Diovan Hct Information
Diovan hct (Valsartan/ hydrochlorothiazide) Indications And Usage
Diovan HCT (valsartan and hydrochlorothiazide, USP) is indicated for the treatment of hypertension.
Diovan HCT may be used in patients whose blood pressure is not adequately controlled on monotherapy.
Diovan hct (Valsartan/ hydrochlorothiazide) Dosage And Administration
The side effects of valsartan are generally rare and appear independent of dose. Those of hydrochlorothiazide are a mixture of dose-dependent (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter [].
Dose once-daily. Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.
Diovan HCT may be administered with or without food.
Diovan HCT may be administered with other antihypertensive agents.
A patient whose blood pressure is not adequately controlled with valsartan (or another ARB) alone or hydrochlorothiazide alone may be switched to combination therapy with Diovan HCT.
A patient who experiences dose-limiting adverse reactions on either component alone may be switched to Diovan hct (Valsartan/ hydrochlorothiazide) containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions. The clinical response to Diovan hct (Valsartan/ hydrochlorothiazide) should be subsequently evaluated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dose may be titrated up to a maximum of 320/25 mg.
The usual starting dose is Diovan HCT 160/12.5 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 320/25 mg tablet once daily as needed to control blood pressure [ (14.2)]. Diovan HCT is not recommended as initial therapy in patients with intravascular volume depletion [ (5.2)].
Diovan hct (Valsartan/ hydrochlorothiazide) Dosage Forms And Strengths
80/12.5 mg tablets, imprinted CG/HGH (Side 1/Side 2)
160/12.5 mg tablets, imprinted CG/HHH
160/25 mg tablets, imprinted NVR/HXH
320/12.5 mg tablets, imprinted NVR/HIL
320/25 mg tablets, imprinted NVR/CTI
Diovan hct (Valsartan/ hydrochlorothiazide) Contraindications
Diovan HCT (valsartan and hydrochlorothiazide, USP) is 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.
Diovan hct (Valsartan/ hydrochlorothiazide) Warnings And Precautions
Diovan HCT can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus
Drugs that act on the renin-angiotensin system can cause fetal and neonatal morbidity and mortality when used in pregnancy. In several dozen published cases, ACE inhibitor use during the second and third trimesters of pregnancy was associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death [].
Intrauterine exposure to thiazide diuretics is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.
Excessive reduction of blood pressure was rarely seen (0.7%) in patients with uncomplicated hypertension treated with Diovan HCT in controlled trials. In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur. This condition should be corrected prior to administration of Diovan HCT, or the treatment should start under close medical supervision.
If hypotension occurs, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
Hydrochlorothiazide
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Hydrochlorothiazide
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Hydrochlorothiazide
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see
Drug Interactions
(7)
In controlled clinical trials of Diovan HCT (valsartan and hydrochlorothiazide, USP), the average change in serum potassium was near zero in subjects who received Diovan HCT 160/12.5 mg, 320/12.5 mg or 320/25 mg, but the average subject who received Diovan HCT 80/12.5 mg, 80/25 mg or 160/25 mg experienced a mild reduction in serum potassium.
In clinical trials, the opposite effects of valsartan (80, 160 or 320 mg) and hydrochlorothiazide (12.5 mg) on serum potassium approximately balanced each other in many patients. In other patients, one or the other effect may be dominant. Periodic determinations of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.
Hypokalemia may develop, especially with brisk diuresis, when severe cirrhosis is present, or after prolonged therapy.
Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).
Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.
Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
In diabetic patients, dosage adjustments of insulin or oral hypoglycemic agents may be required. Hyperglycemia may occur with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide therapy.
The antihypertensive effects of the drug may be enhanced in the postsympathectomy patient.
If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy.
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
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In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen have been reported. In a 4-day trial of valsartan in 12 patients with unilateral renal artery stenosis, no significant increases in serum creatinine or blood urea nitrogen were observed. There has been no long-term use of valsartan in patients with unilateral or bilateral renal artery stenosis, but an effect similar to that seen with ACE inhibitors should be anticipated.
Diovan hct (Valsartan/ hydrochlorothiazide) Adverse Reactions
Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Hypertension
Diovan HCT (valsartan and hydrochlorothiazide, USP) has been evaluated for safety in more than 5,700 patients, including over 990 treated for over 6 months, and over 370 for over 1 year. Adverse experiences have generally been mild and transient in nature and have only infrequently required discontinuation of therapy. The overall incidence of adverse reactions with Diovan HCT was comparable to placebo.
The overall frequency of adverse reactions was neither dose-related nor related to gender, age, or race. In controlled clinical trials, discontinuation of therapy due to side effects was required in 2.3% of valsartan-hydrochlorothiazide patients and 3.1% of placebo patients. The most common reasons for discontinuation of therapy with Diovan HCT were headache and dizziness.
The only adverse reaction that occurred in controlled clinical trials in at least 2% of patients treated with Diovan HCT and at a higher incidence in valsartan-hydrochlorothiazide (n=4372) than placebo (n=262) patients was nasopharyngitis (2.4% vs. 1.9%).
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 Diovan HCT.
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:
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.
Other reported reactions seen less frequently in clinical trials included chest pain, syncope, anorexia, vomiting, and angioedema.
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 Diovan HCT as initial therapy and in patients treated with valsartan as initial therapy. Comparing the groups treated with Diovan HCT (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 Diovan HCT and 0% of patients receiving valsartan. There were no reported cases of syncope in either treatment group. Laboratory changes with Diovan HCT as initial therapy in patients with severe hypertension were similar to those reported with Diovan HCT in patients with less severe hypertension [ ].
The following additional adverse reactions have been reported in valsartan or valsartan/hydrochlorothiazide postmarketing experience:
Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.
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.
Diovan hct (Valsartan/ hydrochlorothiazide) Drug Interactions
Coadministration of valsartan and warfarin did not change the pharmacokinetics of valsartan or the time-course of the anticoagulant properties of warfarin.
Diovan hct (Valsartan/ hydrochlorothiazide) Use In Specific Populations
Diovan HCT, like other drugs that act on the renin-angiotensin system, can cause fetal and neonatal morbidity and death when used during the second or third trimester of pregnancy. Diovan HCT can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Angiotensin II receptor antagonists, like valsartan, and angiotensin-converting enzyme (ACE) inhibitors exert similar effects on the renin-angiotensin system. In several dozen published cases, ACE inhibitor use during the second and third trimesters of pregnancy was associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios was also reported, presumably from decreased fetal renal function. In this setting, oligohydramnios was associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus were also reported, although it is not clear whether these occurrences were due to exposure to the drug. In a retrospective study, first trimester use of ACE inhibitors, a specific class of drugs acting on the renin-angiotensin system, was associated with a potential risk of birth defects.
When pregnancy occurs in a patient using Diovan HCT, the physician should discontinue Diovan HCT treatment as soon as possible. The physician should inform the patient about potential risks to the fetus based on the time of gestational exposure to Diovan HCT (first trimester only or later). If exposure occurs beyond the first trimester, an ultrasound examination should be done.
In rare cases when another antihypertensive agent can not be used to treat the pregnant patient, serial ultrasound examinations should be performed to assess the intraamniotic environment. Routine fetal testing with non-stress tests, biophysical profiles, and/or contraction stress tests may be appropriate based on gestational age and standards of care in the community. If oligohydramnios occurs in these situations, individualized decisions about continuing or discontinuing Diovan HCT treatment and about pregnancy management should be made by the patient, her physician, and experts in the management of high-risk pregnancy. Patients and physicians should be aware that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Infants with histories of exposure to Diovan HCT should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, these infants may require blood pressure and renal perfusion support. Exchange transfusion or dialysis may be required to reverse hypotension and/or support decreased renal function.
Healthcare professionals who prescribe drugs acting directly on the renin-angiotensin system should counsel women of childbearing potential about the risks of these agents during pregnancy. [ ]
Diovan hct (Valsartan/ hydrochlorothiazide) Overdosage
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/m basis. (Calculations assume an oral dose of 320 mg/day valsartan in combination with 25 mg/day hydrochlorothiazide and a 60-kg patient.)
Diovan hct (Valsartan/ hydrochlorothiazide) Description
Diovan HCT (valsartan and hydrochlorothiazide, USP) is a combination of valsartan, an orally active, specific angiotensin II receptor blocker (ARB) acting on the AT receptor subtype, and hydrochlorothiazide, a diuretic.
Valsartan, a nonpeptide molecule, is chemically described as -(1-oxopentyl)--[[2′-(1-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-L-Valine. Its empirical formula is CHNO, 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 -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-2-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.
Hydrochlorothiazide is a thiazide diuretic. Its empirical formula is CHClNOS, its molecular weight is 297.73, and its structural formula is
Diovan HCT tablets are formulated for oral administration to contain valsartan and hydrochlorothiazide, USP 80/12.5 mg, 160/12.5 mg, 160/25 mg, 320/12.5 mg and 320/25 mg. The inactive ingredients of the tablets are colloidal silicon dioxide, crospovidone, hydroxypropyl methylcellulose, iron oxides, magnesium stearate, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide.
Diovan hct (Valsartan/ hydrochlorothiazide) Clinical Pharmacology
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 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 receptor found in many tissues, but AT is not known to be associated with cardiovascular homeostasis. Valsartan has much greater affinity (about 20,000-fold) for the AT receptor than for the AT receptor. The primary metabolite of valsartan is essentially inactive with an affinity for the AT receptor about one 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.
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.
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.
Hydrochlorothiazide
In a study of patients with impaired renal function (mean creatinine clearance of 19 mL/min), the half-life of hydrochlorothiazide elimination was lengthened to 21 hours.
Distribution
Metabolism
Excretion
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).
Hydrochlorothiazide
Diovan hct (Valsartan/ hydrochlorothiazide) Nonclinical Toxicology
2
Mutagenicity assays did not reveal any valsartan-related effects at either the gene or chromosome level. These assays included bacterial mutagenicity tests with (Ames) and ; 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 about 6 times the maximum recommended human dose on a mg/m basis. (Calculations assume an oral dose of 320 mg/day and a 60-kg patient.)
Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella Typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 1300 mcgm/mL, and in the Aspergillus Nidulans non-disjunction assay at an unspecified concentration.
Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to mating and throughout gestation. These doses of hydrochlorothiazide in mice and rats represent 19 and 1.5 times, respectively, the maximum recommended human dose on a mg/m basis. (Calculations assume an oral dose of 25 mg/day and a 60-kg patient.)
2
Fetotoxicity was observed in association with maternal toxicity in rats and rabbits at valsartan doses of ≥200 and 10 mg/kg/day, respectively, in combination with hydrochlorothiazide doses of ≥63 and 3 mg/kg/day. Fetotoxicity in rats was considered to be related to decreased fetal weights and included fetal variations of sternebrae, vertebrae, ribs and/or renal papillae. Fetotoxicity in rabbits included increased numbers of late resorptions with resultant increases in total resorptions, postimplantation losses and decreased number of live fetuses. The no observed adverse effect doses in mice, rats and rabbits for valsartan were 600, 100 and 3 mg/kg/day, respectively, in combination with hydrochlorothiazide doses of 188, 31 and 1 mg/kg/day. These no adverse effect doses in mice, rats and rabbits, respectively, represent 9, 3 and 0.18 times the MRHD of valsartan and 38, 13 and 0.5 times the MRHD of hydrochlorothiazide on a mg/m basis. (Calculations assume an oral dose of 320 mg/day valsartan in combination with 25 mg/day hydrochlorothiazide and a 60-kg patient.)
2
2
Diovan hct (Valsartan/ hydrochlorothiazide) Clinical Studies
Three other controlled trials investigated the addition of hydrochlorothiazide to patients who did not respond adequately to valsartan 80 mg to valsartan 320 mg, resulted in the additional lowering of systolic and diastolic blood pressure by approximately 4-12/2-5 mmHg.
The maximal antihypertensive effect was attained 4 weeks after the initiation of therapy, the first time point at which blood pressure was measured in these trials.
In long-term follow-up studies (without placebo control) the effect of the combination of valsartan and hydrochlorothiazide appeared to be maintained for up to two years. The antihypertensive effect is independent of age or gender. The overall response to the combination was similar for Black and non-Black patients.
There was essentially no change in heart rate in patients treated with the combination of valsartan and hydrochlorothiazide in controlled trials.
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 Diovan 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.
The safety and efficacy of Diovan HCT as initial therapy for patients with severe hypertension (defined as a sitting diastolic blood pressure ≥110 mmHg and systolic blood pressure ≥140 mmHg off all antihypertensive therapy) was studied in a 6-week multicenter, randomized, double-blind study. Patients were randomized to either Diovan HCT (valsartan and hydrochlorothiazide 160/12.5 mg once daily) or to valsartan (160 mg once daily) and followed for blood pressure response. Patients were force-titrated at 2-week intervals. Patients on combination therapy were subsequently titrated to 160/25 mg followed by 320/25 mg valsartan/hydrochlorothiazide. Patients on monotherapy were subsequently titrated to 320 mg valsartan followed by a titration to 320 mg valsartan to maintain the blind.
The study randomized 608 patients, including 261 (43%) females, 147 (24%) Blacks, and 75 (12%) ≥65 years of age. The mean blood pressure at baseline for the total population was 168/112 mmHg. The mean age was 52 years. After 4 weeks of therapy, reductions in systolic and diastolic blood pressure were 9/5 mmHg greater in the group treated with Diovan HCT compared to valsartan. Similar trends were seen when the patients were grouped according to gender, race or age.
Diovan hct (Valsartan/ hydrochlorothiazide) How Supplied/storage And Handling
Diovan HCT (valsartan and hydrochlorothiazide, USP) is available as non-scored tablets containing valsartan/hydrochlorothiazide 80/12.5 mg, 160/12.5 mg, 160/25 mg, 320/12.5 mg and 320/25 mg. Strengths are available as follows.
Bottles of 90 NDC 0078-0314-34
Bottles of 14,000 NDC 0078-0314-33
Unit Dose (blister pack) NDC 0078-0314-06
Box of 100 (strips of 10)
Bottles of 90 NDC 0078-0315-34
Bottles of 7,000 NDC 0078-0315-17
Unit Dose (blister pack) NDC 0078-0315-06
Box of 100 (strips of 10)
Unit Dose (blister pack of 30) NDC 0078-0315-15
Bottles of 90 NDC 0078-0383-34
Bottles of 7,000 NDC 0078-0383-17
Unit Dose (blister pack) NDC 0078-0383-06
Box of 100 (strips of 10)
Unit Dose (blister pack of 30) NDC 0078-0383-15
Bottles of 90 NDC 0078-0471-34
Bottles of 3,500 NDC 0078-0471-11
Unit Dose (blister pack) NDC 0078-0471-06
Box of 100 (strips of 10)
Unit Dose (blister pack of 30) NDC 0078-0471-15
Bottles of 90 NDC 0078-0472-34
Bottles of 3,500 NDC 0078-0472-11
Unit Dose (blister pack) NDC 0078-0472-06
Box of 100 (strips of 10)
Unit Dose (blister pack of 30) NDC 0078-0472-15
Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF) [see USP Controlled Room Temperature].
Protect from moisture.
Dispense in tight container (USP).
Diovan hct (Valsartan/ hydrochlorothiazide) Patient Counseling Information
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.
Diovan hct (Valsartan/ hydrochlorothiazide)
Diovan hct (Valsartan/ hydrochlorothiazide)
Diovan hct (Valsartan/ hydrochlorothiazide) Principal Display Panel
(valsartan and hydrochlorothiazide, USP)
Each tablet contains 160 mg valsartan and 12.5 mg of hydrochlorothiazide
Diovan hct (Valsartan/ hydrochlorothiazide)
Diovan hct (Valsartan/ hydrochlorothiazide)
Diovan hct (Valsartan/ hydrochlorothiazide) Principal Display Panel
(valsartan and hydrochlorothiazide, USP)
Each tablet contains 160 mg valsartan and 25 mg of hydrochlorothiazide
Diovan hct (Valsartan/ hydrochlorothiazide) Principal Display Panel
(valsartan and hydrochlorothiazide, USP)
Each tablet contains 320 mg valsartan and 12.5 mg of hydrochlorothiazide
Diovan hct (Valsartan/ hydrochlorothiazide)
Diovan hct (Valsartan/ hydrochlorothiazide)
Diovan hct (Valsartan/ hydrochlorothiazide) Principal Display Panel
(valsartan and hydrochlorothiazide, USP)
Each tablet contains 320 mg valsartan and 25 mg of hydrochlorothiazide
