progesterone

REMS

Crinone, Prometrium, and Oil for Injection

Secondary amenorrhea.

Oil for injection

Abnormal uterine bleeding.

Prometrium

Prevention of endometrial hyperplasia in postmenopausal women who have not had a hysterectomy (with estrogen).

Crinone and Endometrin

Part of assisted reproductive technology in the management of infertility.

Action ⬆ ⬇

Produces:
- Secretory changes in the endometrium,
- Increase in basal body temperature,
- Histologic changes in vaginal epithelium,
- Relaxation of uterine smooth muscle,
- Mammary alveolar tissue growth,
- Pituitary inhibition,
- Withdrawal bleeding in the presence of estrogen.

Therapeutic effects:

Restoration of hormonal balance with control of uterine bleeding.
Successful outcome in assisted reproduction.

Pharmacokinetics ⬆ ⬇

Absorption: Micronization ↑ oral and vaginal absorption.

Distribution: Unknown.

Protein Binding: ≥90%.

Metabolism/Excretion: Metabolized by the liver; 50–60% eliminated by kidneys; 10% eliminated in feces.

Half-Life: Several min.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2–4 hr	unknown
Vaginal	unknown	34.8–55 hr	unknown
IM	unknown	19.6–28 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Hypersensitivity to parabens or sesame oil/seeds (IM suspension only);
Hypersensitivity to peanuts (Prometrium only);
Undiagnosed vaginal bleeding;
Thromboembolic disease;
Cerebrovascular disease;
Severe hepatic impairment;
Breast or genital cancer;
Missed abortion;
OB: Pregnancy.

Use Cautiously in:

Long-term use (more than 4–5 yr); may ↑ risk of MI, stroke, invasive breast cancer, pulmonary emboli (PE), deep vein thrombosis (DVT), and dementia in postmenopausal women;
Hepatic impairment;
Cardiovascular disease;
Depression;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant.

Adv. Reactions/Side Effects ⬆ ⬇

CV: DVT, edema, MI, thrombophlebitis

Derm: chloasma, melasma, rash

EENT: retinal thrombosis

Endo: amenorrhea, breakthrough bleeding, breast tenderness, changes in menstrual flow, galactorrhea, spotting

GI: ↓weight, constipation, hepatitis, nausea

GU: cervical erosions, pelvic pain, vaginal discharge

Local: irritation or pain at IM injection site

Metab: weight gain

Neuro: depression, headache, STROKE

Resp: PE

Misc: gingival bleeding, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), MALIGNANCY (BREAST, ENDOMETRIAL, OVARIAN)

Interactions ⬆ ⬇

Drug-drug:

May ↓ effectiveness of bromocriptine when used concurrently for galactorrhea and amenorrhea.

Route/Dosage ⬆ ⬇

Secondary Amenorrhea

PO (Adults ): 400 mg once daily in the evening for 10 days.
(Adults ): 45 mg (1 applicatorful of 4% gel) once every other day for up to 6 doses; may ↑ to 90 mg (1 applicatorful of 8% gel) once every other day for up to 6 doses.
IM (Adults ): 100–150 mg (single dose) or 5–10 mg once daily for 6–8 days, given 8–10 days before expected menstrual period.

Abnormal Uterine Bleeding

IM (Adults ): 5–10 mg once daily for 6 days.

Prevention of Endometrial Hyperplasia

PO (Adults ): 200 mg once daily at bedtime for 12 days sequentially per 28-day cycle.

Assisted Reproductive Technology

(Adults ): Patients who require progesterone supplementation: 90 mg (1 applicatorful of 8% gel) once daily; if pregnancy occurs, may continue for up to 10–12 wk or 100 mg insert 2 or 3 times daily starting the day after oocyte retrieval and continuing for up to 10 wk total duration; Patients with partial or complete ovarian failure who require progesterone replacement (intravaginal gel): 90 mg (1 applicatorful of 8% gel) twice daily; if pregnancy occurs, may continue for up to 10–12 wk.

Availability ⬆ ⬇

(Generic available)

Capsules (Prometrium): 100 mg; 200 mg
Oil for intramuscular injection: 50 mg/mL
Vaginal gel (Crinone): 4%; 8%
Vaginal insert (Endometrin): 100 mg
In combination with: estradiol (Bijuva). See Appendix [not included in this PDA edition].

Assessment ⬆ ⬇

Monitor BP periodically during therapy.
Monitor intake and output ratios and weekly weight. Report significant discrepancies or steady weight gain.
Monitor for fluid retention; may exacerbate conditions such as HR or renal impairment.
Assess periodically for signs or symptoms of PE (dyspnea, chest pain, cough, tachycardia) or DVT (lower extremity edema, erythema, pain with movements or walking).
Amenorrhea: Assess patient’s usual menstrual history. Administration of drug usually begins 8–10 days before anticipated menstruation. Withdrawal bleeding usually occurs 48–72 hr after course of therapy. Therapy should be discontinued if menses occur during injection series.
Dysfunctional Bleeding: Monitor pattern and amount of vaginal bleeding (pad count). Bleeding should end by 6th day of therapy. Discontinue therapy if menses occur during injection series.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor hepatic function before and periodically during therapy. May cause ↑ alkaline phosphatase levels.
- May ↓ pregnanediol excretion concentrations.
- May cause ↑ low-density lipoprotein cholesterol and ↓ high-density lipoprotein cholesterol.
- May alter thyroid function test results.

Implementation ⬆ ⬇

Discontinuation of oral dose ≥4–6 wk prior to surgery associated with an ↑ risk of thromboembolism or prolonged immobilization is recommended.
PO: Administer at bedtime. For patients who experience difficulty swallowing the capsules, take with a full glass of water while in the standing position.
- Handle intact tablets or capsules with single gloves; use double gloves, respiratory protection, and a protective gown in the preparation of tablets or capsules, including cutting, crushing, or manipulating, or the handling of uncoated tablets; optimally prepare in a ventilated control device.
IM: Shake vial before preparing IM dose. Administer deep IM. Rotate sites.
Vaginal gel and insert are administered with disposable applicator provided by manufacturer.
- Allow ≥6 hr after any other vaginal treatment before using vaginal gel.
- Vaginal insert is not recommended for use with other vaginal products.
- If dose ↑ is required from 4% gel to 8% gel, doubling the volume of the 4% gel will not accomplish dose ↑; changing to 8% gel is required.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of progesterone to patient. Instruct them to take medication as directed. Patient should not use tampons during therapy. Do not share medication with others, even if they have similar symptoms; may be harmful. Keep out of children's reach. Advise patient to read Patient Information sheet before starting therapy and with each Rx refill in case of changes.
Emphasize the importance of routine follow-up physical exams, including BP; breast, abdomen, and pelvic examinations; and Pap smears.
Advise patient to report signs and symptoms of fluid retention (swelling of ankles and feet or weight gain) or hepatic impairment (yellowed skin or eyes, itchy skin, dark urine, light-colored stools).
Advise patient to promptly report signs and symptoms of changes in vision or speech, sudden new severe headaches, severe pains in chest or legs with or without shortness of breath, weakness, or fatigue promptly to health care professional immediately.
Instruct patient to notify health care professional if unusual vaginal bleeding, change in vaginal bleeding pattern, or spotting occurs.
Instruct patient not to use vaginal gel concurrently with other vaginal agents. If these agents must be used concurrently, administer ≥6 hr before or after vaginal gel. Small white globules may appear as a vaginal discharge possibly due to gel accumulation, even several days after use.
Caution patient that cigarette smoking, high BP, high cholesterol, diabetes, and being overweight during progesterone therapy may ↑ risk of DVT or PE.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications or having surgery to avoid potential drug interactions.
Rep: Advise females of reproductive potential to notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇