Medroxyprogesterone

Medroxyprogesterone is a prescription medication used for the treatment of metastatic endometrial carcinoma, metastatic renal carcinoma, secondary amenorrhea, abnormal uterine bleeding, and the prevention of endometrial hyperplasia, endometriosis-associated pain, and pregnancy in females of reproductive age.

• Medroxyprogesterone is available under the following different brand names: Depo-Provera, Depo-SubQ Provera 104, MPA, Provera

Adult dosage

Tablet

• 2.5mg
• 5mg
• 10mg

Injectable IM suspension

• 150mg/mL
• 400mg/mL

Prefilled syringe suspension

• 104mg/0.65mL

Metastatic Endometrial Carcinoma

Adult dosage

Depo-Provera only

• 400-1000 mg IM once weekly initially

Metastatic Renal Carcinoma

Adult dosage

Depo-Provera only

• 400-1000 mg IM once weekly  initially

Secondary Amenorrhea

Adult dosage

Provera only

• 5 or 10 mg orally once daily  for 5-10 days; therapy may start at any time

Abnormal Uterine Bleeding

Provera only

• 5 or 10 mg orally once daily for 5-10 days; begin day 16 or 21 of the menstrual cycle

Endometrial Hyperplasia Reduction

Provera only

• 5 or 10 mg orally once daily for 12-14 consecutive days per month, in postmenopausal women receiving daily 0.625 mg conjugated estrogens, either beginning on the 1st day or 16th day of the cycle; start at the lowest dose

Contraception

Adult and pediatric dosage

Depo-Provera SubQ 104 only

• 104 mg SC every 12-14 weeks

Endometriosis-Associated Pain

Adult and pediatric dosage

Depo-Provera SubQ 104 only

• 104 mg SC every 12-14 weeks

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Medroxyprogesterone include:

• spotting or breakthrough bleeding,
• changes in the menstrual periods,
• vaginal itching or discharge,
• breast tenderness or discharge,
• headache,
• dizziness,
• feeling nervous or depressed,
• bruising or swelling of the veins,
• bloating,
• fluid retention,
• mood changes,
• sleep problems (insomnia),
• itching,
• rash,
• acne,
• hair growth,
• loss of scalp hair,
• stomach discomfort,
• bloating,
• nausea,
• weight gain, and
• vision changes or difficulty wearing contact lenses.

Serious side effects of Medroxyprogesterone include:

• vaginal bleeding (if already gone through menopause),
• lightheadedness,
• breast lump,
• depression,
• sleep problems (insomnia),
• dizziness,
• mood changes,
• headache,
• fever,
• yellowing of the skin or eyes (jaundice),
• swelling in your hands, ankles, or feet,
• chest pain or pressure,
• pain spreading to the jaw or shoulder,
• nausea,
• sweating,
• sudden numbness or weakness,
• sudden severe headache,
• slurred speech,
• vision problems,
• problems with the balance,
• sudden cough,
• wheezing,
• rapid breathing,
• coughing up blood, and
• pain in the leg (or both) with swelling, warmth, and redness.

Rare side effects of Medroxyprogesterone include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Medroxyprogesterone has severe interactions with no other drugs.
• Medroxyprogesterone has serious interactions with the following drugs:
  • abametapir
  • acitretin
  • apalutamide
  • brigatinib
  • darunavir
  • fexinidazole
  • idelalisib
  • ivosidenib
  • lesinurad
  • lorlatinib
  • mifepristone
  • nelfinavir
  • ribociclib
  • ritonavir
  • saquinavir
  • sugammadex sodium
  • tucatinib
  • voriconazole
  • voxelotor
• Medroxyprogesterone has moderate interactions with at least 66 other drugs.
• Medroxyprogesterone has minor interactions with the following drugs:
  • maitake
  • taurine

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• 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 (e.g., stroke, MI), or a history of these conditions
• Known anaphylactic reaction or angioedema
• Known liver impairment or disease
• Known or suspected pregnancy

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Medroxyprogesterone?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Medroxyprogesterone?”

Cautions

• Use caution in patients with asthma, diabetes mellitus, history of depression, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas
• Therapy reduces serum estrogen levels and is associated with significant loss of bone mineral density (BMD); BMD should be evaluated when a woman needs to continue to receive therapy long-term; in adolescents, interpretation of BMD results should take into account patient age and skeletal maturity
• Prolonged use of SC or IM use may result in significant loss of bone density; long-term use is not recommended (i.e., above 2 years) as a birth control method or medical therapy for endometriosis-associated pain unless other options are considered inadequate
• In women with osteoporosis risk factors, other birth control methods or therapies for endometriosis-associated pain should be considered a risk/benefit analysis for SC use; SC can pose an additional risk in patients with risk factors for osteoporosis (e.g., metabolic bone disease, chronic alcohol and/or tobacco use, anorexia nervosa, strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids)
• Consider ectopic pregnancy if a woman receiving therapy becomes pregnant or complains of severe abdominal pain
• Provide emergency medical treatment if anaphylaxis occurs
• Not for use in children before menarche
• Inform medroxyprogesterone contraceptive does not protect against HIV infection and other sexually transmitted diseases
• Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer
• In some epidemiologic studies, use of estrogen plus progestin and estrogen-only products, in particular for 5 or more years, has been associated with increased risk of ovarian cancer; however, duration of exposure associated with increased risk is not consistent across all epidemiologic studies, and some report no association
• Depression and other mood disorders have been reported; discontinue if it occurs
• Most women experienced changes in menstrual bleeding patterns, such as amenorrhea, irregular unpredictable spotting or bleeding, prolonged spotting or bleeding, or heavy bleeding; in cases of unexpected abnormal vaginal bleeding, adequate diagnostic measures are indicated
• Monitor blood pressure at regular intervals with estrogen plus progestin therapy
• In women with preexisting hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis; consider discontinuation of treatment if pancreatitis occurs
• Progestins may cause some degree of fluid retention; women with conditions influenced by fluid retention including epilepsy, migraine, asthma, cardiac or renal dysfunction, require careful observation
• Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur
• Therapy should be discontinued pending examination if there is a 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
• Patients may exhibit suppressed adrenal function; medroxyprogesterone acetate may have cortisol-like glucocorticoid activity and provide negative feedback to hypothalamus or pituitary; this may result in decreased plasma cortisol levels, decreased cortisol secretion, and low plasma ACTH levels; use of sterile aqueous suspension may, due to its cortisol-like glucocorticoid activity, also produce Cushingoid symptoms such as weight gain, edema/fluid retention, and facial swelling
• Monitor patients for hepatic dysfunction periodically and temporarily interrupt therapy if the patient develops hepatic dysfunction; do not resume use until markers of liver function return to normal
• Any multidose use of vials may lead to contamination unless a strict aseptic technique is observed
• Treatment with progestin may mask the onset of the climacteric
• Persistent injection site reactions may occur after administration due to inadvertent SC administration or release of the drug into SC space while removing the needle
• Some patients receiving progestins may exhibit a decrease in glucose tolerance; therefore, patients with diabetes may be at greater risk of hyperglycemia
• Delayed return of ovulation or fertility
  • Return to ovulation is likely to be delayed after stopping SC injection
  • The median time to ovulation was 10 months after the last injection
  • The earliest return to ovulation was 6 months after the last injection
• Cardiovascular disorders
  • An increased risk of PE, DVT, stroke, and MI has been reported with estrogen plus progestin therapy
  • Discontinue estrogen plus progestin therapy immediately if any of these events occur or be suspected,
  • Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) should be managed appropriately
• Malignant neoplasms
  • Studies of the addition of a progestin for above 10 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; possible risks associated with the use of progestins with estrogens compared to estrogen-alone regimens include an increased risk of breast cancer
  • Monitor women with a strong family history of breast cancer
  • Use may mask the onset of menopause in women treated for endometrial cancer

Pregnancy and Lactation

• There is no use for medroxyprogesterone in pregnancy and therefore should be discontinued during pregnancy
• Women who may have been exposed to medroxyprogesterone injections had little or no increased risk of birth defects in early pregnancy
• It is unknown whether medroxyprogesterone acetate can cause fetal harm when administered to a pregnant woman
• Fertility
  • Medroxyprogesterone acetate at high doses is an antifertility drug and high doses would be expected to impair fertility until discontinuing treatment
• Lactation
  • Published studies report the presence of medroxyprogesterone acetate in human milk
  • Exercise caution when medroxyprogesterone acetate is administered to a nursing woman
  • Although medroxyprogesterone acetate is detectable in the milk of mothers receiving DMPA-IM, milk composition, quality, and amount do not appear to be adversely affected
  • Effects on milk production and lactation initiation/duration remain unclear when administered before 6 weeks after delivery.