Losartan
Losartan
Generic Name
Losartan
Mechanism
Losartan competitively blocks AT₁ receptors on vascular smooth muscle, cardiac myocytes, and juxtaglomerular cells, preventing angiotensin‑II‑mediated effects:
• Vasodilation → ↓ systemic vascular resistance
• Reduced aldosterone release → ↑ potassium excretion, ↓ sodium retention
• Attenuated sympathetic drive → ↓ heart rate and renin secretion
• Decreased glomerular capillary pressure → slows progression of proteinuria
These actions culminate in lowered blood pressure and renoprotection.
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Pharmacokinetics
- Absorption → Oral bioavailability ~30‑50 % (first‑pass metabolism)
- Peak concentration 1–2 h post‑dose (sustained‑release formulation)
- Distribution → Plasma protein binding 85‑90 %
- Metabolism → Hepatic CYP2C9 and CYP3A4 convert to the active metabolite carbasalate; 35–60 % of total exposure is from metabolites
- Elimination → Renal (≈30 %) and fecal (≈60 %); total half‑life ≈2‑4 h for parent, 14‑32 h for metabolites
- Special populations: mild ↑ exposure in hepatic impairment; reduced clearance in severe renal disease; no dose adjustment needed for mild‑moderate renal impairment
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Indications
- Hypertension (both primary and secondary including hypertensive nephropathy)
- Diabetic nephropathy – slows progression to ESRD (albumin excretion >30 mg/day)
- Heart failure with reduced EF – improves survival and reduces rehospitalization when used ≤6 months of ACE inhibitor therapy
- ACE‑inhibitor withdrawal – to mitigate cough or angioedema
- Maintenance therapy for metabolic syndrome (off‑label)
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Contraindications
- Pregnancy (class X) – teratogenic, fetal renal dysgenesis
- Hypersensitivity to losartan or any component
- Severe hyperkalemia or hyperkalemia risk
- Renal artery stenosis (monotherapy)
- Advanced renal impairment (CrCl < 30 mL/min) – dose reduction or avoid
- Combination with ACE inhibitors or ARBs – increased risk of renal dysfunction, hyperkalemia, hypotension
- Additive CNS depression when combined with opioids or ethanol (rare)
Warnings
• Hypotension especially post‑first dose; monitor BP closely
• Renal function and electrolytes (potassium) monitored 1 wk after dose change, then monthly
• Pulmonary edema in acute decompensated heart failure; losartan is not indicated for rapid BP reduction
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Dosing
| Indication | Starting dose | Titration | Maintenance | Notes |
| Hypertension | 25 mg PO daily (sustained‑release) | ↑ by 25 mg weekly to max 150 mg/d | 50–150 mg/d | May split into 2 × 50 mg for better tolerance |
| Diabetic nephropathy | 50 mg PO daily | Adjust for renal function | 50 mg daily (max 150 mg/d) | Only sustained‑release |
| HF‑reduced EF | 12.5 mg PO daily | ↑ by 12.5 mg weekly to 25 mg, then 50 mg | 50 mg bid | Avoid >6 mo post‑ACE inhibitor withdrawal |
| Post‑ACE inhibitor for cough | 25 mg PO daily | Titrate as above | 25–150 mg/d | Monitor for hyperkalemia |
• Timing: Taken 1–2 h after a meal to improve absorption (if using immediate‑release).
• Adjustments: Decrease by 50 % in CrCl 30–50 mL/min, avoid >65 mL/min. Add $? consider 50 mg daily.
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Adverse Effects
Common (↕ 1–5 %)
• Dizziness, light‑headedness, syncope (especially first‑dose)
• Orthostatic hypotension
• Headache
• Fatigue
Serious (≤1 %)
• Hyperkalemia (↑ serum K⁺ >5.5 mmol/L)
• Renal impairment (rapid rise in serum creatinine)
• Angioedema (rare)
• Pregnancy‑related fetal toxicity (excluded)
• Gastro‑intestinal distress (nausea, diarrhea)
*Drug interactions:*
• Potassium‑sparing diuretics ↑ hyperkalemia risk
• NSAIDs → ↑ serum creatinine, ↓ antihypertensive effect
• Digoxin → ↑ serum digoxin levels (monitor)
• CYP3A4 inhibitors (ketoconazole) → ↑ losartan exposure
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Monitoring
- Baseline & follow‑up:
- Blood pressure (home and clinic)
- Serum creatinine & BUN (first 1–2 weeks, then monthly)
- Serum electrolytes (K⁺, Na⁺) (first 1–2 weeks, then monthly)
- Urine albumin/creatinine ratio (every 3 mo in diabetic nephropathy)
- Pregnancy test before initiation in women of childbearing age
- Renal protection: Evaluate eGFR decline >30 % → consider dose reduction or switch
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Clinical Pearls
1. ARBs vs ACE‑Inhibitors – Losartan preserves renal hemodynamics better than ACE inhibitors in patients with advanced diabetic nephropathy due to less intraglomerular pressure increase.
2. Start Low, Go Slow – First‑dose hypotension occurs in up to 10 % of patients; split the initial dose or give overnight for high‑risk profiles (elderly, low BP).
3. Heart Failure Lag – Losartan’s benefit in heart failure is seen only when introduced ≤6 months after withdrawing an ACE inhibitor; otherwise, switching alone gives no survival advantage.
4. Uric Acid Risk – Losartan can modestly raise serum uric acid; monitor in patients with gout or pre‑existing hyperuricemia.
5. Drug–Drug Synergy – Co‑administration with diuretics (e.g., indapamide) amplifies antihypertensive effect but calls for close potassium monitoring; titrate diuretic downward if K⁺ rises.
6. Carbasalate Fact – The metabolite is pharmacologically active and accounts for ~40 % of the antihypertensive effect; patients on CYP2C9 inhibitors can experience higher exposure.
7. Renal Protection Beyond BP – In diabetic nephropathy, 50 mg daily can achieve 50 % reduction in annual albumin excretion even when BP is already controlled—an important consideration when debating dual ARB/ACE therapy.
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• *References:*
• 2022 ESC Guidelines for the management of arterial hypertension
• 2023 KDIGO Clinical Practice Guideline for diabetic kidney disease
• 2021 American College of Cardiology/HFSA Guideline for the Management of Heart Failure
*(All data are based on peer‑reviewed literature up to 2024 and may be updated with emerging evidence.)*