Valsartan (Monograph)

Brand names: Diovan, Exforge (combination), Exforge HCT (combination)
Drug class: Angiotensin II Receptor Antagonists
VA class: CV805
Chemical name: N-(1-Oxopentyl)-N-[[2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-yl]methyl)]-l-valine
Molecular formula: C₂₄H₂₉N₅O₃
CAS number: 137862-53-4

Medically reviewed by Drugs.com on Oct 26, 2023. Written by ASHP.

Warning

May cause fetal and neonatal morbidity and mortality if used during pregnancy.¹ ¹¹⁴ ¹¹⁵ ¹¹⁶ ^a (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
If pregnancy is detected, discontinue as soon as possible.¹ ¹¹⁵ ¹¹⁶ ^a

Introduction

Valsartan is an angiotensin II type 1 (AT₁) receptor antagonist (i.e., angiotensin II receptor blocker, ARB).¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹¹⁶ ^a

Uses for Valsartan

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents);¹ ² ³ ⁴ ⁵ ⁶ ⁸ ⁹ ¹¹⁶ ¹³⁴ ¹²⁰⁰ ^a may be used in fixed combination with amlodipine and/or hydrochlorothiazide when such combined therapy is indicated.¹¹⁶ ¹³⁴ ^a

Angiotensin II receptor antagonists are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include ACE inhibitors, calcium-channel blockers, and thiazide diuretics.⁵⁰¹ ⁵⁰² ⁵⁰³ ⁵⁰⁴ ¹²⁰⁰ While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.⁵⁰¹ ⁵⁰² ⁵⁰³ ⁵⁰⁴ ¹²⁰⁰ ¹²¹³

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).⁵⁰¹ ⁵⁰² ⁵⁰³ ⁵⁰⁴ ⁵¹⁵ ¹²⁰⁰ ¹²⁰¹

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.¹²⁰⁰ (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200
Category	SBP (mm Hg)		DBP (mm Hg)
Normal	<120	and	<80
Elevated	120–129	and	<80
Hypertension, Stage 1	130–139	or	80–89
Hypertension, Stage 2	≥140	or	≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.¹²⁰⁰ However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.⁵⁰¹ ⁵⁰³ ⁵⁰⁴ ⁵⁰⁵ ⁵⁰⁶ ⁵⁰⁷ ⁵⁰⁸ ⁵¹⁵ ⁵²³ ⁵²⁶ ⁵³⁰ ¹²⁰⁰ ¹²⁰¹ ¹²⁰⁷ ¹²⁰⁹ ¹²²² ¹²²³ ¹²²⁹

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.¹²⁰⁰ In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.¹²⁰⁰ These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.¹²⁰⁰ ¹²⁰² ¹²¹⁰

Previous hypertension guidelines generally have based target BP goals on age and comorbidities.⁵⁰¹ ⁵⁰⁴ ⁵³⁶ Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients⁵⁰¹ ⁵⁰⁴ ⁵³⁶ compared with those recommended by the 2017 ACC/AHA hypertension guideline.¹²⁰⁰

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the current ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.¹²²² ¹²²³ ¹²²⁴ ¹²²⁹

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient’s BP treatment goal.¹²⁰⁰ ¹²²⁰ ¹²²⁹

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.¹²⁰⁰ ¹²⁰⁷ ASCVD risk assessment recommended by ACC/AHA for all adults with hypertension.¹²⁰⁰

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).¹²⁰⁰

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.¹²⁰⁰

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.¹²⁰⁰

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.¹²⁰⁰ Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.¹²⁰⁰

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to angiotensin II receptor antagonists.⁵⁰¹ ⁵⁰⁴ ¹²⁰⁰ However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.¹²⁰⁰

Angiotensin II receptor antagonists or ACE inhibitors may be particularly useful in hypertensive patients with diabetes mellitus or CKD; angiotensin II receptor antagonists also may be preferred, as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or post-MI.⁵⁰¹ ⁵⁰² ⁵⁰⁴ ⁵²³ ⁵²⁴ ⁵²⁷ ⁵³⁴ ⁵³⁵ ⁵³⁶ ⁵⁴³ ¹²⁰⁰ ¹²¹⁴ ¹²¹⁵

Heart Failure

Used in the management of heart failure.¹ ³⁸ ⁵² ¹³² ¹³³

Because of their established benefits, ACE inhibitors have been the preferred drugs for inhibition of the renin-angiotensin-aldosterone (RAA) system in patients with heart failure and reduced left ventricular ejection fraction (LVEF);⁵²⁴ however, some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.⁷⁰⁰ ⁷⁰¹ ⁷⁰² ⁷⁰³

Angiotensin II receptor antagonists may be used as an alternative for those patients in whom use of an ACE inhibitor or ARNI is inappropriate.⁵²⁴ ⁵²⁸ ⁷⁰⁰

No additional therapeutic benefit when angiotensin II receptor antagonist used in combination with an ACE inhibitor.¹

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced LVEF (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.⁷⁰⁰

Heart Failure or Left Ventricular Dysfunction After Acute MI

Valsartan is used to reduce the risk of cardiovascular mortality in clinically stable patients who have demonstrated clinical signs of heart failure or left ventricular dysfunction following MI.¹ ¹¹⁰ ¹¹¹

While ACE inhibitors generally are the preferred agents for this use because of their established benefits, angiotensin II receptor antagonists may be substituted in patients who are intolerant to ACE inhibitor therapy.⁵²⁷ ¹¹⁰⁰

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria^{† [off-label]} who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.⁵⁹ ⁶⁰ ⁶¹ ⁶² ⁶³ ⁵³⁵ ⁵³⁶ ¹²³²

Valsartan Dosage and Administration

General

BP Monitoring and Treatment Goals

Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.¹²⁰⁰
If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.¹²¹⁶
If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., calcium-channel blocker, thiazide diuretic).¹²⁰⁰ ¹²¹⁶ Many patients will require at least 2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved with 2 antihypertensive agents, add a third drug.¹²⁰⁰ ¹²¹⁶

Administration

Oral Administration

Administer valsartan orally once or twice daily without regard to meals.¹ ⁹ ^a

Administer valsartan as extemporaneously prepared oral suspension in pediatric patients unable to swallow tablets or in those for whom the calculated daily dosage does not correspond to the available tablet strengths.¹

Reconstitution

Preparation of extemporaneous suspension containing valsartan 4 mg/mL: Add 80 mL of suspending vehicle (e.g., Ora-Plus) to an amber glass bottle containing 8 valsartan 80-mg tablets; shake the contents for ≥2 minutes.¹ Allow concentrated suspension to stand for ≥1 hour, then shake for ≥1 additional minute.¹ Dilute the concentrated suspension with 80 mL of sweetening vehicle (e.g., Ora-Sweet SF); shake the contents for ≥10 seconds.¹ Shake suspension for ≥10 seconds before dispensing each dose.¹

Dosage

Pediatric Patients

Hypertension

Oral

Children 6–16 years of age: Initially, valsartan 1.3 mg/kg (up to 40 mg) once daily.¹ ¹¹⁵⁰ Adjust dosage according to patient response;¹ some experts state dosage may be increased every 2–4 weeks until BP controlled, maximum dosage reached, or adverse effects occur.¹¹⁵⁰ Dosages >2.7 mg/kg (up to 160 mg) once daily have not been studied in children.¹ ¹¹⁵⁰

May need to increase dosage when converting from extemporaneously prepared suspension to oral tablet, since exposure to valsartan with the suspension is 1.6 times greater than with the tablet.¹

Adults

Hypertension

Valsartan Therapy

Oral

Manufacturers recommend initial dosage of 80 or 160 mg once daily as monotherapy in adults without intravascular volume depletion.¹ ^a

Usual dosage is 80–320 mg once daily.¹ ¹²⁰⁰ However, at dosages >80 mg daily, addition of diuretic produces greater BP reduction than increases in valsartan dosage.¹

Valsartan/Amlodipine Fixed-combination Therapy

Oral

Fixed-combination preparation may be used for initial treatment of hypertension in patients likely to require combination therapy with multiple antihypertensive agents to control BP.¹¹⁶ Consider potential benefits and risks of initiating therapy with the fixed combination, including whether the patient is likely to tolerate the lowest available dosage of the combined drugs.¹¹⁶

If the patient’s baseline BP is 160/100 mm Hg, the estimated probability of achieving SBP control (SBP <140 mm Hg) is 47, 67, or 80% and of achieving DBP control (DBP <90 mm Hg) is 62, 80, or 85% with valsartan (320 mg daily) alone, amlodipine (10 mg daily) alone, or valsartan combined with amlodipine (same dosages), respectively.¹¹⁶

In studies using valsartan/amlodipine fixed combination in dosages of valsartan 160–320 mg daily and amlodipine 5–10 mg daily, BP response increased with increasing dosages of the drugs.¹¹⁶

If BP is not adequately controlled by monotherapy with valsartan (or another angiotensin II receptor antagonist) or amlodipine (or another dihydropyridine-derivative calcium-channel blocker), can switch to valsartan/amlodipine fixed combination.¹¹⁶

If dose-limiting adverse effects have developed during monotherapy with valsartan or amlodipine, can switch to a fixed combination containing a lower dose of that drug to achieve similar BP control; adjust dosage according to patient’s response after 3–4 weeks of therapy.¹¹⁶

If BP is controlled with valsartan and amlodipine (administered separately), can switch to the fixed-combination preparation containing the corresponding individual doses for convenience.¹¹⁶

When used for initial therapy of hypertension in patients likely to require combination therapy with multiple antihypertensive agents, recommended initial dosage is valsartan 160 mg and amlodipine 5 mg once daily in those who are not volume depleted.¹¹⁶

Increase to maximum dosage of valsartan 320 mg and amlodipine 10 mg once daily, if needed, to control BP.¹¹⁶ May adjust dosage at intervals of 1–2 weeks, since most of the antihypertensive effect of a given dosage is achieved within 2 weeks after a change in dosage.¹¹⁶

Valsartan/Hydrochlorothiazide Fixed-combination Therapy

Oral

Fixed-combination preparation may be used for initial treatment of hypertension in patients likely to require combination therapy with multiple antihypertensive agents to control BP.^a Consider potential benefits and risks of initiating therapy with the fixed combination.^a Not recommended as initial therapy in patients who are volume depleted.^a

If the patient’s baseline BP is 160/100 mm Hg, the estimated probability of achieving SBP control (SBP <140 mm Hg) is 41, 50, or 84% and of achieving DBP control (DBP <90 mm Hg) is 60, 57, or 80% with valsartan (320 mg daily) alone, hydrochlorothiazide (25 mg daily) alone, or valsartan combined with hydrochlorothiazide (same dosages), respectively.^a

If BP is not adequately controlled by monotherapy with valsartan (or another angiotensin II receptor antagonist) or hydrochlorothiazide, can switch to fixed-combination tablets containing valsartan 160 mg and hydrochlorothiazide 12.5 mg once daily.^a

If dose-limiting adverse effects have developed during monotherapy with valsartan or hydrochlorothiazide, can switch to a fixed combination containing a lower dose of that drug to achieve similar BP control; adjust dosage according to patient’s response after 3–4 weeks of therapy.^a

If BP is controlled with valsartan and hydrochlorothiazide (administered separately), can switch to the fixed-combination preparation containing the corresponding individual doses for convenience.^a

When used for initial therapy of hypertension in patients likely to require combination therapy with multiple antihypertensive agents, recommended initial dosage is valsartan 160 mg and hydrochlorothiazide 12.5 mg daily in those who are not volume depleted.^a Adjust dosage according to patient’s response after 1–2 weeks of therapy.^a

Increase to maximum dosage of valsartan 320 mg and hydrochlorothiazide 25 mg daily, if needed, to control BP.^a Maximum antihypertensive effect of a given dosage is achieved within 2–4 weeks after a change in dosage.^a

Valsartan/Amlodipine/Hydrochlorothiazide Fixed-combination Therapy

Oral

Manufacturers state fixed-combination preparation should not be used for initial treatment of hypertension.¹³⁴

Can switch to fixed-combination valsartan/amlodipine/hydrochlorothiazide tablets if BP is not adequately controlled by combined therapy with any 2 of the following drug classes: angiotensin II receptor antagonists, calcium-channel blockers, or diuretics.¹³⁴

In patients who experience dose-limiting adverse effects of valsartan, amlodipine, or hydrochlorothiazide while receiving any dual combination of these drugs, may switch to the triple fixed-combination preparation containing a lower dose of that component.¹³⁴

Can use the fixed combination as a substitute for the individually titrated drugs.¹³⁴

May increase dosage of the fixed combination after 2 weeks if additional BP control is needed (up to maximum of valsartan 320 mg, amlodipine 10 mg, and hydrochlorothiazide 25 mg once daily).¹³⁴

Heart Failure

Oral

Initially, valsartan 40 mg twice daily recommended by manufacturer;¹ some experts recommend initial dosage of 20–40 mg twice daily.⁵²⁴ Increase dosage to 160 mg twice daily (maximum dosage used in clinical trials) or highest tolerated dosage.¹ ⁵²⁴ (See Hypotension under Cautions.)

Heart Failure or Left Ventricular Dysfunction After Acute MI

Oral

Manufacturers state that valsartan therapy may be initiated ≥12 hours post-MI with a dosage of 20 mg twice daily.¹ May increase dosage to 40 mg twice daily within 7 days, with subsequent titration to a target maintenance dosage of 160 mg twice daily, as tolerated.¹

Consider dosage reduction if symptomatic hypotension or renal dysfunction occurs.¹

Special Populations

The following information addresses dosage of valsartan in special populations. Dosages of drugs administered in fixed combination with valsartan also may require adjustment in certain patient populations; the need for such dosage adjustments must be considered in the context of cautions, precautions, and contraindications specific to that population and drug.¹¹⁶ ^a

Hepatic Impairment

No adjustment of initial valsartan dosage necessary in patients with mild to moderate hepatic impairment.¹ ¹¹⁶ Cautious dosing recommended in patients with hepatic impairment.¹ ¹¹⁶ ^a

Amount of amlodipine in valsartan/amlodipine fixed combinations exceeds the recommended initial dosage of amlodipine (2.5 mg daily) in patients with hepatic impairment.¹¹⁶ ¹³⁴ ¹³⁵

Renal Impairment

No adjustment of initial valsartan dosage necessary in patients with mild to moderate renal impairment.¹ ¹¹⁶ ^a Cautious dosing recommended in adults with severe impairment.¹ ¹¹⁶ Use of valsartan in pediatric patients with GFR <30 mL/minute per 1.73 m² not studied.¹

Safety and efficacy of valsartan/hydrochlorothiazide fixed combination not established in patients with severe impairment (Cl_cr ≤30 mL/minute).^a

Geriatric Patients

No adjustment of initial valsartan dosage is necessary.¹ ¹¹⁶ ^a

Amount of amlodipine in valsartan/amlodipine fixed combinations exceeds the recommended initial dosage of amlodipine (2.5 mg daily) in patients ≥75 years of age.¹¹⁶ ¹³⁴ ¹³⁵

Volume- and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of valsartan therapy or initiate therapy under close medical supervision.¹ ¹¹⁶ ¹³⁴ ^a

Cautions for Valsartan

Contraindications

Known hypersensitivity to valsartan or any ingredient in the formulation.¹ ¹¹⁶ ¹³⁴ ^a
Concomitant use of aliskiren and valsartan in patients with diabetes mellitus.¹ ¹¹⁶ ¹³⁴ ⁵⁵⁰ ^a (See Specific Drugs under Interactions.)
When valsartan is used in fixed combination with hydrochlorothiazide or amlodipine, consider contraindications associated with the concomitant agent.¹¹⁶ ¹³⁴ ^a

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when drugs that act directly on the renin-angiotensin system (e.g., angiotensin II receptor antagonists, ACE inhibitors) are used during the second and third trimesters of pregnancy.¹ ¹⁶ ¹⁷ ²⁰ ²¹ ²² ²³ ²⁴ ²⁵ ²⁶ ²⁷ ²⁸ ²⁹ ³¹ ³² ³³ ³⁴ ³⁵ ³⁶ ¹¹⁶ ^a (See Boxed Warning.) ACE inhibitors also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.¹¹⁴ ¹¹⁵

Discontinue valsartan as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.¹ ¹¹⁴ ¹¹⁵ ¹¹⁶ ^a Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.¹⁷ ²⁵

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible with angiotensin II receptor antagonists;¹ ¹¹⁶ ¹¹⁸ ^a extreme caution in patients with a history of angioedema associated with or unrelated to ACE inhibitor or angiotensin II receptor antagonist therapy.¹¹⁷ ¹¹⁹

Other Warnings and Precautions

Hypotension

Possible symptomatic hypotension with valsartan, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics).¹ ¹¹⁶ ^a (See Volume- and/or Salt-Depleted Patients under Dosage and Administration.)

Transient hypotension is not a contraindication to additional doses; may reinstate valsartan therapy cautiously after BP is stabilized (e.g., with volume expansion).¹ ¹¹⁶ ^a

Initiate valsartan therapy and subsequent dosage adjustments under close medical supervision in patients with heart failure;¹ consider reducing diuretic dosage.¹

Malignancies

In July 2010, FDA initiated a safety review of angiotensin II receptor antagonists after a published meta-analysis found a modest but statistically significant increase in risk of new cancer occurrence in patients receiving an angiotensin II receptor antagonist compared with control.¹²⁰ ¹²¹ ¹²³ ¹²⁶ However, subsequent studies, including a larger meta-analysis conducted by FDA, have not shown such risk.¹²⁶ ¹²⁷ ¹²⁸ ¹²⁹ Based on currently available data, FDA has concluded that angiotensin II receptor antagonists do not increase the risk of cancer.¹²⁶

Renal Effects

Possible acute renal failure in patients with severe heart failure, renal artery stenosis, CKD, or volume depletion.¹ ¹¹⁶ ^a

Hyperkalemia

Hyperkalemia may occur, especially in patients with heart failure and preexisting renal impairment.¹ ¹¹⁶

Use of Fixed Combinations

When valsartan is used in fixed combination with amlodipine and/or hydrochlorothiazide, consider the cautions, precautions, contraindications, and interactions associated with the concomitant agent(s).¹¹⁶ ¹³⁴ ^a Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug in the fixed combination.¹¹⁶ ¹³⁴ ^a

Specific Populations

Pregnancy

Category D.¹ ¹¹⁶ ^a

Can cause fetal and neonatal morbidity and death when administered to a pregnant woman.¹ ¹¹⁶ ^a (See Boxed Warning.)

Lactation

Valsartan is distributed into milk in rats; not known whether valsartan is distributed into human milk.¹ ¹¹⁶ ^a Discontinue nursing or the drug.¹ ¹¹⁶ ^a

Pediatric Use

Safety and efficacy of valsartan in pediatric patients 6–16 years of age with hypertension established in a controlled clinical trial.¹ Some evidence of efficacy in controlled clinical trials in pediatric patients 6 months to 5 years of age;¹ ⁵⁵¹ ⁵⁵³ however, 2 deaths and 3 cases of transaminase elevations were observed in an open-label extension study in patients 1–5 years of age.¹ Although causal relationship to valsartan has not been established, use is not recommended in pediatric patients <6 years of age.¹

Safety and efficacy of valsartan not established in children with GFR <30 mL/minute per 1.73 m².¹

Safety and efficacy of valsartan in fixed combination with amlodipine and/or hydrochlorothiazide not established in children.¹¹⁶ ¹³⁴ ^a

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults, but increased sensitivity to valsartan alone or in fixed combination with amlodipine and/or hydrochlorothiazide cannot be ruled out.¹ ¹¹⁶ ¹³⁴ ^a

Hepatic Impairment

Systemic exposure to valsartan may be increased (see Absorption: Special Populations, under Pharmacokinetics).¹ ¹¹⁶ ⁵⁵² ^a Use with caution.¹ ¹¹⁶ ^a

Renal Impairment

Valsartan not studied in patients with Cl_cr <10 mL/minute; use with caution in adults with severe renal impairment.¹ ¹⁸ ¹¹⁶ ^a Valsartan not studied in children with GFR <30 mL/minute per 1.73 m².¹

Deterioration of renal function may occur.¹ ¹¹⁶ ^a (See Renal Effects under Cautions.)

Valsartan in fixed combination with hydrochlorothiazide not studied in patients with Cl_cr ≤30 mL/minute.^a

Black Patients

BP reduction with angiotensin II receptor antagonists may be smaller in black patients than in patients of other races.¹ ^a (See Hypertension under Uses.)

Common Adverse Effects

Viral infection,¹ fatigue,¹ abdominal pain;¹ also, dizziness,¹ hypotension,¹ postural dizziness or hypotension,¹ hyperkalemia,¹ arthralgia,¹ diarrhea,¹ and back pain in patients with heart failure.¹

Drug Interactions

When valsartan is used in fixed combination with hydrochlorothiazide and/or amlodipine, also consider interactions associated with the concomitant agent.¹¹⁶ ¹³⁴ ^a

Valsartan is minimally metabolized by CYP2C9 and does not inhibit CYP enzymes at therapeutic concentrations.¹

In vitro data suggest that valsartan is a substrate of organic anion transporter protein (OATP) 1B1 (hepatic uptake transporter) and multidrug resistance protein MRP2 (hepatic efflux transporter).¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Drug interactions mediated by CYP enzymes unlikely.¹

Drugs That Inhibit Hepatic Transport Systems

Inhibitors of OATP 1B1 or MRP2: Possible increased systemic exposure to valsartan.¹

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors	Increased risk of renal impairment, hyperkalemia, and hypotension^a	Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly^a
Aliskiren	Increased risk of renal impairment, hyperkalemia, and hypotension^a ⁵⁵⁰	Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly^a ⁵⁵⁰ Concomitant use contraindicated in patients with diabetes mellitus^a ⁵⁵⁰ Avoid concomitant use in patients with GFR <60 mL/minute^a ⁵⁵⁰
Amlodipine	Pharmacokinetic interaction unlikely¹ ¹¹⁶ ^a
Angiotensin II receptor antagonists	Increased risk of renal impairment, hyperkalemia, and hypotension^a	Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly^a
Atenolol	Pharmacokinetic interaction unlikely¹ ¹¹⁶ ^a Additive antihypertensive effect; heart rate unaffected¹ ¹¹⁶ ^a
Cimetidine	Pharmacokinetic interaction unlikely¹ ¹¹⁶ ^a
Cyclosporine	Possible increased systemic exposure to valsartan¹
Digoxin	Pharmacokinetic interactions unlikely¹ ¹¹⁶ ^a
Diuretics, potassium-sparing (e.g., amiloride, spironolactone, triamterene)	Possible additive hyperkalemic effects;¹ ¹¹⁶ ^a possible increase in S_cr in patients with heart failure¹ ¹¹⁶	Monitor serum potassium concentrations¹ ¹¹⁶ ^a
Furosemide	Pharmacokinetic interactions unlikely¹ ¹¹⁶ ^a
Glyburide	Pharmacokinetic interactions unlikely¹ ¹¹⁶ ^a
Heparin	Possible additive hyperkalemic effect;¹ ¹¹⁶ ^a possible increase in S_cr in patients with heart failure¹ ¹¹⁶ ^a	Monitor serum potassium concentrations¹ ¹¹⁶ ^a
Hydrochlorothiazide	Pharmacokinetic interactions unlikely¹ ¹¹⁶ ^a Additive hypotensive effects¹ ^a
Indomethacin	Pharmacokinetic interactions unlikely¹ ¹¹⁶ ^a
Lithium	Increased serum lithium concentrations; possible toxicity¹ ¹¹⁶ ^a	Monitor serum lithium concentrations¹ ¹¹⁶ ^a
NSAIAs, including selective cyclooxygenase-2 (COX-2) inhibitors	Possible deterioration of renal function in geriatric, volume-depleted, or renally impaired patients¹ Possible reduced antihypertensive effects¹	Monitor renal function periodically¹
Potassium supplements and potassium-containing salt substitutes	Possible additive hyperkalemic effect;¹ ¹¹⁶ ^a possible increase in S_cr in patients with heart failure¹ ¹¹⁶	Monitor serum potassium concentrations¹ ¹¹⁶ ^a
Rifampin	Possible increased systemic exposure to valsartan¹
Ritonavir	Possible increased systemic exposure to valsartan¹
Warfarin	Pharmacokinetic interactions unlikely; INR unaffected¹ ¹¹⁶ ^a

Valsartan Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability of valsartan tablets is about 25% (range: 10–35%).¹ ¹¹⁶ ^a Bioavailability of extemporaneously prepared suspension (see Reconstitution under Dosage and Administration) is 1.6 times greater than that of the tablets.¹

Peak plasma concentration of valsartan reached about 2–4 hours following oral administration.¹ ¹¹⁶ ^a

Onset

Antihypertensive effect of valsartan evident within 2 weeks, with maximum BP reduction after 4 weeks.¹ ^a

Food

Food may decrease rate and extent (e.g., AUC decreased by about 40%) of absorption of valsartan.¹ ⁹ ¹¹⁶ ^a

Special Populations

In patients with mild to moderate chronic liver disease, systemic exposure to valsartan is doubled.¹ ¹¹⁶ ^a

Distribution

Extent

Valsartan crosses the placenta and is distributed in the fetus in animals.¹ ^a

Valsartan is distributed into milk in rats; not known whether valsartan is distributed into human milk.¹ ¹¹⁶ ^a

Plasma Protein Binding

Valsartan: 95% (mainly albumin).¹ ¹¹⁶ ^a

Elimination

Metabolism

Minimally metabolized in the liver by CYP2C9.¹ ¹¹⁶ ¹³⁴ ^a

Elimination Route

Valsartan is eliminated mainly as unchanged drug in feces (83%) and urine (13%).¹ ¹¹⁶ ^a

Half-life

Biexponential; average half-life of valsartan is approximately 6 hours following IV administration.¹ ¹¹⁶ ^a

Valsartan clearance is similar in adults and children.¹

Special Populations

Valsartan is not removed by hemodialysis.¹ ¹¹⁶ ^a

Stability

Storage

Oral

Extemporaneous Suspension

Valsartan 4 mg/mL in Ora-Sweet SE and Ora-Plus (see Reconstitution under Dosage and Administration), stored in amber glass bottle with child-resistant screw-cap closure: Up to 30 days at <30ºC or up to 75 days at 2–8ºC.¹

Tablets

Valsartan, valsartan/amlodipine, valsartan/hydrochlorothiazide, and valsartan/amlodipine/hydrochlorothiazide tablets: Tight container at 25°C (may be exposed to 15–30°C).¹ ¹¹⁶ ¹³⁴ ^a Protect from moisture.¹ ¹¹⁶ ¹³⁴ ^a

Actions

Valsartan blocks the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects.¹ ⁶ ¹⁰ ¹¹⁶ ^a
Valsartan does not interfere with response to bradykinins and substance P.¹ ⁴ ⁶ ¹⁰ ¹¹⁶ ^a

Valsartan does not share the ACE inhibitor common adverse effect of dry cough.¹ ⁴ ⁶ ¹⁰

Advice to Patients

When valsartan is used in fixed combination with hydrochlorothiazide and/or amlodipine, importance of advising patients of important precautionary information about the concomitant agent(s).¹¹⁶ ¹³⁴ ^a
Risks of use during pregnancy.¹ ¹¹⁴ ¹¹⁵ ¹¹⁶ ¹³⁴ ^a
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹ ¹¹⁶ ^a
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).¹ ¹¹⁶ ^a
Importance of contacting clinician if dizziness or faintness develops or if unexplained weight gain or swelling of the feet, ankles, or hands occurs.¹ ¹¹⁶ ^a
Importance of informing patients of other important precautionary information.¹ ¹¹⁶ ^a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Valsartan
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	40 mg*	Diovan (scored)	Novartis
			Valsartan Tablets
		80 mg*	Diovan	Novartis
			Valsartan Tablets
		160 mg*	Diovan	Novartis
			Valsartan Tablets
		320 mg*	Diovan	Novartis
			Valsartan Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Valsartan Combinations
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	80 mg with Hydrochlorothiazide 12.5 mg*	Diovan HCT	Novartis
			Valsartan and Hydrochlorothiazide Tablets
		160 mg with Amlodipine Besylate 5 mg (of amlodipine)*	Amlodipine Besylate and Valsartan Tablets
			Exforge	Novartis
		160 mg with Amlodipine Besylate 5 mg (of amlodipine) and Hydrochlorothiazide 12.5 mg*	Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets
			Exforge HCT	Novartis
		160 mg with Amlodipine Besylate 5 mg (of amlodipine) and Hydrochlorothiazide 25 mg*	Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets
			Exforge HCT	Novartis
		160 mg with Amlodipine Besylate 10 mg (of amlodipine)*	Amlodipine Besylate and Valsartan Tablets
			Exforge	Novartis
		160 mg with Amlodipine Besylate 10 mg (of amlodipine) and Hydrochlorothiazide 12.5 mg*	Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets
			Exforge HCT	Novartis
		160 mg with Amlodipine Besylate 10 mg (of amlodipine) and Hydrochlorothiazide 25 mg*	Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets
			Exforge HCT	Novartis
		160 mg with Hydrochlorothiazide 12.5 mg*	Diovan HCT	Novartis
			Valsartan and Hydrochlorothiazide Tablets
		160 mg with Hydrochlorothiazide 25 mg*	Diovan HCT	Novartis
			Valsartan and Hydrochlorothiazide Tablets
		320 mg with Amlodipine Besylate 5 mg (of amlodipine)*	Amlodipine Besylate and Valsartan Tablets
			Exforge	Novartis
		320 mg with Amlodipine Besylate 10 mg (of amlodipine)*	Amlodipine Besylate and Valsartan Tablets
			Exforge	Novartis
		320 mg with Amlodipine Besylate 10 mg (of amlodipine) and Hydrochlorothiazide 25 mg*	Amlodipine Besylate, Valsartan, and Hydrochlorothiazide Tablets
			Exforge HCT	Novartis
		320 mg with Hydrochlorothiazide 12.5 mg*	Diovan HCT	Novartis
			Valsartan and Hydrochlorothiazide Tablets
		320 mg with Hydrochlorothiazide 25 mg*	Diovan HCT	Novartis
			Valsartan and Hydrochlorothiazide Tablets

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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a. Novartis. Diovan (valsartan) tablets prescribing information. East Hanover, NJ; 2015 Jul.

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