Valsartan Prescribing Information
- When pregnancy is detected, discontinue valsartan as soon as possible. ()5.1 Fetal Toxicity
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
[see Use in Specific Populations ]. - Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ()5.1 Fetal Toxicity
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
[see Use in Specific Populations ].
Valsartan tablets are an angiotensin II receptor blocker (ARB) indicated for:
- Hypertension,to lower blood pressure in adults and children 1 year and older. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions ()1.1 Hypertension
Valsartan tablets are indicated for the treatment of hypertension, to lower blood pressure in adults and pediatric patients one year 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 may be used alone or in combination with other antihypertensive agents.
- Heart failure(NYHA class II-IV), to reduce hospitalization for heart failure in adults ()1.2 Heart Failure
Valsartan tablets are indicated to reduce the risk of hospitalization for heart failure in adult patients with heart failure (NYHA class II to class IV). There is no evidence that valsartan tablets provides added benefits when it is used with an adequate dose of an angiotensin converting enzyme (ACE) inhibitor
[see Clinical Studies ]. - Post-myocardial infarction, for the reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction in adults ()1.3 Post-Myocardial Infarction
In clinically stable adult patients with left ventricular failure or left ventricular dysfunction following myocardial infarction, valsartan tablets are indicated to reduce the risk of cardiovascular mortality
[see Clinical Studies ].
Indication | Starting Dose | Dose Range* |
| Hypertension Adults ( 2.2 Adult Hypertension The recommended starting dose of valsartan 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 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 may be administered with other antihypertensive agents. | 80 mg to 160 mg once daily | 80 mg to 320 mg once daily |
| 1 year to 16 years ( 2.3 Pediatric Hypertension 1 Year to 16 Years of Age The usual recommended starting dose is 1 mg/kg once daily (up to 40 mg total). A higher starting dose of 2 mg/kg may be considered in selected cases when a greater reduction of blood pressure is needed. The dosage should be adjusted according to blood pressure response and tolerability, up to a maximum dose of 4 mg/kg once daily (maximum daily dose 160 mg). No data are available in pediatric patients either undergoing dialysis or with a glomerular filtration rate < 30 mL/min/1.73 m2 [see Use in Specific Populations ]. Use of valsartan is not recommended in children less than 1 year of age [see Adverse Reactions (6.1), Pediatric Use in Specific Populations , Nonclinical Toxicology ]. | 1 mg/kg once daily Up to 40 mg daily | 1 mg/kg to 4 mg/kg once daily Up to 160 mg daily |
| Heart Failure ( 2.4 Heart Failure 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. | 40 mg twice daily | 40 mg to 160 mg twice daily |
| Post-Myocardial Infarction ( 2.5 Post-Myocardial Infarction Valsartan may be initiated as early as 12 hours after a myocardial infarction. The recommended starting dose of valsartan 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 may be given with other standard post-myocardial infarction treatment, including thrombolytics, aspirin, beta-blockers and statins. | 20 mg twice daily | 20 mg to 160 mg twice daily |
| *As tolerated by patient | ||
Valsartan tablets USP, 40 mg are light yellow to yellow colored, oval shaped, beveled edge, film-coated tablets debossed with "T" and "4" on either side of scoreline on one side and plain on the other side.
Valsartan tablets USP, 80 mg are light pink-to-pink colored, oval shaped, beveled edge film-coated tablets, debossed with "T7" on one side and plain on other side.
Valsartan tablets USP, 160 mg are light yellow-to-yellow colored, oval shaped, beveled edge, film-coated tablets, debossed with "277" on one side and plain on other side.
Valsartan tablets USP, 320 mg are light brown-to-brown colored, oval shaped, beveled edge, film-coated tablets, debossed with "278" on one side and plain on other side.
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.
Valsartan was detected in the milk of lactating rats 15 minutes after oral administration of a 3 mg/kg dose.
Because clinical studies are conducted under widely varying conditions, adverse reaction 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.
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 mg to 160 mg (2% to 4%).
Valsartan has been evaluated for safety in 290 pediatric patients aged 1 year to less than 6 years and over 400 patients aged 6 years to 17 years. No relevant differences were identified between the adverse experience profile for pediatric patients and that previously reported for adult patients. Hyperkalemia was more frequently observed in pediatric patients aged 1 year to 17 years with underlying chronic kidney disease (CKD).
Cases of elevated ALT and/or AST have been reported in pediatric patients 1 year to less than 6 years of age. These events occurred in a study population which frequently had significant comorbidities; hence, a causal relationship to valsartan could not be established.
In the Valsartan Heart Failure Trial (Val-HeFT), 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 | 17% | 9% |
| Hypotension | 7% | 2% |
| Diarrhea | 5% | 4% |
| Arthralgia | 3% | 2% |
| Fatigue | 3% | 2% |
| Back Pain | 3% | 2% |
| Dizziness, postural | 2% | 1% |
| Hyperkalemia | 2% | 1% |
| Hypotension, postural | 2% | 1% |
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.
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% |
The antihypertensive effects of valsartan have been evaluated in 5 clinical studies in pediatric patients from 1 year to 16 years of age
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.
Use of valsartan is not recommended in children less than 1 year of age.
No data are available in pediatric patients either undergoing dialysis or with a glomerular filtration rate less than 30 mL/min/1.73 m2.
Daily oral dosing of neonatal/juvenile rats with valsartan at doses as low as 1 mg/kg/day (about 10% of the maximum recommended pediatric dose on a mg/m2basis) from postnatal day 7 to postnatal day 70 produced persistent, irreversible kidney damage. These kidney effects in neonatal rats represent expected exaggerated pharmacological effects that are observed if rats are treated during the first 13 days of life. This period coincides with 36 weeks of gestation in humans, which could occasionally extend up to 44 weeks after conception in humans. In humans, nephrogenesis is thought to be complete around birth; however, maturation of other aspects of kidney function (such as glomerular filtration and tubular function) may continue until approximately 2 years of age. It is unknown whether post-natal use of valsartan before maturation of renal function is complete has long-term deleterious effects on the kidney
Do not use in patients with known hypersensitivity to any component.
Do not coadminister aliskiren with valsartan in patients with diabetes
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
Do not coadminister aliskiren with valsartan in patients with diabetes. Avoid use of aliskiren with valsartan in patients with renal impairment (GFR < 60 mL/min).