PRODUCT MONOGRAPH

PrDom-MEDROXYPROGESTERONE (Medroxyprogesterone acetate Tablets USP) 2.5mg, 5 mg and 10 mg

Progestin

DOMINION PHARMACAL

Date of Preparation:

6111 Royalmount Avenue, Suite 100 May 05, 2003 Montreal, Quebec H4P 2T4 Date of Revision: May 10, 2004

Control #: 084985

PRODUCT MONOGRAPH

PrDom-MEDROXYPROGESTERONE (Medroxyprogesterone acetate Tablets USP) 2.5mg, 5 mg and 10 mg

PHARMACOLOGICAL CLASSIFICATION

Progestin

Warning

As the Women's Health Initiative (WHI) study results indicated increased risk of myocardial infarction (MI), stroke, invasive breast cancer, pulmonary emboli and deep venous thrombosis in postmenopausal women receiving treatment with combined conjugated equine estrogens and medroxyprogesterone acetate compared to those receiving placebo tablets, the following should be highly considered: Estrogens with or without progestins should not be prescribed for primary or secondary prevention of cardiovascular diseases. Estrogens with or without progestins should be prescribed at the lowest effective dose for the approved indication. Estrogen with or without progestins should be prescribed for the shortest period possible for the recognized indication.

ACTION AND CLINICAL PHARMACOLOGY

Dom-MEDROXYPROGESTERONE (medroxyprogesterone acetate) is an orally active progestational steroid (progestin) derived from a natural source (soybeans). When administered to women with adequate levels of estrogen (endogenous or exogenous), Dom- MEDROXYPROGESTERONE transforms a proliferative endometrium into a secretory endometrium. Furthermore, the anti-cancer activity of Dom-MEDROXYPROGESTERONE at pharmacologic doses, may be dependent on its effect on the hypothalamic/ pituitary/ gonadal axis, estrogen receptors and metabolism of steroids at the tissue level.

Clinical Pharmacology

Medroxyprogesterone acetate is a progestational agent devoid of androgenic and estrogenic activity.

Endocrine:

In appropriate doses, medroxyprogesterone acetate suppresses the secretion of pituitary gonadotropins which in turn, prevents follicular maturation, producing anovulation in the reproductive aged woman. Medroxyprogesterone acetate, like progesterone, is thermogenic. At the very high dosage levels used in the treatment of certain cancers (500 mg daily or more), corticoid-like activity may be observed. Suppression of the Leydig cell function in the male (i.e. suppresses endogenous testosterone production) occurs after appropriate doses of medroxyprogesterone acetate.

Reproductive Tract:

Medroxyprogesterone acetate, when administered to women with adequate levels of estrogen (endogenous or exogenous), transforms a proliferative endometrium into a secretory endometrium. Withdrawal bleeding is anticipated within 7 days after stopping medroxyprogesterone acetate. Microscopically, the secretory change is associated with glycoprotein-rich stromal cells which surround the glands and vessels and assist them in maintaining their integrity during hormonal withdrawal. The result is an orderly regression and remodelling, and preservation of the functional layer of the endometrium. Medroxyprogesterone acetate decreases both cytoplasmic and nuclear estrogen receptors in endometrial cells. In addition, medroxyprogesterone acetate induces estradiol dehydrogenase (E2DH) activity, the enzyme mechanism by which endometrial cells metabolize and excrete estrogens. Medroxyprogesterone is added for protection against endometrial hyperplasia during long-term estrogen therapy of women with intact uteri. Oral medroxyprogesterone acetate also produces typical progestational changes in the cervical mucous (inhibits ferning) and increases the intermediate cell count in the maturation index of the vaginal epithelium.

Skeletal system:

Presently there are no conclusive data concerning the mechanism of action of progestins on bone. Clinically, research to date has shown women treated with medroxyprogesterone acetate to prevent estrogenic hyperstimulation of the endometrium do not lose protection against osteoporosis .

Cardiovascular

: There is no conclusive evidence that medroxyprogesterone acetate produces adverse coagulation changes in women receiving the progestin alone, or as part of a sequential regimen with estrogen.

Research indicates that medroxyprogesterone acetate has little, if any, adverse effect on blood pressure. Results from studies show no significant difference between estrogen-treated and estrogen-medroxyprogesterone acetate-treated patients for the development of hypertension. Medroxyprogesterone acetate shows small or undetectable effects on lipoproteins when used at therapeutic dosages. Furthermore, research demonstrates that the use of medroxyprogesterone acetate with estrogen in hormone replacement therapy maintains the estrogenic effects on lipid profile.

Metabolic:

In studies which examined metabolic changes, a decrease in glucose tolerance has been associated with progestins, including medroxyprogesterone acetate.

Pharmacokinetics of Dom-MEDROXYPROGESTERONE

Medroxyprogesterone acetate has an apparent half-life of approximately 30 hours. Medroxyprogesterone acetate is rapidly absorbed from the gastrointestinal tract and metabolized in the liver to several progestin metabolites. The major drug-related material found in circulation following oral administration has been characterized as both free and glucuronide-conjugated metabolites of medroxyprogesterone acetate. Medroxyprogesterone acetate is primarily eliminated via fecal excretion, to which biliary secretion may contribute. Approximately 44% of an oral dose is eliminated through urinary excretion in the form of metabolites. The major metabolite of medroxyprogesterone acetate is a 6 alpha-methyl-6 beta, 17 alpha, 21- trihydroxy-4-pregnene-3, 20-dione-17-acetate, which is eliminated in the urine. This accounts for approximately 8% of an oral dose, and is found to be excreted as a glucuronide conjugate. A comparative, single-dose, two-way bioavailability study was performed on two 5 mg medroxyprogesterone acetate tablet formulations, Dom-MEDROXYPROGESTERONE 5 mg tablets and Provera(r) 5 mg tablets. The pharmacokinetic data calculated for a single oral dose of 2 X 5 mg tablets (medroxyprogesterone acetate tablet formulations Dom- MEDROXYPROGESTERONE versus PROVERA(r)) under fasting conditions are tabulated below: Pharmacokinetic Indices for Medroxyprogesterone Acetate

*For the Tmax and T1/2 parameters these are the arithmetic means (standard deviation). * *Provera(r) manufactured by The Upjohn Company of Canada.

CONTRAINDICATIONS

Dom-MEDROXYPROGESTERONE (medroxyprogesterone acetate) is contraindicated in patients with any of the following disorders: Active hepatic dysfunction or disease, especially the obstructive type Personal history of known or suspected estrogen/progestin-dependent neoplasia such as carcinoma of the breast or endometrial cancer, with the exception of cases where Dom- MEDROXYPROGESTERONE is used in the adjunctive and/or palliative treatment of such cancers. Undiagnosed abnormal genital bleeding Undiagnosed urinary tract bleeding Known or suspected pregnancy or for use as a pregnancy test (see WARNINGS) Active or past history of cerebral apoplexy or arterial thromboembolic disease (eg. Stroke, myocardial infarction, coronary heart disease) Classical migraine Active or past history of confirmed venous thromboembolism (such as deep venous thrombosis or pulmonary embolism) or active thrombophlebitis Partial or complete loss of vision due to ophthalmic vascular disease Known or suspected hypersensitivity to medroxyprogesterone acetate or any component of the product (see PHARMACEUTICAL INFORMATION)

WARNINGS

See Boxed Warnings at the front page. Liver function tests should be carried out periodically in patients who have or are suspected of having hepatic disease. The physician should watch for the earliest signs of impaired liver function. If these occur or are suspected, treatment should be terminated and the patient's condition re-evaluated.

Cardiovascular Disorders

Available epidemiological data indicate that use of estrogen with or without progestin is associated with an increased risk of stroke, and coronary heart disease. WHI-trial's results concluded that there are more risks than benefits among women using combined Hormone Replacement Therapy (HRT), compared to the group using placebo. In 10,000 women on combined HRT (conjugated equine estrogens/ medroxyprogesterone acetate) over one year period, there were seven more cases of coronary heart disease (37 on combined HRT versus 30 on placebo) and eight more cases of strokes (29 vs. 21). In the Heart and Estrogen/progestin Replacement Study (HERS) of postmenopausal women with documented heart disease(n=2763; average age 66.7 years), a randomized placebo-controlled clinical trial of secondary prevention of coronary heart disease (CHD), treatment with 0.625 mg/day oral conjugated equine estrogen (CEE) plus 2.5 mg medroxyprogesterone acetate (MPA) demonstrated no cardiovascular benefit. Specifically, during an average follow-up of 4.1 years, treatment with CEE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the hormone-treated group than in the placebo group in year 1, but not during the subsequent years. From the original HERS trial, 2321 women consented to participate in an open label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. After 6.8 years, hormone therapy did not reduce the risk of cardiovascular events in women with CHD.

Breast Cancer

Current epidemiological data indicate that the use of combined HRT is associated with an increased risk of invasive breast cancer. WHI-trial's results concluded that there are more risks than benefits among women using combined HRT (conjugated equine estrogens/ medroxyprogesterone acetate), compared to the group using placebo. In 10, 000 women on combined HRT over one year period, there were eight more cases of invasive breast cancer (38 on combined HRT versus 30 on placebo). The WHI study reported that the invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology but were larger (mean[SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P=0.04) and were at a more advanced stage compared with those diagnosed in the placebo group. The WHI trial also reported that the percentage of women with abnormal mammograms (recommendations for short-interval follow-up, a suspicious abnormality, or highly suggestive of malignancy) was significantly higher in the estrogen plus progestin group versus the placebo group. This difference appeared at year one and persisted in each year thereafter. It is recommended that estrogens with or without progestins not be given to women with existing breast cancer or those with a previous history of the disease. There is a need for caution in prescribing estrogens with or without progestins for women with known risk factors associated with the development of breast cancer, such as strong family history of breast cancer (first degree relative) or who present a breast condition with an increased risk (abnormal mammograms and/or atypical hyperplasia at breast biopsy). Other known risk factors for the development of breast cancer such as nulliparity, obesity, early menarche, late age at first full term pregnancy and at menopause should be evaluated. It is recommended that women undergo mammography prior to the start of HRT treatment and at regular intervals during treatment as deemed appropriate by the treating physician and according to the perceived risks for each patient. The overall benefits and possible risks of hormone replacement therapy should be fully considered and discussed with patients. It is important that the modest increased risk of being diagnosed with breast cancer after 4 years of treatment with HRT (as reported in the results of WHI-trial) be discussed with the patient and weighed against its known benefits. Instructions for regular self-examination of the breasts should be included in this counseling.

Venous Thromboembolism

Recent epidemiological data indicate that use of estrogen with or without progestin is associated with an increased risk of developing venous thromboembolism (VTE). WHI-trial's results concluded that there are more risks than benefits among women using combined HRT (conjugated equine estrogens/ medroxyprogesterone acetate), compared to the group using placebo. In 10,000 women on combined HRT over a period of one year, there were eighteen more cases of total blood clots in the lungs and legs (34 on combined HRT versus 16 on placebo). Generally recognized risk factors for VTE include a personal history, a family history (the occurrence of VTE in a direct relative at a relatively early age may indicate genetic predisposition) and severe obesity (body mass index>30 kg/m2). The risk of VTE also increases with age and smoking. The risk of VTE may be temporarily increased with prolonged immobilization, major elective surgery or posttraumatic surgery, or major trauma (if feasible, estrogens with or without progestins should be discontinued at least 4 weeks before major surgery which may be associated with an increased risk of thromboembolism, or during periods of prolonged immobolization). In women on HRT, attention should be given to prophylactic measures to prevent VTE following surgery. Also, patients with varicose veins should be closely supervised. The physician should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, retinal thrombosis, cerebral embolism and pulmonary embolism). If these occur or are suspected, hormone therapy should be discontinued immediately.

Dementia

Current epidemiological evidence indicates that the use of combined HRT is associated with a significantly increased risk of developing probable dementia. The Women's Health Initiative Memory Study, a clinical substudy of WHI, followed 4532 post-menopausal women age 65 and over and free of dementia at baseline. There was a reported two-fold increase in the relative risk of developing probable dementia after an average follow-up of 4.05 years in the group treated with daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone versus those treated with placebo (hazard ratio[HR] 2.05, 95% confidence interval [CI] 1.21-3.48). This increased risk would result in an additional 23 cases of dementia per 10,000 women per year (45 vs 22 per 10,000 person-years; P = .01).

Additional Warnings

Usage in pregnancy is not advised. Progestational agents should also not be used as a diagnostic test for pregnancy (see CONTRAINDICATIONS). If the patient is exposed to medroxyprogesterone acetate during pregnancy or if she becomes pregnant while taking the drug, she should be apprised of the potential risk to the fetus. If there is a sudden loss of vision, whether partial or complete, or sudden onset of proptosis, diplopia or migraine, an examination should be carried out. Upon examination, if papilledema or retinal vascular lesions are found, the drug should be discontinued. Clinical suppression of adrenocortical function has not been observed at low dose levels. However, the high doses of medroxyprogesterone acetate used in the treatment of certain cancers, in some cases, produce Cushingoid symptoms (e.g., "moon' facies, fluid retention, glucose intolerance, and blood pressure elevation). Detectable amounts of progestin have been identified in the milk of mothers receiving the drug. Infants exposed to medroxyprogesterone via breast milk have been studied for developmental and behavioral effects through puberty. No adverse effects have been noted. Anaphylactic and anaphylactoid reactions have occurred at times in people taking medroxyprogesterone acetate.

PRECAUTIONS

Before DOM-MEDROXYPROGESTERONE is administered, the patient should have a complete physical examination including a blood pressure determination. Breasts and pelvic organs should be appropriately examined and a Papanicolaou smear should be performed. Endometrial biopsy should be done when indicated. Baseline tests should include mammography, measurements of blood glucose, calcium, triglycerides and cholesterol, and liver function tests. The first follow-up examination should be done within 3-6 months after initiation of treatment to assess response to treatment. Thereafter, examinations should be made at intervals at least once a year and should include at least those procedures outlined above. It is important that patients are encouraged to practice frequent self-examination of the breasts. Abnormal vaginal bleeding due to its prolongation, irregularity or heaviness, occurring during therapy should prompt diagnostic measures like hysteroscopy endometrial biopsy or curettage to rule out the possibility of uterine malignancy and the treatment should be re-evaluated. Patients should be advised of the menstrual bleeding patterns expected with the sequential regimen. (see DOSAGE AND ADMINISTRATION). Upon sequential administration of Dom-MEDROXYPROGESTERONE to women with adequate levels of estrogen (endogenous or exogenous), withdrawal bleeding usually occurs within 7 days after stopping Dom-MEDROXYPROGESTERONE. Bleeding that occurs during Dom-MEDROXYPROGESTERONE administration indicates a need for a longer duration, or a higher dose of Dom-MEDROXYPROGESTERONE (see DOSAGE AND ADMINISTRATION). Patients who develop visual disturbances, classical migraine, transient aphasia, paralysis, or loss of consciousness should discontinue medication. If feasible, estrogens with or without progestins should be discontinued at least 4 weeks before major surgery which may be associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. Women using hormonal replacement therapy (HRT) sometimes experience increased blood pressure. Blood pressure should be monitored with HRT use. Elevation of blood pressure in previously normotensive or hypertensive patients should be investigated and HRT therapy may have to be discontinued. Progestins may cause fluid retention. Therefore, particular caution is indicated in cardiac or renal dysfunction, epilepsy or asthma. Treatment should be stopped if there is an increase in epileptic seizures. If, in any of the above mentioned conditions, a worsening of the underlying disease is diagnosed or suspected during treatment, the benefits and risks of treatment should be reassessed based on the individual case. Because the prolonged use of estrogens with or without progestins influences the metabolism of calcium and phosphorus, estrogens should be used with caution in patients with metabolic and malignant bone diseases associated with hypercalcemia and in patients with renal insufficiency. A worsening of glucose tolerance and lipid metabolism has been observed in a significant percentage of peri-and post-menopausal patients. A decrease in glucose tolerance has been observed in some patients on progestins. The mechanism of this is obscure. Therefore, diabetic patients or those with a predisposition to diabetes should be observed closely to detect any alterations in carbohydrate or lipid metabolism, especially in triglyceride levels. Women with familial hypertriglyceridemia or porphyria need special surveillance. Lipid lowering measures are recommended additionally, before treatment is started. Liver function tests should be done periodically in subjects who are suspected of having hepatic disease. For information on endocrine and liver function tests, see the section under Laboratory Tests. Patients with a history of mental depression should be carefully monitored while receiving therapy with Dom-MEDROXYPROGESTERONE. Some patients may complain of premenstrual like depression while on Dom-MEDROXYPROGESTERONE. The age of the patient constitutes no absolute limiting factor although treatment with progestins may mask the onset of the climacteric.

DRUG INTERACTIONS

Rifampin can increase the metabolism of exogenously administered progestational agents. The extent to which rifampin may alter the metabolism of Dom-MEDROXYPROGESTERONE remains to be determined; the possibility of an interaction should be considered. Preparations inducing liver enzymes (e.g., barbiturates, hydantoins, carbamazepine, meprobamates, phenylbutazone or rifampicin) may interfere with the activity of orally administered progestins. Clinical pharmacokinetic studies have not demonstrated any consistent effect of antibiotics (other than rifampin) on plasma concentrations of synthetic steroids. Concomitant administration of aminoglutethimide with medroxyprogestrone acetate (MPA) may significantly reduce the bioavailability of MPA. A small study in patients with advanced breast cancer studied the influence of MPA given orally in high doses (500 mg twice daily) on the pharmacokinetics of antipyrine (1000 mg dose; N=9), digitoxin (dose unspecified; N=3), and warfarin (0.30 mg/kg dose; N=4). The half-life of antipyrine was decreased, while that of warfarin was increased when MPA was taken concomitantly. Small changes in clearance were noted for antipyrine, digitoxin and warfarin. In the case of warfarin, the minor decrease in clearance that was observed may be clinically important. Coagulation tests should be appropriately monitored. It was found that some herbal products (e.g. St. John's Wort) which are available as OTC products might effect metabolism, and therefore, efficacy and safety of estrogen/ progestin products. Red clover isoflavones have affinity for estradiol-alpha and -beta receptors and may act as both agonists and antagonists. Red clover may enhance the estrogenic effects of hormonal contraceptives and may have antiprogestin effects. Physicians and other health care providers should be aware of other non-prescription products concomitantly used by the patient, including herbal and natural products obtained from the widely spread health stores.

Laboratory Tests

The results of certain endocrine and liver function tests may be affected by progestin-containing products: Reduced response to the METOPIRONE test; Impaired glucose tolerance Reduced serum folate concentration; Change in lipoprotein levels Gonadotropin levels Plasma progesterone levels Urinary progesterone levels Plasma testosterone levels (in the male) Plasma estrogen levels (in the female) Plasma cortisol levels The results of the above laboratory tests should not be considered reliable unless therapy has been discontinued for two to four weeks. The pathologist should be informed that the patient is receiving HRT therapy when relevant specimens are submitted.

SYMPTOMS AND TREATMENT OF OVERDOSAGE

Symptoms

Progestin (norethindrone acetate) over dosage has been characterized by depressed mood, tiredness, acne and hirsutism. In females, an overdose could cause a period of amenorrhea of a variable length and could be followed by irregular menses for several cycles. There have been no overdoses reported in males. If overdose were to occur in males however, there would probably be no symptoms. Doses as high as 1000 mg have been taken for the treatment of endometrial carcinoma without any adverse reaction.

Treatment

There is no specific treatment for overdose with medroxyprogesterone.

DOSAGE AND ADMINISTRATION

Hormone Replacement Therapy: Progestin Challenge Test: Subsequent to the diagnosis of menopause, the progestin challenge test is recommended for amenorrheic women with an intact uterus. Dom- MEDROXYPROGESTERONE 10 mg daily should be administered for 10 days. A negative test is identified by the absence of withdrawal bleeding, and implies the absence of endometrial stimulation due to insufficient estrogen secretion. In these women, hormone replacement therapy consisting of estrogen therapy, and concurrent Dom- MEDROXYPROGESTERONE, should be considered. A positive test is indicated by the presence of withdrawal bleeding which occurs within 7 days after stopping Dom-MEDROXYPROGESTERONE treatment. Withdrawal bleeding implies the presence of sufficient endogenous estrogen to stimulate the endometrium. Dom- MEDROXYPROGESTERONE therapy should be administered, as above, until withdrawal bleeding no longer occurs. This cessation of withdrawal bleeding indicates the absence of endometrial stimulation due to a decline in estrogen secretion. In these women, hormone replacement therapy consisting of estrogen therapy, and concurrent Dom- MEDROXYPROGESTERONE, should be considered.

Sequential Therapy:

In women with an intact uterus receiving estrogen replacement therapy, Dom- MEDROXYPROGESTERONE tablets may be given in a dosage of 5-10 mg daily for 12-14 days. The recommended starting dose for Dom-MEDROXYPROGESTERONE should be 10 mg/day, administered for 12-14 days. A dose of 5 mg/day Dom-MEDROXYPROGESTERONE for 12-14 days may be appropriate for some women. Note: The lowest dose of Dom-MEDROXYPROGESTERONE required to protect the endometrium from estrogenic-hyperstimulation should be used. A good indicator is the lowest dose of Dom-MEDROXYPROGESTERONE that will consistently result in withdrawal bleeding within 7 days after stopping Dom-MEDROXYPROGESTERONE treatment. Bleeding that occurs during the Dom-MEDROXYPROGESTERONE treatment indicates a need for a longer duration, or higher dose of Dom-MEDROXYPROGESTERONE. Functional Menstrual Disorders: Secondary Amenorrhea: After ruling out pregnancy, Dom-MEDROXYPROGESTERONE (medroxyprogesterone acetate) can be used in doses ranging from 5-10 mg daily depending on the amount of endometrial stimulation required. The dose should be given daily for 12-14 days every month. Note: In patients with an underdeveloped endometria, standard estrogen therapy should be administered in combination with Dom-MEDROXYPROGESTERONE. Withdrawal bleeding normally occurs within 3 days of commencement of combination therapy of estrogen and Dom- MEDROXYPROGESTERONE. Dysfunctional Uterine Bleeding: Dom-MEDROXYPROGESTERONE can be administered in doses ranging from 5-10 mg for 10-14 days commencing on the assumed or calculated 12-16th day of the cycle. This regimen should be repeated for 2 subsequent cycles or longer if necessary. When bleeding is caused by a lack of both ovarian hormones, as evidenced by an under-developed proliferative endometrium, estrogens should be given in combination with medroxyprogesterone acetate. If this controls the bleeding satisfactorily, treatment should be maintained for at least two subsequent cycles. If dysfunctional uterine bleeding is not controlled by hormone therapy, appropriate diagnostic measures should be undertaken to rule out uterine pathology. Endometrial Cancer: 200 - 400 mg/day is the usual dose. It is suggested that if neither subjective nor objective improvement is noted within 2 to 3 months, therapy should be discontinued. Where improvement is noted and the disease process appears to be stabilized, it may be possible to maintain this improvement with a 200 mg/day dose. Dom-MEDROXYPROGESTERONE should only be used as adjunctive and palliative treatment in advanced, inoperable cases including those with recurrent metastatic disease, and is not recommended as primary therapy. Note: Response to hormonal therapy for endometrial or breast cancer may not be evident until 8 to 10 weeks of therapy. Rapid progression of disease at any time during therapy should result in termination of treatment with Dom-MEDROXYPROGESTERONE. Breast Cancer: The recommended dose is 400 mg daily, given in divided doses. The patient should be continued on therapy as long as she is responding to treatment. Although doses of up to 2400 mg daily have been reported, controlled studies using 800 mg daily did not demonstrate any appreciable increase in response rates compared to the 400 mg daily dose. Dom-MEDROXYPROGESTERONE should only be used as adjunctive and palliative treatment in advanced, inoperable cases including those with recurrent metastatic disease, and is not recommended as primary therapy. Note: Response to hormonal therapy for endometrial or breast cancer may not be evident until 8 to 10 weeks of therapy. Rapid progression of disease at any time during therapy should result in termination of treatment with Dom-MEDROXYPROGESTERONE.

PHARMACEUTICAL INFORMATION

DRUG SUBSTANCE

Proper Name:

Medroxyprogesterone Acetate

Chemical Name:

17-Hydroxy-6 a-methylpregn-4-ene-3,20-dione

acetate.

Structural Formula:

Molecular Formula: C24H34O4 Molecular Weight: 386.53

Description:

White to off-white odorless crystalline powder, stable in air, with a melting point of 205/C. It is freely soluble in chloroform, soluble in acetone and dioxane, sparingly soluble in ethanol and methanol, slightly soluble in ether and insoluble in water.

Non-medicinal Ingredients:

Dom-MEDROXYPROGESTERONE tablets contain: calcium stearate, lactose, light mineral oil, sorbic acid, starch (corn), sucrose, talc. Colouring Agents: 2.5 mg tablets: FD & C Yellow #6 Lake; 5 mg tablets FD & C Blue #2 Lake.

Stability and Storage Recommendations:

Bottles of medroxyprogesterone acetate tablets should be stored in tight, light-resistant containers at a temperature between 15/-30/C.

AVAILABILITY OF DOSAGE FORMS

Dom-MEDROXYPROGESTERONE (medroxyprogesterone acetate) 2.5 mg tablets are peach coloured, round, scored and engraved with 'P2.5' on one side and contain 2.5 mg of medroxyprogesterone acetate. They are available in bottles of 100 and 500. Dom-MEDROXYPROGESTERONE 5 mg tablets are blue, round, engraved with 'P5' and contain 5 mg of medroxyprogesterone acetate. They are available in bottles of 100 and 500. Dom-MEDROXYPROGESTERONE 10 mg tablets are white, round, engraved with 'P10' and contain 10 mg of medroxyprogesterone acetate. They are available in bottles of 100 and 500.