What is the appropriate management of an amlodipine (calcium‑channel blocker) overdose, including decontamination and hemodynamic support?

Management of Amlodipine Overdose

Initiate simultaneous multimodal therapy with intravenous calcium, high-dose insulin euglycemia therapy (HIET), and vasopressors for all patients with hemodynamically significant amlodipine overdose. 1, 2

Initial Stabilization and Monitoring

• Establish continuous cardiac monitoring immediately to detect bradycardia, conduction abnormalities (especially AV blocks), and dysrhythmias that commonly occur with calcium channel blocker toxicity. 2

• Secure intravenous access—preferably central venous access if prolonged intensive therapy is anticipated—as amlodipine overdose can cause hypotension lasting several days. 2, 3

• Place an arterial line for continuous blood pressure monitoring in shock states to guide aggressive titration of therapies. 2

• Obtain baseline laboratory studies including serum glucose, potassium, ionized calcium, and renal function to guide therapy and monitor for complications (hypoglycemia, hypokalemia, hypercalcemia). 2, 4

• Administer activated charcoal (1-2 g/kg) only if presentation is within 1-2 hours of ingestion and the airway is protected; do not delay definitive therapy for decontamination. 2

• Contact poison control center (1-800-222-1222) or a medical toxicologist immediately for all amlodipine overdoses to guide therapy. 2

First-Line Multimodal Pharmacologic Therapy

The 2023 American Heart Association guidelines recommend three interventions be initiated simultaneously, not sequentially. 1, 4

Intravenous Calcium (Class 2a Recommendation)

• Administer calcium chloride 10% at 0.2 mL/kg (or calcium gluconate 10% at 0.6 mL/kg) IV over 5-10 minutes as an initial bolus. 4

• Follow immediately with continuous infusion of 0.3 mEq/kg per hour, titrated to hemodynamic response. 4

• Target ionized calcium levels up to twice the normal range while avoiding severe hypercalcemia (>2× upper limit of normal). 1, 4

• Critical caveat: Calcium alone is insufficient for most patients and must be combined with HIET and vasopressors—do not rely on calcium monotherapy. 1, 4

• Monitor ionized calcium levels during infusions to guide dosing and prevent toxicity. 2

High-Dose Insulin Euglycemia Therapy (HIET) (Class 1 Recommendation)

HIET is the most effective therapy for severe calcium channel blocker toxicity, improving cardiac contractility with lower rates of vasoconstrictive complications than vasopressor-only therapy. 2, 3

• Administer 1 U/kg regular insulin IV bolus with simultaneous 0.5 g/kg dextrose bolus. 2

• Initiate continuous infusion of 0.5-1 U/kg/hour insulin, titrating up to 10 U/kg/hour based on clinical response and hemodynamic improvement. 4

• Administer concurrent dextrose infusion at 0.5 g/kg/hour, adjusted to maintain serum glucose 100-250 mg/dL. 4

• Monitor serum glucose every 15 minutes initially during titration, then hourly once stable to prevent hypoglycemia. 2, 4

• Monitor serum potassium every 1-2 hours and replace aggressively to prevent hypokalemia, a common complication of HIET. 1, 4

• Begin HIET early—preferably before marked hemodynamic collapse—and escalate aggressively if myocardial dysfunction persists. 4

Vasopressor Therapy (Class 1 Recommendation)

• Norepinephrine is the preferred first-line vasopressor, with retrospective data demonstrating excellent survival rates at doses up to 100 μg/min in adults with low rates of ischemic complications. 1, 3, 4

• Add epinephrine when cardiogenic shock predominates or when additional inotropic support is needed. 4

• Consider dobutamine as an adjunct when confirmed myocardial dysfunction is present despite other therapies. 4

Second-Line and Adjunctive Therapies

Atropine (Class 2a Recommendation)

• Atropine may be administered for symptomatic bradycardia as a temporizing measure while preparing definitive therapies, but treatment failures are common and efficacy is limited. 1, 4

Glucagon (Class 2b Recommendation—Uncertain Utility)

• Glucagon has variable response rates with common adverse effects including vomiting and rapid tachyphylaxis. 1, 4

• Consider glucagon only as adjunctive therapy in refractory cases, not as primary treatment. 2

Methylene Blue

• Methylene blue may be effective specifically for refractory vasodilatory shock from amlodipine overdose (a dihydropyridine calcium channel blocker). 1

• Responses are mixed and effects may be transient; reserve for cases with preserved cardiac contractility but profound vasodilation. 1

Temporary Cardiac Pacing (Class 2b Recommendation)

• Consider transcutaneous or transvenous pacing for unstable bradycardia or high-grade AV block only when myocardial function is preserved. 4

• Important pitfall: Pacing is often ineffective in complete AV nodal blockade or in the setting of vasodilatory shock with myocardial dysfunction—do not delay other therapies while attempting pacing. 1, 4

Rescue Therapy for Refractory Shock

Veno-Arterial ECMO (Class 2a Recommendation)

VA-ECMO may be lifesaving for persistent cardiogenic shock refractory to maximal pharmacologic therapy, with reported survival rates as high as 77%. 1, 3, 4

• Consider VA-ECMO early when shock remains refractory to combined calcium, HIET, and high-dose vasopressors. 2

• VA-ECMO is especially beneficial when pump failure (cardiogenic component) predominates over vasodilatory shock. 4

• Deploy VA-ECMO promptly if available for refractory cardiac arrest in the setting of amlodipine overdose. 4

Albumin Dialysis

• Albumin dialysis (e.g., MARS therapy) has shown efficacy in case reports for removing highly protein-bound amlodipine and reversing refractory vasoplegic shock when cardiac contractility is preserved. 5

• Consider albumin dialysis as an alternative to VA-ECMO when distributive shock predominates with preserved cardiac function, making VA-ECMO less preferable. 5

Therapies NOT Recommended

Intravenous Lipid Emulsion (ILE) (Class 3: No Benefit)

The 2023 American Heart Association guidelines advise against routine use of ILE for calcium channel blocker poisoning. 1, 4

• A large retrospective study found no benefit from ILE therapy in calcium channel blocker overdose. 1

• Clinical and experimental data suggest ILE may increase absorption of lipophilic drugs like amlodipine from the gastrointestinal tract, potentially worsening oral overdose. 1, 4

• Reserve ILE only for refractory shock or periarrest states unresponsive to all other therapies, recognizing uncertain benefit and potential harm. 4

Hemodialysis

• Standard hemodialysis is not effective for amlodipine removal because amlodipine is highly protein-bound (>95%). 6

Cardiac Arrest Management

• During ACLS, administer an IV calcium bolus in addition to standard resuscitation measures. 4

• Consider concurrent IV lipid emulsion therapy if cardiac arrest is refractory to standard measures, despite lack of strong evidence. 4

• Deploy VA-ECMO immediately if available for refractory cardiac arrest, as retrospective data show improved outcomes in drug toxicity-related arrest. 4

Key Pitfalls to Avoid

• Do not use calcium as monotherapy—most patients require combined calcium, HIET, and vasopressors for survival. 1, 4

• Do not use ILE routinely—it may worsen toxicity by enhancing gastrointestinal absorption of oral amlodipine. 1, 4

• Do not rely on electrical pacing in patients with significant myocardial dysfunction or vasodilatory shock, as it is likely ineffective. 1, 4

• Do not delay HIET—initiate early before marked hemodynamic collapse for best outcomes. 4

• Do not underdose insulin—titrate aggressively up to 10 U/kg/hour based on clinical response. 4

• Monitor for and correct hypokalemia and volume overload during HIET, as these are common complications. 1, 4