April 26, 2001
Diprivan (propofol) Safety Information
Audience: Health professionals.
Washington, DC (SafetyAlerts) - The FDA has determined
that there may be important safety concerns when propofol, marketed by AstraZeneca as
DIPRIVAN (propofol) Injectable Emulsion, is used for sedation in the Intensive Care Unit
(ICU) in pediatric patients. Healthcare professionals are reminded that propofol is not
approved in the U.S. for sedation in pediatric ICU patients.
A copy of the AstraZeneca "Dear Healthcare Provider" letter is printed below.
Letter to healthcare professionals...
Dear Health Care Provider,
I am writing to inform you that based on a recent
review of new clinical trial data,the Food and Drug Administration (FDA)has determined
that there may be important safety concerns when propofol,marketed by AstraZeneca as
DIPRIVAN ? (propofol)Injectable Emulsion, is used for sedation in the Intensive Care Unit
(ICU) in pediatric patients.I would like to remind you that propofol is not approved in
the US for sedation in pediatric ICU patients and should not be used for this purpose.
The FDA's determination was made based on the review of data from a randomized,controlled,
clinical trial that evaluated the safety and effectiveness of DIPRIVAN versus standard
sedative agents (SSA)in pediatric ICU patients.In that study a total of 327 pediatric
patients were randomized to receive either DIPRIVAN 2%(113 patients), DIPRIVAN 1%(109
patients), or an SSA (eg, lorazepam, chloral hydrate, fentanyl, ketamine, morphine, or
phenobarbital). DIPRIVAN therapy was initiated at an infusion rate of 5.5 mg/kg/hr
and titrated as needed to maintain sedation at a standardized level. The results of the
study showed an increase in the number of deaths in patients treated with DIPRIVAN as
compared to SSAs. A total of 25 patients died during the trial or within the 28-day
follow-up period:12 (11%)in the DIPRIVAN 2%treatment group, 9 (8%)in the DIPRIVAN 1%
treatment group,and 4 (4%) in the SSA treatment group. In the opinion of FDA,careful
review of the deaths failed to reveal a correlation with underlying disease status, nor
did the review reveal a definite pattern to the causes of death. In order to better
understand this potential safety issue AstraZeneca will initiate a new clinical trial
designed specifically to evaluate any differences in adverse events and deaths in
pediatric patients randomized to propofol or SSAs for ICU sedation.
We would like to reemphasize that
propofol is currently not approved for sedation in pediatric ICU patients in the US and
should not be used for this purpose. It is important that you forward
any adverse event information involving propofol to AstraZeneca (for DIPRIVAN) at the
Information Center 1-800-236-9933, 8 am -7 pm or to the FDA via the MedWatch system.
Copies of the MedWatch form are available on the
FDA web site (http://www.fda.gov/medwatch/index.html
If you would like additional information related
to the trial,please call the AstraZeneca Information Center.
Medical Leader for Pain,Anesthesia and Infection Products