Premphase (estrogens, conjugated/medroxyprogesterone acetate)

Dosage of conjugated estrogens USP, synthetic conjugated estrogens A, and synthetic conjugated estrogens B must be individualized according to the condition being treated and the tolerance and therapeutic response of the patient. To minimize the risk of adverse effects, the lowest possible effective dosage should be used. Because of the potential increased risk of cardiovascular events, breast cancer, and venous thromboembolic events, therapy with estrogen, estrogen/progestin, or conjugated estrogens in fixed combination with bazedoxifene should be limited to the lowest effective doses and shortest duration of therapy consistent with treatment goals and risks for the individual woman. Therapy with estrogen, estrogen/progestin, or conjugated estrogens in fixed combination with bazedoxifene should be periodically reevaluated.

Estrogen therapy is administered in a continuous daily dosage regimen or, alternatively, in a cyclic regimen. When estrogens are administered cyclically, the drugs usually are given once daily for 3 weeks followed by 1 week without the drugs or once daily for 25 days followed by 5 days off, and then the respective regimen is repeated as necessary.

While estrogen therapy alone (estrogen replacement therapy, ERT) may be appropriate in women who have undergone a hysterectomy, a progestin generally is added to estrogen therapy (hormone replacement therapy, HRT) in women with an intact uterus. Addition of a progestin for 10 or more days of a cycle of estrogen or daily with estrogen in a continuous regimen reduces the incidence of endometrial hyperplasia and the attendant risk of endometrial carcinoma in women with an intact uterus. Morphologic and biochemical studies of the endometrium suggest that 10-13 days of progestin are needed to provide maximum maturation of the endometrium and to eliminate any hyperplastic changes. As an alternative to progestins, the use of bazedoxifene (an estrogen agonist-antagonist) in fixed combination with conjugated estrogens reduces the risk of endometrial hyperplasia.

When estrogen therapy is used in conjunction with a progestin or in fixed combination with bazedoxifene, the usual precautions associated with progestins or bazedoxifene should be observed. Clinicians prescribing estrogens in conjunction with progestins or conjugated estrogens in fixed combination with bazedoxifene should be aware of the risks associated with these drugs and the manufacturers' labeling should be consulted. Clinical studies indicate that addition of a progestin to estrogen replacement therapy does not interfere with the efficacy of estrogen therapy in the management of vasomotor symptoms associated with menopause, treatment of vulvar and vaginal atrophy, or prevention of osteoporosis. The choice and dosage of a progestin may be important factors in minimizing potential adverse effects.

Exposure to conjugated estrogens USP vaginal cream has been reported to weaken latex condoms. The potential for conjugated estrogens USP vaginal cream to weaken and contribute to the protective failure of latex or rubber condoms, diaphragms, or cervical caps should be considered.

Medroxyprogesterone acetate (alone or in fixed combination with estrogens (i.e., conjugated estrogens, estradiol cypionate)) is administered orally, subcutaneously, or IM. When used as a contraceptive in females, medroxyprogesterone acetate is administered subcutaneously or IM; the drug is administered subcutaneously for the management of pain associated with endometriosis. Medroxyprogesterone acetate is administered IM in the treatment of cancer or male sexual deviance+ (paraphilia). Because of the prolonged action, parenteral administration of the drug is not recommended for the treatment of secondary amenorrhea or abnormal uterine bleeding.

Medroxyprogesterone acetate injectable suspension (containing medroxyprogesterone acetate alone or in fixed combination with estradiol cypionate) must be vigorously shaken immediately before each use to ensure complete suspension of the drug(s). IM injection of medroxyprogesterone acetate alone (Depo-Provera(R) Contraceptive, Depo-Provera(R), Medroxyprogesterone Acetate Contraceptive) or in combination with estradiol cypionate (Lunelle(R) Monthly Contraceptive) should be made deep into the gluteal, deltoid, or anterior thigh muscle. Subcutaneous injection of medroxyprogesterone acetate (depo-subQ provera 104(R)) is made into the anterior thigh or abdomen; the preparation for subcutaneous administration should not be administered IM.

Oral dosage preparations containing medroxyprogesterone acetate in combination with conjugated estrogens as monophasic or biphasic regimens are commercially available in a mnemonic dispensing package that is designed to aid the user in complying with the prescribed dosage schedule. The monophasic combination (Prempro(R)) is available in a 28-day dosage preparation that contains 28 tablets of conjugated estrogens (0.625 mg) in fixed combination with medroxyprogesterone acetate (2.5 or 5 mg). The monophasic combination (Prempro(R)) also is available in a 28-day dosage preparation that contains 28 tablets of conjugated estrogens USP (0.3 or 0.45 mg) in fixed combination with medroxyprogesterone acetate (1.5 mg). The biphasic combination (Premphase(R)) also is available in a 28-day dosage preparation that contains 14 tablets of conjugated estrogens (0.625 mg) and 14 tablets of conjugated estrogens (0.625 mg) in fixed combination with medroxyprogesterone acetate (5 mg).

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

No enhanced messaging available.

Although progestins have been used beginning in the first trimester of pregnancy to prevent habitual abortion or to treat threatened abortion, there is no adequate evidence from well-controlled studies to substantiate the efficacy of progestins for these uses; however, there is evidence of potential adverse effects on the fetus when these drugs are administered within the first 4 months of pregnancy. In addition, in most women, the cause of abortion is a defective ovum, which progestins could not be expected to influence. Because of their uterine-relaxant effects, progestins may delay spontaneous abortion of fertilized defective ova. Masculinization of the female fetus has reportedly occurred when progestins were used during pregnancy. Clitoral hypertrophy and fusion of the labia have been reported in a few female neonates born to women who had received medroxyprogesterone during pregnancy; hypospadias in male neonates born to women receiving progestational agents occurs at approximately twice the rate of occurrence in male neonates born to women not receiving the drugs. Postpartum bleeding, postabortal bleeding, and missed abortion have been reported in women who received the drug during pregnancy. An association between intrauterine exposure to female sex hormones and congenital anomalies, including cardiovascular and limb defects, has been suggested. (See Cautions: Pregnancy, Fertility, and Lactation, in Estrogen-Progestin Combinations 68:12.) Use of progestins, including medroxyprogesterone, is not recommended during the first 4 months of pregnancy. If a woman becomes pregnant while receiving medroxyprogesterone or is inadvertently exposed to the drug during the first 4 months of pregnancy, she should be advised of the potential risks to the fetus. To increase ensurance that the drug is not administered inadvertently to a pregnant woman, it is important that use of the drug be initiated only during the first 5 days after onset of normal menses, within 5 days postpartum if the woman is not lactating, or at the sixth postpartum week if she is. If more than 13-14 weeks has elapsed since the last dose of medroxyprogesterone, appropriate assessment should be performed to ensure that the woman is not pregnant prior to administering a dose.

When medroxyprogesterone is used as a contraceptive, unintended pregnancies that occur within 1-2 months after IM injection of the drug may be characterized by impaired fetal growth as evidenced by low birthweights, which theoretically could result in an increased risk of neonatal death. However, the attributable risk of this adverse effect is low because such pregnancies are unlikely. The risk of low birthweight was particularly evident when conception was estimated to occur within 4 weeks of medroxyprogesterone injection. While an increase in polysyndactyly, particularly among offspring of women younger than 30 years of age, and chromosomal anomalies also have been observed in neonates born to women who received IM medroxyprogesterone contraception, the unrelated nature of these effects, the lack of confirmation from other studies, the prolonged period of time between use of the drug and conception in many cases, and chance effects resulting from the multiple statistical comparisons applied make an association between these effects and the drug unlikely.

The possibility of ectopic pregnancy should be considered in any women using medroxyprogesterone contraception if pregnancy occurs or the woman develops complaints of severe abdominal pain.

Medroxyprogesterone should not be used to induce withdrawal bleeding as a test for pregnancy.

Progestins reportedly are distributed into milk, and detectable amounts of medroxyprogesterone have been identified in milk of lactating women receiving the drug IM. Milk composition, quality, and volume are not affected adversely by medroxyprogesterone use. While the manufacturers warn that the possible effects of progestins in milk on nursing infants have not been determined, study of infants exposed to the drug via breast milk has revealed no evidence of adverse developmental or behavioral effects through puberty.

The effects of combined medroxyprogesterone acetate and estradiol cypionate therapy on lactation and nursing infants have not been established. However, because adverse effects such as jaundice and breast enlargement have been reported in nursing infants of women receiving estrogen-progestin combination oral contraceptives, the usual cautions and precautions associated with estrogens must be considered in lactating women receiving IM medroxyprogesterone acetate in fixed combination with estradiol cypionate. The manufacturer states that use of estrogen-progestin combination contraceptives should be deferred until 6 weeks postpartum. For additional information, see Cautions: Pregnancy, Fertility, and Lactation, in Estrogen-Progestin Combinations 68:12.

No enhanced messaging available.