Drug Interactions between elafibranor and pravastatin

MONITOR: Concomitant use of HMG-CoA reductase inhibitors (statins) with elafibranor may increase the risk of myopathy, including rhabdomyolysis. The mechanism of this interaction has not been fully characterized. In a multicenter, randomized, double-blind placebo-controlled study (Study 1) in 161 adults with primary biliary cholangitis, 4 out of 108 adult patients (4%) receiving elafibranor (80 mg daily) experienced increases in creatine phosphokinase (CPK) to greater than 3 times the upper limit of normal compared to none in the placebo group. Likewise, 4% of patients on elafibranor experienced myalgia compared to only 2% of those receiving placebo. Half of the affected patients (2 out of 4) in each group were also on a statin, compared to none of the patients in the placebo group. In addition, CPK elevation combined with myalgia, as well as rhabdomyolysis combined with acute kidney injury (AKI), each occurred in 1 out of 108 subjects on elafibranor (1%) compared to none of those receiving placebo. Both patients who experienced either an increased CPK with myalgia, or rhabdomyolysis with AKI were also on a concomitant statin.

MANAGEMENT: Caution is advised when a statin is coadministered with elafibranor. The manufacturer recommends assessing patients for the presence of muscle pain and myopathy prior to initiating elafibranor. Patients on concomitant therapy with a statin should be more closely monitored for signs and symptoms of muscle injury, including periodic assessments (e.g., clinical exam and CPK levels) during treatment. Patients should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be interrupted if new onset or worsening of muscle pain or myopathy develops.