Premplus

used to manage moderate to severe vasomotor symptoms associated with menopause. Also indicated in atrophic vaginitis, vulvar kraurosis, hypogonadism and female castration and primary chronic failure. Conjugated Estrogens (Premplus) used in conjunction with other therapeutic measures (eg diet, calcium, physical therapy) to retard osteoporosis associated with estrogen deficiency in menopausal women.

Conjugated Estrogens (Premplus) and Medroxyprogesterone (Premplus) are a mixture of estrogen hormones. Estrogen is a female sex hormone produced by the ovaries that is necessary for many processes in the body.

Medroxyprogesterone (Premplus) is also a female hormone, usually called "progesterone." It is important for the regulation of ovulation and menstruation.

The combination of Conjugated Estrogens (Premplus) and Medroxyprogesterone (Premplus) is used to treat the symptoms of menopause such as hot flashes, and vaginal dryness, burning, and irritation, and to prevent thinning of the bones (osteoporosis).

Conjugated Estrogens (Premplus) and Medroxyprogesterone (Premplus) should not be used to prevent heart disease or dementia, because this medication may actually increase your risk of developing these conditions.

Conjugated Estrogens (Premplus) and Medroxyprogesterone (Premplus) may also be used for purposes not listed in this medication guide.

Usual Adult Dose for Osteoporosis

Regimen 1 (Cyclic Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 5 mg orally once a day for 14 days per month.

-or-

Regimen 2 (Continuous Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.3 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 1.5 mg orally once a day or Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 2.5 mg or 5 mg orally once a day.

Long-term therapy (for more than 5 years) is generally necessary in order to obtain substantive benefits in reducing the risk of bone fracture. Maximal benefits are obtained if estrogen therapy is initiated as soon after menopause as possible. The optimal duration of therapy has not been definitively determined.

In addition to hormonal therapy, adequate calcium intake is important for postmenopausal women who require treatment or prevention of osteoporosis. The average diet of older American women contains 400 to 600 mg of calcium per day. 1500 mg per day has been suggested as optimal intake. If dietary intake is insufficient to achieve 1500 mg per day, dietary supplementation may be useful in women who have no contraindication to calcium supplementation.

Usual Adult Dose for Postmenopausal Symptoms

Regimen 1 (Cyclic Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 5 mg orally once a day for 14 days per month.

-or-

Regimen 2 (Continuous Combined Estrogen-Progestin Therapy): : Conjugated Estrogens (Premplus) 0.3 mg or 0.45 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 1.5 mg orally once a day.

In general, the duration of hormone therapy for the treatment of postmenopausal symptoms should be limited. Treatment for one to five years is generally sufficient.

Usual Adult Dose for Atrophic Urethritis

Regimen 1 (Cyclic Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 5 mg orally once a day for 14 days per month.

-or-

Regimen 2 (Continuous Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.45 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 1.5 mg orally once a day or Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 2.5 mg or 5 mg orally once a day.

In general, the duration of hormone therapy for the treatment of postmenopausal symptoms like atrophic vaginitis, kraurosis vulvae, or atrophic urethritis should be limited. Treatment for one to five years is generally sufficient.

Usual Adult Dose for Atrophic Vaginitis

Regimen 1 (Cyclic Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 5 mg orally once a day for 14 days per month.

-or-

Regimen 2 (Continuous Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.45 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 1.5 mg orally once a day or Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 2.5 mg or 5 mg orally once a day.

In general, the duration of hormone therapy for the treatment of postmenopausal symptoms like atrophic vaginitis, kraurosis vulvae, or atrophic urethritis should be limited. Treatment for one to five years is generally sufficient.

Usual Adult Dose for Oophorectomy

Regimen 1 (Cyclic Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 5 mg orally once a day for 14 days per month.

-or-

Regimen 2 (Continuous Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.45 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 1.5 mg orally once a day or Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 2.5 mg or 5 mg orally once a day.

Usual Adult Dose for Primary Ovarian Failure

Regimen 1 (Cyclic Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 5 mg orally once a day for 14 days per month.

-or-

Regimen 2 (Continuous Combined Estrogen-Progestin Therapy): Conjugated Estrogens (Premplus) 0.45 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 1.5 mg orally once a day or Conjugated Estrogens (Premplus) 0.625 mg orally once a day AND Medroxyprogesterone (Premplus) acetate 2.5 mg or 5 mg orally once a day.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

The hepatic metabolism of Conjugated Estrogens (Premplus) may be impaired in patients with liver disease and caution is recommended if patients with liver disease must receive conjugated estrogen therapy. The use of Medroxyprogesterone (Premplus) is considered to be contraindicated for use in patients with liver disease.

Precautions

Regimen 1 and Regimen 2 (the combined regimens) are contraindicated in patients with established hyperlipidemia or ischemic heart disease.

Combined hormone replacement therapy should not be initiated or continued in women for prevention of coronary heart disease because the health risks may exceed the benefits. The Women's Health Initiative (WHI) study was terminated early because a significantly higher risk of invasive breast cancer, stroke and myocardial infarction was associated with long-term use of Premplus. In addition, the results of the Heart and Estrogen/progestin Replacement Study Follow-up (HERS II) have indicated that long-term use increases the risk of thromboembolism, heart attacks, and biliary surgery.

Dialysis

Data not available

See also:
What is the most important information I should know about Premplus?

Angioedema or anaphylactic reaction to estrogen, Medroxyprogesterone (Premplus) or any component of the formulation; undiagnosed abnormal genital bleeding; DVT or PE (current or history of); active or history of arterial thromboembolic disease (eg, stroke, MI); breast cancer (known, suspected or history of); estrogen-dependent tumor (known or suspected); hepatic impairment or disease; known protein C, protein S, antithrombin deficiency or other known thrombophilic disorders; pregnancy.

Documentation of allergenic cross-reactivity for estrogens and progestins is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Use Premplus as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Premplus. Talk to your pharmacist if you have questions about this information.
• Take Premplus by mouth with food or right after a meal to prevent stomach upset.
• Eating grapefruit or drinking grapefruit juice may increase the risk of Premplus's side effects. Talk to your doctor before including grapefruit or grapefruit juice in your diet while you are taking Premplus.
• Premplus works best if it is taken at the same time each day.
• Continue to take Premplus even if you feel well. Do not miss any doses.
• If you miss a dose of Premplus, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Premplus.

Use: Labeled Indications

Osteoporosis prevention (female): Prevention of postmenopausal osteoporosis

Limitations of use: For use only in women at significant risk of postmenopausal osteoporosis; consider use of nonestrogen medications.

Vasomotor symptoms associated with menopause: Treatment of moderate to severe vasomotor symptoms associated with menopause.

Vulvar and vaginal atrophy associated with menopause: Treatment of moderate to severe vulvar and vaginal atrophy associated with menopause.

Limitations of use: When used solely for the treatment of vulvar and vaginal atrophy, topical vaginal products should be considered.

Note: The International Society for the Study of Women

See also:
What other drugs will affect Premplus?

*blood thinner such as warfarin (Coumadin);

*a thyroid medication such as levothyroxine (Synthroid);

*insulin or diabetes medicine taken by mouth;

*rifampin (Rifadin, Rifater, Rifamate, Rimactane);

*ketoconazole (Nizoral) or itraconazole (Sporanox);

*seizure medicines such as phenytoin (Dilantin), carbamazepine (Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), or primidone (Mysoline);

*a barbiturate such as amobarbital (Amytal), butabarbital (Butisol), mephobarbital (Mebaral), secobarbital (Seconal), or phenobarbital (Luminal, Solfoton); or

*antidepressants such as amitriptyline (Elavil, Etrafon), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Janimine, Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), or trimipramine (Surmontil).

See also:
What are the possible side effects of Premplus?

Adverse Reactions

Also see individual agents.

>10%:

Central nervous system: Headache (15% to 19%)

Gastrointestinal: Abdominal pain (7% to 17%)

Genitourinary: Mastalgia (13% to 36%), dysmenorrhea (3% to 13%)

1% to 10%:

Cardiovascular: Edema (≤4%), peripheral edema (2% to 3%), hypertension (2%), vasodilation (≤2%), chest pain (1%), palpitations (≤1%)

Central nervous system: Depression (7% to 8%), pain (5%), emotional lability (3%), dizziness (2% to 3%), migraine (2% to 3%), nervousness (1% to 3%), anxiety (2%), hypertonia (1% to 2%), insomnia (1% to 2%)

Dermatologic: Pruritus (2% to 6%), skin rash (2%), acne vulgaris (≤2%), alopecia (≤2%), skin discoloration (1% to 2%), diaphoresis (≤1%), xeroderma (≤1%)

Endocrine & metabolic: Weight gain (3%), decreased glucose tolerance (≤1%), hypermenorrhea (≤1%)

Gastrointestinal: Nausea (6% to 8%), flatulence (4% to 8%), diarrhea (≤6%), constipation (2%), increased appetite (≤2%), eructation (≤1%)

Genitourinary: Leukorrhea (3% to 8%), breast hypertrophy (2% to 5%), pelvic pain (2% to 5%), vaginal hemorrhage (≤5%), vaginitis (2% to 4%), breakthrough bleeding (1% to 4%), uterine spasm (1% to 4%), vulvovaginal candidiasis (1% to 4%), cervical changes (1% to 3%), abnormal Pap smear (≤2%), breast engorgement (≤1%), urinary incontinence (≤1%)

Hematologic & oncologic: Malignant neoplasm of breast (≤1%)

Infection: Candidiasis (≤2%), infection (≤1%)

Neuromuscular & skeletal: Weakness (3% to 6%), back pain (2% to 7%), leg cramps (2% to 4%)

Respiratory: Pharyngitis (>5%), sinusitis (>5%), flu-like symptoms (≤1%)

<1%, postmarketing, and/or case reports: Abnormal uterine bleeding, amenorrhea, anaphylactoid reaction, anaphylaxis, angioedema, bloating, breast tenderness, cerebrovascular accident, change in appetite, change in cervical secretions, change in libido, chloasma, cholestatic jaundice, contact lens intolerance, cough, deep vein thrombosis, dementia, endometrial carcinoma, endometrial hyperplasia, erythema multiforme, erythema nodosum, exacerbation of asthma, exacerbation of epilepsy, exacerbation of tics, fibrocystic breast changes, galactorrhea, gallbladder disease, hirsutism, hypersensitivity reaction, increased serum triglycerides, irritability, ischemic colitis, malignant neoplasm of ovary, meningioma (benign; possible growth), myalgia, myocardial infarction, nipple discharge, pancreatitis, pulmonary embolism, retinal thrombosis, rhinitis, superficial venous thrombosis, thrombophlebitis, upper respiratory tract infection, urticaria, uterine fibroids (increase in size), vomiting, vulvovaginal candidiasis, weight loss