Prometrium

progesterone

Crinone, Endometrin, Prometrium

Pharmacologic class: Progestin

Therapeutic class: Hormone

Pregnancy risk category B (oral), D (injection),NR (vaginal)

FDA Box Warning

• Estrogen plus progestin therapy shouldn't be used for prevention of cardiovascular disease or dementia.

• The Women's Health Initiative (WHI) estrogen plus progestin substudy reported increased risk of stroke, deep vein thrombosis, pulmonary embolism, and myocardial infarction in postmenopausal women (ages 50 to 79) during 5.6 years of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo.

• The substudy also demonstrated increased risk of invasive breast cancer.

• The WHI Memory Study estrogen plus progestin ancillary study of the WHI reported increased risk of dementia in postmenopausal women ages 65 and older.

Action

Suppresses ovulation by altering the vaginal epithelium, relaxing uterine smooth muscle, and promoting mammary tissue growth. Also inhibits pituitary activity and causes withdrawal bleeding in presence of estrogen.

Availability

Injection (in sesame or peanut oil with benzyl alcohol): 50 mg/ml in 10-ml vials

Micronized capsules (oral) in peanut oil: 100 mg, 200 mg

Micronized vaginal gel: 4%, 8%

Indications and dosages

➣ Secondary amenorrhea

Adults: 400 mg/day P.O. in evening for 10 days, or 5 to 10 mg/day I.M. for 6 to 8 days, given 8 to 10 days before expected menstrual period. Or 45 mg (one applicatorful of 4% gel) vaginally once every other day for up to six doses; may increase to 90 mg (one applicatorful of 8% gel) once every other day for up to six doses.

➣ Dysfunctional uterine bleeding

Adults: 5 to 10 mg I.M. daily for 6 days

➣ To prevent postmenopausal estrogen-induced endometrial hyperplasia

Adults: 200 mg/day P.O. at bedtime for 14 days on days 8 to 21 of 28-day cycle or on days 12 to 25 of 30-day cycle. If patient currently receives estrogen 1.25 mg/day, 300 mg progesterone in two divided doses (100 mg 2 hours after breakfast and 200 mg at bedtime); further adjustment may be required.

➣ Corpus luteum insufficiency; assisted reproduction technology

Adults: For luteal-phase support, 90 mg (one applicatorful of 8% gel) vaginally once daily. For in vitro fertilization, 90 mg (one applicatorful of 8% gel) vaginally once daily, starting within 24 hours of embryo transfer and continued through day 30 after transfer; if pregnancy occurs, treatment may continue for up to 12 weeks. For partial or complete ovarian failure, 90 mg (one applicatorful of 8% gel) vaginally b.i.d. while patient undergoes donor oocyte transfer; if pregnancy occurs, treatment may last up to 12 weeks.

Contraindications

• Hypersensitivity to drug, peanuts (injection, micronized capsules), or sesame (injection)

• Thromboembolic disease

• Cerebrovascular disease

• Severe hepatic disease

• Porphyria

• Breast or reproductive system cancer

• Missed abortion

• Undiagnosed vaginal bleeding

• Diagnosis of pregnancy

Precautions

Use cautiously in:

• renal or cardiovascular disease, seizure disorders, fluid retention, diabetes mellitus, asthma, migraine, depression

• history of hepatic disease

• breastfeeding patients.

Administration

• Before first dose, make sure patient has read package insert regarding adverse effects. Reinforce written information with oral review.

See Before first I.M. dose, ask if patient has allergy to peanuts or sesame. Before giving micronized capsules, ask about peanut allergy.

• Inject I.M. dose deep into muscle. Rotate injection sites.

Adverse reactions

CNS: depression, emotional lability, cerebrovascular accident

CV: thrombophlebitis, thromboembolism

EENT: retinal thrombosis

GI: abdominal cramps

GU: amenorrhea, breakthrough bleeding, spotting, cervical erosions, breast tenderness, menstrual flow changes, galactorrhea

Hepatic: hepatitis

Respiratory: pulmonary embolism

Skin: melasma, rash, angioedema

Other: gingival bleeding, weight gain or loss, hypersensitivity reactions including anaphylaxis

Interactions

Drug-drug. Conjugated estrogens: increased levels of both drugs

Drug-diagnostic tests. Alkaline phosphatase, amino acids, low-density lipoproteins: increased levels

Chloride and sodium excretion: reduced (with high doses)

High-density lipoproteins: decreased level

Pregnanediol excretion: reduced

Thyroid function tests: altered results

Drug-herbs. Red clover: interference with drug effects

Drug-behaviors. Smoking: increased risk of thromboembolic effects

Patient monitoring

See Watch for evidence of thromboembolic disorders, including cerebrovascular accident, pulmonary embolism, diplopia, proptosis, or sudden partial or complete vision loss (may signal retinal thrombosis). If these occur, discontinue drug and notify prescriber immediately.

See Assess for emotional lability and depression.

Patient teaching

See Teach patient to recognize and immediately report signs and symptoms of thromboembolic disorders.

See Instruct patient and significant other to stay alert for and immediately report depression.

• Advise patient to monitor weight regularly and report significant changes.

• Tell female patient that drug may cause menstrual abnormalities.

• Advise female patient to discuss breastfeeding with prescriber before taking drug.

See Instruct patient to immediately report possible pregnancy.

• Tell patient that smoking increases thromboembolism risk. Encourage her to stop smoking if she smokes.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.

progesterone

(proe-jess-te-rone) progesterone,

Crinone

(trade name),

Endometrin

(trade name),

Prochieve

(trade name),

Prometrium

(trade name)

Classification

Therapeutic: hormones
Pharmacologic: progestins
Pregnancy Category: D

Indications

Secondary amenorrhea and abnormal uterine bleeding due to hormonal imbalance.Prometrium: Prevention of cell overgrowth in the uterine lining in postmenopausal women who have not had a hysterectomy (with estrogen).Part of assisted reproductive technology (ART) in the management of infertility (4% and 8% vaginal gel).Endometrin: Support of embryo implantation and early pregnancy.Corpus luteum dysfunction.

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 increases oral and vaginal absorption.Distribution: Enters breast milk.Protein Binding: ≥90%.Metabolism and Excretion: Metabolized by the liver; 50–60% eliminated by kidneys; 10% eliminated in feces.Half-life: Several minutes.

Time/action profile (blood levels)

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

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Hypersensitivity to parabens or sesame oil (IM suspension only);Hypersensitivity to peanuts (Prometrium only);Thromboembolic disease;Cerebrovascular disease;Severe liver disease;Breast or genital cancer;Porphyria;Missed abortion; Obstetric: Contraindicated except in corpus luteum dysfunction.Use Cautiously in: History of liver disease;Renal disease;Cardiovascular disease;Seizure disorders;Mental depression.

Adverse Reactions/Side Effects

Central nervous system

depression

Ear, Eye, Nose, Throat

retinal thrombosis

Cardiovascular

pulmonary embolism (life-threatening)
thromboembolism (life-threatening)
thrombophlebitis

Gastrointestinal

gingival bleeding
hepatitis

Genitourinary

cervical erosions

Dermatologic

chloasma
melasma
rashes

Endocrinologic

amenorrhea
breakthrough bleeding
breast tenderness
changes in menstrual flow
galactorrhea
spotting

Fluid and Electrolyte

edema

Local

irritation or pain at IM injection site

Miscellaneous

allergic reactions including anaphylaxis and angioedema (life-threatening)
weight gain
weight loss

Interactions

Drug-Drug interaction

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

Route/Dosage

Oral (Adults) Secondary amenorrhea—400 mg once daily in the evening for 10 days; prevention of postmenopausal estrogen-induced endometrial hyperplasia—200 mg once daily at bedtime for 14 days on days 8–21 of a 28-day cycle or on days 12–25 of a 30-day cycle; if patient currently receives ≥1.25 mg/day of estrogen, then a daily of dose of 300 mg of progesterone as 100 mg 2 hr after breakfast and 200 mg at bedtime is used; further adjustments may be required.Vaginal (Adults) Secondary amenorrhea—45 mg (1 applicatorful of 4% gel) once every other day for up to 6 doses, may be ↑ to 90 mg (1 applicatorful of 8% gel) once every other day for up to 6 doses; Corpus luteum insufficiency or assisted reproduction technology—For luteal phase support: 90 mg (1 applicatorful of 8% gel) once daily; for in vitro fertilization: 90 mg (1 applicatorful of 8% gel) once daily beginning within 24 hr of embryo transfer and continued through day 30 post-transfer (if pregnancy occurs, treatment may be continued for up to 10–12 wk); partial or complete ovarian failure—90 mg (1 applicatorful of 8% gel) twice daily while undergoing donor oocyte transfer (if pregnancy occurs, treatment may be continued for up to 10–12 wk) Support of embryo implantation and early pregnancy—100 mg insert 2 or 3 times daily for up to 10 wk.Intramuscular (Adults) Secondary amenorrhea—100–150 mg (single dose) or 5–10 mg daily for 6–8 days given 8–10 days before expected menstrual period. Dysfunctional uterine bleeding—5–10 mg daily for 6 days. Corpus luteum insufficiency—12.5 mg/day at onset of ovulation for 2 wk; may continue until 11th wk of gestation (unlabeled).

Availability (generic available)

Micronized capsules (Prometrium): 100 mg, 200 mg Bioadhesive vaginal gel (Crinone, Prochieve): 4%, 8% Vaginal tablets (Endometrin): 100 mg Injection: 50 mg/mL

Nursing implications

Nursing assessment

BP be monitored periodically during therapy.
- Monitor intake and output ratios and weekly weight. Report significant discrepancies or steady weight gain.
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. Therapy should be discontinued if menses occur during injection series.
Lab Test Considerations: Monitor hepatic function before and periodically during therapy.
- May cause ↑ plasma amino acid and alkaline phosphatase levels.
- May ↓ pregnanediol excretion concentrations.
- May cause ↑ serum concentrations of LDL and ↓ concentrations of HDL.
- High doses may ↑ sodium and chloride excretion.
- May alter thyroid function test results.

Potential Nursing Diagnoses

Sexual dysfunction (Indications)

Implementation

Intramuscular: Shake vial before preparing IM dose. Administer deep IM. Rotate sites.
Vaginal: Vaginal gel and insert are administered with disposable applicator provided by manufacturer.
- If dose increase is required from 4% gel to 8% gel, doubling the volume of the 4% gel will not accomplish dose increase; changing to 8% gel is required.

Patient/Family Teaching

Advise patient to report signs and symptoms of fluid retention (swelling of ankles and feet, weight gain), thromboembolic disorders (pain, swelling, tenderness in extremities, headache, chest pain, blurred vision), mental depression, or hepatic dysfunction (yellowed skin or eyes, pruritus, dark urine, light-colored stools) to health care professional.
Instruct patient to notify health care professional if change in vaginal bleeding pattern or spotting occurs.
Instruct patient to stop taking medication and notify health care professional if pregnancy is suspected.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Advise patient to notify health care professional of medication regimen before treatment or surgery.
Emphasize the importance of routine follow-up physical exams, including BP; breast, abdomen, and pelvic examinations; and Pap smears.
Vaginal: Instruct patient not to use vaginal gel concurrently with other vaginal agents. If these agents must be used concurrently, administer at least 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.

Evaluation/Desired Outcomes

Development of normal cyclic menses.
Successful outcome in assisted reproduction.

Prometrium®

Micronized progesterone Gynecology A formulation of progesterone for treating 2º amenorrhea and preventing endometrial hyperplasia in postmenopausal ♀ who have not had hysterectomy and who are receiving conjugated estrogen Contraindications Peanut allergy, severe liver disease, breast CA. See Endometrial hyperplasia.