Losartan

Generic Name: Losartan
Drug Class: Angiotensin II Receptor Blocker (ARB)
ATC Code: C09CA01
Regulatory Status: Prescription-only medication
Common Brand Names: Cozaar, Losazide (with hydrochlorothiazide), Hyzaar, Fortzaar (region-specific)

---

Mechanism of Action

Losartan selectively and competitively inhibits the binding of angiotensin II to the angiotensin II type 1 (AT1) receptor. Angiotensin II is a potent vasoconstrictor and key effector of the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure, fluid balance, and vascular tone. By blocking AT1 receptors:

• Vasodilation is promoted, reducing systemic vascular resistance and arterial pressure

• Aldosterone secretion is decreased, leading to reduced sodium and water retention

• Sympathetic stimulation is suppressed

• Cardiac and vascular remodeling is inhibited

• Renal protection is achieved, particularly in diabetic nephropathy

Losartan does not inhibit ACE (angiotensin-converting enzyme) and therefore does not affect bradykinin metabolism, making it less likely to cause cough or angioedema compared to ACE inhibitors.

---

Therapeutic Indications

1. Hypertension (essential):

   • Management of high blood pressure in adults and children ≥6 years

   • Monotherapy or in combination with other antihypertensives

2. Heart Failure (off-label in some regions):

   • Used when ACE inhibitors are not tolerated, or in combination with β-blockers and diuretics

3. Diabetic Nephropathy in Type 2 Diabetes Mellitus:

   • Reduces proteinuria and slows progression of kidney disease in patients with hypertension and proteinuria

4. Stroke Risk Reduction:

   • In patients with left ventricular hypertrophy (LVH) and hypertension, losartan lowers the risk of stroke

5. Chronic Kidney Disease (CKD):

   • Protective effect in non-diabetic renal disease with proteinuria

6. Post-myocardial infarction:

   • In ACE-intolerant patients with LV dysfunction

---

Formulations and Dosage

Available Dosage Forms:

• Oral tablets: 25 mg, 50 mg, 100 mg

• Fixed-dose combinations:

  • Losartan + hydrochlorothiazide (e.g., 50/12.5 mg, 100/25 mg)

Usual Adult Dosage:

• Hypertension:

  • Starting dose: 50 mg once daily

  • May be increased to 100 mg once daily (or divided doses) based on BP response

• Type 2 Diabetes with Nephropathy:

  • Target dose: 100 mg once daily

• Elderly or patients with hepatic impairment:

  • Consider 25 mg once daily as starting dose

• Heart failure (off-label):

  • Initial: 25 mg once daily

  • Titrate to 50–100 mg/day if tolerated

Pediatric Dosage (≥6 years):

• 0.7 mg/kg once daily (max 50 mg/day)

---

Pharmacokinetics

• Absorption: Rapid, oral bioavailability ~33%

• Onset of action: 1 hour

• Peak plasma levels: 1–2 hours (losartan), 3–4 hours (active metabolite EXP3174)

• Metabolism: Hepatic (CYP2C9, CYP3A4)

• Active metabolite: EXP3174, more potent and longer-acting than parent drug

• Half-life: Losartan ~2 hours; EXP3174 ~6–9 hours

• Excretion: 35% renal, 60% biliary/fecal

---

Contraindications

• Hypersensitivity to losartan or any component of the formulation

• Pregnancy (especially 2nd and 3rd trimesters)

• Severe hepatic impairment

• Concomitant use with aliskiren in diabetic patients or those with renal impairment

• History of angioedema (rare but caution advised)

---

Warnings and Precautions

• Hypotension: Particularly in volume-depleted individuals (e.g., diuretics, dehydration)

• Hyperkalemia: Risk increased with potassium supplements, salt substitutes, potassium-sparing diuretics

• Renal Impairment: Monitor renal function regularly, especially in patients with renal artery stenosis or heart failure

• Hepatic Impairment: Reduced metabolism may increase drug exposure

• Angioedema: Rare, but discontinue if it occurs

• Dual blockade of RAAS: Avoid combination with ACE inhibitors or aliskiren unless necessary

• Pregnancy/Breastfeeding:

  • Category D: Contraindicated in pregnancy due to fetal toxicity (renal dysfunction, skull hypoplasia, death)

  • Lactation: Not recommended due to unknown excretion in breast milk

---

Adverse Reactions

Common (>1%):

• Dizziness, fatigue

• Hypotension

• Hyperkalemia

• Nasal congestion

• Back pain

• Upper respiratory infection

• Cough (less common than ACE inhibitors)

Uncommon/Rare:

• Angioedema

• Elevated liver enzymes

• Anemia

• Myalgia

• Rash or pruritus

• Sleep disturbances

• Photosensitivity

Laboratory Abnormalities:

• Increased serum potassium

• Elevated creatinine or BUN (especially in renal disease)

• Slight rise in ALT/AST

---

Drug Interactions

1. Potassium-Sparing Agents and Supplements:

• Risk of hyperkalemia; avoid or monitor potassium closely

2. NSAIDs (e.g., ibuprofen, naproxen):

• May reduce antihypertensive effect and worsen renal function

• Avoid long-term NSAID use in high-risk patients

3. Diuretics (especially loop and thiazide):

• May enhance antihypertensive effect; monitor for hypotension

4. Lithium:

• Reduced lithium clearance → toxicity risk; monitor serum lithium levels

5. Rifampin:

• May reduce losartan plasma levels (induces CYP enzymes)

6. Fluconazole:

• Inhibits CYP2C9, may increase losartan concentrations

7. CYP3A4 inhibitors:

• May influence losartan metabolism

8. Aliskiren:

• Increased risk of hypotension, hyperkalemia, and renal impairment when combined in diabetic or renally impaired patients

---

Monitoring Parameters

• Blood pressure (baseline and periodically)

• Renal function: serum creatinine, eGFR

• Serum potassium

• Liver enzymes (if long-term or hepatic concern)

• Signs of angioedema or allergic reaction

• Proteinuria in patients with diabetic nephropathy

---

Use in Special Populations

Elderly:

• No dosage adjustment needed, but monitor renal function

Renal Impairment:

• No initial dosage adjustment needed for mild to moderate impairment

• Use with caution in severe impairment

Hepatic Impairment:

• Lower starting dose (25 mg); monitor for toxicity

Pregnancy:

• Contraindicated; discontinue immediately upon detection of pregnancy

Breastfeeding:

• Use not recommended due to lack of safety data

---

Comparative Notes

Feature	Losartan	Enalapril	Valsartan	Candesartan
Cough risk	Low	High	Low	Low
Half-life	~2 hrs (parent), ~9 hrs (active metabolite)	~11 hrs	~6 hrs	~9 hrs
Dosing	25–100 mg/day	5–40 mg/day	80–320 mg/day	8–32 mg/day
Hepatic metabolism	Yes (CYP2C9/3A4)	Minimal	Minimal	Minimal

Patient Counseling Points

• Take at the same time each day, with or without food

• Do not use potassium supplements or salt substitutes unless directed

• Monitor for signs of hypotension, especially when starting

• Inform your doctor if pregnant or planning pregnancy

• Get regular blood tests to monitor kidney function and potassium

• May cause dizziness; avoid driving until effects are known

• Store at room temperature, away from moisture and heat

---

Storage and Stability

• Store at 20–25°C (68–77°F)

• Protect from light and moisture

• Keep out of reach of children

---

Clinical Trials and Evidence

• LIFE Study (Losartan Intervention For Endpoint reduction in hypertension):
  Showed losartan was superior to atenolol in reducing stroke risk in hypertensive patients with LVH

• RENAAL Trial:
  Demonstrated renoprotective effect of losartan in diabetic nephropathy

• HEAAL Trial (in heart failure):
  Supported the use of higher-dose losartan (150 mg) over 50 mg for better outcomes in heart failure patients intolerant to ACEIs