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Provera (medroxyprogesterone acetate) tablets for oral use

Summary about Provera

Provera tablets contain medroxyprogesterone acetate, which is a derivative of progesterone, a female hormone that helps regulate ovulation (the release of an egg from an ovary) and menstrual periods.

 

 

Provera is used to treat conditions such as absent or irregular menstrual periods, or abnormal uterine bleeding. This medicine is also used to decrease the risk of endometrial hyperplasia (a condition that may lead to uterine cancer) while taking estrogens. Provera is also used to prevent overgrowth in the lining of the uterus in postmenopausal women who are receiving estrogen hormone replacement therapy.

 

 

Provera (medroxyprogesterone acetate) tablets

Active Ingredient

medroxyprogesterone acetate

Administration Route

Oral

Alcohol Warning

Although there are no known interactions, high amount of alcohol should be avoided during Provera administration.

Available Strength

2.5mg, 5mg and 10mg Tablets

Breastfeeding Warning

Use is not recommended.

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

Pharmacodynamics

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

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

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Form

Tablets for oral use

Dose Schedule

Dosing Adults:

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

G03DA — Pregnen derivatives

Drug Unit

mg

Food Warning

Bioavailability of the oral tablet is increased when taken with food; half-life is unchanged. Administer without regard to food.

Included In
Health Insurance Plan

100% of Medicare Part D and Medicare Advantage plans cover this drug.

Interacting Drugs

If a woman on hormonal contraceptives takes a drug or herbal product that induces enzymes, including

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

Yes

Is Proprietary

Yes

Label Details

https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011839s071lbl.pdf

Legal Status

Legal.

Is not subject to the Controlled Substances Act.

Manufacturer

Pfizer

Maximum Intake

10 mg for 10 days.

Mechanism of Action

Medroxyprogesterone acetate (MPA) inhibits the production of gonadotropin, preventing follicular maturation and ovulation, which is responsible for it’s ability to prevent pregnancy. This action also thins the endometrium MPA reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium. MPA can also induce p53 dependant apoptosis in certain cancer cell lines, and inhibit GABA-A receptors.

Non Proprietary Name

Medroxyprogesterone

Overdosage

In animals Provera has been shown to be capable of exerting an adreno-corticoid effect, but this has not been reported in the human, following usual dosages. The oral administration of Provera at a rate of 100 mg per day has been shown to have no effect on adrenal function.

Pregnancy Category

Use is contraindicated.

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

Pregnancy Warning

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

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

https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011839s071lbl.pdf

Prescription Status

Prescription only

Proprietary Name

Provera

Related Drugs

Progesterone, Hydroxyprogesterone, Gestonorone

RxCUI

1182477

Warning

Estrogens with progestins should not be used for the prevention of cardiovascular disease or dementia. The Women’s Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis (DVT) 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 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

 

References:

Drugs.com [Internet]. Medroxyprogesterone Information from Drugs.com; c1996-2019 [Updated: 10 March 2019, Cited: 28 November 2019]. Available from: https://www.drugs.com/medroxyprogesterone.html

Drugbank.ca [Internet Medroxyprogesterone Information from Drugbank.ca; c1996-2019 [Updated: 28 November 2019, Cited: 28 November 2019]. Available from: https://www.drugbank.ca/drugs/DB00603

Uptodate.com [Internet]. Cholecalciferol Information from Uptodate.com; c1996-2019 [Updated: 21 November 2019, Cited: 28 November 2019]. Available from: https://www.uptodate.com/contents/medroxyprogesterone-acetate-drug-information?search=medroxyprogesterone&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#F191983

Cundy T, Farquhar CM, Cornish J, Reid IR. Short-term effects of high dose oral medroxyprogesterone acetate on bone density in premenopausal women. J Clin Endocrinol Metab. 1996 Mar;81(3):1014-7

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