Diabetes Drug Linked to Severe Statin Toxicity Case

A drug interaction between canagliflozin (Invokana) and rosuvastatin (Crestor) used to be thought to cause liver and muscle toxicity in a lady in Canada, in step with a case narrative.

The 76-twelve months-passe woman had been on rosuvastatin 40 mg day by day for more than 5 years. Fifteen days after initiating treatment with canagliflozin 100 mg day by day, she supplied to the health heart with contemporary-onset muscle effort and danger walking. Her bilateral thigh effort and weakness, first seen 3 days after initiating canagliflozin, had gradually stepped forward and spread to the upper extremities.

Lab results showed rhabdomyolysis, hepatocellular damage, a thyroid-stimulating hormone concentration of 6.82 mIU/Lacreatinine concentration of 194 μmol/L, and no C-reactive protein, antinuclear antibodies, or antibodies directed against extractable nuclear antigens.

“The plasma rosuvastatin concentration on admission used to be 176 ng/mL, which is more than 15-fold better than the mean price anticipated in patients receiving 40 mg per day,” David Juurlink, MD, PhD, of Sunnybrook Well being Sciences Centre in Toronto, and colleagues reported within the Annals of Interior Remedy.

The lady stopped both rosuvastatin and canagliflozin and got IV crystalloid fluids within the health heart. Over the next few days, her muscle effort subsided and her weakness gradually improved. Upon discharge 10 days after admission, she could presumably perhaps trek with a walker and had advance-full normalization of all laboratory abnormalities.

“We speculate that, in our patient, the addition of canagliflozin enhanced intestinal rosuvastatin absorption, inhibited its hepatocellular uptake, and impaired its excretion into bile canaliculi and the proximal tubule, resulting in rosuvastatin accumulation and resulting in hepatotoxicity and myotoxicity,” the authors said.

Thus, clinicians will contain to peer out for positive aspects of such toxicity when canagliflozin and rosuvastatin are co-prescribed, they urged.

“To our knowledge, this is the first printed narrative of a drug interaction between rosuvastatin and canagliflozin. The chance of such an interaction is important on account of these treatment are taken by millions of patients worldwide and are more and more prescribed together,” the authors wrote.

Canagliflozin is licensed for glycemic control, cardiovascular prevention, and renal prevention in kind 2 diabetes. The SGLT2 inhibitor lowers blood glucose by blockading reabsorption of glucose by the kidney, rising glucose excretion in an instant into urine.

FDA reviewers contain previously warned of renal and atomize dangers connected with the drug. Moreover, an FDA boxed warning has seemed on canagliflozin products on account of the put up-advertising and marketing cardiovascular outcomes trial CANVAS showed an uptick in leg and foot amputations amongst users.

“Extra scientific knowledge would be helpful to treasure the relationships between drug initiation and the irregular liver and renal feature,” in step with Kenneth Mahaffey, MD, of Stanford College, California, who used to be not half of Juurlink’s team.

Formal pharmacokinetics reports contain been conducted with canagliflozin and simvastatin without showing any drug-drug interactions, Mahaffey noteworthy, adding that no statin-canagliflozin interactions contain been stumbled on both within the wide CANVAS and CREDENCE applications (for which he used to be an investigator).

The patient within the case narrative had a medical historical previous that incorporated coronary artery disease, stage 3B chronic kidney disease, and beauty 2 diabetes. Moreover rosuvastatin and canagliflozin, she had been on bisoprolol, aspirin, metformin, L-thyroxine, and risedronate.

On pharmacogenetic prognosis, the patient grew to become out to be heterozygous for a polymorphism within the ABCG2 gene for breast cancer resistance protein, which reduces intestinal absorption whereas improving biliary and renal elimination.

An in vitro gaze had previously stumbled on canagliflozin to be both a substrate for and competitive inhibitor of breast cancer resistance protein, in step with the authors.