A 25 y/o old female presents to the clinic after a 5 day blood pressure monitor trial. Based on these readings, she definitely meets the criteria for hypertension and you decide to start her on low-dose hydrochlorothiazide (a thiazide diuretic). She's otherwise in good health
with no other significant medical history. She tells you she's allergic to sulfa drugs. Upon further questioning, she states she's taken trimethoprim/sulfamethoxazole [Bactrim®] for a UTI without any problems.

Do you start the thiazide or not? Why or why not?
 

** THANKS to Dr Angela Allerman, BCPS, of the DoD Pharmacoeconomic Center
for her help with this week's Pearl **

Yes. I'd suggest you can give the thiazide pretty safely. A recent review in the New England Journal of Medicine (2003;349:1628-35) found about 10% (96/969) of patients with a previous allergic or hypersensitivity reaction to a sulfonamide antibiotic had a reaction to a sulfonamide NON-antibiotic (like a thiazide or sulfonylurea). Contrarily, only 1.6% (315/19,257) of patients without a previous allergic or hypersensitivity reaction to a sulfonamide antibiotic had a reaction to a sulfonamide NONantibiotic. A history of allergy to a sulfonamide antibiotic does NOT necessarily contraindicate the use of a sulfonamide NON-antibiotic. The authors concluded this association appears to be due to a predisposition
to allergic reactions rather than a cross-reactivity with other sulfonamide-based drugs.

From MICROmedex for the hard-core molecular folks:

Hypersensitivity reactions to sulfonamides are reported to be the result of metabolism of the drug to electrophilic metabolites that covalently bond to cell macromolecules that cause direct cytotoxicity as well as the initiation of an immunologic response (Gupta et al, 1992). There is a known cross-sensitivity of some sulfonamide allergic patients to furosemide,
thiazide diuretics, sulfonylureas, or carbonic anhydrase inhibitors.

Sulfonamide metabolism and haptenation.

Sulfonamides are metabolized by N4

-oxidation by cytochrome P450 enzymes, or by N4 - acetylation. N-acetyl sulfonamides and glutathionyl (GSH)-sulfonamides are then excreted. Free sulfonamides, N-acetyl sulfonamides, and GSH-sulfonamides have the potential to act as univalent inhibitors of antibody-mediated reactions. Carrier haptenation can occur after N-oxidation if the
capacity for GSH conjugation is exceeded.

There are structural similarities and a cross sensitivity between penicillins and cephalosporins. Estimates vary but the most commonly quoted number is between 5 and 10%. In general,  cephalosporins can be given to patients with penicillin allergies UNLESS the patient's reaction to the penicillin was anaphylactic (shortness of breath, tongue swelling, hives, etc). If the reaction was only a skin rash, most providers would give the
cephalosporin.

REFERENCES

- Strom BL, et al. Absence of Cross-reactivity between sulfonamide antibiotics and sulfonamide non-antibiotics. N Engl J Med 2003;349:1628-35.
- Ray WA. Population based studies of adverse drug events. N Engl J Med. 2003;349:1592-4.

** Addendum ** - as many people correctly pointed out in the last Pearl, the frequency for Td (tetanus/diphtheria) booster SHOULD be every TEN years versus every year as originally stated in the Pearl. My fingers were working faster than my brain - Thanks for bringing this to my attention.

** "Pearls" are taking a well-deserved Holiday Break. Pearls should return
on 14 January 2004. Happy Holidays and see you next year! **

This Pearl is meant for academic and educational purposes only. This Pearl is meant to raise important points regarding the safe and cost-effective pharmacotherapy of patients. It is not meant to be the definitive reference for the treatment or prophylaxis of various diseases. Although every effort is taken to ensure this Pearl is correct and factual, errors may occur. The Pharmacoeconomic Center assumes no liability for incorrect information or harm that may occur from the use of the information included in this Pearl.