25th April 2001
Author:
Catrin Barker, Principal Pharmacist, DIAL
The United States Food and Drug Administration (FDA) have raised safety concerns about the use of propofol (Diprivan) in children. Their concerns are based on the review of data from a randomised controlled clinical trial that evaluated the safety and effectiveness of Diprivan against other standard sedative agents in paediatric ICU patients. In the study a total of 327 paediatric patients were randomised to receive either Diprivan 2% (113 patients), Diprivan 1% (109 patients) or a standard sedative agent (eg. lorazepam, chloral hydrate, fentanyl, ketamine, morphine or phenobarbital). Diprivan was initiated at an infusion rate of 5.5mg/kg/hr and titrated as needed to maintain sedation at a required level.
25 patients died during the trial or during a 28 day follow up period: 11%,8% and 4% in each of the respective groups. In the FDAs opinion, careful review of the deaths failed to reveal a correlation with underlying disease status or a definite pattern to the causes of death. Astra Zeneca are initiating a new clinical trial designed specifically to evaluate any differences in adverse events and deaths in paediatric patients randomised to propofol or standard sedative agents for ICU sedation.
Comment: Propofol (Diprivan) is not licensed in the USA or in the UK for sedation of children under 16 years of age in intensive care. In 1992 The Committee On Safety of Medicines in the UK warned about serious adverse effects and fatalities in children associated with the use of propofol (Diprivan) for sedation in ICU.(1) In 1998, Bray (2) published a series of case reports in 18 children who had received propofol infusions and had suffered serious adverse effects, described as “propofol infusion syndrome”. An association with a mean dose greater than 4mg/kg/hr and a duration of 48 hours or longer was reported. However a causative relationship could not be proven because of the nature of the study and the small number of patients included.
Propofol infusion is sometimes used (off licence) for sedation of paediatric patients on PICU but the maximum infusion rate is usually limited to 4mg/kg/hr and the duration to 24 hours. High dose, long term infusion in children is not recommended. (2)
death nice side effect....not
asprin has just been banned to all under 16yrs old(fever never give for) as it causes reyes syndrome(side effect)
FDA Warn Health Professionals of Occular Side Effects of Topiramate (Topamax).
Date:
5ht October 2001
Author:
Catrin Barker, Principal Pharmacist, DIAL
Janssen Cilag (US) are issuing a “Dear Doctor” letter in the USA to advise possible occular toxiciy with Topiramate. The labelled warnings for Topiramate have been revised following 23 reported cases (22 adult and 1 child) of acute myopia and secondary acute angle-closure glaucoma.
Janssen Cilag in the UK are in discussion with the Medicines Control Agency and expect to circulate a similar “Dear Doctor” letter in the near future.
The letter issued in the US can be viewed at
http://www.fda.gov/medwatch.safety/2001/safety01.htm
Prepared by Susan Wileman (Medicines Information Technician DIAL)
Date of Preparation: 5th October 2001