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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
MedroxyPROGESTERone may be confused with hydroxyprogesterone, methylPREDNISolone, methylTESTOSTERone
Provera® may be confused with Covera®, Parlodel®, Premarin®
The injection dosage form is available in different formulations. Carefully review prescriptions to assure the correct formulation and route of administration.
Pronunciation
(me DROKS ee proe JES te rone)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Endometrial carcinoma or renal carcinoma; secondary amenorrhea or abnormal uterine bleeding due to hormonal imbalance; reduction of endometrial hyperplasia in nonhysterectomized postmenopausal women receiving conjugated estrogens; prevention of pregnancy; management of endometriosis-associated pain
Pregnancy Risk Factor
X
Pregnancy Considerations
There is an increased risk of minor birth defects in children whose mothers take progesterones during the first 4 months of pregnancy. Hypospadias has been reported in male and mild masculinization of the external genitalia has been reported in female babies exposed during the first trimester. High doses are used to impair fertility. Low birth weight has been reported in neonates from unexpected pregnancies which occurred 1-2 months following injection of medroxyprogesterone (MPA) contraceptive. Ectopic pregnancies have been reported with use of the MPA contraceptive injection. When therapy is discontinued, fertility returns sooner in women of lower body weight. Median time to conception/return to ovulation following discontinuation of MPA contraceptive injection is 10 months following the last injection.
Lactation
Enters breast milk/compatible
Breast-Feeding Considerations
Composition, quality and quantity of breast milk are not affected; adverse developmental and behavioral effects have not been noted following exposure of infant to MPA while breast-feeding.
Contraindications
Hypersensitivity to medroxyprogesterone or any component of the formulation; history of or current thrombophlebitis or venous thromboembolic disorders (including DVT, PE); cerebral vascular disease; severe hepatic dysfunction or disease; carcinoma of the breast or genital organs, undiagnosed vaginal bleeding; missed abortion, diagnostic test for pregnancy, pregnancy
Warnings/Precautions
Boxed warnings:
• Bone mineral density loss: See “Concerns related to adverse effects” below.
• Long-term use: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• Bone mineral density loss: [U.S. Boxed Warning]: Prolonged use of medroxyprogesterone contraceptive injection may result in a loss of bone mineral density (BMD). Loss is related to the duration of use, and may not be completely reversible on discontinuation of the drug. The impact on peak bone mass in adolescents should be considered in treatment decisions.
• Breast cancer: An increased risk of invasive breast cancer was observed in postmenopausal women using medroxyprogesterone acetate (MPA) in combination with conjugated equine estrogens (CEE). An increase in abnormal mammograms has also been reported with estrogen and progestin therapy.
• Dementia: The risk of dementia may be increased in postmenopausal women; increased incidence was observed in women ?65 years of age taking MPA in combination with CEE.
• Retinal vascular thrombosis: Discontinue pending examination in cases of sudden partial or complete vision loss, sudden onset of proptosis, diplopia, or migraine; discontinue permanently if papilledema or retinal vascular lesions are observed on examination.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease or dysfunction. MPA used in combination with estrogen may increase the risks of hypertension, myocardial infarction (MI), stroke, pulmonary emboli (PE), and deep vein thrombosis; incidence of these effects was shown to be significantly increased in postmenopausal women using CEE in combination with MPA. MPA in combination with estrogens should not be used to prevent coronary heart disease.
• Depression: Use with caution in patients with a history of depression.
• Diabetes: Use with caution in patients with diabetes mellitus; may cause glucose intolerance.
• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including asthma, epilepsy, migraine, diabetes, or renal dysfunction.
• Osteoporosis: Consider other methods of birth control in women with (or at risk for) osteoporosis.
Special populations:
• Pediatrics: Not for use prior to menarche.
• Surgical patients: Whenever possible, progestins in combination with estrogens should be discontinued at least 4 weeks prior to and for 2 weeks following elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.
Other warnings/precautions:
• Long-term use: [U.S. Boxed Warning]: Long-term use (ie, >2 years) should be limited to situations where other birth control methods are inadequate.
• Risks vs. benefits: Before prescribing progestin therapy in combination with estrogen to postmenopausal women, the risks and benefits must be weighed for each patient. Women should be informed of these risks and benefits, as well as possible effects of estrogen when added to progestin therapy. Progestins with or without estrogen should be used for shortest duration possible consistent with treatment goals. Conduct periodic risk:benefit assessments.
Adverse Reactions
Adverse effects as reported with any dosage form; percent ranges presented are noted with the MPA contraceptive injection:
>5%:
Central nervous system: Dizziness, headache, nervousness
Endocrine & metabolic: Libido decreased, menstrual irregularities (includes bleeding, amenorrhea, or both)
Gastrointestinal: Abdominal pain/discomfort, weight changes (average 3-5 pounds after 1 year, 8 pounds after 2 years)
Neuromuscular & skeletal: Weakness
1% to 5%:
Cardiovascular: Edema
Central nervous system: Depression, fatigue, insomnia, irritability, pain
Dermatologic: Acne, alopecia, rash
Endocrine & metabolic: Anorgasmia, breast pain, hot flashes
Gastrointestinal: Bloating, nausea
Genitourinary: Cervical smear abnormal, leukorrhea, menometrorrhagia, menorrhagia, pelvic pain, urinary tract infection, vaginitis, vaginal infection, vaginal hemorrhage
Local: Injection site atrophy, injection site reaction, injection site pain
Neuromuscular & skeletal: Arthralgia, backache, leg cramp
Respiratory: Respiratory tract infections
<1%: Allergic reaction, anemia, angioedema, appetite changes, asthma, axillary swelling, blood dyscrasia, body odor, breast cancer, breast changes, cervical cancer, chest pain, chills, chloasma, convulsions, deep vein thrombosis, diaphoresis, drowsiness, dry skin, dysmenorrhea, dyspareunia, dyspnea, facial palsy, fever, galactorrhea, genitourinary infections, glucose tolerance decreased, hirsutism, hoarseness, jaundice, lack of return to fertility, lactation decreased, libido increased, melasma, nipple bleeding, osteoporosis, paralysis, paresthesia, pruritus, pulmonary embolus, rectal bleeding, scleroderma, sensation of pregnancy, somnolence, syncope, tachycardia, thirst, thrombophlebitis, uterine hyperplasia, vaginal cysts, varicose veins; residual lump, sterile abscess, or skin discoloration at the injection site
Postmarketing and/or case reports: Anaphylaxis, anaphylactoid reactions, bone mineral density decreased, osteoporotic fractures
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Induces CYP3A4 (weak)
Drug Interactions
Acitretin: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk X: Avoid combination
Aminoglutethimide: May increase the metabolism of Progestins. Risk D: Consider therapy modification
Aprepitant: May decrease the serum concentration of Contraceptive (Progestins). Risk D: Consider therapy modification
Barbiturates: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
CarBAMazepine: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Fosaprepitant: May decrease the serum concentration of Contraceptive (Progestins). The active metabolite aprepitant is likely responsible for this effect. Risk D: Consider therapy modification
Griseofulvin: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk X: Avoid combination
Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Risk C: Monitor therapy
Maraviroc: CYP3A4 Inducers may decrease the serum concentration of Maraviroc. Risk D: Consider therapy modification
Phenytoin: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Rifamycin Derivatives: May decrease the serum concentration of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
St Johns Wort: May diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Contraceptive (Progestins) may diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase risk of osteoporosis).
Food: Bioavailability of the oral tablet is increased when taken with food; half-life is unchanged.
Herb/Nutraceutical: St John's wort may diminish the therapeutic effect of progestin contraceptives (contraceptive failure is possible).
Storage
Store at controlled room temperature.
Mechanism of Action
Inhibits secretion of pituitary gonadotropins, which prevents follicular maturation and ovulation; causes endometrial thinning
Pharmacodynamics/Kinetics
Absorption: Oral: Well absorbed; I.M.: 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
Time to peak: Oral: 2-4 hours
Half-life elimination: Oral: 12-17 hours; I.M. (Depo-Provera® Contraceptive): 50 days; SubQ: ?40 days
Excretion: Urine
Dosage
Adolescents and Adults:
Amenorrhea: Oral: 5-10 mg/day for 5-10 days
Abnormal uterine bleeding: Oral: 5-10 mg for 5-10 days starting on day 16 or 21 of cycle
Contraception:
Depo-Provera® Contraceptive: I.M.: 150 mg every 3 months
depo-subQ provera 104™: SubQ: 104 mg every 3 months (every 12-14 weeks)
Endometriosis: depo-subQ provera 104™: SubQ: 104 mg every 3 months (every 12-14 weeks)
Adults:
Endometrial or renal carcinoma (Depo-Provera®): I.M.: 400-1000 mg/week
Accompanying cyclic estrogen therapy, postmenopausal: Oral: 5-10 mg for 12-14 consecutive days each month, starting on day 1 or day 16 of the cycle; lower doses may be used if given with estrogen continuously throughout the cycle
Dosing adjustment in hepatic impairment: Use is contraindicated with severe impairment. Consider lower dose or less frequent administration with mild-to-moderate impairment. Use of the contraceptive injection has not been studied in patients with hepatic impairment; consideration should be given to not readminister if jaundice develops
Administration: I.M.
Depo-Provera® Contraceptive: Administer first dose during the first 5 days of menstrual period, or within the first 5 days postpartum if not breast-feeding, or at the sixth week postpartum if breast feeding exclusively. Shake vigorously prior to administration. Administer by deep I.M. injection in the gluteal or deltoid muscle.
Administration: Other
SubQ: depo-subQ provera 104™: Administer first dose during the first 5 days of menstrual period, or at the sixth week postpartum if breast-feeding. Shake vigorously prior to administration. Administer by SubQ injection in the upper thigh or abdomen; avoid boney areas and the umbilicus. Administer over 5-7 seconds. Do not rub the injection area. When switching from combined hormonal contraceptives (estrogen plus progestin), the first injection should be within 7 days after the last active pill, or removal of patch or ring. If switching from the I.M. to SubQ formulation, the next dose should be given within the prescribed dosing period for the I.M. injection.
Monitoring Parameters
Before starting therapy, a physical exam with reference to the breasts and pelvis are recommended, including a Papanicolaou smear. Exam may be deferred if appropriate prior to administration of MPA contraceptive injection; pregnancy should be ruled out prior to use. Monitor patient closely for loss of vision; sudden onset of proptosis, diplopia, or migraine; signs and symptoms of thromboembolic disorders; signs or symptoms of depression; glucose in patients with diabetes; or blood pressure.
Test Interactions
The following tests may be decreased: Steroid levels (plasma and urinary), gonadotropin levels, SHBG concentration, T3 uptake
The following tests may be increased: Protein-bound iodine, butanol extractable protein-bound iodine, Factors II, VII, VIII, IX, X
Pathologist should be advised of estrogen/progesterone therapy when specimens are submitted.
Dietary Considerations
Ensure adequate calcium and vitamin D intake when used for the prevention of pregnancy
Patient Education
Follow dosage schedule and do not take more than prescribed. You may experience sensitivity to sunlight (use sunblock, wear protective clothing and eyewear, and avoid extensive exposure to direct sunlight); dizziness, anxiety, depression (use caution when driving or engaging in tasks that require alertness until response to drug is known); changes in appetite; maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake and diet; decreased libido or increased body hair (reversible when drug is discontinued); hot flashes (cool clothes and environment may help). May cause discoloration of stool (green). Report swelling of face, lips, or mouth; absence or altered menses; abdominal pain; vaginal itching, irritation, or discharge; heat, warmth, redness, or swelling of extremities; or sudden onset change in vision. Pregnancy precaution: Inform prescriber if you are pregnant. Consult prescriber for instruction on appropriate contraceptive measures.
Injection for contraception: This product does not protect against HIV or other sexually-transmitted diseases.
Dental Health: Effects on Dental Treatment
Progestins may predispose the patient to gingival bleeding.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness, headache, depression, insomnia, nervousness, irritability, and mood disturbances
Mental Health: Effects on Psychiatric Treatment
The Women's Health Initiative (WHI) Memory Study reported an increased risk of developing dementia in postmenopausal women ?65 years of age during 4 years of treatment with oral conjugated equine estrogens and medroxyprogesterone acetate relative to placebo (1.8% vs 0.9%). Relative risk was 2.05 (95% CI 1.21-3.48). Therefore, estrogens and progestins should not be used for the prevention of dementia. The WHI also reported an increased risk of stroke (29 vs 21 per 10,000 women-years) compared to women receiving placebo. The increase in risk was observed after the first year and persisted. May cause hypertriglyceridemia; monitor in patients receiving antipsychotics especially clozapine, olanzapine, and quetiapine.
Nursing: Physical Assessment/Monitoring
Monitor for effectiveness of therapy and adverse effects. Instruct patient on appropriate dose scheduling (according to purpose of therapy), possible side effects, and symptoms to report. Pregnancy risk factor X: Determine that patient is not pregnant before starting therapy. Do not give to sexually-active female patients unless capable of complying with contraceptive use.
Oncology: Emetic Potential
Very low (<10%)
Oncology: Vesicant
No
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, suspension, as acetate: 150 mg/mL (1 mL)
Depo-Provera®: 400 mg/mL (2.5 mL)
Depo-Provera® Contraceptive: 150 mg/mL (1 mL) [prefilled syringe or vial]
depo-subQ provera 104™: 104 mg/0.65 mL (0.65 mL) [prefilled syringe]
Tablet, as acetate: 2.5 mg, 5 mg, 10 mg
Provera®: 2.5 mg, 5 mg, 10 mg
Pricing: U.S. (www.drugstore.com)
Suspension (Depo-Provera)
150 mg/mL (1): $79.99
400 mg/mL (2.5): $169.75
Suspension (Depo-SubQ Provera 104)
104 mg/0.65 mL (0.65): $99.83
Suspension (MedroxyPROGESTERone Acetate)
150 mg/mL (1): $49.99
150 mg/mL (1): $52.99
Tablets (MedroxyPROGESTERone Acetate)
2.5 mg (30): $12.99
5 mg (90): $19.00
10 mg (30): $12.99
Tablets (Provera)
2.5 mg (30): $35.99
5 mg (30): $44.99
10 mg (30): $54.99
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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