Dear Colleagues,
Below is the full text of the lomotrigine Dear Doctor Letter sent
to US health professionals requested by Annalisa Campomori. The
boxed warning reproduced in the letter is now required at the
beginning of the professional product labeling (package insert).
Best regards, =
Larry
GlaxoWellcome =
IMPORTANT
DRUG
WARNING
Dear Health Care Professional:
Glaxo Wellcome would like to advise you of new warnings in the
labeling for LAMICTAL (lamotrigine) Tablets, an antiepileptic
drug indicated for adjunctive therapy of partial seizures in
adults with epilepsy. These new warnings pertain to reports of
severe,potentially life-threatening rash, including
Stevens-Johnson syndrome, and rarely, toxic epidermal necrolysis,
reported in association with the use of LAMICTAL
The revised labeling now includes a boxed warning which
emphasizes that LAMICTAL is not indicated for use in patients
below the age of 16 years. =
Specifically, reports from clinical trials suggest that as many
as 1 in 50 to 1 in 100 pediatric patients treated with LAMICTAL
develop a potentially life-threatening rash, as compared with a
rate of approximately one in every thousand adults.
These revisions to the labeling, agreed in consultation with the
US Food and Drug Administration, reflect additional information
obtained through worldwide clinical experience in an estimated
600,000 patients and the ongoing Glaxo Wellcome clinical
development program for LAMICTAL.
Other related changes have been made in the INDICATIONS,
WARNINGS, PRECAUTIONS, ADVERSE EVENTS, and DOSAGE and
ADMINISTRATION sections of the labeling. A full copy of the
revised package insert is enclosed; the major changes are
summarized below:
A boxed warning has been added, as follows:
SEVERE, POTENTIALLY LIFE-THREATENING RASHES HAVE BEEN REPORTED IN
ASSOCIATION WITH THE USE OF LAMICTAL. THESE REPORTS, OCCURRING
IN APPROXIMATELY ONE IN EVERY THOUSAND ADULTS, HAVE INCLUDED
STEVENSJOHNSON SYNDROME (SJS), AND RARELY, TOXIC EPIDERMAL
NECROLYSIS (TEN). RARE DEATHS HAVE BEEN REPORTED, BUT THEIR
NUMBERS ARE TOO FEW TO PERMIT A PRECISE ESTIMATE OF THE RATE.
THE INCIDENCE OF SEVERE, POTENTIALLY LIFE-THREATENING RASH IN
PEDIATRIC PATIENTS, HOWEVER, IS VERY MUCH HIGHER THAN THAT
REPORTED IN ADULTS USING LAMICTAL; SPECIFICALLY, REPORTS FROM
CLINICAL TRIALS SUGGEST AS MANY AS 1 IN 50 TO 1 IN 1 00 PEDIATRIC
PATIENTS DEVELOP A POTENTIALLY LIFE THREATENING RASH. IT BEARS
EMPHASIS, ACCORDINGLY, THAT LAMICTAL IS NOT APPROVED FOR USE IN
PATIENTS BELOW THE AGE OF 16 (SEE INDICATIONS).
OTHER THAN AGE, THERE ARE AS YET NO FACTORS IDENTIFIED THAT ARE
KNOWN TO PREDICT THE RISK OF OCCURRENCE OR THE SEVERITY OF RASH
ASSOCIATED WITH LAMICTAL. THERE ARE SUGGESTIONS, YET TO BE
PROVEN, THAT THE RISK OF RASH MAY ALSO BE INCREASED BY 1)
COADMINISTRATION OF LAMICTAL WITH VALPROIC ACID (VPA); 2)
EXCEEDING THE RECOMMENDED INITIAL DOSE OF LAMICTAL; OR 3) =
EXCEEDING THE RECOMMENDED DOSE ESCALATION FOR LAMICTAL. HOWEVER,
CASES HAVE BEEN REPORTED IN THE ABSENCE OF THESE FACTORS.
NEARLY ALL CASES OF LIFE-THREATENING RASHES ASSOCIATED WITH
LAMICTAL HAVE OCCURRED WITHIN 2 TO 8 WEEKS OF TREATMENT
INITIATION. HOWEVER, ISOLATED CASES HAVE BEEN REPORTED AFTER
PROLONGED TREATMENT (E.G., 6 MONTHS). =
ACCORDINGLY, DURATION OF THERAPY CANNOT BE RELIED UPON AS A MEANS
TO PREDICT THE POTENTIAL RISK HERALDED BY THE FIRST APPEARANCE OF
A RASH.
ALTHOUGH BENIGN RASHES ALSO OCCUR WITH LAMICTAL, IT IS NOT
POSSIBLE TO PREDICT RELIABLY WHICH RASHES WILL PROVE TO BE
LIFE-THREATENING. =
ACCORDINGLY, LAMICTAL SHOULD BE DISCONTINUED AT THE FIRST SIGN OF
RASH, UNLESS THE RASH IS CLEARLY NOT DRUG-RELATED. =
DISCONTINUATION OF TREATMENT MAY NOT PREVENT A RASH FROM BECOMING
LIFE-THREATENING OR PERMANENTLY DISABLING OR DISFIGURING.
The WARNINGS section has been revised to include the following
information regarding hypersensitivity reactions:
"Hypersensitivity reactions: Hypersensitivity reactions, some
fatal or life-threatening, have also occurred. Some of these
reactions have included clinical features of multiorgan
dysfunction such as hepatic abnormalities and evidence of
disseminated intravascular coagulation. It is important to note
that early manifestations of hypersensitivity (e.g., fever,
lymphadenopathy) may be present even though a rash is not
evident. If such signs or symptoms are present, the patient
should be evaluated immediately. LAMICTAL should be discontinued
if an alternative etiology for the signs or symptoms cannot be
established.
Prior to initiation of treatment with LAMICTAL, the patient
should be instructed that a rash or other signs or symptoms of
hypersensitivity (e.g., fever, lymphadenopathy) may herald a
serious medical event and that the patient should report any such
occurrence to a physician immediately."
The medical community can further our understanding of LAMICTAL
by reporting adverse events to the Glaxo Wellcome Product
Surveillance Department at 1-800-334-4153 or to the FDA MEDWATCH
program by phone 1-800-FDA-1088, by FAX at 1-800-FDA-0178, by
modem 1-800-FDA-7737, or by mail:
MEDWATCH HF-2
FDA
5600 Fishers Lane
Rockville, MD 20857
Glaxo Wellcome is committed to helping you treat your epilepsy
patients, and encourages you to familiarize yourself with these
changes to the package insert so that the proper use of LAMICTAL
may be facilitated through your clinical care and treatment of
patients. If you have any questions about the new information in
the package insert for LAMICTAL Tablets, please contact the Drug
Information Department at Glaxo Wellcome (1-800-334-0089).
Sincerely,
Richard S. Kent, MD
Vice President and Chief Medical Officer
Glaxo Wellcome Inc.