Save up to 80% by drug discount in your pharmacy with "Pharmacy Near Me - National Drug Discount Card"
You can scan QR Code(just open camera on your phone/scan by application) from the image on prescription drug discount card to save it to your mobile phone. Or just click on image if you're on mobile phone.
| Product NDC Code | 72819-184 | ||||
|---|---|---|---|---|---|
| Drug Name | Valsartan |
||||
| Type | Generic | ||||
| Pharm Class | Angiotensin 2 Receptor Antagonists [MoA], Angiotensin 2 Receptor Blocker [EPC] |
||||
| Active Ingredients |
|
||||
| Route | ORAL | ||||
| Dosage Form | TABLET, COATED | ||||
| RxCUI drug identifier | 349199, 349200, 349201, 349483 |
||||
| Application Number | ANDA205347 | ||||
| Labeler Name | Archis Pharma LLC | ||||
| Packages |
|
||||
| Check if available Online | Get Medication Prices online with Discount |
Overdosage of valsartan
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10 OVERDOSAGE Limited data are available related to overdosage in humans. The most likely manifestations of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Depressed level of consciousness, circulatory collapse and shock have been reported. If symptomatic hypotension should occur, institute supportive treatment. Valsartan is not removed from the plasma by hemodialysis. Valsartan was without grossly observable adverse effects at single oral doses up to 2000 mg/kg in rats and up to 1000 mg/kg in marmosets, except for salivation and diarrhea in the rat and vomiting in the marmoset at the highest dose (60 and 31 times, respectively, the maximum recommended human dose on a mg/m 2 basis). (Calculations assume an oral dose of 320 mg/day and a 60-kg patient.)
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 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 RK Pharma Inc at 1-844-757-4276 (1-844-RKPHARMA) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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. Adult Hypertension Valsartan tablets have 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 tablets 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 2.0% of placebo patients. The most common reasons for discontinuation of therapy with valsartan tablets were headache and dizziness. The adverse reactions that occurred in placebo-controlled clinical trials in at least 1% of patients treated with valsartan tablets 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 tablets 320 mg (8%) compared to 10 to 160 mg (2% to 4%). Pediatric Hypertension Valsartan tablets have been evaluated for safety in over 400 patients aged 6 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 with underlying chronic kidney disease (CKD). Heart Failure 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. 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 tablet-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 tablets 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) .] Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation's Diovan (valsartan) tablets. However, due to Novartis Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled with that information. 6.2 Postmarketing Experience The following additional adverse reactions have been reported in postmarketing use of valsartan tablets. 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 tablets should not be re-administered to patients who have had angioedema. Digestiv e : 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
valsartan Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7 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 level and lithium toxicity ( 7.4 ) 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.
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Valsartan tablets blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis. There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Valsartan has much greater affinity (about 20,000-fold) for the AT1 receptor than for the AT2 receptor. The increased plasma levels of angiotensin II following AT1 receptor blockade with valsartan may stimulate the unblocked AT2 receptor. The primary metabolite of valsartan is essentially inactive with an affinity for the AT1 receptor about one-200th (1/200th) that of valsartan itself. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because valsartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Valsartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of valsartan on blood pressure. 12.2 Pharmacodynamics Valsartan inhibits the pressor effect of angiotensin II infusions. An oral dose of 80 mg inhibits the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. No information on the effect of larger doses is available. Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin and consequent rise in angiotensin II plasma concentration in hypertensive patients. Minimal decreases in plasma aldosterone were observed after administration of valsartan; very little effect on serum potassium was observed. In multiple-dose studies in hypertensive patients with stable renal insufficiency and patients with renovascular hypertension, valsartan had no clinically significant effects on glomerular filtration rate, filtration fraction, creatinine clearance, or renal plasma flow. In multiple-dose studies in hypertensive patients, valsartan had no notable effects on total cholesterol, fasting triglycerides, fasting serum glucose, or uric acid. 12.3 Pharmacokinetics Absorption In healthy volunteers, valsartan peak plasma concentration is reached 2 to 4 hours after dosing. Valsartan shows bi-exponential decay kinetics following intravenous administration, with an average elimination half-life of about 6 hours. Absolute bioavailability for valsartan tablets is about 25% (range 10% to 35%). The bioavailability of the suspension [See Dosage and Administration (2.2) ] is 1.6 times as great as with the tablet. AUC and C max values of valsartan increase approximately linearly with increasing dose over the clinical dosing range (80-320 mg). Valsartan does not accumulate appreciably in plasma following repeated administration of 200 mg once daily. In heart failure patients, the average time to peak plasma concentration and elimination half-life of valsartan are similar to those observed in healthy volunteers. The average accumulation factor is about 1.7 in heart failure patients following repeated administration of 160 mg twice daily. AUC and C max values of valsartan increase linearly and are almost proportional with increasing dose from 40 to 160 mg twice a day. Effect of Food With the tablet, food decreases the exposure (as measured by AUC) to valsartan by about 40% and peak plasma concentration (C max ) by about 50%. Valsartan tablets can be administered with or without food. Distribution The steady state volume of distribution of valsartan after intravenous administration is small (17 L), indicating that valsartan does not distribute into tissues extensively. Valsartan is highly bound to serum proteins (95%), mainly serum albumin. Metabolism The primary metabolite, accounting for about 9% of dose, is valeryl 4-hydroxy valsartan. In vitro metabolism studies involving recombinant CYP 450 enzymes indicated that the CYP 2C9 isoenzyme is responsible for the formation of valeryl-4-hydroxy valsartan. Valsartan does not inhibit CYP 450 isozymes at clinically relevant concentrations. CYP 450 mediated drug interaction between valsartan and coadministered drugs are unlikely because of the low extent of metabolism. Excretion Valsartan, when administered as an oral solution, is primarily recovered in feces (about 83% of dose) and urine (about 13% of dose). The recovery is mainly as unchanged drug, with only about 20% of dose recovered as metabolites. Following intravenous administration, plasma clearance of valsartan is about 2 L/h and its renal clearance is 0.62 L/h (about 30% of total clearance). The apparent clearance of valsartan following oral administration is approximately 4.5 L/h in heart failure patients. Age does not affect the apparent clearance in heart failure patients. Specific Populations Geriatric Exposure (measured by AUC) to valsartan is higher by 70% and the half-life is longer by 35% in the elderly than in the young [See Use in Specific Populations (8.5) ] . Pediatric In a study of pediatric hypertensive patients (n=26, 1 to 16 years of age) given single doses of a suspension of Valsartan tablets (mean: 0.9 to 2 mg/kg), the clearance (L/h/kg) of valsartan for children was similar to that of adults receiving the same formulation. Valsartan pharmacokinetics have not been investigated in pediatric patients less than 1 year of age. Gender Pharmacokinetics of valsartan does not differ significantly between males and females. Renal Insufficiency There is no apparent correlation between renal function (measured by creatinine clearance) and exposure (measured by AUC) to valsartan in patients with different degrees of renal impairment (down to creatinine clearance of 10 mL/min). Valsartan is not removed from the plasma by hemodialysis [See Use in Specific Populations (8.6) ] . Hepatic Insufficiency On average, patients with mild-to-moderate chronic liver disease have twice the exposure (measured by AUC values) to valsartan of healthy volunteers (matched by age, sex, and weight) [See Use in Specific Populations (8.7) ] . Drug Interaction Studies No clinically significant pharmacokinetic interactions were observed when valsartan tablets were coadministered with amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide, hydrochlorothiazide, or indomethacin. The valsartan-atenolol combination was more antihypertensive than either component, but it did not lower the heart rate more than atenolol alone. Coadministration of valsartan and warfarin did not change the pharmacokinetics of valsartan or the time-course of the anticoagulant properties of warfarin. Transporters The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1 and the hepatic efflux transporter MRP2. Coadministration of inhibitors of the uptake transporter (rifampin, cyclosporine) or efflux transporter (ritonavir) may increase the systemic exposure to valsartan.
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Valsartan tablets blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis. There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Valsartan has much greater affinity (about 20,000-fold) for the AT1 receptor than for the AT2 receptor. The increased plasma levels of angiotensin II following AT1 receptor blockade with valsartan may stimulate the unblocked AT2 receptor. The primary metabolite of valsartan is essentially inactive with an affinity for the AT1 receptor about one-200th (1/200th) that of valsartan itself. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because valsartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Valsartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of valsartan on blood pressure.
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics Valsartan inhibits the pressor effect of angiotensin II infusions. An oral dose of 80 mg inhibits the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. No information on the effect of larger doses is available. Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin and consequent rise in angiotensin II plasma concentration in hypertensive patients. Minimal decreases in plasma aldosterone were observed after administration of valsartan; very little effect on serum potassium was observed. In multiple-dose studies in hypertensive patients with stable renal insufficiency and patients with renovascular hypertension, valsartan had no clinically significant effects on glomerular filtration rate, filtration fraction, creatinine clearance, or renal plasma flow. In multiple-dose studies in hypertensive patients, valsartan had no notable effects on total cholesterol, fasting triglycerides, fasting serum glucose, or uric acid.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics Absorption In healthy volunteers, valsartan peak plasma concentration is reached 2 to 4 hours after dosing. Valsartan shows bi-exponential decay kinetics following intravenous administration, with an average elimination half-life of about 6 hours. Absolute bioavailability for valsartan tablets is about 25% (range 10% to 35%). The bioavailability of the suspension [See Dosage and Administration (2.2) ] is 1.6 times as great as with the tablet. AUC and C max values of valsartan increase approximately linearly with increasing dose over the clinical dosing range (80-320 mg). Valsartan does not accumulate appreciably in plasma following repeated administration of 200 mg once daily. In heart failure patients, the average time to peak plasma concentration and elimination half-life of valsartan are similar to those observed in healthy volunteers. The average accumulation factor is about 1.7 in heart failure patients following repeated administration of 160 mg twice daily. AUC and C max values of valsartan increase linearly and are almost proportional with increasing dose from 40 to 160 mg twice a day. Effect of Food With the tablet, food decreases the exposure (as measured by AUC) to valsartan by about 40% and peak plasma concentration (C max ) by about 50%. Valsartan tablets can be administered with or without food. Distribution The steady state volume of distribution of valsartan after intravenous administration is small (17 L), indicating that valsartan does not distribute into tissues extensively. Valsartan is highly bound to serum proteins (95%), mainly serum albumin. Metabolism The primary metabolite, accounting for about 9% of dose, is valeryl 4-hydroxy valsartan. In vitro metabolism studies involving recombinant CYP 450 enzymes indicated that the CYP 2C9 isoenzyme is responsible for the formation of valeryl-4-hydroxy valsartan. Valsartan does not inhibit CYP 450 isozymes at clinically relevant concentrations. CYP 450 mediated drug interaction between valsartan and coadministered drugs are unlikely because of the low extent of metabolism. Excretion Valsartan, when administered as an oral solution, is primarily recovered in feces (about 83% of dose) and urine (about 13% of dose). The recovery is mainly as unchanged drug, with only about 20% of dose recovered as metabolites. Following intravenous administration, plasma clearance of valsartan is about 2 L/h and its renal clearance is 0.62 L/h (about 30% of total clearance). The apparent clearance of valsartan following oral administration is approximately 4.5 L/h in heart failure patients. Age does not affect the apparent clearance in heart failure patients. Specific Populations Geriatric Exposure (measured by AUC) to valsartan is higher by 70% and the half-life is longer by 35% in the elderly than in the young [See Use in Specific Populations (8.5) ] . Pediatric In a study of pediatric hypertensive patients (n=26, 1 to 16 years of age) given single doses of a suspension of Valsartan tablets (mean: 0.9 to 2 mg/kg), the clearance (L/h/kg) of valsartan for children was similar to that of adults receiving the same formulation. Valsartan pharmacokinetics have not been investigated in pediatric patients less than 1 year of age. Gender Pharmacokinetics of valsartan does not differ significantly between males and females. Renal Insufficiency There is no apparent correlation between renal function (measured by creatinine clearance) and exposure (measured by AUC) to valsartan in patients with different degrees of renal impairment (down to creatinine clearance of 10 mL/min). Valsartan is not removed from the plasma by hemodialysis [See Use in Specific Populations (8.6) ] . Hepatic Insufficiency On average, patients with mild-to-moderate chronic liver disease have twice the exposure (measured by AUC values) to valsartan of healthy volunteers (matched by age, sex, and weight) [See Use in Specific Populations (8.7) ] . Drug Interaction Studies No clinically significant pharmacokinetic interactions were observed when valsartan tablets were coadministered with amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide, hydrochlorothiazide, or indomethacin. The valsartan-atenolol combination was more antihypertensive than either component, but it did not lower the heart rate more than atenolol alone. Coadministration of valsartan and warfarin did not change the pharmacokinetics of valsartan or the time-course of the anticoagulant properties of warfarin. Transporters The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1 and the hepatic efflux transporter MRP2. Coadministration of inhibitors of the uptake transporter (rifampin, cyclosporine) or efflux transporter (ritonavir) may increase the systemic exposure to valsartan.
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.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 (7.3) ]. Known hypersensitivity to any component. Do not coadminister aliskiren with valsartan tablets in patients with diabetes ( 4 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION Valsartan tablets, USP are a nonpeptide, orally active, and specific angiotensin II receptor blocker acting on the AT 1 receptor subtype. Valsartan is chemically described as N -(1-oxopentyl)- N -[[2′-(1 H -tetrazol-5-yl) [1,1′-biphenyl]-4-yl]methyl]-L-valine. Its molecular formula is C 24 H 29 N 5 O 3 , its molecular weight is 435.52 and its structural formula is: Valsartan, USP is a white to practically white fine powder. It is soluble in ethanol and methanol and slightly soluble in water. Valsartan tablets are available as tablets for oral administration, containing 40 mg, 80 mg, 160 mg or 320 mg of valsartan.The inactive ingredients of the tablets are colloidal anhydrous silica, crospovidone, microcrystalline cellulose, magnesium stearate, polyethylene glycol, hydroxypropyl methylcellulose, titanium dioxide and iron oxides (yellow, black and/or red). Valsartan Structural Formula
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION Indication Starting Dose Dose Range * Adult Hypertension ( 2.2 ) 80 or 160 mg once daily 80-320 mg once daily 6-16 years ( 2.3 ) 1mg/kg once daily (up to 40 mg total) 1-4mg/kg once daily (up to 160 mg total) Heart Failure ( 2.4 ) 40 mg twice daily 40-160 mg twice daily Post-Myocardial Infarction ( 2.5 ) 20 mg twice daily 20-160 mg twice daily * As tolerated by patient 2.1 Important Dosage and Preparation Information Valsartan tablets and oral suspension are not substitutable on a milligram-per-milligram basis. Do not combine two dosage forms to achieve the total dose. The systemic exposure to valsartan (AUC) is 60% higher with the suspension compared to tablets [ S ee Clinical Pharmacology (12.3) ] . Use of the oral suspension is recommended: in patients ≥ 6 years of age who cannot swallow tablets and in pediatric patients for whom the calculated dose (mg/kg) does not correspond to the available tablet strengths of valsartan tablets When switching between suspension and tablets, the dose of valsartan may need to be adjusted. 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 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. Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation's Diovan (valsartan) tablets. However, due to Novartis Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled with that information 2.2 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. 2.3 Pediatric Hypertension 6 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 [ S ee Use in Specific Populations (8.4 ) ] . Use of valsartan tablets are not recommended in children less than 1 year of age [ S ee Adverse Reactions (6.1) , Pediatric Use in Specific Populations (8.4) , Nonclinical Toxicology (13.2) ]. Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation's Diovan (valsartan) tablets. However, due to Novartis Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled with that information. 2.4 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. 2.5 Post-Myocardial Infarction 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. 2.6 Missed Dose If a dose of valsartan tablets are missed, it should be administered as soon as possible, unless it is almost time for the next dose. The dose should not be doubled to make up for a missed dose.
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS 40 mg are deep yellow colored oval shaped coated tablet, engraved “S026” on one side and break line on other side. 80 mg are pink colored almond shaped coated tablet, engraved “S023” on one side and other side is plain. 160 mg are yellow colored almond shaped coated tablet, engraved “S024” on one side and other side is plain. 320 mg are brown colored almond shaped coated tablet, engraved “S025” on one side and other side is plain. Tablets (mg) : 40 (scored), 80, 160, 320 (3)
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE Valsartan tablets are an angiotensin II receptor blocker (ARB) indicated for: Hypertension ,to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions ( 1.1 ) 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 dysfunction following myocardial infarction ( 1.3 ) 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 may be used alone or in combination with other antihypertensive agents. Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation's Diovan (valsartan) tablets. However, due to Novartis Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled with that information 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 they are used with an adequate dose of an ACE inhibitor [See Clinical Studies (14.2) ] . 1.3 Post-Myocardial Infarction In clinically stable 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 (14.3) ] .
Spl product data elements
Usually a list of ingredients in a drug product.Valsartan valsartan SILICON DIOXIDE CROSPOVIDONE HYPROMELLOSE, UNSPECIFIED MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE POLYETHYLENE GLYCOL, UNSPECIFIED TITANIUM DIOXIDE FERRIC OXIDE YELLOW FERRIC OXIDE RED FERROSOFERRIC OXIDE VALSARTAN VALSARTAN S026 Valsartan valsartan FERRIC OXIDE YELLOW HYPROMELLOSE, UNSPECIFIED FERROSOFERRIC OXIDE VALSARTAN VALSARTAN CROSPOVIDONE SILICON DIOXIDE MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE POLYETHYLENE GLYCOL 8000 FERRIC OXIDE RED TITANIUM DIOXIDE S023 Valsartan valsartan FERROSOFERRIC OXIDE SILICON DIOXIDE CROSPOVIDONE HYPROMELLOSE, UNSPECIFIED MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE POLYETHYLENE GLYCOL, UNSPECIFIED FERRIC OXIDE RED TITANIUM DIOXIDE FERRIC OXIDE YELLOW VALSARTAN VALSARTAN S024 Valsartan valsartan FERROSOFERRIC OXIDE SILICON DIOXIDE CROSPOVIDONE HYPROMELLOSE, UNSPECIFIED MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE POLYETHYLENE GLYCOL, UNSPECIFIED FERRIC OXIDE RED TITANIUM DIOXIDE FERRIC OXIDE YELLOW VALSARTAN VALSARTAN S025
Animal pharmacology and or toxicology
Information from studies of the drug in animals, if the data were not relevant to nor included in other parts of the labeling. Most labels do not contain this field.13.2 Animal Toxicology and/or Pharmacology 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/m2 basis) 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. [See Use in Specific Populations (8.4) ] .
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility There was no evidence of carcinogenicity when valsartan was administered in the diet to mice and rats for up to 2 years at doses up to 160 and 200 mg/kg/day, respectively. These doses in mice and rats are about 2.6 and 6 times, respectively, the MRHD on a mg/m2 basis (Calculations assume an oral dose of 320 mg/day and a 60-kg patient). Mutagenicity assays did not reveal any valsartan-related effects at either the gene or chromosome level. These assays included bacterial mutagenicity tests with Salmonella (Ames) and E coli; a gene mutation test with Chinese hamster V79 cells; a cytogenetic test with Chinese hamster ovary cells; and a rat micronucleus test. Valsartan had no adverse effects on the reproductive performance of male or female rats at oral doses up to 200 mg/kg/day. This dose is 6 times the MRHD on a mg/m2 basis (Calculations assume an oral dose of 320 mg/day and a 60-kg patient).
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility There was no evidence of carcinogenicity when valsartan was administered in the diet to mice and rats for up to 2 years at doses up to 160 and 200 mg/kg/day, respectively. These doses in mice and rats are about 2.6 and 6 times, respectively, the MRHD on a mg/m2 basis (Calculations assume an oral dose of 320 mg/day and a 60-kg patient). Mutagenicity assays did not reveal any valsartan-related effects at either the gene or chromosome level. These assays included bacterial mutagenicity tests with Salmonella (Ames) and E coli; a gene mutation test with Chinese hamster V79 cells; a cytogenetic test with Chinese hamster ovary cells; and a rat micronucleus test. Valsartan had no adverse effects on the reproductive performance of male or female rats at oral doses up to 200 mg/kg/day. This dose is 6 times the MRHD on a mg/m2 basis (Calculations assume an oral dose of 320 mg/day and a 60-kg patient). 13.2 Animal Toxicology and/or Pharmacology 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/m2 basis) 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. [See Use in Specific Populations (8.4) ] .
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PRINCIPAL DISPLAY PANEL - 40 mg NDC 72819-181-03 Valsartan Tablets, USP 40 mg Rx only 30 Tablets Each tablet contains : Valsartan, USP 40 mg Usual Dosage: See packaging insert for complete dosaging instruction. Dispense in tight container Keep this and all drugs out of the reach of children. Storage condition: Store at 25 o C (77 o F). excursion permitted 15 o C TO 30 o C (59 o F TO 86 o F) [See USP controlled room temperature] Protect from moisture. Made by: Square Pharmaceuticals Ltd. Bangladesh. Mfg. Lic. No.: 235 & 460 Distributed by: Archis Pharma LLC 15 Corporate Place South, Suite 108 Piscataway, NJ 08854, U.S.A. Valsartan Tablets, USP 40 mg Bottle Label
PRINCIPAL DISPLAY PANEL - 80 mg NDC 72819-182-09 Valsartan Tablets, USP 80 mg Rx only 90 Tablets Each tablet contains : Valsartan, USP 80 mg Usual Dosage : See packaging insert for complete dosaging instruction. Dispense in tight container Keep this and all drugs out of the reach of children. Storage condition : Store at 25 o C (77 o F). excursion permitted 15 o C TO 30 o C (59 o F TO 86 o F) [See USP controlled room temperature] Protect from moisture. Distributed by: Archis Pharma LLC 15 Corporate Place South, Suite 108 Piscataway, NJ 08854, U.S.A. Valsartan Tablets, USP 80 mg Bottle Label
PRINCIPAL DISPLAY PANEL - 160 mg NDC 72819-183-09 Valsartan Tablets, USP 160 mg Rx only 90 Tablets Each tablet contains: Valsartan, USP 160 mg Usual Dosage : See packaging insert for complete dosaging instruction. Dispense in tight container Keep this and all drugs out of the reach of children. Storage condition : Store at 25 o C (77 o F). excursion permitted 15 o C TO 30 o C (59 o F TO 86 o F) [See USP controlled room temperature] Protect from moisture. Distributed by: Archis Pharma LLC 15 Corporate Place South, Suite 108 Piscataway, NJ 08854, U.S.A. Made by: Square Pharmaceuticals Ltd. Bangladesh. Mfg. Lic. No.: 235 & 460 Valsartan Tablets, USP 160 mg Bottle Label
PRINCIPAL DISPLAY PANEL - 320 mg NDC 72819-184-09 Valsartan Tablets, USP 320 mg Rx only 90 Tablets Each tablet contains: Valsartan, USP 320 mg Usual Dosage : See packaging insert for complete dosaging instruction. Dispense in tight container Keep this and all drugs out of the reach of children. Storage condition: Store at 25 o C (77 o F). excursion permitted 15 o C TO 30 o C (59 o F TO 86 o F) [See USP controlled room temperature] Protect from moisture Distributed by: Archis Pharma LLC 15 Corporate Place South, Suite 108 Piscataway, NJ 08854, U.S.A. Made by: Square Pharmaceuticals Ltd. Bangladesh. Mfg. Lic. No.: 235 & 460 Valsartan Tablets, USP 320 mg Bottle Label
valsartan: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Pregnancy : Advise female patients of childbearing age about the consequences of exposure to valsartan tablets during pregnancy. Discuss treatment options with women planning to become pregnant. Ask patients to report pregnancies to their healthcare provider as soon as possible [See Warnings and Precautions (5.1 ) , Use in Specific Populations (8.1) ] . Lactation : Advise women not to breastfeed during treatment with valsartan tablets [See Use in Specific Populations (8.2) ]. Symptomatic Hypotension : Advise patients that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to their healthcare provider. Tell patients that if syncope occurs to discontinue valsartan tablets until the physician has been consulted. Caution all patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope [See Warnings and Precautions (5.2) ] . Hyperkalemia : Advise patients not to use salt substitutes without consulting their healthcare provider [See Drug Interactions (7.1) ]. Manufactured by: Square Pharmaceuticals Ltd. Dhaka Unit, Kaliakoir, Gazipur-1750, Bangladesh Distributed by: Archis Pharma LLC 15 Corporate Place South, Suite 108 Piscataway, NJ 08854, U.S.A. Revised: 10/2022 PI-VLS-00
Spl patient package insert
Information necessary for patients to use the drug safely and effectively.Patient Information Valsartan (val sar′ tan)Tablets, What is the most important information I should know about valsartan tablets? Valsartan tablets can cause harm or death to an unborn baby. Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant. If you become pregnant during treatment with valsartan tablets, stop taking valsartan tablets and tell your healthcare provider right away. What is valsartan tablets? Valsartan tablets are a prescription medicine used in: • adults and children 6 years of age and older to lower high blood pressure (hypertension). Valsartan Tablets may be used alone or in combination with other blood pressure medicines. • adults to treat heart failure. Valsartan tablets may help decrease your need for hospitalization that happens with heart failure. • adults with certain types of heart failure, to increase the chance of living longer after a heart attack (myocardial infarction). Valsartan tablets should not be used to treat high blood pressure in children less than 1 year of age. It is not known if valsartan tablets are safe and effective in children with certain kidney problems. Do not take valsartan tablets if you: • are allergic to any of the ingredients in valsartan tablets. See the end of this leaflet for a complete list of ingredients in valsartan tablets. • have diabetes and are also taking aliskiren. Talk to your healthcare provider if you are not sure. Before taking valsartan tablets, tell your healthcare provider about all of your medical conditions including, if you : • have heart problems • have kidney problems • are pregnant or plan to become pregnant. See “What is the most important information I should know about valsartan tablets? • are breastfeeding or plan to breastfeed. It is not known if valsartan passes into your breast milk. You should not breastfeed during treatment with valsartan tablets. Talk with your healthcare provider about the best way to feed your baby during your treatment with valsartan tablets. Tell your healthcare provider about all the medicines you take including prescription and over- the-counter medicines, vitamins and herbal supplements. Valsartan tablets may affect the way other medicines work. Especially tell your healthcare provider if you take: • other medicines for high blood pressure or a heart problem. • water pills (also called “diuretics”). • potassium-containing medicines, potassium supplements or salt substitutes containing potassium. Your healthcare provider may check the amount of potassium in your blood regularly. • nonsteroidal anti-inflammatory drugs (NSAIDs). • Lithium. Your healthcare provider will check the amount of lithium in your blood regularly. Know the medicines you take. Keep a list of your medicines with you to show to your healthcare provider and pharmacist when a new medicine is prescribed. Talk to your healthcare provider or pharmacist before you start taking any new medicine. How should I take valsartan tablets? • Take valsartan tablets exactly as prescribed by your healthcare provider. • For treatment of high blood pressure, take valsartan tablets 1 time each day • For children: Your pharmacist will mix valsartan tablets as a liquid suspension for your child, if: o your child is ≥ 6 years of age and cannot swallow tablets, or o if tablets are not available in the prescribed strength needed for your child • If your child switches between taking the tablet and the suspension, your healthcare provider will adjust the dose as needed. o Shake the bottle of suspension well for at least 10 seconds before pouring the dose of medicine to give to your child • For adults with heart failure or who have had a heart attack, take valsartan tablets 2 times each day. Your healthcare provider may start you on a low dose of valsartan tablets and may increase the dose during your treatment. • Valsartan tablets can be taken with or without food. • If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Take the next dose at your regular time. If you take too much valsartan tablets, call your healthcare provider, or go to the nearest hospital emergency room. What are the possible side effects of valsartan tablets? • Valsartan tablets can cause serious side effects, including: See “What is the most important information I should know about valsartan tablets?” • Low blood pressure (hypotension) . Low blood pressure can happen with valsartan tablets, especially when you first start taking it and can cause you to feel lightheaded. Feeling lightheaded is most likely to happen if you: o take water pills o are dehydrated (decreased body fluids) due to vomiting and diarrhea o are on a low-salt diet o you sweat excessively o get dialysis treatments o have heart problems o do not drink enough liquids Lie down, if you feel lightheaded, dizzy or faint. Call your healthcare provider right away. • Kidney problems. Kidney problems may get worse in people that already have kidney disease or heart problems. Your doctor may do blood tests to check for this. • Increased potassium in your blood. Some people may develop increased potassium in the blood during treatment with valsartan tablets. Your doctor may do a blood test to check your potassium levels as needed. The most common side effects of valsartan tablets used to treat people with high blood pressure include: •headache •dizziness •flu symptoms •tiredness •stomach (abdominal) pain The most common side effects of valsartan tablets used to treat people with heart failure include: •dizziness •low blood pressure •diarrhea •joint and back pain •tiredness •high blood potassium The most Common side effects of valsartan tablets used to treat people after a heart attack which caused them to stop taking the drug include: •low blood pressure •cough •high blood creatinine (decreased kidney function)•rash You should not stop taking valsartan tablets without talking to your healthcare provider. These are not all of the possible side effects of valsartan tablets. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to RK Pharma Inc at 1-844-757-4276 (1-844-RKPHARMA) or FDA at 1-800-FDA-1088. How should I store valsartan tablets? •Store valsartan tablets at room temperature between 59°F- 86°F (15ºC - 30ºC). • Keep valsartan tablets container tightly closed and in a dry place to protect from moisture. • Valsartan suspension is provided in a glass bottle with a child-resistant screw-cap closure. • Store bottles of valsartan suspension at room temperature less than 86ºF (30ºC) for up to 30 days, or refrigerate between 35ºF to 46ºF (2ºC to 8ºC) for up to 75 days. Keep valsartan tablets and all medicines out of the reach of children. General information about valsartan tablets Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use valsartan tablets for a condition for which it was not prescribed. Do not give valsartan tablets to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about valsartan tablets that is written for health professionals What are the ingredients in valsartan tablets? Active ingredient : valsartan Inactive ingredients : colloidal anhydrous silica, crospovidone, microcrystalline cellulose, magnesium stearate, polyethylene glycol, hydroxypropyl methylcellulose, titanium dioxide and iron oxides (yellow, black and/or red). Manufactured by: Square Pharmaceuticals Ltd. Dhaka Unit, Kaliakoir, Gazipur-1750, Bangladesh Distributed by : Archis Pharma LLC 15 Corporate Place South, Suite 108 Piscataway, NJ 08854, U.S.A. Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation's Diovan (valsartan) tablets. However, due to Novartis Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled with that information. This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 10/2022
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14 CLINICAL STUDIES 14.1 Hypertension Adult Hypertension The antihypertensive effects of valsartan tablets were demonstrated principally in 7 placebo-controlled, 4- to 12-week trials (1 in patients over 65 years) of dosages from 10 to 320 mg/day in patients with baseline diastolic blood pressures of 95-115 mmHg. The studies allowed comparison of once-daily and twice-daily regimens of 160 mg/day; comparison of peak and trough effects; comparison (in pooled data) of response by gender, age, and race; and evaluation of incremental effects of hydrochlorothiazide. Administration of valsartan to patients with essential hypertension results in a significant reduction of sitting, supine, and standing systolic and diastolic blood pressure, usually with little or no orthostatic change. In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs at approximately 2 hours, and maximum reduction of blood pressure is achieved within 6 hours. The antihypertensive effect persists for 24 hours after dosing, but there is a decrease from peak effect at lower doses (40 mg) presumably reflecting loss of inhibition of angiotensin II. At higher doses, however (160 mg), there is little difference in peak and trough effect. During repeated dosing, the reduction in blood pressure with any dose is substantially present within 2 weeks, and maximal reduction is generally attained after 4 weeks. In long-term follow-up studies (without placebo control), the effect of valsartan appeared to be maintained for up to 2 years. The antihypertensive effect is independent of age, gender or race. The latter finding regarding race is based on pooled data and should be viewed with caution, because antihypertensive drugs that affect the renin-angiotensin system (that is, ACE inhibitors and angiotensin-II blockers) have generally been found to be less effective in low-renin hypertensives (frequently blacks) than in high-renin hypertensives (frequently whites). In pooled, randomized, controlled trials of valsartan tablets that included a total of 140 blacks and 830 whites, valsartan and an ACE inhibitor control were generally at least as effective in blacks as whites. The explanation for this difference from previous findings is unclear. Abrupt withdrawal of valsartan has not been associated with a rapid increase in blood pressure. The blood pressure-lowering effect of valsartan and thiazide-type diuretics are approximately additive. The 7 studies of valsartan monotherapy included over 2,000 patients randomized to various doses of valsartan and about 800 patients randomized to placebo. Doses below 80 mg were not consistently distinguished from those of placebo at trough, but doses of 80, 160 and 320 mg produced dose-related decreases in systolic and diastolic blood pressure, with the difference from placebo of approximately 6-9/3-5 mmHg at 80 to 160 mg and 9/6 mmHg at 320 mg. In a controlled trial the addition of HCTZ to valsartan 80 mg resulted in additional lowering of systolic and diastolic blood pressure by approximately 6/3 and 12/5 mmHg for 12.5 and 25 mg of HCTZ, respectively, compared to valsartan 80 mg alone. Patients with an inadequate response to 80 mg once daily were titrated to either 160 mg once daily or 80 mg twice daily, which resulted in a similar response in both groups. In controlled trials, the antihypertensive effect of once-daily valsartan 80 mg was similar to that of once-daily enalapril 20 mg or once-daily lisinopril 10 mg. There are no trials of valsartan tablets demonstrating reductions in cardiovascular risk in patients with hypertension, but at least one pharmacologically similar drug has demonstrated such benefits. There was essentially no change in heart rate in valsartan-treated patients in controlled trials. Pediatric Hypertension Children Between 6 to 16 Years of Age In a clinical study involving 261 hypertensive pediatric patients 6 to 16 years of age, patients who weighed less than 35 kg received 10, 40 or 80 mg of valsartan daily (low, medium and high doses), and patients who weighed greater than or equal to 35 kg received 20, 80, and 160 mg of valsartan daily (low, medium and high doses). Renal and urinary disorders, and essential hypertension with or without obesity were the most common underlying causes of hypertension in children enrolled in this study. At the end of 2 weeks, valsartan reduced both systolic and diastolic blood pressure in a dose-dependent manner. Overall, the three dose levels of valsartan (low, medium and high) significantly reduced systolic blood pressure by 8, 10, and 12 mm Hg from the baseline, respectively. Patients were re-randomized to either continue receiving the same dose of valsartan or were switched to placebo. In patients who continued to receive the medium and high doses of valsartan, systolic blood pressure at trough was 4 and 7 mm Hg lower than patients who received the placebo treatment. In patients receiving the low dose of valsartan, systolic blood pressure at trough was similar to that of patients who received the placebo treatment. Overall, the dose-dependent antihypertensive effect of valsartan was consistent across all the demographic subgroups. Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation's Diovan (valsartan) tablets. However, due to Novartis Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled with that information 14.2 Heart Failure The Valsartan Heart Failure Trial (Val-HeFT) was a multinational, double-blind study in which 5,010 patients with NYHA class II (62%) to IV (2%) heart failure and LVEF < 40%, on baseline therapy chosen by their physicians, were randomized to placebo or valsartan (titrated from 40 mg twice daily to the highest tolerated dose or 160 mg twice daily) and followed for a mean of about 2 years. Although Val-HeFT’s primary goal was to examine the effect of valsartan when added to an ACE inhibitor, about 7% were not receiving an ACE inhibitor. Other background therapy included diuretics (86%), digoxin (67%), and beta-blockers (36%). The population studied was 80% male, 46% 65 years or older and 89% Caucasian. At the end of the trial, patients in the valsartan group had a blood pressure that was 4 mmHg systolic and 2 mmHg diastolic lower than the placebo group. There were two primary endpoints, both assessed as time to first event: all-cause mortality and heart failure morbidity, the latter defined as all-cause mortality, sudden death with resuscitation, hospitalization for heart failure, and the need for intravenous inotropic or vasodilatory drugs for at least 4 hours. These results are summarized in the following table. Placebo (N = 2,499) Valsartan (N = 2,511) Hazard Ratio (95% CI CI = Confidence Interval ) Nominal p-value All-cause mortality 484 (19.4%) 495 (19.7%) 1.02 (0.90-1.15) 0.8 HF morbidity 801 (32.1%) 723 (28.8%) 0.87 (0.79-0.97) 0.009 Although the overall morbidity result favored valsartan, this result was largely driven by the 7% of patients not receiving an ACE inhibitor, as shown in the following table. Without ACE Inhibitor With ACE Inhibitor Placebo (N = 181) Valsartan (N = 185) Placebo (N = 2,318) Valsartan (N = 2,326) Events (%) 77 (42.5%) 46 (24.9%) 724 (31.2%) 677 (29.1%) Hazard ratio (95% CI) 0.51 (0.35, 0.73) 0.92 (0.82, 1.02) p-value 0.0002 0.0965 The modest favorable trend in the group receiving an ACE inhibitor was largely driven by the patients receiving less than the recommended dose of ACE inhibitor. Thus, there is little evidence of further clinical benefit when valsartan is added to an adequate dose of ACE inhibitor. Secondary endpoints in the subgroup not receiving ACE inhibitors were as follows. Placebo (N = 181) Valsartan (N = 185) Hazard Ratio (95% CI) Components of HF morbidity All-cause mortality 49 (27.1%) 32 (17.3%) 0.59 (0.37, 0.91) Sudden death with resuscitation 2 (1.1%) 1 (0.5%) 0.47 (0.04, 5.20) CHF therapy 1 (0.6%) 0 (0.0%) – CHF hospitalization 48 (26.5%) 24 (13.0%) 0.43 (0.27, 0.71) Cardiovascular mortality 40 (22.1%) 29 (15.7%) 0.65 (0.40, 1.05) Nonfatal morbidity 49 (27.1%) 24 (13.0%) 0.42 (0.26, 0.69) In patients not receiving an ACE inhibitor, valsartan-treated patients had an increase in ejection fraction and reduction in left ventricular internal diastolic diameter (LVIDD). Effects were generally consistent across subgroups defined by age and gender for the population of patients not receiving an ACE inhibitor. The number of black patients was small and does not permit a meaningful assessment in this subset of patients. 14.3 Post-Myocardial Infarction The VALsartan In Acute myocardial iNfarcTion trial (VALIANT) was a randomized, controlled, multinational, double-blind study in 14,703 patients with acute myocardial infarction and either heart failure (signs, symptoms or radiological evidence) or left ventricular systolic dysfunction (ejection fraction ≤ 40% by radionuclide ventriculography or ≤ 35% by echocardiography or ventricular contrast angiography). Patients were randomized within 12 hours to 10 days after the onset of myocardial infarction symptoms to one of three treatment groups: valsartan (titrated from 20 or 40 mg twice daily to the highest tolerated dose up to a maximum of 160 mg twice daily), the ACE inhibitor, captopril (titrated from 6.25 mg three times daily to the highest tolerated dose up to a maximum of 50 mg three times daily), or the combination of valsartan plus captopril. In the combination group, the dose of valsartan was titrated from 20 mg twice daily to the highest tolerated dose up to a maximum of 80 mg twice daily; the dose of captopril was the same as for monotherapy. The population studied was 69% male, 94% Caucasian, and 53% were 65 years of age or older. Baseline therapy included aspirin (91%), beta-blockers (70%), ACE inhibitors (40%), thrombolytics (35%) and statins (34%). The mean treatment duration was 2 years. The mean daily dose of valsartan tablets in the monotherapy group was 217 mg. The primary endpoint was time to all-cause mortality. Secondary endpoints included (1) time to cardiovascular (CV) mortality, and (2) time to the first event of cardiovascular mortality, reinfarction, or hospitalization for heart failure. The results are summarized in the following table. Valsartan vs. Captopril Valsartan + Captopril vs. Captopril (N = 4,909) (N = 4,909) (N = 4,885) (N = 4,909) No. of Deaths Valsartan/Captopril Hazard Ratio CI p-value No. of Deaths Comb/Captopril Hazard Ratio CI p-value All-cause mortality 979 (19.9%)/ 958 (19.5%) 1.001 (0.902, 1.111) 0.98 941 (19.3%)/ 958 (19.5%) 0.984 (0.886, 1.093) 0.73 CV mortality 827 (16.8%)/ 830 (16.9%) 0.976 (0.875, 1.090) CV mortality, hospitalization for HF, and recurrent nonfatal MI 1,529 (31.1%)/ 1,567 (31.9%) 0.955 (0.881, 1.035) There was no difference in overall mortality among the three treatment groups. There was thus no evidence that combining the ACE inhibitor captopril and the angiotensin II blocker valsartan was of value. The data were assessed to see whether the effectiveness of valsartan could be demonstrated by showing in a non-inferiority analysis that it preserved a fraction of the effect of captopril, a drug with a demonstrated survival effect in this setting. A conservative estimate of the effect of captopril (based on a pooled analysis of 3 post-infarction studies of captopril and 2 other ACE inhibitors) was a 14% to 16% reduction in mortality compared to placebo. Valsartan would be considered effective if it preserved a meaningful fraction of that effect and unequivocally preserved some of that effect. As shown in the table, the upper bound of the CI for the hazard ratio (valsartan/captopril) for overall or CV mortality is 1.09 to 1.11, a difference of about 9% to 11%, thus making it unlikely that valsartan has less than about half of the estimated effect of captopril and clearly demonstrating an effect of valsartan. The other secondary endpoints were consistent with this conclusion. Effects on Mortality Amongst Subgroups in VALIAN There were no clear differences in all-cause mortality based on age, gender, race, or baseline therapies, as shown in the figure above. Effects on Mortality Amongst Subgroups in VALIANT
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.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.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use The antihypertensive effects of valsartan tablets have been evaluated in two randomized, double-blind clinical studies in pediatric patients from 1-5 and 6-16 years of age [See Clinical Studies (14.1) ] . The pharmacokinetics of valsartan have been evaluated in pediatric patients 1 to 16 years of age [See Clinical Pharmacology (12.3) ] . Valsartan tablets were 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 tablets are 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 2 . Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation's Diovan (valsartan) tablets. However, due to Novartis Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled with that information .
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)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 tablets 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 2-4% and 15-20%, 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 caesarean 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 tablets 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 2 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.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS Lactation :Breastfeeding is not recommended ( 8.2 ) Pediatrics : Use of valsartan tablets is not recommended in children less than 1 year of age ( 6.1 , 8.4 , 13.2 ) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation's Diovan (valsartan) tablets. However, due to Novartis Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled with that information . Revised: 10/2022 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 tablets 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 2-4% and 15-20%, 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 caesarean 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 tablets 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 2 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 tablets. 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 tablets have been evaluated in two randomized, double-blind clinical studies in pediatric patients from 1-5 and 6-16 years of age [See Clinical Studies (14.1) ] . The pharmacokinetics of valsartan have been evaluated in pediatric patients 1 to 16 years of age [See Clinical Pharmacology (12.3) ] . Valsartan tablets were 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 tablets are 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 2 . Additional pediatric use information is approved for Novartis Pharmaceuticals Corporation's Diovan (valsartan) tablets. However, due to Novartis Pharmaceuticals Corporation's marketing exclusivity rights, this drug product is not labeled with that information . 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. 8.6 Renal Impairment Safety and effectiveness of valsartan tablets in patients with severe renal impairment (CrCl ≤ 30 mL/min) have not been established. No dose adjustment is required in patients with mild (CrCl 60 to 90 mL/min) or moderate (CrCl 30 to 60 mL/min) renal impairment. 8.7 Hepatic Impairment No dose adjustment is necessary for patients with mild-to-moderate liver disease. No dosing recommendations can be provided for patients with severe liver disease.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING Valsartan tablets are available as tablets containing valsartan 40 mg, 80 mg, 160 mg, or 320 mg. All strengths are packaged in bottles as described below The 40 mg tablets are scored on one side and oval shaped. The 80 mg, 160 mg, and 320 mg tablets are unscored and almond-shaped. Tablet Color Deboss NDC 72819-###-## Side 1 Side 2 Bottle of 30 90 100 500 1000 40 mg Deep Yellow S026 Break line 181-03 181-09 181-10 181-11 181-12 80 mg Pink S023 Plain 182-03 182-09 182-10 182-11 182-12 160 mg Yellow S024 Plain 183-03 183-09 183-10 183-11 183-12 320 mg Brown S025 Plain 184-03 184-09 184-10 184-11 184-12 Store at 25°C (77°F); excursions permitted to 15°C- 30°C (59°F- 86°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in tight container (USP).
| 30 | 90 | 100 | 500 | 1000 | ||||
| 181-03 | 181-09 | 181-10 | 181-11 | 181-12 | ||||
| 182-03 | 182-09 | 182-10 | 182-11 | 182-12 | ||||
| 183-03 | 183-09 | 183-10 | 183-11 | 183-12 | ||||
| 184-03 | 184-09 | 184-10 | 184-11 | 184-12 | ||||
Boxed warning
Information about contraindications or serious warnings, particularly those that may lead to death or serious injury.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 death to the developing fetus. ( 5.1 ) 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 death to the developing fetus. ( 5.1 )
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API