medroxyprogesterone (Rx)

>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

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

History or suspected malignancy of breast

Undiagnosed vaginal bleeding

Known anaphylactic reaction or angioedema

Significant 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

Depo-subQ medroxyprogesterone 104 long-term not recommended (ie, >2 years) as birth control method or medical therapy for endometriosis-associated pain unless other options considered inadequate; bone mineral density (BMD) should be evaluated when a woman needs to continue on therapy; in adolescents, interpretation of BMD results should take into account patient age and skeletal maturity

In women with osteoprosys risk factors, other birth control methods or therapies for endometriosis-associated pain should be considered risk/benefit analysis for use of depo-subQ medroxyprogesterone 104; depo-subQ medroxyprogesterone 104 can pose an additional risk in patients with risk factors for osteoporosis (eg, metabolic bone disease, chronic alcohol and/or tobacco use, anorexia nervosa, strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids)

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 (3% of depo-subQ medroxyprogesterone 104-treated patients) and other mood disorders have been reported; discontinue if it occurs

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

Most women using depo-subQ medroxyprogesterone 104 experienced changes in menstrual bleeding patterns, such as amenorrhea, irregular unpredictable spotting or bleeding, prolonged spotting or bleeding, or heavy bleeding; 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

Persistent injection site reactions may occur after administration due to inadvertent subcutaneous administration or release of drug into subcutaneous space while removing the needle

Some patients receiving progestins may exhibit a decrease in glucose tolerance; therefore, patients with diabetes may be at greater risk of hyperglycemia

Delayed return of ovulation or fertility

• Return to ovulation is likely to be delayed after stopping depo-subQ medroxyprogesterone 104, as demonstrated in a study of 15 women who received multiple doses of depo-subQ medroxyprogesterone 104
  • Median time to ovulation was 10 months after last injection
  • Earliest return to ovulation was 6 months after last injection
  • 12 women (80%) ovulated within 1 year of last injection
• However, ovulation has occurred as early as 14 weeks after single dose of depo-subQ medroxyprogesterone 104; therefore, administer next depo-subQ medroxyprogesterone 104 12 to 14 weeks after last injection
• Return to fertility is likely to be delayed after stopping therapy; among 28 women using depo-subQ medroxyprogesterone 104 for contraception who stopped treatment to become pregnant, 7 women were lost to follow-up; one woman became pregnant within one year of her last injection and another woman became pregnant 443 days after her last injection; the remaining 19 women had not become pregnant; it is not known if these 19 women were still attempting to become pregnant or if they had started a new contraceptive method

Pregnancy

Although therapy should not be used during pregnancy, there appears to be little or no increased risk of birth defects in women who have inadvertently been exposed to medroxyprogesterone acetate injections in early pregnancy; neonates exposed to medroxyprogesterone acetate in-utero and followed to adolescence showed no evidence of any adverse effects on their health including their physical, intellectual, sexual or social development

Lactation

Although the drug is detectable in the milk of mothers receiving therapy, milk composition, quality, and amount are not adversely affected; neonates and infants exposed to medroxyprogesterone acetate from breast milk have been studied for developmental and behavioral effects through puberty, and no adverse effects have been noted

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.

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