Estratest

Name: Estratest

Clinical pharmacology

Estrogens: Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level.

The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women.

Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue.

Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.

Estrogen Pharmacokinetics

Distribution

The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Estrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and albumin.

Metabolism

Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens.

Excretion

Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates.

Drug Interactions

In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St. John's Wort preparations (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.

Clinical Studies

Women's Health Initiative Studies

The Women's Health Initiative (WHI) enrolled a total of 27,000 predominantly healthy postmenopausal women to assess the risks and benefits of either the use of oral 0.625 mg conjugated estrogens (CE) per day alone or the use of oral 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate (MPA) per day compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome studied. A "global index" included the earliest occurrence of CHD, invasive breast cancer, stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, or death due to other cause. The study did not evaluate the effects of CE or CE/MPA on menopausal symptoms.

The CE-only substudy has concluded. The impact of those results are under review. The CE/MPA substudy was stopped early because, according to the predefined stopping rule, the increased risk of breast cancer and cardiovascular events exceeded the specified benefits included in the "global index." Results of the CE/MPA substudy, which included 16,608 women (average age of 63 years, range 50 to 79; 83.9% White, 6.5% Black, 5.5% Hispanic), after an average follow-up of 5.2 years are presented in Table 1 below.

TABLE 1: Relative and Absolute Risk Seen in the CE/MPA Substudy of WHIa

Eventc Relative Risk CE/MPA versus placebo at 5.2 Years (95% CI*) Placebo
n = 8102
CE/MPA
n = 8506
Absolute Risk per 10,000 Women-years
CHD events 1.29 (1.02-1.63) 30 37
  Non-fatal MI 1.32 (1.02-1.72) 23 30
  CHD death 1.18 (0.70-1.97) 6 7
Invasive breast cancerb 1.26 (1.00-1.59) 30 38
Stroke 1.41 (1.07-1.85) 21 29
Pulmonary embolism 2.13 (1.39-3.25) 8 16
Colorectal cancer 0.63 (0.43-0.92) 16 10
Endometrial cancer 0.83 (0.47-1.47) 6 5
Hip fracture 0.66 (0.45-0.98) 15 10
Death due to causes other than the events above 0.92 (0.74-1.14) 40 37
Global Index c 1.15 (1.03-1.28) 151 170
Deepvein thrombosisd 2.07 (1.49-2.87) 13 26
Vertebral fractures d 0.66 (0.44-0.98) 15 9
Other osteoporotic fractures d 0.77 (0.69-0.86) 170 131
a adapted from JAMA, 2002; 288:321-333
b includes metastatic and non-metastatic breast cancer with the exception ofin situ breast cancer
c a subset of the events was combined in a "global index," defined as the earliest occurrence of CHD events, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hipfracture, or deathdue to other causes
d not included in Global Index
*nominal confidence intervals unadjusted formultiple looks and multiplecomparisons

For those outcomes included in the "global index," the absolute excess risks per 10,000 women-years in the group treated with CE/MPA were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while the absolute risk reductions per 10,000 women-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the "global index" was 19 per 10,000 women-years. There was no difference between the groups in terms of all-cause mortality. (See BOXED WARNINGS, WARNINGS, and PRECAUTIONS.)

Women's Health Initiative Memory Study

The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older (47% were age 65 to 69 years, 35% were 70 to 74 years, and 18% were 75 years of age and older) to evaluate the effects of CE/MPA (0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate) on the incidence of probable dementia (primary outcome) compared with placebo.

After an average follow-up of 4 years, 40 women in the estrogen/progestin group (45 per 10,000 women-years) and 21 in the placebo group (22 per 10,000 women-years) were diagnosed with probable dementia. The relative risk of probable dementia in the hormone therapy group was 2.05 (95% CI, 1.21 to 3.48) compared to placebo. Differences between groups became apparent in the first year of treatment. It is unknown whether these findings apply to younger postmenopausal women. (See BOXED WARNINGS and WARNINGS, Dementia.)

Androgens: Endogenous androgens are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as beard, pubic, chest, and axillary hair, laryngeal enlargement, vocal cord thickening, alterations in body musculature, and fat distribution. Drugs in this class also cause retention of nitrogen, sodium, potassium, phosphorus, and decreased urinary excretion of calcium. Androgens have been reported to increase protein anabolism and decrease protein catabolism. Nitrogen balance is improved only when there is sufficient intake of calories and protein. Androgens are responsible for the growth spurt of adolescence and for the eventual termination of linear growth which is brought about by fusion of the epiphyseal growth centers. In children, exogenous androgens accelerate linear growth rates, but may cause a disproportionate advancement in bone maturation. Use over long periods may result in fusion of the epiphyseal growth centers and termination of growth process. Androgens have been reported to stimulate the production of red blood cells by enhancing the production of erythropoietic stimulating factor.

Androgen Pharmacokinetics

Testosterone given orally is metabolized by the gut and 44 percent is cleared by the liver in the first pass. Oral doses as high as 400 mg per day are needed to achieve clinically effective blood levels for full replacement therapy. The synthetic androgens (methyltestosterone and fluoxymesterone) are less extensively metabolized by the liver and have longer half-lives. They are more suitable than testosterone for oral administration.

Testosterone in plasma is 98 percent bound to a specific testosterone-estradiol binding globulin, and about 2 percent is free. Generally, the amount of this sex-hormone binding globulin in the plasma will determine the distribution of testosterone between free and bound forms, and the free testosterone concentration will determine its half-life.

About 90 percent of a dose of testosterone is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6 percent of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. Testosterone is metabolized to various 17-keto steroids through two different pathways. There are considerable variations of the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes.

In many tissues the activity of testosterone appears to depend on reduction to dihydrotestosterone, which binds to cytosol receptor proteins. The steroid-receptor complex is transported to the nucleus where it initiates transcription events and cellular changes related to androgen action.

Patient information

ESTRATEST®‡ (esterified estrogens and methyltestosterone) and ESTRATEST® H.S.‡
(Esterified Estrogens and Methyltestosterone) Tablets

Read this PATIENT INFORMATION before you start taking ESTRATEST (esterified estrogens and methyltestosterone) ® and ESTRATEST (esterified estrogens and methyltestosterone) ® H.S. Tablets and read what you get each time you refill ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT ESTRATEST (esterified estrogens and methyltestosterone) AND ESTRATEST (esterified estrogens and methyltestosterone) H.S. TABLETS (A COMBINATION OF ESTROGEN AND ANDROGEN HORMONES)?

  • Estrogens increase the chances of getting cancer of the uterus.

Report any unusual vaginal bleeding right away while you are taking estrogens. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.

  • Do not use estrogens with or without progestins to prevent heart disease, heart attacks, or strokes.

Using estrogens with or without progestins may increase your chances of getting heart attacks, strokes, breast cancer, and blood clots. Using estrogens with progestins may increase your risk of dementia. You and your healthcare provider should talk regularly about whether you still need treatment with ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets.

What is ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets?

ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets are medicines that contain estrogen and androgen hormones.

What is ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets used for?

ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets are used after menopause to:

  • reduce moderate to severe hot flashes. Estrogens are hormones made by a woman's ovaries. The ovaries normally stop making estrogens when a woman is between 45 to 55 years old. This drop in body estrogen levels causes the "change of life" or menopause (the end of monthly menstrual periods). Sometimes, both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes "surgical menopause."

When the estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating ("hot flashes" or "hot flushes"). In some women, the symptoms are mild, and they will not need estrogens. In other women, symptoms can be more severe. You and your healthcare provider should talk regularly about whether you still need treatment with ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets.

  • treat moderate to severe dryness, itching, and burning in and around the vagina. You and your healthcare provider should talk regularly about whether you still need treatment with ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets to control these problems. If you use ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets only to treat your dryness, itching, and burning in and around your vagina, talk with your healthcare provider about whether a topical vaginal product would be better for you.

Who should not take ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets?

Do not start taking ESTRATEST (esterified estrogens and methyltestosterone) or ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets if you:

  • have unusual vaginal bleeding.
  • currently have or have had certain cancers. Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. If you have or had cancer, talk with your healthcare provider about whether you should take ESTRATEST (esterified estrogens and methyltestosterone) or ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets.
  • had a stroke or heart attack in the past year.
  • currently have or have had blood clots.
  • currently have or have had liver problems.
  • are allergic to ESTRATEST (esterified estrogens and methyltestosterone) or ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets or any of their ingredients. See the end of this leaflet for a list of ingredients in ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets.
  • think you may be pregnant.

Tell your healthcare provider:

  • if you are breastfeeding. The hormones in ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets can pass into your milk.
  • about all of your medical problems. Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), migraine, endometriosis, lupus, problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.
  • about all the medicines you take. This includes prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may affect how ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets work. ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets may also affect how your other medicines work.
  • if you are going to have surgery or will be on bed rest. You may need to stop taking estrogens.

How should I take ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets?

Estrogens should be used at the lowest dose possible for your treatment only as long as needed. The lowest effective dose of ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets has not been determined. You and your healthcare provider should talk regularly (for example, every 3 to 6 months) about the dose you are taking and whether you still need treatment with ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets.

What are the possible side effects of estrogens?

Less common but serious side effects include:

  • Breast cancer
  • Cancer of the uterus
  • Stroke
  • Heart attack
  • Blood clots
  • Dementia
  • Gallbladder disease
  • Ovarian cancer

These are some of the warning signs of serious side effects:

  • Breast lumps
  • Unusual vaginal bleeding
  • Dizziness and faintness
  • Changes in speech
  • Severe headaches
  • Chest pain
  • Shortness of breath
  • Pains in your legs
  • Changes in vision
  • Vomiting

Call your healthcare provider right away if you get any of these warning signs, or any other unusual symptom that concerns you.

Common side effects include:

  • Headache
  • Breast pain
  • Irregular vaginal bleeding or spotting
  • Stomach/abdominal cramps, bloating
  • Nausea and vomiting
  • Hair loss

Other side effects include:

  • High blood pressure
  • Liver problems
  • High blood sugar
  • Fluid retention
  • Enlargement of benign tumors of the uterus ("fibroids")
  • Vaginal yeast infection

These are not all the possible side effects of ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets. For more information, ask your healthcare provider or pharmacist.

What can I do to lower my chance of a serious side effect with ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets?

  • Talk with your healthcare provider regularly about whether you should continue taking ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets.
  • If you have a uterus, talk to your healthcare provider about whether the addition of a progestin is right for you.
  • See your healthcare provider right away if you get vaginal bleeding while taking ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets.
  • Have a breast exam and mammogram (breast X-ray) every year unless your healthcare provider tells you something else. If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often.
  • If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances for getting heart disease. Ask your healthcare provider for ways to lower your chances for getting heart disease.

General information about safe and effective use of ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not take ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets for conditions for which it was not prescribed. Do not give ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets to other people, even if they have the same symptoms you have. It may harm them.

Keep ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets out of the reach of children.

This leaflet provides a summary of the most important information about ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets. If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets that is written for health professionals. You can get more information by calling the toll free number 1-800-241-1643.

What are the ingredients in ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets?

ESTRATEST H.S. is a combination of Esterified Estrogens and Methyltestosterone. Each capsule-shaped, light green, sugar-coated tablet contains the following active ingredients: 0.625 mg of Esterified Estrogens, USP and 1.25 mg of Methyltestosterone, USP.

ESTRATEST is a combination of Esterified Estrogens and Methyltestosterone. Each capsule-shaped, dark green, sugar-coated tablet contains the following active ingredients: 1.25 mg of Esterified Estrogens, USP and 2.5 mg of Methyltestosterone, USP.

ESTRATEST (esterified estrogens and methyltestosterone) and ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets contain the following inactive ingredients: acacia, acetylated monoglycerides, calcium carbonate, carboxymethylcellulose sodium, carnauba wax NF, citric acid, colloidal silicon dioxide, gelatin, iron oxide, lactose, magnesium stearate, methylparaben, microcrystalline cellulose, pharmaceutical glaze, povidone, propylene glycol, propylparaben, shellac glaze, sodium benzoate, sodium bicarbonate, sorbic acid, starch, sucrose, talc, titanium dioxide, and tribasic calcium phosphate.

ESTRATEST (esterified estrogens and methyltestosterone) Tablets also include: FD&C Blue No. 1 Lake, FD&C Yellow No. 6 Lake, and D&C Yellow No. 10 Lake.

ESTRATEST (esterified estrogens and methyltestosterone) H.S. Tablets also include: D&C Yellow No. 10 Lake, FD&C Blue No. 1 Lake, FD&C Blue No. 2 Lake, FD&C Yellow No. 6 Lake, and FD&C Red No. 40 Lake.

Store at controlled room temperature 15° to 30°C (59° to 86°F).

‡This product has not obtained FDA pre-market approval applicable for new drugs.

Estratest Drug Class

Estratest is part of the drug classes:

  • 3 oxoandrosten 4 derivatives

  • Androgens and female sex hormones in combination with other drugs

What happens if i miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What is Estratest (esterified estrogens and methyltestosterone)?

Esterified estrogens are female sex hormones necessary for many processes in the body.

Methyltestosterone is a man-made form of testosterone, a naturally occurring sex hormone that is produced in a man's testicles. Small amounts of testosterone are also produced in a woman's ovaries and adrenal system.

The combination of esterified estrogens and methyltestosterone is used to treat symptoms of menopause such as hot flashes, and vaginal dryness, burning, and irritation.

This medication may also be used for purposes not listed in this medication guide.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Uses For Estratest

Esterified estrogens and methyltestosterone combination is used to treat the symptoms of menopause in patients who did not get relief after being treated with estrogens alone. These symptoms may include a feeling of heat, sweating, and warmth in the face, neck, or chest ("hot flashes"); and dryness, burning, and itching in the vagina.

Esterified estrogens are a man-made mixture of estrogens. Estrogen is a hormone that is produced by the body in greater amounts in females. It is necessary for normal sexual development of the female and for regulation of the menstrual cycle during the childbearing years. Methyltestosterone is a man-made form of testosterone, a hormone that is produced by the body in greater amounts in males and small amounts in females. Menopause symptoms occur when the hormone balance changes in the female body. This combination of hormones will relieve the symptoms of menopause by adding more hormones to the body.

This medicine is available only with your doctor's prescription.

Before Using Estratest

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

The use of esterified estrogens and methyltestosterone combination is not recommended in children.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of esterified estrogens and methyltestosterone combination in the elderly. However, elderly patients are more likely to develop dementia and age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving this medicine.

Pregnancy

Pregnancy Category Explanation
All Trimesters X Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Anisindione
  • Bupropion
  • Dicumarol
  • Donepezil
  • Phenprocoumon

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Clarithromycin
  • Ginseng
  • Ketoconazole
  • Levothyroxine
  • Licorice
  • Tipranavir
  • Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Abnormal vaginal bleeding, undiagnosed or
  • Blood clotting problems (e.g., deep vein thrombosis, pulmonary embolism), history of or
  • Breast cancer, or history of or
  • Heart attack, recent or history of or
  • Liver disease, severe or
  • Stroke, recent or history of—Should not be used in patients with these conditions.
  • Asthma or
  • Cancer (e.g., breast, cervix, liver, vagina) or
  • Depression, history of or
  • Diabetes or
  • Edema (fluid retention) or
  • Endometriosis (problem with the lining of the uterus) or
  • Epilepsy or
  • Eye or vision problems (e.g., retinal vascular thrombosis) or
  • Gallbladder disease or
  • Hepatitis (including cholestatic jaundice), history of or
  • Hypercalcemia (high calcium in the blood) or
  • Hypocalcemia (high calcium in the blood) or
  • Hypothyroidism (underactive thyroid) or
  • Migraine headaches, history of or
  • Porphyria (enzyme problem) or
  • Systemic lupus erythematosus—Use with caution. May make these conditions worse.
  • Heart or blood vessel disease or
  • Hypercholesterolemia (high cholesterol in the blood) or
  • Hypertension (high blood pressure) or
  • Hypertriglyceridemia (high triglycerides or fat in the blood) or
  • Venous thromboembolism (clot in the veins), history of—May increase risk for more serious side effects.

Precautions While Using Estratest

It is very important that your doctor check your progress at regular visits to make sure the medicine is working properly and to decide if you should continue to take it. These visits should be every 6 to 12 months or as otherwise directed by your doctor.

It is unlikely that a postmenopausal woman may become pregnant. But, you should know that using this medicine while you are pregnant could harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.

Very rarely, this medicine can cause serious side effects such as a heart attack or stroke. You are much more likely to have these side effects if you smoke cigarettes or are overweight, or if you have diabetes, high blood pressure, or a high blood cholesterol. Talk with your doctor if you think you might be at risk.

Using large doses of estrogen alone over a long period of time may increase the risk of some kinds of cancer (e.g., endometrial cancer). Talk with your doctor about this risk. If you have vaginal bleeding with this medicine, call your doctor right away.

This medicine may increase the risk of getting breast cancer. It is very important that you check your breasts on a regular basis for any unusual lumps or discharge, and that you have breast x-rays every year as directed by your doctor. These exams are very important if you have a family member with a history of breast cancer. Talk with your doctor about this risk.

This medicine may increase the risk of getting dementia in elderly women (above 65 years of age). Talk with your doctor if this concerns you.

Check with your doctor right away if blurred vision, difficulty with reading, or any other change in vision occurs during or after treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

Using large doses of methyltestosterone over a long period of time may increase the risk of serious liver problems (e.g., peliosis hepatis or liver cancer). Talk with your doctor about this risk.

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine. Also, you may need to stop using this medicine for a few weeks before and after having surgery, or if you are inactive for a long period of time.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Estratest Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Absent, missed, or irregular menstrual periods
  • acne or oily skin
  • decreased breast size
  • enlarging clitoris
  • hoarseness or deepening of the voice
  • menstrual changes
  • stopping of menstrual bleeding
  • unnatural hair growth or loss
Rare
  • Continuing nausea
  • cough
  • dark-colored urine
  • difficulty with swallowing
  • dizziness
  • fast heartbeat
  • fever
  • hives
  • itching
  • light-colored stools
  • loss of appetite
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • purple or red-colored spots on the body or inside the mouth or nose
  • shortness of breath
  • skin rash
  • sore throat
  • tightness in the chest
  • unusual tiredness or weakness
  • vomiting
  • wheezing
Incidence not known
  • Abdominal or stomach bloating, cramps, or pain
  • anxiety
  • bleeding from gums or nose
  • blistering, peeling, or loosening of the skin
  • bloating
  • bloody or cloudy urine
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • change in vaginal discharge
  • changes in skin color, pain, or tenderness
  • chest pain or discomfort
  • chills
  • clay-colored stools
  • clear or bloody discharge from nipple
  • confusion
  • constipation
  • convulsions
  • darkening of urine
  • decrease in amount of urine
  • diarrhea
  • difficult, burning, or painful urination
  • difficulty with breathing
  • difficulty with moving
  • difficulty with speaking
  • dimpling of the breast skin
  • dizziness or lightheadedness
  • double vision
  • eye pain
  • fainting
  • fever
  • fluid-filled skin blisters
  • frequent urge to urinate
  • headache
  • heavy bleeding
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • indigestion
  • inverted nipple
  • irregular heartbeats
  • itching of the vagina or genital area
  • joint or muscle pain
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • light-colored stools
  • loss of appetite
  • lump in the breast or under the arm
  • mood or mental changes
  • muscle cramps in the hands, arms, feet, legs, or face
  • muscle pain or stiffness
  • nausea
  • noisy, rattling breathing
  • numbness and tingling around the mouth, fingertips, or feet
  • pain
  • pain during sexual intercourse
  • pain in the ankles or knees
  • pain or discomfort in the arms, jaw, back, or neck
  • pain or feeling of pressure in pelvis
  • painful, red lumps under the skin, mostly on the legs
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • pelvic pain
  • persistent crusting or scaling of the nipple
  • pinpoint red or purple spots on the skin
  • poor insight and judgment problems with memory or speech
  • red, irritated eyes
  • redness or swelling of the breast
  • ringing in the ears
  • sensitivity to the sun
  • shortness of breath
  • skin thinness
  • slow speech
  • sore on the skin of the breast that does not heal
  • sore throat
  • sores, ulcers, or white spots in the mouth or on the lips
  • stomach pain
  • sudden shortness of breath or troubled breathing
  • sweating
  • swelling
  • swelling of the fingers, hands, feet, or lower legs
  • tenderness of the breast
  • thick, white curd-like vaginal discharge without odor or with mild odor
  • tiredness
  • tremor
  • trouble recognizing objects
  • trouble thinking and planning
  • trouble walking
  • troubled breathing at rest
  • unexpected or excess milk flow from breasts
  • unpleasant breath odor
  • vaginal bleeding
  • vision changes
  • vomiting of blood
  • weakness
  • weight gain
  • yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known
  • Blemishes on the skin
  • brown, blotchy spots on the exposed skin
  • decreased interest in sexual intercourse
  • depression
  • headache, severe and throbbing
  • inability to have or keep an erection
  • increase or decrease in weight
  • increased hair growth, especially on the face
  • increased in sexual ability, desire, drive, or performance
  • increased interest in sexual intercourse
  • irritability
  • leg cramps
  • loss in sexual ability, desire, drive, or performance
  • loss of hair
  • mental depression
  • pimples
  • redness of the skin
  • swelling or inflammation of the mouth
  • twitching, uncontrolled movements of the tongue, lips, face, arms, or legs

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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