Usual Adult Dose for Endometriosis

104 mg subcutaneously once every 3 months (12 to 14 weeks)
Duration of therapy: No longer than two years

Comments:

• For sexually active women having regular menses, the first injection should only be given within the first 5 days of a normal menstrual period or at 6 weeks postpartum, if the patient is breast feeding.
• If the period between injections is more than 14 weeks, pregnancy should be ruled out prior to administering.
• The impact of long-term use of the subcutaneous injection on bone mineral density (BMD) should be considered.
• If symptoms return after discontinuation of treatment, BMD should be evaluated prior to retreatment.

Use: Management of endometriosis-associated pain

Usual Adult Dose for Endometrial Hyperplasia - Prophylaxis

Oral tablets:
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 16 th day of the cycle

Comments:

• Postmenopausal woman with a uterus taking estrogens should also initiate progestin therapy to reduce the risk of endometrial cancer.
• Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration. Starting dose should be the lowest.
• Periodically re-evaluation (e.g., 3 to 6 month intervals) to determine if treatment is still necessary is recommended.
• In women with uterus, endometrial sampling should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.

Use: Prevention of endometrial hyperplasia in non-hysterectomized postmenopausal women who are receiving daily oral conjugated estrogens 0.625 mg tablets

Usual Adult Dose for Contraception

Intramuscular injection:

• 150 mg once every 3 months (13 weeks) in the gluteal or deltoid muscle

Subcutaneous injection:

• 104 mg once every 3 months (12 to 14 weeks) into the anterior thigh or abdomen

First injection:

• Ensure the patient is not pregnant at the time of the first injection.
• The first injection should be given only during the first 5 days of a normal menstrual period, within the first 5-days postpartum if not breast-feeding, and at the sixth postpartum week if breast-feeding.

Switching from other methods of contraception:

• IM injection: The first injection should be given on the day after the last active contraception tablet, or at the latest, on the day following the final inactive contraception tablet.
• SC injection: The first injection should be given within 7 days after the last day taking the last active contraceptive tablet, or after removing the patch or ring. Similarly, contraceptive coverage will be maintained when switching from 150 mg IM injection, provided the next injection is given within the prescribed dosing period for the IM injection.

Comments:

• If the time interval between injections is greater than 13 weeks, pregnancy should be excluded before administering the drug.
• The efficacy of the IM suspension depends on adherence to the dosage schedule of administration.
• The risk/benefit of loss of bone mineral density (BMD) in women of all ages and the impact on peak bone mass in adolescents should be considered, along with the decrease in BMD that occurs during pregnancy and/or lactation, should be assessed when using this IM injection long-term.

Use: Prevention of pregnancy in women of child bearing potential

Usual Adult Dose for Abnormal Uterine Bleeding

Oral tablets:

• 5 or 10 mg daily for 5 to 10 days, beginning on the 16 th or 21 st day of the menstrual cycle

• Dose to produce an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen: 10 mg daily for 10 days beginning on the 16 th day of the cycle

Comments:

• Withdrawal bleeding usually occurs within 3 to 7 days after discontinuing therapy with the oral tablets.
• Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with the oral tablets.

Use: Abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as fibroids or uterine cancer

Usual Adult Dose for Amenorrhea

Oral tablets:

• 5 or 10 mg daily for 5 to 10 days

Dose for inducing an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen:

• 10 mg daily for 10 day

Comments:

• Therapy may be started at any time.
• Withdrawal bleeding usually occurs within 3 to 7 days after discontinuing therapy with this drug.

Use: Treatment of secondary amenorrhea due to hormonal imbalance in the absence of organic pathology, such as fibroids or uterine cancer

Usual Adult Dose for Renal Cell Carcinoma

Initial dose: 400 to 1000 mg IM once a week
Maintenance dose: Reduce dose to 400 mg IM once a month to maintain improvement

Comments:

• This drug is not recommended as primary therapy.
• Greater sensitivity in the geriatric population cannot be ruled out.
• The frequency of administration may be reduced if improvement or stabilization occurs, usually within a few weeks to months.

Use: Adjunctive therapy and palliative treatment in advanced inoperable cases including those with recurrent or metastatic endometrial or renal carcinoma

Usual Adult Dose for Endometrial Carcinoma

Initial dose: 400 to 1000 mg IM once a week
Maintenance dose: Reduce dose to 400 mg IM once a month to maintain improvement

Comments:

• This drug is not recommended as primary therapy.
• Greater sensitivity in the geriatric population cannot be ruled out.
• The frequency of administration may be reduced if improvement or stabilization occurs, usually within a few weeks to months.

Use: Adjunctive therapy and palliative treatment in advanced inoperable cases including those with recurrent or metastatic endometrial or renal carcinoma

Usual Pediatric Dose for Contraception

Postmenarchal children and adolescents:
Intramuscular injection:

• 150 mg once every 3 months (13 weeks) in the gluteal or deltoid muscle

Subcutaneous injection:

• 104 mg once every 3 months (12 to 14 weeks) into the anterior thigh or abdomen

First injection:

• Ensure the patient is not pregnant at the time of the first injection.
• The first injection should be given only during the first 5 days of a normal menstrual period, within the first 5-days postpartum if not breast-feeding, and at the sixth postpartum week if breast-feeding.

Switching from other methods of contraception:

• IM injection: The first injection should be given on the day after the last active contraception tablet, or at the latest, on the day following the final inactive contraception tablet.
• SC injection: The first injection should be given within 7 days after the last day taking the last active contraceptive tablet, or after removing the patch or ring. Similarly, contraceptive coverage will be maintained when switching from 150 mg IM injection, provided the next injection is given within the prescribed dosing period for the IM injection.

Comments:

• If the time interval between injections is greater than 13 weeks, pregnancy should be excluded before administering the drug.
• The efficacy of the IM suspension depends on adherence to the dosage schedule of administration.
• The risk/benefit of loss of bone mineral density (BMD) in women of all ages and the impact on peak bone mass in adolescents should be considered, along with the decrease in BMD that occurs during pregnancy and/or lactation, should be assessed when using the injection long-term.

Use: Prevention of pregnancy in women of child bearing potential

Renal Dose Adjustments

No studies have been performed.

Liver Dose Adjustments

Contraindicated in liver impairment or disease.

Precautions

US BOXED WARNINGS:
CARDIOVASCULAR DISORDERS AND PROBABLE DEMENTIA: Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. The Women's Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625] mg combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo. The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

BREAST CANCER: The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins. Progestins with estrogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

LOSS OF BONE MINERAL DENSITY: Women using this drug may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible. It is unknown if use of MPA Injectable Suspension, USP during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk for osteoporotic fracture in later life. This drug should not be used as a long-term birth control method (i.e., longer than 2 years) unless other birth control methods are considered inadequate. Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT MPA (a progestin hormone)?

• Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes, or dementia (decline in brain function).
• Using estrogens with progestins may increase your chance of getting heart attacks, strokes, breast cancer, and blood clots.
• Using estrogens with progestins may increase your chance of getting dementia, based on a study of women age 65 years or older.
• You and your healthcare provider should talk regularly about whether you still need treatment with MPA tablets.

Oral tablets: Safety and efficacy have not been established in patients younger than 18 years.

Subcutaneous and intramuscular injection: Not indicated before menarche.

Intramuscular injection has not been studied in post-menopausal women and is not indicated in this population.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
Injection:

• Shake vigorously before use to create a uniform suspension.
• Rotate the sites with every injection.
• Dosage does not need to be adjusted for body weight.
• Do not use as a long-term birth control method (i.e. longer than 2 years) unless other birth control methods are considered inadequate.
• To avoid an inadvertent subcutaneous injection, body habitus should be assessed prior to each injection to determine if a longer needle is necessary, particularly for gluteal IM injection.
• The lowest effective doses and the shortest duration of therapy is recommended.

General:

• A complete personal and family medical history should be taken, before initiating or reinstituting therapy with this drug.
• Annual history and physical examinations (e.g., blood pressure, breasts, abdomen and pelvic organs, including cervical cytology and relevant laboratory tests) in patients using this drug is recommended.

Monitoring:

• Musculoskeletal: Bone mineral density
• Cardiovascular: Blood pressure.
• Carbohydrate metabolism: Monitor diabetic patients carefully

Patient advice:

• Patients should report exposure to this drug in early pregnancy.
• Patients taking hormonal contraceptive should have a yearly visit with their healthcare provider for a blood pressure check and for other indicated healthcare.
• The IM injection does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
• At the beginning of the treatment, menstrual cycle may be disrupted causing irregular and unpredictable bleeding or spotting that usually decreases as treatment continues.
• Use a back-up method or alternative method of contraception when enzyme inducers are used with this drug.

Frequently asked questions

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