 |
 |
 |
 |
 |
 |
 |
|
|
|
|||||||||
|
|||||||||||
Head, Clinical Pharmacology, Clinical Activities British Columbia Centre for Excellence in HIV/AIDS St. Paul's Hospital 1081 Burrard Street, Room 667 Vancouver, British Columbia V6Z1Y6, Canada fax 604/806-8527 ephillips{at}cfenet.ubc.ca
Drug Safety Pharmacist Sunnybrook and Women's College Health Sciences Centre Toronto, Ontario, Canada
Published Online, May 31, 2005. www.theannals.com, DOI 10.1345/aph.1E350a
In the article, amprenavir and its prodrug fosamprenavir are erroneously represented as nonsulfonylarylamines. Amprenavir shares this sulfonylarylamine structure with another protease inhibitor currently in Phase III studies, TMC-114, and both can be differentiated from the sulfonamide protease inhibitor tipranavir, which is a sulfonamide derivative without the aromatic amine ring.2 The risk of cross-reactivity between sulfonylarylamines and nonsulfonylarylamines appears to be low and may be predicated on general factors associated with host predisposition to drug reactions rather than chemical structure.3 The cross-reactivity between drugs that share the sulfonylarylamine structure is largely unknown and would be difficult to measure since reactions to sulfonamide antimicrobials, such as trimethoprim/sulfamethoxazole (TMP/SMX), may not be reproducible within the same patient across time.4
However, this issue is of particular relevance to HIV therapeutics since hypersensitivity reactions to sulfonamide antimicrobials such as TMP/SMX are common in this population and decisions have to be made about future use of sulfonylarylamine protease inhibitors, such as amprenavir, fosamprenavir, and TMC-114, in patients who have experienced hypersensitivity or more severe cutaneous reactions associated with TMP/SMX. The putative mechanism by which hypersensitivity to sulfonamide antimicrobials occurs is thought to be in part by the generation of cytotoxic and immunogenic reactive hydroxylamine and nitrosamine metabolites. Oxidative formation of these reactive metabolites is cytochrome P450 mediated and is thought to occur at the N4 arylamine group that sulfonylarylamine drugs share.5
In conclusion, although there is limited information as to clinical cross-reactivity between drugs sharing the sulfonylarylamine structure (ie, amprenavir, fosamprenavir, TMC-114), this group should be separated from the nonsulfonylarylamine group drugs in that there is at least, in theory, a risk of clinical cross-reactivity between these drugs and sulfonamide antimicrobials such as sulfamethoxazole.
References
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
 |
 |
 |
 |
