Conjugated estrogens

What is Conjugated estrogens?

• Conjugated estrogens (Premarin) is a mixture of estrogens used in menopausal hormone therapy and for various other indications.
• It is a mixture of the sodium salts of estrogen conjugates found in horses, such as estrone sulfate and equilin sulfate.
• Purified orally bioavailable female sex hormones isolated from pregnant mare urine or synthetically derived from plant materials and primarily conjugated as sulfate esters.

What are the uses of this medicine?

Conjugated estrogens (Premarin) is used after menopause to:

• Reduce moderate to severe hot flashes
• Treat menopausal changes in and around the vagina
• Help reduce your chances of getting osteoporosis (thin weak bones)

PREMARIN is also used to:

• Treat certain conditions in women before menopause if their ovaries do not make enough estrogen naturally.
• Ease symptoms of certain cancers that have spread through the body, in men and women.

How does this medicine work?

• Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics.
• 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 in the peripheral tissues. Thus, estrone and the sulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women.
• Estrogen binds to and activates specific nuclear receptors, which, in turn, bind to estrogen response elements (EREs) in target genes, resulting in histone acetylation, alteration of chromatin conformation, and initiation of transcription.
• Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and FSH, through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these gonadotropins seen in postmenopausal women.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• have unusual vaginal bleeding
• currently have or have had certain cancers
• had a stroke or heart attack
• currently have or have had blood clots
• currently have or have had liver problems
• have been diagnosed with a bleeding disorder
• are allergic to PREMARIN or any of its ingredients
• think you may be pregnant

What drug interactions can this medicine cause?

• Inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as St. John's Wort (Hypericum perforatum) preparations, 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.

Is this medicine FDA approved?

• Premarin, the major brand of CEEs in use, is manufactured by Pfizer and was first marketed in 1941 in Canada and in 1942 in the United States.
• It is the most commonly used form of estrogen in menopausal hormone therapy in the United States.

How should this medicine be used?

Recommended dosage: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause:

• Patients should be treated with the lowest effective dose.
• Generally, women should be started at 0.3 mg PREMARIN daily.
• Subsequent dosage adjustment may be made based upon the individual patient response.

Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause:

• Patients should be treated with the lowest effective dose.
• Generally, women should be started at 0.3 mg PREMARIN daily.
• Subsequent dosage adjustment may be made based upon the individual patient response.

Treatment of Hypoestrogenism due to Hypogonadism, Castration, or Primary Ovarian Failure:

• PREMARIN therapy should be initiated and maintained with the lowest effective dose to achieve clinical goals.
• Female hypogonadism: 0.3 mg or 0.625 mg daily, administered cyclically (e.g., three weeks on and one week off).

• Female castration or primary ovarian failure: 1.25 mg daily, cyclically.

Treatment of Breast Cancer (for Palliation Only) in Appropriately Selected Women and Men with Metastatic Disease:

• Suggested dosage is 10 mg three times daily, for a period of at least three months.

Treatment of Advanced Androgen-Dependent Carcinoma of the Prostate (for Palliation Only):

• 1.25 mg to 2 × 1.25 mg three times daily.
• The effectiveness of therapy can be judged by phosphatase determinations as well as by symptomatic improvement of the patient.

Prevention of Postmenopausal Osteoporosis:

• PREMARIN therapy may be given continuously, with no interruption in therapy, or in cyclical regimens (regimens such as 25 days on drug followed by 5 days off drug), as is medically appropriate on an individual basis.
• Patients should be treated with the lowest effective dose.
• Generally, women should be started at 0.3 mg PREMARIN daily.

Administration:

• Take one PREMARIN tablet at the same time each day
• If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your normal schedule. Do not take 2 doses at the same time.
• Estrogens should be used at the lowest dose possible for your treatment only as long as needed. 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 PREMARIN.
• If you see something that resembles a tablet in your stool, talk to your healthcare provider.
• Take PREMARIN with or without food.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Premarin, are available in the form of oral tablets (0.3 mg, 0.625 mg, 0.9 mg, 1.25 mg, or 2.5 mg), creams for topical or vaginal administration (0.625 mg/g), and vials for intravenous or intramuscular injection (25 mg/vial).

This medicine is available in fallowing brand namesː

• Premarin; Premarin vaginal

What side effects can this medication cause?

The most common side effects of this medicine include:

• Headache
• Breast pain
• Irregular vaginal bleeding or spotting
• Stomach or abdominal cramps, bloating
• Nausea and vomiting
• Hair loss
• Fluid retention
• Vaginal yeast infection
• Reactions from inserting PREMARIN Vaginal Cream, such as vaginal burning, irritation, and itching

Serious, but less common side effects include:

• Heart attack
• Stroke
• Blood clots
• Dementia
• Breast cancer
• Cancer of the lining of the uterus (womb)
• Cancer of the ovary
• High blood pressure
• High blood sugar
• Gallbladder disease
• Liver problems
• Enlargement of benign tumors of the uterus ("fibroids")
• Severe allergic reaction

What special precautions should I follow?

• Estrogens increase the risk of gallbladder disease.
• Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs.
• Monitor thyroid function in women on thyroid replacement therapy.
• Estrogen administration may lead to severe hypercalcemia in women 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.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• nausea
• vomiting
• breast tenderness
• abdominal pain
• drowsiness
• fatigue
• withdrawal bleeding

Treatment of overdosage:

• Treatment of overdose consists of discontinuation of PREMARIN therapy with institution of appropriate symptomatic care.

Can this medicine be used in pregnancy?

• PREMARIN should not be used during pregnancy.
• There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy.

Can this medicine be used in children?

• Safety and effectiveness in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• PREMARIN contains a mixture of conjugated estrogens, which are a mixture of sodium estrone sulfate and sodium equilin sulfate and other components including sodium sulfate conjugates, 17 α-dihydroequilin, 17 α-estradiol, and 17 β-dihydroequilin.
• PREMARIN 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, and 1.25 mg tablets also contain the following inactive ingredients: calcium phosphate tribasic, hydroxypropyl cellulose, microcrystalline cellulose, powdered cellulose, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, sucrose and titanium dioxide.

Who manufactures and distributes this medicine?

• Packager: Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.

What should I know about storage and disposal of this medication?

• Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).
• Dispense in a well-closed container, as defined in the USP.

Gallery

• 
  Estrone sulfate
• 
  Equilin sulfate
• Estradiol
  Estradiol
• 17_-Dihydroequilin
  17_-Dihydroequilin
• 
  Testosterone levels with different estrogen therapies in men with prostate cancer

• Dailymed label info on Conjugated estrogens
• FDA Conjugated estrogens