PRAC to Review Canagliflozin and Direct-Acting Antivirals

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PRAC said it has plans to review both canagliflozin and several direct-acting antivirals, after new study data showed potential risks associated with the drugs.

The European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) says it has plans to review the safety of canagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor used to lower blood sugar in patients with Type 2 diabetes. The committee will also extend the review of several direct-acting antivirals for the treatment of hepatitis C, PRAC said in an April 15, 2016 announcement.

PRAC said it would review the safety of canagliflozin, the active substance used in Invokana and Vokanamet, after CANVAS, an ongoing clinical trial, showed a slight increase in the incidence of lower limb amputations, specifically toe amputations, in patients taking the medications. Another clinical study, CANVAS-R, showed a similar small increase in amputations, PRAC notes. This is particularly evident for patients with poorly controlled diabetes and preexisting heart and blood vessel issues. PRAC said it plans to review data from the drugs, as well as from other SGLT2 inhibitors, to determine if canagliflozin causes an increase in lower limb amputations.

FDA recently added warning labels to Type 2 diabetes medications containing saxagliptin and alogliptin. Review from FDA determined that the drugs may increase the risk of heart failure, particularly in patients with kidney or heart diseases. Canagliflozin is also approved in the United States to treat Type 2 diabetes. FDA notes that SGLT2 inhibitors, including canagliflozin, can lead to blindness, nerve and kidney damage, and heart disease. However, FDA has not made any comment on the possible increase in lower limb amputations. 

In March 17, 2016, PRAC said it would review several direct-acting antivirals for the treatment of hepatitis C including Daklinza, Exviera, Harvoni, Olysio, Sovaldi, and Viekirax. Until recently, Direct-acting antivirals were part of treatment regiments for hepatitis B and C, which may be simultaneously present in a patient, PRAC notes. The committee decided to review use of antivirals after hepatitis B reactivation occurred in some patients.


PRAC made the decision to extend the review after new data became available in April 2016. The committee says data “became available regarding the risk of liver cancer (hepatocellular carcinoma) coming back in patients who were treated with direct-acting antivirals for hepatitis C.” According to PRAC, the study suggests patients treated with direct acting antivirals were at risk of cancer coming back earlier, than those not treated with the antivirals.

Source: EMA