Regulatory Decision Summary for pms-Progesterone

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.

Product type:


Medicinal ingredient(s):

progesterone capsules

Therapeutic area:

Sex Hormones and Modulators of the Genital System

Type of submission:

New Drug Submission

Control number:

What was the purpose of this submission?


This New Drug Submission (NDS) was filed to seek market authorization for pms-Progesterone (micronized progesterone capsules, 200 mg) for use in women with an intact uterus as an adjunct to postmenopausal estrogen replacement therapy to reduce the risk of endometrial hyperplasia and carcinoma.


Why was the decision issued?


Pharmascience Inc. was required to file a NDS as opposed to an Abbreviated New Drug Submission (ANDS) because this new 200 mg strength was considered to fall outside of the current approved labelling (in the event of a missed dose) for Prometrium. The proposed 200 mg strength is intended to provide dosage flexibility for optimal patient management.

Neither non-clinical nor clinical studies were provided in support of the proposed product, pms-Progesterone (200 mg capsules). Instead, data from a bioequivalence study (Study #830-14) were provided in order to bridge the proposed pms-Progesterone 200 mg capsules to the Canadian Reference Product, Prometrium (100 mg capsules). The results of the bioequivalence study demonstrated that pms-Progesterone 200 mg capsules met the reference-scaled average comparative bioavailability standards with Prometrium (2 x 100 mg capsules) when administered under fasting conditions.

Estrogen therapy has been used for the management of menopausal symptoms, including vulvar and vaginal atrophy and vasomotor symptoms. A regimen that combines a progestin drug with estrogen has been shown to reduce the risk of estrogen-induced endometrial hyperplasia. The adverse events (AEs) that could be considered to be possibly associated with micronized progesterone therapy are: breakthrough bleeding, spotting, and menstrual irregularity. Under the recommended conditions of use, dizziness, somnolence, cramps or nausea have been reported occasionally. Fatigue, headache, vertigo, light-headedness or migraine have been reported rarely. Breast tenderness may occur with the use of pms-Progesterone. Other AEs which are generally attributed to synthetic progestins and which may possibly occur during pms-Progesterone treatment include: chloasma, pruritus, jaundice, rash, fluid retention, mental depression and thrombotic disorders. The addition of progestins to estrogen therapy may also be associated with increases in the risk of a variety of serious AEs, such as breast cancer, thromboembolic events, and myocardial infarction.

Overall, Health Canada considers that the benefit-harm-uncertainty profile of pms-Progesterone 200 mg capsules is similar to other formulations of progesterone and that the benefit-harm-uncertainty profile of pms-Progesterone 200 mg capsules is favourable when used under the supervision of a health care provider for the specified indication.


Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.