ARB Overdose

Angiotensin receptor blocker overdose usually causes dose dependent hypotension, mild bradycardia or tachycardia, and sometimes hyperkalaemia. It is less toxic than ACE inhibitor overdose in most reports, and angioedema is rare.

ARBs (losartan, valsartan, candesartan, irbesartan, telmisartan, olmesartan) are widely prescribed. Serious toxicity is uncommon and usually follows large ingestions, such as over 1 g of losartan, or ingestion with other antihypertensives or in hypovolaemic patients.

Risk factors for harm. Hypovolaemia, renal impairment, co-ingestion of other antihypertensives or diuretics, and potassium supplementation.

Course. Peak effect at 2 to 6 hours with duration of 24 hours or longer for long acting agents such as candesartan and telmisartan.

Pathophysiology.

Blockade of AT1 receptors prevents angiotensin II-mediated vasoconstriction, causing vasodilatation and loss of efferent arteriolar tone.

Aldosterone falls, so potassium may rise.

• Dizziness, postural hypotension, headache and nausea.
• Hypotension, which may be prolonged and refractory to fluids in large ingestions.
• Mild tachycardia or bradycardia, hyperkalaemia and acute kidney injury.
• Angioedema is rare.

Red flags.

• Systolic blood pressure under 90 mmHg despite fluids.
• Potassium over 6.5 mmol/L.
• Oliguria or rising creatinine.

• History of the drug, dose and co-ingestants; paracetamol and salicylate levels.
• Blood pressure, ECG, electrolytes, urea and creatinine, glucose, lactate and venous gas.
• Urine output and repeated potassium and creatinine over 24 hours.

Differential diagnosis. ACE inhibitor, calcium channel blocker or beta blocker overdose, hypovolaemia, sepsis and adrenal insufficiency.

• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 1 hour of a large ingestion 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.
• Hypotension: lie flat, give intravenous 0.9% sodium chloride 10 to 20 mL/kg, then noradrenaline 0.05 micrograms/kg/minute intravenously if fluids fail, 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. Refractory shock may respond to vasopressin 0.01 to 0.04 units/minute.
• Hyperkalaemia with ECG changes: calcium gluconate 10% 30 mL intravenously over 10 minutes, repeated after 10 minutes if ECG changes persist. Maximum 3 doses. Monitor ECG continuously and extravasation. Avoid in digoxin toxicity.
• Insulin 10 units (soluble) intravenously with glucose 25 g (50 mL of 50%) over 15 minutes. Maximum 2 doses; repeat every 30 to 60 minutes as needed. Monitor glucose hourly for 6 hours; reduce insulin to 5 units in severe renal impairment.
• Haemodialysis is ineffective for most ARBs because of high protein binding, and is used for renal failure or intractable hyperkalaemia only.
• Observe for at least 6 hours (24 hours for long acting agents, large ingestions or renal impairment), with blood pressure, potassium and creatinine rechecked before discharge.
• Withhold the drug until blood pressure and renal function recover, then review the need.

Monitoring. Blood pressure, potassium and creatinine every 6 hours; urine output.

Referral and escalation. Poisons information centre for large ingestions; intensive care for shock; nephrology for renal failure.

Special groups. Pregnancy: ARBs are foetotoxic, so review the prescription after recovery. Older adults: higher risk of kidney injury.