Archived – Important New Safety Information Clarifying Risk Factors for Severe, Life-threatening and Fatal Hepatotoxicity with VIRAMUNE® (Nevirapine)

Starting date:

February 20, 2004

Posting date:

March 12, 2004

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Issue:

Important Safety Information

Audience:

Healthcare Professionals

Identification number:

RA-17000875

This is duplicated text of a letter from Boehringer Ingelheim (Canada) Ltd.
Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on VIRAMUNE (nevirapine)

February 20, 2004

Dear Health Care Professional,

Subject: Important New Safety Information Clarifying Risk Factors for Severe, Life-threatening and Fatal Hepatotoxicity with Viramune^® (nevirapine)

Boehringer Ingelheim (Canada) Ltd., following discussions with Health Canada, is writing to inform you of important new labelling information being added to the Warnings Section of the Product Monograph for VIRAMUNE Tablets, 200 mg, a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents. Specifically, we wish to draw your attention to the following:

Women with CD4+ counts >250 cells/mm³ at initiation of therapy, including pregnant women receiving chronic treatment for HIV infection, are at considerably higher risk (12-fold) of hepatotoxicity, which in some cases has been fatal. This subset of patients was identified by analyses of CD4 count at the time of initiation of VIRAMUNE therapy.

The greatest risk of severe and potentially fatal hepatic events (often associated with rash) occurs in the first 6 weeks of VIRAMUNE treatment. However, the risk continues after this time and patients should be closely monitored for the first 18 weeks of treatment.

In some cases, hepatic injury progresses despite discontinuation of the drug.

This new information is the result of recent post-marketing surveillance data and further analysis of the VIRAMUNE clinical trial database.

Although this new information describes patients at increased risk, it is important to note that any patient can experience hepatic events and should be monitored carefully. It may be prudent initially to conduct clinical and laboratory monitoring more often than once per month, for example, liver function tests at baseline, prior to dose escalation and at two weeks post dose escalation.

All patients developing a rash, at any time during VIRAMUNE treatment, but particularly during the first 18 weeks, should have liver function tests performed at that time. After the initial 18 week period, frequent clinical and laboratory monitoring should continue throughout VIRAMUNE treatment. Patients with rash and moderate to severe elevations (AST or ALT > 5xULN) should be permanently discontinued from VIRAMUNE. VIRAMUNE must be permanently discontinued in any patient experiencing severe rash or a rash accompanied by constitutional symptoms such as fever, blistering, oral lesions, conjunctivitis, facial edema, muscle or joint aches, or general malaise.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis may be preceded by a prodrome of flu-like symptoms including fever, malaise, rhinitis, nausea, chest pain, vomiting, sore throat, cough, dizziness, diarrhea, headache, myalgia and arthralgia. Patients should be closely monitored if flu-like symptoms and/or an isolated rash occurs.

It is important to counsel all patients that if signs or symptoms of hepatitis, severe skin reactions or hypersensitivity reactions occur, they should discontinue VIRAMUNE treatment and seek medical attention immediately. VIRAMUNE should not be restarted in these patients.

Based upon our Canadian post-marketing data, since 1998 there has been one reported case of life threatening Stevens-Johnson Syndrome with hepatitis (non fatal) in a woman treated with VIRAMUNE in combination with other antiretroviral agents.

Reporting rates determined on the basis of spontaneously reported post-marketing adverse events are generally presumed to underestimate the risks associated with drug treatments.

Due to the significance of this information, Boehringer Ingelheim (Canada) Ltd. is currently working with Health Canada to include this new safety information in the Product Monograph.

The identification, characterization, and management of drug-related adverse events are dependent on the active participation of health care professionals in adverse drug reaction reporting programs. Health care professionals are asked to report any suspected adverse reactions in patients receiving VIRAMUNE antiretroviral therapy directly to Boehringer Ingelheim (Canada) Ltd. or to the Marketed Health Products Directorate:

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.

Should you have any questions or require additional information regarding the use of VIRAMUNE (nevirapine) , please contact Boehringer Ingelheim (Canada) Ltd., Medical Information at 1-800-263-5103 Ext. 4512 or 905-631-4512 from 8:00 AM to 5:00 PM Monday to Friday Eastern Standard Time.

Sincerely,

original signed by

Tomasz Uscinowicz MD
Vice President, Medical