Adult Dosing

Moderate to severe vasomotor symptoms/vulvar and vaginal atrophy due to menopause

Prempro

• 1 tablet PO qd [estrogen conjugated 0.3 mg/medroxyprogesterone 1.5 mg - estrogen conjugated 0.625 mg/medroxyprogesterone 5 mg]
• Start with estrogen conjugated 0.3 mg/medroxyprogesterone 1.5 mg PO qd; subsequent dose adjustment may be made based upon individual patient response

Premphase 14/14

• 1 tablet PO qd from day 1-14 [estrogen conjugated 0.625 mg] followed by 1 tablet [estrogen conjugated 0.625 mg/medroxyprogesterone 5 mg] PO qd from day 15-28

Prevention of postmenopausal osteoporosis

Prempro

• 1 tablet PO qd [estrogen conjugated 0.3 mg/medroxyprogesterone 1.5 mg - estrogen conjugated 0.625 mg/medroxyprogesterone 5 mg]
• Start with estrogen conjugated 0.3 mg/medroxyprogesterone 1.5 mg PO qd; subsequent dose adjustment may be made based upon individual patient response

Premphase 14/14

• 1 tablet PO qd from day 1-14 [estrogen conjugated 0.625 mg] followed by 1 tablet [estrogen conjugated 0.625 mg/medroxyprogesterone 5 mg] PO qd from day 15-28

• Use the lowest effective dose for the shortest duration consistent with treatment goals and risks for the individual woman
• Re-evaluate postmenopausal women periodically to determine if treatment is still necessary

Pediatric Dosing

• Not indicated

[Outline]

• Adult Dosing
• Pediatric Dosing

• Indicated in women with intact uteri for
• Treatment of moderate to severe vasomotor symptoms associated with the menopause
• Treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause
• Prevention of postmenopausal osteoporosis

• Hypersensitivity to any of the ingredients of the product
• Undiagnosed abnormal vaginal bleeding
• Active or history of breast cancer
• Known or suspected estrogen-dependent neoplasia
• Active or history of deep vein thrombosis or pulmonary embolism
• Active or recent arterial thromboembolism within 12 months
• Liver dysfunction/disease
• Known thrombophilic disorders
• Known or suspected pregnancy
• Hysterectomy

• Do not use estrogens with progestins for the prevention of cardiovascular disease or dementia
• As per the study conducted by Women’s Health Initiative (WHI), daily oral conjugated estrogen 0.625 mg alone therapy increased the risk of stroke and deep vein thrombosis (DVT) in postmenopausal women (50-79 years of age) during 7.1 yrs of treatment; also an increased risk of stroke, deep vein thrombosis (DVT), pulmonary embolism, and myocardial infarction was reported in postmenopausal women (50-79 yrs of age) during 5.6 years of treatment with daily oral conjugated estrogen 0.625 mg in combination with medroxyprogesterone acetate 2.5 mg, relative to placebo
• As per the WHI Memory Study (WHIMS), oral conjugated estrogen alone (0.625 mg) or in combination with medroxyprogesterone (2.5 mg) increased the risk of developing probable dementia in postmenopausal women 65 years of age during 5.2 and 4 years of treatment respectively, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women
• The WHI estrogen plus progestin substudy also reported an increased risk of invasive breast cancer
• Use of unopposed estrogens in women with intact uteri increases the risk of endometrial cancer. It has been reported that adding a progestin to estrogen therapy reduces the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Use adequate diagnostic measures like endometrial sampling to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal vaginal bleeding
• Other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins are not studied; however, these risks should be assumed to be similar. Use the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman

Renal Dose Adjustment

• Severe renal impairment: Use with caution, dose adjustments not defined

Hepatic Dose Adjustment

• Active hepatic disease: Contraindicated

See Supplemental Patient Information

• Estrogen alone or in combination with progestin therapy increases the risk of stroke, DVT, pulmonary embolism, and myocardial infarction [US Black Box Warning]
• Statistically non-significant increased risk of coronary heart disease events has been reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo
• Risk factors for arterial vascular disease and/or venous thromboembolism should be managed appropriately
• Estrogen alone or in combination with progestin therapy increases the risk of venous thromboembolism. Discontinue estrogen therapy 4-6 wks before surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization
• Use of unopposed estrogens in women with intact uteri increases the risk of endometrial cancer 2-12 times greater than in non-users [US Black Box warning]
• Use of estrogens and progestins in postmenopausal women has been reported to increase the risk of breast cancer. Perform regular breast examinations and mammograms based on patient age, risk factors, and prior mammogram results; advise patients to perform breast self-examinations every month
• Prolonged use of estrogen-plus progestin and estrogen-only therapy has been associated with an increased risk of ovarian cancer
• Estrogen and estrogen/progestin therapy has been reported to increase the risk of dementia in postmenopausal women 65 years of age and older [US Black Box warning]
• Increased risk of gallbladder disease by 2 to 4 fold has been reported in postmenopausal women receiving estrogen therapy
• Estrogen therapy may cause severe hypercalcemia in women with breast cancer and bone metastases. Discontinue therapy and provide appropriate measures if hypercalcemia occurs
• Retinal vascular thrombosis may occur in women receiving estrogens. Discontinue the drug if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia or migraine. Permanently discontinue therapy if papilledema or retinal vascular lesions are seen on examination
• Use of progestin with estrogen in a continuous regimen may lower the incidence of endometrial hyperplasia than would be induced by estrogen-alone treatment. However, there is possible increased risk of breast cancer, adverse effects on lipoprotein metabolism and impairment of glucose tolerance with the use of progestins along with estrogens compared to estrogen-alone regimens
• Estrogen use may cause substantial increases in blood pressure; monitor BP at regular intervals
• Estrogen therapy may elevate plasma triglycerides in women with preexisting hypertriglyceridemia, leading to pancreatitis and other complications; discontinue therapy if pancreatitis occurs
• Use cautiously in patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; discontinue the drug in case of recurrence
• Estrogen administration may cause increased thyroid-binding globulin (TBG) levels. Patients on thyroid hormone replacement therapy receiving estrogens may require increased doses of their thyroid replacement therapy. Monitor thyroid function regularly to maintain free thyroid hormone levels in an acceptable range
• Estrogen plus progestins may cause fluid retention; use cautiously in patients with conditions like asthma, epilepsy, migraine, and cardiac or renal dysfunction
• Administration of estrogen therapy in women treated post-hysterectomy may exacerbate endometriosis; consider adding progestin to the therapy for women known to have residual endometriosis post-hysterectomy

Cautions: Use cautiously in

• Renal impairment
• Risk of cardiovascular disease
• Hypertension
• Hypertriglyceridemia
• History of cholestatic jaundice with estrogens or pregnancy
• Hypothyroidism
• Hypoparathyroidism
• Asthma
• Diabetes mellitus
• Epilepsy
• Migraine
• Severe hypocalcemia
• Surgery or prolonged immobilization
• Porphyria
• Systemic lupus erythematosus
• Hepatic hemangiomas
• Endometriosis
• Smoking
• Obesity
• Chorea
• Seizure disorder

Supplemental Patient Information

• Explain postmenopausal women of the importance of reporting abnormal vaginal bleeding to their physician as early as possible
• Inform postmenopausal women of possible serious and common adverse reactions of estrogen plus progestin therapy such as cardiovascular disorders, malignant neoplasms, probable dementia, headache, breast tenderness, nausea and vomiting

Pregnancy Category:X

Breastfeeding: Progestin-only contraceptives such as depot medroxyprogesterone acetate are considered the hormonal contraceptives of choice during lactation as it does not adversely affect the composition of milk, the growth and development of the infant, or the milk supply. Expert opinion states that the advantages of using progestin-only contraceptive products generally outweigh the theoretical or proven risks before 4 weeks postpartum. However, it is advisable to give it no sooner than 3 days postpartum when lactation is established. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 15 June 2011). Estrogen administration during breastfeeding interferes with lactation by decreasing the quantity and quality of the milk. Detectable amounts of estrogen and progestin have been secreted in breast milk. Manufacturer advises to use cautiously in nursing mothers.

• CV: Deep and superficial venous thrombosis, pulmonary embolism, thromboembolism, thrombophlebitis, myocardial infarction, stroke, hypertension
• CNS: Headache, dizziness, insomnia, nervousness, dementia, migraine, seizure exacerbation
• NEURO: Chorea exacerbation, hypertonia
• PSYCHIATRY: Mood changes, depression, anxiety
• GI: Abdominal pain/bloating, diarrhea, dyspepsia, flatulence, nausea, vomiting, cholestatic jaundice, gallbladder diseases, pancreatitis, hepatic hemangioma enlargement, ischemic colitis
• RESP: Pharyngitis, rhinitis, sinusitis, URTI, increased cough, exacerbation of asthma
• GU: Breast cancer, breast pain, breast enlargement, cervix disorder, cervical secretion changes, dysmenorrhea, leukorrhea, vaginal hemorrhage, vaginal spotting, vaginitis, vaginal moniliasis, endometrial cancer, endometrial hyperplasia, ovarian cancer, uterine fibroid enlargement, vulvovaginal candidiasis, libido changes
• METABOLIC: Peripheral edema, hypocalcemia, severe hypercalcemia (metastatic breast cancer), fluid retention, glucose intolerance, weight changes
• MUSC: Back pain, arthralgia, leg cramps, myalgia
• DERM: Pruritus, rash, erythema multiforme, erythema nodosum, hair loss, hirsutism, melasma/chloasma
• EENT: Retinal thrombosis, contact lens intolerance, vision changes
• HEMA: Porphyria exacerbation
• IMMU: SLE exacerbation
• HYPERSENSITIVITY: Anaphylactoid reaction
• LABTESTS: Increased triglycerides
• MISC: Accidental injury, asthenia, flu syndrome, infection, pain, pelvic pain

Estrogen conjugated

• Estrogen; binds to estrogen receptors and is responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. By negative feedback mechanism, it regulates the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH)
• Metabolized by liver; CYP450: 3A4. Also undergoes enterohepatic recirculation; active metabolites: estradiol, estrone
• Renally excreted
• Half-life
• Estradiol: 1-2 hrs
• Estrone: 4-18 hrs

Medroxyprogesterone Acetate

• Progestin; binds to the progesterone receptor and reduces the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunts the pre-ovulatory LH surge
• Metabolized by liver; CYP450: Unknown
• Renally excreted
• Half-life: 16.6 hrs

US Trade Name(s)

• Premphase 14/14
• Prempro

US Availability

Premphase 14/14 (estrogen conjugated; estrogen conjugated/medroxyprogesterone)

• TABS: 0.625 mg; 0.625 mg/5 mg

Prempro (estrogen conjugated/medroxyprogesterone)

• TABS
• 0.3 mg/1.5 mg
• 0.45 mg/1.5 mg
• 0.625 mg/2.5 mg
• 0.625 mg/5 mg

Canadian Trade Name(s)

• Premplus
• Premplus Cycle

Canadian Availability

Premplus (estrogen conjugated/medroxyprogesterone)

• TABS
• 0.625 mg/2.5 mg
• 0.625 mg/5 mg

Premplus Cycle (estrogen conjugated; estrogen conjugated/medroxyprogesterone)

• TABS: 0.625 mg; 0.625 mg/10 mg

UK Trade Name(s)

• Premique
• Premique Cycle
• Premique Low Dose

UK Availability

Premique (oestrogens conjugated/medroxyprogesterone)

• TABS:0.625 mg/5 mg

Premique Cycle (oestrogens conjugated; estrogen conjugated/medroxyprogesterone)

• TABS: 0.625 mg; 0.625 mg/10 mg

Premique Low Dose (oestrogens conjugated/medroxyprogesterone)

• TABS: 0.3 mg/1.5 mg

Australian Trade Name(s)

• Premia 2.5 Continuous
• Premia 5 Continuous

Australian Availability

Premia 2.5 Continuous (conjugated oestrogens /medroxyprogesterone)

• TABS: 0.625 mg/2.5 mg

Premia 5 Continuous (conjugated oestrogens/medroxyprogesterone)

• TABS: 0.625 mg/5 mg

[Outline]

Obstetrics/Gynecology

Contraceptives

Estrogen And Progestin Combination

Pricing data from www.DrugStore.com in U.S.A.

• Prempro 0.3-1.5 MG TABS [Disp Pack] (WYETH)
  28 mg = $85.99
  84 mg = $236.98
• Prempro 0.625-2.5 MG TABS [Disp Pack] (WYETH)
  28 mg = $85.99
  84 mg = $235.98
• Prempro 0.625-5 MG TABS [Disp Pack] (WYETH)
  28 mg = $85.99
  84 mg = $239.96
• Prempro 0.45-1.5 MG TABS [Disp Pack] (WYETH)
  28 mg = $85.99
  84 mg = $245.98

Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.