What is the overdose range for amlodipine (calcium channel blocker)?

Amlodipine Overdose Range

Amlodipine overdose begins at ingestions exceeding 40 mg (4 times the maximum therapeutic dose of 10 mg daily), with severe toxicity and fatalities reported at doses of 50-800 mg. 1, 2, 3

Defining Toxic Doses

Documented Overdose Cases

• Mild-to-moderate toxicity: 50-100 mg ingestion produced sustained hypotension (BP 79/50 to 113/76 mmHg), sinus tachycardia (92-129 bpm), and serum amlodipine concentration of 88 ng/mL (normal 3-11 ng/mL) 2
• Severe toxicity: 800 mg ingestion (eighty 10 mg tablets) caused refractory hypotension requiring ECMO support and ultimately resulted in death from anoxic brain injury 3
• Moderate-severe toxicity: 480 mg ingestion produced extreme vasoplegia refractory to maximal standard therapy, requiring albumin dialysis 4

Animal Toxicity Data

• Lethal doses in animals: 40 mg/kg in mice and 100 mg/kg in rats caused death 1
• Dogs: ≥4 mg/kg (11 times the maximum human dose on mg/m² basis) caused marked peripheral vasodilation and hypotension 1

Clinical Manifestations of Overdose

Cardiovascular Effects

• Profound hypotension from excessive peripheral vasodilation is the hallmark finding 1, 2, 3
• Reflex tachycardia occurs in response to vasodilation 1, 2
• Refractory shock may develop despite aggressive treatment 3, 4

Prolonged Duration of Toxicity

• Amlodipine has an elimination half-life of 40-60 hours under normal conditions, resulting in prolonged hemodynamic effects 5
• In overdose, effects can persist for 5-7 days requiring extended vasopressor support 3, 4
• Serum levels remain elevated for extended periods (79 ng/mL at 35 hours post-ingestion in one case) 2

Critical Management Considerations

Standard Supportive Care

• Immediate decontamination: Activated charcoal and whole bowel irrigation should be initiated early 2
• Cardiovascular monitoring: Frequent blood pressure measurements are essential 1
• Fluid resuscitation: Use cautiously as pulmonary edema can develop even with relatively low-volume fluid replacement (1.5 L caused pulmonary edema in one case) 2

Specific Antidotal Therapy

• Calcium chloride: 2000 mg (20 mL of 10% solution) or calcium gluconate 6000 mg (60 mL of 10% solution) every 10-20 minutes, or continuous infusion 6
• High-dose insulin therapy: 1 unit/kg IV bolus followed by 0.5-10 units/kg/h infusion with glucose supplementation 6
• Glucagon: 3-10 mg IV with infusion of 3-5 mg/h 6
• Vasopressors: Phenylephrine or other agents with attention to circulating volume 1

Refractory Cases

• Lipid emulsion: 1.5 mL/kg up to 100 mL bolus, followed by 0.25 mL/kg/min infusion 6
• Methylene blue: 1-2 mg/kg repeated every hour if needed for vasodilatory shock 6, 3, 4
• Albumin dialysis (MARS): May reduce amlodipine half-life to 7.6 hours in severe cases 4
• ECMO: Consider for refractory shock to maintain perfusion 3

Key Clinical Pitfalls

• Hemodialysis is ineffective because amlodipine is highly protein-bound (>95%) 1
• Extended monitoring required: Patients need observation for at least 24-48 hours due to delayed onset and prolonged effects 2
• Avoid excessive fluid resuscitation: Risk of pulmonary edema is significant 2
• Insulin resistance: Hyperglycemia may be refractory to very high insulin doses in severe overdose 4