- When pregnancy is detected, discontinue Valsartan and hydrochlorothiazide 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)
Valsartan and hydrochlorothiazide tablet USP is indicated for the treatment of hypertension, to lower blood pressure. 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 hydrochlorothiazide and the ARB class to which valsartan principally belongs. There are no controlled trials demonstrating risk reduction with valsartan and hydrochlorothiazide tablets USP.
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 (for example, 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 and hydrochlorothiazide tablets USP may be used in patients whose blood pressure is not adequately controlled on monotherapy.
Valsartan and hydrochlorothiazide tablets USP may be substituted for the titrated components.
Valsartan and hydrochlorothiazide tablets USP may be used as initial therapy in patients who are likely to need multiple drugs to achieve blood pressure goals.
The choice of valsartan and hydrochlorothiazide tablets USP as initial therapy for hypertension should be based on an assessment of potential benefits and risks.
Patients with stage 2 hypertension are at a relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. The decision to use a combination as initial therapy should be individualized and should be shaped by considerations such as baseline blood pressure, the target goal and the incremental likelihood of achieving goal with a combination compared to monotherapy. Individual blood pressure goals may vary based upon the patient’s risk.
Data from the high dose multifactorial trial [see CLINICAL STUDIES (14.1)] provides estimates of the probability of reaching a target blood pressure with valsartan and hydrochlorothiazide tablets compared to valsartan or hydrochlorothiazide monotherapy. The figures below provide estimates of the likelihood of achieving systolic or diastolic blood pressure control with valsartan and hydrochlorothiazide tablets USP, 320 mg/25 mg, based upon baseline systolic or diastolic blood pressure. The curve of each treatment group was estimated by logistic regression modeling. The estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures.
For example, a patient with a baseline blood pressure of 160/100 mmHg has about a 41% likelihood of achieving a goal of <140 mmHg (systolic) and 60% likelihood of achieving <90 mmHg (diastolic) on valsartan alone and the likelihood of achieving these goals on HCTZ alone is about 50% (systolic) or 57% (diastolic). The likelihood of achieving these goals on valsartan and hydrochlorothiazide tablets rises to about 84% (systolic) or 80% (diastolic). The likelihood of achieving these goals on placebo is about 23% (systolic) or 36% (diastolic).
80 mg/12.5 mg tablets, light pink colored, capsule shaped, film-coated biconvex tablets, debossed with "LU" on one side and "P11" on the other side.
160 mg/12.5 mg tablets, reddish brown colored, capsule shaped, film-coated biconvex tablets, debossed with "LU" on one side and "P12" on the other side.
160 mg/25 mg tablets, light orange colored, capsule shaped, film-coated biconvex tablets, debossed with "LU" on one side and "P13" on other side.
320 mg/12.5 mg tablets, pink, capsule shaped, film-coated biconvex tablets debossed with 'LU' on one side and 'P14' on the other side.
320 mg/25 mg tablets, yellow, capsule shaped, film-coated biconvex tablets debossed with 'LU' on one side and 'P15' on the other side.
Valsartan and hydrochlorothiazide are contraindicated in patients who are hypersensitive to any component of this product.
Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
Do not co-administer aliskiren with valsartan and hydrochlorothiazide tablets in patients with diabetes [see DRUG INTERACTIONS (7)].
Dose-related orthostatic effects were seen in fewer than 1% of patients. In individual trials, a dose-related increase in the incidence of dizziness was observed in patients treated with valsartan and hydrochlorothiazide.
Other adverse reactions that have been reported with valsartan-hydrochlorothiazide (>0.2% of valsartan-hydrochlorothiazide patients in controlled clinical trials) without regard to causality, are listed below:
Cardiovascular: Palpitations and tachycardia
Ear and Labyrinth: Tinnitus and vertigo
Gastrointestinal: Dyspepsia, diarrhea, flatulence, dry mouth, nausea, abdominal pain, abdominal pain upper, and vomiting
General and Administration Site Conditions: Asthenia, chest pain, fatigue, peripheral edema and pyrexia
Infections and Infestations: Bronchitis, bronchitis acute, influenza, gastroenteritis, sinusitis, upper respiratory tract infection and urinary tract infection
Investigations: Blood urea increased
Musculoskeletal: Arthralgia, back pain, muscle cramps, myalgia, and pain in extremity
Nervous System: Dizziness postural, paresthesia, and somnolence
Psychiatric: Anxiety and insomnia
Renal and Urinary: Pollakiuria
Reproductive System: Erectile dysfunction
Respiratory, Thoracic and Mediastinal: Dyspnea, cough, nasal congestion, pharyngolaryngeal pain and sinus congestion
Skin and Subcutaneous Tissue: Hyperhidrosis and rash
Other reported reactions seen less frequently in clinical trials included abnormal vision, anaphylaxis, bronchospasm, constipation, depression, dehydration, decreased libido, dysuria, epistaxis, flushing, gout, increased appetite, muscle weakness, pharyngitis, pruritus, sunburn, syncope, and viral infection.
Initial Therapy - Hypertension
In a clinical study in patients with severe hypertension (diastolic blood pressure =110 mmHg and systolic blood pressure =140 mmHg), the overall pattern of adverse reactions reported through six weeks of follow-up was similar in patients treated with valsartan and hydrochlorothiazide as initial therapy and in patients treated with valsartan as initial therapy. Comparing the groups treated with valsartan and hydrochlorothiazide (force-titrated to 320/25 mg) and valsartan (force-titrated to 320 mg), dizziness was observed in 6% and 2% of patients, respectively. Hypotension was observed in 1% of those patients receiving valsartan and hydrochlorothiazide and 0% of patients receiving valsartan. There were no reported cases of syncope in either treatment group. Laboratory changes with valsartan and hydrochlorothiazide as initial therapy in patients with severe hypertension were similar to those reported with valsartan and hydrochlorothiazide in patients with less severe hypertension [see CLINICAL STUDIES (14.2) and DRUG INTERACTIONS (7)].
Valsartan: 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 dry cough when they had previously received ACE inhibitors, the incidences of cough in patients who received valsartan, hydrochlorothiazide, or lisinopril were 20%, 19%, 69% respectively (p <0.001).
Other reported reactions seen less frequently in clinical trials included chest pain, syncope, anorexia, vomiting, and angioedema.
Hydrochlorothiazide: Other adverse reactions not listed above that have been reported with hydrochlorothiazide, without regard to causality, are listed below:
Body As A Whole: weakness;
Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation;
Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia;
Hypersensitivity: purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions;
Metabolic: hyperglycemia, glycosuria, hyperuricemia;
Musculoskeletal: muscle spasm;
Nervous System/Psychiatric: restlessness;
Renal: renal failure, renal dysfunction, interstitial nephritis;
Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis;
Special Senses: transient blurred vision, xanthopsia.
Clinical Laboratory Test Findings
In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of valsartan and hydrochlorothiazide .
Creatinine/Blood Urea Nitrogen (BUN): Minor elevations in creatinine and BUN occurred in 2% and 15% respectively, of patients taking valsartan and hydrochlorothiazide and 0.4% and 6% respectively, given placebo in controlled clinical trials.
Hemoglobin and Hematocrit: Greater than 20% decreases in hemoglobin and hematocrit were observed in less than 0.1% of valsartan and hydrochlorothiazide patients, compared with 0% in placebo-treated patients.
Liver Function Tests: Occasional elevations (greater than 150%) of liver chemistries occurred in valsartan and hydrochlorothiazide -treated patients.
Neutropenia: Neutropenia was observed in 0.1% of patients treated with valsartan and hydrochlorothiazide and 0.4% of patients treated with placebo.
No clinically significant pharmacokinetic interactions were observed when valsartan was 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.
CYP 450 Interactions
In vitro metabolism studies indicate that CYP 450 mediated drug interactions between valsartan and co-administered drugs are unlikely because of the low extent of metabolism [see CLINICAL PHARMACOLOGY (12.3)].
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. Co-administration of inhibitors of the uptake transporter (rifampin, cyclosporine) or efflux transporter (ritonavir) may increase the systemic exposure to valsartan.
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, coa-dministration 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.
Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium 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.
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. Closely monitor blood pressure, renal function and electrolytes in patients on valsartan and hydrochlorothiazide and other agents that affect the RAS.
Do not co-administer aliskiren with valsartan and hydrochlorothiazide tablets in patients with diabetes. Avoid use of aliskiren with valsartan and hydrochlorothiazide tablets in patients with renal impairment (GFR <60 mL/min).
When administered concurrently, the following drugs may interact with thiazide diuretics:
Antidiabetic Drugs (Oral Agents and Insulin)
Dosage adjustment of the antidiabetic drug may be required.
Diuretic agents increase the risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with valsartan and hydrochlorothiazide. Monitoring of serum lithium concentrations is recommended during concurrent use.
Nonsteroidal Anti-inflammatory Drugs (NSAIDS and COX-2 Selective Inhibitors)
When valsartan and hydrochlorothiazide and nonsteroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
May lead to symptomatic hyponatremia.
Ion Exchange Resins
Staggering the dosage of hydrochlorothiazide and ion exchange resins (e.g., cholestyramine, colestipol) such that hydrochlorothiazide is administered at least 4 hours before or 4 to 6 hours after the administration of resins would potentially minimize the interaction. [see CLINICAL PHARMACOLOGY (12.3)].
Concomitant treatment with cyclosporine may increase the risk of hyperuricemia and gout-type complications.
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, supportive treatment should be instituted.
Valsartan is not removed from the plasma by dialysis.
The degree to which hydrochlorothiazide is removed by hemodialysis has not been established. The most common signs and symptoms observed in patients are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
In rats and marmosets, single oral doses of valsartan up to 1524 and 762 mg/kg in combination with hydrochlorothiazide at doses up to 476 and 238 mg/kg, respectively, were very well tolerated without any treatment-related effects. These no adverse effect doses in rats and marmosets, respectively, represent 46.5 and 23 times the maximum recommended human dose (MRHD) of valsartan and 188 and 113 times the MRHD of hydrochlorothiazide on a mg/m2 basis. (Calculations assume an oral dose of 320 mg/day valsartan in combination with 25 mg/day hydrochlorothiazide and a 60-kg patient.)
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/m2 basis). (Calculations assume an oral dose of 320 mg/day and a 60-kg patient.)
The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats, which represents 2027 and 4054 times, respectively, the maximum recommended human dose on a mg/m2 basis. (Calculations assume an oral dose of 25 mg/day and a 60-kg patient.)
Valsartan and hydrochlorothiazide tablet USP is a combination of valsartan, an orally active, specific angiotensin II receptor blocker (ARB) acting on the AT1 receptor subtype, and hydrochlorothiazide, a diuretic.
Valsartan, a nonpeptide molecule, is chemically described as N-(1-oxopentyl)-N-[[2’-(1H-tetrazol-5-yl)[1,1’-biphenyl]-4-yl]methyl]-L-Valine. Its empirical formula is C24H29N5O3, its molecular weight is 435.5, and its structural formula is
Valsartan is a white to practically white fine powder. It is soluble in ethanol and methanol and slightly soluble in water.
Hydrochlorothiazide USP is a white, or practically white, practically odorless, crystalline powder. It is slightly soluble in water; freely soluble in sodium hydroxide solution, in n-butylamine, and in dimethylformamide; sparingly soluble in methanol; and insoluble in ether, in chloroform, and in dilute mineral acids. Hydrochlorothiazide is chemically described as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.
Hydrochlorothiazide is a thiazide diuretic. Its empirical formula is C7H8ClN3O4S2, its molecular weight is 297.73, and its structural formula is
Valsartan and hydrochlorothiazide tablets USP are formulated for oral administration to contain valsartan and hydrochlorothiazide, 80 mg/12.5 mg, 160 mg/12.5 mg, 160 mg/25 mg, 320 mg/12.5 mg and 320 mg/25 mg. The inactive ingredients of the tablets are colloidal silicon dioxide, croscarmellose sodium, crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose, pregelatinized starch, polyethylene glycol, titanium dioxide and additional colorants as below.
80 mg/12.5 mg: iron oxide red and iron oxide yellow
160 mg/12.5 mg: iron oxide red
160 mg/25 mg: iron oxide black, iron oxide red and iron oxide yellow
320 mg/12.5 mg: iron oxide black and iron oxide red
320 mg/25 mg: iron oxide yellow
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.
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.
The mechanism of the antihypertensive effect of thiazides is unknown.
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.
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 co-administered drugs are unlikely because of the low extent of metabolism.
Is not metabolized.
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).
About 70% of an orally administered dose of hydrochlorothiazide is eliminated in the urine as unchanged drug.
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. A limited amount of data suggest that the systemic clearance of hydrochlorothiazide is reduced in both healthy and hypertensive elderly subjects compared to young healthy volunteers.
Pharmacokinetics of valsartan does not differ significantly between males and females.
Pharmacokinetic differences due to race have not been studied.
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. Valsartan has not been studied in patients with severe impairment of renal function (creatinine clearance <10 mL/min). Valsartan is not removed from the plasma by hemodialysis.
In a study in individuals with impaired renal function, the mean elimination half-life of hydrochlorothiazide was doubled in individuals with mild/moderate renal impairment (30 < CLcr < 90 mL/min) and tripled in severe renal impairment (= 30 mL/min), compared to individuals with normal renal function (CLcr > 90 mL/min). [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)].
Drugs That Alter Gastrointestinal Motility: The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents (e.g. atropine, biperiden), apparently due to a decrease in gastrointestinal motility and the stomach emptying rate. Conversely, pro-kinetic drugs may decrease the bioavailability of thiazide diuretics.
Cholestyramine: In a dedicated drug interaction study, administration of cholestyramine 2 hours before hydrochlorothiazide resulted in a 70% reduction in exposure to hydrochlorothiazide. Further, administration of hydrochlorothiazide 2 hours before cholestyramine resulted in 35% reduction in exposure to hydrochlorothiazide.
Antineoplastic agents (e.g. Cyclophosphamide, Methotrexate): Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance their myelosuppressive effects.
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 two 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 7 studies of valsartan monotherapy included over 2000 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 80-160 mg and 9/6 mmHg at 320 mg.
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 comparable response in both groups.
In another 4-week study, 1876 patients randomized to valsartan 320 mg once daily had an incremental blood pressure reduction 3/1 mmHg lower than did 1900 patients randomized to valsartan 160 mg once daily.
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 was essentially no change in heart rate in valsartan-treated patients in controlled trials.
Valsartan and hydrochlorothiazide tablets USP are available as non-scored tablets containing valsartan/hydrochlorothiazide 80 mg/12.5 mg, 160 mg/12.5 mg, 160 mg/25 mg, 320 mg/12.5 mg and 320 mg/25 mg. Strengths are available as follows.
80 mg/12.5 mg Tablet - Light pink colored, capsule shaped, film-coated biconvex tablets, debossed with "LU" on one side and "P11" on the other side.
|Bottles of 90 ||NDC 68180-103-09|
|Bottles of 500 ||NDC 68180-103-02|
|Bottles of 1000||NDC 68180-103-03|
|10 X 10’ Blister Pack ||NDC 68180-103-13|
160 mg/12.5 mg Tablet - Reddish brown colored, capsule shaped, film-coated biconvex tablets, debossed with "LU" on one side and "P12" on the other side.
|Bottles of 90 ||NDC 68180-104-09|
|Bottles of 500 ||NDC 68180-104-02|
|Bottles of 1000||NDC 68180-104-03|
|10 X 10’ Blister Pack ||NDC 68180-104-13|
160 mg/25 mg Tablet - Light orange colored, capsule shaped, film-coated biconvex tablets, debossed with "LU" on one side and "P13" on other side.
|Bottles of 90 ||NDC 68180-105-09|
|Bottles of 500 ||NDC 68180-105-02|
|Bottles of 1000||NDC 68180-105-03|
|10 X 10’ Blister Pack ||NDC 68180-105-13|
320 mg/12.5 mg Tablet - Pink, capsule shaped, film-coated biconvex tablets debossed with "LU" on one side and "P14" on the other side.
|Bottles of 90 ||NDC 68180-101-09|
|Bottles of 500 ||NDC 68180-101-02|
|10 X 10’ Blister Pack ||NDC 68180-101-13|
320 mg/25 mg Tablet - Yellow, capsule shaped, film-coated biconvex tablets debossed with ‘LU’ on one side and ‘P15’ on the other side.
|Bottles of 90 ||NDC 68180-102-09|
|Bottles of 500||NDC 68180-102-02|
|10 X 10’ Blister Pack ||NDC 68180-102-13|
Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].
Protect from moisture.
Dispense in tight container (USP).
Information for Patients
Female patients of childbearing age should be told about the consequences of exposure to valsartan and hydrochlorothiazide tablets during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.
A patient receiving valsartan and hydrochlorothiazide tablets should be cautioned that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to the prescribing physician. The patients should be told that if syncope occurs, valsartan and hydrochlorothiazide tablets should be discontinued until the physician has been consulted.
All patients should be cautioned 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.
A patient receiving valsartan and hydrochlorothiazide tablets should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician.
Lupin Pharmaceuticals, Inc.
Baltimore, Maryland 21202
Goa - 403 722
January 2013 ID#: 229952
What are valsartan and hydrochlorothiazide tablets?
Valsartan and hydrochlorothiazide tablets contains two prescription medicines:
- valsartan, an angiotensin receptor blocker (ARB)
- hydrochlorothiazide (HCTZ), a water pill (diuretic)
Valsartan and hydrochlorothiazide tablets may be used to lower high blood pressure (hypertension) in adults-
- when one medicine to lower your high blood pressure is not enough
- as the first medicine to lower high blood pressure if your doctor decides you are likely to need more than one medicine.
Valsartan and hydrochlorothiazide tablets have not been studied in children under 18 years of age.
Who should not take valsartan and hydrochlorothiazide tablets?
Do not take valsartan and hydrochlorothiazide tablets if you:
- are allergic to any of the ingredients in valsartan and hydrochlorothiazide tablets. See the end of this leaflet for a complete list of ingredients in valsartan and hydrochlorothiazide tablets.
- make less urine due to kidney problems
- are allergic to medicines that contain sulfonamides.
What should I tell my doctor before taking valsartan and hydrochlorothiazide tablets?
Tell your doctor about all your medical conditions including if you:
- are pregnant or plan to become pregnant. See " What is the most important information I should know about valsartan and hydrochlorothiazide tablets?"
- are breast-feeding. Valsartan and hydrochlorothiazide tablets passes into breast milk. You should choose either to take valsartan and hydrochlorothiazide tablets or breast-feed, but not both.
- have liver problems
- have kidney problems
- have or had gallstones
- have Lupus
- have low levels of potassium (with or without symptoms such as muscle weakness, muscle spasms, abnormal heart rhythm) or magnesium in your blood
- have high levels of calcium in your blood (with or without symptoms such as nausea, vomiting, constipation, stomach pain, frequent urination, thirst, muscle weakness and twitching).
- have high levels of uric acid in the blood.
- have ever had a reaction called angioedema to another blood pressure medication. Angioedema causes swelling of the face, lips, tongue, throat and may cause difficulty breathing.
Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Some of your other medicines and valsartan and hydrochlorothiazide tablets could affect each other, causing serious side effects. Especially, tell your doctor if you take:
- other medicines for high blood pressure or a heart problem
- water pills (diuretics)
- potassium supplements. Your doctor may check the amount of potassium in your blood periodically.
- a salt substitute. Your doctor may check the amount of potassium in your blood periodically.
- antidiabetic medicines including insulin
- narcotic pain medicines
- sleeping pills
- lithium, a medicine used in some types of depression (Eskalith®, Lithobid®, Lithium Carbonate, Lithium Citrate)
- aspirin or other medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), like ibuprofen or naproxen
- digoxin or other digitalis glycosides (a heart medicine)
- muscle relaxants (medicines used during operations)
- certain cancer medicines, like cyclophosphamide or methotrexate
- certain antibiotics (rifamycin group), a drug used to protect against transplant rejection (cyclosporin) or an antiretroviral drug used to treat HIV/AIDS infection (ritonavir). These drugs may increase the effect of valsartan.
Ask your doctor if you are not sure if you are taking one of these medicines.
Know the medicines you take. Keep a list of your medicines with you to show to your doctor and pharmacist when a new medicine is prescribed. Talk to your doctor or pharmacist before you start taking any new medicine. Your doctor or pharmacist will know what medicines are safe to take together.
How should I take valsartan and hydrochlorothiazide tablets?
- Take valsartan and hydrochlorothiazide tablets exactly as prescribed by your doctor. Your doctor may change your dose if needed.
- Take valsartan and hydrochlorothiazide tablets once each day.
- Valsartan and hydrochlorothiazide 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. Just take the next dose at your regular time.
- If you take too much valsartan and hydrochlorothiazide tablets, call your doctor or Poison Control Center, or go to the nearest hospital emergency room.
What should I avoid while taking valsartan and hydrochlorothiazide tablets?
You should not take valsartan and hydrochlorothiazide tablets during pregnancy. See "What is the most important information I should know about valsartan and hydrochlorothiazide tablets?"
What are the possible side effects of valsartan and hydrochlorothiazide tablets?
Valsartan and hydrochlorothiazide tablets may cause serious side effects including:
• Harm to an unborn baby causing injury and even death. See "What is the most important information I should know about valsartan and hydrochlorothiazide tablets?"
• Low blood pressure (hypotension). Low blood pressure is most likely to happen if you:
- take water pills
- are on a low salt diet
- get dialysis treatments
- have heart problems
- get sick with vomiting or diarrhea
- drink alcohol
Lie down if you feel faint or dizzy. Call your doctor right away.
• Allergic reactions. People with and without allergy problems or asthma who take valsartan and hydrochlorothiazide tablets may get allergic reactions.
• Worsening of Lupus. Hydrochlorothiazide, one of the medicines in valsartan and hydrochlorothiazide tablets may cause Lupus to become active or worse.
• Fluid and electrolyte (salt) problems. Tell your doctor about any of the following signs and symptoms of fluid and electrolyte problems:
- dry mouth
- lack of energy (lethargic)
- muscle pain or cramps
- muscle fatigue
- very low urine output
- fast heartbeat
- nausea and vomiting
• Kidney problems. Kidney problems may become worse in people that already have kidney disease. Some people will have changes on blood tests for kidney function and may need a lower dose of valsartan and hydrochlorothiazide tablets. Call your doctor if you get swelling in your feet, ankles, or hands, or unexplained weight gain. If you have heart failure, your doctor should check your kidney function before prescribing valsartan and hydrochlorothiazide tablets.
• Skin rash. Call your doctor right away if you have an unusual skin rash.
• Eye Problems. One of the medicines in valsartan and hydrochlorothiazide tablets can cause eye problems that may lead to vision loss. Symptoms of eye problems can happen within hours to weeks of starting valsartan and hydrochlorothiazide tablets. Tell your doctor right away if you have:
- drowsiness decrease in vision
- drowsiness eye pain
Other side effects were generally mild and brief. They generally have not caused patients to stop taking valsartan and hydrochlorothiazide tablets.
Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of valsartan and hydrochlorothiazide tablets. For a complete list, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.You may also report side effect to Lupin Pharmaceuticals, Inc. at 1-800-399-2561.
How do I store valsartan and hydrochlorothiazide tablets?
- Store valsartan and hydrochlorothiazide tablets at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].
- Keep valsartan and hydrochlorothiazide tablets in a closed container in a dry place.
Keep valsartan and hydrochlorothiazide tablets and all medicines out of the reach of children.
General information about valsartan and hydrochlorothiazide tablets
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use valsartan and hydrochlorothiazide tablets for a condition for which it was not prescribed. Do not give valsartan and hydrochlorothiazide tablets to other people, even if they have the same symptoms you have. It may harm them.
This leaflet summarizes the most important information about valsartan and hydrochlorothiazide tablets. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about valsartan and hydrochlorothiazide tablets that is written for health professionals. For more information about valsartan and hydrochlorothiazide tablets, go to www.lupinpharmaceuticals.com or call 1-800-399-2561.
What are the ingredients in valsartan and hydrochlorothiazide tablets?
Active ingredients: Valsartan and hydrochlorothiazide
Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose, pregelatinized starch, polyethylene glycol, titanium dioxide and additional colorants as below.
80 mg/12.5 mg: iron oxide red and iron oxide yellow
160 mg/12.5 mg: iron oxide red
160 mg /25 mg: iron oxide black, iron oxide red and iron oxide yellow
320 mg /12.5 mg: iron oxide black and iron oxide red
320 mg /25 mg: iron oxide yellow
What is high blood pressure (hypertension)?
Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too much. Valsartan and hydrochlorothiazide tablets can help your blood vessels relax and reduce the amount of water in your body so your blood pressure is lower. Medicines that lower blood pressure lower your risk of having a stroke or heart attack.
High blood pressure makes the heart work harder to pump blood throughout the body and causes damage to the blood vessels. If high blood pressure is not treated, it can lead to stroke, heart attack, heart failure, kidney failure, and vision problems.
The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.
Lupin Pharmaceuticals, Inc.
Baltimore, Maryland 21202
Goa - 403 722
January 2013 ID:# 229953