Symptoms of Losartan Overdose
The most likely manifestations of losartan overdose are hypotension and tachycardia, with bradycardia possible from parasympathetic (vagal) stimulation. 1
Primary Clinical Manifestations
The FDA drug label provides the definitive guidance on losartan overdose presentation based on animal toxicity data and limited human experience:
- Hypotension is the predominant expected finding, resulting from excessive angiotensin II receptor blockade and subsequent vasodilation 1
- Tachycardia typically accompanies hypotension as a compensatory reflex response 1
- Bradycardia may paradoxically occur due to vagal stimulation, though this is less common than tachycardia 1
Lethal Dose Information
Animal studies establish the toxicity threshold, though direct human correlation is limited:
- Significant lethality occurred in mice at oral doses of 1000 mg/kg (approximately 44 times the maximum recommended human dose on a mg/m² basis) 1
- In rats, lethal doses were 2000 mg/kg (approximately 170 times the maximum recommended human dose on a mg/m² basis) 1
Management Approach
If symptomatic hypotension occurs, supportive treatment should be instituted immediately. 1
Key management considerations include:
- Hemodialysis is ineffective for removing losartan or its active metabolite E-3174 from the circulation 1
- Supportive care focuses on maintaining adequate blood pressure and perfusion through IV fluids and vasopressors as needed 1
- Monitor for both tachycardia and the less common bradycardia, adjusting supportive measures accordingly 1
Important Clinical Context
The active metabolite E-3174 has a terminal half-life of 6-9 hours and is 10-40 fold more potent than losartan itself, meaning prolonged monitoring may be necessary even after initial stabilization 2. The pharmacokinetics are linear and dose-proportional, suggesting that higher overdoses will produce proportionally greater effects 2.
Critical caveat: Patients with pre-existing conditions that make them sensitive to reduced renal plasma flow (bilateral renal artery stenosis, severe heart failure, or severe volume depletion) may experience more severe manifestations, including acute renal failure, as their renal function is angiotensin-dependent 3.
Human overdose data remain limited, so clinical vigilance for unexpected manifestations beyond the classic triad of hypotension, tachycardia, and possible bradycardia is warranted 1.