Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
Information Bulletin #10 April/May 2000
A research team from France found that a reduced Agenerase dose should be used for people with liver disease. The standard dose of Agenerase is 1,200mg taken twice daily. Doctors measure liver damage using a special scoring system called the Child-Pugh score. For people whose liver damage measures between 5 to 8 on the Child-Pugh score, the French researchers recommend that the dose of Agenerase should be reduced to 450mg twice daily. For people with more severe liver damage that falls between 9 and 15 on the Child-Pugh score, the researchers recommend an Agenerase dose of 300mg twice daily. The reason for the dose reduction is that liver damage slows down the processing of Agenerase, leading to higher levels of the drug in the body than normal.
The full cite for this study is: Single-dose pharmacokinetics of amprenavir, a human immunodeficiency virus type 1 protease inhibitor, in subjects with normal or impaired hepatic function. Veronese L, et al. Antimicrob Agents Chemother. 2000 Apr;44(4):821-6. The study summary can be read on the Internet at http://aac.asm.org/cgi/content/abstract/44/4/821
Safety Warning on Agenerase Oral Solution
Agenerase can be taken in two ways, either as a pill or a liquid solution. The liquid version is mainly for children who can't swallow large pills. The company that makes Agenerase, Glaxo-Wellcome, has issued a warning that the liquid version of Agenerase contains a large amount of a substance called propylene glycol. Propylene glycol is a chemical substance that helps Agenerase dissolve in the liquid. The warning letter says that because there is a risk of toxicity from the propylene glycol, Agenerase oral solution should only be used if Agenerase pills or another approved protease inhibitor cannot be used instead.
The warning letter also says that certain people are at greater risk for toxicity from propylene glycol due to the way it is processed and eliminated by the body. As a result, Agenerase oral solution should never be used in children under 4 years old, pregnant women, people with liver or kidney failure and people taking the drugs disulfiram (trade name Antabuse) or metronidazole (Flagyl). Certain ethnic groups (Asians, Eskimos and Native Americans) and women of all ethnicities may also be at greater risk of propylene glycol toxicity due to slower processing and elimination by their bodies.
The warning letter further says that anyone that has to use Agenerase oral solution should be monitored for signs of propylene glycol toxicity. The symptoms can include seizures, stupor (a trance-like or sluggish state), rapid heart beat, hyperosmolality (changes in blood chemistry), kidney toxicity, lactic acidosis (a dangerous build up of lactic acid) and hemolysis (red cell damage). Additionally, people using Agenerase oral solution should not drink alcohol.
The complete text of the Glaxo-Wellcome warning letter to health professionals can be downloaded from the Internet at: http://www.fda.gov/medwatch/safety/2000/agener.pdf
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