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Medroxyprogesterone Acetate

Pronunciation

Class: Progestins
ATC Class: G03AC06
VA Class: HS800
Chemical Name: (6α)-17-(Acetyloxy)-6-methyl-pregn-4-ene-3,20-dione
Molecular Formula: C24H34O4
CAS Number: 71-58-9
Brands: Depo-Provera, Depo-subQ provera 104, Lunelle Monthly Contraceptive Injection, Premphase, Prempro, Provera

Warning(s)

  • Bone Mineral Density
  • Use of parenteral medroxyprogesterone preparations (i.e., Depo-Provera Contraceptive, depo-subQ provera 104, or medroxyprogesterone acetate contraceptive injection) may result in loss of bone mineral density (BMD).134 c e Bone loss is greater with increasing duration of therapy and may not be completely reversible.134 c e

  • Not known whether use of these parenteral preparations in young women (e.g., during adolescence, early adulthood) will reduce peak bone mass and increase risk of osteoporotic fractures later in life.134 c e Loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion.134 c e

  • Use parenteral medroxyprogesterone for long-term contraception (e.g., >2 years) only if other contraceptive methods are inadequate.134 c e

Introduction

Synthetic progestin; derivative of 17 α-hydroxyprogesterone.a

Uses for Medroxyprogesterone Acetate

Prevention of Endometrial Changes Associated with Estrogens

Reduction of the incidence of endometrial hyperplasia and the attendant risk of endometrial carcinoma in postmenopausal women receiving estrogen replacement therapy.111 113 b

Contraception in Females

Prevention of pregnancy.131 134 c e

Parenteral medroxyprogesterone: Consider benefits vs risks (e.g., loss of BMD in women of all ages, possible impact on peak bone mass in adolescents, additional impact of pregnancy and/or nursing on BMD).134 c e (See Boxed Warning and Effects on Bone under Cautions.)

Endometriosis

Management of pain associated with endometriosis.c Benefit of therapy for >6 months not established.c Consider benefits vs risk of BMD loss in women of all ages and the possible impact on peak bone mass in adolescents.c (See Boxed Warning and Effects on Bone under Cautions.)

Slideshow: 2014 Update: First Time Brand-to-Generic Switches

Amenorrhea

Treatment of secondary amenorrhea.b

Uterine Bleeding

Treatment of abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology such as fibroids or uterine cancer.b

Endometrial Carcinoma

Adjunctive therapy and palliative treatment of inoperable, recurrent, and metastatic endometrial carcinoma.d

Renal Carcinoma

Has been used for treatment of metastatic renal cell carcinoma;d however, other agents are preferred.a

Paraphilia in Males

Management of paraphilia (e.g., homosexual, heterosexual, or bisexual pedophilia; heterosexual fetishism, voyeurism, sexual sadism, or exhibitionism; transvestism) in males.a

Precocious Puberty

Management of GnRH-dependent (central) forms of precocious puberty; 24 25 29 30 31 100 101 102 103 104 105 106 107 108 however, GnRH analogs generally are preferred.100 101 102 105 106 107 108

Management of GnRH-independent (peripheral) forms of precocious puberty, 24 25 29 30 31 100 101 102 103 104 105 106 107 108 including familial male precocious puberty (testotoxicosis) and McCune-Albright syndrome.100 101 102 104 105 106 107 108 109 110

Medroxyprogesterone Acetate Dosage and Administration

Administration

Administer orally, IM, or sub-Q.131 134 b c d e

Oral Administration

Administer orally.111 113 b

Oral dosage preparations containing medroxyprogesterone acetate in combination with conjugated estrogens USP 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.111

IM Administration

Administer by IM injection deeply into gluteal, deltoid, or anterior thigh muscle.131 134 d e

Vigorously shake injectable suspension immediately before each use.131 c d

Sub-Q Administration

depo-subQ provera 104: Administer by sub-Q injection into anterior thigh or abdomen; not formulated for IM injection.c

Vigorously shake injectable suspension before administration.c

Dosage

Available as medroxyprogesterone acetate; dosage expressed in terms of the salt.131 b c d

When used as a contraceptive or for the management of endometriosis, dosage does not need to be adjusted based on weight.134 c e

Adults

Prevention of Endometrial Changes Associated with Estrogens
Oral

1.5–5 mg daily.111 Alternatively, 5–10 mg daily for 12–14 consecutive days per month.111 b

Contraception in Females
Medroxyprogesterone (Depo-Provera Contraceptive, medroxyprogesterone acetate contraceptive)
IM

150 mg every 3 months.134 e Exclude possibility of pregnancy before administering the first dose and whenever ≥13 weeks have elapsed since the previous dose.134 e Initiate during the first 5 days of a normal menstrual cycle, at 6 weeks postpartum in women who breast-feed, or within 5 days postpartum in those who do not breast-feed.134 e

Medroxyprogesterone/Estradiol Fixed Combination (Lunelle)
IM

Medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (0.5 mL) monthly (every 28–30 days; not to exceed 33 days).131 Initiate during the first 5 days of a normal menstrual cycle, within 5 days of a complete first-trimester abortion, no earlier than 6 weeks postpartum in women who breast-feed, or no earlier than 4 weeks postpartum in those who do not breast-feed.131

If >33 days have elapsed since the previous injection, use an alternative (i.e., barrier) method of contraception and rule out pregnancy prior to continuing Lunelle.131 Shortening the injection interval may alter menstrual pattern.131

When switching from other contraceptive methods, initiate Lunelle in a manner that ensures continuous contraceptive coverage based on the mechanism of action of both methods (e.g., patients switching from oral contraceptives should be given an initial injection within 7 days after taking the last hormonally active tablet).131

Medroxyprogesterone (depo-subQ provera 104)
Sub-Q

104 mg every 3 months (12–14 weeks).c Exclude possibility of pregnancy before administering the first dose and whenever ≥14 weeks have elapsed since the previous dose.c Initiate during the first 5 days of a normal menstrual cycle or ≥ 6 weeks postpartum in women who breast-feed.c

When switching from other contraceptive methods, initiate depo-subQ provera 104 in a manner that ensures continuous contraceptive coverage based on the mechanism of action of both methods.c Patients switching from combined contraceptives (estrogen plus progestin) should be given an initial injection within 7 days after taking the last hormonally active tablet or removing a transdermal patch or vaginal ring.131 Contraceptive coverage will be maintained when switching from medroxyprogesterone acetate contraceptive IM injection (e.g., Depo Provera contraceptive injection) to depo-subQ provera 104 if the next injection is given within the dosing period recommended for the IM contraceptive injection.c

Endometriosis
Sub-Q

depo-subQ provera 104: 104 mg every 3 months (12–14 weeks).c Exclude possibility of pregnancy before administering the first dose and whenever ≥14 weeks have elapsed since the previous dose.c Initiate during the first 5 days of a normal menstrual cycle or ≥ 6 weeks postpartum in women who breast-feed.c

Benefit of therapy for >6 months not established; treatment for >2 years not recommended.c (See Effects on Bone under Cautions.)

Amenorrhea
Oral

5–10 mg daily for 5–10 days.b

To induce optimum secretory transformation of an endometrium that has been adequately primed with endogenous or exogenous estrogen, 10 mg daily for 10 days.b

Uterine Bleeding
Oral

5–10 mg daily for 5–10 days beginning on the assumed or calculated 16th or 21st day of the menstrual cycle.b

To induce optimum secretory transformation of an endometrium that has been adequately primed with endogenous or exogenous estrogen, 10 mg daily for 10 days, beginning on the calculated 16th day of the menstrual cycle.b

Endometrial Carcinoma
IM

Initially, 400–1000 mg once weekly.d When improvement is noted and disease has stabilized (within weeks or months), maintain response with as little as 400 mg/month.d

Renal Carcinoma
IM

Initially, 400–1000 mg once weekly.d When improvement is noted and disease has stabilized (within weeks or months), maintain response with as little as 400 mg/month.d

Paraphilia in Males
IM

Initially, 200 mg 2 or 3 times daily.a Alternatively, 500 mg once weekly.a

Adjust dose and/or frequency to an effective maintenance level according to patient response and tolerance and/or plasma testosterone concentration.a Consult published protocols for more specific dosage information in these males.a

Cautions for Medroxyprogesterone Acetate

Contraindications

  • Active thrombophlebitis, current or past history of thromboembolic disorders, or cerebrovascular disease.134 b c e

  • Undiagnosed vaginal bleeding.134 b c e

  • Known or suspected pregnancy.134 b c e

  • Liver dysfunction or disease.134 b c e

  • Known or suspected malignancy of the breast.134 b c e

  • Known hypersensitivity to medroxyprogesterone or any ingredient in the formulation.134 b c e

  • Use as a pregnancy test.134 b e

Warnings/Precautions

Warnings

Effects on Bone

When used IM or sub-Q as a contraceptive or sub-Q for the management of endometriosis, possible increased rate of bone loss, especially during initial years of therapy.134 135 136 137 138 139 c e Bone loss is greater with increasing duration of therapy; may not be reversible.134 c e (See Boxed Warning.)

Use as a long-term contraceptive (e.g., >2 years) only if other contraceptive methods are inadequate and benefits are expected to outweigh risks.134 c e Evaluate BMD periodically when used long term; consider patient’s age (adult or adolescent) and skeletal maturity when evaluating BMD results.134 c e

Consider other therapies in women with existing risk factors for osteoporosis, since use of medroxyprogesterone may pose additional risk.134 c e

When used for the management of endometriosis, evaluate BMD prior to initiating a second course of therapy.c

Effects of BMD changes in women receiving medroxyprogesterone acetate in fixed combination with estradiol cypionate (Lunelle) not established.131

Thromboembolic Disorders

Possible thromboembolic and thrombotic disorders (e.g., thrombophlebitis, pulmonary embolism, cerebrovascular insufficiency, coronary occlusion, retinal thrombosis, mesenteric thrombosis).131 134 b c d e Observe patients for these effects; discontinue immediately and do not readminister if these disorders occur or are suspected.131 134 b c d e

Bleeding Irregularities

When used as a contraceptive, possible breakthrough or irregular vaginal bleeding; rarely may be heavy or continuous.131 134 c e If abnormal bleeding persists or is severe, consider organic pathology and perform adequate diagnostic tests in patients with undiagnosed vaginal bleeding.131 134 c e

Carcinoma of Reproductive Organs and Breast

Depo-Provera contraceptive injection associated with slight or no increased risk of breast cancer; no increase in risk of ovarian or cervical cancer, reduced risk of endometrial cancer.134 c e

When used with estrogen replacement therapy in postmenopausal women, reduced risk of endometrial cancer compared with estrogen use alone.111 Perform diagnostic tests (including endometrial sampling) in women with undiagnosed, persistent, or abnormal vaginal bleeding.111

Addition of medroxyprogesterone to estrogen replacement therapy increases the risk of breast cancer beyond that associated with estrogen use alone.117 121 128 129

Fetal/Neonatal Morbidity and Mortality

Potential adverse effects on the fetus when administered within the first 4 months of pregnancy (masculinization of the female fetus, hypospadias in male neonates, low birth weight).131 134 b d e (See Contraindications under Cautions.)

Ectopic Pregnancy

Consider the possibility of ectopic pregnancy if pregnancy or severe abdominal pain occurs in women using medroxyprogesterone contraception.134 b c e

Ocular Effects

If unexplained, sudden or gradual, partial or complete loss of vision; proptosis or diplopia; papilledema; or retinal vascular lesions occur, discontinue and initiate appropriate diagnostic and therapeutic measures.131 134 e Do not reinitiate therapy if ocular examination reveals evidence of papilledema or retinal vascular lesions.134 b c d e

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and anaphylactoid reactions reported.131 134 b c d e Institute appropriate measures if anaphylactic/anaphylactoid reaction occurs.131 134 c e

Possible allergic reactions, including urticaria, pruritus, angioedema, generalized rash (with or without pruritus).131 b d

General Precautions

Physical Examination and Follow-up

Annual medical history and physical examination advised.131 134 b c d e Physical examination may be deferred until after initiation of parenteral medroxyprogesterone if requested by the woman and judged appropriate by the clinician.131 134 c d e Physical examination should include special attention to BP, breasts, abdomen, and pelvic organs and should include a Papanicolaou test (Pap smear) and relevant laboratory tests.131 134 b c d e Exercise particular care in women with a strong family history of breast cancer or those who have breast nodules.131 134 b c d e

Fluid Retention

Fluid retention may occur.131 134 b c d e Exercise caution and carefully monitor patients with conditions (seizures, migraine headache, asthma, cardiac impairment, renal impairment) that might be aggravated by fluid retention.131 134 b c d e

Weight Change

Possible weight gain.131 134 a c e

Fertility

Contraceptive effect is prolonged.134 c e Median time to conception after the last dose of parenteral medroxyprogesterone (Depo-Provera Contraceptive Injection) is 10 months (range: 4–31 months) and is unrelated to the duration of contraceptive use.134 e

Median time to ovulation was 10 months after last injection of depo-subQ provera 104 and 80% of women ovulated within 1 year; ovulation may occur as early as 14 weeks after a single dose.c

Depression

Possible depression.131 134 b d e Exercise caution in women with a history of depression; discontinue if severe depression recurs during use.131 134 b c d e

Seizures

Seizures reported with IM contraceptive use.134 d e

Injection Site Reactions

Injection site reactions, including persistent skin changes (e.g., small areas of induration or atrophy), reported with sub-Q administration.c

Sexually Transmitted Diseases

Does not protect against HIV or other sexually transmitted infections.134 c e

Endocrine and Metabolic Effects

Possible decreased glucose tolerance.131 134 b c d e Monitor diabetic patients carefully.131 134 b c d e

Prolonged Therapy

Effect of long-term therapy on pituitary, ovarian, adrenal, hepatic, or uterine function not determined.b d

Climacteric

Onset of climacteric may be masked in women.b d

Hepatic Effects

Possible hepatic dysfunction (e.g., jaundice); discontinue therapy and reevaluate patient if such manifestations occur or are suspected.134 c e

Estrogen Therapy

Medroxyprogesterone may adversely affect some beneficial estrogen-associated metabolic effects (lipid metabolism, glucose tolerance).111 113 114 115 116

When used in fixed combination with conjugated estrogens or estradiol cypionate, consider the cautions, precautions, and contraindications associated with estrogens.111 131

Specific Populations

Pregnancy

Category X.131 134 b d e (See Contraindications and also Fetal/Neonatal Morbidity and Mortality, under Cautions.)

Lactation

Distributed into milk.131 134 b c d e No evidence of adverse developmental or behavioral effects through puberty found in infants exposed to the drug via breast milk.134 c e

Pediatric Use

Safety and efficacy not established.b c d

Not indicated before menarche.134 c e Possible loss of BMD with parenteral medroxyprogesterone; loss of BMD is of particular concern during adolescence.134 c e (See Boxed Warning and Effects on Bone under Cautions.)

Safety and efficacy of parenteral medroxyprogesterone in postmenarchal adolescents expected to be the same as in adult women.134 c e

Hepatic Impairment

Contraindicated in patients with liver dysfunction or disease.134 b c e

Common Adverse Effects

Menstrual abnormalities (amenorrhea; frequent, irregular, prolonged, or infrequent bleeding), abdominal pain or discomfort, weight changes, dizziness, headache, asthenia, nervousness.134 c e

Interactions for Medroxyprogesterone Acetate

Specific Drugs

Drug

Interaction

Comment

Aminoglutethimide

Decreased medroxyprogesterone concentrations131 134 b c d e

Decreased efficacy with concomitant use134 e

Medroxyprogesterone Acetate Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from the GI tract; peak plasma concentrations achieved within 2–4 hours.b

Peak plasma concentrations attained approximately 1 week following sub-Q injection.c

Food

Food increases peak plasma concentrations and AUC.b

Distribution

Extent

Distributed into human milk.134 c e

Plasma Protein Binding

Approximately 86–90% (primarily albumin).131 c b

Elimination

Metabolism

Metabolized in the liver by ring A and/or side-chain hydroxylation.131 b c

Elimination Route

Excreted in urine, principally as glucuronide conjugates.131 b

Half-life

Oral doses: Approximately 12 hours (single dose) or 17 hours (multiple doses).b

IM doses: 50 days reported for Depo-Provera Contraceptive Injection;134 15 days reported for Lunelle Monthly Contraceptive Injection.131

Sub-Q doses: approximately 40 days for depo-subQ provera 104.c

Special Populations

In patients with advanced liver disease, clearance is reduced.b

Stability

Storage

Oral

Tablets

20–25°C.b

Parenteral

Injection

20–25°C.134 c e

Actions

  • Transforms a proliferative endometrium into a secretory one.b

  • Androgenic and anabolic effects have been reported; no estrogenic activity reported.b

  • At usual IM or sub-Q dosages, inhibits secretion of pituitary gonadotropins, preventing follicular maturation and ovulation and resulting in endometrial thinning.134 b c d These actions produce a contraceptive effect.134 c Usual oral dosages do not exhibit these effects.b

Advice to Patients

  • Importance of women informing clinicians immediately if they are or plan to become pregnant.131 b c d Necessity for clinicians to advise pregnant women of the risk to fetus.131 b c d

  • Importance of reading the manufacturer’s patient information.131 b c d

  • Importance of advising patients of anticipated menstrual effects.a

  • Importance of patients notifying their clinician if signs and symptoms of thromboembolic and thrombotic disorders occur.a

  • When used as a contraceptive, importance of adhering to the injection schedule.131 134 c e

  • Importance of women informing clinicians if they are breast-feeding or plan to breast-feed.131 b c d

  • Importance of informing patients of other important precautionary information.131 b c d (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Medroxyprogesterone Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

2.5 mg*

Provera (scored)

Pfizer

Medroxyprogesterone Acetate Tablets

Barr, Duramed, Greenstone, Major

5 mg*

Provera (scored)

Pfizer

Medroxyprogesterone Acetate Tablets

Barr, Duramed, Greenstone, Major

10 mg*

Provera (scored)

Pfizer

Parenteral

Injectable suspension

104 mg/0.65 mL

depo-subQ provera 104 (with parabens and povidone, available in prefilled syringes with UltraSafe Passive needle guard)

Pfizer

150 mg/mL*

Depo-Provera Contraceptive (with parabens)

Pfizer

Medroxyprogesterone Acetate Contraceptive

Sicor

400 mg/mL

Depo-Provera

Pfizer

Medroxyprogesterone Acetate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, monophasic regimen

1.5 mg with Conjugated Estrogens 0.3 mg (28 tablets)

Prempro (with povidone)

Wyeth

1.5 mg with Conjugated Estrogens 0.45 mg (28 tablets)

Prempro (with povidone)

Wyeth

2.5 mg with Conjugated Estrogens 0.625 mg (28 tablets)

Prempro (with povidone)

Wyeth

5 mg with Conjugated Estrogens 0.625 mg (28 tablets)

Prempro (with povidone)

Wyeth

Tablets, biphasic regimen

5 mg with Conjugated Estrogens 0.625 mg (14 tablets) and Conjugated Estrogens 0.625 mg (14 tablets)

Premphase (with povidone)

Wyeth

Parenteral

Injectable Suspension

25 mg/0.5 mL with Estradiol Cypionate 5 mg/0.5 mL

Lunelle Monthly Contraceptive Injection

Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Depo-Provera 150MG/ML Suspension (PFIZER U.S.): 1/$100.78 or 3/$268.74

Depo-Provera 400MG/ML Suspension (PFIZER U.S.): 3/$191.59 or 8/$541.99

MedroxyPROGESTERone Acetate 10MG Tablets (GREENSTONE): 30/$18.99 or 60/$27.97

MedroxyPROGESTERone Acetate 150MG/ML Suspension (GREENSTONE): 1/$52.99 or 2/$95.98

MedroxyPROGESTERone Acetate 150MG/ML Suspension (GREENSTONE): 1/$55.99 or 3/$159.96

MedroxyPROGESTERone Acetate 2.5MG Tablets (GREENSTONE): 30/$12.99 or 60/$20.98

MedroxyPROGESTERone Acetate 5MG Tablets (GREENSTONE): 90/$18.99 or 180/$25.97

Provera 10MG Tablets (PFIZER U.S.): 30/$62.99 or 90/$178.48

Provera 2.5MG Tablets (PFIZER U.S.): 30/$37.79 or 90/$97.62

Provera 5MG Tablets (PFIZER U.S.): 30/$50.39 or 90/$142.78

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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b. Pharmacia & Upjohn. Provera (medroxyprogesterone acetate) tablets prescribing information. Kalamazoo, MI; 1998 Aug.

c. Pharmacia. depo-subQ provera 104 (medroxyprogesterone acetate) injectable suspension 104 mg/0.65 mL prescribing information. New York; NY: 2005 Mar 22.

d. Pharmacia & Upjohn. Depo-Provera (medroxyprogesterone acetate) injectable suspension prescribing information. Kalamazoo, MI; 1999 Jun.

e. Sicor. Medroxyprogesterone acetate injectable suspension contraceptive injection prescribing information. Irvine, CA: 2004 Dec.

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