rior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining simvastatin with esomeprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
Esomeprazole; Naproxen: Simvastatin is a HMG-CoA reductase inhibitor (statin) recognized as a substrate and inhibitor of the P-glycoprotein (P-gp) transport system. Likewise, studies show that lansoprazole, omeprazole, and pantoprazole are also substrates and inhibitors of P-gp. Due to competitive inhibition of the P-gp transport system, coadministration may lead to increased intestinal absorption and/or decreased hepatic excretion of either product. The resulting increased drug bioavailability could lead to increased adverse events, including serious myopathies in the case of higher than normal statin plasma concentrations. For example, P-gp inhibition was suspected in a case report involving a patient presenting to the emergency room with rhabdomyolysis, causing third-degree AV block. The patient's medication history included atorvastatin (> 1 year history), esomeprazole (6-week history), and clarithromycin (500 mg x 3 doses prior to admission). Symptoms of weakness, shortness of breath, and chest pain coincided with the start of esomeprazole therapy. Due to the timing of symptom onset, clinicians suspected that esomeprazole likely increased atorvastatin plasma concentrations leading to rhabdomyolysis and further complications. Although competitive inhibition of CYP isoenzyme metabolism could have played a minor role in the interaction, the main pathway was thought to be competitive P-gp inhibition. Caution is therefore warranted when combining simvastatin with esomeprazole. Substituting with dexlansoprazole or rabeprazole may represent a safer alternative. Treatment with pravastatin, fluvastatin, and rosuvastatin may also decrease the risk of a P-gp interaction.
Etoposide, VP-16: Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with simvastatin. Simvastatin is an inhibitor of P-glycoprotein (P-gp) and etoposide, VP-16 is a P-gp substrate. Coadministration may increase etoposide concentrations.
Etravirine: The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors. Concomitant use of etravirine and simvastatin (CYP3A4 substrate) may result in lower plasma concentrations of the HMG-CoA reductase inhibitor; dose adjustments for may be necessary.
Everolimus: Immunosuppressants such as everolimus, especially when used along with cyclosporine, can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine. Deterioration of renal function increases the risk for myopathy and rhabomyolysis with lipid-lowering therapy such as the HMG-CoA reductase inhibitors (statins). Carefully monitor |
