Acute Kidney Injury from Excessive Potentiation of Calcium-channel Blocker via Synergistic CYP3A4 Inhibition by Clarithromycin Plus Voriconazole

Intern Med. 2017;56(13):1687-1690. doi: 10.2169/internalmedicine.56.8313. Epub 2017 Jul 1.

Abstract

CYP3A4-inhibitors can potentiate the hypotensive effect of calcium-channel blockers. However, insufficient attention to such drug interactions may result in serious adverse reactions. A 71-year-old hypertensive man prescribed nifedipine was hospitalized for infectious endophthalmitis. Antimicrobial therapy with voriconazole lowered the blood pressure, and then clarithromycin further lowered it through the excessively elevated nifedipine concentration, leading to ischemic acute kidney injury. After the discontinuation of clarithromycin and voriconazole, the blood pressure and renal function were recovered. The combination of CYP3A4-inhibitors such as clarithromycin plus voriconazole can synergistically potentiate calcium-channel blockers. Co-prescription of multiple CYP3A4-inhibitors with calcium-channel blockers increases the risk of hypotension and acute kidney injury.

Keywords: CYP3A4; acute kidney injury; calcium-channel blockers; drug interaction; hypertension; nifedipine.

Publication types

  • Case Reports

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / adverse effects*
  • Calcium Channel Blockers / therapeutic use
  • Clarithromycin / pharmacology*
  • Clarithromycin / therapeutic use
  • Cytochrome P-450 CYP3A Inhibitors / pharmacology*
  • Cytochrome P-450 CYP3A Inhibitors / therapeutic use
  • Drug Synergism
  • Humans
  • Hypertension / drug therapy
  • Hypotension / chemically induced
  • Male
  • Nifedipine / adverse effects*
  • Nifedipine / pharmacology
  • Nifedipine / therapeutic use
  • Voriconazole / pharmacology*
  • Voriconazole / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Calcium Channel Blockers
  • Cytochrome P-450 CYP3A Inhibitors
  • Clarithromycin
  • Nifedipine
  • Voriconazole