Glaxo Wellcome Inc., is notifying health professionals of a revised
warning in the labeling for Ziagen (abacavir sulfate) about fatal hypersensitivity
reactions to abacavir in patients presenting with respiratory symptoms.
Ziagen is a nucleoside analogue reverse transcriptase inhibitor indicated
for use in combination with other antiretroviral drugs for the treatment
of HIV-1 infection.
Since its approval in December 1998, the labeling for Ziagen has included
a WARNING and description of fatal hypersensitivity reactions to Ziagen.
Although presentations vary markedly between patients, frequently occurring
features of these hypersensitivity reactions are fever, rash, gastrointestinal
symptoms (nausea, vomiting, diarrhea, or abdominal pain) and fatigue or
malaise. While respiratory symptoms have been recognized as part of the
hypersensitivity reaction in some patients, recent information underscores
Fatalities in patients treated with Ziagen who developed hypersensitivity
reactions in which the initial presentation included respiratory symptoms
of dyspnea, cough, or pharyngitis have been reported. Deaths have been
reported in patients receiving Ziagen who were initially diagnosed with
an acute respiratory disease (pneumonia, bronchitis, or flu-like illness)
who were later recognized to have had a hypersensitivity reaction to abacavir
that included respiratory symptoms. A delay in diagnosis of hypersensitivity
can result in Ziagen being continued or re-introduced, leading to more
severe hypersensitivity reactions, including life-threatening hypotension
Review of reports of hypersensitivity in patients receiving Ziagen indicates
that respiratory symptoms (including cough, dyspnea, and pharyngitis) have
occurred in approximately 20% of patients who have had hypersensitivity
reactions. In contrast to some allergic reactions, wheezing or bronchospasm
have occurred only infrequently in patients with hypersensitivity reactions
The diagnosis of hypersensitivity reaction should be carefully considered
for patients presenting with symptoms of acute respiratory diseases and
other symptoms associated with hypersensitivity to abacavir, even if alternative
respiratory diagnoses (pneumonia, bronchitis, pharyngitis, or flu-like
illness) are possible. If the clinical presentation of an acute illness
cannot be clearly differentiated from a hypersensitivity reaction, Ziagen
must be permanently discontinued. Ziagen should not be restarted following
a hypersensitivity reaction because more severe symptoms will recur within
hours and may include life-threatening hypotension and death.
This updated warning about fatal hypersensitivity reactions to abacavir
in patients presenting with respiratory symptoms is now included in the
revised labeling for Ziagen. In addition, this revised warning is reflected
in the Patient Medication Guide and Warning Card and should be discussed
with patients treated with Ziagen.
This information is provided to help in the management of patients
prescribed Ziagen Tablets or Ziagen Oral Solution. Please take the time
to read the enclosed revised package insert, including the revised boxed
warning shown below (with the revision underlined), for additional product
information and other risks associated with the recommended use of Ziagen.
FATAL HYPERSENSITIVITY REACTIONS HAVE BEEN ASSOCIATED WITH THERAPY WITH
ZIAGEN. PATIENTS DEVELOPING SIGNS OR SYMPTOMS OF HYPERSENSITIVITY (WHICH
INCLUDE FEVER; SKIN RASH; FATIGUE; GASTROINTESTINAL SYMPTOMS SUCH AS NAUSEA,
VOMITING, DIARRHEA, OR ABDOMINAL PAIN; AND RESPIRATORY SYMPTOMS SUCH
AS PHARYNGITIS, DYSPNEA, OR COUGH) SHOULD DISCONTINUE ZIAGEN AS SOON
AS A HYPERSENSITIVITY REACTION IS SUSPECTED. ZIAGEN SHOULD NOT BE RESTARTED
FOLLOWING A HYPERSENSITIVITY REACTION BECAUSE MORE SEVERE SYMPTOMS WILL
RECUR WITHIN HOURS AND MAY INCLUDE LIFE-THREATENING HYPOTENSION AND DEATH
(see WARNINGS PRECAUTIONS: Information for Patients, and ADVERSE REACTIONS).
LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, INCLUDING FATAL
CASES, HAVE BEEN REPORTED WITH THE USE OF NUCLEOSIDE ANALOGUES ALONE OR
IN COMBINATION, INCLUDING ZIAGEN AND OTHER ANTIRETROVIRALS (SEE WARNINGS).
ZIAGEN in combination with other antiretroviral agents is indicated
for the treatment of HIV-1 infection. This indication is based on analyses
of surrogate markers in controlled studies of up to 24 weeks in duration.
At present, there are no results from controlled trials evaluating long-term
suppression of HIV RNA or disease progression with ZIAGEN.
Although hypersensitivity reaction is described in the package insert
for Ziagen, you can assist us in continuing to monitor the safety of Ziagen
products by reporting all cases of hypersensitivity reaction occurring
in patients treated with Ziagen to the Abacavir Hypersensitivity Reaction
Registry at Glaxo Wellcome at 1-800-270-0425 or to the FDA MedWatch program
by telephone at 1-800-FDA-1088, via fax at 1-800-FDA-0178, or by mail at
MedWatch HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857.
We appreciate the opportunity to provide this information to facilitate
the care of patients. Any questions from health care professionals
may be directed to our Drug Information Department at 1-800-334-0089.