Glaxo Wellcome have issued important changes to US health care professionals regarding the labelling of the oral solution of their protease inhibitor amprenavir. The warning concerns the potential risks of exposure to the large amounts of the excipient propylene glycol, used to achieve adequate solubility of amprenavir.
Some patients are not able to metabolise and eliminate propylene glycol adequately, with its accumulation leading to potential adverse events. As yet no death or serious injury has been attributed to the propylene glycol content of amprenavir oral solution.
However, as a result of the high content of propylene glycol in amprenavir oral solution, Glaxo Wellcome have issued a statement that some patients, including infants and children below the age of 4 years, pregnant women, patients with hepatic or renal failure, and patients treated with disulfiram or metronidazole, should not use the liquid formulation of amprenavir. Additionally, women, Asians, Native Americans and Eskimos may be at increased risk of adverse events. Glaxo Wellcome recommend that such patients should be switched to amprenavir capsules as soon as they are able to take them.
Amprenavir oral solution should only be continued by those patients for whom amprenavir capsules or other protease inhibitors are not therapeutic options. Under such circumstances, close monitoring for propylene glycol-associated adverse events, including seizures, stupor, tachycardia, hyperosmolality, lactic acidosis, renal toxicity, and hemolysis should be carried out.
Alcohol consumption is not recommended among those patients taking the oral solution. If overdosage of the oral solution occurs, monitoring and management of acid-base abnormalities is recommended. Propylene glycol can be removed by hemodialysis.
Glaxo Wellcome's statement can be read at Medwatch in pdf form.
Amprenavir, though an approved antiretroviral in the US, is currently unlicensed in European Union member states.