indication

Used as a contraceptive and to treat secondary amenorrhea, abnormal uterine bleeding, pain associated with endometriosis, endometrial and renal cell carcinomas, paraphilia in males, GnRH-dependent forms of precocious puberty, as well as to prevent endometrial changes associated with estrogens.

pharmacology

Medroxyprogesterone is a synthetic progestin more potent than progesterone.

mechanism of action

Progestins diffuse freely into target cells in the female reproductive tract, mammary gland, hypothalamus, and the pituitary and bind to the progesterone receptor. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge.

toxicity

Side effects include loss of bone mineral density, BMD changes in adult women, bleeding irregularities, cancer risks, and thromboembolic disorders.

biotransformation

Hepatic

absorption

Rapidly absorbed from GI tract

half life

50 days

route of elimination

Following oral dosing, MPA is extensively metabolized in the liver via hydroxylation, with subsequent conjugation and elimination in the urine. Most MPA metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates.

drug interactions

Acenocoumarol: Medroxyprogesterone may increase the anticoagulant effect of acenocoumarol.

Amobarbital: The enzyme inducer, amobarbital, decreases the effect of the hormone agent, medroxyprogesterone.

Anisindione: Medroxyprogesterone may increase the anticoagulant effect of anisindione.

Aprobarbital: The enzyme inducer, aprobarbital, decreases the effect of the hormone agent, medroxyprogesterone.

Artemether: Artemether may decrease the effectiveness of medroxyprogesterone by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.

Bexarotene: Bexarotene may decrease the serum concentration of Contraceptives (Progestins). Since bexarotene is teratogenic and can lower serum concentrations of medroxyprogesterone, it is advised that women of childbearing potential use two forms of contraception (including at least one non-hormonal form).

Bosentan: Bosentan may decrease the contraceptive effect of medroxyprogesterone. Hormonal contraception should not be relied on alone during concomitant therapy with bosentan.

Butabarbital: The enzyme inducer, butabarbital, decreases the effect of the hormone agent, medroxyprogesterone.

Butalbital: The enzyme inducer, butalbital, decreases the effect of the hormone agent, medroxyprogesterone.

Butethal: The enzyme inducer, butethal, decreases the effect of the hormone agent, medroxyprogesterone.

Colesevelam: Bile Acid Sequestrants may decrease the serum concentration of Contraceptives (Progestins). Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Consider alternatives in order to avoid this combination when possible, due to the risk for impaired contraceptive effectiveness.

Dicumarol: Medroxyprogesterone may increase the anticoagulant effect of dicumarol.

Ethotoin: The enzyme inducer, ethotoin, decreases the effect of the hormone agent, medroxyprogesterone.

Fosphenytoin: The enzyme inducer, fosphenytoin, may decrease the effect of the hormone, medroxyprogesterone.

Griseofulvin: The enzyme inducer, griseofulvin, may decrease the effect of the hormone, medroxyprogesterone.

Heptabarbital: The enzyme inducer, heptabarbital, decreases the effect of the hormone agent, medroxyprogesterone.

Hexobarbital: The enzyme inducer, hexobarbital, decreases the effect of the hormone agent, medroxyprogesterone.

Mephenytoin: The enzyme inducer, mephenytoin, decreases the effect of the hormone agent, medroxyprogesterone.

Methohexital: The enzyme inducer, methohexital, decreases the effect of the hormone agent, medroxyprogesterone.

Methylphenobarbital: The enzyme inducer, methylphenobarbital, decreases the effect of the hormone agent, medroxyprogesterone.

Pentobarbital: The enzyme inducer, pentobarbital, decreases the effect of the hormone agent, medroxyprogesterone.

Phenobarbital: The enzyme inducer, phenobarbital, may decrease the effect of the hormone, medroxyprogesterone.

Phenytoin: The enzyme inducer, phenytoin, may decrease the effect of medroxyprogesterone.

Primidone: The enzyme inducer, primidone, may decrease the effect of the hormone, medroxyprogesterone.

Secobarbital: The enzyme inducer, secobarbital, decreases the effect of the hormone agent, medroxyprogesterone.

Talbutal: The enzyme inducer, talbutal, decreases the effect of the hormone agent, medroxyprogesterone.

Thiopental: Thiopental may decrease the effect of Medroxyprogesterone. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Warfarin: Medroxyprogesterone may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if medroxyprogesterone is initiated, discontinued or dose changed.