Ethinyl Estradiol Tablets USP 10mcg Taj Pharma

1. Name of the medicinal product
a) Ethinyl Estradiol Tablets USP 10mcg Taj Pharma
b) Ethinyl Estradiol Tablets USP 50mcg Taj Pharma

2. Qualitative and quantitative composition
a) Each uncoated tablet contains:
Ethinylestradiol USP 10mcg
Excipients q.s.

b) Each uncoated tablet contains:
Ethinylestradiol USP 50mcg
Excipients q.s.

3. Pharmaceutical form
White, biconvex, uncoated tablets. For oral administration

4. Clinical particulars
4.1 Therapeutic indications
Post menopausal symptoms due to estrogen deficiency.

Prevention of osteoporosis in postmenopausal women at high risk of future fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of osteoporosis.

Palliative treatment of prostatic cancer.

Hormone replacement therapy for failure of ovarian development e.g. in patients with gonadal dysgenesis where initial estrogen therapy is later followed by combined estrogen/progestogen therapy.

Disorders of menstruation, given in conjunction with a progestogen.

4.2 Posology and method of administration
Ethinylestradiol Tablets is an estrogen-only preparation of hormone replacement therapy (HRT) for oral administration.

Post menopausal symptoms due to estrogen deficiency including prevention of postmenopausal osteoporosis: for initiation and continuation of treatment of postmenopausal symptoms, the lowest effective dose for the shortest duration should be used. The usual dose range is 10 to 50 micrograms daily, usually on a cyclical basis (e.g., 3 weeks on and 1 week off).

For women without a uterus, who did not have endometriosis diagnosed, it is not recommended to add a progestogen.

In women with an intact uterus (or in endometriosis when endometrial foci may be present despite hysterectomy), where a progestogen is necessary, it should be added for at least 12-14 days every month/28 day cycle to reduce the risk to the endometrium.

The benefits of the lower risk of endometrial hyperplasia and endometrial cancer due to adding progestogen should be weighed against the increased risk of breast cancer

Therapy with Ethinylestradiol Tablets may start at any time in women with established amenorrhoea or who are experiencing long intervals between spontaneous menses. In women who are menstruating, it is advised that therapy starts on the first day of bleeding. As Ethinylestradiol Tablets are usually taken on a cyclical basis direct switching from other estrogen-only HRT preparations taken cyclically is possible.

Palliative treatment of prostatic cancer: 150 micrograms to 1.5 mg daily. Larger dose Ethinylestradiol Tablets are available.

Hormone replacement therapy for failure of ovarian development e.g. in patients with gonadal dysgenesis: 10 to 50 micrograms daily, usually on a cyclical basis. Initial estrogen therapy should be followed by combined estrogen/progestogen therapy.

Disorders of menstruation: 20 to 50 micrograms daily from day 5 to day 25 of each cycle. A progestogen is given daily in addition, either throughout the cycle or from days 15 to 25 of the cycle.

If a dose is forgotten it should be taken as soon as it is remembered. If it is nearly time for the next dose then the patient should wait until then. Two doses should not be taken together. Forgetting a dose may increase the likelihood of break-through bleeding and spotting.

4.3 Contraindications
Active or recent arterial thromboembolic disease, e.g. angina, myocardial infarction
• Current or previous idiopathic venous thromboembolism (deep venous thrombosis, pulmonary embolism)
• Known, past or suspected breast cancer or other known or suspected estrogen dependent tumours (e.g. endometrial cancer)
• Untreated endometrial hyperplasia
• Undiagnosed genital bleeding
• Acute liver disease or a history of liver disease as long as liver function tests have failed to return to normal
• Porphyria
• Known hypersensitivity to the active substance or to any of the excipients

4.4 Special warnings and precautions for use

Warnings about the ingredients in Ethinylestradiol
Ethinylestradiol contains lactose. It is not suitable for people who are unable to tolerate a sugar called lactose. This rare condition may have been passed down from someone in your family. Tell your doctor or pharmacist before taking your tablets if this applies to you.
For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as benefit outweighs the risk.

Medical examination/follow-up
Before initiating or reinstituting HRT, a complete personal and family medical history should be taken. Physical (including pelvic and breast) examination should be guided by this and by the contraindications and warnings for use. During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman. Women should be advised what changes in their breasts should be reported to their doctor or nurse (see ‘Breast cancer’ below). Investigation, including mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual.

Conditions which need supervision
If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised. It should be taken into account that these conditions may recur or be aggravated during treatment with ethinylestradiol tablets, in particular:
• Risk factors for estrogen dependent tumours e.g. 1^st degree heredity for breast cancer
• Leimyoma (uterine fibroids) or endometriosis
• A history of, or risk factors for, thromboembolic disorders (see below)
• Hypertension
• Liver disorders (e.g. liver adenoma)
• Diabetes Mellitus with or without vascular involvement
• Cholelithiasis
• Otosclerosis
• Asthma
• Migraine or (severe) headache and epilepsy
• Systemic Lupus erythematosis
• Hyperplasia of the endometrium (see below)

Reasons for immediate withdrawal of therapy
• Jaundice or deterioration in liver function
• Significant increase in blood pressure
• New onset of migraine-type headache
• Pregnancy

Endometrial hyperplasia
The risk of endometrial hyperplasia and carcinoma is increased when estrogens are administered alone for prolonged periods (see Section 4.8). The addition of a progestogen for at least 12 days of the cycle in non-hysterectomised women greatly reduces this risk.
The reduction in risk to the endometrium should be weighed against the increase in the risk of breast cancer of added progestogen (see ‘Breast cancer’ below and in Section 4.8)
Break-through bleeding and spotting may occur during the first months of treatment. If break-through bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy.
Unopposed estrogen stimulation may lead to premalignant or malignant transformation in the residual foci of endometriosis. Therefore, the addition of progestogens to estrogen replacement therapy should be considered in women who have undergone hysterectomy because of endometriosis, especially if they are known to have residual endometriosis (but see above).

Breast cancer
A randomised placebo-controlled trial, the Women’s Health Initiative study (WHI) and epidemiological studies, including the Million Women Study (MWS), have reported an increased risk of breast cancer in women taking oestragens, estrogen-progestogen combinations or tibolone for HRT for several years (See Section 4.8). For all HRT, an excess risk becomes apparent within a few years of use and increases with duration of intake but returns to baseline within a few (at most five) years after stopping treatment.
In the MWS, the relative risk of breast cancer with conjugated equine estrogens (CEE) or estradiol (E2) was greater when a progestogen was added, either sequentially or continuously, and regardless of type of progestogen. There was no evidence of a difference in risk between the different routes of administration.
In the WHI study, the continuous combined conjugated equine estrogen and medroxyprogesterone acetate (CEE + MPA) product used was associated with breast cancers that were slightly larger in size and more frequently had local lymph node metastases compared to placebo.
HRT, especially estrogen-progestogen combined treatment, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.

Ovarian Cancer
Long-term (at least 5 to 10 years) use of estrogen-only HRT products in hysterectomised women has been associated with an increased risk of ovarian cancer in some epidemiological studies. It is uncertain whether long-term use of combined HRT confers a different risk than estrogen-only products.

Venous thromboembolism
–HRT is associated with a higher relative risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. One randomised controlled trial and epidemiological studies found a two- to three fold higher risk for users compared with non-users. For non-users, it is estimated that the number of cases of VTE that will occur over a 5 year period is about 3 per 1000 women aged 50 – 59 years and 8 per 1000 women aged between 60 – 69 years. It is estimated that in healthy women who use HRT for 5 years, the number of additional cases of VTE over a 5 year period will be between 2 and 6 (best estimate = 4) per 1000 women aged 50 – 59 years and between 5 and 15 (best estimate = 9) per 1000 women aged 60 – 69 years. The occurrence of such an event is more likely in the first year of HRT than later.
—Generally recognised risk factors for VTE include a personal history or family history, severe obesity (BMI > 30 kg/m²) and systemic lupus erythematosus (SLE). There is no consensus about the possible role of varicose veins in VTE.
–Patients with a history of VTE or known thrombophilic states have an increased risk of VTE. HRT may add further to this risk. Personal or strong family history of recurrent thromboembolism or recurrent spontaneous abortion, should be investigated in order to exclude a thrombophilic predisposition. Until a thorough evaluation of thrombophilic factors has been made or anticoagulant treatment initiated, use of HRT in such patients should be viewed as contraindicated. Those women already on anticoagulant treatment require careful consideration of the benefit-risk of use of HRT.
–The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery. As in all postoperative patients, scrupulous attention should be given to prophylactic measures to prevent VTE following surgery. Where prolonged immobilisation is liable to follow elective surgery, particularly abdominal or orthopaedic surgery to the lower limbs, consideration should be given to temporarily stopping HRT 4 to 6 weeks earlier, if possible. Treatment should not be restarted until the woman is completely mobilised.
–If VTE develops after initiating therapy, the drug should be discontinued. Patients should be told to contact their doctors immediately when they are aware of a potential thromboembolic symptom (e.g., painful swelling of a leg, sudden pain in the chest, dyspnoea).

Stroke
One large randomised clinical trial (WHI-trial) found, as a secondary outcome, an increased risk of ischaemic stroke in healthy women during treatment with continuous combined continuous estrogens and medroxyprogesterone acetate (MPA). For women who do not use HRT, it is estimated that the number of cases of stroke that will occur over a 5 year period is about 3 per 1000 women aged 50 – 59 years and 11 per 1000 women aged 60 – 69 years. It is estimated that for women who use conjugated estrogens and MPA for 5 years, the number of additional cases will be between 0 and 3 (best estimate = 1) per 1000 users aged 50 – 59 years and between 1 and 9 (best estimate = 4) per 1000 users aged 60 – 69 years. It is unknown whether the increased risk also extends to other HRT products.

Coronary Artery Disease (CAD)
There is no evidence from randomised controlled trials of cardiovascular benefit with continuous combined conjugated estrogens and MPA. Two large clinical trials (WHI and HERS i.e. Heart and Estrogen/progestin Replacement Study) showed a possible increased risk of cardiovascular morbidity in the first year of use and no overall benefit. For other HRT products there are limited data from randomised controlled trials examining effects in cardiovascular morbidity or mortality. Therefore, it is uncertain whether these findings also extend to other HRT products.

Other conditions
• Estrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction should be carefully observed. Patients with terminal renal insufficiency should be closely observed, since it is expected that the level of circulating active ingredients in Ethinylestradiol Tablets is increased.
• Women with pre-existing hypertriglyceridemia should be followed closely during estrogen replacement or hormone replacement therapy, since rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported with estrogen therapy in this condition.
• Estrogens increase thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by radio-immunoassay) or T3 levels (by radio-immunoassay). T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Other binding proteins may be elevated in serum, i.e. corticoid binding globulin (CBG), sex-hormone-binding globulin (SHBG) leading to increased circulating corticosteroids and sex steroids, respectively. Free or biological active hormone concentrations are unchanged. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-I-antitrypsin, ceruloplasmin).
• There is no conclusive evidence for improvement of cognitive function. There is some evidence from the WHI trial of increased risk of probable dementia in women who start using continuous combined CEE and MPA after the age of 65. It is unknown whether the findings apply to younger post-menopausal women or other HRT products.
• Patients with rare hereditary problems of galactose intolerance, the Lapp-lactose deficiency, or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction
• The metabolism of estrogens may be increased by concomitant use of substances known to induce drug metabolising enzymes, specifically cytochrome P450 enzymes, such as anti-convulsants (e.g. phenobarbitol, phenytoin, carbamazepine), anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz) and modafinil.
• Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones. Herbal preparations containing St Johns Wort (Hypericum Perforatum) may induce the metabolism of estrogens.
• Clinically, an increased metabolism of estrogens may lead to decreased effect and changes in the uterine bleeding profile.
• Ethinylestradiol doses greater than 50 micrograms per day may cause imipramine toxicity in patients on concomitant therapy.
• Through its effects on the coagulation system, ethinylestradiol may reduce the effects of anticoagulants such as warfarin, phenindione or nicoumalone.
• The doses of insulin or hypoglycaemic drugs may need to be adjusted due to the mild diabetogenic effect of ethinylestradiol.
• Ethinylestradiol may inhibit the metabolism of theophylline and reduce its clearance.
• Ethinylestradiol has been shown to decrease serum concentrations of lamotrigine when the two drugs are co-administered.

4.6 Fertility, pregnancy and lactation
Ethinylestradiol Tablets are not indicated during pregnancy. If pregnancy occurs during medication with Ethinylestradiol Tablets treatment should be withdrawn immediately. The results of most epidemiological studies to date relevant to inadvertent fetal exposure to estrogens indicate no teratogenic or fetotoxic effects.
Ethinylestradiol Tablets are not indicated during lactation

4.7 Effects on ability to drive and use machines
Non Stated

4.8 Undesirable effects
Breast cancer
According to evidence from a large number of epidemiological studies and one randomised placebo-controlled trial, the Women’s Health Initiative (WHI), the overall risk of breast cancer increases with increasing duration of HRT use in current or recent HRT users.
For estrogen-only HRT, estimates of relative risk (RR) from a reanalysis of original data from 51 epidemiological studies (in which >80% of HRT use was estrogen-only HRT) and from the epidemiological Million Women Study (MWS) are similar at 1.35 (95%CI 1.21 – 1.49) and 1.30 (95%CI 1.21 – 1.40), respectively.
For estrogen plus progestogen combined HRT, several epidemiological studies have reported an overall higher risk for breast cancer than with estrogens alone.
The MWS reported that, compared to never users, the use of various types of estrogen-progestogen combined HRT was associated with a higher risk of breast cancer (RR = 2.00, 95%CI: 1.88 – 2.12) than use of estrogens alone (RR = 1.30, 95%CI: 1.21 – 1.40) or use of tibolone (RR=1.45; 95%CI 1.25- 1.68).
The WHI trial reported a risk estimate of 1.24 (95%CI 1.01 – 1.54) after 5.6 years of use of estrogen-progestogen combined HRT (CEE + MPA) in all users compared with placebo.
The absolute risks calculated from the MWS and the WHI trial are presented below:
The MWS has estimated, from the known average incidence of breast cancer in developed countries, that:

For women not using HRT, about 32 in every 1000 are expected to have breast cancer diagnosed between the ages of 50 and 64 years.
• For 1000 current or recent users of HRT, the number of additionalcases during the corresponding period will be
For users of estrogen-onlyreplacement therapy
– between 0 and 3 (best estimate = 1.5) for 5 years’ use
– between 3 and 7 (best estimate = 5) for 10 years’ use.
For users of estrogen plus progestogencombined HRT,
– between 5 and 7 (best estimate = 6) for 5 years’ use
– between 18 and 20 (best estimate = 19) for 10 years’ use.

The WHI trial estimated that after 5.6 years of follow-up of women between the ages of 50 and 79 years, an additional 8 cases of invasive breast cancer would be due to estrogen-progestogen combined HRT (CEE + MPA) per 10,000 women years.

According to calculations from the trial data, it is estimated that:

For 1000 women in the placebo group,
– about 16 cases of invasive breast cancer would be diagnosed in 5 years.
For 1000 women who used estrogen + progestogen combined HRT (CEE + MPA), the number of additional cases would be
– between 0 and 9 (best estimate = 4) for 5 years’ use.
The number of additional cases of breast cancer in women who use HRT is broadly similar for women who start HRT irrespective of age at start of use (between the ages of 45-65)

Endometrial cancer
In women with an intact uterus, the risk of endometrial hyperplasia and endometrial cancer increases with increasing duration of use of unopposed estrogens. According to the data from epidemiological studies, the best estimate of the risk of endometrial cancer is that for women not using HRT, about 5 in every 1000 are expected to have endometrial cancer diagnosed between the ages of 50 and 65. Depending on the duration of treatment and estrogen dose, the reported increase in endometrial cancer risk among unopposed estrogen users varies from 2-to 12-fold greater compared with non- users. Adding a progestogen to estrogen-only therapy greatly reduces this this increased risk.

Other adverse reactions have been reported in association with estrogen treatment;

Genito-urinary tract: endometrial neoplasia, endometrial cancer, intermenstrual bleeding, increase in the size of uterine fibromyomata, endometrial proliferation or aggravation of endometriosis, excessive production of cervical mucus.

Breast: tenderness, pain, enlargement, secretion.

Gastro-intestinal tract: nausea, vomiting, cholelithiasis, cholestatic jaundice.

Cardiovascular system: hypertension, thrombosis, thrombophlebitis, thromboembolism, myocardial infarction, stroke.
Venous thromboembolism, i.e. deep leg or pelvic venous thrombosis and pulmonary embolism, is more frequent among hormone replacement therapy users than among non-users.

Skin: erythema nodosum, erythema multiforme, vascular purpura, rash, chloasma.

Eyes: corneal discomfort if contact lenses are used.

CNS: headache, migraine, mood changes (elation or depression), probable dementia

Metabolic: sodium and water retention, reduced glucose tolerance and change in body weight, hypercalcaemia.

In men: feminisation, gynaecomastia, testicular atrophy and impotence.

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.

4.9 Overdose
Acute overdose of ethinylestradiol may cause nausea and vomiting and may result in withdrawal bleeding in females.

5. Pharmacological properties

5.1 Pharmacodynamic properties
The active ingredient, ethinylestradiol, is chemically and biologically identical to endogenous human oestradiol. It substitutes for the loss of estrogen production in menopausal women, and alleviates menopausal symptoms. Estrogens prevent bone loss following menopause or ovariectomy.

Estrogen deficiency at menopause is associated with an increasing bone turnover and decline in bone mass. The effect of estrogens on the bone mineral density is dose-dependent. Protection appears to be effective for as long as treatment is continued.

After discontinuation of HRT, bone mass is lost at a rate similar to that in untreated women.

Evidence from the WHI trial and meta-analysed trials shows that current use of HRT, alone or in combination with a progestagen – given to predominantly healthy women – reduces the risk of hip, vertebral, and other osteoporotic fractures. HRT may also prevent fractures in women with low bone density and/or established osteoporosis, but the evidence for that is limited.

The main therapeutic use of exogenous estrogens is replacement in deficiency states.

5.2 Pharmacokinetic properties
Ethinylestradiol is rapidly and completely absorbed from the gut but it undergoes some first pass metabolism in the gut wall.

Ethinylestradiol is rapidly distributed throughout most body tissues with the largest concentration found in adipose tissue. It distributes into breast milk in low concentrations. More than 80% of ethinylestradiol in serum is conjugated as the sulphate and almost all the conjugated form is bound to albumin.

Ethinylestradiol is metabolised in the liver. Hydroxylation appears to be the main metabolic pathway. 60% of a dose is excreted in the urine and 40% in the faeces. About 30% is excreted in the urine and bile as the glucuronide or sulphate conjugate.

The rate of metabolism of ethinylestradiol is affected by several factors, including enzyme-inducing agents, antibiotics and cigarette smoking.

After oral administration, an initial peak occurs in plasma at 2 to 3 hours, with a secondary peak at about 12 hours after dosing; the second peak is interpreted as evidence for extensive enterohepatic circulation of ethinylestradiol.

The elimination half-life of ethinylestradiol ranges from 5 to 16 hours.

5.3 Preclinical safety data
None stated

6. Pharmaceutical particulars

6.1 List of excipients
Lactose monohydrate
Starch Maize
Magnesium Stearate
IMS 99%
Purified water

6.2 Incompatibilities
Not applicable.

6.3 Shelf life
36 months

6.4 Special precautions for storage
Store below 25°C.

6.5 Nature and contents of container
Pigmented polypropylene container fitted with a tamper evident closure containing 21 or 100 tablets. All pack sizes may not be marketed.

6.6 Special precautions for disposal and other handling
Not applicable.

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

Package leaflet: Information for the patient

a) Ethinyl Estradiol Tablets USP 10mcg Taj Pharma
b) Ethinyl Estradiol Tablets USP 50mcg Taj Pharma

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

1. WHAT ETHINYL ESTRADIOL TABLETS ARE AND WHAT THEY ARE USED FOR
Ethinylestradiol belongs to a group of medicines called oestrogens (female sex hormones). Ethinylestradiol is a synthetic (man-made) oestrogen.
Oestrogens are a group of naturally occurring hormones which have a wide range of actions in the body. These include effects on the development of the body and maintaining the menstrual cycle (periods) in women.
During the menopause (sometimes called “the change of life”) a woman’s body slowly produces less oestrogen. This may cause hot flushes, night sweats, mood swings and dryness in the vagina. Over a long time it may also cause a thinning of the bones, which may be more likely to then break (osteoporosis). Ethinylestradiol is used for:
• Hormone Replacement Therapy (HRT) – This is the most common use of Ethinylestradiol. The tablets replace the naturally occurring oestrogen if not enough is being produced. This can be in older women going through, or after the menopause or in younger women whose ovaries have not developed properly.
• Period Problems – You may be prescribed Ethinylestradiol if you are suffering from problems associated with your periods. If you still have your womb and are prescribed an oestrogen, such as Ethinylestradiol, then your doctor should normally prescribe a progestogen as well.
• Osteoporosis – Women who have passed through the menopause and are at a high risk of future fractures may be prescribed Ethinylestradiol if they are unable to take other medicines for this condition.
• Prostate Cancer – Oestrogen is also a naturally occurring hormone in men and Ethinylestradiol may be prescribed to treat men suffering from prostate cancer.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE ETHINYL ESTRADIOL TABLETS
Before you take Ethinyl Estradiol
You are allergic to ethinylestradiol
• You are allergic to any of the other ingredients in Ethinylestradiol (see section 6)
• You have ever had heart disease or any problems with your heart or circulation. This includes any blood clots (thrombosis), problems with your blood (e.g. sickle cell, polycythaemia or porphyria), varicose veins, migraine, high blood pressure, heart attack, stroke or angina
• You have or have had breast cancer
• You have or have had a tumour that may be affected by oestrogen e.g. endometrial cancer (cancer or the womb)
• You suffer from a condition where the lining of the womb builds up more than usual (endometrial hyperplasia)
• You suffer from unexplained vaginal bleeding • You have ever had liver or gall bladder disease. This includes gallstones or jaundice due to pregnancy or the contraceptive pill
If any of the above applies to you talk to your doctor or pharmacist.
Check with your doctor before taking Ethinylestradiol if:
• You still have your womb. If this is the case the ethinylestradiol should normally be taken with another type of hormone tablet to reduce the risk of cancer in the lining of the womb. If you suffer from fibroids (growths in the womb) they may be made worse by ethinylestradiol
• You are diabetic – Ethinylestradiol may effect how your body controls sugar and therefore your diabetic treatment may need adjusting
• You have had any problems with your kidneys • You have ever suffered from hearing loss
• You suffer from asthma
• You wear contact lenses
• You have been told by your doctor that you suffer from increased blood lipids
Safety of HRT
As well as benefits, HRT has some risks which you may wish to discuss with your doctor when you are deciding whether to start HRT, or whether to carry on taking it.
Medical check-ups
Before you start using HRT, your doctor should ask you about your own and your family’s medical history. Your doctor may decide to examine your breasts and/or your abdomen and may do an internal examination
– but only if these examinations are necessary for you, or if you have any special concerns. Once you have started on HRT, you should see your doctor for regular check-ups (at least once a year). At these check-ups, your doctor may discuss with you the benefits and risks of continuing to take HRT.
Be sure to:
• Go for regular breast screening and cervical smear tests.
• Regularly check your breasts for any changes such as dimpling of the skin, changes in the nipple, or any lumps you can see or feel.
Effects on your heart or circulation
– Heart disease
HRT is not recommended for women who have or have recently had heart disease. If you have ever had heart disease, talk to your doctor to see if you should be taking HRT.
HRT will not help to prevent heart disease. Studies with one typ e of HRT (containing conjugated oestrogen plus the progestogen MPA) have shown that women may be slightly more likely to get heart disease during the first year of taking the medication. For other types of HRT, the risk is likely to be similar, although this is not yet certain.
If you get:
A pain in your chest that spreads to your arm or neck. See a doctor as soon as possible and do not take any more HRT until your doctor says you can. This pain could be a sign of heart disease.

– Stroke
Recent research suggests that HRT slightly increases the risk of having a stroke. Other things that can increase the risk of stroke include:
• Getting older
• High blood pressure
• Smoking
• Drinking too much alcohol
• An irregular heartbeat.
If you are worried about any of these things, or if you have had a stroke in the past, talk to your doctor to see if you should take HRT. Compare:
− Looking at women in their 50s who are not taking HRT – on average, over a 5-year period, 3 in 1000 would be expected to have a stroke.
− For women in their 50s who are taking HRT, the figure would be 4 in 1000.
− Looking at women in their 60s who are not taking HRT – on average, over a 5-year period, 11 in 1000 would be expected to have a stroke. − For women in their 60s who are taking HRT, the figure would be 15 in 1000.
If you get:
Unexplained migraine-type headaches, with or without disturbed vision. See a doctor as soon as possible and do not take any more HRT until your doctor says you can. These headaches may be an early warning sign of a stroke.

Blood clots
HRT may increase the risk of blood clots in the veins (also called deep vein thrombosis, or DVT), especially during the first year of taking it.
These blood clots are not always serious, but if one travels to the lungs, it can cause chest pain, breathlessness, collapse or even death. This condition is called pulmonary embolism, or PE. DVT and PE are examples of a condition called venous thromboembolism, or VTE. You are more likely to get a blood clot if:
• You are seriously overweight
• You have had a blood clot before
• Any of your close family have had blood clots • You have had one or more miscarriages
• You have any blood clotting problem that needs treatment with a medicine such as warfarin
• You’re off your feet for a long time because of major surgery, injury or illness
• You have a rare condition called SLE
If any of these things apply to you, talk to your doctor to see if you should take HRT.
Compare:
− Looking at women in their 50s who are not taking HRT – on average, over a 5-year period, 3 in 1000 would be expected to get a blood clot.
− For women in their 50s who are taking HRT, the figure would be 7 in 1000.
− Looking at women in their 60s who are not taking HRT – on average, over a 5-year period, 8 in 1000 would be expected to get a blood clot.
− For women in their 60s who are taking HRT, the figure would be 17 in 1000.
If you get:
• painful swelling in your leg
• sudden chest pain
• difficulty breathing.
You must see a doctor as soon as possible and do not take any more HRT until your doctor says you can. These may be signs of a blood clot. – Surgery
If you’re going to have surgery, make sure your doctor knows about it. You may need to stop taking HRT about 4 to 6 weeks before the operation, to reduce the risk of a blood clot. Your doctor will tell you when you can start taking HRT again.
Effects on your risk of developing cancer – Breast cancer
Women who have breast cancer, or have had breast cancer in the past, should not take HRT. Taking HRT slightly increases the risk of breast cancer; so does having a later menopause. The risk for a post-menopausal woman taking oestrogen-only HRT for 5 years is about the same as for a woman of the same age who is still having periods over that time and not taking HRT. The risk for a woman who is taking oestrogen plus progestogen HRT is higher than for oestrogen-only HRT (but oestrogen plus progestogen HRT is beneficial for the endometrium, see ‘Endometrial cancer’ below). For all kinds of HRT, the extra risk of breast cancer goes up the longer you take it, but returns to normal within about 5 years after stopping HRT.
Your risk of breast cancer is also higher if you:
• have a close relative (mother, sister or grandmother) who has had breast cancer
• are seriously overweight.
Compare:
− Looking at women aged 50 who are not taking HRT – on average, 32 in 1000 will be diagnosed with breast cancer by the time they reach the age of 65.
− For women who start taking oestrogen-only HRT at age 50 and take it for 5 years, the figure will be 33 and 34 in 1000 (i.e. an extra 1-2 cases).
− If they take oestrogen-only HRT for 10 years, the figure will be 37 in 1000 (i.e. an extra 5 cases).
− For women who start taking oestrogen plus progestogen HRT at age 50 and take it for 5 years, the figure will be 38 in 1000 (i.e. an extra 6 cases).
− If they take oestrogen plus progestogen HRT for 10 years, the figure will be 51 in 1000 (i.e. an extra 19 cases).
If you notice any changes in your breast, e.g: • dimpling of the skin
• changes in the nipple
• any lumps you can see or feel Make an appointment to see your doctor as soon as possible.
Endometrial cancer (cancer of the lining of the womb)
Taking oestrogen-only HRT for a long time can increase the risk of cancer of the lining of the womb (the endometrium). Taking a progestogen as well as the oestrogen helps to lower the extra risk.
If you still have your womb, your doctor will usually prescribe a progestogen as well as oestrogen. These may be prescribed separately, or as a combined HRT product.
If you have had your womb removed (a hysterectomy), your doctor will discuss with you whether you can safely take oestrogen without a progestogen.
If you’ve had your womb removed because of endometriosis, any endometrium left in your body may be at risk. So your doctor may prescribe HRT that includes a progestogen as well as an oestrogen.
Ethinylestradiol Tablets is an oestrogen-only product.
Compare
− Looking at women who still have a uterus and who are not taking HRT – on average 5 in 1000 will be diagnosed with endometrial cancer between the ages of 50 and 65.
− For women who take oestrogen-only HRT, the number will be 2 to 12 times higher, depending on the dose and how long you take it. − The addition of a progestogen to oestrogen- only HRT substantially reduces the risk of endometrial cancer.
If you get breakthrough bleeding or spotting, it’s usually nothing to worry about, especially during the first few months of taking HRT.
If the bleeding or spotting:
• carries on for more than the first few months
• starts after you’ve been on HRT for a while
• carries on even after you’ve stopped taking HRT.
You must make an appointment to see your doctor. It could be a sign that your endometrium has become thicker. – Ovarian cancer

Ovarian cancer (cancer of the ovaries) is very rare, but it is serious. It can be difficult to diagnose, because there are often no obvious signs of the disease.
Some studies have indicated that taking oestrogen-only HRT for more than 5 years may increase the risk of ovarian cancer. It is not yet known whether other kinds of HRT increase the risk in the same way.

Dementia
HRT will not prevent memory loss. In one study of women who started using combined HRT after the age of 65, a small increase in the risk of dementia was observed.
Tell your doctor if you are taking any of the following medicines:
• Medicines to thin the blood (e.g. warfarin, pheninidone or acenocoumarol)
• Medicines for tuberculosis (e.g. rifampicin or rifabutin)
• Medicines for fungal infections (e.g. nevirapine, efavirenz, ritonavir or nelfinavir)
• Medicines for your breathing (e.g. theophylline)
• Medicines for epilepsy (e.g. phenytoin, phenobarbitol, carbamazepine and lamotrigine)
• Medicines for narcolepsy (e.g. modafinil)
• Medicines for the treatment of depression (e.g. imipramine or St John’s Wort)
• Any other medicine, including medicines obtained without a prescription.
Pregnancy and breast-feeding
Do not take Ethinylestradiol if you are pregnant or breast feeding. If you become pregnant whilst taking Ethinylestradiol you should stop taking your tablets immediately and talk to your doctor. Warnings about the ingredients in Ethinylestradiol
Ethinylestradiol contains lactose. It is not suitable for people who are unable to tolerate a sugar called lactose. This rare condition may have been passed down from someone in your family. Tell your doctor or pharmacist before taking your tablets if this applies to you.

3. HOW TO TAKE ETHINYL ESTRADIOL TABLETS
Always take Ethinylestradiol exactly as your doctor has told you.
IMPORTANT:
Your doctor will choose the dose that is right for you. Your dose will be shown clearly on the label that your pharmacist puts on your medicine. If it does not, or you are not sure, ask your doctor or pharmacist.
Remember: Your tablets should be taken once a day and at the same time each day. They should be swallowed whole with a drink of water.
The dose you have been prescribed will depend on the condition being treated. The following are usual doses.
Hormone Replacement Therapy
• 10 to 50 micrograms daily on a cyclical basis (three weeks on and one week off).
• If you have a womb a progestogen should normally also be prescribed to lower the risk of endometrial cancer. Your doctor will explain this to you if necessary.
Period Disorders
• 20 to 50 micrograms daily from day 5 to day 25 of each cycle.
• A progestogen should be given daily in addition, either throughout the cycle or from day 15 to day 25 of the cycle. Your doctor will explain this to you if necessary.
• As Ethinylestradiol tablets are usually taken on a cyclical basis direct switching from other oestrogen-only HRT preparations taken cyclically is possible.
Prostate Cancer
150 micrograms to 1.5 milligrams daily. Medical check-ups
Once you are taking this medicine:
• Regularly check your breasts for any changes. If you notice dimpling of the skin, changes in the nipple, or any lumps you must see your doctor as soon as possible.
• Go for regular breast screening
• Go for cervical smear tests
• See your doctor for regular check-ups (at least once a year). At these check-ups, your doctor will discuss with you the benefits and risks of continuing to take HRT.
If you take more Ethinylestradiol than you should
If you have taken too many tablets, contact the nearest hospital casualty department or your doctor immediately. Take this leaflet and any remaining tablets with you to show the doctor. Taking too many tablets at once may make you feel sick or be sick. It can also make women have a period afterwards.
If you forget to take Ethinylestradiol
• Do not take a double dose to make up for a missed dose. Simply take the next dose as planned. • Forgetting a dose may increase the chances of breakthrough bleeding in woman with an intact womb.
If you stop taking Ethinylestradiol
Do not stop taking Ethinylestradiol without first talking to your doctor. If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS
Like all medicines Ethinylestradiol can cause side effects, although not everybody gets them. If you suffer from any of the following you should see your doctor as soon as possible and do not take any more tablets until your doctor tells you too:
• Unexpected migraine, with or without disturbed vision (these headaches could be an early warning sign of a stroke)
• Painful swelling in your leg , sudden chest pain or difficulty breathing (these problems may be a sign of a blood clot)
• A pain in your chest that spreads to your arm and neck (this pain could be a sign of heart disease)
See your doctor as soon as possible if you get any of the following symptoms:
• If you notice any changes in your breast such as a lump, dimpling in the skin or the nipple changing
• If bleeding or spotting carries on for more than the first few months, or starts after you have been taking the tablets for a while
• If bleeding or spotting carries on even after you’ve stopped taking HRT.
Important: All the symptoms in the lists above are signs that you may be developing a serious problem. If you ignore these symptoms they may become worse.
Other possible side effects
• You may feel or be sick
• You may get headaches or migraine
• You may have mood changes
• Your breasts may become tender, enlarge or leak
• Your eyes may hurt if you wear contact lenses
• You may get a skin rash, including skin discolouration known as chloasma
• You may be more likely to have high blood pressure, blood clots, gallstones or jaundice
• You may get unexplained pains, particularly in your calves.
• You may retain fluid and put on weight
• You may have high levels of calcium building up in the blood, particularly if you have a malignant tumour
• If you suffer from endometriosis or fibroids they may become worse
• Men may develop breasts, their testicles may stop working, may look more female and become impotent during treatment.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

5. HOW TO STORE ETHINYL ESTRADIOL TABLETS
Keep out of the reach and sight of children. Do not use Ethinylestradiol after the expiry date on the container. The expiry date refers to the last day of that month.
Store below 25°C. Keep your tablets in the container they came in.
Medicines should not be disposed of via wastewater or household waste. Return any medicine you no longer need to your pharmacist.

6. Further Information

What Ethinyl Estradiol Soluble Tablets contain
The active substance is ethinylestradiol.
a) Each uncoated tablet contains: Ethinylestradiol USP 10mcg
b) Each uncoated tablet contains: Ethinylestradiol USP 50mcg
The other ingredients are lactose monohydrate, starch maize and magnesium stearate

What Ethinyl Estradiol Tablets look like and contents of the pack
Ethinylestradiol 10 mcg are white, biconvex, uncoated tablets.
Ethinylestradiol 50 mcg are white flat bevel edged uncoated tablets.
The 10 micrograms tablets come in packs of 21, 100 and 500. The 50 micrograms tablets come in packs of 21 and 100.
Not all pack sizes may be marketed.