Medically Reviewed by Dr. Rafael Morales, PharmD, BCACP, CDE
Clinical Pharmacist — Diabetes & Metabolic Disease
Last reviewed: March 29, 2026
Losartan potassium (Cozaar) is an angiotensin II receptor blocker (ARB) used to treat high blood pressure, protect the kidneys in type 2 diabetes, and reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy. Unlike ACE inhibitors, losartan does not cause a dry cough and carries a significantly lower risk of angioedema.
Typical Cost
$4–$15/month
Status
Rx
Generic
Brand Only
Irbesartan is the lowest-cost ARBs at $4-$25/month/month
Uses & Indications
FDA-Approved Indications:
Hypertension (adults and pediatric patients ≥6 years):
- Treatment of hypertension to reduce blood pressure and lower the risk of cardiovascular events
- Can be used as monotherapy or in combination with other antihypertensives
- Pediatric use: approved for children ≥6 years with eGFR >30 mL/min/1.73m²
Diabetic Nephropathy (type 2 diabetes with proteinuria and hypertension):
- Reduces the rate of progression of nephropathy as measured by doubling of serum creatinine or ESRD
- RENAAL trial: 25% reduction in doubling of serum creatinine, 28% reduction in ESRD (n=1,513)
- Reduces proteinuria (urinary albumin-to-creatinine ratio)
Stroke Risk Reduction (hypertension with left ventricular hypertrophy):
- Reduces the risk of stroke in patients with hypertension and electrocardiographic evidence of LVH
- LIFE trial: 25% greater stroke reduction vs. atenolol; particularly pronounced in Black patients
- Note: This benefit does not apply to Black patients for the overall cardiovascular endpoint
Guideline-Recommended Uses (off-label but strongly supported):
- Heart failure with reduced ejection fraction (HFrEF): Alternative to ACE inhibitors in ACE-intolerant patients (AHA/ACC guidelines); HEAAL trial supports 150 mg dose
- Hypertension with gout: Preferred ARB due to unique uricosuric effect (lowers uric acid 15–20%)
- CKD with proteinuria (non-diabetic): Reduces proteinuria and slows GFR decline
- Marfan syndrome: Reduces aortic root dilation progression (small RCT evidence)
Losartan vs. Lisinopril — Which Is Right for You?
Both are first-line blood pressure medications that block the RAAS system and protect the kidneys in diabetes, but they work at different points in the pathway — and only one causes a dry cough.
Losartan (ARB)
Blocks AT1 receptor — angiotensin II is made but can't act
No cough; also lowers uric acid (uricosuric effect)
Lisinopril (ACE Inhibitor)
Blocks ACE enzyme — prevents angiotensin II production
Dry cough in 10–20% of patients (bradykinin accumulation)
Key Advantage
Choose losartan if you can't tolerate ACE inhibitor cough or have gout
Both ~$4–$15/month generic; similar BP & kidney protection
Dosage & Administration
Dosing by Indication:
| Indication | Starting Dose | Usual Maintenance | Maximum |
|---|---|---|---|
| Hypertension (adults) | 50 mg once daily | 50–100 mg once daily | 100 mg/day |
| Hypertension (volume-depleted) | 25 mg once daily | 50–100 mg once daily | 100 mg/day |
| Diabetic nephropathy | 50 mg once daily | 100 mg once daily | 100 mg/day |
| Stroke prevention (LVH) | 50 mg once daily | 50–100 mg once daily | 100 mg/day |
| Heart failure (off-label) | 12.5–25 mg once daily | 50–150 mg once daily | 150 mg/day |
| Hypertension (pediatric ≥6y) | 0.7 mg/kg once daily (max 50 mg) | 0.7–1.4 mg/kg/day | 100 mg/day |
Renal Dose Adjustment:
| eGFR (mL/min/1.73m²) | Recommendation |
|---|---|
| ≥30 | No dose adjustment required |
| 15–29 | Use with caution; start at 25 mg; monitor potassium and creatinine |
| <15 (dialysis) | Not recommended; limited data; if used, start at 25 mg |
| Pediatric <30 | Contraindicated |
Hepatic Dose Adjustment:
- Mild-to-moderate hepatic impairment: Start at 25 mg once daily (reduced first-pass metabolism increases exposure ~2-fold)
- Severe hepatic impairment: Not recommended (no data)
Administration:
- Take with or without food
- Can be administered as an oral suspension for patients who cannot swallow tablets
- If a dose is missed, take as soon as remembered; skip if almost time for next dose; do not double up
How It Works
Mechanism of Action — AT1 Receptor Blockade
Losartan is a selective, competitive antagonist of the angiotensin II type 1 (AT1) receptor. Unlike ACE inhibitors, losartan does not prevent the formation of angiotensin II — instead, it blocks angiotensin II from binding to its primary receptor.
Step-by-step mechanism:
-
Renin-angiotensin-aldosterone system (RAAS) activation: Renin converts angiotensinogen to angiotensin I; ACE converts angiotensin I to angiotensin II via multiple pathways (including chymase, independent of ACE).
-
AT1 receptor blockade: Losartan and its active metabolite EXP3174 bind selectively and competitively to AT1 receptors in vascular smooth muscle, adrenal glands, kidneys, and heart — blocking vasoconstriction, aldosterone secretion, and sodium retention.
-
AT2 receptor sparing: Because losartan does not reduce angiotensin II levels (unlike ACE inhibitors), angiotensin II remains available to stimulate unblocked AT2 receptors, which mediate vasodilation, anti-proliferative, and cardioprotective effects.
-
No bradykinin accumulation: Unlike ACE inhibitors, losartan does not inhibit ACE and therefore does not cause bradykinin accumulation — explaining the absence of dry cough and the much lower risk of angioedema.
Active metabolite EXP3174:
- Losartan is a prodrug; ~14% is converted to the active metabolite EXP3174 by CYP2C9
- EXP3174 is 10–40× more potent than losartan at the AT1 receptor
- EXP3174 has a longer half-life (6–9 hours vs. 2 hours for losartan), providing sustained 24-hour blood pressure control
Uricosuric effect (unique to losartan among ARBs):
- Losartan inhibits the URAT1 urate transporter in the proximal renal tubule, reducing uric acid reabsorption
- Results in a 15–20% reduction in serum uric acid levels
- This effect is independent of blood pressure lowering and is not shared by other ARBs (valsartan, olmesartan, irbesartan)
- Clinically meaningful in patients with hypertension and gout or hyperuricemia
Side Effects
Serious Side Effects
Common Side Effects
Rare Side Effects
Warnings & Precautions
BLACK BOX WARNING — Fetal Toxicity: Losartan can cause fetal harm when administered to pregnant women. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. When pregnancy is detected, discontinue losartan as soon as possible.
Hyperkalemia:
- Monitor serum potassium in patients with renal impairment, diabetes, or concurrent use of potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes
- Risk is additive with ACE inhibitors, direct renin inhibitors (aliskiren), NSAIDs, and trimethoprim
- Avoid dual RAAS blockade (ARB + ACE inhibitor + aliskiren) — ONTARGET trial showed no additional benefit and increased risk of hypotension, hyperkalemia, and renal impairment
Hypotension:
- Symptomatic hypotension may occur in volume-depleted patients (diuretics, low-sodium diet, dialysis)
- Correct volume depletion before initiating therapy or start at 25 mg
- Patients with heart failure may be especially sensitive to first-dose hypotension
Impaired Renal Function:
- Monitor renal function and serum electrolytes in patients with bilateral renal artery stenosis or stenosis of a solitary kidney — may cause acute kidney injury
- Increases in serum creatinine are common and often reversible; persistent elevation >30% above baseline warrants dose reduction or discontinuation
- Avoid in patients with eGFR <15 mL/min/1.73m² (pediatric) or use with caution in adults with eGFR 15–29
Hepatic Impairment:
- Losartan exposure is doubled in hepatic impairment due to reduced first-pass metabolism
- Start at 25 mg once daily in patients with mild-to-moderate hepatic impairment
Contraindications
Absolute Contraindications:
- Hypersensitivity to losartan or any component of the formulation
- Pregnancy (2nd and 3rd trimester) — fetal toxicity black box warning
- Concomitant use with aliskiren in patients with diabetes (increased risk of renal impairment, hypotension, and hyperkalemia)
Relative Contraindications / Use with Caution:
- Bilateral renal artery stenosis or stenosis of a solitary kidney
- Severe hepatic impairment (no data; avoid if possible)
- Pediatric patients with eGFR <30 mL/min/1.73m² (contraindicated)
- Volume depletion (correct before initiating or start at 25 mg)
- Concurrent ACE inhibitor use (dual RAAS blockade — avoid; ONTARGET trial showed harm)
- Hyperkalemia (K+ >5.5 mEq/L) — address before initiating
Drug Interactions
Clinically Important Drug Interactions:
| Drug/Class | Interaction | Management |
|---|---|---|
| Potassium-sparing diuretics (spironolactone, eplerenone, amiloride) | Additive hyperkalemia risk | Monitor K+ closely; avoid unless necessary |
| Potassium supplements / salt substitutes | Additive hyperkalemia | Avoid or monitor K+ |
| ACE inhibitors | Dual RAAS blockade — increased hyperkalemia, hypotension, renal failure | Avoid combination (ONTARGET) |
| Aliskiren (in diabetes) | Dual RAAS blockade — contraindicated | Contraindicated in diabetic patients |
| NSAIDs (ibuprofen, naproxen) | Reduced antihypertensive effect; additive renal risk | Avoid or use lowest dose; monitor BP and renal function |
| Lithium | Losartan reduces lithium clearance → lithium toxicity | Monitor lithium levels; consider dose reduction |
| CYP2C9 inhibitors (fluconazole, amiodarone) | Reduced conversion to active metabolite EXP3174 → attenuated effect | Monitor BP; may need dose increase |
| CYP2C9 inducers (rifampin) | Increased losartan metabolism → reduced effect | Monitor BP; may need dose increase |
| Diuretics (thiazides, loop) | Additive hypotension (especially first dose) | Start losartan at 25 mg; monitor BP |
| Digoxin | Losartan may increase digoxin levels (~15%) | Monitor digoxin levels |
Note on uricosuric interaction: Losartan's uric acid-lowering effect may reduce the efficacy of uricosuric agents (probenecid) — monitor uric acid levels if combining.
Use in Specific Populations
Pregnancy:
- First trimester: Category C — use only if benefit outweighs risk; switch to a safer antihypertensive (methyldopa, nifedipine, labetalol) as soon as pregnancy is confirmed
- Second and third trimesters: Category D / BLACK BOX WARNING — can cause fetal renal dysfunction, oligohydramnios, skull hypoplasia, limb contractures, and death. Discontinue immediately when pregnancy is detected.
- Perform serial ultrasound examinations if losartan is used during pregnancy
Lactation:
- It is not known whether losartan is excreted in human breast milk
- Due to potential for serious adverse effects in nursing infants, breastfeeding is not recommended during losartan therapy
Pediatric Patients (≥6 years):
- Approved for hypertension in children ≥6 years with eGFR >30 mL/min/1.73m²
- Starting dose: 0.7 mg/kg once daily (maximum 50 mg); titrate to 1.4 mg/kg/day (maximum 100 mg/day)
- Oral suspension available for children who cannot swallow tablets
- Not approved for children <6 years or those with eGFR <30 mL/min/1.73m²
Geriatric Patients (≥65 years):
- No dose adjustment required based on age alone
- Greater sensitivity to hypotension; start at lower end of dosing range
- Monitor renal function and electrolytes more frequently
Renal Impairment:
- eGFR ≥30: No dose adjustment required
- eGFR 15–29: Start at 25 mg; monitor closely
- eGFR <15 / Dialysis: Not recommended; not removed by hemodialysis
Hepatic Impairment:
- Mild-to-moderate: Start at 25 mg once daily (AUC doubled)
- Severe: Avoid (no data)
Race:
- In the LIFE trial, the benefit of losartan over atenolol for the composite cardiovascular endpoint was not observed in Black patients
- Blood pressure lowering is effective in Black patients, but the stroke benefit may be attenuated
- Consider thiazide diuretics or calcium channel blockers as first-line in Black patients per JNC 8 guidelines
Overdosage
Overdosage:
Symptoms of overdose include hypotension (most common), tachycardia, and bradycardia. Hyperkalemia may occur.
Management:
- Supportive care: IV fluids for hypotension; vasopressors if refractory
- Activated charcoal may be considered if ingestion is recent and airway is protected
- Losartan and EXP3174 are NOT removed by hemodialysis
- Monitor serum electrolytes, renal function, and blood pressure
Contact Poison Control (1-800-222-1222) or emergency services for significant overdose.
Frequently Asked Questions
Why doesn't losartan cause a dry cough like lisinopril?
ACE inhibitors like lisinopril block the ACE enzyme, which also breaks down bradykinin. When bradykinin accumulates in the lungs, it triggers a dry cough in 10–20% of patients. Losartan works differently — it blocks the AT1 receptor where angiotensin II acts, but does not affect ACE or bradykinin levels. This is why losartan is the standard alternative for patients who cannot tolerate ACE inhibitor-induced cough.
What is the uricosuric effect of losartan?
Losartan is the only ARB that lowers serum uric acid levels. It inhibits the URAT1 urate transporter in the kidney, increasing uric acid excretion in the urine. This typically reduces serum uric acid by 15–20%. This effect makes losartan a preferred choice for patients who have both hypertension and gout or hyperuricemia. No other ARB (valsartan, olmesartan, irbesartan, telmisartan) shares this property.
What did the LIFE trial show about losartan?
The LIFE trial (2002) compared losartan to atenolol in 9,193 patients with hypertension and left ventricular hypertrophy over 4.8 years. Losartan reduced the composite of cardiovascular death, MI, and stroke by 13% compared to atenolol, despite similar blood pressure reduction. The stroke reduction was 25% greater with losartan. This trial established losartan as the preferred agent for hypertension with LVH.
Can losartan be used in patients with diabetes and kidney disease?
Yes — losartan is specifically FDA-approved for diabetic nephropathy. The RENAAL trial showed that losartan reduced the risk of doubling serum creatinine by 25% and end-stage renal disease by 28% in patients with type 2 diabetes and nephropathy. It also significantly reduced proteinuria. Losartan is recommended by JNC 8, ADA, and KDIGO guidelines as first-line therapy for hypertension in patients with type 2 diabetes and CKD.
What is the difference between losartan and valsartan?
Both are ARBs with similar blood pressure-lowering efficacy, but losartan has two unique properties: (1) a uricosuric effect (lowers uric acid 15–20%) not shared by valsartan, and (2) it is a prodrug converted to the active metabolite EXP3174 by CYP2C9. Valsartan is active itself and not metabolized by CYP2C9, making it less affected by CYP2C9 drug interactions. Valsartan also has stronger evidence in heart failure (Val-HeFT trial) and post-MI (VALIANT trial).
Is losartan safe during pregnancy?
No — losartan carries a BLACK BOX WARNING for fetal toxicity. During the second and third trimesters, losartan can cause fetal renal dysfunction, oligohydramnios (low amniotic fluid), fetal lung hypoplasia, skeletal deformations, and death. Discontinue losartan as soon as pregnancy is detected and switch to a pregnancy-safe antihypertensive such as methyldopa, labetalol, or nifedipine.
Can I take losartan with an ACE inhibitor like lisinopril?
No — combining an ARB with an ACE inhibitor (dual RAAS blockade) is not recommended. The ONTARGET trial showed that the combination of losartan + ramipril did not reduce cardiovascular outcomes compared to either drug alone, but significantly increased the risk of hypotension, hyperkalemia, and acute kidney injury. Guidelines recommend using either an ACE inhibitor or an ARB, but not both together.
How long does it take for losartan to lower blood pressure?
Losartan begins lowering blood pressure within 1–2 hours of the first dose, with peak effect at 6 hours. However, the full antihypertensive effect typically takes 3–6 weeks of consistent daily dosing. The active metabolite EXP3174 provides sustained 24-hour blood pressure control with once-daily dosing. If blood pressure is not adequately controlled after 3–4 weeks at 50 mg, the dose can be increased to 100 mg once daily.
Medical Disclaimer
The information on RxGuide is intended for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician, pharmacist, or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.