Indications And Usage
Valsartan tablets are indicated for the treatment of hypertension, to lower blood pressure in adults and pediatric patients six years of age and older. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which valsartan principally belongs. There are no controlled trials in hypertensive patients demonstrating risk reduction with valsartan tablets.
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (e.g., patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.
Valsartan tablets may be used alone or in combination with other antihypertensive agents.
Valsartan tablets are indicated to reduce the risk of hospitalization for heart failure in patients with heart failure (NYHA class II-IV). There is no evidence that valsartan tablets provides added benefits when it is used with an adequate dose of an ACE inhibitor
In clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction, Valsartan tablets is indicated to reduce the risk of cardiovascular mortality.
The recommended starting dose of valsartan tablets is 80 mg or 160 mg once daily when used as monotherapy in patients who are not volume-depleted. Patients requiring greater reductions may be started at the higher dose. Valsartan tablets may be used over a dose range of 80 mg to 320 mg daily, administered once a day.
The antihypertensive effect is substantially present within 2 weeks and maximal reduction is generally attained after 4 weeks. If additional antihypertensive effect is required over the starting dose range, the dose may be increased to a maximum of 320 mg or a diuretic may be added. Addition of a diuretic has a greater effect than dose increases beyond 80 mg.
Valsartan tablets may be administered with other antihypertensive agents.
Pediatric Hypertension 6 to 16 Years of Age:
For pediatric patients who can swallow tablets, the usual recommended starting dose is 1.3 mg/kg once daily (up to 40 mg total). The dosage should be adjusted according to blood pressure response. Doses higher than 2.7 mg/kg (up to 160 mg) once daily have not been studied in pediatric patients 6 to 16 years old.
For pediatric patients who cannot swallow tablets, or children for whom the calculated dosage (mg/kg) does not correspond to the available tablet strengths of valsartan, the use of a suspension is recommended. Follow the suspension preparation instructions below to administer valsartan as a suspension. When the suspension is replaced by a tablet, the dose of valsartan may have to be increased. The exposure to valsartan with the suspension is 1.6 times greater than with the tablet.
No data are available in pediatric patients either undergoing dialysis or with a glomerular filtration rate <30 mL/min/1.73 m2
Valsartan tablets are not recommended for patients <6 years old
Preparation of Suspension (for 160 mL of a 4 mg/mL suspension)
Add 80 mL of Ora-Plus®* oral suspending vehicle to an amber glass bottle containing 8 valsartan 80 mg tablets, and shake for a minimum of 2 minutes. Allow the suspension to stand for a minimum of 1 hour. After the standing time, shake the suspension for a minimum of 1 additional minute. Add 80 mL of Ora-Sweet SF®* oral sweetening vehicle to the bottle and shake the suspension for at least 10 seconds to disperse the ingredients. The suspension is homogenous and can be stored for either up to 30 days at room temperature (below 30°C/86°F) or up to 75 days at refrigerated conditions (2°C-8°C/35°F-46°F) in the glass bottle with a child-resistant screw-cap closure. Shake the bottle well (at least 10 seconds) prior to dispensing the suspension.
*Ora-Sweet SF® and Ora-Plus® are registered trademarks of Paddock Laboratories, Inc.
The recommended starting dose of valsartan is 40 mg twice daily. Uptitrate to 80 mg and 160 mg twice daily or to the highest dose tolerated by the patient. Consider reducing the dose of concomitant diuretics. The maximum daily dose administered in clinical trials is 320 mg in divided doses.
Valsartan tablets may be initiated as early as 12 hours after a myocardial infarction. The recommended starting dose of valsartan tablets is 20 mg twice daily. Patients may be uptitrated within 7 days to 40 mg twice daily, with subsequent titrations to a target maintenance dose of 160 mg twice daily, as tolerated by the patient. If symptomatic hypotension or renal dysfunction occurs, consider dosage reduction. Valsartan tablets may be given with other standard post-myocardial infarction treatment, including thrombolytics, aspirin, beta-blockers, and statins.
Do not use in patients with known hypersensitivity to any component. Do not coadminister aliskiren with valsartan in patients with diabetes
Valsartan can cause fetal harm when administered to a pregnant woman. 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. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue valsartan as soon as possible
Excessive hypotension was rarely seen (0.1%) in patients with uncomplicated hypertension treated with valsartan alone. In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur. This condition should be corrected prior to administration of valsartan, or the treatment should start under close medical supervision.
Patients with heart failure or post-myocardial infarction patients given valsartan commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed. In controlled trials in heart failure patients, the incidence of hypotension in valsartan-treated patients was 5.5% compared to 1.8% in placebo-treated patients. In the VALsartan In Acute myocardial iNfarcTion trial (VALIANT), hypotension in post-myocardial infarction patients led to permanent discontinuation of therapy in 1.4% of valsartan-treated patients and 0.8% of captopril-treated patients.
If excessive hypotension occurs, place the patient in the supine position and, if necessary, give intravenous normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
Impaired Renal Function:
Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on valsartan. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on valsartan.
Some patients with heart failure have developed increases in potassium. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of valsartan may be required
Central nervous system: Dizziness (17%); hypertension (2% to 8%)
Renal: Increased blood urea nitrogen (>50% increase: 17%)
1% to 10%:
Cardiovascular: Hypotension (6% to 7%; hypertension: <1%), orthostatic hypotension (2%), syncope (>1%; hypertension: <1%)
Central nervous system: Fatigue (2% to 3%), orthostatic dizziness (≤2%), headache (>1%), vertigo (>1%)
Endocrine & metabolic: Hyperkalemia (2%)
Gastrointestinal: Diarrhea (5%), abdominal pain (hypertension: 2%), nausea (>1%), upper abdominal pain (>1%)
Hematologic & oncologic: Neutropenia (2%)
Infection: Viral infection (hypertension: 3%)
Neuromuscular & skeletal: Arthralgia (3%), back pain (3%; hypertension: <1%)
Ophthalmic: Blurred vision (>1%)
Renal: Increased serum creatinine (≤4%), renal insufficiency (>1%)
Respiratory: Dry cough (hypertension: 3%)
<1%, postmarketing, and/or case reports:
Alopecia, angioedema, anorexia, anxiety, asthenia, bullous dermatitis, chest pain, constipation, drowsiness, dyspepsia, dyspnea, flatulence, hepatitis, hypersensitivity reaction, impotence, increased liver enzymes, insomnia, muscle cramps, myalgia, palpitation, paresthesia, pruritus, renal failure syndrome, rhabdomyolysis, skin rash, thrombocytopenia, vasculitis, vomiting, xerostomia
Pregnancy and lactation
This drug is not recommended for use during pregnancy unless there are no alternatives and the benefit outweighs the risk; use is contraindicated per some authorities.
US FDA pregnancy category: Not assigned.
Risk Summary: 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.Excreted into human milk: Unknown
Renal and liver Impairment
Hepatic impairment: Use with caution in patients with hepatic impairment (exposure to valsartan is increased).
Renal artery stenosis: Use with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.
Renal impairment: Use with caution in patients with renal impairment.
Patients >65 years of age (very complex/poor health): Target BP <150/90 mm Hg is recommended.
Baseline and periodic BP, electrolyte panels, renal function.
Heart failure: Within 1 to 2 weeks after initiation, reassess BP (including postural blood pressure changes), renal function, and serum potassium; follow closely after dose changes. Patients with systolic BP <80 mm Hg, low serum sodium, diabetes mellitus, and impaired renal function should be closely monitored (ACC/AHA [Yancy 2013])
Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2018]):
Confirmed hypertension and known CVD or 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%: Target BP <130/80 mm Hg is recommended.
Confirmed hypertension without markers of increased ASCVD risk: Target BP <130/80 mm Hg may be reasonable.
Diabetes and hypertension: The American Diabetes Association (ADA) guidelines (ADA 2020):
Patients 18 to 65 years of age, without ASCVD, and 10-year ASCVD risk <15%: Target BP <140/90 mm Hg is recommended.
Patients 18 to 65 years of age and known ASCVD or 10-year ASCVD risk ≥15%: Target BP <130/80 mm Hg may be appropriate if it can be safely attained.
Patients >65 years of age (healthy or complex/intermediate health): Target BP <140/90 mm Hg is recommended.