VALSARTAN tablet

United States - English - NLM (National Library of Medicine)

Buy It Now

Active ingredient:
VALSARTAN (UNII: 80M03YXJ7I) (VALSARTAN - UNII:80M03YXJ7I)
Available from:
Medsource Pharmaceuticals
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
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. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Pr
Product summary:
Valsartan is available as tablets containing valsartan 40 mg, 80 mg, 160 mg, or 320 mg. All strengths are packaged in bottles and unit dose blister packages (10 strips of 10 tablets) as described below. Valsartan tablets USP, 40 mg: Yellow colored, oval shaped, biconvex, film coated tablets, debossed with L128 and breakline on one side and 40 on the other side. NDC 62332-044-30    bottle of 30 tablets NDC 62332-044-90    bottle of 90 tablets NDC 62332-044-71    bottle of 500 tablets NDC 62332-044-91    bottle of 1000 tablets NDC 62332-044-10    cartons of 100 (10X10 unit-dose blisters)    Valsartan tablets USP,  80 mg: Pink colored, oval shaped, biconvex, film coated tablets, debossed with L129 on one side and 80 on the other side. NDC 62332-045-30    bottle of 30 tablets NDC 62332-045-90    bottle of 90 tablets NDC 62332-045-71    bottle of 500 tablets NDC 62332-045-91    bottle of 1000 tablets NDC 62332-045-10    cartons of 100 (10X10 unit-dose blisters)    Valsartan tablets USP, 160 mg: Yellow colored, oval shaped, biconvex, film coated tablets, debossed with L130 on one side and 160 on the other side. NDC 62332-046-30    bottle of 30 tablets NDC 62332-046-90   bottle of 90 tablets NDC 62332-046-71    bottle of 500 tablets NDC 62332-046-91    bottle of 1000 tablets NDC 62332-046-10    cartons of 100 (10X10 unit-dose blisters) Valsartan tablets USP, 320 mg: Purple colored, oval shaped, biconvex, film coated tablets, debossed with L127 on one side and 320 on the other side. NDC 62332-047-30    bottle of 30 tablets NDC 62332-047-90    bottle of 90 tablets NDC 62332-047-71    bottle of 500 tablets  NDC 62332-047-91    bottle of 1000 tablets Store at 25°C (77°F); excursions permitted to 15-30°C (59 - 86°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in tight container (USP).
Authorization status:
Abbreviated New Drug Application
Authorization number:
45865-114-60

Read the complete document

VALSARTAN- valsartan tablet

Medsource Pharmaceuticals

----------

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use VALSARTAN TABLETS safely and

effectively. See full prescribing information for VALSARTAN TABLETS.

VALSARTAN tablets, for oral use

Initial U.S. Approval: 1996

WARNING: FETAL TOXICITY

See full prescribing information for complete boxed warning.

When pregnancy is detected, discontinue valsartan tablets as soon as possible. (5.1)

Drugs that act directly on the renin-angiotensin system can cause injury and even death to the

developing fetus. (5.1)

INDICATIONS AND USAGE

Valsartan tablets is an angiotensin II receptor blocker (ARB) indicated for: (1)

Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal

cardiovascular events, primarily strokes and myocardial infarctions (1.1)

Treatment of heart failure (NYHA class II-IV); valsartan tablets significantly reduced hospitalization for heart failure

(1.2)

Post-myocardial infarction; for the reduction of cardiovascular mortality in clinically stable patients with left ventricular

failure or left ventricular (1.3)

DOSAGE AND ADMINISTRATION

Indic atio n

Starting Dose

Dose Range

Target Maintenance

Do se*

Adult Hypertension (2.1)

80 or 160 mg once daily

80 to 320 mg once daily

Pediatric Hypertension (6 to 16

years) (2.2)

1.3 mg/kg once daily (up to

40 mg total)

1.3 to 2.7 mg/kg once daily (up to 40-

160 mg total)

Heart Failure (2.3)

40 mg twice daily

40 to 160 mg twice daily

160 mg twice daily

Post-Myocardial Infarction (2.4) 20 mg twice daily

20 to 160 mg twice daily

160 mg twice daily

* as tolerated by patient (2)

DOSAGE FORMS AND STRENGTHS

Tablets (mg): 40 (scored), 80, 160, 320 (3)

CONTRAINDICATIONS

Known hypersensitivity to any component.

Do not coadminister aliskiren with valsartan tablets in patients with diabetes (4) (4)

WARNINGS AND PRECAUTIONS

Observe for signs and symptoms of hypotension (5.2)

Monitor renal function and potassium in susceptible patients (5.3, 5.4)

ADVERSE REACTIONS

Hypertension:Most common adverse reactions are headache, dizziness, viral infection, fatigue and abdominal pain (6.1)

Heart Failure:Most common adverse reactions are dizziness, hypotension, diarrhea, arthralgia, back pain, fatigue and

hyperkalemia (6.1)

Post-Myocardial Infarction: Most common adverse reactions which caused patients to discontinue therapy are

hypotension, cough and increased blood creatinine (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals Limited at 1-866-210-9797

or FDA at 1-800-FDA-1088, or http://www.fda.gov/medwatch

DRUG INTERACTIONS

Potassium-sparing diuretics, potassium supplements or salt substitutes may lead to increases in serum potassium, and

in heart failure patients, increases in serum creatinine (7.1)

NSAID use may lead to increased risk of renal impairment and loss of antihypertensive effect (7.2)

Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia

(7.3)

Lithium: Increases in serum lithium levels and lithium toxicity (7.4)

USE IN SPECIFIC POPULATIONS

Lactation: Breastfeeding is not recommended (8.2)

Pediatrics: Efficacy and safety data support use in 6 to 16 year old patients; use is not recommended in patients <6 years

old (6.1, 8.4) (8)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 10/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: FETAL TOXICITY

1 INDICATIONS AND USAGE

1.1 Hypertension

1.2 Heart Failure

1.3 Post-Myocardial Infraction

2 DOSAGE AND ADMINISTRATION

2.1 Adult Hypertension

2.2 Pediatric Hypertension 6 to 16 Years of Age

2.3 Heart Failure

2.4 Post-Myocardial Infraction

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Fetal Toxicity

5.2 Hypotension

5.3 Impaired Renal Function

5.4 Hyperkalemia

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Agents Increasing Serum Potassium

7.2 Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors

(COX-2 Inhibitors)

7.3 Dual Blockade of the Renin-Angiotensin System (RAS)

7.4 Lithium

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Hypertension

14.2 Heart Failure

14.3 Post-Myocardial Infraction

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

WARNING: FETAL TOXICITY

When pregnancy is detected, discontinue valsartan tablets as soon as possible. (5.1)

Drugs that act directly on the renin-angiotensin system can cause injury and even death

to the developing fetus. (5.1)

1 INDICATIONS AND USAGE

1.1 Hypertension

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.

Control of high blood pressure should be part of comprehensive cardiovascular risk management,

including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation,

exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood

pressure goals. For specific advice on goals and management, see published guidelines, such as those

of the National High Blood Pressure Education Program’s Joint National Committee on Prevention,

Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

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, USP may be used alone or in combination with other antihypertensive agents.

Sections or subsections omitted from the full prescribing information are not listed.

1.2 Heart Failure

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 provide added benefits when it is

used with an adequate dose of an ACE inhibitor [see Clinical Studies (14.2)].

1.3 Post-Myocardial Infraction

In clinically stable patients with left ventricular failure or left ventricular dysfunction following

myocardial infarction, valsartan tablet is indicated to reduce the risk of cardiovascular mortality [see

Clinical Studies (14.3)].

2 DOSAGE AND ADMINISTRATION

2.1 Adult Hypertension

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.

2.2 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 tablets, 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 m

[see Use in Specific Populations (8.4)].

Valsartan tablets are not recommended for patients <6 years old [see Adverse Reactions (6.1), Clinical

Studies (14.1)].

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 tablets of

valsartan 80 mg, 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 to

8°C/35°F to 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.

2.3 Heart Failure

The recommended starting dose of valsartan tablets 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.

2.4 Post-Myocardial Infraction

Valsartan tablets may be initiated as early as 12 hours after a myocardial infarction. The recommended

starting dose of valsartan tablet 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.

3 DOSAGE FORMS AND STRENGTHS

40 mg are yellow colored, oval shaped, biconvex, film coated tablets debossed with L128 and breakline

on one side and 40 on the other side.

80 mg are pink colored, oval shaped, biconvex, film coated tablets debossed with L129 on one side and

80 on the other side.

160 mg are yellow colored, oval shaped, biconvex, film coated tablets debossed with L130 on one side

and 160 on the other side.

320 mg are purple colored, oval shaped, biconvex, film coated tablets debossed with L127 on one side

and 320 on the other side.

4 CONTRAINDICATIONS

Do not use in patients with known hypersensitivity to any component.

Do not coadminister aliskiren with valsartan tablets in patients with diabetes [see Drug Interactions(7)].

5 WARNINGS AND PRECAUTIONS

5.1 Fetal Toxicity

Valsartan tablets 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 tablets as soon as possible [see Use in Specific Populations (8.1)].

5.2 Hypotension

Excessive hypotension was rarely seen (0.1%) in patients with uncomplicated hypertension treated with

valsartan tablets 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 tablets, or the treatment should start

under close medical supervision.

Patients with heart failure or post-myocardial infarction patients given valsartan tablets 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.

5.3 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 tablets . 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 tablets [see Drug Interactions (7)].

5.4 Hyperkalemia

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 tablets may be required [see Adverse Reactions

(6.1)].

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reactions rates

observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of

another drug and may not reflect the rates observed in practice.

Adult Hypertension

Valsartan has been evaluated for safety in more than 4,000 patients, including over 400 treated for over

6 months, and more than 160 for over 1 year. Adverse reactions have generally been mild and transient

in nature and have only infrequently required discontinuation of therapy. The overall incidence of

adverse reactions with valsartan was similar to placebo.

The overall frequency of adverse reactions was neither dose-related nor related to gender, age, race,

or regimen. Discontinuation of therapy due to side effects was required in 2.3% of valsartan patients and

2% of placebo patients. The most common reasons for discontinuation of therapy with valsartan were

headache and dizziness.

The adverse reactions that occurred in placebo-controlled clinical trials in at least 1% of patients

treated with valsartan and at a higher incidence in valsartan (n=2,316) than placebo (n=888) patients

included viral infection (3% vs. 2%), fatigue (2% vs. 1%), and abdominal pain (2% vs. 1%).

In trials in which valsartan was compared to an ACE inhibitor with or without placebo, the incidence of

dry cough was significantly greater in the ACE-inhibitor group (7.9%) than in the groups who received

valsartan (2.6%) or placebo (1.5%). In a 129-patient trial limited to patients who had had dry cough when

they had previously received ACE inhibitors, the incidences of cough in patients who received

valsartan, HCTZ, or lisinopril were 20%, 19%, and 69% respectively (p <0.001).

Dose-related orthostatic effects were seen in less than 1% of patients. An increase in the incidence of

dizziness was observed in patients treated with valsartan 320 mg (8%) compared to 10 to 160 mg (2% to

4%).

Pediatric Hypertension

Valsartan has been evaluated for safety in over 400 pediatric patients aged 6 to 17 years and more than

160 pediatric patients aged 6 months to 5 years. No relevant differences were identified between the

adverse experience profile for pediatric patients aged 6 to 16 years and that previously reported for

adult patients. Headache and hyperkalemia were the most common adverse events suspected to be study

drug-related in older children (6 to 17 years old) and younger children (6 months to 5 years old),

respectively. Hyperkalemia was mainly observed in children with underlying renal disease.

Neurocognitive and developmental assessment of pediatric patients aged 6 to 16 years revealed no

overall clinically relevant adverse impact after treatment with valsartan for up to 1 year. Valsartan is not

recommended for pediatric patients under 6 years of age. In a study (n=90) of pediatric patients (1 to 5

years), two deaths and three cases of on-treatment transaminase elevations were seen in the one-year

open-label extension phase. These 5 events occurred in a study population in which patients frequently

had significant co-morbidities. A causal relationship to valsartan has not been established. In a second

study of 6-months duration in 75 children aged 1 to 5 years, there were no deaths; one case of marked

liver transaminase elevations occurred following 6 months of treatment. The most common adverse

reaction in children less than 6 years old was hyperkalemia. Hyperkalemia was mainly observed in

children with underlying renal disease.

Heart Failure

In the Valsartan Heart Failure Trial, comparing valsartan in total daily doses up to 320 mg (n=2,506) to

placebo (n=2,494), 10% of valsartan patients discontinued for adverse reactions vs. 7% of placebo

patients.

The table shows adverse reactions in double-blind short-term heart failure trials, including the first 4

months of the Valsartan Heart Failure Trial, with an incidence of at least 2% that were more frequent in

valsartan-treated patients than in placebo-treated patients. All patients received standard drug therapy for

heart failure, frequently as multiple medications, which could include diuretics, digitalis, beta-

blockers. About 93% of patients received concomitant ACE inhibitors.

Valsartan (n=3,282)

Placebo (n=2,740)

Dizziness

Hypotension

Diarrhea

Arthralgia

Fatigue

Back Pain

Dizziness, postural

Hyperkalemia

Hypotension, postural

Discontinuations occurred in 0.5% of valsartan-treated patients and 0.1% of placebo patients for each of

the following: elevations in creatinine and elevations in potassium.

Other adverse reactions with an incidence greater than 1% and greater than placebo included headache,

nausea, renal impairment, syncope, blurred vision, upper abdominal pain and vertigo.

From the long-term data in the Valsartan Heart Failure Trial, there did not appear to be any significant

adverse reactions not previously identified.

Post-Myocardial Infarction

The table shows the percentage of patients discontinued in the valsartan and captopril-treated groups in

the VALsartan In Acute myocardial iNfarcTion trial (VALIANT) with a rate of at least 0.5% in either

of the treatment groups.

Discontinuations due to renal dysfunction occurred in 1.1% of valsartan-treated patients and 0.8% of

captopril-treated patients.

Valsartan (n=4,885)

Captopril (n=4,879)

Discontinuation for adverse reaction

5.8%

7.7%

Adverse reactions

Hypotension NOS

1.4%

0.8%

Cough

0.6%

2.5%

Blood creatinine increased

0.6%

0.4%

Rash NOS

0.2%

0.6%

Clinical Laboratory Test Findings

Creatinine: In heart failure trials, greater than 50% increases in creatinine were observed in 3.9% of

valsartan-treated patients compared to 0.9% of placebo-treated patients. In post-myocardial infarction

patients, doubling of serum creatinine was observed in 4.2% of valsartan-treated patients and 3.4% of

captopril-treated patients.

Neutropenia: Neutropenia was observed in 1.9% of patients treated with valsartan and 0.8% of patients

treated with placebo.

Blood Urea Nitrogen (BUN): In heart failure trials, greater than 50% increases in BUN were observed

in 16.6% of valsartan-treated patients compared to 6.3% of placebo-treated patients [see Warnings and

Precautions (5.3)].

6.2 Postmarketing Experience

The following additional adverse reactions have been reported in post-marketing use of valsartan.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always

possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity:Angioedema has been reported. Some of these patients previously experienced

angioedema with other drugs including ACE inhibitors. Valsartan should not be re-administered to

patients who have had angioedema.

Digestive: Elevated liver enzymes and very rare reports of hepatitis

Musculoskeletal: Rhabdomyolysis

Renal: Impaired renal function, renal failure

Dermatologic: Alopecia, bullous dermatitis

Blood and Lymphatic: Thrombocytopenia

Vascular: Vasculitis

7 DRUG INTERACTIONS

7.1 Agents Increasing Serum Potassium

Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium-

sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, salt substitutes

containing potassium or other drugs that may increase potassium levels (e.g., heparin) may lead to

increases in serum potassium and in heart failure patients to increases in serum creatinine. If co-

medication is considered necessary, monitoring of serum potassium is advisable.

7.2 Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors

(COX-2 Inhibitors)

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised

renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II

receptor antagonists, including valsartan, may result in deterioration of renal function, including

possible acute renal failure. These effects are usually reversible. Monitor renal function periodically

in patients receiving valsartan and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including valsartan, may be attenuated

by NSAIDs including selective COX-2 inhibitors.

7.3 Dual Blockade of the Renin-Angiotensin System (RAS)

Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is

associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including

acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS

inhibitors do not obtain any additional benefit compared to monotherapy [see Clinical Studies (14.3)]. In

general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and

electrolytes in patients on valsartan tablets and other agents that affect the RAS.

Do not coadminister aliskiren with valsartan tablets in patients with diabetes. Avoid use of aliskiren with

valsartan tablets in patients with renal impairment (GFR <60 mL/min).

7.4 Lithium

Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant

administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during

concomitant use.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

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. Most epidemiologic studies examining

fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished

drugs affecting the renin-angiotensin system from other antihypertensive agents. Published reports

include cases of anhydramnios and oligohydramnios in pregnant women treated with valsartan ( see

Clinical Considerations).

When pregnancy is detected, consider alternative drug treatment and discontinue valsartan as soon as

possible.

The estimated background risk of major birth defects and miscarriage for the indicated population is

unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In

the U.S. general population, the estimated background risk of major birth defects and miscarriage in

clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes,

premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum

hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine

death. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Fetal/Neonatal Adverse Reactions

Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second

and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to

anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia,

hypotension and death. In the unusual case that there is no appropriate alternative to therapy with drugs

affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to

the fetus.

In patients taking valsartan during pregnancy, perform serial ultrasound examinations to assess the intra-

amniotic environment. Fetal testing may be appropriate, based on the week of gestation. Patients and

physicians should be aware, however, that oligohydramnios may not appear until after the fetus has

sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment.

Closely observe neonates with histories of in utero exposure to valsartan for hypotension, oliguria, and

hyperkalemia. In neonates with a history of in utero exposure to valsartan, if oliguria or hypotension

occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required

as a means of reversing hypotension and replacing renal function.

Data

Animal Data

No teratogenic effects were observed when valsartan was administered to pregnant mice and rats at oral

doses of up to 600 mg/kg/day (9 and 18 times the MRHD on a mg/m

basis) and to pregnant rabbits at

oral doses of up to 10 mg/kg/day.

In rats, oral valsartan administered at maternally toxic doses (600 mg/kg/day) during organogenesis or

late gestation and lactation, resulted in decreased fetal and pup weight, pup survival and delayed

developmental milestones. In rabbits administered maternally toxic doses of 5 and 10 mg/kg/day,

fetotoxicity was observed.

8.2 Lactation

Risk Summary

There is no information regarding the presence of valsartan in human milk, the effects on the breastfed

infant, or the effects on milk production. Valsartan is present in rat milk. Because of the potential for

serious adverse reactions in breastfed infants from exposure to valsartan, advise a nursing woman that

breastfeeding is not recommended during treatment with valsartan.

Data

Valsartan was detected in the milk of lactating rats 15 minutes after oral administration of a 3 mg/kg

dose.

8.4 Pediatric Use

The antihypertensive effects of valsartan has been evaluated in two randomized, double-blind clinical

studies in pediatric patients from 1 to 5 and 6 to 16 years of age [see Clinical Studies (14.1)]. The

pharmacokinetics of valsartan has been evaluated in pediatric patients 1 to 16 years of age [see Clinical

Pharmacology (12.3)]. Valsartan was generally well tolerated in children 6 to 16 years and the adverse

experience profile was similar to that described for adults.

In children and adolescents with hypertension where underlying renal abnormalities may be more

common, renal function and serum potassium should be closely monitored as clinically indicated.

Valsartan is not recommended for pediatric patients under 6 years of age due to safety findings for

which a relationship to treatment could not be excluded [see Adverse Reactions (6.1)].

No data are available in pediatric patients either undergoing dialysis or with a glomerular filtration rate

<30 mL/min/1.73 m

There is limited clinical experience with valsartan in pediatric patients with mild to moderate hepatic

impairment [see Warnings and Precautions (5.3)].

8.5 Geriatric Use

In the controlled clinical trials of valsartan, 1,214 (36.2%) hypertensive patients treated with valsartan

were ≥65 years and 265 (7.9%) were ≥75 years. No overall difference in the efficacy or safety of

valsartan was observed in this patient population, but greater sensitivity of some older individuals

cannot be ruled out. Exposure (measured by AUC) to valsartan is higher by 70% in the elderly than in

the young, however no dosage adjustment is necessary [see Clinical Pharmacology (12.3)].

Of the 2,511 patients with heart failure randomized to valsartan in the Valsartan Heart Failure Trial, 45%

(1,141) were 65 years of age or older. In the VALsartan In Acute myocardial iNfarcTion trial

(VALIANT), 53% (2,596) of the 4,909 patients treated with valsartan and 51% (2,515) of the 4,885

patients treated with valsartan + captopril were 65 years of age or older. There were no notable

differences in efficacy or safety between older and younger patients in either trial.

Similar products

Search alerts related to this product

View documents history

Share this information