Pharmacokinetic drug-drug interaction of calcium channel blockers with cyclosporine in hematopoietic stem cell transplant children

Ann Pharmacother. 2014 Dec;48(12):1580-4. doi: 10.1177/1060028014550644. Epub 2014 Oct 3.

Abstract

Background: Cyclosporine (CsA) is frequently responsible for hypertension in bone marrow transplant children. Calcium channel blockers (CCBs) are considered to be the best treatment for CsA-induced hypertension, but they may alter the exposure and the effect of CsA by inhibiting the CYP3A4 pathway of CsA metabolism or P-gp. However, the inhibitory effect on CYP3A4 may vary among CCBs.

Methods: This study aimed to quantify the pharmacokinetic drug-drug interaction between CsA and nicardipine, amlodipine, and lacidipine. In all, 51 children who received CsA and CCB concomitantly were included.

Results: Dose-normalized CsA trough blood concentrations significantly increased in patients treated with nicardipine and amlodipine, whereas they remained stable in patients treated with lacidipine.

Conclusions: Because lacidipine appears to have no effect on CsA exposure, it may be the best option among CCBs for treating high blood pressure caused by CsA in children.

Keywords: bone marrow transplantation; calcium-channel blockers; cyclosporine; drug interactions; pediatrics.

MeSH terms

  • Adolescent
  • Amlodipine / pharmacokinetics
  • Amlodipine / therapeutic use
  • Calcium Channel Blockers / pharmacokinetics*
  • Calcium Channel Blockers / therapeutic use
  • Child
  • Child, Preschool
  • Cyclosporine / adverse effects
  • Cyclosporine / pharmacokinetics*
  • Dihydropyridines / pharmacokinetics
  • Dihydropyridines / therapeutic use
  • Drug Interactions
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Hypertension / chemically induced
  • Hypertension / drug therapy
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacokinetics*
  • Infant
  • Male
  • Nicardipine / pharmacokinetics
  • Nicardipine / therapeutic use
  • Retrospective Studies

Substances

  • Calcium Channel Blockers
  • Dihydropyridines
  • Immunosuppressive Agents
  • Amlodipine
  • lacidipine
  • Cyclosporine
  • Nicardipine