Drug Interactions between amlodipine / atorvastatin and vadadustat

Consumer information for this interaction is not currently available.

ADJUST DOSE: Coadministration with vadadustat, an inhibitor of breast cancer resistance protein (BCRP), may increase the plasma concentrations and pharmacologic effects of drugs that are substrates of BCRP such as atorvastatin, rosuvastatin, and simvastatin. The proposed mechanism involves decreased clearance due to inhibition of BCRP by vadadustat. According to product labeling, when vadadustat was coadministered with the BCRP substrates simvastatin and rosuvastatin, systemic exposure (AUC) of the substrates increased 2-fold, and 2 to 3-fold, respectively. High levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity, such as myopathy and rarely, rhabdomyolysis.

MANAGEMENT: When concomitant use of vadadustat is required, product labeling recommends limiting the starting dose of simvastatin to 5 mg and the daily dose to 20 mg, and the daily dose of rosuvastatin to 5 mg. The prescribing information for other BCRP substrates should be consulted for any dosage adjustments that may be required during coadministration and/or following the discontinuation of a BCRP inhibitor. Patients should be advised to monitor for signs and symptoms of adverse effects and promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.

AmLODIPine may increase the blood levels of atorvastatin. This can increase the risk of side effects such as liver damage and a rare but serious condition called rhabdomyolysis that involves the breakdown of skeletal muscle tissue. In some cases, rhabdomyolysis can cause kidney damage and even death. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Let your doctor know immediately if you have unexplained muscle pain, tenderness, or weakness while taking these medications, especially if these symptoms are accompanied by fever or dark colored urine. You should also seek immediate medical attention if you develop fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with vadadustat may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 and/or CYP450 2C8 isoenzymes. Vadadustat is an inhibitor of CYP450 3A4 and CYP450 2C8 in vitro. However, clinical data are not available.

MANAGEMENT: Some authorities recommend using caution when vadadustat is used concomitantly with drugs that are substrates of CYP450 3A4 and/or CYP450 2C8, particularly sensitive substrates or those with a narrow therapeutic range. Monitoring for signs and symptoms of increased exposure to the CYP450 3A4 and/or CYP450 2C8 substrate should be considered whenever vadadustat is added to or withdrawn from therapy. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of a CYP450 3A4 and/or CYP450 2C8 inhibitor.