The proposed sNDA included adding language regarding the risks of anaphylaxis and angioedema in the Contraindications, Hypersensitivity Reactions, Postmarketing Experience, and Patient Counseling Information sections of the package insert and in the medication guide. Also, the Pharmacokinetics section regarding the mean steady-state volume of distribution of canagliflozin following a single intravenous (IV) infusion.
The Contraindication section for both drugs has been updated to include a history of a serious hypersensitivity reaction, such as anaphylaxis or angioedema.
In the Hypersensitivity Reactions under Warnings and Precautions, language has been added to describe that hypersensitivity reactions to canagliflozin or metformin (for Invokamet), including angioedema and anaphylaxis, have generally occurred within hours to days after initiating the drug. If hypersensitivity reactions occur, the drug should be discontinued and the patient treated and monitored until signs and symptoms resolve.
The Postmarketing Experience section has also listed anaphylaxis and angioedema as additional adverse reactions that have been identified during post-approval use of Invokana.
In the Patient Counseling Information section, patients are advised to report immediately any signs or symptoms suggesting allergic reaction, and to discontinue the drug until they have consulted prescribing physicians.
Invokana is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Invokamet is a combination of an SGLT2 and a biguanide indicated as adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled on a regimen containing metformin or canagliflozin or in patients already being treated with both canagliflozin and metformin.