Valsartan

Generic Name

Valsartan

Brand Names

Diovan

Exforge (valsartan + amlodipine)

Entresto (sacubitril + valsartan)

Co-Diovan (valsartan + hydrochlorothiazide)

Valzaar

Tareg

Valent

Valtan

Drug Class

Angiotensin II Receptor Blocker ARB

Antihypertensive

RAAS Renin–Angiotensin–Aldosterone System Inhibitor

Mechanism of Action

Valsartan selectively blocks the binding of angiotensin II to the AT1 receptor subtype in vascular smooth muscle and adrenal gland

Prevents vasoconstriction aldosterone secretion sympathetic activation sodium reabsorption and cellular proliferation normally mediated by angiotensin II

Results in vasodilation decreased peripheral vascular resistance reduction in blood pressure and reduced aldosterone-mediated sodium and water retention

Does not inhibit ACE enzyme therefore does not increase bradykinin

No significant effect on heart rate

Indications

Treatment of hypertension in adults and pediatric patients aged 6 years and older

Heart failure NYHA Class II–IV to reduce hospitalization and mortality

Post-myocardial infarction to reduce cardiovascular mortality in clinically stable patients with left ventricular systolic dysfunction

Used in combination therapy with hydrochlorothiazide or calcium channel blockers when monotherapy is insufficient

Used in heart failure management as part of dual therapy in combination with neprilysin inhibitor sacubitril in Entresto

Dosage and Administration

Hypertension

Initial dose 80 mg to 160 mg once daily

Maintenance dose 80 mg to 320 mg once daily

Maximum daily dose is 320 mg

Can be used alone or with other antihypertensive agents

May be administered with or without food

Heart Failure

Starting dose 40 mg twice daily

Titrated to 80 mg to 160 mg twice daily based on tolerability

Target dose is 160 mg twice daily

Post-Myocardial Infarction

Initial dose 20 mg twice daily

Titrated to 160 mg twice daily within 7 days if tolerated

Pediatric Use

Dosing is weight-based

1.3 mgkg once daily for children aged 6 to 16 years

Maximum dose 160 mg once daily

Renal or Hepatic Impairment

Mild to moderate renal impairment no dose adjustment

Severe renal impairment creatinine clearance <10 mLmin caution advised

Mild to moderate hepatic impairment without cholestasis no adjustment needed

Avoid in patients with severe hepatic impairment or biliary cirrhosis

Pharmacokinetics

Oral bioavailability approximately 25 percent

Peak plasma concentrations reached in 2 to 4 hours

High protein binding ~95 percent mainly to albumin

Metabolized minimally with inactive metabolites

Primarily eliminated in feces via biliary excretion

Elimination half-life about 6 hours

Steady-state achieved within 3 days

Contraindications

Known hypersensitivity to valsartan or any component

Pregnancy category D due to risk of fetal toxicity

Concomitant use with aliskiren in patients with diabetes

Severe hepatic impairment

Bilateral renal artery stenosis or renal artery stenosis in a solitary kidney

History of angioedema related to previous ARB or ACE inhibitor therapy

Warnings and Precautions

Avoid use during pregnancy due to risk of fetal harm especially in second and third trimesters

Discontinue immediately if pregnancy is detected

Can cause hypotension especially in volume-depleted or salt-depleted patients

Monitor renal function and serum potassium especially in patients with renal impairment diabetes or those on diuretics or potassium supplements

Risk of hyperkalemia increases when used with potassium-sparing diuretics potassium supplements or other RAAS inhibitors

Use cautiously in patients with aortic or mitral stenosis or obstructive cardiomyopathy

Rarely associated with angioedema

Risk of acute kidney injury especially when used in combination with NSAIDs or in hypovolemic states

Adverse Effects

Common

Headache

Dizziness

Fatigue

Abdominal pain

Viral infection in pediatric patients

Hypotension

Less common

Hyperkalemia

Cough

Back pain

Elevated blood urea nitrogen or serum creatinine

Rare

Angioedema

Impaired renal function

Hepatotoxicity

Rash

Thrombocytopenia

Anaphylactic reactions

Overdose

Symptoms

Marked hypotension

Dizziness

Tachycardia or bradycardia

Management

Supportive treatment

IV fluids for hypotension

No specific antidote

Hemodialysis is not effective due to high protein binding

Drug Interactions

Potassium-sparing diuretics spironolactone eplerenone increase risk of hyperkalemia

Potassium supplements or salt substitutes containing potassium may cause dangerous elevations

NSAIDs reduce antihypertensive effect and increase risk of renal dysfunction

Diuretics may cause excessive blood pressure lowering and increased renal impairment

Lithium levels may increase leading to lithium toxicity

Dual RAAS blockade with ACE inhibitors or aliskiren increases risk of renal failure hyperkalemia and hypotension

Avoid concomitant use with aliskiren in diabetic patients

Rifampin and St John’s Wort may reduce valsartan levels due to increased metabolism

CYP450 interactions are minimal

Use in Special Populations

Pregnancy

Contraindicated

Drugs that act on the RAAS can cause fetal renal dysfunction oligohydramnios and fetal death

Lactation

Unknown if excreted in breast milk

Not recommended during breastfeeding

Pediatrics

Approved in children 6 years and older for hypertension

Geriatrics

No overall difference in safety or efficacy

Monitor renal function more frequently

Renal Impairment

Caution with severe impairment

Monitor serum creatinine potassium and blood pressure

Hepatic Impairment

Avoid in severe impairment or biliary cirrhosis

Dose adjustment not needed in mild or moderate impairment

Monitoring Parameters

Blood pressure response

Serum potassium and sodium levels

Renal function serum creatinine and BUN

Signs of hypotension or volume depletion

Monitor for symptoms of hyperkalemia muscle weakness arrhythmias

Assess adherence and response especially during titration

Comparative Pharmacology

Compared to ACE inhibitors valsartan does not cause bradykinin accumulation thus lower incidence of dry cough and angioedema

Compared to other ARBs similar efficacy in lowering blood pressure

Telmisartan has longer half-life

Losartan has active metabolites and uricosuric effects

Olmesartan more potent but linked with rare enteropathy

Compared to beta-blockers and calcium channel blockers ARBs are preferred in patients with diabetes or CKD

Better renal and cardiovascular protective effects

Compared to Entresto sacubitrilvalsartan provides additional benefit in HFrEF by blocking neprilysin-mediated breakdown of natriuretic peptides

Formulations Available

Tablets 40 mg 80 mg 160 mg 320 mg

Combination products with

Amlodipine Exforge

Hydrochlorothiazide Co-Diovan

Sacubitril Entresto

Administered orally once or twice daily depending on indication

Regulatory and Legal Status

Prescription-only medication

Approved globally by FDA EMA and other authorities

Not a controlled substance

Listed on WHO Model List of Essential Medicines

Subject to past recalls due to nitrosamine contamination in some batches