Summary

• Hypersensitivity reactions, including angioedema and anaphylaxis, have been reported with canagliflozin. These reactions generally occurred within hours to days after initiating canagliflozin. If hypersensitivity reactions occur, discontinue use of canagliflozin; treat per standard of care and monitor until signs and symptoms resolve.¹
• Canagliflozin, the active ingredient of INVOKANA^®, is a C-glucoside with a thiophene ring. The thienyl component within canagliflozin contains a sulfur atom.^2,3
• Canagliflozin does not fall in the class of compounds referred to as sulfonamides. At present, there is insufficient information available to support cross-sensitivity reactions between sulfonamides and C-glucoside compounds. Studies have not been conducted evaluating the sulfonamide allergy risk with canagliflozin.

BACKGROUND

Traditionally, the term “sulfa” refers to a derivative of sulfanilamide, an antimicrobial agent.  However more recently, the term has been associated to a diverse group of drugs, all containing the sulfonamide chemical formula (-SO₂NH₂).⁴ See Figure: Structural Formula for Sulfonamide Moiety.

STRUCTURE AND REACTIVITY

• Canagliflozin, the active ingredient of INVOKANA^®, is chemically known as (1S)-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol hemihydrate and its molecular formula is C24H25FO5S•1/2 H2O.¹ Canagliflozin is a C-glucoside with a thiophene ring. The thienyl moiety within canagliflozin contains a sulfur atom (see Figure: Thienyl within Canagliflozin - Structural Formula for Canagliflozin with Thienyl Moiety Encircled).^1-3
• The chemical structure of canagliflozin does not contain a sulfonamide moiety, therefore canagliflozin does not fall in the class of compounds referred to as sulfonamides or “sulfa drugs”. At present, there is insufficient information available to support cross-sensitivity reactions between sulfonamides and C-glucoside compounds with a thienyl moiety.
• Studies have not been conducted to evaluate whether patients with a history of sulfa allergy are at greater risk of hypersensitivity reactions associated with the use of canagliflozin.

• As can be seen in the Figures, there is negligible overlap between the chemical structure of a thienyl moiety and that of sulfonamide moiety.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 09 September 2024.