Premarin

Premarin Uses, Dosage, Side Effects, Food Interaction and all others data.

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, which is 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 estrogen 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 gonadotropins seen in postmenopausal women.

The binding of estrogens to the estrogen receptor produces the activation of nuclear receptors in order to bind to estrogen response elements in certain target genes. This mechanistic cascade results in histone acetylation, alteration of chromatin conformation and the initiation of transcription of certain specific drugs.

In preclinical studies, the conjugated estrogens are known to have a similar estrogenic potency than estrone and the equilin components of the conjugated estrogens have similar potency in the liver when compared to bioidentical estradiol. It has also been tested and confirmed that conjugated estrogens present a selective estrogen receptor modulator profile which allows it to have a large beneficial effect on the bone and cardiovascular system.

Clinically, the administration of conjugated estrogens is known to promote vasomotor stability, maintain genitourinary function, and normal growth and development of female sex hormones. It has also been shown to prevent accelerated bone loss by inhibiting bone resorption and restoring the balance of bone resorption. In the hormonal area, it is shown to inhibit luteinizing hormone and decrease the serum concentration of testosterone.

Premarin
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Premarin
Generic	Conjugated Estrogens
Conjugated Estrogens Other Names	Conjugated equine estrogens, Conjugated estrogens, Estrogens, Conjugated, Estrogens,conjugated
Weight	25mg/5ml, 0.625mg/gm, 0.625mg, 1.25mg, , 0.3mg, 0.6%w/w, 0.45mg, 0.9mg
Type	Tablet, Injection, Vaginal Cream, Vag Cream, Oral Tablet, Powder, Lyophilized, For Solution, Intravenous
Protein binding	Conjugated estrogens are bound to plasma proteins and this bound state can represent around 50-80% of the administered dose. It circulates in the blood mainly bound to sex-hormone binding globulin and albumin.
Groups	Approved
Therapeutic Class	Female Sex hormones
Manufacturer	Pfizer Ltd, Wyeth Pharmaceuticals Limited, Wyeth-ayerst Laboratories, Pfizer Laboratories Ltd,, Pfizer Limited
Available Country	India, Bangladesh, Canada, Australia, Pakistan, United Kingdom, United States,
Last Updated:	September 19, 2023 at 7:00 am

Uses

Premarin vaginal cream is used for the treatment of atrophic vaginitis, dyspareunia and kraurosis vulvae. Premarin with or without progestins should not be used for the prevention of cardiovascular disease or dementia.

Premarin is also used to associated treatment for these conditions: Atrophic Vaginitis, Atrophy of vulva, Kraurosis Vulvae caused by Menopause, Metastatic Breast Cancer, Osteoporosis, Premature Ovarian Failure (POF), Vasomotor Symptoms Associated With Menopause, Vulvovaginal Atrophy, Androgen-dependent tumor Advanced Prostate Carcinoma, Hypoestrogenism, Moderate Dyspareunia, Severe Dyspareunia

How Premarin works

The conjugated estrogens, equally to the normal physiological estrogen, work by agonistically binding to the estrogen receptors alpha and beta. The estrogen receptors vary in quantity and proportion according to the tissues and hence, the activity of this conjugated estrogens is very variable.

The activity made by the conjugated estrogens is driven by the increase in the synthesis of DNA, RNA and various proteins in responsive tissues which in order will reduce the release of gonadotropin-releasing hormone, follicle-stimulating hormone and leuteinizing hormone.

The specific mechanism of action cannot be described only in terms of total estrogenic action as the pharmacokinetic profile, the tissue specificity and the tissue metabolism is different for each component of the product.

Dosage

Premarin dosage

Menopausal vasomotor symptoms: 0.45 mg/day, up to 1.25 mg/day. Attempt to discontinue medication at 3-6-mth intervals.

Vulvular and vaginal atrophy: 0.3 mg/day.

Female hypogonadism: 0.3-0.625 mg/day in a cyclical regimen. Add progestin treatment once skeletal maturity is achieved.

Female castration, Primary ovarian failure: 1.25 mg/day in a cyclical regimen. Palliation in prostate carcinoma 1.25-2.5 mg 3 times/day.

Osteoporosis prophylaxis in postmenopausal women: Initial: 0.3 mg/day in a cyclical or continuous regimen depending on patient's condition.

Side Effects

Breast pain, tenderness or enlargement, Headache/migraine, Gut disturbances, such as nausea, abdominal pain, bloating, flatulence, indigestion, Legcramps, Fatigue, Weightchanges, Vaginalthrush, Depression, Anxiety, Dizziness, Changes in sex drive, Rise in blood pressure, Gall bladder disease, Swelling of the ankles due to to fluid retention (peripheral oedema), Skin reactions such as rash and itch, Steepening of corneal curvature which may make contact lenses uncomfortable, Premenstrual-like symptoms, Disturbance in liver function, Irregular brown patches on the skin, usually of the face (chloasma), Blood clots in the blood vessels.

Toxicity

The reported oral LD50 in the rat is of more than 5000 mg/kg. Serious overdosage symptoms have not been reported. There have been only reports of nausea, vomiting, and withdrawal in bleeding in females.

Long-term continuous administration of estrogens is correlated to increased risk on the incidence of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.

Precaution

Asthma, epilepsy, migraine; heart or kidney dysfunction; CV disease; cerebrovascular disorders; diabetes, hypercalcaemia; gall bladder disease; porphyria. Children. Lactation.

Lactation: Use controversial; estrogens are excreted into breast milk in small quantities; use with caution

Interaction

The metabolism of estrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes, such as anticonvulsants (e.g. phenobarbital, phenytoin, carbamazepine) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz).

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Food Interaction

Take with or without food. Consult individual product monograph for specific instructions.

Volume of Distribution

The physiological distribution of estrogens in the body is very similar to what is seen in endogenous estrogens and hence, it is widely distributed. The conjugated estrogens are mainly found in the sex hormone target organs.

Elimination Route

The conjugated estrogens are well absorbed in the gastrointestinal tract and the maximum plasma concentration of the conjugated estrogens is reached after 7 hours depending on the estrone component. The maximal plasma concentration of conjugated estrogens after multiple doses of 0.45 mg is reported to be of 2.6 ng/ml with an AUC in the steady state of 35 ng.h/ml. Unconjugated estrogens are known to be cleared from the circulation at a faster rate than their ester forms.

Half Life

The median half-life of the conjugated estrogens is reported to be of 17 hours.

Clearance

The reported normal clearance rate for estrogens is of approximately 615 L/m2.

Elimination Route

The conjugated estrogens are eliminated mainly in the urine. In this renal elimination, it is possible to find 17 beta-estradiol, estrone, estriol, as well as the glucuronide and sulfate conjugates of the estrogens.

Pregnancy & Breastfeeding use

For women with a uterus: If pregnancy occurs during medication with Conjugated Oestrogens treatment should be withdrawn immediately. The results of most epidemiological studies to date relevant to inadvertent foetal exposure to estrogens indicate no teratogenic or foetotoxic effects.

Lactation: Conjugated Oestrogens is not indicated during lactation.

Contraindication

Known or suspected pregnancy; undiagnosed abnormal uterine bleeding; known, suspected, or history of past breast cancer; known or suspected estrogen-dependent neoplasia (e.g., endometrial cancer, endometrial hyperplasia); active or history of arterial thromboembolic disease (e.g., stroke, myocardial infarction or venous thromboembolism (such as deep venous thrombosis, pulmonary embolism); active or chronic liver dysfunction or disease; known thrombophilic disorders (e.g., protein C, protein S, or antithrombin deficiency); hypersensitivity to any component of this medication.

Acute Overdose

Symptoms of overdosage of estrogen containing products in adults and children may include nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue; withdrawal bleeding may occur in females. There is no specific antidote and further treatment if necessary should be symptomatic.