Side Effects of Prometrium (progesterone)

Prometrium (progesterone) is a man-made medication derived from a plant source and is identical to the female hormone progesterone produced in the ovaries used to help regulate the uterine lining in post-menopausal women.

Progesterone is involved in the following:

• promoting the development of the mammary glands,
• causing changes in the endometrium, which lines the uterus,
• relaxing uterine smooth muscles,
• blocking ovulation within the ovaries, and
• maintaining pregnancy. 

Common side effects of Prometrium include

• headache,
• dizziness,
• fatigue,
• abdominal pain,
• nausea,
• breast tenderness,
• joint pain,
• depression,
• mood swings, and
• hot flashes.

Serious side effects of Prometrium include

• cardiovascular disorders,
• breast cancer, and
• possibly dementia in postmenopausal women.

Drug interactions of Prometrium include

• ketoconazole,
• clarithromycin, and
• erythromycin because they slow the breakdown of progesterone and increase its levels in the body.

Prometrium should not be used during pregnancy. Prometrium may be found in trace amounts in breast milk. Consult your doctor before breastfeeding.

Side effects of progesterone are

• headache,
• dizziness,
• fatigue,
• abdominal pain,
• nausea,
• breast tenderness,
• joint pain,
• depression,
• mood swings, and
• hot flashes.

Progesterone also is associated with

• cardiovascular disorders,
• breast cancer, and
• possibly dementia in postmenopausal women.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In a multicenter, randomized, double-blind, placebo-controlled clinical trial, the effects of Prometrium Capsules on the endometrium was studied in a total of 875 postmenopausal women.

Table 6 lists adverse reactions greater than or equal to 2 percent of women who received cyclic Prometrium Capsules 200 mg daily (12 days per calendar month cycle) with 0.625 mg conjugated estrogens or placebo.

TABLE 6. Adverse Reactions (≥ 2%) Reported in an 875 Patient Placebo-Controlled Trial in Postmenopausal Women Over a 3-Year Period [Percentage (%) of Patients Reporting]

Effects On Secondary Amenorrhea

In a multicenter, randomized, double-blind, placebo-controlled clinical trial, the effects of Prometrium Capsules on secondary amenorrhea was studied in 49 estrogen-primed postmenopausal women.

Table 7 lists adverse reactions greater than or equal to 5 percent of women who received Prometrium Capsules or placebo.

TABLE 7. Adverse Reactions (≥ 5%) Reported in Patients Using 400 mg/day in a Placebo- Controlled Trial in Estrogen-Primed Postmenopausal Women

In a multicenter, parallel-group, open label postmarketing dosing study consisting of three consecutive 28-day treatment cycles, 220 premenopausal women with secondary amenorrhea were randomized to receive daily conjugated estrogens therapy (0.625 mg conjugated estrogens) and Prometrium Capsules, 300 mg per day (n=113) or Prometrium Capsules, 400 mg per /day (n=107) for 10 days of each treatment cycle.

Overall, the most frequently reported treatment-emergent adverse reactions, reported in greater than or equal to 5 percent of subjects, were

• nausea,
• fatigue,
• vaginal mycosis,
• nasopharyngitis,
• upper respiratory tract infection,
• headache, dizziness,
• breast tenderness,
• abdominal distension,
• acne,
• dysmenorrhea,
• mood swing, and
• urinary tract infection.

Postmarketing Experience

The following additional adverse reactions have been reported with Prometrium Capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Genitourinary System

endometrial carcinoma, hypospadia, intra-uterine death, menorrhagia, menstrual disorder, metrorrhagia, ovarian cyst, spontaneous abortion.

Cardiovascular

circulatory collapse, congenital heart disease (including ventricular septal defect and patent ductus arteriosus), hypertension, hypotension, tachycardia.

Gastrointestinal

acute pancreatitis, cholestasis, cholestatic hepatitis, dysphagia, hepatic failure, hepatic necrosis, hepatitis, increased liver function tests (including alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased), jaundice, swollen tongue.

Skin

alopecia, pruritus, urticaria.

Eyes

blurred vision, diplopia, visual disturbance.

Central Nervous System

aggression, convulsion, depersonalization, depressed consciousness, disorientation, dysarthria, loss of consciousness, paresthesia, sedation, stupor, syncope (with and without hypotension), transient ischemic attack, suicidal ideation.

During initial therapy, a few women have experienced a constellation of many or all of the following symptoms: extreme dizziness and/or drowsiness, blurred vision, slurred speech, difficulty walking, loss of consciousness, vertigo, confusion, disorientation, feeling drunk, and shortness of breath.

Miscellaneous

abnormal gait, anaphylactic reaction, arthralgia, blood glucose increased, choking, cleft lip, cleft palate, difficulty walking, dyspnea, face edema, feeling abnormal, feeling drunk, hypersensitivity, asthma, muscle cramp, throat tightness, tinnitus, vertigo, weight decreased, weight increased.

Drug-Laboratory Test Interactions

The following laboratory results may be altered by the use of estrogen plus progestin therapy:

• Increased sulfobromophthalein retention and other hepatic function tests.
• Coagulation tests: increase in prothrombin factors VII, VIII, IX and X.
• Pregnanediol determination.
• Thyroid function: increase in PBI, and butanol extractable protein bound iodine and decrease in T3
uptake values.