DailyMed Label: Valsartan

DailyMed Label: Valsartan

2021

DailyMed Prescription

Valsartan

Valsartan

A-S Medication Solutions

NDC: 50090-4824

NDC: 50090-4824

NDC: 50090-4824

NDC: 50090-4824

Valsartan USP is a nonpeptide, orally active, and specific angiotensin II receptor blocker acting on the AT 1 receptor subtype.   Valsartan USP 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 435.5, 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 USP is 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 silicon dioxide, crospovidone, hypromellose, iron oxides (yellow, black and/or red), microcrystalline cellulose, magnesium stearate, polyethylene glycol, talc and titanium dioxide.

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 ) •  Heart failure (NYHA class II-IV), to reduce hospitalization for heart failure in adults ( 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 in adults ( 1.3 )

Indication     Starting Dose     Dose Range*    Hypertension Adults ( 2.2 )    80 -160 mg once daily    80-320 mg once daily    1-16 years ( 2.3 )    1 mg/kg once daily Up to 40 mg daily    1-4 mg/kg once daily Up to 160 mg daily    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

40 mg are yellow oval shaped biconvex film coated scored tablets debossed with “L12” on either side of break line on one side and plain on other side. 80 mg are pale red oval shaped biconvex film coated tablets debossed with “L13” on one side and plain on other side. 160 mg are grey-orange oval shaped biconvex film coated tablets debossed with “L14” on one side and plain on other side. 320 mg are dark grey-violet oval shaped biconvex film coated tablets debossed with “L15” on one side and plain on other side

Do not use in patients with known hypersensitivity to any component. Do not coadminister aliskiren with valsartan in patients with diabetes [see Drug Interactions ( 7.3 )].

.  Observe for signs and symptoms of hypotension ( 5.2 ) .  Monitor renal function and potassium in susceptible patients ( 5.3 , 5.4 )

• 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 ) • Non-Steroidal Anti-Inflammatory Drug (NSAID) use may lead to increased risk of renal impairment and loss of antihypertensive effect ( 7.2 )  •  Dual inhibition of the Renin-Angiotensin System (RAS): Increased risk of renal impairment, hypotension, and hyperkalemia ( 7.3 ) •  Lithium: Increases in serum lithium level and lithium toxicity ( 7.4 )

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 )

Product: 50090-4824 NDC: 50090-4824-0 30 TABLET, FILM COATED in a BOTTLE NDC: 50090-4824-1 90 TABLET, FILM COATED in a BOTTLE

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 blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 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 AT 2 receptor found in many tissues, but AT 2 is not known to be associated with cardiovascular homeostasis. Valsartan has much greater affinity (about 20,000-fold) for the AT 1 receptor than for the AT 2 receptor. The increased plasma levels of angiotensin II following AT 1 receptor blockade with valsartan may stimulate the unblocked AT 2 receptor. The primary metabolite of valsartan is essentially inactive with an affinity for the AT 1 receptor about one-200th (1/200 th ) 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

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, MRHD on a mg/m 2 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/m 2 basis (Calculations assume an oral dose of 320 mg/day and a 60-kg patient).

Adult Hypertension The antihypertensive effects of valsartan 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 to 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 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 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 1 to Less Than 6 Years of Age The antihypertensive effect of valsartan in 290 children aged between 1 to less than 6 years of age has been evaluated in three randomized, double-blind clinical studies. In the first study in 90 patients, patients who weighed less than 18 kg received 5, 20 or 40 mg of valsartan daily (low, medium and high doses), and patients who weighed greater than or equal to 18 kg received 10, 40, and 80 mg of valsartan daily (low, medium and high doses). At the end of 2 weeks, the three dose levels of valsartan (low, medium and high) reduced systolic blood pressure from the baseline by 8.4, 8.3, and 8.6 mmHg, respectively, but a dose response could not be demonstrated. In the second study of 74 patients, higher doses (1 mg/kg and 4 mg/kg daily) of valsartan were associated with numerically greater blood pressure reductions than the lowest dose (0.25 mg/kg) at the end of 6-weeks treatment. The third study was a 6 week, randomized double-blind study to evaluate the dose response of valsartan in 126 children 1 to 5 years of age with hypertension, with or without chronic kidney disease (CKD) randomized to receive either valsartan 0.25 mg/kg or 4 mg/kg daily. At the end of 6 weeks, dose dependent reductions in mean systolic blood pressure (MSBP) were observed. The reduction in MSBP was 8.5 mmHg with valsartan 4 mg/kg and 4.1 mmHg with valsartan 0.25 mg/kg. Similarly, the CKD subgroup showed reductions in MSBP with valsartan 4 mg/kg compared to 0.25 mg/kg (9.2 mmHg vs 1.2 mmHg). 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.

Valsartan Tablets (val-SAR-tan) 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 healthcare provider 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 is a prescription medicine used in: • adults and children 1 year 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 is 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 v alsartan 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 1 to 5 years of age, or o your child is older than 5 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 when 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 when 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 when used to treat people after a heart attack that cause them to stop taking valsartan tablets include: • low blood pressure • cough • high blood creatinine (decreased kidney function) 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 FDA at 1-800-FDA¬1088. How should I store valsartan tablets? • Store valsartan tablets at room temperature between 68ºF to 77ºF (20ºC to 25 ºC). • 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 the safe and effective use of 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 silicon dioxide, crospovidone, hypromellose, iron oxides (yellow, black and/or red), microcrystalline cellulose, magnesium stearate, polyethylene glycol, talc and titanium dioxide. Manufactured for : Macleods Pharma USA, Inc. Plainsboro, NJ 08536 Manufactured by : Macleods Pharmaceuticals Ltd. Daman (U.T.) INDIA For more information, call 1-888-943-3210 or 1-855-926-3384. Revised : May 2021 This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 5/2021