Mail converted by MHonArc
2.6.10
PIENO Google Custom Search
The P-I-E-N-O Parkinsn's List Drug Database
|
Mail converted by MHonArc
2.6.10
|
PIENO Google Custom Search
|
conjugated estrogens / PremarinTM , EstrogenTM ,ProgestinTM , BreviconTM , DemulenTM , DesogenTM ,EnovidTM , GenoraTM , LevlenTM
HORMONE REPLACEMENT :
Description: Conjugated estrogens are a mixture of the water soluble sodium salts of sulfate esters from estrone and equine; other related steroids also may be present. The mixture may be derived from equine urine or synthesized from estrone and equilin. Estrogens, either administered alone or in combination with a progestin, have been shown in a meta-analysis to reduce the risk for osteoporotic hip fracture by 25%.ID Conjugated estrogens are used for numerous abnormalities related to gonadotropin homone dysfunction (see Indications). Conjugated estrogen products were officially approved by the newly-formed FDA in 1938.
Mechanism of Action: Estrogens increase the rate of synthesis of DNA, RNA, and some proteins. Pituitary mass also increases. The secretion of gonadotropin-releasing hormone by the hypothalamus is reduced during estrogen administration, causing reduction in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary.
Exogenous estrogens elicit all of the actions of endogenous estrogens. Estrogens are responsible for the growth and development of female sex organs and the maintenance of sex characteristics including growth of axillary and pubic hair and shaping of body contours and skeleton. At the cellular level, estrogens increase cervical secretions, cause proliferation of the endometrium, and increase uterine tone. Paradoxically, prolonged administration of estrogen can shrink the endometrium. During the preovulatory or nonovulatory phase of the menstrual cycle, withdrawal of estrogen can initiate menstruation; in the ovulatory phase, the decrease in progesterone secretion is the more significant factor causing menstruation.
Estrogens have a weak anabolic effect and also can affect bone calcium deposition and accelerate epiphysial closure. Estrogens generally have a favorable effect on blood lipids, and lack of estrogen is now recognized as a risk factor for myocardial infarction. Estrogens reduce LDL- and increase HCL-cholesterol concentrations. Serum triglycerides increase with estrogen administration. Estrogens, with or without a progestin, exert favorable changes in lipid profiles of postmenopausal women.D Estrogens also enhance sodium and fluid retention.
Pharmacokinetics: Unconjugated estrogens are poorly bioavailable when administered orally. Conjugated estrogens are rapidly absorbed from the GI tract. Estrogens are widely distributed in the body and moderately bound to plasma proteins. Estrogens are metabolized primarily in the liver and eliminated in the urine.
CONTRAINDICATIONS/PRECAUTIONS: Prospective studies in postmenopausal women have shown an increase in risk of breast carcinoma in women given supplemental estrogen, especially with long-term use. Consequently, estrogens are contraindicated in patients with breast carcinoma, except in selected patients with metastatic diseases. Authors have questioned the absolute contraindication of exogenous estrogen (for indications such as preventing heart disease, osteoprosis, etc.) in postmenopausal women with a previous history of breast carcinoma, but without active disease. Benefit versus risk should be determined individually.
Estrogens are contraindicated in patients with abnormal and undiagnosed vaginal bleeding because this may indicate the presence of endometrial hyperplasia or carcinoma, the growth of which would be promoted by the estrogen.
Estrogens are relatively contraindicated in patients with hypercalcemia. Administration of estrogen in patients with breast cancer can cause severe hypercalcemia.
Estrogens are relatively contraindicated in thrombophlebitis or in patients with thromboembolic disease. A positive relationship between estrogen dosage and thromboembolic disease has been demonstrated. Tobacco smoking is an additional risk factor for a thromboembolic event occurring in patients receiving estrogen therapy. Estrogens should be prescribed cautiously to patients who are cigarette smokers.
Estrogens are relatively contraindicated in patients with endometriosis because they can aggravate endometrial implants.
Estrogens are relatively contraindicated during pregnancy because they are associated with urogenital tract abnormalities in the neonate.
Estrogens are relatively contraindicated in patients with hepatic disease because metabolism may be impaired. They are relatively contraindicated in patients with jaundice during pregnancy because they can increase the risk of recurrence. Estrogens are relatively contraindicated in patients with acute intermittent, or variegate hepatic porphyria, which can be exacerbated.
Estrogens are relatively contraindicated in patients with uterine leiomyomata (fibroids) since they can exacerbate fibroid growth.
Estrogens are relatively contraindicated during breast-feeding because they are secreted in milk and cause unpredictable effects in the infant. An alternative feeding method should be used.
Estrogens are relatively contraindicated in children because estrogens promote epiphysial closure.
Blood pressure can increase during therapy with estrogens. Patients with hypertension should be monitored closely for increases in blood pressure if estrogens are administered.
DRUG INTERACTIONS: Estrogens can cause amenorrhea and interfere with the effects of bromocriptine. Concurrent use is not recommended.
Estrogens can increase calcium absorption. In general, the interaction between calcium salts and estrogen is beneficial and is used to therapeutic advantage in postmenopausal women who have osteoporosis.
Estrogens can inhibit the metabolism of cyclosporine. Delayed cyclosporine clearance and elevated cyclosporine concentrations can lead to nephrotoxicity and/or hepatotoxicity. Estrogens should be avoided whenever possible in patients receiving cyclosporine. If this combination cannot be avoided, cyclosporine concentrations should be monitored closely after the addition of the estrogen until a new steady-state level is achieved.
Estrogens have reportedly potentiated the anti-inflammatory effects of hydrocortisone and delayed the clearance of prednisolone. Studies involving other corticosteroids have failed to show an interaction. Estrogens may decrease corticosteroid metabolism secondary to enzyme inhibition, compete at metabolism sites, or alter the protein binding of corticosteroids. Patients should be monitored for increased corticosteroid effects when estrogens are used in patients receiving either hydrocortisone or prednisolone. No interaction was seen between estrogen and dexamethasone, methylprednisolone, or prednisone.
Estrogens interact with hepatotoxic medications, particularly dantrolene, by increasing the risk of hepatotoxicity. Women over 35 years and patients with a history of liver disease are especially at risk.
Estrogens interact with growth hormone (somatropin and somatrem) during prepuberty by accelerating epiphysial maturation.
Estrogens can increase the hepatic synthesis of vitamin K- dependent clotting factors. Because of this, patients receiving warfarin should be monitored for loss of anticoagulant effect if an estrogen is added.
Tamoxifen exerts its effects by blocking estrogen receptors. Since tamoxifen and estrogens are pharmacological opposites, it would be illogical to coadminister them.
Ethinyl estradiol has been reported to intensify side effects from imipramine. One explanation for this interaction is that the estrogen inhibits hepatic metabolism of imipramine. Patients should be monitored for increased tricyclic antidepressant side effects if an estrogen is added.
Cimetidine has been reported to reduce the hepatic clearance of estradiol. While the clinical significance of cimetidine's action on exogenous estrogens is uncertain, this interaction may partially explain the association between cimetidine therapy and gynecomastia.
Rifampin, a potent hepatic enzyme inducer, increases the elimination of estrogen. In addition, free hormone concentrations are decreased because rifampin increases estrogenic protein binding ability. Like other anti-infectives, rifampin indirectly inhibits the enterohepatic recirculation of estrogen through disruption of GI flora growth and this may also be a contributory factor. Concurrent administration of other hepatic enzyme inducers with estrogen, including barbiturates, carbamazepine, griseofulvin, phenytoin and primidone, may produce similar results.
A multiple-dose, placebo-controlled, randomized two-way crossover study investigated the use of lansoprazole with a low-dose oral contraceptive containing ethinylestradiol and levonorgestrel. The bioavailability of oral contraceptives was not affected by lansoprazole.D
ADVERSE REACTIONS: NOTE: Prospective studies in postmenopausal women have shown an increase in risk of breast carcinoma in women given supplemental estrogen, especially with long-term use. Conflicting data, however, continue to be published. The effect of concurrent progestin on the risk of estrogen-induced breast cancer is less clear; combination hormonal therapy is relatively new. Recent data suggest that the addition of progestins to estrogen therapy does not reduce the risk of breast cancer in postmenopausal women. Comparing the benefits of supplemental estrogen versus risks in individual patients is probably best-advised. Supplemental estrogen therapy can promote endometrial hyperplasia and increase the risk of endometrial carcinoma. In recent years, progestins have been used concurrently with estrogens to decrease the risk of endometrial cancer. A recent long term trial studying supplemental estrogens in postmenopausal women supports this practice.
A variety of endocrine effects can occur during therapy with estrogens including breakthrough bleeding or spotting, amenorrhea, or menorrhagia. Breast changes include mastalgia (breast pain) and breast enlargement including gynecomastia in men. Changes in sexuality can occur including libido increase or libido decrease.
GI effects from estrogen administration are relatively limited unless estrogens are administered in large doses such as when used as a postcoital contraceptive. In these larger doses, nausea/vomiting can be significant. At lower doses, abdominal bloating or cramping, or anorexia can occur. Nevertheless, abdominal pain can indicate gallbladder obstruction, hepatitis, hepatoma, peliosis hepatis, or pancreatitis. Estrogen-containing oral contraceptives cause an increased concentration of cholesterol in the bile and cholelithiasis, and cholecystitis is twice as frequent in women taking oral contraceptives compared with controls. Roughly one-third of patients who develop jaundice due to oral contraceptives also have a history of intrahepatic cholestasis during pregnancy. Hormonal contraceptive agents should be discontinued in any patient developing jaundice or severe abdominal pain.
Migraine headaches have been associated with estrogen therapy, although this reaction occurs infrequently.
Thromboembolism and thrombus formation are occasional, serious adverse reactions to estrogen therapy. A positive association has been noted between dosage and thrombotic disorders. In addition, cigarette smokers are at a higher risk. Patients requiring estrogen therapy should be strongly encouraged to discontinue smoking.
Estrogens can cause sodium and fluid retention. They should be prescribed cautiously to patients in whom edema formation would be detrimental. In addition, estrogens also can slightly increase blood pressure, occasionally causing hypertension.
PATIENT INFORMATION:
What do conjugated estrogens tablets do?
Conjugated estrogens (PremarinTM ) are a mixture of naturally occurring different estrogen female hormones. Estrogens are essential for maintaining normal female functions, such as ovulation, menstruation, pregnancy to term, and normal female development. Conjugated estrogens can help relieve symptoms of the menopause (hot flashes, night sweats, mood changes, and vaginal dryness and irritation), and also help to prevent the onset of osteoporosis (a loss of bone mass, so that bones become brittle and easily broken). Conjugated estrogens can be given to patients with inoperable breast cancers (in men or women) or prostate cancer. Generic conjugated estrogen tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take conjugated estrogens?
They need to know if you have any of these conditions:
How should I take this medicine?
Take conjugated estrogen tablets by mouth. Follow the directions on the prescription label. Swallow the tablet with a drink of water. Take the tablets with food. Take your doses at regular intervals; conjugated estrogens work best when taken at the same time each day. Do not take your medicine more often than directed.
Special precautions for use in children:
This medicine is not for children.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with conjugated estrogens?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking conjugated estrogens?
Serious side effects with conjugated estrogens include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with conjugated estrogens include: change in sexual desire mild stomach upset mood changes, anxiety, depression, frustration, anger, or emotional outbursts increased or decreased appetite skin rash, acne, or brown spots on the face tiredness vaginal yeast infection (irritation and white discharge) weight gain Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take conjugated estrogens?
Visit your doctor for regular checks on your progress. You should have a complete check-up every 6 to 12 months. If you have any unusual bleeding contact your doctor for advice.
Conjugated estrogens can make your body retain fluid, making your fingers, hands, or ankles swell. Your blood pressure can go up. Contact your doctor if you feel you are retaining fluid.
If you have any reason to think you are pregnant; stop taking conjugated estrogens at once and contact your doctor.
Tobacco smoking increases the risk of getting a blood clot or having a stroke while you are taking conjugated estrogens, especially if you are more than 35 years old. You are strongly advised not to smoke. If you wear contact lenses and notice visual changes, or if the lenses begin to feel uncomfortable, consult your eye doctor.
Check with your doctor if you develop a spotty darkening of the skin while you are taking conjugated estrogens.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Throw away any unused medicine after the expiration date.
The P-I-E-N-O Parkinsn's List Drug Database Index
John Cottingham is the webmaster of this site.
