Life-threatening interaction of mibefradil and beta-blockers with dihydropyridine calcium channel blockers

JAMA. 1998 Jul 8;280(2):157-8. doi: 10.1001/jama.280.2.157.


Mibefradil is a T-type and L-type calcium channel blocker (CCB) released in the United States in 1997 for management of hypertension and chronic stable angina. Postmarketing surveillance revealed a potential serious interaction between mibefradil and beta-blockers, digoxin, verapamil, and diltiazem, especially in elderly patients. The manufacturer voluntarily withdrew mibefradil on June 8, 1998. We describe 4 cases of cardiogenic shock in patients taking mibefradil and beta-blockers who began taking dihydropyridine CCBs. One case resulted in death; the other 3 survived episodes of cardiogenic shock with intensive support of heart rate and blood pressure. Physicians who are preparing to switch patients' medications from mibefradil to other antihypertensive agents should be aware of these potentially life-threatening drug-drug interactions.

Publication types

  • Case Reports

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Aged
  • Benzimidazoles / pharmacology*
  • Calcium Channel Blockers / pharmacology*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors
  • Dihydropyridines / pharmacology*
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Mibefradil
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Shock, Cardiogenic / chemically induced*
  • Sinoatrial Node / drug effects
  • Tetrahydronaphthalenes / pharmacology*


  • Adrenergic beta-Antagonists
  • Benzimidazoles
  • Calcium Channel Blockers
  • Cytochrome P-450 Enzyme Inhibitors
  • Dihydropyridines
  • Tetrahydronaphthalenes
  • Mibefradil
  • 1,4-dihydropyridine
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A