What are the potential adverse effects of losartan (angiotensin II receptor antagonist) in an adult patient with hypertension or kidney disease?

Adverse Effects of Losartan

Losartan is generally well-tolerated with an adverse event profile similar to placebo, with dizziness being the only consistently drug-related side effect occurring more frequently than placebo. 1, 2

Common Adverse Effects

The most frequently reported adverse effects in hypertensive patients include:

• Upper respiratory infection (8% vs. 7% placebo), dizziness (3% vs. 2% placebo), nasal congestion (2% vs. 1% placebo), and back pain (2% vs. 1% placebo) 1
• Headache (14.1% vs. 17.2% placebo), indicating this is not truly drug-related 2
• Cough occurs in only 3.1% of losartan patients compared to 2.6% with placebo and 8.8% with ACE inhibitors, making losartan an excellent alternative for patients with ACE inhibitor-induced cough 1, 2

In patients with type 2 diabetes and diabetic nephropathy, the most common adverse effects are:

• Diarrhea, tiredness, low blood sugar, chest pain, high blood potassium, and low blood pressure 1

Serious Adverse Effects Requiring Monitoring

Hyperkalemia

• Monitor serum potassium periodically, particularly in patients with chronic kidney disease, diabetes, or those taking potassium-sparing diuretics or potassium supplements 1
• Hyperkalemia (>6 mEq/L) requiring discontinuation is rare, occurring in only 1 out of 112 patients with renal impairment in clinical trials 3
• The American Heart Association recommends checking potassium within 1-2 weeks after starting losartan or increasing the dose 4

Renal Function Deterioration

• Acute renal failure can occur in patients with bilateral renal artery stenosis, severe heart failure, or volume depletion whose renal function depends on angiotensin II activity 1
• Monitor renal function periodically and consider withholding therapy if clinically significant decline occurs 1
• A modest rise in serum creatinine (10-20%) after starting losartan is expected and hemodynamic in nature, not indicative of kidney injury unless persistent 5
• In clinical trials of patients with renal impairment, creatinine clearance and glomerular filtration rate remained stable on losartan 3

Hypotension

• Symptomatic hypotension may occur in volume- or salt-depleted patients (e.g., those on high-dose diuretics) 1
• Correct volume or salt depletion prior to initiating losartan 1
• First-dose hypotension is uncommon with losartan, likely due to its slower onset of action 6, 2

Fetal Toxicity

• Losartan causes fetal harm when used during the second and third trimesters of pregnancy, resulting in oligohydramnios, fetal lung hypoplasia, skeletal deformations, skull hypoplasia, anuria, hypotension, renal failure, and death 1
• Discontinue losartan immediately when pregnancy is detected 1

Less Common Adverse Effects

Additional adverse effects reported in <2% of patients include:

• Cardiovascular: Palpitations, syncope, atrial fibrillation, cerebrovascular accident 1
• Gastrointestinal: Abdominal pain, constipation, nausea, vomiting 1
• Dermatologic: Urticaria, pruritus, rash, photosensitivity 1
• Musculoskeletal: Myalgia, arthralgia 1
• Neurologic: Somnolence, sleep disorders, paresthesia, migraine, vertigo, tinnitus 1
• Reproductive: Impotence 1
• Hematologic: Anemia 1
• Psychiatric: Depression 1

Rare but Serious Adverse Effects

• Angioedema has been reported in postmarketing surveillance, involving swelling of the face, lips, throat, or tongue requiring immediate discontinuation and emergency medical attention 1, 6

Discontinuation Rates

• Only 2.3% of patients discontinued losartan due to adverse events compared to 3.7% with placebo, demonstrating excellent tolerability 1, 2
• In patients with renal impairment, only 6 out of 112 patients (5.4%) withdrew due to clinical or laboratory adverse experiences 3

Critical Drug Interactions Increasing Adverse Effects

• Never combine losartan with ACE inhibitors or aliskiren (especially in diabetic patients), as this increases risks of hyperkalemia, syncope, and acute kidney injury without additional benefit 7, 4, 1
• Avoid combining with potassium supplements, potassium-sparing diuretics, or salt substitutes containing potassium due to compounded hyperkalemia risk 7, 1
• NSAIDs may increase risk of renal dysfunction when used with losartan 1

Special Populations

Renal Impairment

• Losartan was well-tolerated in patients with mild, moderate-to-severe renal insufficiency, and those on hemodialysis, with stable renal function parameters throughout 12 weeks of treatment 3
• No dosage adjustment is recommended for renal impairment, though closer monitoring is warranted 3

Hepatic Impairment

• Start with 25 mg daily in patients with hepatic impairment due to 5-fold increase in losartan plasma concentrations 4

Elderly Patients

• No clinically important differences in safety profile were observed based on age, gender, or race 2