Prometrium Restarting After Acute Illness: A Clinical Guide

What the Prometrium label schedules

Prometrium is oral micronized progesterone. The labeled endometrial-protection regimen is 200 mg as a single daily dose at bedtime for 12 days sequentially per 28-day cycle, for a postmenopausal woman with a uterus who is receiving daily conjugated estrogens tablets [1]. For secondary amenorrhea, the labeled dose is 400 mg at bedtime for 10 days [1]. The label's studies and dosing use conjugated estrogens, not estradiol [1].

Bedtime is part of the label. The patient leaflet says to take it at bedtime because some women become very drowsy or dizzy [2]. The label warns that Prometrium may cause transient dizziness and drowsiness and should be used with caution when driving or operating machinery, and that it should be taken as a single daily dose at bedtime [1]. In the 3-year endometrial trial, dizziness was reported by 15% of women taking cyclic Prometrium 200 mg plus conjugated estrogens and 9% taking placebo; the placebo group took no hormones [2]. The label also reports that during initial therapy a few women had extreme dizziness or drowsiness, blurred vision, slurred speech, difficulty walking, loss of consciousness, vertigo, confusion, disorientation, feeling drunk, and shortness of breath [1][2].

Food is separate from the bedtime instruction. In a food-effect study at 200 mg in postmenopausal women, food increased progesterone bioavailability relative to fasting [2].

What acute illness can change

The most directly relevant label limits are the contraindications. Prometrium is contraindicated in active deep vein thrombosis or pulmonary embolism or a history of these, active arterial thromboembolic disease such as stroke or MI or a history of these, and known liver dysfunction or disease [1]. The label says to stop immediately if a PE, DVT, stroke or MI occurs or is suspected [2]. If feasible, it says to discontinue at least 4 to 6 weeks before surgery of a type associated with increased thromboembolism risk, or during prolonged immobilization [2].

Other label cautions: progesterone may cause some degree of fluid retention, and women with cardiac or renal dysfunction warrant careful observation [1]. The capsules contain peanut oil, and peanut allergy is a contraindication [1]. The label states that the pharmacokinetics of Prometrium have not been studied in hepatic or renal impairment [2].

The restart question

For endometrial protection, the labeled schedule is 200 mg at bedtime for 12 days per 28-day cycle with daily conjugated estrogens. For secondary amenorrhea, it is 400 mg at bedtime for 10 days [1]. The label gives no separate schedule for resuming after an illness, and it does not give a time to resume after surgery or prolonged immobilization [1][2].