The type 2 diabetes treatments Invokana and Invokamet have been updated to include new warnings for acute kidney injury and impaired renal function.
Invokana contains the drug ingredient canagliflozin. Invokamet contains canagliflozin in combination with the first-line diabetes treatment metformin. The medications were approved by the Food and Drug Administration (FDA) in 2013 and 2014, respectively. Invokana and Invokamet work by inhibiting sodium glucose co-transporter 2, a carrier that aids in the reabsorption of glucose into the bloodstream through the kidneys, and eliminated through the urine.
The new warning states: Invokana and Invokamet cause intravascular volume contraction and can cause renal impairment. There have been postmarking reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving Invokana or Invokamet; some reports involved patients younger than 65 years of age.
Health care providers are advised to consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs), before prescribing the drugs, and to consider temporarily discontinuing the medications in any setting of reduced oral intake (such as acute illness or fasting) or fluid losses (such as gastrointestinal illness or excessive heat exposure); monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue Invokana or Invokamet promptly and institute treatment.
The warning also advises that renal function be evaluated prior to initiation of Invokana or Invokamet and monitored periodically thereafter.
Since the medications were approved, the FDA has required updates to the safety label to include warnings for increased fracture risk, decreased bone mineral density, serious urinary tract infections, increased lower limb amputations, and ketoacidosis, a life threatening condition in which too much acid builds up in the blood.