Rosuvastatin Myotoxicity After Starting Canagliflozin Treatm
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A drug interaction between canagliflozin (Invokana) and rosuvastatin (Crestor) was thought to cause liver and muscle toxicity in a woman, according to a case report published in Annals of Internal Medicine.

The 76-year-old woman had been on rosuvastatin 40 mg daily for more than 5 years. 15 days after starting treatment with canagliflozin 100 mg daily, she presented to the hospital with new-onset muscle pain and difficulty walking. Her bilateral thigh pain and weakness, first noticed 3 days after starting canagliflozin, had gradually progressed and spread to the upper extremities.

Lab results showed rhabdomyolysis, hepatocellular injury, a TSH concentration of 6.82 mIU/L, a creatinine concentration of 194 mol/L, and no CRP, ANA, or antibodies directed against extractable nuclear antigens. "The plasma rosuvastatin concentration on admission was 176 ng/mL, which is more than 15-fold higher than the mean value expected in patients receiving 40 mg per day," authors reported.

The woman stopped both rosuvastatin and canagliflozin and received IV crystalloid fluids in the hospital. Over the next few days, her muscle pain subsided and her weakness gradually improved. Upon discharge 10 days after admission, she could walk with a walker and had near-complete normalization of all laboratory abnormalities.

Authors speculate that 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 leading to hepatotoxicity and myotoxicity.

"To our knowledge, this is the first published report of a drug interaction between rosuvastatin and canagliflozin. The possibility of such an interaction is important because these drugs are taken by millions of patients worldwide and are increasingly prescribed together," the authors wrote.

Source: https://www.acpjournals.org/doi/10.7326/L20-0549
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