Amlodipine Overdose

Amlodipine overdose causes profound vasodilatory shock, with preserved or reflex increased heart rate, non-cardiogenic pulmonary oedema and, in large ingestions, bradycardia and multiorgan failure. It is the most important dihydropyridine calcium channel blocker poisoning.

Amlodipine is among the most prescribed drugs, and overdoses are increasing. Serious toxicity is likely above 0.5 mg/kg or 10 mg in children, and above 30 to 50 mg in adults. Deaths occur with ingestions over 100 mg.

Risk factors for harm. Co-ingestion with beta blockers or other antihypertensives, older age, cardiac disease and large ingestions.

Course. Onset can be delayed by 6 hours or more, and shock persists for 24 to 72 hours because of the long half life (30 to 50 hours).

Pathophysiology.

Blockade of L-type calcium channels in vascular smooth muscle causes vasodilatation and reduced systemic vascular resistance. At high doses, blockade extends to the myocardium and pancreatic beta cells.

Impaired insulin release causes hyperglycaemia, and metabolic derangement worsens shock.

• Dizziness, flushing, headache, nausea and tachycardia in early or mild poisoning.
• Profound hypotension, warm peripheries and often reflex tachycardia, later bradycardia.
• Non-cardiogenic pulmonary oedema (about 10 to 30% of severe cases), acute respiratory distress and confusion.
• Hyperglycaemia, lactic acidosis, acute kidney injury and mesenteric ischaemia.

Red flags.

• Systolic blood pressure under 90 mmHg despite fluids.
• Pulmonary oedema or rising lactate.
• Co-ingestion of beta blockers or other cardiovascular drugs.

• History of dose, formulation and co-ingestants; paracetamol and salicylate levels.
• ECG and continuous monitoring; arterial or intraosseous blood pressure monitoring for significant ingestions.
• Glucose (typically high), electrolytes (including calcium), lactate, renal function, creatine kinase and blood gas.
• Chest imaging for pulmonary oedema; echocardiography when shock persists.

Differential diagnosis. Other calcium channel blocker (verapamil, diltiazem), beta blocker or ACE inhibitor overdose, sepsis, anaphylaxis, cardiogenic shock and haemorrhage.

• Resuscitation: airway, oxygen and cautious fluids (up to 10 to 20 mL/kg), watching for pulmonary oedema.
• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 1 hour (2 hours for large ingestions) if the airway is protected. Monitor the airway for aspiration. Avoid with reduced consciousness, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Calcium chloride 10% 10 mL (6.8 mmol) intravenously over 5 to 10 minutes through a central line (or calcium gluconate 10% 30 mL peripherally), repeated every 10 to 20 minutes up to 3 doses, then infusion of calcium gluconate 10% 0.2 to 0.4 mL/kg/hour. Maximum 3 bolus doses in the first hour. Monitor ionised calcium (target upper normal), ECG and extravasation. Avoid in digoxin toxicity; use caution in renal impairment and hypercalcaemia.
• High dose insulin with euglycaemia (early, for shock): insulin 1 unit/kg intravenously as a bolus, then 1 unit/kg/hour infusion, titrated every 30 minutes up to 10 units/kg/hour; give glucose 25 g (50 mL of 50%) with the bolus and then glucose 0.5 g/kg/hour (10% or 20%) titrated to a glucose of 5 to 10 mmol/L. Maximum 10 units/kg/hour. Monitor glucose every 15 to 30 minutes, potassium (replace to 2.5 to 3.0 mmol/L or higher) and phosphate; avoid fluid overload.
• Vasopressors: noradrenaline 0.05 micrograms/kg/minute intravenously, titrated to a mean arterial pressure of 65 mmHg or higher. Maximum 1 microgram/kg/minute. Give by central line; monitor blood pressure, extravasation and arrhythmia. Add vasopressin 0.01 to 0.04 units/minute if shock persists.
• Vasoplegia that does not respond to these measures: methylene blue 1 to 2 mg/kg intravenously over 20 minutes, repeated once if needed. Maximum 4 mg/kg in total. Monitor methaemoglobin, serotonin toxicity and haemolysis. Avoid in G6PD deficiency and with serotonergic drugs.
• Intravenous lipid emulsion for peri-arrest or refractory shock: 20% lipid emulsion 1.5 mL/kg bolus, then 0.25 mL/kg/minute for 30 to 60 minutes. Maximum 10 mL/kg in total. Monitor pancreatitis, interference with laboratory tests and fluid load. Avoid with severe lipid disorders.
• Pulmonary oedema: positive airway pressure, ventilation and avoidance of excess fluids.
• Extracorporeal membrane oxygenation for refractory shock or arrest (specialist centre).
• Observe for at least 24 hours for modified release or large ingestions (48 hours for large doses), in a monitored setting.

Monitoring. Continuous ECG and arterial pressure; glucose, potassium, calcium and lactate every 1 to 2 hours during insulin therapy.

Referral and escalation. Early poisons information centre and intensive care; cardiothoracic centre for extracorporeal support.

Special groups. Children: even single tablets may be dangerous. Pregnancy: the same treatment applies, with obstetric input.