What is the reversal for Cardizem (Diltiazem)?

From the Guidelines

The reversal for Cardizem (diltiazem) overdose primarily involves calcium gluconate or calcium chloride administration, as recommended by the most recent guidelines 1. For acute reversal, give 1-3 grams of calcium gluconate IV (or 1 gram of calcium chloride) over 5-10 minutes, which can be repeated as needed based on clinical response. This approach is supported by the understanding that calcium channel blockers like diltiazem can cause severe toxicity, including shock from bradycardia, vasodilation, or loss of inotropy, as highlighted in the 2023 American Heart Association focused update 1. The following steps are crucial in managing the overdose:

• Vasopressor support if hypotension persists, typically with norepinephrine or epinephrine infusions
• High-dose insulin therapy (1 unit/kg bolus followed by 0.5-1 unit/kg/hour infusion) with glucose supplementation for severe cases
• Atropine to manage bradycardia
• Temporary cardiac pacing in extreme cases Calcium works as an antidote by competing with diltiazem at calcium channels, counteracting its negative inotropic and chronotropic effects, which is a key concept in the management of calcium channel blocker overdose 1. It's also important to note that hemodialysis is not effective for diltiazem removal due to its high protein binding, making supportive care including airway management, IV fluids, and continuous cardiac monitoring essential throughout the reversal process. Key considerations in the management of diltiazem overdose include:
• The distinction between dihydropyridines and nondihydropyridines, with the latter having more pronounced effects on cardiac tissue 1
• The potential for prolonged effects due to the sustained-release forms or long half-lives of calcium channel blockers 1
• The importance of monitoring for signs of toxicity, including bradycardia, hypotension, and loss of inotropy, and being prepared to intervene promptly.

From the FDA Drug Label

The effectiveness of intravenous calcium administration to reverse the pharmacological effects of diltiazem overdose has been inconsistent. In some cases intravenous calcium has been administered (1 g calcium chloride or 3 g calcium gluconate) over 5 minutes and repeated every 10 to 20 minutes as necessary. Calcium gluconate has also been administered as a continuous infusion at a rate of 2 g per hour for 10 hours. Infusions of calcium for 24 hours or more may be required. Patients should be monitored for signs of hypercalcemia

The reversal for Cardizem (diltiazem) overdose may involve the administration of intravenous calcium, such as calcium chloride or calcium gluconate, although its effectiveness has been inconsistent 2.

• The dosage of calcium can be administered as a bolus or as a continuous infusion, with monitoring for signs of hypercalcemia.
• Other supportive measures, such as atropine, isoproterenol, vasopressors, and inotropic agents, may also be considered depending on the severity of the clinical situation.

From the Research

Reversal for Cardizem

• Cardizem, also known as diltiazem, is a calcium channel blocker used to treat various cardiovascular conditions, including angina, hypertension, and supraventricular tachycardia 3, 4.
• In cases of diltiazem overdose, treatment options are limited, and conventional decontamination measures are often ineffective 5, 6.
• Management of calcium antagonist overdose, including diltiazem, typically involves gut decontamination, ECG monitoring, and supportive care, such as atropine or isoprenaline for bradycardia and conduction defects, and calcium chloride or calcium gluconate for depressed myocardial contractility 6.
• Research has explored the use of drug-scavenging liposomes as a potential antidote for calcium channel blocker overdose, including diltiazem, with promising results in animal studies 5.
• In the context of atrial fibrillation with rapid ventricular response, calcium chloride pre-treatment has been investigated as a means to prevent diltiazem-induced hypotension, but its effectiveness is unclear 7.
• The use of calcium chloride before intravenous diltiazem in the management of atrial fibrillation has been studied, with results suggesting that it may not significantly blunt the drop in systolic blood pressure, although it appears to be safe 7.