What are the dosing guidelines, contraindications, precautions, monitoring parameters, and special population considerations for prescribing losartan?

Losartan: Precautions, Contraindications, and Special Population Considerations

Absolute Contraindications

Losartan is absolutely contraindicated in pregnancy due to serious fetal toxicity including renal dysfunction, oligohydramnios, skull hypoplasia, and fetal death. 1

• Upon pregnancy detection, discontinue losartan immediately and switch to pregnancy-compatible antihypertensives such as methyldopa, labetalol, or extended-release nifedipine 1
• Women of childbearing potential should be counseled about this risk before initiating therapy 1

Never combine losartan with ACE inhibitors or direct renin inhibitors (aliskiren) because dual renin-angiotensin system blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without providing additional cardiovascular benefit 1, 2

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Critical Monitoring Parameters

Initial and Dose-Adjustment Monitoring

Check serum creatinine/eGFR and potassium within 1–2 weeks after initiating losartan or increasing doses, particularly in patients with diabetes, chronic kidney disease, or concomitant potassium-sparing agents 1

• Monitor at least annually during maintenance therapy 1
• A modest creatinine increase of 0.1–0.3 mg/dL is expected and reflects hemodynamic changes rather than tubular injury; discontinuation is not required unless urinalysis shows acute tubular necrosis 1

Blood Pressure Monitoring

• Re-evaluate blood pressure every 2–4 weeks during titration, aiming for a target of <130/80 mmHg within three months of therapy initiation 1
• Home blood pressure monitoring is endorsed; a home reading ≥135/85 mmHg corresponds to office hypertension ≥140/90 mmHg 1

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Special Population Considerations

Elderly and Frail Patients (≥85 years)

Increase losartan dose more gradually (every 2–4 weeks rather than weekly) and monitor closely for symptomatic hypotension and orthostatic changes 1

• Measure blood pressure in both sitting and standing positions (after 5 minutes seated, then at 1 minute and 3 minutes after standing) before initiating or intensifying therapy to detect orthostatic hypotension 1
• Continue lifelong antihypertensive treatment beyond age 85 when well tolerated, because discontinuation raises cardiovascular risk 1

Hepatic Impairment

For patients with hepatic impairment, start losartan at 25 mg daily due to a 5-fold increase in losartan plasma concentrations 1, 3

• Titrate more slowly in this population 1

Renal Impairment

• Losartan is recommended for chronic kidney disease with eGFR >30 mL/min per 1.73 m² 1
• Losartan can be continued as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit 1
• No dosage adjustment is necessary in patients with various degrees of renal insufficiency 3
• Losartan or its E3174 metabolite is not removed during hemodialysis 3

Diabetic Nephropathy

The target dose of losartan for diabetic nephropathy is 100 mg once daily for patients with albuminuria (UACR ≥300 mg/g) as first-line therapy 1

• The RENAAL trial demonstrated losartan reduced the risk of the primary composite renal outcome by 20% (P = 0.01) and lowered the risk of doubling serum creatinine by 28% (P = 0.002) 1

Heart Failure with Reduced Ejection Fraction

For heart failure patients, the target dose is 100–150 mg daily; the HEAAL trial showed 150 mg was superior to 50 mg, achieving a 10% relative risk reduction in death or heart failure hospitalization (P = 0.027) 1, 2

• In heart failure patients with baseline low blood pressure, start at the lowest dose and up-titrate slowly with small increments every 1–2 weeks, monitoring closely for symptomatic hypotension 1
• Therapy should be adjusted no more frequently than every 2 weeks to target doses or maximally tolerated doses 1

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Dosing Guidelines by Indication

Hypertension

Initiate losartan at 50 mg once daily and titrate to 100 mg once daily if blood pressure remains ≥140/90 mmHg after 2–4 weeks 1, 4

• The maximum recommended daily dose for hypertension is 100 mg, which can be given as a once-daily dose or split into 50 mg twice daily 1, 3
• Losartan can be administered without regard to food 3
• There are no clinically significant effects of age, sex, or race on the pharmacokinetics of losartan 3

Combination Therapy for Uncontrolled Hypertension

If blood pressure remains uncontrolled on losartan 100 mg daily after 4–8 weeks, add hydrochlorothiazide 12.5–25 mg once daily for additional reduction 1

• For grade 2 hypertension (≥160/100 mmHg), initiate two antihypertensive agents from the outset 1
• When triple therapy is required, add a dihydropyridine calcium-channel blocker (e.g., amlodipine) to the ARB-diuretic combination 1
• Fixed-dose single-pill combination therapy markedly improves medication adherence and persistence 1

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Important Drug Interactions

Cytochrome P450 System

• The major metabolic pathway for losartan is via CYP3A4, 2C9, and 2C10 isoenzymes 3
• Losartan has a favorable drug-drug interaction profile with no clinically relevant interactions with hydrochlorothiazide, warfarin, or digoxin 3

Potassium-Sparing Agents

Monitor potassium closely when losartan is used with potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium due to increased hyperkalemia risk 1

• Avoid combining losartan with ACE inhibitors and aldosterone antagonists, as this triple combination is potentially harmful 1

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Common Pitfalls and How to Avoid Them

Underdosing

Less than 25% of patients are ever titrated to target doses in clinical practice, which represents a major pitfall 1

• Higher doses of losartan (100–150 mg daily) provide better cardiovascular outcomes than lower doses 1, 5
• The dose of 50 mg losartan is probably too low for optimal clinical efficacy; losartan should preferably be prescribed at 100 mg/day or higher 5

Premature Discontinuation for Hyperkalemia

Do not prematurely discontinue losartan for mild hyperkalemia; instead, implement potassium-lowering strategies (dietary restriction, discontinue potassium supplements, add a loop diuretic) before stopping the medication 1

Timing of Administration

Preferential bedtime administration of losartan is not recommended because earlier studies suggesting benefit have not been replicated in later trials 1

• Both morning and evening dosing are acceptable; the primary goal is sustained 24-hour blood pressure control 1

Adherence Issues

Simplify regimens with once-daily dosing and, when multiple agents are needed, use single-pill combination products to enhance adherence 1

• Assess medication adherence before escalating therapy, as non-adherence is a common cause of apparent treatment failure 1

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Adverse Effect Profile

Losartan is well tolerated, with an adverse effect profile similar to placebo 6, 7

• The most frequently reported adverse events are headache, upper respiratory tract infection, dizziness, and asthenia/fatigue, but only dizziness occurs more frequently (≥1%) than placebo 7
• Cough occurs in 3.1% of patients treated with losartan versus 2.6% with placebo—significantly lower than with ACE inhibitors 6, 7
• Adverse effects related to treatment occur in only 0.2% of patients 4

Angioedema Risk

Although ARBs have a lower incidence of angioedema than ACE inhibitors, patients with prior ACE-inhibitor-induced angioedema may still develop this reaction; extreme caution is required when substituting losartan in this population 1

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Pharmacokinetic Considerations

• Following oral administration, losartan is rapidly absorbed, reaching maximum concentrations 1–2 hours post-administration 3
• Approximately 14% of a losartan dose is converted to the pharmacologically active E3174 metabolite, which is 10- to 40-fold more potent than losartan 3
• The estimated terminal half-life of E3174 ranges from 6 to 9 hours 3
• The pharmacokinetics of losartan and E3174 are linear, dose-proportional, and do not substantially change with repetitive administration 3