medroxyprogesterone (DepoProvera, Depo-SubQ Provera 104, MPA, Provera)

Dosing and uses of Depo-Provera, Depo-SubQ Provera 104 (medroxyprogesterone)

• Adult
• Pediatric

 

Adult dosage forms and strengths

tablet

• 2.5mg
• 5mg
• 10mg

injectable suspension

• 150mg/mL
• 400mg/mL

prefilled syringe suspension

• 104mg/0.65mL

 

Amenorrhea, Uterine Bleeding

Uterine bleeding: 5-10 mg/day PO for 5-10 days; beginning day 16 or 21 of the menstrual cycle; withdrawal bleeding may be expected within 3 to 7 days after discontinuing medroxyprogesterone

Amenorrhea, secondary: 5-10 mg/day PO for 5-10 days; may be started at any time; withdrawal bleeding may be expected within 3-7 days after discontinuing medroxyprogesterone

 

Contraception

150 mg deep IM or 104 mg SC every 3 months

 

Endometriosis

Prefilled syringe suspension: 104 mg SC every 3 months for no longer than 2 years

Dosing considerations

• Give initial injection during first 5 days of menstrual cycle to avoid inadvertent administration to pregnant woman
• If patient is nursing, give initial injection no earlier than 6 weeks post partum

 

Paraphilia (Off-label)

100-600 mg IM weekly; alternatively, 100-500 mg PO qDay; maintenance: 100 mg IM every 1-4 weeks

 

Immune Thrombocytopenic Purpura (Orphan)

Orphan indication sponsor

• ZaBeCor Pharmaceutical Company, LLC; 821 Westview Street; Philadelphia, PA 19119

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

Depo-Provera, Depo-SubQ Provera 104 (medroxyprogesterone) adverse (side) effects

>10%

Amenorrhea

Breakthrough bleeding

Change in menstrual flow

Spotting

Edema

Anorexia

Weakness

Pain at injection site

 

Frequency not defined

Angioedema

Change in weight

Depression

Dizziness

Headache

Nervousness

Somnolence

Breast tenderness

Galactorrhea

Abdominal pain

Nausea and vomiting

Cholestatic jaundice

Deep vein thrombosis (DVT)

Thrombophlebitis

 

Postmarketing reports

Rash (allergic) with and without pruritus, change in weight (increase or decrease), pyrexia, edema/fluid retention, fatigue, decreased glucose tolerance

Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides

Injection site reaction, injection site pain/tenderness, injection site persistent atrophy/indentation/dimpling, lipodystrophy acquired, injection site nodule/lump

 

Warnings

Black box warnings

Bone mineral density loss (injection)

• Medroxyprogesterone contraceptive injection may cause significant loss of bone mineral density
• Bone loss is greater with increasing duration of use and may not be completely reversible
• Unknown whether use during critical period of bone accretion (adolescence or early adulthood) will reduce peak bone mass and increase osteoporotic fracture risk in later life
• Use for long-term (>2 years) birth control only if other contraceptive methods are inadequate or poorly tolerated

Cardiovascular risks (oral)

• Estrogens with progestins should not be used to prevent cardiovascular disease
• Women’s Health Initiative (WHI) Estrogen Plus Progestin substudy reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary embolism, and DVT in postmenopausal women aged 50-79 years undergoing 5.6 years of treatment with oral conjugated estrogens (CE) 0.625 mg/day plus medroxyprogesterone acetate (MPA) 2.5 mg/day versus placebo

Dementia risks (oral)

• Estrogens with progestins should not be used to prevent dementia
• Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of probable dementia in postmenopausal women aged 65 years or older undergoing 4 years of treatment with CE 0.625 mg/day plus MPA 2.5 mg/day versus placebo
• Unknown whether this finding applies to younger postmenopausal women

Dose & duration (oral)

• In the absence of comparable data, cardiovascular and dementia risks should be assumed to be similar for other doses of CE and MPA and for other combinations and dosage forms of estrogens and progestins
• Accordingly, estrogens, with or without progestins, should be prescribed at lowest effective dosage and for shortest duration consistent with treatment goals and individual risks

 

Contraindications

Known or suspected pregnancy or as a diagnostic test for pregnancy

Active thrombophlebitis, or current or past history of thromboembolic disorders, or cerebral vascular disease

Known or suspected malignancy of breast

Malignancy of breast or genital organs

Missed abortion

Undiagnosed vaginal bleeding

Known or suspected estrogen-or progesterone-dependent neoplasia.

Known anaphylactic reaction or angioedema

Known liver impairment or disease

Documented hypersensitivity

 

Cautions

Use caution in patients with asthma, diabetes mellitus, history of depression, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas

Not recommended as primary therapy for renal or endometrial cancer

If used with conjugated estrogens, may increase risk of MI, stroke, pulmonary emboli, DVT, breast cancer; discontinue therapy in patients who develop thrombosis

Depo-Provera: Prolonged use may result in significant loss of bone density

Monitor women with a strong family history of breast cancer

Consider ectopic pregnancy if a woman receiving therapy becomes pregnant or complains of severe abdominal pain

Provide emergency medical treatment if anaphylaxis occurs

Discontinue if jaundice or disturbances of liver function develop

Use may mask onset of menopause in women treated for endometrial cancer

Not for use in children prior to menarche

Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer

In some epidemiologic studies, use of estrogen plus progestin and estrogen-only products, in particular for 5 or more years, has been associated with increased risk of ovarian cancer; however, duration of exposure associated with increased risk is not consistent across all epidemiologic studies and some report no association

Discontinue if the following develop: hepatic impairment/ cholestatic jaundice, visual problems, 4-6 wk before major surgery, any symptoms of VTE, massive BP increase, unusually severe migraines or first-time migraines, depression

Studies of addition of progestin for 10 or more days of cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone; possible risks associated with the use of progestins with estrogens compared to estrogen-alone regimens include an increased risk of breast cancer

In cases of unexpected abnormal vaginal bleeding, adequate diagnostic measures are indicated

Blood pressure should be monitored at regular intervals with estrogen plus progestin therapy

In women with preexisting hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis; consider discontinuation of treatment if pancreatitis occurs

Progestins may cause some degree of fluid retention; women with condition influenced by fluid retention including epilepsy, migraine, asthma, cardiac or renal dysfunction, require careful observation

Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur

Therapy should be discontinued pending examination if there is a sudden partial or complete loss of vision, or if there is a sudden onset of proptosis; diplopia or migraine; if examination reveals papilledema or retinal vascular lesions, medication should be withdrawn

Patients may exhibit suppressed adrenal function; medroxyprogesterone acetate may have cortisol-like glucocorticoid activity and provide negative feedback to hypothalamus or pituitary; this may result in decreased plasma cortisol levels, decreased cortisol secretion, and low plasma ACTH levels; use of sterile aqueous suspension may, due to its cortisol-like glucocorticoid activity, also produce Cushingoid symptoms such as weight gain, edema/fluid retention, and facial swelling

Medroxyprogesterone acetate reduces serum estrogen levels when given as 150 mg IM every 3 months and is associated with loss of bone mineral density (BMD); this loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion; unknown if use by younger women will reduce peak bone mass and increase risk for osteoporotic fracture in later life; an evaluation of BMD may be appropriate in some patients who use higher doses of medroxyprogesterone acetate for long-term treatment of endometrial or renal carcinoma

Monitor patients for hepatic dysfunction periodically and temporarily interrupt therapy if patient develops hepatic dysfunction; do not resume use until markers of liver function return to normaL

Any multi-dose use of vials may lead to contamination unless strict aseptic technique is observed

Treatment with progestin may mask the onset of the climacteric

 

Pregnancy and lactation

Pregnancy category: X

Lactation: Safe

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Depo-Provera, Depo-SubQ Provera 104 (medroxyprogesterone)

Mechanism of action

Progestin; inhibits secretion of gonadotropins from pituitary gland, prevents follicular maturation and ovulation, and stimulates growth of mammary tissues

 

Absorption

Bioavailability: PO, 0.6-10%

Duration: IM, 3 months

Peak plasma time: IM, 3 wk; PO, 2-4 hr

 

Distribution

Protein bound: 90%

 

Metabolism

Metabolized by liver

Metabolites: At least 16 have been identified

 

Elimination

Half-life: IM, 50 days

Excretion: Urine