How should I write a prescription for Prometrium (micronized progesterone) 100 mg for its approved indications?

How to Prescribe Prometrium (Micronized Progesterone) 100mg

For endometrial protection in women on estrogen therapy with an intact uterus, prescribe Prometrium 200mg orally at bedtime for 12-14 consecutive days every 28 days, using two 100mg capsules. 1, 2

Standard Dosing Regimen

Sequential (Cyclic) Dosing:

• Dose: 200mg daily (two 100mg capsules) 1
• Duration: 12-14 consecutive days per 28-day cycle 1, 2
• Timing: Administer at bedtime to minimize drowsiness and dizziness 3, 4
• Expected outcome: Withdrawal bleeding will occur after each progestin cycle 2

Alternative route if oral not tolerated:

• Vaginal administration: 200mg daily for 12-14 days every 28 days 1, 2
• Vaginal route provides adequate endometrial protection despite lower systemic progesterone levels due to direct vagina-to-uterus transport 5

Clinical Context and Rationale

Why micronized progesterone is preferred:

• Micronized progesterone (MP) is the first-choice progestin due to its superior safety profile compared to synthetic progestins 1
• Lower risk of cardiovascular disease and venous thromboembolism compared to synthetic progestins like medroxyprogesterone acetate (MPA) 1, 3
• Provides adequate endometrial protection when used cyclically 1, 3
• Better metabolic profile and reduced breast cancer risk compared to synthetic progestins 3, 4

Baseline Assessment

Before initiating therapy:

• Perform baseline transvaginal ultrasound to confirm appropriate endometrial thickness 2
• This ensures no pre-existing endometrial pathology before starting progestin therapy 2

Continuous Regimen (If Avoiding Withdrawal Bleeding)

For patients who cannot tolerate or wish to avoid withdrawal bleeding:

• Continuous dosing requires higher daily doses than available with 100mg formulation alone 1
• Minimum continuous dose: 2.5mg MPA daily or 5mg dydrogesterone daily 1
• Note: Standard 100mg Prometrium capsules are not designed for continuous daily use; sequential dosing is the evidence-based approach for this formulation 1, 2

Administration Instructions

Patient counseling points:

• Take at bedtime to minimize side effects of drowsiness and dizziness 3, 4
• These neurosteroid effects can be beneficial for sleep and anxiety but may impair daytime functioning if taken in the morning 3
• Expect withdrawal bleeding 2-3 days after completing each 12-14 day cycle 2
• If vaginal route is used, the bioadhesive gel formulation provides controlled sustained release 5

Common Pitfalls to Avoid

Dosing errors:

• Do not prescribe 100mg daily for endometrial protection—this is insufficient 1, 2
• The standard protective dose is 200mg daily for 12-14 days, requiring two 100mg capsules 1, 2

Duration errors:

• Do not prescribe for fewer than 12 days per cycle—inadequate endometrial protection 1, 2
• 12-14 days is the evidence-based duration for preventing endometrial hyperplasia 1, 2, 4

Timing considerations:

• Avoid progestins with anti-androgenic effects in women with low testosterone or sexual dysfunction 1
• Micronized progesterone does not have anti-androgenic properties, making it suitable for these patients 1

Sample Prescription Format

Rx: Prometrium 100mg capsules

• Sig: Take 2 capsules (200mg total) by mouth at bedtime daily for 14 consecutive days, starting on day 15 of each 28-day cycle
• Dispense: 28 capsules (for one cycle)
• Refills: As appropriate for ongoing therapy