Date: 2003-06-09

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MHPD-DPSC

IMPORTANT SAFETY INFORMATION
ON ESTROGEN PLUS PROGESTIN (PREMPLUS™ TABLETS)

May 28, 2003

Dear Health Care Professional,

Data from the Women's Health Initiative Memory Study (WHIMS), a substudy of the Women's Health Initiative (WHI) conducted in women age 65 and older, have been published in the May 28, 2003 issue of the Journal of the American Medical Association (JAMA). These reports have added to our knowledge concerning the effects of postmenopausal estrogen plus progestin therapy on dementia and cognition.

WHIMS RESULTS

WHIMS, a substudy of WHI supported by Wyeth, was a randomized, placebo-controlled prospective study that evaluated whether postmenopausal estrogen and progestin hormone therapy would reduce the risk of dementia in women age 65 and older¹. WHIMS followed 4,532 women for an average of 4.1 years.

The authors of the WHIMS publications state that women taking combination estrogen plus progestin therapy had an increased relative risk (2.05, 95% CI, 1.21-3.48) of developing probable dementia (PD) compared to women taking placebo. In both groups, the absolute risk for developing PD was low (45 cases/10,000 women per year for women taking the active drug, 22 cases/10,000 women per year for women taking placebo). The increase in the relative risk was observed in all age groups studied, began in the second year, and persisted. The absolute risk was highest in the oldest age group studied (women 75 and older), which comprised 18.4% of the sample size of the treatment arm.

In a separate report on WHIMS, the effect of hormone therapy on global cognitive function was evaluated². Overall, there was no clinically significant difference between the groups. The average cognitive test score for these women improved in both the active drug group and the control group. However, the treated group improved somewhat less than the control group. Additionally, more women in the estrogen plus progestin group had a substantial and clinically important decline in cognitive function.

An independent study arm of WHIMS evaluating the effect of estrogen alone on probable dementia and cognitive function in a similar population is currently ongoing.

PRESCRIBING CONSIDERATIONS

Wyeth recognizes the potential relevance of this information to all women, particularly for those age 65 and older. WHIMS evaluated women who were on average 71 years of age, and, therefore, the applicability of these results to younger women is unclear. Even so, the company believes that the WHIMS results should be considered part of the individual assessment of risk and benefit for women who are taking or considering initiating estrogen plus progestin therapy. Wyeth continues to support the appropriate use of hormone therapy for its labeled indications-relief of menopausal symptoms such as hot flashes, night sweats, and vaginal dryness and the concomitant prevention of postmenopausal osteoporosis. Hormone therapy should be prescribed at the lowest dose for the shortest duration consistent with individual treatment goals and risks for the individual woman.

Wyeth will work with Health Canada to determine what implications the WHIMS data have for labeling. A copy of this revised label information will be provided to you in a separate communication as soon as available .

The identification, characterization, and management of drug-related adverse events is dependent on the active participation of health care professionals in adverse drug reaction reporting programmes. Health care professionals are asked to report any suspected adverse reactions in patients receiving Premplus Tablets (estrogen plus progestin) to at the following address:

Wyeth Canada
Medical Information & Pharmacovigilance Department
50 Minthorn Boulevard
MARKHAM, Ontario, L3T 7Y2
Tel: 1-800-461-8844
Fax: (905)-470-4385

Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed drug use.

If you have any questions about this information, please contact Wyeth Medical Information at 1-800-461-8844.

Sincerely,

original signed by

Neil Maresky, M.B., B.Ch.,
Vice-President
Scientific Affairs

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