The following is reproduced from the Health Canada website, with annotations. I apologise for any breach of copyright to the involved parties, but I felt it important to get this official information out into the wider public domain as soon as possible:

May 12, 2008

Dear Health Care Professional:

Tibotec, a division of Janssen-Ortho Inc. (”Tibotec”), in cooperation with Health Canada, would like to inform you of important new safety information regarding hepatotoxicity [liver toxicity- C] in association with the use of PREZISTA (darunavir). PREZISTA, co-administered with ritonavir (rtv) and other antiretroviral agents, is indicated for treatment of human immunodeficiency virus (HIV) infection in adult patients who have failed prior antiretroviral therapy.

Drug-induced hepatotoxicity has been reported in patients receiving PREZISTA therapy in combination with rtv during clinical trials and post-marketing use.

Appropriate laboratory testing should be conducted prior to initiating therapy with PREZISTA/rtv and patients should be monitored during treatment. Increased AST/ALT monitoring, especially during the first several months of PREZISTA/rtv, should be considered in patients with underlying chronic hepatitis (including hepatitis B or C virus co-infection) or cirrhosis, as well as in patients with elevated liver enzymes prior to treatment.

If new or worsening liver dysfunction (including significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) develops in patients using PREZISTA/rtv, interruption or discontinuation of treatment must be considered. When deciding to re-initiate a drug that may have induced hepatotoxicity, physicians should be aware that more severe hepatic injury may ensue.

Tibotec is working with Health Canada to incorporate this new safety information in the Canadian Product Monograph for PREZISTA. [Supplementary Note: I have forwarded the surrounding information to NZAF, and presumably they’ll notify Pharmac and Medsafe about the information available from Health Canada].

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of serious hepatotoxicity or other serious or unexpected adverse reactions in patients receiving PREZISTA should be reported to Tibotec or Health Canada.

[Supplementary Note: New Zealand has a similar pharmacovigilance system for reporting adverse reactions to medication and related therapies.

Aforementioned Source:

Health Canada Advisory Re: Duronavir/Prezista (15.05.08):

Health Canada: Advisories, Warnings and Information for
Health Professionals: Duronavir/Prezista (15.05.08):

http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/2008/prezista_hpc-cps_e.html