coprotein (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 atorvastatin, lovastatin, red yeast rice (structurally similar to lovastatin), or simvastatin with esomeprazole, lansoprazole, omeprazole, or pantoprazole. 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.
Lanthanum Carbonate: Oral compounds known to interact with antacids, like HMG-CoA reductase inhibitors, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
Ledipasvir; Sofosbuvir: Caution and close monitoring of adverse reactions, such as myopathy and rhabdomyolysis, is advised with concomitant administration of simvastatin and ledipasvir; sofosbuvir. Both ledipasvir and simvastatin are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp); sofosbuvir is a P-gp substrate. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
Lomitapide: Concomitant use of simvastatin and lomitapide approximately doubles the exposure to simvastatin increasing the risk for myopathy, including rhabdomyolysis. The dose of simvastatin should be reduced by 50% when initiating lomitapide. While taking lomitapide, limit the simvastatin dose to 20 mg/day PO or 40 mg/day PO for patients who have previously tolerated simvastatin 80 mg/day PO for at least one year without evidence of muscle toxicity.
Loperamide: The plasma concentration of loperamide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with simvastatin, a P-gp inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Loperamide; Simethicone |