Desogestrel and Ethinyl Estradiol 150mcg/30mcg tablets Taj Pharma.

1. Name of the medicinal product

Desogestrel and Ethinyl Estradiol 150 mcg/20 mcg tablets Taj Pharma.
Desogestrel and Ethinyl Estradiol 150 mcg/30 mcg tablets Taj Pharma.

2. Qualitative and quantitative composition

a)Desogestrel and Ethinyl Estradiol 150 mcg/20 mcg tablets Taj Pharma.
Each uncoated tablet contains:
Desogestrel USP and 150mcg
Ethinyl Estradiol USP 20mcg
Excipients                          q.s

b) Desogestrel and Ethinyl Estradiol 150 mcg/30 mcg tablets Taj Pharma.
Each uncoated tablet contains:
Desogestrel USP and 150mcg
Ethinyl Estradiol USP 30mcg
Excipients                          q.s

For a full list of excipients, see section 6.1.

3.Pharmaceutical form

Tablet

4. Clinical particulars

4.1 Therapeutic indications

Oral contraception

The decision to prescribe Desogestrel and Estradiolshould take into consideration the individual woman’s current risk factors, particularly those for venous thromboembolism (VTE), and how the risk of VTE with Desogestrel and Estradiolcompares with other CHCs (see sections 4.3 and 4.4).

4.2 Posology and method of administration

Route of administration: Oral use

How to take Desogestrel and EstradiolTablets

The tablets must be taken every day at about the same time, if necessary with a little liquid, in the order shown on the blister pack. One tablet is to be taken daily for 21 consecutive days. Each subsequent pack is started after a 7-day tablet-free interval; during which time a withdrawal bleeding usually occurs. This usually starts on day 2-3 after the last tablet and may not have finished before the next pack is started.

How to start Desogestrel and EstradiolTablets

No preceding hormonal contraceptive use (in the past month)

Tablet-taking has to start on day 1 of the woman’s natural cycle (i.e. the first day of her menstrual bleeding). Tablet intake is also allowed to start on day 2-5, but during the first cycle concurrent use of a barrier method for the first 7 days of tablet intake is advisable.

• Changing from a combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring or transdermal patch)

The woman should start taking Desogestrel and EstradiolTablets preferably on the day after the last active tablet (the last tablet containing the active substances) of her previous COC, but at the latest on the day following the usual tablet-free or placebo tablet interval of her previous COC. In case a vaginal ring or a transdermal patch has been used, the woman should start using preferably on the day of removal, but at the latest when the next application would have been due.

• Changing from a progestogen-only-method (progestogen-only-pill, injection, implant) or from a progestogen-releasing intrauterine system (IUS)

The woman may switch any day from the progestogen-only pills (from an implant or the IUS on the day of its removal; from an injectable when the next injection would be due) but should in all of these cases be advised to additionally use a barrier method for the first 7 days of tablet-taking.

• Following first-trimester abortion

The woman may start immediately. When doing so, she need not take additional contraceptive measures.

• Following delivery or second-trimester abortion

The woman should be advised to start at day 21 to 28 after delivery or second-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days. However if intercourse has already occurred, pregnancy should be excluded before the actual start of COC use or the woman has to wait for her first menstrual period.

For breastfeeding women – see section 4.6.

Management of missed tablets

If the user is less than 12 hours late in taking any tablet, contraceptive protection is not reduced.

The woman should take the tablet as soon as she remembers, and should take further tablets at usual time.

If she is more than 12 hours late in taking any tablet, contraceptive protection may be reduced. The management of missed tablets can be guided by the following two basic rules:

1. tablet-taking must never be discontinued for longer than 7 days
2. 7 days of uninterrupted tablet-taking are required to attain adequate suppression of the hypothalamus-pituitary-ovarian-axis.

Accordingly the following advice can be given in daily practice:

• Week 1

The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. In addition, a barrier method such as a condom should be used for the next 7 days. If intercourse took place in the preceding 7 days, the possibility of a pregnancy should be considered. The more tablets are missed and the closer they are to the regular tablet-free interval, the higher the risk of a pregnancy.

• Week 2

The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. Provided that the woman has taken her tablets correctly in the 7 days preceding the first missed tablet, there is no need to use extra contraceptive precautions. However, if she has missed more than 1 tablet, the woman should be advised to use extra precautions for 7 days.

• Week 3

The risk of reduced reliability is imminent because of the forthcoming 7-day tablet-free interval. However, by adjusting the tablet-intake schedule, reduced contraceptive protection can still be prevented. By adhering to either of the following two options, there is therefore no need to use extra contraceptive precautions, provided that in the 7 days preceding the first missed tablet the woman has taken all tablets correctly. If this is not the case, she should follow the first of these two options and use extra precautions for the next 7 days as well.

1. The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. The next blister pack must be started as soon as the current blister pack is finished, i.e., no gap should be left between packs. The user is unlikely to have a withdrawal bleed until the end of the second pack, but she may experience spotting or breakthrough bleeding on tablet-taking days.
2. The woman may also be advised to discontinue tablet-taking from the current blister pack. She should then have a tablet-free interval of up to 7 days, including the days she missed tablets, and subsequently continue with the next blister pack.

If the woman missed tablets and subsequently has no withdrawal bleed in the first normal tablet-free interval, the possibility of a pregnancy should be considered.

Advice in case of gastro-intestinal disturbances

In case of severe gastro-intestinal disturbances (e.g., vomiting or diarrhoea), absorption may not be complete and additional contraceptive measures should be taken. If vomiting occurs within 3-4 hours after tablet-taking, a new (replacement) tablet should be taken as soon as possible. The new tablet should be taken within 12 hours of the usual time of tablet-taking if possible. If more than 12 hours elapse, the advice concerning missed tablets, under section “Management of missed tablets”, is applicable. If the woman does not want to change her normal tablet-taking schedule, she has to take the extra tablet(s) from another blister pack.

How to postpone a withdrawal bleed

To delay a period the woman should continue with another blister pack of Desogestrel and EstradiolTablets without a tablet-free interval. The extension can be carried on for as long as wished until the end of the second pack. During the extension the woman may experience breakthrough-bleeding or spotting. Regular intake of Desogestrel and EstradiolTablets is then resumed after the usual 7-day tablet-free interval.

To shift her periods to another day of the week than the woman is used to with her current scheme, she can be advised to shorten her forthcoming tablet-free interval by as many days as she likes. The shorter the interval, the higher the risk that she does not have a withdrawal bleed and will experience breakthrough-bleeding and spotting during the subsequent pack (just as when delaying a period).

4.3 Contraindications

Combined oral contraceptives (COCs) should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first during COC use, the product should be stopped immediately

– Pancreatitis or a history thereof if associated with severe hypertriglyceridemia

– Presence or history of severe hepatic disease as long as liver function values have not returned to normal.

– Presence or history of liver tumours (benign or malignant).

– Known or suspected sex steroid-influenced malignancies (e.g. of the genital organs or the breasts)

– Undiagnosed vaginal bleeding.

– History of migraine with focal neurological symptoms

– Hypersensitivity to the active substances or to any of the excipients of Desogestrel and EstradiolTablets.

Desogestrel and Estradiolis contraindicated for concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir (see sections 4.4 and section 4.5).

• 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 antiphospholipid-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:

4.4 Special warnings and precautions for use

Warnings

If any of the conditions or risk factors mentioned below is present, the suitability of Desogestrel and Estradiolshould 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 Desogestrel and Estradiolshould be discontinued.

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.

Risk of venous thromboembolism (VTE)

Circulatory disorders

The use of any combined oral contraceptive 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 ever uses a combined oral contraceptive. Products that contain levonorgestrel, norgestimate or norethisterone are associated with the lowest risk of VTE. Other products such as Desogestrel and Estradiolmay 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 Cimizt, 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 estimated¹that out of 10,000 women who use a CHC containing desogestrel between 9 and 12 women will develop a VTE in one year; this compares with about 6²in 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 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).

Desogestrel and Estradiolis 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

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). Desogestrel and Estradiolis 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 greaterthan 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

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; motor disturbances;

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

– sudden confusion, trouble speaking or understanding; slurred speech or aphasia;

– sudden trouble seeing in one or both eyes; diplopia

– sudden, severe or prolonged headache with no known cause

– loss of consciousness or fainting/collapse with or without seizure.

-acute abdomen

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.

The presence of one serious risk factor or multiple risk factors for venous or arterial disease, respectively, can also constitute a contra-indication. The possibility of anticoagulant therapy should also be taken into account. COC users should be specifically pointed out to contact their physician in case of possible symptoms of thrombosis. In case of suspected or confirmed thrombosis, COC use should be discontinued. Adequate alternative contraception should be initiated because of the teratogenicity of anticoagulant therapy (coumarins).

The increased risk of thromboembolism in the puerperium must be considered (for information on “Pregnancy and lactation” – see section 4.6).

An increase in frequency or severity of migraine during use of COCs (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC.

Tumours

An increased risk of cervical cancer in long-term users of COCs (> 5 years) has been reported in some epidemiological studies, but there continues to be controversy about the extent to which this finding is attributable to the confounding effects of sexual behaviour and other factors such as human papilloma virus (HPV).

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 COCs. The excess risk gradually disappears during the course of the 10 years after cessation of COC use. Because breast cancer is rare in women under 40 years of age, the excess number of breast cancer diagnoses in current and recent users of COCs is small in relation to the overall risk of breast cancer. These studies do not provide evidence for causation. The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in users of COCs, the biological effects of COCs or a combination of both. The breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users.

In rare cases, benign liver tumours, and even more rarely malignant liver tumours have been reported in users of COCs. In isolated cases, these tumours have led to life-threatening intra-abdominal haemorrhages. A hepatic tumour should be considered in the differential diagnosis when severe upper abdominal pain, liver enlargement or signs of intra-abdominal haemorrhage occur in women taking COCs.

With the use of the higher-dosed COCs (50 µg ethinylestradiol) the risk of endometrial and ovarian cancer is reduced. Whether this also applies to lower-dosed COCs remains to be confirmed.

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 frequent in women using ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs) (see sections 4.3 and 4.5).

Other conditions

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

Although small increases in blood pressure have been reported in many women taking COCs, clinically relevant increases are rare. Only in these rare cases an immediate discontinuation of COC use is justified. A systematic relationship between COC use and clinical hypertension has not been established. If, during the use of a COC in preexisting hypertension, constantly elevated blood pressure values or a significant increase in blood pressure do not respond adequately to antihypertensive treatment, the COC must be withdrawn. Where considered appropriate, COC use may be resumed if normotensive values can be achieved with antihypertensive therapy.

The following conditions have been reported to occur or deteriorate with both pregnancy and COC use, but the evidence of an association with COC use is inconclusive: Jaundice and/or pruritus related to cholestasis; gallstones; porphyria; systemic lupus erythematosus; haemolytic uremic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss.

In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.

Acute or chronic disturbances of liver function may necessitate discontinuation of COC use until markers of liver function return to normal. Recurrence of cholestatic jaundice and/or cholestasis-related pruritus which previously occurred during pregnancy or during previous use of sex steroids necessitates the discontinuation of COCs.

Although COCs may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for a need to alter the therapeutic regime in diabetics using low-dose COCs (containing <0.05 mg ethinylestradiol). However, diabetic women should be carefully observed, particularly in the early stage of COC use.

Worsening of endogenous depression, of epilepsy, of Crohn’s disease and of ulcerative colitis has been reported during COC use.

Chloasma may occasionally occur, especially in women with a medical history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to sunlight or ultra-violet radiation whilst taking COCs.

Desogestrel and EstradiolTablets contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Medical examination/consultation

Prior to the initiation or reinstitution of Desogestrel and EstradiolTablets 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 (section 4.3) and warnings (section 4.4). It is important to draw a woman’s attention to the information on venous and arterial thrombosis, including the risk of Desogestrel and Estradiolcompared 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 oral contraceptives do not protect against HIV infections (AIDS) or other sexually transmitted diseases.

Reduced efficacy

The efficacy of COCs may be reduced in the event of e.g. missed tablets (section 4.2.), gastro-intestinal disturbances (section 4.2.) or concomitant medication (section 4.5.).

Reduced cycle control

With all COCs, irregular bleeding (spotting and 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 3 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. These may include curettage.

In some women withdrawal bleeding may not occur during the tablet-free interval. If the COC has been taken according to the directions described in section 4.2, it is unlikely that the woman is pregnant. However, if the COC has not been taken according to these directions prior to the first missed withdrawal bleed or if two withdrawal bleeds are missed, pregnancy must be ruled out before COC use is continued.

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.

Influence of other medical products on Desogestrel and EstradiolTablets

Interactions between oral contraceptives and other medicinal products may lead to breakthrough bleeding and/or contraceptive failure. The following interactions have been reported in the literature.

Hepatic metabolism

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones (e.g. phenytoin, barbiturates, primidone, carbamazepine, rifampicin, bosentan and HIV-medication (e.g. ritonavir, nevirapine) and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing the herbal remedy St. John’s Wort (Hypericum perforatum). Maximal enzyme induction is generally seen in about 10 days but may then be sustained for at least 4 weeks after the cessation of drug therapy.

Interference with Enterohepatic Circulation

Contraceptive failures have also been reported with antibiotics, such as penicillins and tetracyclines. The mechanism of this effect has not been elucidated.

Management

Women on short-term treatment with any of the above-mentioned classes of medicinal products or individual active substances (hepatic enzyme-inducing medicine) besides rifampicin should temporarily use a barrier method in addition to the COC, i.e. during the time of concomitant medicinal product administration and for 7 days after their discontinuation.

For women on rifampicin a barrier method should be used in addition to the COC during the time of rifampicin administration and for 28 days after its discontinuation.

In women on long-term treatment with hepatic enzyme-inducing active substances, another reliable, non-hormonal, method of contraception is recommended.

Women on treatment with antibiotics (besides rifampicin, see above) should use the barrier method until 7 days after discontinuation.

If concomitant medicinal product administration runs beyond the end of the tablets in the COC blister pack, the next COC pack should be started without the usual tablet-free interval.

Influence of Desogestrel and EstradiolTablets on other medicinal products

Oral contraceptives may affect the metabolism of certain other active substances. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine).

Laboratory analyses

The use of contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function; plasma levels of (carrier) proteins, e.g. corticosteroid-binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal laboratory range.

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, Desogestrel and Estradiolusers 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. Desogestrel and Estradiolcan be restarted 2 weeks following completion of treatment with this combination drug regimen.

4.6 Fertility, pregnancy and lactation

Desogestrel and EstradiolTablets is not indicated in pregnancy.

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

If pregnancy occurs during the use of Desogestrel and EstradiolTablets the preparation should be withdrawn immediately. 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 pregnancy.

Lactation may be influenced by COCs as they may reduce the quantity and change the composition of breast milk. Therefore, the use of COCs should generally not be recommended until the breast-feeding mother has completely weaned her child. Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the milk during COC use. These amounts may affect the child.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. No effects on ability to drive and use machines have been observed in users of COCs.

4.8 Undesirable effects

For serious adverse experiences in users of COCs see section 4.4.

There is 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 a COC. For information on differences in risk between COCs, see Section 4.4.

The following serious adverse events have been reported in women using COCs and are discussed in section 4.4:

– Venous thromboembolic disorders;

– Arterial thromboembolic disorders;

– Hypertension;

– Liver tumours;

– Occurrence or deterioration of conditions for which an association with OC use is not conclusive: Crohn’s disease, ulcerative colitis, epilepsy, migraine, endometriosis, 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 estrogens may induce or exacerbate symptoms of angioedema.

The frequency of diagnosis of breast cancer is very slightly increased among OC 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 and 4.4.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.

4.9 Overdose

There has not been any experience of overdose with Desogestrel and EstradiolTablets. On the basis of general experience with combined oral contraceptives, symptoms that may possibly occur in this case are: nausea, vomiting and, in young girls, slight vaginal bleeding. There are no antidotes and further treatment should be symptomatic.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Progestogens and estrogens, fixed combinations

The contraceptive action of COCs is based on interaction of different factors, out of which the most important is the inhibition of ovulation and changes in the cervical secretion. Besides protection against pregnancy, COCs have several positive properties which, next to the negative properties (see Warnings, Undesirable effects), can be useful in deciding on the method of birth control. The cycle is more regular and the menstruation is often less painful and bleeding is lighter. The latter may result in a decrease in the occurrence of iron deficiency. In the largest multicenter trial (n=23 258 cycles), the uncorrected Pearl Index is estimated at 0.1 (95% confidence interval 0.0-0.3). Furthermore, 4.5% of the women reported absence of withdrawal bleeding and 9.2% reported occurrence of irregular bleeding after 6 treatment cycles.

Desogestrel and EstradiolTablets is a COC with ethinylestradiol and the progestogen desogestrel.

Ethinylestradiol is a well known synthetic estrogen.

Desogestrel is a synthetic progestogen. After oral administration it has a strong ovulation-inhibiting activity.

With the use of the higher-dosed COCs (50μg ethinylestradiol) the risk of endometrial and ovarian cancer is reduced. Whether this also applies to lower-dosed COCs remains to be confirmed.

5.2 Pharmacokinetic properties

Desogestrel

Absorption

After oral administration of desogestrel 150 micrograms and ethinylestradiol 30 micrograms tablets, desogestrel is rapidly absorbed and converted into 3-keto-desogestrel. Peak plasma levels are reached after 1.5 hours. The absolute bioavailability of 3-keto-desogestrel is 62-81%.

Distribution

3-keto-desogestrel is 95.5-99% bound to the plasma proteins, mainly albumin and SHBG. The ethinyl-oestradiol-induced increase in SHBG influences both the amount of bindings and distribution of 3-keto-deosgestrel in the plasma proteins. As a consequence the concentration of 3-keto-desogestrel rises slowly during treatment until steady state is reached within 3-13 days.

Metabolism

The phase-I metabolism of desogestrel includes cytochrome P-450 catalysed hydroxylation and subsequent dehydrogenation at C3. The active metabolite of 3-keto-desogestrel is further reduced, the degradation products are conjugated to sulphate and glucuronides. Animal studies indicate that the enterohepatic circulation has no relevance for the gestagenic activity of desogestrel.

Elimination

3-keto-desogestrel is eliminated with a mean half-life of approx. 31 hours (24-38 hours), plasma clearance varies from 5.0-9.5 l/hour. Desogestrel and its metabolites are eliminated via the urine and in the faeces, either as free steroids or conjugates. Ratio for elimination in urine or faeces is 1.5:1.

Steady-State Conditions

In steady-state conditions the serum level of 3-keto-desogestrel is elevated by two- to threefold.

Ethinylestradiol

Absorption

Ethinyl estradiol is rapidly absorbed and peak plasma levels are reached after 1.5 hours. As a consequence of presystemic conjugation and first-pass metabolism the absolute bioavailability is 60%. The area under the curve and Cmax may be expected to rise slightly over time.

Distribution

Ethinyl estradiol is 98.8% bound to the plasma proteins, almost exclusively to albumin.

Metabolism

Ethinyl estradiol undergoes presystemic conjugation both in the mucosa of the small intestine and in the liver. Hydrolysis of the direct conjugates of ethinyl estradiol with the aid of the intestinal flora gives ethinyl estradiol, which can be re-absorbed, and an enterohepatic circulation is hereby set up. The primary pathway of ethinyl estradiol metabolism is cytochrome P-450-mediated hydroxylation in which the primary metabolites are 2-OH-EE and 2-methoxy-EE. 2-OH-EE is further metabolised to chemically reactive metabolites.

Elimination

Ethinyl estradiol disappears from plasma with a half-life of approx. 29 hours (26-33 hours), plasma clearance varies from 10-30 l/hour. The conjugates of ethinyl estradiol and its metabolites are excreted via urine and faeces (ratio 1:1).

Steady-state conditions

Steady-state conditions are obtained after 3 to 4 days, when the serum drug level is approx. 30 to 40% higher than after the administration of a single dose.

5.3 Preclinical safety data

Toxicological studies have not revealed other effects than those, which can be explained, based on the hormone profile of Desogestrel and EstradiolTablets.

6. Pharmaceutical particulars

6.1 List of excipients

all-rac-alpha-tocopherol, Potato starch, Povidone, Stearic acid, Silica, colloidal anhydrous, Lactose, anhydrous

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Do not store above 25°C and store in the original package in order to protect from moisture and light.

6.5 Nature and contents of container

Clear transparent PVC/PVdC- Aluminium blister of 21 tablets per calender blister strip available in packs containing 1×21, 3×21 or 6×21 tablets. Each blister is packed in trilaminated pouch.

Clear transparent PVC/PVdC- Aluminium blister of 21 tablets per calender blister strip available in packs containing 1×21, 3×21 or 6×21 tablets. Each blister is packed in trilaminated pouch along with 2g molecular sieve.

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

Desogestrel 150 mcg and Estradiol 30 microgram Tablets

PACKAGE LEAFLET: INFORMATION FOR THE USER

Desogestrel and Estradiol

 150/30 Tablets

Desogestrel 150 micrograms & Ethinylestradiol 30 micrograms

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.

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”).

What is in this leaflet    

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

1. What Desogestrel and Estradiol Tablets are and what they are used for

Desogestrel and Estradiol tablet is a combined oral contraceptive, also called the pill. Each tablet contains a small amount of two types of female hormones, namely, a progestogen, desogestrel and an oestrogen, ethinylestradiol.

These help to stop you from getting pregnant, just as your natural hormones would stop you conceiving again when you are already pregnant.

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

1. stop the ovary from releasing an egg each month (ovulation),
   2. thicken the fluid at the neck of the womb making it more difficult for the sperm to reach the egg,
   3. alter the lining of the womb to make it less likely to accept a fertilised egg.

2. What you need to know before you take Desogestrel and Estradiol Tablets

General notes

Before you start using Desogestrel and Estradiol Tablets you 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 Desogestrel and Estradiol Tablets, 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 Desogestrel and Estradiol Tablets, or where the reliability of the pill may 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 Desogestrel and Estradiol Tablets alters the monthly changes of body temperature and of cervical mucus.

Desogestrel and Estradiol Tablets, like other hormonal contraceptives, does not protect against HIV infection (AIDS) or any other sexually transmitted disease.

Do not take tablets

You should not use Desogestrel and Estradiol Tablets if 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 have (or have ever had) an inflammation of the pancreas (pancreatitis);
• if you have (or have ever had) a liver disease and your liver function is still not normal;
• if you have (or have ever had) a tumour in the liver;
• if you have (or have ever had) or if you are suspected to having breast cancer or cancer of the genital organs;
• if you have any unexplained bleeding from the vagina;
• if you have hepatitis C and are taking the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir (see also the section on “Other medicines and Desogestrel and Estradiol Tablets”)
• if you are allergic to ethinylestradiol or desogestrel, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

When should you contact your doctor?

Seek urgent medical attention

• if you notice possible signs of a blood clot that may mean you are suffering from a blood clot in the leg (i.e. deep vein thrombosis), a blood clot in the lung (i.e. pulmonary embolism), a heart attack or a stroke (see ‘Blood Clots’ (thrombosis) section below).

For a description of the symptoms of these serious side effects please go to “How to recognise a blood clot”

In some situations you need to take special care while using Desogestrel and Estradiol Tablets or 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 any of the following conditions applies to you, tell your doctor before starting to use Desogestrel and Estradiol Tablets. Also if any of the following applies or if any of the conditions develops or worsens while you are using Desogestrel and Estradiol Tablets consult your doctor:

• 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 Crohn’s disease or ulcerative colitis (chronic inflammatory bowel disease);
• 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 epilepsy (see “Other medicines and Desogestrel and Estradiol Tablets”);
• if you have systemic lupus erythematosus (SLE a disease affecting your natural defence system);
• 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. In this case you are at an increased risk of blood clots. You should ask your doctor how soon after delivery you can start taking Desogestrel and Estradiol;
• if you have an inflammation in the veins under the skin (superficial thrombophlebitis);
• if you have varicose veins;
• if you have a disease that first appeared during pregnancy or 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. In this case, 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 in breathing.

Psychiatric disorders

Some women using hormonal contraceptives including Desogestrel and Estradiol have 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 Desogestrel and Estradiol increases 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 Desogestrel and Estradiol is 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;

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’).

Pulmonary embolism

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;
• 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.

Heart attack

• 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 Desogestrel and Estradiol your 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 Desogestrel and Estradiol is 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 desogestrel, such as Desogestrel and Estradiol, 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 pregnant About 2 out of 10,000 women

Women using a combined hormonal contraceptive pill containing levonorgestrel, norethisterone or norgestimate About 5-7 out of 10,000 women

Women using Desogestrel and Estradiol About 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 Desogestrel and Estradiol 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 years). 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 Desogestrel and Estradiol may need to be stopped several weeks before surgery or while you are less mobile. If you need to stop Desogestrel and Estradiol ask your doctor when you can start using it again;
• as you get older (particularly above the age of 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 (>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 Desogestrel and Estradiol needs to be stopped.

If any of the above conditions change while you are using Desogestrel and Estradiol, 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 Desogestrel and Estradiol is very small but can increase:

• with increasing age (beyond about the age of about 35 years);
• if you smoke. When using a combined hormonal contraceptive like Desogestrel and Estradiol 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 than about the age of 50 years); 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 Desogestrel and Estradiol, 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.

The pill 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 Desogestrel and Estradiol Tablets, you 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 you must do if no bleeding occurs in 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 Desogestrel and Estradiol Tablets

Always tell the doctor which medicines or herbal products you are already using. Also tell any other doctor or dentist who prescribes another medicine (or the pharmacist) that you use Desogestrel and Estradiol Tablets. They can tell you if you need to take additional contraceptive precautions (for example condoms) and if so, for how long.

Some medicines can make Desogestrel and Estradiol Tablets less effective in preventing pregnancy, or can cause unexpected bleeding. These include:

• Medicines used for the treatment of:
• epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbamazepine);
• tuberculosis (e.g. rifampicin);
• HIV infections (ritonavir, nevirapine) or other infections (antibiotics such as griseofulvin, penicillin, tetracycline);
• The herbal remedy St. John’s wort.

Desogestrel and Estradiol Tablets may influence the effect of other medicines, e.g.

• medicines containing cyclosporin,
• the anti-epileptic lamotrigine (this could lead to an increased frequency of seizures).

Do not use Desogestrel and Estradiol Tablets 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. Desogestrel and Estradiol Tablets can be restarted approximately 2 weeks after completion of this treatment. See the section on “Do not take Desogestrel and Estradiol Tablets”

Ask your doctor or pharmacist for advice before taking any medicine.

Desogestrel and Estradiol Tablets with food and drink

Desogestrel and Estradiol Tablets may 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

If you are pregnant, do not take Desogestrel and Estradiol Tablets. If you become pregnant while taking Desogestrel and Estradiol Tablets stop immediately and contact your doctor. If you want to become pregnant, you can stop taking the pill at any time.

Ask your doctor or pharmacist for advice before taking any medicine.

Breast-feeding

Use of Desogestrel and Estradiol Tablets is 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.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

There is no information suggesting that use of Desogestrel and Estradiol Tablets affects driving or use of machines.

Desogestrel and Estradiol Tablets contain lactose

This product contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before you take this product.

3. How to take Desogestrel and Estradiol Tablets

Take one tablet of Desogestrel and Estradiol Tablets every day, if necessary with a small amount of water. You may take the tablets with or without food, but you should take the tablets every day around the same time.

The strip contains 21 tablets. Next to each tablet is printed the day of the week that it should be taken. If, for example you start on a Wednesday, take a tablet with “WED” next to it. Follow the direction of the arrow on the strip until all 21 tablets have been taken.

Then take no tablets for 7 days. In the course of these 7 tablet-free days (otherwise called a stop or gap week) bleeding should begin. This is so-called “withdrawal bleeding” usually starts on the 2^nd or 3^rd day of the gap week.

On the 8^th day after the last tablet of Desogestrel and Estradiol (that is, after the 7-day gap week), you should start with the following strip, whether your bleeding has stopped or not. This means that you should start every strip on the same day of the week and that the withdrawal bleed should occur on the same days each month.

If you use Desogestrel and Estradiol Tablets in this manner, you are also protected against pregnancy during the 7 days when you are not taking a tablet.

When can you start with the first strip?

• If you have not used a contraceptive with hormones in the previous month
  Begin with Desogestrel and Estradiol on the first day of the cycle (that is the first day of your period). If you start Desogestrel and Estradiol on the first day of your period you are immediately protected against pregnancy. You may also begin on day 2-5 of the cycle, but then you must use extra protective measures (for example, a condom) for the first 7 days.
• Changing from a combination hormonal contraceptive, or combination contraceptive vaginal ring or patch
  You can start Desogestrel and Estradiol 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 progestogen-only-method (progestogen-only pill, injection, implant or a progestogen-releasing IUD)
  You may switch any day from the progestogen-only pill (from an implant or an IUD on the day of its removal, from an injectable when the next injection would be due) but in all of these cases use extra protective measures (for example, a condom) for the first 7 days of tablet-taking.
• After a miscarriage
  Follow the advice of your doctor.
• After having a baby
  You can start Desogestrel and Estradiol between 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 Desogestrel and Estradiol use. If, after having a baby, you have had sex before starting Desogestrel and Estradiol (again), be sure that you are not pregnant or wait until your next period.
• If you are breastfeeding and want to start Desogestrel and Estradiol Tablets (again) after having a baby
  Read the section on “Breast feeding”.

Ask your doctor what to do if you are not sure when to start.

If you take more Desogestrel and Estradiol Tablets than you should

There are no reports of serious harmful results of taking too many Desogestrel and Estradiol Tablets. If you take several tablets at once then you may have symptoms of nausea or vomiting. Young girls may have bleeding from the vagina. If you have taken too many Desogestrel and Estradiol Tablets, or you discover that a child has taken some, ask your doctor or pharmacist for advice.

What to do if you forget to take Desogestrel and Estradiol Tablets

• If you are less than 12 hours late taking a tablet, the protection against pregnancy is not reduced. Take the tablet as soon as you remember and then take the following tablets again at the usual time.
• If you are more than 12 hours late taking a tablet, the protection against pregnancy may be reduced. The greater the number of tablets that you have forgotten, the greater is the risk of becoming pregnant.

The risk of incomplete protection against pregnancy is greatest if you forget a tablet at the beginning or the end of the strip. Therefore, you should keep to the following rules (see the diagram):

• More than one tablet forgotten in this strip

Contact your doctor.

• One tablet forgotten in week 1

Take the forgotten tablet as soon as you remember, even if that means that you have to take two tablets at the same time. Continue taking the tablets at the usual time and use extra precautions for the next 7 days, for example, a condom. If you have had sex in the week before forgetting the tablet you may be pregnant. In that case, contact your doctor.

• One tablet forgotten in week 2

Take the forgotten tablet as soon as you remember, even if that means that you have to take two tablets at the same time. Continue taking the tablets at the usual time. The protection against pregnancy is not reduced, and you do not need to take extra precautions.

• One tablet forgotten in week 3

You can choose between two possibilities:

1. Take the forgotten tablet as soon as you remember, even if that means that you have to take two tablets at the same time. Continue taking the tablets at the usual time. Instead of taking the tablet-free period start the next strip.

Most likely, you will have a period at the end of the second strip but you may also have light or menstruation like bleeding during the second strip.

2. You can also stop the strip and go directly to the tablet-free period of 7 days (record the day on which you forgot your tablet). If you want to start a new strip on the day you always start, make the tablet-free period less than 7 days.

If you follow one of these two recommendations, you will remain protected against pregnancy.

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

What to do in case of vomiting or severe diarrhoea

If you vomit within 3-4 hours of taking a tablet or you have severe diarrhoea, there is a risk that the active substances in the tablet are not fully absorbed into your body. The situation is almost the same as forgetting a tablet. After vomiting or diarrhoea, take another tablet from a reserve strip as soon as possible. If possible take it within 12 hours of when you normally take your pill. If this is not possible or 12 hours have passed, you should follow the advice given under “What to do if you forget to take Desogestrel and Estradiol Tablets”.

Delay of menstrual period: what you need to know

Even though it is not recommended, you can delay your menstrual period by going straight to a new strip of Desogestrel and Estradiol Tablets instead of the tablet-free period, and finishing it. You may experience light or menstruation-like bleeding while using this second strip. After the usual tablet-free period of 7 days, start the next strip.

You might ask your doctor for advice before deciding to delay your menstrual period.

Changing of the first day of your menstrual period: what you must know

If you take the tablets according to the instructions, then your period will begin during the tablet-free week. If you have to change this day, reduce the number of the tablet-free days (but never increase them 7 is the maximum). For example, if your tablet-free days normally begin on a Friday, and you want to change this to a Tuesday (3 days earlier) start a new strip 3 days earlier than usual. If you make the tablet-free interval very short (for example, 3 days or less) you may not have any bleeding during these days. You may then experience light or menstruation-like bleeding.

If you are not sure what to do, consult your doctor.

If you want to stop taking Desogestrel and Estradiol Tablets

You can stop taking Desogestrel and Estradiol Tablets whenever you want. If you do not want to become pregnant, ask your doctor for advice about other reliable methods of birth control. If you want to become pregnant, stop taking Desogestrel and Estradiol Tablets and wait for a period before trying to become pregnant. You will be able to calculate the expected delivery date more easily.

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

4. Possible side effects

Like all medicines, Desogestrel and Estradiol Tablets 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 Desogestrel and Estradiol, 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 take Desogestrel and Estradiol tablets”.

Serious reactions

More serious reactions associated with combined hormonal contraceptive pills are detailed above in section 2 under “Blood Clots” and “The pill and cancer”. Please read these subsections carefully, and if you have any questions, ask your doctor.

The following serious side effects have been reported in women using the pill: Crohn’s disease or ulcerative colitis (chronic inflammatory bowel diseases), systemic lupus erythematosus (SLE, a disease of the connective tissue), epilepsy, the rash known as herpes gestationis, chorea (a movement disease), a blood disorder called haemolytic uraemic syndrome – HUS (a disorder where blood clots cause the kidneys to fail), brown patches on the face and body (chloasma), movement disorder called Sydenham’s chorea, yellowing of the skin, gynaecological disorders (endometriosis, uterine myoma).

Other possible side effects

The following side effects have been reported in women using the pill, which can occur in the first few months after starting Desogestrel and Estradiol Tablets, but they usually stop once your body has adjusted to the pill. The most commonly reported side effects (more than 1 in every 10 users may be affected) are irregular bleeding and weight gain.

Common or uncommon (between 1 and 100 in every 1,000 users may be affected): none or reduced bleeding, tender breasts, breast enlargement, breast pain, decreased sexual desire, depression, headache, nervousness, migraine, dizziness, nausea, vomiting, acne, rash, nettle-rash (urticaria), fluid retention, high blood pressure.

Rare (between 1 and 10 in every 10,000 users may be affected): vaginal candidiasis (fungal infection), impaired hearing (otosclerosis), thromboembolism, hypersensitivity, increased sexual desire, eye irritation due to contact lens, loss of hair (alopecia), itching, skin disorders (erythema nodosum – a skin disease associated with joint pain, fever, hypersensitivity, or infection, and characterized by small, painful, pink to blue nodules under the skin and on the shins that tend to recur; erythema multiforme – a skin disease characterized by solid raised spots on the skin or fluid-filled blisters lesions and reddening or discoloration of the skin often in concentric zones about the lesions), vaginal discharge, breast discharge, harmful blood clots in a vein or artery for example:

• in a leg or foot (i.e. DVT);
• in a lung (i.e. PE);
• heart attack;
• stroke;
• mini-stroke or temporary stroke-like symptoms, known as a transient ischaemic attack (TIA);
• 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).

Before you have any blood tests

Tell your doctor or the laboratory staff that you are taking the pill, because oral contraceptives can affect the results of some tests.

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

Reporting of side effects

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

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Desogestrel and Estradiol Tablets

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

Do not store above 25°C. Store in the original package in order to protect from moisture and light.

Expiry date

Do not use this medicine after the expiry date which is stated on the package 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.

6. Contents of the pack and other information

What Desogestrel and Estradiol Tablets contain

The active substances are desogestrel and ethinylestradiol.

The other ingredients are:

All-rac-alpha-tocopherol, potato starch, povidone, stearic acid, silica colloidal anhydrous and lactose anhydrous.

What Desogestrel and Estradiol tablets look like and contents of the pack

Each uncoated tablet is round, white to off-white, uncoated, biconvex,

Each strip of Desogestrel and Estradiol Tablets contains 21 white tablets.

Each box of Desogestrel and Estradiol Tablets contains 1, 3 or 6 strips of 21 tablets.

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