August 1, 2006

Dear Healthcare Professional,

GlaxoSmithKline Inc. (GSK), following discussions with Health Canada, would like to inform you of important new safety information concerning the antiepileptic, LAMICTAL^® (lamotrigine).

Recently published data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry report three cases of isolated, non syndromic cleft palate and two cases of isolated, non syndromic cleft lip without cleft palate in infants from 564 first trimester lamotrigine monotherapy exposures, giving a rate of 8.9 per 1,000.² This compares with a prevalence rate of 0.37 per 1,000 seen in the general population of the Brigham and Women's Hospital (BWH) Surveillance Program (relative risk in lamotrigine-treated patients vs. BWH general population of 24; 95% CI 10.0-57.4). The NAAED data did not show an increase in the overall risk of major congenital malformations associated with lamotrigine (15/564 = 2.7% or 27 per 1000).

Data from additional Pregnancy Registries

Data from additional pregnancy registries are currently being assessed to provide a more complete picture. Given the heterogeneity in data collection processes across the registries, and the variety of factors considered to play a role in the risk of oral clefts, including genetics, the optimal route for analysis of all data remains to be decided. Follow-up information will be provided via the appropriate channels when available.

Updates to Prescribing Information

GlaxoSmithKline is in discussion with regulatory authorities around the world about these newly reported data and other relevant information, including outcomes in over 2000 pregnancies from other pregnancy registries, to further understand the significance of this finding. GSK will update prescribing information as necessary and patient information, as appropriate, on conclusion of these discussions. As is currently stated in the Product Monograph, patients should be advised to notify their physicians if they become pregnant or intend to become pregnant during therapy. Although pregnant women and their unborn children may face significant health risks from uncontrolled epilepsy, LAMICTAL^® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

To facilitate monitoring fetal outcomes of pregnant women exposed to lamotrigine, physicians are encouraged to register patients, before fetal outcome (e.g., ultrasound, results of amniocentesis, birth, etc.) is known, and can obtain information by calling the Lamotrigine Pregnancy Registry at (800) 336-2176 (toll-free). Patients can enroll themselves in the NAAED Pregnancy Registry by calling (888) 233-2334 (toll-free).

GSK continues to work closely with Health Canada to monitor adverse event reporting and to ensure that up-to-date information regarding the use of lamotrigine is available.

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of cleft lip and/or cleft palate or other serious or unexpected adverse reactions in patients receiving LAMICTAL^® should be reported to GlaxoSmithKline Inc., or Health Canada at the following addresses:

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

Any questions from health care professionals may be directed to Medical Information via GSK Customer service at 1-800-387-7374.

Sincerely,

original signed by

Dr John A Dillon MB BCh MFPM
VP, Medical Division and Chief Medical Officer
GlaxoSmithKline Inc.

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