Full Prescribing Info
Medroxyprogesterone acetate.
Provera also contains calcium stearate, cornstarch, lactose, mineral oil, sorbic acid, sucrose and talc as inactive ingredients.
Medroxyprogesterone acetate, a derivative of progesterone, is a white to off-white, odorless crystalline powder, stable in air and melting between 200°C 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.
Medroxyprogesterone acetate is pregn-4-ene-3,20-dione,17-(acetyloxy)-6-methyl-,(6α).
Medroxyprogesterone acetate, administered orally or parenterally in the recommended doses to women with adequate endogenous estrogen, transforms proliferative into secretory endometrium.
Androgenic and anabolic effects have been noted, but the drug is apparently devoid of significant estrogenic activity. While parenterally administered medroxyprogesterone acetate inhibits gonadotropin production, which in turn prevents follicular maturation and ovulation, available data indicate that this does not occur when the usually recommended oral dosage is given as single daily doses.
Secondary amenorrhea; abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology eg, fibroids or uterine cancer; habitual and threatened abortion; pregnancy test.
Dosage/Direction for Use
Secondary Amenorrhea: Provera may be given in dosages of 5-10 mg daily for 5-10 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 Provera daily for 10 days. In cases of secondary amenorrhea, therapy may be started at any time. Progestin withdrawal bleeding usually occurs within 3-7 days after discontinuing Provera 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, 5-10 mg of medroxyprogesterone acetate may be given daily for 5-10 days. To produce an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen, 10 mg of medroxyprogesterone acetate daily for 10 days beginning on the 16th day of the cycle is suggested. Progestin withdrawal bleeding usually occurs within 3-7 days after discontinuing therapy with Provera. Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with Provera.
Thrombophlebitis, thromboembolic disorders, cerebral apoplexy or patients with 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 Provera.
The use of progestational agents during the first 4 months of pregnancy is not recommended.
Progestational agents have been used beginning with the 1st trimester of pregnancy in an attempt to prevent habitual abortion or treat threatened abortion. There is no adequate evidence that such use is effective and there is evidence of potential harm to the fetus when such drugs are given during the first 4 months of pregnancy. Furthermore, in the vast majority of women, the cause of abortion is a defective ovum, which progestational agents could not be expected to influence. In addition, the use of progestational agents, with their uterine-relaxant properties, in patients with fertilized defective ova may cause a delay in spontaneous abortion. Therefore, the use of such drugs during the first 4 months of pregnancy is not recommended.
Several reports suggest an association between intrauterine exposure to female sex hormones and congenital anomalies including congenital heart defects and limb reduction defects. One study estimated a 4.7-fold increased risk of limb reduction defects in infants exposed in utero to sex hormones (oral contraceptives, hormone withdrawal tests for pregnancy or attempted treatment for threatened abortion). Some of these exposures were very short and involved only a few days of treatment. The data suggest that the risk of limb reduction defects in exposed fetuses is somewhat <1 in 1000.
If the patient is exposed to Provera (medroxyprogesterone acetate) during the first 4 months of pregnancy or if she becomes pregnant while taking this drug, she should be apprised of the potential risks to the fetus.
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 infant has not been determined.
Use in pregnancy is not recommended.
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. The estimate of the relative risk of thromboembolism in the study by Vessey and Doll was about 7-fold, while Sartwell and associates 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 non-users. 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.
Special Precautions
The pre-treatment 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 eg, 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.
A decrease in glucose tolerance has been observed in a small percentage of patients on estrogen-progestin combination drugs. The mechanism of this decrease is obscure. For this reason, 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 occasional occurrence of thrombotic disorders (thrombophlebitis, pulmonary embolism, retinal thrombosis, 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.
Adverse Reactions
Pregnancy (see Warnings for possible adverse effects on the fetus).
Breast: Breast tenderness or galactorrhea has been reported rarely.
Skin: Sensitivity reactions consisting of urticaria, pruritus, edema and generalized rash have occurred in an occasional patient. Acne, alopecia and hirsutism have been reported in a few cases.
Thromboembolic Phenomena: Thrombophlebitis and pulmonary embolism have been reported.
The following adverse reactions have been observed in women taking progestins including Provera: Breakthrough bleeding, spotting, change in menstrual flow, amenorrhea, edema, change in weight (increase or decrease), changes in cervical erosion and cervical secretions, cholestatic jaundice, anaphylactoid reactions and anaphylaxis, rash (allergic) with and without pruritus, mental depression, pyrexia, insomnia, nausea, somnolence.
A statistically significant association has been demonstrated between use of estrogen-progestin combination drugs and the following serious adverse reactions: Thrombophlebitis; pulmonary embolism and cerebral thrombosis and embolism. For this reason, patients on progestin therapy should be carefully observed.
Although available evidence is suggestive of an association, such a relationship has been neither confirmed nor refuted for the following serious adverse reactions: Neuro-ocular lesions eg, retinal thrombosis and optic neuritis.
The following adverse reactions have been observed in patients receiving estrogen-progestin combination drugs: Rise in blood pressure in susceptible individuals, premenstrual-like syndrome, changes in libido, changes in appetite, cystitis-like syndrome, headache, nervousness, fatigue, backache, hirsutism, loss of scalp hair, erythema multiforme, erythema nodosum, hemorrhagic eruption, itching, dizziness.
In view of these observations, patients on progestin therapy should be carefully observed.
The following laboratory results may be altered by the use of estrogen-progestin combination drugs: Increased sulfobromophthalein retention and other hepatic function tests.
Coagulation Tests: Increase in prothrombin factors VII, VIII, IX and X.
Metyrapone Test. Pregnanediol determination.
Thyroid Function: Increase in PBI and butanol extractable protein bound iodine and decrease in T3 uptake values.
Store at controlled room temperature 15-30°C (59-86°F).
ATC Classification
G03DA02 - medroxyprogesterone ; Belongs to the class of pregnen (4) derivative progestogens.
Tab 2.5 mg (scored, round, light brown) x 100's. 5 mg (hexagon, white) x 100's. 10 mg (scored, round, white) x 100's.
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