Fisiopred may be available in the countries listed below.
Prednisolone 21-(disodium phosphate) (a derivative of Prednisolone) is reported as an ingredient of Fisiopred in the following countries:
International Drug Name Search
Zep may be available in the countries listed below.
Omeprazole is reported as an ingredient of Zep in the following countries:
Zinc Sulfate is reported as an ingredient of Zep in the following countries:
International Drug Name Search
Salbutamol Lch may be available in the countries listed below.
Salbutamol is reported as an ingredient of Salbutamol Lch in the following countries:
International Drug Name Search
Troxérutine Sandoz may be available in the countries listed below.
Troxerutin is reported as an ingredient of Troxérutine Sandoz in the following countries:
International Drug Name Search
USAN
0009009-29-4
Antianemic agent
Polyferose
International Drug Name Search
Glossary
| OS | Official Synonym |
| USAN | United States Adopted Name |
Estroffik may be available in the countries listed below.
Estradiol hemihydrate (a derivative of Estradiol) is reported as an ingredient of Estroffik in the following countries:
International Drug Name Search
In the US, Basiliximab (basiliximab systemic) is a member of the drug class interleukin inhibitors and is used to treat Organ Transplant, Rejection Prophylaxis.
US matches:
Rec.INN
L04AA09,L04AC02
0179045-86-4
C6378-H9844-N1698-O1997-S48
143801
Immunomodulator
Immunoglobulin G 1 (human-mouse monoclonal CH1621 heavy chain antihuman interleukin 2 receptor), disulfide with human-mouse monoclonal CH1621 light chain, dimer
International Drug Name Search
Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Lisinopril/Hydrochlorothiazid Actavis may be available in the countries listed below.
Hydrochlorothiazide is reported as an ingredient of Lisinopril/Hydrochlorothiazid Actavis in the following countries:
Lisinopril dihydrate (a derivative of Lisinopril) is reported as an ingredient of Lisinopril/Hydrochlorothiazid Actavis in the following countries:
International Drug Name Search
Vomistop may be available in the countries listed below.
Domperidone is reported as an ingredient of Vomistop in the following countries:
International Drug Name Search
Denosine may be available in the countries listed below.
Ganciclovir is reported as an ingredient of Denosine in the following countries:
International Drug Name Search
Apo-Moclob may be available in the countries listed below.
Moclobemide is reported as an ingredient of Apo-Moclob in the following countries:
International Drug Name Search
Cebion Febbre may be available in the countries listed below.
Ascorbic Acid sodium salt (a derivative of Ascorbic Acid) is reported as an ingredient of Cebion Febbre in the following countries:
Paracetamol is reported as an ingredient of Cebion Febbre in the following countries:
International Drug Name Search
Gen-Tizanidine may be available in the countries listed below.
Tizanidine hydrochloride (a derivative of Tizanidine) is reported as an ingredient of Gen-Tizanidine in the following countries:
International Drug Name Search
Depersolon may be available in the countries listed below.
Mazipredone hydrochloride (a derivative of Mazipredone) is reported as an ingredient of Depersolon in the following countries:
International Drug Name Search
Poviyodo may be available in the countries listed below.
Povidone-Iodine is reported as an ingredient of Poviyodo in the following countries:
International Drug Name Search
Quinogal may be available in the countries listed below.
Chloroquine is reported as an ingredient of Quinogal in the following countries:
International Drug Name Search
Cacit may be available in the countries listed below.
UK matches:
Calcium Carbonate is reported as an ingredient of Cacit in the following countries:
International Drug Name Search
Glossary
| SPC | Summary of Product Characteristics (UK) |
Platof may be available in the countries listed below.
Pentoxifylline is reported as an ingredient of Platof in the following countries:
International Drug Name Search
Picasum may be available in the countries listed below.
Capsaicin is reported as an ingredient of Picasum in the following countries:
International Drug Name Search
Misodex may be available in the countries listed below.
Misoprostol is reported as an ingredient of Misodex in the following countries:
International Drug Name Search
Torasemida Stada may be available in the countries listed below.
Torasemide is reported as an ingredient of Torasemida Stada in the following countries:
International Drug Name Search
Aciclo Basics may be available in the countries listed below.
Aciclovir is reported as an ingredient of Aciclo Basics in the following countries:
International Drug Name Search
Felobits may be available in the countries listed below.
Atenolol is reported as an ingredient of Felobits in the following countries:
International Drug Name Search
Rec.INN
R01AA09
0001082-57-1
C13-H17-N3
215
Vasoconstrictor ORL, local
1H-Imidazole-2-amine, 4,5-dihydro-N-(5,6,7,8-tetrahydro-1-naphthalenyl)-
International Drug Name Search
Glossary
| BAN | British Approved Name |
| BANM | British Approved Name (Modified) |
| IS | Inofficial Synonym |
| JAN | Japanese Accepted Name |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
OM-Dicynone may be available in the countries listed below.
Etamsylate is reported as an ingredient of OM-Dicynone in the following countries:
International Drug Name Search
Ecron may be available in the countries listed below.
Vecuronium Bromide is reported as an ingredient of Ecron in the following countries:
International Drug Name Search
Diclofenaco Alter may be available in the countries listed below.
Diclofenac sodium salt (a derivative of Diclofenac) is reported as an ingredient of Diclofenaco Alter in the following countries:
International Drug Name Search
Méthocarbamol may be available in the countries listed below.
Méthocarbamol (DCF) is known as Methocarbamol in the US.
International Drug Name Search
Glossary
| DCF | Dénomination Commune Française |
Nicardipine hydrochloride (a derivative of Nicardipine) is reported as an ingredient of Cardene I.V. in the following countries:
International Drug Name Search
Q-Ten may be available in the countries listed below.
Ubidecarenone is reported as an ingredient of Q-Ten in the following countries:
International Drug Name Search
Tamsulosin HCl Pliva may be available in the countries listed below.
Tamsulosin hydrochloride (a derivative of Tamsulosin) is reported as an ingredient of Tamsulosin HCl Pliva in the following countries:
International Drug Name Search
Glycerol PSM may be available in the countries listed below.
Glycerol is reported as an ingredient of Glycerol PSM in the following countries:
International Drug Name Search
Kipling may be available in the countries listed below.
Ethinylestradiol is reported as an ingredient of Kipling in the following countries:
Gestodene is reported as an ingredient of Kipling in the following countries:
International Drug Name Search
Ometab may be available in the countries listed below.
Omeprazole is reported as an ingredient of Ometab in the following countries:
Omeprazole magnesium salt (a derivative of Omeprazole) is reported as an ingredient of Ometab in the following countries:
International Drug Name Search
Fenofibrat Stada may be available in the countries listed below.
Fenofibrate is reported as an ingredient of Fenofibrat Stada in the following countries:
International Drug Name Search
Esomezol may be available in the countries listed below.
Esomeprazole magnesium, trihydrate (a derivative of Esomeprazole) is reported as an ingredient of Esomezol in the following countries:
International Drug Name Search
Labosona may be available in the countries listed below.
Betamethasone 17α,21-dipropionate (a derivative of Betamethasone) is reported as an ingredient of Labosona in the following countries:
International Drug Name Search
Syneclav may be available in the countries listed below.
Amoxicillin is reported as an ingredient of Syneclav in the following countries:
Clavulanic Acid potassium (a derivative of Clavulanic Acid) is reported as an ingredient of Syneclav in the following countries:
International Drug Name Search
Dropilton may be available in the countries listed below.
Pilocarpine hydrochloride (a derivative of Pilocarpine) is reported as an ingredient of Dropilton in the following countries:
International Drug Name Search
Koortslip DA may be available in the countries listed below.
Aciclovir is reported as an ingredient of Koortslip DA in the following countries:
International Drug Name Search
Fenazon-Koffein may be available in the countries listed below.
Caffeine is reported as an ingredient of Fenazon-Koffein in the following countries:
Phenazone is reported as an ingredient of Fenazon-Koffein in the following countries:
International Drug Name Search
bal-SAL-a-zide
In the U.S.
Available Dosage Forms:
Therapeutic Class: Gastrointestinal Agent
Chemical Class: Salicylate, Non-Aspirin
Balsalazide is used to treat active ulcerative colitis in patients 5 years of age and older. It helps to decrease inflammation in the colon by blocking the production of certain chemicals that cause the bowel to become overactive.
balsalazide is available only with your doctor's prescription.
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 balsalazide, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to balsalazide 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.
Appropriate studies have not been performed on the relationship of age to the effects of balsalazide in children below 5 years of age. Safety and efficacy have not been established .
Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing the use of balsalazide in the elderly with use in other age groups.
| Pregnancy Category | Explanation | |
|---|---|---|
| All Trimesters | B | Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus. |
Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using balsalazide.
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 balsalazide, 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 balsalazide 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.
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. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
The presence of other medical problems may affect the use of balsalazide. Make sure you tell your doctor if you have any other medical problems, especially:
.
If you cannot swallow the capsule, you may open it and pour the medicine into a small amount of applesauce. Stir this mixture well and swallow right away. Do not keep the mixture for future use .
You may take balsalazide with or without food .
The dose of balsalazide will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of balsalazide. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of balsalazide, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
It is important that your doctor check your progress at regular visits. This will allow your doctor to check for any unwanted effects.
If your symptoms become worse, check with your doctor.
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:
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:
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.
See also: balsalazide side effects (in more detail)
The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.
The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.
In the US, Amitone (calcium carbonate systemic) is a member of the following drug classes: antacids, minerals and electrolytes and is used to treat Duodenal Ulcer, Erosive Esophagitis, GERD, Indigestion and Stomach Ulcer.
US matches:
Ketotifen fumarate (a derivative of Ketotifen) is reported as an ingredient of Amitone in the following countries:
International Drug Name Search
InnoLet 50R may be available in the countries listed below.
Insulin Injection, Biphasic Isophane human (a derivative of Insulin Injection, Biphasic Isophane) is reported as an ingredient of InnoLet 50R in the following countries:
International Drug Name Search
Haliborange may be available in the countries listed below.
Ascorbic Acid is reported as an ingredient of Haliborange in the following countries:
International Drug Name Search
Fintrid may be available in the countries listed below.
Finasteride is reported as an ingredient of Fintrid in the following countries:
International Drug Name Search
Tamoxifeno R may be available in the countries listed below.
Tamoxifen is reported as an ingredient of Tamoxifeno R in the following countries:
International Drug Name Search
Aciclovir Aguettant may be available in the countries listed below.
Aciclovir is reported as an ingredient of Aciclovir Aguettant in the following countries:
International Drug Name Search
Amiodaron HCl PCH may be available in the countries listed below.
Amiodarone hydrochloride (a derivative of Amiodarone) is reported as an ingredient of Amiodaron HCl PCH in the following countries:
International Drug Name Search
Anginar may be available in the countries listed below.
Dipyridamole is reported as an ingredient of Anginar in the following countries:
International Drug Name Search
In some countries, this medicine may only be approved for veterinary use.
Kanamycin sulfate (a derivative of Kanamycin) is reported as an ingredient of Kantrim in the following countries:
International Drug Name Search
Ramipril Ur may be available in the countries listed below.
Ramipril is reported as an ingredient of Ramipril Ur in the following countries:
International Drug Name Search
Klexane may be available in the countries listed below.
Enoxaparin is reported as an ingredient of Klexane in the following countries:
Enoxaparin sodium salt (a derivative of Enoxaparin) is reported as an ingredient of Klexane in the following countries:
International Drug Name Search
Palin may be available in the countries listed below.
Domperidone is reported as an ingredient of Palin in the following countries:
Pantoprazole is reported as an ingredient of Palin in the following countries:
Pipemidic Acid is reported as an ingredient of Palin in the following countries:
International Drug Name Search
Spectroderm may be available in the countries listed below.
Mupirocin is reported as an ingredient of Spectroderm in the following countries:
International Drug Name Search
Propylthiouracil DHA may be available in the countries listed below.
Propylthiouracil is reported as an ingredient of Propylthiouracil DHA in the following countries:
International Drug Name Search
Zentralin may be available in the countries listed below.
Flunarizine dihydrochloride (a derivative of Flunarizine) is reported as an ingredient of Zentralin in the following countries:
International Drug Name Search
Pravastatin Nycomed may be available in the countries listed below.
Pravastatin sodium salt (a derivative of Pravastatin) is reported as an ingredient of Pravastatin Nycomed in the following countries:
International Drug Name Search
Kanis may be available in the countries listed below.
Clotrimazole is reported as an ingredient of Kanis in the following countries:
International Drug Name Search
Dufulvin may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Griseofulvin is reported as an ingredient of Dufulvin in the following countries:
International Drug Name Search
Prostatil may be available in the countries listed below.
Terazosin hydrochloride (a derivative of Terazosin) is reported as an ingredient of Prostatil in the following countries:
International Drug Name Search
Tylopharm may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Tylosin is reported as an ingredient of Tylopharm in the following countries:
International Drug Name Search
Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures including endometrial sampling, when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is currently no evidence that the use of "natural" estrogens results in a different endometrial risk profile than "synthetic" estrogens at equivalent estrogen doses. (See WARNINGS, malignant neoplasms, Endometrial cancer.)
Estrogens with and without progestins should not be used for the prevention of cardiovascular disease. (See WARNINGS, Cardiovascular disorders.)
The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo. (See CLINICAL PHARMACOLOGY, Clinical Studies.)
The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or to women taking estrogen-alone therapy. (See CLINICAL PHARMACOLOGY, Clinical Studies.)
Other doses of conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Depo-Estradiol Injection contains estradiol cypionate for intramuscular use. Each mL contains:
5 mg/mL—5 mg estradiol cypionate, 5.4 mg chlorobutanol anhydrous (chloral derivative) added as preservative; in 913 mg cottonseed oil.
Warning: Chlorobutanol may be habit forming. The structural formula is represented below:
Depo-Estradiol contains an oil soluble ester of estradiol 17β. The chemical name for estradiol cypionate is estradiol 17-cyclopentanepropionate.
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.
When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks.
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.
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.
Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates.
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.
Estrogen drug products administered by non oral routes are not subject to first-pass metabolism, but also undergo significant hepatic uptake, metabolism, and enterohepatic recycling.
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 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/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:
| Event † | Relative Risk CE/MPA vs placebo at 5.2 Years (95% CI‡) | Placebo n = 8102 | CE/MPA n = 8506 |
|---|---|---|---|
| Absolute Risk per 10,000 Person-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 cancer § | 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 † | 1.15 (1.03–1.28) | 151 | 170 |
| Deep vein thrombosis ¶ | 2.07 (1.49–2.87) | 13 | 26 |
| Vertebral fractures ¶ | 0.66 (0.44–0.98) | 15 | 9 |
| Other osteoporotic fractures ¶ | 0.77 (0.69–0.86) | 170 | 131 |
For those outcomes included in the "global index," the absolute excess risks per 10,000 person-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 absolute risk reductions per 10,000 person-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.)
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.)
Comparative clinical studies have demonstrated that estradiol cypionate produces estrogenic effects that are qualitatively the same as those produced by other estradiol esters. In menopausal women, the average duration of estrogenic effect (as measured by vaginal smear) following a single injection of 5 mg of estradiol cypionate was found to be approximately 3 to 4 weeks. Relief of vasomotor symptoms was observed to occur within 1 to 5 days and to be maintained for 1 to 8 weeks, with an average of approximately 5 weeks.
Depo-Estradiol Injection is indicated in the treatment of:
Estrogens should not be used in individuals with any of the following conditions:
There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins from oral contraceptives inadvertently during early pregnancy. (See PRECAUTIONS.)
See BOXED WARNINGS
Estrogen and estrogen/progestin therapy have been associated with an increased risk of cardiovascular events such as myocardial infarction and stroke, as well as venous thrombosis and pulmonary embolism (venous thromboembolism or VTE). Should any of these occur or be suspected, estrogens should be discontinued immediately.
Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.
In the Women's Health Initiative (WHI) study, an increase in the number of myocardial infarctions and strokes has been observed in women receiving CE compared to placebo. These observations are preliminary, and the study is continuing. (See CLINICAL PHARMACOLOGY, Clinical Studies.)
In the CE/MPA substudy of WHI, an increased risk of coronary heart disease (CHD) events (defined as nonfatal myocardial infarction and CHD death) was observed in women receiving CE/MPA compared to women receiving placebo (37 vs. 30 per 10,000 women-years). The increase in risk was observed in year one and persisted.
In the same substudy of WHI, an increased risk of stroke was observed in women receiving CE/MPA compared to women receiving placebo (29 vs. 21 per 10,000 women-years). The increase in risk was observed after the first year and persisted.
In postmenopausal women with documented heart disease (n = 2,763, average age 66.7 years) a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study; HERS) treatment with CE/MPA (0.625 mg/2.5 mg per day) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE/MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE/MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand three hundred and twenty-one women from the original HERS trial agreed to participate in an open-label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE/MPA group and the placebo group in HERS, HERS II, and overall.
Large doses of estrogen (5 mg conjugated estrogens per day), comparable to those used to treat cancer of the prostate and breast, have been shown in a large prospective clinical trial in men to increase the risks of nonfatal myocardial infarction, pulmonary embolism, and thrombophlebitis.
In the Women's Health Initiative (WHI) study, in women receiving CE compared to placebo, the risk of VTE (including both DVT and PE) was increased 33% (28 vs. 21 per 10,000 person-years) although only the increased rate of DVT reached statistical significance (p = 0.03). (See CLINICAL PHARMACOLOGY, Clinical Studies.)
In the CE/MPA treatment substudy of WHI, a 2-fold greater rate of VTE, including deep venous thrombosis and pulmonary embolism, was observed in women receiving treatment with CE/MPA compared to women receiving placebo. The rate of VTE was 34 per 10,000 woman-years in the CE/MPA group compared to 16 per 10,000 woman-years in the placebo group. The increase in VTE risk was observed during the first year and persisted.
If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
The use of unopposed estrogens in women with intact uteri has been associated with an increased risk of endometrial cancer. The reported endometrial cancer risk among unopposed estrogen users was about 2-to-12-fold greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than one year. The greatest risk appears associated with prolonged use, with increased risks of 15-to-24-fold for five to ten years or more and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued.
Clinical surveillance of all women taking estrogen/progestin combinations is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.
The use of estrogens and progestins by postmenopausal women has been reported to increase the risk of breast cancer. The most important randomized clinical trial providing information about this issue is the Women's Health Initiative (WHI) substudy of CE/MPA (see CLINICAL PHARMACOLOGY, Clinical Studies). The results from observational studies are generally consistent with those of the WHI clinical trial and report no significant variation in the risk of breast cancer among different estrogens or progestins, doses, or routes of administration.
The CE/MPA substudy of WHI reported an increased risk of breast cancer in women who took CE/MPA for a mean follow-up of 5.6 years. Observational studies have also reported an increased risk for estrogen/progestin combination therapy, and a smaller increased risk for estrogen-alone therapy, after several years of use. In the WHI trial and from observational studies, the excess risk increased with duration of use. From observational studies, the risk appeared to return to baseline in about five years after stopping treatment. In addition, observational studies suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen/progestin combination therapy as compared to estrogen-alone therapy.
In the CE/MPA substudy, 26% of the women reported prior use of estrogen-alone and/or estrogen/progestin combination hormone therapy. After a mean follow-up of 5.6 years during the clinical trial, the overall relative risk of invasive breast cancer was 1.24 (95% confidence interval 1.01–1.54), and the overall absolute risk was 41 vs. 33 cases per 10,000 women-years, for CE/MPA compared with placebo. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 vs. 25 cases per 10,000 women-years, for CE/MPA compared with placebo. Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 vs. 36 cases per 10,000 women-years for CE/MPA compared with placebo. In the same substudy, invasive breast cancers were larger and diagnosed at a more advanced stage in the CE/MPA group compared with the placebo group. Metastatic disease was rare with no apparent difference between the two groups. Other prognostic factors such as histologic subtype, grade and hormone receptor status did not differ between groups.
The use of estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results.
In the Women's Health Initiative Memory Study (WHIMS), 4,532 generally healthy postmenopausal women 65 years of age and older were studied, of whom 35% were 70 to 74 years of age and 18% were 75 or older. After an average follow-up of 4 years, 40 women being treated with CE/MPA (1.8%, n= 2,229) and 21 women in the placebo group (0.9%, n= 2,303) received diagnoses of probable dementia. The relative risk for CE/MPA versus placebo was 2.05 (95% confidence interval 1.21 – 3.48), and was similar for women with and without histories of menopausal hormone use before WHIMS. The absolute risk of probable dementia for CE/MPA versus placebo was 45 versus 22 cases per 10,000 women-years. It is unknown whether these findings apply to younger postmenopausal women. (See CLINICAL PHARMACOLOGY, Clinical Studies and PRECAUTIONS, Geriatric Use.)
A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogen has been reported.
Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level.
Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued.
Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer.
There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include a possible increased risk of breast cancer, adverse effects on lipoprotein metabolism (e.g., lowering HDL, raising LDL) and impairment of glucose tolerance.
In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo-controlled clinical trial, a generalized effect of estrogens on blood pressure was not seen. Blood pressure should be monitored at regular intervals with estrogen use.
In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications.
Estrogens may be poorly metabolized in patients with impaired liver function. For patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised and in the case of recurrence, medication should be discontinued.
Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Patients with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.
Because estrogens may cause some degree of fluid retention, patients with conditions that might be influenced by this factor, such as a cardiac or renal dysfunction, require careful observation when estrogens are prescribed.
Estrogens should be used with caution in individuals with severe hypocalcemia.
The CE/MPA substudy of WHI reported that estrogen plus progestin increased the risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE/MPA versus placebo was 1.58 (95% confidence interval 0.77 – 3.24) but was not statistically significant. The absolute risk for CE/MPA versus placebo was 20 versus 12 cases per 10,000 women-years. In some epidemiologic studies, the use of estrogen alone, in particular for ten or more years, has been associated with an increased risk of ovarian cancer. Other epidemiologic studies have not found these associations.
Endometriosis may be exacerbated with administration of estrogens. A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy. For patients known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered.
Estrogens may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine or porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.
Physicians are advised to discuss the PATIENT INFORMATION leaflet with patients for whom they prescribe Depo-Estradiol.
Estrogen administration should be initiated at the lowest dose for the approved indication and then guided by clinical response, rather than by serum hormone levels (e.g., estradiol, FSH).
Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver. (See BOXED WARINGS, WARNINGS and PRECAUTIONS.)
Depo-Estradiol should not be used during pregnancy. See CONTRAINDICATIONS and Boxed WARNINGS.
Estrogen administration to nursing mothers has been shown to decrease the quantity and quality of the milk. Detectable amounts of estrogens have been identified in the milk of mothers receiving this drug. Caution should be exercised when Depo-Estradiol is administered to a nursing woman.
In the Women's Health Initiative Memory Study, including 4,532 women 65 years of age and older, followed for an average of 4 years, 82% (n= 3,729) were 65 to 74 while 18% (n= 803) were 75 and over. Most women (80%) had no prior hormone therapy use. Women treated with conjugated estrogens plus medroxyprogesterone acetate were reported to have a two-fold increase in the risk of developing probable dementia. Alzheimer's disease was the most common classification of probable dementia in both the conjugated estrogens plus medroxyprogesterone acetate group and the placebo group. Ninety percent of the cases of probable dementia occurred in the 54% of women that were older than 70. (See WARNINGS, Dementia.)
See BOXED WARNINGS, WARNINGS and PRECAUTIONS.
The following additional adverse reactions have been reported with estrogens and/or progestin therapy.
Chlorobutanol anhydrous (chloral derivative) added as a preservative may be habit forming.
Serious ill effects have not been reported following acute ingestion of large doses of estrogen-containing oral contraceptives by young children. Overdosage of estrogen may cause nausea and vomiting, and withdrawal bleeding may occur in females.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Warming and shaking the vial should redissolve any crystals that may have formed during storage at temperatures lower than recommended.
Depo-Estradiol INJECTION IS FOR INTRAMUSCULAR USE ONLY.
When estrogen is prescribed for a woman with a uterus, progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be reevaluated periodically as clinically appropriate (e.g., 3-month to 6-month intervals) to determine if treatment is still necessary. (See BOXED WARNINGS and WARNINGS.) For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
Depo-Estradiol Injection is available in the following concentration containing per mL:
5 mg estradiol cypionate; also 5.4 mg chlorobutanol anhydrous (chloral deriv.) added as preservative; in 913 mg cottonseed oil— in 5 mL vials, NDC 0009-0271-01.
WARNING: Chlorobutanol may be habit forming.
Store at controlled room temperature 20° to 25° C (68° to 77° F) [see USP].
The text of the patient insert for estrogen-containing drug products is set forth below.
Depo-Estradiol®
Brand of estradiol cypionate injection, USP
Read this PATIENT INFORMATION before you start taking Depo-Estradiol and read what you get each time you refill Depo-Estradiol. 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.
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 uterine (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. You and your healthcare provider should talk regularly about whether you still need treatment with Depo-Estradiol.
What is Depo-Estradiol?
Depo-Estradiol injection is an estrogen product. The information below is that which the U.S. Food and Drug Administration requires be provided for all patients taking estrogens. For further information ask your doctor.
What is Depo-Estradiol used for?
Depo-Estradiol is used during and after menopause to:
When the estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feeling of warmth in the face, neck and chest or sudden strong feelings of heat and sweating ("hot flashes" or "hot flushes"). Using estrogen drugs can help the body adjust to lower estrogen levels and reduce these symptoms. Most women have only mild menopause symptoms or none at all and do not need estrogen drugs for these symptoms.
Depo-Estradiol is also used to:
Who should not take Depo-Estradiol?
Do not start taking Depo-Estradiol if you:
