Valsartan and Hydrochlorothiazide

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Overview

What is Valsartan and Hydrochlorothiazide?

Valsartan and hydrochlorothiazide tablets are 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 USP 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

Valsartan and hydrochlorothiazide tablets, USP 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, red iron oxide, yellow iron oxide, black iron oxide, magnesium stearate, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide.

Drug product complies with USP Dissolution Test 2.

What does Valsartan and Hydrochlorothiazide look like?

What are the available doses of Valsartan and Hydrochlorothiazide?

Tablets (Valsartan/HCTZ mg): 80/12.5, 160/12.5, 160/25, 320/12.5, 320/25 (3)

What should I talk to my health care provider before I take Valsartan and Hydrochlorothiazide?

Nursing Mothers

How should I use Valsartan and Hydrochlorothiazide?

Valsartan and hydrochlorothiazide tablets are 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. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension e.g., patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Add-On Therapy

Valsartan and hydrochlorothiazide tablets may be used in patients whose blood pressure is not adequately controlled on monotherapy.

Replacement Therapy

Valsartan and hydrochlorothiazide tabletsmay be substituted for the titrated components.

Initial Therapy

Valsartan and hydrochlorothiazide tablets 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 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 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 320/25 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).

The usual starting dose is valsartan and hydrochlorothiazide tablets 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 tablet once daily as needed to control blood pressure Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.

What interacts with Valsartan and Hydrochlorothiazide?

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What are the warnings of Valsartan and Hydrochlorothiazide?

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What are the precautions of Valsartan and Hydrochlorothiazide?

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What are the side effects of Valsartan and Hydrochlorothiazide?

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What should I look out for while using Valsartan and Hydrochlorothiazide?

Valsartan and hydrochlorothiazide tablets 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

What might happen if I take too much Valsartan and Hydrochlorothiazide?

Valsartan – Hydrochlorothiazide:

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.)

Valsartan:

Hydrochlorothiazide:

How should I store and handle Valsartan and Hydrochlorothiazide?

Vials should be stored refrigerated at 2°-8°C (36°-46°F). Vials may be transferred to room temperature storage for a period not to exceed 2 months. Upon transfer, vial cartons must be marked by the dispensing pharmacist with a "DISCARD BY" date (2 months from the transfer date or the labeled expiration date, whichever comes first). Protect from light until administration.Vials should be stored refrigerated at 2°-8°C (36°-46°F). Vials may be transferred to room temperature storage for a period not to exceed 2 months. Upon transfer, vial cartons must be marked by the dispensing pharmacist with a "DISCARD BY" date (2 months from the transfer date or the labeled expiration date, whichever comes first). Protect from light until administration.Valsartan and Hydrochlorothiazide Tablets, USP are available as non-scored tablets containing valsartan/hydrochlorothiazide 320/25 mg. Strengths are available as follows.320 mg/25 mg TabletNDC 71205-015-30 bottle of 30 tabletsNDC 71205-015-60 bottle of 60 tabletsNDC 71205-015-90 bottle of 90 tablets Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF). [see USP Controlled Room Temperature].Protect from moisture.Dispense in tight container (USP).Valsartan and Hydrochlorothiazide Tablets, USP are available as non-scored tablets containing valsartan/hydrochlorothiazide 320/25 mg. Strengths are available as follows.320 mg/25 mg TabletNDC 71205-015-30 bottle of 30 tabletsNDC 71205-015-60 bottle of 60 tabletsNDC 71205-015-90 bottle of 90 tablets Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF). [see USP Controlled Room Temperature].Protect from moisture.Dispense in tight container (USP).Valsartan and Hydrochlorothiazide Tablets, USP are available as non-scored tablets containing valsartan/hydrochlorothiazide 320/25 mg. Strengths are available as follows.320 mg/25 mg TabletNDC 71205-015-30 bottle of 30 tabletsNDC 71205-015-60 bottle of 60 tabletsNDC 71205-015-90 bottle of 90 tablets Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF). [see USP Controlled Room Temperature].Protect from moisture.Dispense in tight container (USP).Valsartan and Hydrochlorothiazide Tablets, USP are available as non-scored tablets containing valsartan/hydrochlorothiazide 320/25 mg. Strengths are available as follows.320 mg/25 mg TabletNDC 71205-015-30 bottle of 30 tabletsNDC 71205-015-60 bottle of 60 tabletsNDC 71205-015-90 bottle of 90 tablets Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF). [see USP Controlled Room Temperature].Protect from moisture.Dispense in tight container (USP).Valsartan and Hydrochlorothiazide Tablets, USP are available as non-scored tablets containing valsartan/hydrochlorothiazide 320/25 mg. Strengths are available as follows.320 mg/25 mg TabletNDC 71205-015-30 bottle of 30 tabletsNDC 71205-015-60 bottle of 60 tabletsNDC 71205-015-90 bottle of 90 tablets Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF). [see USP Controlled Room Temperature].Protect from moisture.Dispense in tight container (USP).

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Clinical Information

Chemical Structure

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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.

Non-Clinical Toxicology

Valsartan and hydrochlorothiazide tablets 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

Specific drug interaction studies have not been conducted with ophthalmic ciprofloxacin. However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, enhance the effects of the oral anticoagulant, warfarin, and its derivatives and has been associated with transient elevations in serum creatinine in patients receiving cyclosporine concomitantly.

Pregnancy Category D

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue valsartan and hydrochlorothiazide tabletsas soon as possible .

Intrauterine exposure to thiazide diuretics is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

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Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

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