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Valsartan

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
Brands: Diovan, Exforge (combination), Exforge HCT (combination)

Medically reviewed on Nov 5, 2018

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 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 (Clcr ≤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 Clcr <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 Clcr ≤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

Interactions for Valsartan

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 hypotensiona

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantlya

Aliskiren

Increased risk of renal impairment, hyperkalemia, and hypotensiona 550

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantlya 550

Concomitant use contraindicated in patients with diabetes mellitusa 550

Avoid concomitant use in patients with GFR <60 mL/minutea 550

Amlodipine

Pharmacokinetic interaction unlikely1 116 a

Angiotensin II receptor antagonists

Increased risk of renal impairment, hyperkalemia, and hypotensiona

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantlya

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 Scr 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 Scr 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 Scr 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

AHFS DI Essentials™. © Copyright 2019, Selected Revisions November 5, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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