Medroxyprogesterone Acetate Description

Medroxyprogesterone Acetate Tablets contain medroxyprogesterone acetate, which is a derivative of progesterone. It is a white to off-white, odorless, crystalline powder, stable in air, melting between 200 and 210°C. It is freely soluble in chloroform, soluble in acetone and in dioxane, sparingly soluble in alcohol and in methanol, slightly soluble in ether, and insoluble in water.

The chemical name for medroxyprogesterone acetate is Pregn-4-ene-3,20-dione, 17-(acetyloxy)-6-methyl-, (6?)-. The structural formula is:

Each tablet, for oral administration, contains 2.5 mg, 5 mg or 10 mg of medroxyprogesterone acetate. In addition, each tablet contains the following inactive ingredients: crospovidone, lactose monohydrate, magnesium stearate, methylcellulose, pregelatinized starch, and sodium lauryl sulfate.

Medroxyprogesterone Acetate Indications And Usage

Medroxyprogesterone Acetate Tablets are indicated for secondary amenorrhea and for abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as fibroids or uterine cancer. Medroxyprogesterone Acetate Tablets are also indicated to reduce the incidence of endometrial hyperplasia in nonhysterectomized postmenopausal women receiving 0.625 mg conjugated estrogen.

Medroxyprogesterone Acetate Contraindications

• Thrombophlebitis, thromboembolic disorders, cerebral apoplexy or patients with a past history of these conditions.
• Liver dysfunction or disease.
• Known or suspected malignancy of breast or genital organs.
• Undiagnosed vaginal bleeding.
• Missed abortion.
• As a diagnostic test for pregnancy.
• Known sensitivity to medroxyprogesterone acetate tablets.
• Known or suspected pregnancy.

Medroxyprogesterone Acetate Side Effects

• The physician should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, cerebrovascular disorders, pulmonary embolism, and retinal thrombosis). Should any of these occur or be suspected, the drug should be discontinued immediately.
• Beagle dogs treated with medroxyprogesterone acetate developed mammary nodules some of which were malignant. Although nodules occasionally appeared in control animals, they were intermittent in nature, whereas the nodules in the drug-treated animals were larger, more numerous, persistent, and there were some breast malignancies with metastases. Their significance with respect to humans has not been established.
• Discontinue medication pending examination if there is 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.
• Detectable amounts of progestin have been identified in the milk of mothers receiving the drug. The effect of this on the nursing neonate and infant has not been determined.
• Usage in pregnancy is contraindicated.
• Retrospective studies of morbidity and mortality in Great Britain and studies of morbidity in the United States have shown a statistically significant association between thrombophlebitis, pulmonary embolism, and cerebral thrombosis and embolism and the use of oral contraceptives.4?7 The estimate of the relative risk of thromboembolism in the study by Vessey and Doll6 was about sevenfold, while Sartwell and associates7 in the United States found a relative risk of 4.4, meaning that the users are several times as likely to undergo thromboembolic disease without evident cause as nonusers. The American study also indicated that the risk did not persist after discontinuation of administration, and that it was not enhanced by long continued administration. The American study was not designed to evaluate a difference between products.

Medroxyprogesterone Acetate Precautions

General

• The pretreatment physical examination should include special reference to breast and pelvic organs, as well as Papanicolaou smear.
• Because progestogens may cause some degree of fluid retention, conditions which might be influenced by this factor, such as epilepsy, migraine, asthma, cardiac or renal dysfunction, require careful observation.
• In cases of breakthrough bleeding, as in all cases of irregular bleeding per vaginum, nonfunctional causes should be borne in mind. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures are indicated.
• Patients who have a history of psychic depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.
• Any possible influence of prolonged progestin therapy on pituitary, ovarian, adrenal, hepatic or uterine functions awaits further study.
• Diabetic patients should be carefully observed while receiving progestin therapy.
• The age of the patient constitutes no absolute limiting factor although treatment with progestins may mask the onset of the climacteric.
• The pathologist should be advised of progestin therapy when relevant specimens are submitted.
• Because of the occurrence of thrombotic disorders, (thrombophlebitis, pulmonary embolism, retinal thrombosis, and cerebrovascular disorders) in patients taking estrogen-progestin combinations and since the mechanism is obscure, the physician should be alert to the earliest manifestation of these disorders.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term intramuscular administration of medroxyprogesterone acetate has been shown to produce mammary tumors in beagle dogs. There was no evidence of a carcinogenic effect associated with the oral administration of medroxyprogesterone to rats and mice. Medroxyprogesterone acetate was not mutagenic in a battery of in vitro or in vivo genetic toxicity assays.

Medroxyprogesterone acetate at high doses is an antifertility drug and high doses would be expected to impair fertility until the cessation of treatment.

Information For The Patient

See Patient Information at the end of the brochure.

Pregnancy

Pregnancy Category X

Medroxyprogesterone acetate tablets are contraindicated during pregnancy. Several reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and genital abnormalities in male and female fetuses. The risk of hypospadias in male fetuses may be doubled with exposure to these drugs. Some progestational drugs induce mild virilization of the external genitalia of female fetuses.

Nursing Mothers

The administration of any drug to nursing mothers should be done only when clearly necessary since many drugs are excreted in human milk. Detectable amounts of progestin have been identified in the milk of nursing mothers receiving progestins. The effect of this on the nursing infant has not been determined.

Pediatric Use

The safety and effectiveness of medroxyprogesterone acetate tablets in pediatric patients has not been established.