What is the recommended dosing for Losartan (Angiotensin II receptor antagonist) in a patient with hypertension or diabetic nephropathy, considering potential impaired renal function and risk of hyperkalemia?

Losartan Dosing for Hypertension and Diabetic Nephropathy

For hypertension, start losartan at 50 mg once daily and increase to 100 mg once daily as needed for blood pressure control; for diabetic nephropathy, start at 50 mg once daily and increase to 100 mg once daily based on blood pressure response. 1

Standard Dosing Regimens

Hypertension

• Starting dose: 50 mg once daily 1
• Maximum dose: 100 mg once daily 1
• For patients with possible intravascular depletion (e.g., on diuretic therapy), start with 25 mg once daily 1
• If blood pressure remains uncontrolled on 100 mg daily, add hydrochlorothiazide 12.5-25 mg rather than exceeding the maximum losartan dose 2

Diabetic Nephropathy

• Starting dose: 50 mg once daily 1
• Target dose: 100 mg once daily 1, 3
• Research demonstrates that 100 mg daily is significantly more effective than 50 mg daily in reducing albuminuria (48% vs 30% reduction) and blood pressure without differences between 100 mg and 150 mg doses 4
• For patients with albuminuria (UACR ≥300 mg/g), losartan at maximum tolerated dose is strongly recommended as first-line therapy 3

Dosing Modifications for Hepatic Impairment

• Patients with mild-to-moderate hepatic impairment: start with 25 mg once daily 1
• Losartan has not been studied in severe hepatic impairment 1

Monitoring Requirements

Initial Monitoring

• Check serum creatinine/eGFR and potassium within 2-4 weeks after starting or changing dose 3
• More frequent monitoring (within 7-14 days) is recommended by some guidelines 3

Ongoing Monitoring

• Monitor at least annually during maintenance therapy 3
• Monthly monitoring for the first 3 months, then every 3 months thereafter is recommended for patients at higher risk 3

Management of Adverse Effects

Hyperkalemia Management

Do not immediately discontinue losartan for hyperkalemia; instead, implement potassium-lowering measures first: 3

• Review and discontinue concurrent drugs that increase potassium (NSAIDs, potassium supplements)
• Moderate dietary potassium intake
• Consider diuretics, sodium bicarbonate, or GI cation exchangers
• Only reduce dose or stop losartan as a last resort 3

Creatinine Elevation

If creatinine increases >30% from baseline: 3

• Review for causes of acute kidney injury
• Correct volume depletion
• Reassess concomitant medications (diuretics, NSAIDs)
• Consider renal artery stenosis
• Reduce dose or stop only if other measures fail

When to Discontinue or Reduce Dose

Reduce or discontinue losartan in these specific situations: 3

• Symptomatic hypotension unresponsive to management
• Uncontrolled hyperkalemia despite medical treatment
• To reduce uremic symptoms in advanced kidney failure (eGFR <15 mL/min/1.73 m²)

Renal Function Considerations

• Losartan can be continued as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit 3
• No dosage adjustment is necessary for various degrees of renal insufficiency 5, 6
• Losartan is effective and well-tolerated in patients with chronic renal disease, including those on hemodialysis 5
• Losartan is not removed during hemodialysis 6

Critical Safety Warnings

Contraindicated Combinations

Never combine losartan with: 3

• ACE inhibitors (increases risk of hyperkalemia, syncope, and acute kidney injury without added benefit)
• Direct renin inhibitors like aliskiren (same risks as ACE inhibitor combination)
• Another ARB (potentially harmful)

Pregnancy

• Discontinue losartan in women considering pregnancy or who become pregnant 3
• Losartan causes serious fetal toxicity when given in second and third trimesters 6

Common Pitfalls to Avoid

1. Underdosing: Most patients never reach the target dose of 100 mg daily despite evidence showing superior outcomes at higher doses 2, 4

2. Premature discontinuation for hyperkalemia: Implement potassium-lowering strategies before stopping the medication, as the renoprotective and cardiovascular benefits often outweigh manageable hyperkalemia 3

3. Combining with ACE inhibitors: This combination is contraindicated and increases adverse events without improving outcomes 3

4. Inadequate monitoring: Failure to check potassium and creatinine within 2-4 weeks of initiation or dose changes can lead to undetected complications 3

5. Stopping therapy when eGFR declines: Continuation of losartan as kidney function declines to eGFR <30 mL/min/1.73 m² provides cardiovascular benefit 3