Amlodipine makes up half of CCB overdoses, but verapamil, diltiazem remain most toxic

Among the cases of calcium channel blocker (CCB) overdose, dihydropyridines are the most common, with amlodipine accounting for nearly half. On the other hand, more severe toxicities occur with the use of verapamil and diltiazem.

“We found amlodipine to account for an increasing proportion of CCB overdoses and increasing numbers of deaths secondary to this,” the researchers said.

“However, diltiazem and verapamil remain the most toxic agents within the CCB group overall, more commonly requiring intensive care and cardiac interventions,” they added.

In this study, CCB overdoses seen in two toxicology services between 2014 and 2023 were reviewed. Prospectively collected data were then extracted from a clinical database, which included demographics, doses, coingestants, complications, treatments, and outcomes, to compare different CCBs.

A total of 236 CCB overdoses (median age 55 years) were reported, of which the majority were female patients (n=130, 55 percent). [Br J Clin Pharmacol 2025;91:740-747]

A significant increase in dihydropyridine overdoses was observed, with a median of nine cases per year during the study period compared with a median of only three cases per year in the previous decade. Of the overdoses, amlodipine was the most frequent (n=147), followed by lercanidipine (n=28), diltiazem (n=27), verapamil (n=23), and felodipine (n=11).

Higher median defined daily dose ingested was observed with dihydropyridines. Cardiac coingestants were also common, except for verapamil.

The median length of hospital stay among patients with CCB overdoses was 21 h but was longer for those who ingested diltiazem (median 39 h). Fifty-six patients (24 percent) were admitted to the intensive care unit (ICU). ICU admission was most frequent for diltiazem (n=14, 52 percent) and verapamil (n=7, 30 percent).

Nineteen patients had dysrhythmia (diltiazem: n=9; verapamil: n=8; amlodipine: n=2), with 13 experiencing junctional dysrhythmia. In addition, 91 patients (39 percent) developed hypotension, 62 (26 percent) received inotropes/vasopressors (adrenaline, 52 percent; noradrenaline, 77 percent), 21 (9 percent) high-dose insulin, and 44 (19 percent) calcium.

“Adrenaline and high-dose insulin were more commonly given in diltiazem and verapamil overdoses, compared to vasopressors in dihydropyridine overdoses,” the researchers said.

Mortality

Thirty-nine patients also suffered from acute kidney injury (AKI), and seven (3 percent) died.

“AKI is often not recognized in many of these patients because it is only stage I and has minimal impact,” the researchers said. “However, it is a clear indicator of end-organ injury from the overdose and may have impact on long-term kidney functioning leading to chronic kidney disease.”

The rate of mortality for diltiazem and verapamil ranged from 6 percent to 9 percent, which included patients who ingested CCB alone. Such rate was significantly higher than that for dihydropyridines.

“This can be attributed to the broader toxicity spectrum of diltiazem and verapamil, which cause negative inotropy and chronotropy, as well as peripheral vasodilation, compared to … vasodilatory effects seen with dihydropyridines,” the researchers said. [Br J Clin Pharmacol 2016;81:453-461]

CCB overdoses, though less common among cases of pharmaceutical poisonings, may result in significant morbidity and mortality. [Med J Aust 2015;202:438-442; Clin Toxicol (Phila) 2023;61:409-410; BMC Pharmacol Toxicol 2018;19:78]