Is benazepril and Hydrochlorothiazide (HCTZ) a sulfa drug?

From the Guidelines

No, benazepril and Hydrochlorothiazide (HCTZ) is not a sulfa drug in the context of cross-reactivity with sulfonamide antimicrobials.

Rationale

• According to the study 1, Hydrochlorothiazide, a thiazide diuretic, is listed as a drug with no or weak evidence of cross-reactivity in patients with a history of a sulfonamide antimicrobial adverse reaction.
• The study 1 also notes that sulfonamide non-antimicrobials, such as thiazide diuretics, are structurally different from sulfonamide antimicrobials and have minimal concern for cross-reactivity.
• Key points to consider:
  • Benazepril is an ACE inhibitor and is not a sulfonamide.
  • Hydrochlorothiazide is a thiazide diuretic and is not a sulfonamide antimicrobial.
  • The combination of benazepril and Hydrochlorothiazide is not a sulfa drug in the context of cross-reactivity with sulfonamide antimicrobials.

From the FDA Drug Label

Hydrochlorothiazide, USP is the 3,4-dihydro derivative of chlorothiazide. Its chemical name is 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1-dioxide. Benazeprilat, the active metabolite of benazepril, is a non-sulfhydryl angiotensin-converting enzyme inhibitor.

The combination of benazepril and Hydrochlorothiazide (HCTZ) does contain a sulfa drug, specifically Hydrochlorothiazide, which is a sulfonamide derivative.

• Key points:
  • Hydrochlorothiazide contains a sulfonamide group in its chemical structure.
  • Benazepril does not contain a sulfa group.
  • The presence of a sulfonamide group in Hydrochlorothiazide makes it a sulfa drug 2.
  • Benazepril is not a sulfa drug 3.

From the Research

Benazepril and Hydrochlorothiazide (HCTZ) Composition

• Benazepril is a nonsulfhydryl ACE inhibitor prodrug, which is converted in vivo to its active form, benazeprilat 4
• Hydrochlorothiazide (HCTZ) is a diuretic, but its chemical structure does not contain a sulfa group, however the term "sulfa" is often misused to describe all sulfonamide derivatives, HCTZ is a sulfonamide derivative but it is not a "sulfa drug" in the context of antibiotics

Studies on Benazepril and HCTZ

• A study compared the efficacy and safety of benazepril and HCTZ, given alone and in combination, on blood pressure in patients with hypertension 5
• Another study compared the effect of benazepril and HCTZ on functional class in symptomatic mild heart failure, and found that benazepril improved the NYHA functional class in 59% of patients, whereas one patient improved with HCTZ 6
• A study compared the efficacy and safety of olmesartan medoxomil and HCTZ with benazepril and amlodipine besylate in patients with stage 2 hypertension, and found that the combination of olmesartan medoxomil and HCTZ was more effective in reducing blood pressure than the combination of benazepril and amlodipine besylate 7
• A study compared the safety and efficacy of benazepril and other antihypertensive agents alone and in combination with HCTZ, and found that benazepril was as effective as or more effective in lowering diastolic blood pressure than HCTZ, and that the combination of benazepril and HCTZ had a possibly synergistic effect on diastolic blood pressure 8

Sulfa Drug Classification

• There is no evidence to suggest that benazepril is a sulfa drug, as it is a nonsulfhydryl ACE inhibitor prodrug 4
• HCTZ is a sulfonamide derivative, but it is not typically classified as a "sulfa drug" in the context of antibiotics, however it may cause allergic reactions in some individuals who are allergic to sulfa drugs 5, 6, 7, 8