Medroxyprogesterone acetate tablet is a progestin indicated for the treatment of secondary amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as fibroids or uterine cancer. Medroxyprogesterone acetate is also indicated to reduce the incidence of endometrial hyperplasia in nonhysterectomized postmenopausal women receiving daily oral conjugated estrogens 0.625 mg tablets.

Secondary Amenorrhea: Medroxyprogesterone acetate tablets may be given in dosages of 5 or 10 mg daily for 5 to 10 days. A dose for inducing an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen is 10 mg of this tablet daily for 10 days. In cases of secondary amenorrhea, therapy may be started at any time. Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing this tablet therapy.

Abnormal Uterine Bleeding Due to Hormonal Imbalance in the Absence of Organic Pathology: Beginning on the calculated 16th or 21st day of the menstrual cycle, 5 or 10 mg of this tablet may be given daily for 5 to 10 days. To produce an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen, 10 mg of this tablet daily for 10 days beginning on the 16th day of the cycle is suggested. Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing therapy with this tablet. Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with this tablet.

Reduction of Endometrial Hyperplasia in Postmenopausal Women Receiving Daily 0.625 mg Conjugated Estrogens: When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be re-evaluated periodically as clinically appropriate (for example, 3 to 6 month intervals) to determine if treatment is still necessary. For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.

Medroxyprogesterone acetate tablet tablets may be given in dosages of 5 or 10 mg daily for 12 to 14 consecutive days per month, in postmenopausal women receiving daily 0.625 mg conjugated estrogens, either beginning on the 1st day of the cycle or the 16th day of the cycle. Patients should be started at the lowest dose. The lowest effective dose of this tablet has not been determined.

Medroxyprogesterone Acetate is contraindicated in women with any of the following conditions:

• Undiagnosed abnormal genital bleeding.
• Known, suspected, or history of breast cancer.
• Known or suspected estrogen- or progesterone-dependent neoplasia.
• Active DVT, PE, or a history of these conditions
• Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions.
• Known anaphylactic reaction or angioedema to Medroxyprogesterone Acetate
• Known liver impairment or disease.
• Known or suspected pregnancy.

The following adverse reactions have been reported in women taking Medroxyprogesterone Acetate tablets, without concomitant estrogens treatment:

• Genitourinary system: Abnormal uterine bleeding (irregular, increase, decrease), change in menstrual flow, breakthrough bleeding, spotting, amenorrhea, changes in cervical erosion and cervical secretions.
• Breasts: Breast tenderness, mastodynia or galactorrhea has been reported.
• Cardiovascular: Thromboembolic disorders including thrombophlebitis and pulmonary embolism have been reported.
• Gastrointestinal: Nausea, cholestatic jaundice.
• Skin: Sensitivity reactions consisting of urticaria, pruritus, edema and generalized rash have occurred. Acne, alopecia and hirsutism have been reported.
• Eyes: Neuro-ocular lesions, for example, retinal thrombosis, and optic neuritis.
• Central nervous system: Mental depression, insomnia, somnolence, dizziness, headache, nervousness.

Overdose Effects

Overdosage of estrogen plus progestin therapy may cause nausea and vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of CE plus MPA together with institution of appropriate symptomatic care.

Addition of a progestin when a woman has not had a hysterectomy: Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include an increased risk of breast cancer.

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

Elevated blood pressure: Blood pressure should be monitored at regular intervals with estrogen plus progestin therapy.

Hypertriglyceridemia: In women with pre-existing hypertriglyceridemia, estrogen plus progestin therapy may be associated with elevations of plasma triglycerides leading to pancreatitis. Consider discontinuation of treatment if pancreatitis occurs.

Hepatic Impairment and/or past history of cholestatic jaundice: Estrogens plus progestins may be poorly metabolized in women with impaired liver function. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised, and in the case of recurrence, medication should be discontinued.

Fluid Retention: Progestins may cause some degree of fluid retention. Women who have conditions which might be influenced by this factor, such as cardiac or renal impairment, warrant careful observation when estrogen plus progestin are prescribed.

Hypocalcemia: Estrogen plus progestin therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur.

Exacerbation of other conditions: Estrogen plus progestin therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.

Use in Special Populations

Pediatric Use: Medroxyprogesterone Acetate tablets are not indicated in children. Clinical studies have not been conducted in the pediatric population.

Geriatric Use: There have not been sufficient numbers of geriatric women involved in clinical studies utilizing Medroxyprogesterone Acetate alone to determine whether those over 65 years of age differ from younger subjects in their response to Medroxyprogesterone Acetate alone.

Pregnancy & Lactation

Medroxyprogesterone Acetate should not be used during pregnancy. There may be increased risks for hypospadias, clitoral enlargement and labial fusion in children whose mothers are exposed to Medroxyprogesterone Acetate during the first trimester of pregnancy. However, a clear association between these conditions with use of this tablet has not been established. This tablet should not be used during lactation. Detectable amounts of progestin have been identified in the breast milk of nursing mothers receiving progestins.