medroxyprogesterone

IM:

REMS

Prevention of pregnancy.
To decrease endometrial hyperplasia in postmenopausal women receiving concurrent estrogen (0.625 mg/day conjugated estrogens).
Treatment of secondary amenorrhea and abnormal uterine bleeding caused by hormonal imbalance.
Treatment of advanced unresponsive endometrial or renal carcinoma.
‡Prevention of pregnancy.
Management of endometriosis-associated pain (Depo-Sub Q Provera 104 only).

Action ⬆ ⬇

A synthetic form of progesterone; actions include secretory changes in the endometrium, increases in basal body temperature, histologic changes in vaginal epithelium, relaxation of uterine smooth muscle, mammary alveolar tissue growth, pituitary inhibition, and withdrawal bleeding in the presence of estrogen.

Therapeutic effects:

Decreased endometrial hyperplasia in postmenopausal women receiving concurrent estrogen (combination with estrogen decreases vasomotor symptoms and prevents osteoporosis).
Restoration of hormonal balance with control of uterine bleeding.
Management of endometrial or renal cancer.
Prevention of pregnancy.

Pharmacokinetics ⬆ ⬇

Absorption: 0.6–10% absorbed after oral administration.

Distribution: Unknown.

Metabolism/Excretion: Metabolized by the liver. Primarily excreted in the urine as metabolites.

Half-Life: 1st phase: 52 min; 2nd phase: 230 min; biological: 14.5 hr.

Time/Action Profile ⬆ ⬇

(IM = antineoplastic effects)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	unknown	unknown
IM	wk–mos	mo	unknown‡
SC	unknown	1 wk	3 mo

‡Contraceptive effect lasts 3 mo.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Hypersensitivity to parabens (IM suspension only);
Missed abortion;
Thromboembolic disease;
Cerebrovascular disease;
Severe hepatic impairment;
Breast or genital cancer;
Porphyria;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Long-term use (>4–5 yr); may ↑ risk of MI, stroke, invasive breast cancer, pulmonary emboli, deep vein thrombosis, and dementia in postmenopausal women;
History of liver disease;
Renal impairment;
Cardiovascular disease;
Seizure disorders;
Depression.

Adv. Reactions/Side Effects ⬆ ⬇

CV: DEEP VEIN THROMBOSIS, edema, thrombophlebitis

Derm: chloasma, melasma, rash

EENT: retinal thrombosis

Endo: breast tenderness, galactorrhea, hyperglycemia

GI: drug-induced hepatitis, gingival bleeding

GU: amenorrhea, breakthrough bleeding, cervical erosions, changes in menstrual flow, dysmenorrhea

Local: injection site reactions

Metab: weight gain, weight loss

MS: bone loss

Neuro: depression

Resp: PULMONARY EMBOLISM

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS OR ANGIOEDEMA), MALIGNANCY (BREAST, ENDOMETRIAL, OVARIAN)

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, and voriconazole, may ↑ levels; avoid concurrent use.
Strong CYP3A4 inducers, including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, and phenobarbital, may ↓ levels; avoid concurrent use
May ↓ effectiveness of bromocriptine when used concurrently for galactorrhea/amenorrhea.
Contraceptive effectiveness may be ↓ by carbamazepine, phenobarbital, phenytoin, rifampin, or rifabutin.

Drug-Natural Products:

St. John's wort may ↓ levels; avoid concurrent use

Route/Dosage ⬆ ⬇

Postmenopausal Women Receiving Concurrent Estrogen

PO (Adults ): 2.5–5 mg daily concurrently with 0.625 mg conjugated estrogens (monophasic regimen) or 5 mg daily on days 15–28 of the cycle with 0.625 mg conjugated estrogens taken daily throughout cycle (biphasic regimen).

Secondary Amenorrhea

PO (Adults ): 5–10 mg/day for 5–10 days; start at any time in cycle.

Dysfunctional Uterine Bleeding/Induction of Menses

PO (Adults ): 5–10 mg/day for 5–10 days, starting on day 16 or day 21 of menstrual cycle.

Renal or Endometrial Carcinoma

IM (Adults ): 400–1000 mg; may be repeated weekly; if improvement occurs, attempt to ↓ dose to 400 mg monthly.

Endometriosis-Associated Pain

SC (Adults ): 104 mg every 12–14 wk (3 mo), beginning on day 5 of normal menses (not recommended for more than 2 yr).

Prevention of Pregnancy

IM (Adults ): 150 mg within first 5 days of menses or within 5 days postpartum, if not breastfeeding. If breastfeeding, give 6 wk postpartum; repeat every 3 mo.
SC (Adults ): 104 mg within first 5 days of menses or within 5 days postpartum, if not breastfeeding. If breastfeeding, give 6 wk postpartum; repeat every 12–14 wk.

Availability ⬆ ⬇

(Generic available)

Tablets: 2.5 mg; 5 mg; 10 mg; 100 mg
Suspension for intramuscular injection: 50 mg/mL; 150 mg/mL
Suspension for SUBQ injection (Depo-SubQ Provera 104): 104 mg/0.65 mL
In combination with: conjugated estrogens as Prempro (single combination tablet of 0.626 mg conjugated estrogens plus 2.5 or 5 mg medroxyprogesterone) or Premphase (0.625 mg conjugated estrogens tablet for 14 days followed by combination tablet of 0.625 mg conjugated estrogens plus 5 mg medroxyprogesterone for days 15–28) in convenience packages. See Appendix [not included in this PDA edition].

Assessment ⬆ ⬇

Assess for signs and symptoms of deep vein thrombosis (swelling in extremities, warmth, redness, tenderness, pain) or pulmonary embolism (shortness of breath, fatigue).
Monitor BP periodically during therapy.
- Monitor intake and output ratios and weekly weight. Report significant discrepancies or steady weight gain.

Lab Test Considerations:

Monitor hepatic function before and periodically during therapy.
- May cause ↑ alkaline phosphatase levels. May ↓ pregnanediol excretion concentrations.
- May cause ↑ serum LDL concentrations or ↓ HDL concentrations.
- May alter thyroid hormone assays.
- May ↓ glucose tolerance; monitor patients with diabetes closely.

Implementation ⬆ ⬇

Do not confuse Depo-Provera with Depo-SubQ Provera 104. Do not confuse Provera with Proscar or Prozac. Do not confuse medroxyprogesterone with methylprednisolone, or methyltestosterone.
- Contraception: To ensure patient is not pregnant at time of 1st injection, administer ONLY during first 5 days of a normal menstrual period; ONLY within first 5 days postpartum if not breastfeeding; and if exclusively breastfeeding, ONLY at the sixth postpartum wk. If interval between injections >13 wk, use pregnancy test to ensure patient is not pregnant before administration. Only the 150 mg/mL vial or prefilled syringe should be used for contraception.
- When switching from other hormonal contraceptives, administer within dosing period (7 days after taking last active pill, removing patch or ring, or within dosing period for IM injection).
- Injectable medroxyprogesterone may lead to bone loss, especially in women younger than 21 yr; should be used for <2 yr only if other methods of contraception are inadequate. If used long term, women should use supplemental calcium and vitamin D and monitor bone mineral density.
IM and SUBQ injections are to be administered by a health care professional.
SC: Shake vigorously before use to form a uniform suspension. Inject slowly (over 5–7 sec) at a 45° angle into fatty area of anterior thigh or abdomen every 12–14 wk. If more than 14 wk elapse between injections, rule out pregnancy prior to administration. Do not rub area after injection.
IM: Shake vial or prefilled syringe vigorously before preparing IM dose. Administer deep IM into gluteal or deltoid muscle. Rotate sites with each injection. If period between injections is >14 wk, determine that patient is not pregnant before administering the drug.
- In patients with cancer, IM dose may initially be required weekly. Once stabilized, IM dose may be required only monthly.
- Dose for contraception lasts 3 mo and should not be used longer than 2 yr.

Patient/Family Teaching ⬆ ⬇

Explain the importance of adhering to every 3-mo schedule to patients using medroxyprogesterone for contraception.
Advise patients receiving medroxyprogesterone for menstrual dysfunction to anticipate withdrawal bleeding 3–7 days after discontinuing medication.
Emphasize the importance of notifying health care professional if visual changes, sudden weakness, incoordination, difficulty with speech, headache, leg or calf pain, shortness of breath, chest pain, changes in vaginal bleeding pattern, yellow skin, swelling of extremities, depression, or rash occur.
Advise patient to keep a 1-mo supply of medroxyprogesterone available at all times.
Instruct patient in correct method of monthly breast self-examination. Increased breast tenderness may occur.
Advise patient that gingival bleeding may occur. Instruct patient to use good oral hygiene and to receive regular dental care and examinations.
Inform patient that medroxyprogesterone does not protect against HIV infection and other sexually transmitted infections.
Medroxyprogesterone may cause melasma (brown patches of discoloration) on face when patient is exposed to sunlight. Advise patient to avoid sun exposure and to wear sunscreen or protective clothing when outdoors.
Emphasize the importance of routine follow-up physical exams, including BP; breast, abdomen, and pelvic exams; and Papanicolaou smears every 6–12 mo.
Advise females of reproductive potential to notify health care professional if menstrual period is missed or if pregnancy is suspected or if breastfeeding. Patient should not attempt conception for 3 mo after discontinuing medication in order to ↓ risk to fetus. Once discontinued, may delay conception for 10 mo or more.

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy and with each Rx refill or injection. Take missed doses as soon as remembered; do not double doses.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
IM: SC: Advise patient to maintain adequate amounts of dietary calcium and vitamin D to help prevent bone loss.

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