafter, ethinylestradiol serum levels decrease in two phases characterized by half-lives of 1 – 2 hours and about 20 hours. Because of analytical reasons, these parameters can only be calculated following the administration of higher doses. For ethinylestradiol, an apparent volume of distribution of about 5 l/kg and a metabolic clearance rate from serum of about 5ml/min/kg were determined. Ethinylestradiol is highly but non-specifically bound to serum albumin. About 2% of drug levels are present unbound. During absorption and first liver passage, ethinylestradiol is metabolized 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 serum and the daily ingestion, steady-state serum levels are reached after 3 – 4 days and are higher by 30 – 40% as compared to a single dose.

During established lactation, 0.02% of the daily maternal dose could be transferred to the newborn via milk.

The systemic availability 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 CBG (corticoid binding globulin) during continuous use. The extent of SHBG induction, however, depends on the chemical structure and the dose of the co-administered progestogen. During treatment with Femodene, SHBG concentrations in the serum increased from 69nmol/l to 198nmol/l in the first and to 210nmol/l in the third cycle. Serum concentrations of CBG were increased from 37μg/ml to 85μg/ml in the first cycle and remained constant thereafter.

5.3 Preclinical safety data

The combination of ethinylestradiol and gestodene, like other contraceptive steroids, is associated with an increased incidence of neoplastic nodules in the rat liver, the relevance of which to man is unknown. Malignant liver tumours have been reported on rare occasions in long-term users of oral contraceptives.

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

6. Pharmaceutical particulars

6.1 List of excipients

Lactose, maize starch, povidone, magnesium stearate, sodium calcium edetate, sucrose, macrogol 6000, calcium carbonate, talc, montan glycol wax

6.2 Incompatibilities

None known.

6.3 Shelf life

5 years.

6.4 Special precautions for storage

Do not store above 25°C. Protect from light.

6.5 Nature and contents of container

Deep drawn strips made of polyvinyl chloride film with counter-sealing foil made of aluminium with heat sealable coating.

Presentation:

Carton containing memo-packs of either 1 x 21 tablets or 3 x 21 tablets.

6.6 Special precautions for disposal and other handling

No special requirements.

7.Manufactured in India by:

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

Ethinyl Estradiol/Gestodene 30mcg/75mcg & 20mcg/75mcg Film-coated Tablets Taj Pharma

(Ethinylestradiol / Gestodene 20/75, 30/75)

Package leaflet: Information for the user

Important things to know about combined hormonal contraceptives (CHCs):

They are one of the most reliable reversible methods of contraception if used correctly

They slightly increase the risk of having a blood clot in the veins and arteries, especially in the first year or when restarting a combined hormonal contraceptive following a break of 4 or more weeks

Please be alert and see your doctor if you think you may have symptoms of a blood clot (see section 2 “Blood clots”)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again

If you have any further questions, ask your doctor or pharmacist

This medicine has been prescribed for you only.

Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

What is in this leaflet

  1. What Ethinylestradiol / Gestodene 20/75, 30/75 Tablets is and what it is used for
  2. What you need to know before you take Ethinylestradiol / Gestodene 20/75, 30/75 Tablets
  3. How to take Ethinylestradiol / Gestodene 20/75, 30/75 Tablets
  4. Possible side effects
  5. How to store Ethinylestradiol / Gestodene 20/75, 30/75 Tablets
  6. Contents of the pack and other information

 

  1. What Ethinylestradiol / Gestodene 20/75, 30/75tablets is and what it is used for

Ethinylestradiol / Gestodene 20/75, 30/75 is a combined oral contraceptive and belongs to a group of drugs which is frequently called “the Pill”. It contains two types of hormone: an oestrogen, named ethinylestradiol and a progestogen type, named gestodene. These hormones stop the ovary from releasing an egg each month (ovulation). They also thicken the fluid (mucus) at the neck of the womb (cervix) making it more difficult for the sperm to reach the egg, and alter the lining of the womb to make it less likely to accept a fertilised egg.

Medical researches and vast experience have shown that, if taken correctly, the Pill is an effective reversible form of contraception.

Ethinylestradiol / Gestodene 30/75, like other hormonal contraceptives, will not protect you against HIV infection (AIDS) and other sexually transmitted diseases. Only condoms can do this.

How does the Pill work?

The combined contraceptive pills such as Ethinylestradiol / Gestodene 20/75, 30/75contain hormones which are equivalent to those that your body produces (oestrogen and progestogen). These hormones help to prevent you from getting pregnant, just as your natural hormones would stop you from conceiving again when you are already pregnant.

The combined contraceptive pill protects you against getting pregnant in three ways:

You will not release an egg to be fertilised by sperm.

The fluid in the neck of your womb thickens so it is more difficult for sperm to enter.

The lining of your womb does not thicken enough for an egg to start to grow in.

  1. What you need to know before you take Ethinylestradiol / Gestodene 20/75, 30/75 tablets

General notes

Before you start using Ethinylestradiol / Gestodene 20/75, 30/75you should read the information on blood clots in section 2. It is particularly important to read the symptoms of a blood clot – see Section 2 “Blood clots”).

Before you can begin taking Ethinylestradiol / Gestodene 30/75, your doctor will ask you some questions about your personal health history and that of your close relatives. The doctor will also measure your blood pressure, and, depending upon your personal situation, may also carry out some other tests.

In this leaflet, several situations are described where you should stop using Ethinylestradiol / Gestodene 20/75, 30/75, or where the reliability of Ethinylestradiol / Gestodene 20/75, 30/75may be decreased. In such situations you should either not have sex or you should take extra non-hormonal contraceptive precautions, e.g. use a condom or another barrier method. Do not use rhythm or temperature methods. These methods can be unreliable because Ethinylestradiol / Gestodene 20/75, 30/75 alters the monthly changes of body temperature and of the cervical mucus.

Ethinylestradiol / Gestodene 20/75, 30/75, like other hormonal contraceptives, does not protect against HIV infection (AIDS) or any other sexually transmitted disease.

While you are receiving this medication you should see your doctor regularly, according to your doctor’s advice.

If you have any unusual symptoms such as unexplained pains in the chest, abdomen or legs you must consult your doctor immediately.

Do not take Ethinylestradiol / Gestodene 20/75, 30/75

You should not use Ethinylestradiol / Gestodene 20/75, 30/75if you have any of the conditions listed below. If you do have any of the conditions listed below, you must tell your doctor. Your doctor will discuss with you what other form of birth control would be more appropriate.

if you have (or have ever had) a blood clot in a blood vessel of your legs (deep vein thrombosis, DVT), your lungs (pulmonary embolus, PE) or other organs;

if you know you have a disorder affecting your blood clotting – for instance, protein C deficiency, protein S deficiency, antithrombin-III deficiency, Factor V Leiden or antiphospholipid antibodies;

if you need an operation or if you are off your feet for a long time (see section ‘Blood clots’);

if you have ever had a heart attack or a stroke;

if you have (or have ever had) angina pectoris (a condition that causes severe chest pain and may be a first sign of a heart attack) or transient ischaemic attack (TIA – temporary stroke symptoms);

if you have any of the following diseases that may increase your risk of a clot in the arteries:

severe diabetes with blood vessel damage

very high blood pressure

a very high level of fat in the blood (cholesterol or triglycerides)

a condition known as hyperhomocysteinaemia
if you have (or have ever had) a type of migraine called ‘migraine with aura’;

If you are allergic to gestodene, ethinylestradiol or any of the other ingredients of this medicine (listed in section 6).

If you or any members of your close family have any medical condition which causes an increased risk to develop blood clots (see also the section ‘The Pill and thrombosis’).

If you have any of the following conditions now, or have ever had them:

Breast cancer or other cancer, for example ovarian cancer, cervical cancer, or cancer of the uterus (womb).

Severe liver disease, including liver tumour.

Vaginal bleeding of unknown origin.

In case of hepatitis (inflammation of the liver caused by a virus) and until liver function tests return to normal.

If you are pregnant or think you might be.

Do not use Ethinylestradiol / Gestodene 20/75, 30/75if you have hepatitis C and are taking the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir (see also in section Other medicines and Ethinylestradiol / Gestodene 30/75).

Warnings and precautions

In some situations you need to take special care while using Ethinylestradiol / Gestodene 20/75, 30/75or any other combination pill, and your doctor may need to examine you regularly. Tell your doctor if any of the following conditions apply to you. If the condition develops, or gets worse while you are using Ethinylestradiol / Gestodene 30/75, you should also tell your doctor.

if you have Crohn’s disease or ulcerative colitis (chronic inflammatory bowel disease);

if you have systemic lupus erythematosus (SLE – a disease affecting your natural defence system);

if you have haemolytic uraemic syndrome (HUS – a disorder of blood clotting causing failure of the kidneys);

if you have sickle cell anaemia (an inherited disease of the red blood cells);

if you have elevated levels of fat in the blood (hypertriglyceridaemia) or a positive family history for this condition. Hypertriglyceridaemia has been associated with an increased risk  of developing pancreatitis (inflammation of the pancreas);if you need an operation, or you are off your feet for a long time (see in section 2 ‘Blood clots ’);

if you have just given birth you are at an increased risk of blood clots. You should ask your doctor how soon after delivery you can start taking Ethinylestradiol / Gestodene 30/75;

if you have an inflammation in the veins under the skin (superficial thrombophlebitis);

if you have varicose veins.

if a close relative has or has ever had breast cancer

if you have a disease of the liver or the gallbladder

if you have diabetes

if you have depression

if you have epilepsy (see “Other medicines and Ethinylestradiol / Gestodene 30/75”)

if you have a disease that first appeared during pregnancy or during earlier use of sex hormones (for example, hearing loss, a blood disease called porphyria, skin rash with blisters during pregnancy (gestational herpes), a nerve disease causing sudden movements of the body (Sydenham’s chorea))

if you have or have ever had chloasma (a discoloration of the skin especially of the face or neck known as “pregnancy patches”). If so, avoid direct sunlight or ultraviolet light.

if you have hereditary angioedema, products containing oestrogens may cause or worsen symptoms. You should see your doctor immediately if you experience symptoms of angioedema

such as swollen face, tongue and/or throat and/or difficulty swallowing or hives together with difficulty breathing.

Psychiatric disorders:

Some women using hormonal contraceptives including Ethinylestradiol / Gestodene 20/75, 30/75have reported depression or depressed mood. Depression can be serious and may sometimes lead to suicidal thoughts. If you experience mood changes and depressive symptoms contact your doctor for further medical advice as soon as possible.

BLOOD CLOTS

Using a combined hormonal contraceptive such as Ethinylestradiol / Gestodene 20/75, 30/75increases your risk of developing a blood clot compared with not using one. In rare cases a blood clot can block blood vessels and cause serious problems.

Blood clots can develop

in veins (referred to as a ‘venous thrombosis’, ‘venous thromboembolism’ or VTE)

in the arteries (referred to as an ‘arterial thrombosis’, ‘arterial thromboembolism’ or ATE).

Recovery from blood clots is not always complete. Rarely, there may be serious lasting effects or, very rarely, they may be fatal.

 

It is important to remember that the overall risk of a harmful blood clot due to Ethinylestradiol / Gestodene 20/75, 30/75is small.

 

HOW TO RECOGNISE A BLOOD CLOT

Seek urgent medical attention if you notice any of the following signs or symptoms.

 

Are you experiencing any of these signs?What are you possibly suffering from?
swelling of one leg or along a vein in the leg or foot especially when accompanied by:

pain or tenderness in the leg which may be felt only when standing or walking

increased warmth in the affected leg

change in colour of the skin on the leg e.g. turning pale, red or blue

Deep vein thrombosis
sudden unexplained breathlessness or rapid breathing;

sudden cough without an obvious cause, which may bring up blood;

sharp chest pain which may increase with deep breathing;

severe light headedness or dizziness;

rapid or irregular heartbeat

severe pain in your stomach;

Pulmonary embolism
 

If you are unsure, talk to a doctor as some of these symptoms such as coughing or being short of breath may be mistaken for a milder condition such as a respiratory tract infection (e.g. a ‘common cold’).

Symptoms most commonly occur in one eye:

immediate loss of vision or

painless blurring of vision which can progress to loss of vision

Retinal vein thrombosis (blood clot in the eye)
chest pain, discomfort, pressure, heaviness

sensation of squeezing or fullness in the chest, arm or below the breastbone;

Heart attack
fullness, indigestion or choking feeling;

upper body discomfort radiating to the back, jaw, throat, arm and stomach;

sweating, nausea, vomiting or dizziness;

extreme weakness, anxiety, or shortness of breath;

rapid or irregular heartbeats

sudden weakness or numbness of the face, arm or leg, especially on one side of the body;

sudden confusion, trouble speaking or understanding;

sudden trouble seeing in one or both eyes;

sudden trouble walking, dizziness, loss of balance or coordination;

sudden, severe or prolonged headache with no known cause;

loss of consciousness or fainting with or without seizure.

 

Sometimes the symptoms of stroke can be brief with an almost immediate and full recovery, but you should still seek urgent medical attention as you may be at risk of another stroke.

Stroke
swelling and slight blue discolouration of an extremity;

severe pain in your stomach (acute abdomen)

Blood clots blocking other blood vessels

 

BLOOD CLOTS IN A VEIN

What can happen if a blood clot forms in a vein?

The use of combined hormonal contraceptives has been connected with an increase in the risk of blood clots in the vein (venous thrombosis). However, these side effects are rare. Most frequently, they occur in the first year of use of a combined hormonal contraceptive.

If a blood clot forms in a vein in the leg or foot it can cause a deep vein thrombosis (DVT).

If a blood clot travels from the leg and lodges in the lung it can cause a pulmonary embolism.

Very rarely a clot may form in a vein in another organ such as the eye (retinal vein thrombosis).

When is the risk of developing a blood clot in a vein highest?

The risk of developing a blood clot in a vein is highest during the first year of taking a combined hormonal contraceptive for the first time. The risk may also be higher if you restart taking a combined hormonal contraceptive (the same product or a different product) after a break of 4 weeks or more After the first year, the risk gets smaller but is always slightly higher than if you were not using a combined hormonal contraceptive.

When you stop Ethinylestradiol / Gestodene 20/75, 30/75your risk of a blood clot returns to normal within a few weeks.

What is the risk of developing a blood clot?

The risk depends on your natural risk of VTE and the type of combined hormonal contraceptive you are taking.

The overall risk of a blood clot in the leg or lung (DVT or PE) with Ethinylestradiol / Gestodene 20/75, 30/75is small.

Out of 10,000 women who are not using any combined hormonal contraceptive and are not pregnant, about 2 will develop a blood clot in a year.

Out of 10,000 women who are using a combined hormonal contraceptive that contains levonorgestrel, norethisterone, or norgestimate about 5-7 will develop a blood clot in a year.

Out of 10,000 women who are using a combined hormonal contraceptive that contains gestodene such as Ethinylestradiol / Gestodene 20/75 between about 9 and 12 women will develop a blood clot in a year.

The risk of having a blood clot will vary according to your personal medical history (see “Factors that increase your risk of a blood clot” below)

Risk of developing a blood clot in a year
Women who are not using a combined hormonal pill/patch/ring and are not pregnantAbout 2 out of 10,000 women
Women using a combined hormonal contraceptive pill containing levonorgestrel, norethisterone or norgestimateAbout 5-7 out of 10,000 women
Women using Ethinylestradiol / Gestodene 20/75, 30/75About 9-12 out of 10,000 women

 

Factors that increase your risk of a blood clot in a vein

The risk of a blood clot with Ethinylestradiol / Gestodene 20/75, 30/75 is small but some conditions will increase the risk.

Your risk is higher:

if you are very overweight (body mass index or BMI over 30kg/m2);

if one of your immediate family has had a blood clot in the leg, lung or other organ at a young age (e.g. below the age of about 50). In this case you could have a hereditary blood clotting disorder;

if you need to have an operation, or if you are off your feet for a long time because of an injury or illness, or you have your leg in a cast. The use of Ethinylestradiol / Gestodene 20/75, 30/75 may need to be stopped several weeks before surgery or while you are less mobile. If you need to stop Ethinylestradiol / Gestodene 20/75, 30/75 ask your doctor when you can start using it again.

as you get older (particularly above about 35 years);

if you gave birth less than a few weeks ago

The risk of developing a blood clot increases the more conditions you have.

Air travel (longer than 4 hours) may temporarily increase your risk of a blood clot, particularly if you have some of the other factors listed.

It is important to tell your doctor if any of these conditions apply to you, even if you are unsure. Your doctor may decide that Ethinylestradiol / Gestodene 20/75, 30/75needs to be stopped.

If any of the above conditions change while you are using Ethinylestradiol / Gestodene 30/75, for example a close family member experiences a thrombosis for no known reason; or you gain a lot of weight, tell your doctor.

BLOOD CLOTS IN AN ARTERY

What can happen if a blood clot forms in an artery?

Like a blood clot in a vein, a clot in an artery can cause serious problems. For example, it can cause a heart attack or a stroke.

Factors that increase your risk of a blood clot in an artery

It is important to note that the risk of a heart attack or stroke from using Ethinylestradiol / Gestodene 20/75, 30/75 is very small but can increase:

with increasing age (beyond about 35 years);

if you smoke. When using a combined hormonal contraceptive like Ethinylestradiol / Gestodene 20/75, 30/75 you are advised to stop smoking. If you are unable to stop smoking and are older than 35 your doctor may advise you to use a different type of contraceptive;

if you are overweight;

if you have high blood pressure;

if a member of your immediate family has had a heart attack or stroke at a young age (less then about 50). In this case you could also have a higher risk of having a heart attack or stroke;

if you, or someone in your immediate family, have a high level of fat in the blood (cholesterol or triglycerides);

if you get migraines, especially migraines with aura;

if you have a problem with your heart (valve disorder, disturbance of the rhythm called atrial fibrillation)

if you have diabetes.

If you have more than one of these conditions or if any of them are particularly severe the risk of developing a blood clot may be increased even more.

If any of the above conditions change while you are using Ethinylestradiol / Gestodene 30/75, for example you start smoking, a close family member experiences a thrombosis for no known reason; or you gain a lot of weight, tell your doctor.

Ethinylestradiol / Gestodene 20/75, 30/75 and cancer

Breast cancer has been observed slightly more often in women using combination pills, but it is not known whether this is caused by the treatment. For example, it may be that more tumours are detected in women on combination pills because they are examined by their doctor more often. The occurrence of breast tumours becomes gradually less after stopping the combination hormonal contraceptives. It is important to regularly check your breasts and you should contact your doctor if you feel any lump.

In rare cases, benign liver tumours, and in even fewer cases malignant liver tumours have been reported in pill users. Contact your doctor if you have unusually severe abdominal pain.

Bleeding between periods

During the first few months that you are taking Ethinylestradiol / Gestodene 20/75, 30/75you may have unexpected bleeding (bleeding outside the gap week). If this bleeding occurs for more than a few months, or if it begins after some months, your doctor must find out what is wrong.

What to do if no bleeding occurs during the gap week

If you have taken all the tablets correctly, have not had vomiting or severe diarrhoea and you have not taken any other medicines, it is highly unlikely that you are pregnant.

If the expected bleeding does not happen twice in succession, you may be pregnant. Contact your doctor immediately. Do not start the next strip until you are sure that you are not pregnant.

Other medicines and Ethinylestradiol / Gestodene 30/75

Tell your doctor if you are taking, have recently taken or might take any other medicines.

The concomitant administration of some other medicines such as anti-epileptic agents, tranquillisers, antibiotics, drugs to treat fungal or viral infections and tuberculosis, as well as herbal remedies containing St. John’s wort (Hypericum perforatum), phenytoin, griseofulvin, topiramate, barbiturates, rifampicin, rifabutin, phenylbutazone, dexamethasone, primidone, carbamazepine, some protease inhibitors, modafinil and possibly also oxcarbazepine, felbamate, ritonavir and nevirapine may reduce the contraceptive efficacy of Ethinylestradiol / Gestodene 20/75, 30/75.

Atorvastatin, ascorbic acid, paracetamol, indinavir, fluconazole, voriconazole and troleandromycin may increase the serum concentrations of Ethinylestradiol / Gestodene 20/75, 30/75.

Lamotrigine, levothyroxin, valproate, cyclosporine, theophylline and corticosteroids serum level may be changed after concomitant use with Ethinylestradiol / Gestodene 30/75.

You may have to use another method of contraception as well, such as the condom, while you are taking the medicines listed above and for a further seven days afterwards. Your doctor may advise you to use these extra precautions for even longer.

Interactions can involve medicines taken recently or subsequently.

If you are taking Ethinylestradiol / Gestodene 20/75, 30/75and rifampicin concomitantly, you will need to use an additional method of contraception while you are taking rifampicin and for 4 weeks after cessation of treatment. If you suffer from diabetes, your doctor may alter the dose of medicine required to treat your diabetes.

Do not use Ethinylestradiol / Gestodene 20/75, 30/75if 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.

Ethinylestradiol / Gestodene 20/75, 30/75can be restarted approximately 2 weeks after completion of this treatment. See section “Do not use Ethinylestradiol / Gestodene 30/75”.

Ethinylestradiol / Gestodene 20/75, 30/75with food and drink

Ethinylestradiol / Gestodene 20/75, 30/75may be taken with or without food, if necessary with a small amount of water.

Laboratory tests

If you need a blood test, tell your doctor or the laboratory staff that you are taking the Pill, because hormone contraceptives can affect the results of some tests.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

If you are pregnant, do not take Ethinylestradiol / Gestodene 30/75. If you become pregnant while taking Ethinylestradiol / Gestodene 20/75, 30/75stop immediately and contact your doctor. If you want to become pregnant, you can stop taking Ethinylestradiol / Gestodene 20/75, 30/75at any time (see also “If you stop taking Ethinylestradiol / Gestodene 30/75”).

Breast-feeding

Use of Ethinylestradiol / Gestodene 20/75, 30/75is generally not advisable when a woman is breast-feeding. If you want to take the pill while you are breast-feeding you should contact your doctor.

Driving and using machines

Ethinylestradiol / Gestodene 20/75, 30/75has no or only minor influence on the ability to drive and use machines.

Ethinylestradiol / Gestodene 20/75, 30/75 contains lactose monohydrate

Ethinylestradiol / Gestodene 20/75, 30/75 contains 50 mg of lactose monohydrate per tablet.

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 Ethinylestradiol / Gestodene 20/75, 30/75 tablets.

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

This package is designed to help you remember to take your pills.

Before starting to take Ethinylestradiol / Gestodene 30/75, a complete medical and gynaecological examination should be performed to exclude diseases which may cause a risk by using oral contraceptives.

During the use of this medicine, medical check-ups should be repeated regularly.

One tablet should be taken daily, preferably always at the same time, starting on the first day of the monthly period for 21 days.

This is followed by a tablet-free period  of  7  days,  durthing  which  a

menstruation-like bleeding occurs. Intake of the next 21 tablets should be started on the 8   day, even if bleeding has not stopped.
You should start the second pack of Ethinylestradiol / Gestodene 20/75, 30/75 on the same day of the week as the first one. Your periods will be probably lighter but it is not harmful.

How to start Ethinylestradiol / Gestodene 30/75

Taking Ethinylestradiol / Gestodene 20/75, 30/75for the first time

Wait for your period to begin, and take extra contraceptive precautions (use condom or cap plus spermicide). The first tablet should be taken the first day of your period.

You can also start taking your Pills on day 2 to 5 of the menstrual cycle, but ensure that additional contraceptive precautions are taken for the first 7 days of using the Pill during the first cycle.

Changing from a combined contraceptive (combined oral contraceptive -COC, vaginal ring or transdermal patch) to Ethinylestradiol / Gestodene 30/75

You can start taking Ethinylestradiol / Gestodene 20/75, 30/75 preferably on the day after the last active tablet (the last tablet containing active substances) of your previous pill, but at the latest on the day after the tablet-free days of your previous pill (or after the last inactive tablet of your previous pill). When changing from a combination contraceptive vaginal ring or patch, follow the advice of your doctor.

Changing from a progestin-only method (progestin-only pill, injection, implant or a progestogen- releasing intrauterine device (IUD))

You can change from the mini-pill on any day (for an implant or IUD, on the same day it is removed; for an injectable method, when the next injection is due), but in all cases, it is recommended that you use additional methods of contraception (for example, a condom) for the first 7 days of pill-taking.

Use after an abortion in the 1st trimester

After an abortion or miscarriage you can start using Ethinylestradiol / Gestodene 20/75, 30/75immediately, according to the instructions of your doctor. In this case no additional contraceptive precaution is required.

Use after delivery or an abortion in the 2nd trimester

You can start taking Ethinylestradiol / Gestodene 20/75, 30/75between 21 and 28 days after having a baby. If you start later than day 28, use a so-called barrier method (for example, a condom) during the first seven days of taking Ethinylestradiol / Gestodene 20/75 ,30/75.

If, after having a baby, you have had sex before starting Ethinylestradiol / Gestodene 20/75, 30/75 (again), you must first be sure that you are not pregnant or wait until your next period.

After an abortion in the 2nd trimester: Follow the advice of your doctor.

If you take more Ethinylestradiol / Gestodene 20/75, 30/75 than you should

No serious ill-effects have been reported after the intake of a considerable dose of the oral contraceptive. The symptoms which may occur are breast tenderness, dizziness, tummy pain, fatigue, nausea, vomiting and, in young girls, light vaginal bleeding. However, if you have taken more Ethinylestradiol / Gestodene 20/75, 30/75than you should, talk to your doctor or pharmacist immediately

If you forget to take Ethinylestradiol / Gestodene 30/75

If you forget to take the pill at the usual time, you should take it within 12 hours. Take the next pill at your normal time. Your protection against pregnancy is not reduced.

If you are more than 12 hours late in taking a pill, the reliability of the Pill may be reduced. You should take the last missed tablet as soon as you remember, even if it means that you need to take 2 tablets at the same time.

From then onwards you should continue to take the tablets at the usual time. Additional contraceptive precautions are required for the next 7 days of tablet taking.

If less than 7 tablets are left in the current pack you can choose between two possibilities:

you should begin the next pack immediately after you took the last tablet from the current pack; that means no pause between packages. In this case, a withdrawal bleeding should not be expected until the end of the second pack; however, spotting and breakthrough bleeding may occur.

you should stop taking tablets from the current pack. In that case you should observe a tablet- free period for up to 7 days, including the days when you missed the tablets, and then proceed with the next pack.

If no withdrawal bleeding occurs after having finished the second pack, consult your doctor.

If you have forgotten any of the tablets in a strip, and you do not have a bleeding during the first tablet-free period, you may be pregnant. Contact your doctor before you start the next strip.

What to do if you have a stomach upset?

If you have been sick or had diarrhoea within 3-4 hours after taking the Pill, the active substances in the Pill may not be fully absorbed into your body. In this case the advice concerning missed pills, described above, should be followed. In case of vomiting or diarrhoea, use extra contraceptive precautions, such as condom, for any intercourse during the stomach upset and for the next 7 days.

Inducing or postponing a period

In order to induce the menstrual bleeding an earlier day of the week than the usual one would happen by the present tablet intake, it is advised to shorten the following tablet-free interval by the desired number of days. The shorter the tablet-free break, the higher the risk that breakthrough bleeding or spotting will be experienced while taking the tablets from the second pack (like in case of postponement of menstrual bleeding).

In order to postpone the menstrual bleeding, a new pack of Ethinylestradiol / Gestodene 20/75, 30/75should be started the day after finishing the current pack, without a break between them. Postponement of menstrual bleeding may last as long as required up to the end of the second pack. During the use of the second pack breakthrough bleeding or spotting may occur. Regular intake of Ethinylestradiol / Gestodene 20/75, 30/75can be restored after the usual 7 tablet-free days.

If you stop taking Ethinylestradiol / Gestodene 30/75

If you stop taking Ethinylestradiol / Gestodene 20/75, 30/75 before the end of a strip, contraceptive protection will not be full, therefore additional contraceptive precaution is recommended.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. Possible side effects

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also side effects directly.

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you get any side effect, particularly if severe and persistent, or have any change to your health that you think may be due to Ethinylestradiol / Gestodene 30/75, please talk to your doctor.

An increased risk of blood clots in your veins (venous thromboembolism (VTE)) or blood clots in your arteries (arterial thromboembolism (ATE)) is present for all women taking combined hormonal contraceptives. For more detailed information on the different risks from taking combined hormonal contraceptives please see section 2 “What you need to know before you use Ethinylestradiol / Gestodene 30/75”.

The following serious side effects have been reported in women using combined oral contraceptives (see section 2 under “The Pill and thrombosis” and “The Pill and cancer”).

Venous thrombo-embolism (a blood clot in vessels)

Arterial thrombotic disorders (obstruction of an artery)

Cervical cancer (cancer of the neck of the womb).

In case of very severe allergic reaction with very rare cases of nettle rash, painful swelling of skin and mucous membranes (angioedema) and respiratory and circulatory symptoms, contact your doctor immediately.

REASONS FOR STOPPING ETHINYLESTRADIOL / GESTODENE 20/75, 30/75 IMMEDIATELY

If you experience any of the following conditions whilst taking Ethinylestradiol / Gestodene 30/75, take no further tablets and tell your doctor straight away. In the meantime use another non-hormonal method of contraception such as condom.

signs suggestive of thrombosis(chest pain, which may radiate to the left arm; unusually severe pain in the legs; weakness or numbness in any part of your body; breathlessness, unusual cough (especially with blood-tinged sputum); dizziness or fainting; disturbances of vision, hearing, speech; sensory loss; first occurrence or aggravation of migraine; unusually intense, recurrent or persisting headache);

jaundice;

palpable mass in the breasts;

severe abdominal pain of abrupt onset ;

unusually intense vaginal bleeding or absence of menses twice in a row;

prolonged immobilization, or 4 weeks prior to a planned operation;

suspected pregnancy;

increase in blood pressure;

convulsions.

These side effects have been reported in women using the Pill. They may occur during the first few months after starting to take Ethinylestradiol / Gestodene 20/75, 30/75, but they usually stop once your body has adjusted to the Pill.

The very commonly reported undesirable effects (may affect more than 1 in 10 people) are:

fluid retention/oedema, headache, including migraines, irregular bleeding and spotting between periods.

Common side effects (may affect up to 1 in 10 people):

fungal infection of vagina, mood altered including depression, libido disorder, dizziness, nervousness, nausea, vomiting, abdominal pain, acne, breast pain or tender breast, breast enlargement, dysmenorrhoea, amenorrhea, menstrual disorder, change in menstrual flow, changes in weight, irritability.

Uncommon side effects (may affect up to 1 in 100 people)

changes in appetite, abdominal cramps, abdominal distension, rash, chloasma (yellowish-  brown patches on the skin), hairiness, baldness, high blood pressure, increase in blood fat  levels, elevated triglyceride concentration in the blood

Rare side effects (may affect up to 1 in 1,000 people)

anaphylactic reaction, angioedema, nettle rash, glucose intolerance, poor tolerance of contact lenses, jaundice, erythema nodosum (painful nodes on lower extremities), ear  disorders,  change in folate level, harmful blood clots in a vein or artery for example:.

o in a leg or foot (i.e. DVT)

o in a lung (i.e. PE)

o heart attack

o stroke

o mini-stroke or temporary stroke-like symptoms, known as a transient ischaemic attack (TIA)

o blood clots in the liver, stomach/intestine, kidneys or eye.

The chance of having a blood clot may be higher if you have any other conditions that increase this risk (See section 2 for more information on the conditions that increase risk for blood clots and the symptoms of a blood clot)

Very rare side effects (may affect up to 1 in 10,000 people):

liver tumour, a blood disorder called haemolytic uraemic syndrome – HUS (a disorder where blood clots cause the kidneys to fail), exacerbation of auto-immune disease (SLE), porphyria aggravated, exacerbation of chorea, inflammation in the nerve of eye, blood clot in the eye’s artery, aggravation of varicose veins, colitis ischemic, inflammation of the pancreas (pancreatitis), gallbladder disorder, gall stones, erythema multiforme.

Not known (frequency cannot be estimated from available data):

inflammatory bowel disease (Crohn’s disease, colitis ulcerative), hepatocellular injury (hepatitis, hepatic function abnormal).

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

  1. How to store Ethinylestradiol / Gestodene 20/75, 30/75 Tablets

Keep this medicine out of the sight and reach of children.

Do not store above 25oC. Store in the original package.

Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date refers to the last day of that month.

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 informationWhat Ethinylestradiol / Gestodene 20/75, 30/75 Tablets contains

The active ingredients are ethinylestradiol and gestodene. Each tablet contains 30 micrograms ethinylestradiol and 75micrograms gestodene.

The other ingredients are: Common Tablet Core:

Lactose monohydrate, Maize starch, Sodium calcium edetate dihydrate, Povidone K30 and Magnesium stearate

Tablet coating: Opadry White containing Hypromellose, Titanium  dioxide  and Macrogol 400.

What Ethinylestradiol / Gestodene 20/75, 30/75Tablets look like and contents of the pack:

Ethinylestradiol / Gestodene 20/75, 30/75tablets are white to off-white, round, biconvex, approximately 5mm diameter, film coated tablets debossed with “GE3” on one side and plain on the other side.

Ethinylestradiol / Gestodene 20/75, 30/75tablets are available in blister packs containing 21 tablets in packs of 21(1×21), 63 (3×21), 126 (6×21) and 273(13×21) * packaged in cartons.

* Not all pack sizes may be marketed

7.Manufactured in India by:

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