Provera (medroxyprogesterone acetate) tablets for oral use

Provera (medroxyprogesterone acetate) tablets

Active Ingredient

Administration Route

Alcohol Warning

Available Strength

Breastfeeding Warning

Excreted into human milk: Yes

Comments:
-The effects in the nursing infant are unknown.

Although this drug is detectable in the maternal milk, its composition, quality, and amount are not adversely affected. Neonates and infants exposed to this drug from breast milk have been studied for developmental and behavioral effects through puberty, and no adverse effects have been noted.

Clinical Pharmacology

Medroxyprogesterone acetate (MPA) inhibits gonadotropin production, reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium, and induces p53 dependant apoptosis in cancer cell lines. MPA oral tablets have a half life of 40-60 hours and other formulations can have half lives that are considerably longer, so the duration of action is long.  Long term use of MPA is associated with a reduction in bone density and patients who taking MPA during adolescence may have lower peak bone mass than untreated patients, which can also increase the risk of osteoporosis and fractures in the future

Pharmacokinetics

Onset of action: Time to ovulation (after last injection): 10 months (range: 6 to 12 months)

Absorption: Oral: Rapid; IM: Slow

Protein binding: 86% to 90% primarily to albumin; does not bind to sex hormone-binding globulin

Metabolism: Extensively hepatic via hydroxylation and conjugation; forms metabolites

Bioavailability: 0.6% to 10%

Half-life elimination: Oral: 12 to 17 hours; IM (Depo-Provera Contraceptive): ~50 days; SubQ: ~43 days

Time to peak: Oral: 2 to 4 hours; IM (Depo-Provera Contraceptive): ~3 weeks; SubQ: ~1 week

Excretion: Urine

Cost

• 5 mg (per each): $3.01
• 5 mg (per each): $4.52
• 10 mg (per each): $5.89

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Dosage Form

Dose Schedule

Abnormal uterine bleeding: Oral: 5 or 10 mg daily for 5 to 10 days starting on day 16 or 21 of menstrual cycle. A suggested dose of 10 mg daily for 10 days starting on day 16 of the cycle induces optimum secretory transformation of the endometrium when adequately primed with endogenous or exogenous estrogen. Withdrawal bleeding may be expected within 3 to 7 days after discontinuing medroxyprogesterone. Planned menstrual cycling may benefit patients with a history of recurrent episodes of abnormal uterine bleeding.

Abnormal uterine bleeding, acute (off-label): Oral: 20 mg three times a day for 7 days

Amenorrhea, secondary: Oral: 5 or 10 mg daily for 5 to 10 days. Therapy may be started at any time. A dose of 10 mg daily for 10 days induces optimum secretory transformation of the endometrium when adequately primed with endogenous or exogenous estrogen. Withdrawal bleeding may be expected within 3 to 7 days after discontinuing

Endometrial hyperplasia prevention in postmenopausal persons receiving daily conjugated estrogen (alternative agent): Oral: 5 or 10 mg daily for 12 to 14 consecutive days each month, starting on day 1 or day 16 of the cycle. When treating postmenopausal persons, use for the shortest duration possible at the lowest effective dose consistent with treatment goals. Reevaluate patients as clinically appropriate to determine if treatment is still necessary. Treatment is indicated for postmenopausal persons with a uterus to decrease the risk of endometrial cancer; persons who have had a hysterectomy generally do not need a progestin. Due to safety considerations, when a progesterone is needed, use of micronized progesterone is preferred over medroxyprogesterone acetate.

Endometrial hyperplasia, treatment (off-label use):

Atypical endometrial hyperplasia or endometrial intraepithelial neoplasia: Oral: 10 to 20 mg once daily (continuous dosing) or 10 mg to 20 mg once daily (cyclic dosing) for 12 to 14 days per month.

Non-atypical hyperplasia: Oral: 10 mg once daily (continuous dosing) (Orbo 2014) or 10 mg once daily (cyclic dosing) for 10 to 12 days per cycle.

Pediatric doses:

Abnormal uterine bleeding: Adolescents: Oral: 5 to 10 mg for 5 to 10 days starting on day 16 or day 21 of menstrual cycle

Amenorrhea: Adolescents: Oral: 5 to 10 mg/day for 5 to 10 days

Drug Class

Drug Unit

Food Warning

Included In
Health Insurance Plan

Interacting Drugs

CYP3A4, that metabolize contraceptive hormones, counsel her to use additional contraception or a different

method of contraception. Drugs or herbal products that induce such enzymes may decrease the plasma

concentrations of contraceptive hormones, and may decrease the effectiveness of hormonal contraceptives.

Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include:

• barbiturates
• bosentan
• carbamazepine
• felbamate
• griseofulvin
• oxcarbazepine
• phenytoin
• rifampin
• St. John’s wort

HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase ordecrease) in the plasma levels of progestin have been noted in some cases of co-administration of HIV protease inhibitors. Significant changes (increase or decrease) in the plasma levels of the progestin have been noted in some cases of co-administration with non-nucleoside reverse transcriptase inhibitors. Antibiotics: There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids. Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

Is Available Generically

Is Proprietary

Label Details

Legal Status

Is not subject to the Controlled Substances Act.

Manufacturer

Maximum Intake

Mechanism of Action

Non Proprietary Name

Overdosage

Pregnancy Category

AU TGA pregnancy category: D
US FDA pregnancy category: Category X

Pregnancy Warning

US FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

Studies in animals have shown that progestogens, including this drug, may have an adverse effect on the developing fetus, including teratogenicity and fetotoxicity. Other animal studies have shown that high doses of progestogens can cause masculinization of the female fetus.

There may be increased risks for hypospadias, clitoral enlargement and labial fusion in children of mothers exposed to medroxyprogesterone (MPA) tablets during the first trimester of pregnancy. However, a clear association between these conditions with use of MPA tablets has not been established.

A significant increase in polysyndactyly and chromosomal anomalies was observed among infants of injection users, being most pronounced in women under 30 years of age; however, a causal association unlikely.

Children and neonates exposed to this drug in-utero and followed to adolescence showed no evidence of any adverse effects on their health including their physical, intellectual, sexual or social development. There are no controlled data in human pregnancy.

Prescribing Info

Prescription Status

Proprietary Name

Related Drugs

RxCUI

Warning

The Women’s Health Initiative Memory Study (WHIMS), a substudy of the WHI study, reported 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.

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. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman