mph Bangladesh


Valsartan and Hydrochlorothiazide

(val sar' tan) and (hye droe klor oh thye' a zide)

PCI  - Contraindicated in pregnancy

LCI  - Contraindicated in lactation

Molecule Info

| See TERMINOLOGY & ABBREVIATIONS |  
WARNINGs

WARNING: FETAL TOXICITY
ï‚· When pregnancy is detected, discontinue Valsartan-Hydrochlorothiazide (HCTZ) as soon as possible
ï‚· Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus

Indication(s) & Dosage

Valsartan and Hydrochlorothiazide 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-HCTZ.
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 1 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 have also 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.

Add-On Therapy
Valsartan-HCTZ may be used in patients whose blood pressure is not adequately controlled on monotherapy.
Replacement Therapy
Valsartan-HCTZ may be substituted for the titrated components.
Initial Therapy
Valsartan-HCTZ may be used as initial therapy in patients who are likely to need multiple drugs to achieve blood pressure goals.
The choice of Valsartan-HCTZ 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.

HYPERTENSION Adult:Per combination tablet contains valsartan/hydrochlorothiazide: 80/12. 5mg; 160/12. 5mg; 160/25mg; 320/12. 5mg; 320/25mg: Initially, 80/12. 5mg once daily, titrate dose gradually according to response, up to 320/25mg. Not recommended in severe renal failure.

Overdosage

Symptoms: Hypotension, tachycardia, bradycardia, circulatory collapse, electrolyte abnormalities . Management: Treatment is symptomatic and supportive. Effectiveness of haemodialysis is unknown.

Contraindications

Valsartan and Hydrochlorothiazide 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. Do not coadminister aliskiren with Valsartan-HCTZ in patients with diabetes.

Precautions

Hypotension in Volume- and/or Salt-Depleted Patients
Excessive reduction of blood pressure was rarely seen (0.7%) in patients with uncomplicated hypertension treated with Valsartan-HCTZ 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 Valsartan-HCTZ, 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.
Impaired Renal Function
Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at
particular risk of developing acute renal failure on Valsartan-HCTZ. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Valsartan-HCTZ.

Hypersensitivity Reaction
Hydrochlorothiazide: Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.
Systemic Lupus Erythematosus
Hydrochlorothiazide: Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
Lithium Interaction
Hydrochlorothiazide: Lithium generally should not be given with thiazides.
Potassium Abnormalities
Valsartan – Hydrochlorothiazide: In the controlled trials of various doses of Valsartan-HCTZ the incidence of hypertensive patients who developed hypokalemia (serum potassium <3.5 mEq/L) was 3.0%; the incidence of hyperkalemia (serum potassium >5.7 mEq/L) was 0.4%. Hydrochlorothiazide can cause hypokalemia and hyponatremia. Hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Monitor serum electrolytes periodically.
If hypokalemia is accompanied by clinical signs (e.g. muscular weakness, paresis, or ECG alterations), Valsartan-HCTZ should be discontinued. Correction of hypokalemia and any coexisting hypomagnesemia is recommended prior to the initiation of thiazides.
Some patients with heart failure have developed increases in potassium with Diovan therapy. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or Diovan may be required.
Acute Myopia and Secondary Angle-Closure Glaucoma
Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The
primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angleclosure glaucoma may include a history of sulfonamide or penicillin allergy.
Metabolic Disturbances
Hydrochlorothiazide
Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides. Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients. Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Monitor calcium levels in patients with hypercalcemia receiving Valsartan-HCTZ.

Adverse Drug Reaction(s)

Headache, asthenia, fatigue, dizziness, somnolence, insomnia, orthostatic hypotension, paraesthesia, nasopharyngitis, tachycardia, palpitations, tinnitus, vertigo, dyspepsia, diarrhoea, flatulence, dry mouth, nausea, vomiting, abdominal pain, peripheral oedema, pyrexia, increased BUN, elevated LFT, anxiety, erectile dysfunction, glucose intolerance, increased serum cholesterol, triglycerides, uric acid. Electrolyte imbalances e. g. hypomagnesaemia, hypercalcaemia, hyponatraemia, hypochloraemic alkalosis.

Drug Interactions

Increased antihypertensive effect with other antihypertensive drugs. Monitor potassium frequently if used with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or drugs that may affect potassium levels . Reduced antihypertensive effect of valsartan and increased risk of renal impairment with NSAIDs. May reduce renal clearance of cytotoxic drugs . Increased serum calcium with vitamin D or calcium salts. Potentially Fatal: Increased lithium levels with valsartan, monitor lithium levels. Increased risk of cardiac arrhythmia with dofetilide, avoid use.

Lab Interference

Thiazides may decrease serum protein bound iodine levels.

Pregnancy Category (FDA)

Pregnancy: 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-HCTZ as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not
distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Valsartan-HCTZ, unless it is considered
lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Valsartan-HCTZ for hypotension, oliguria, and hyperkalemia.
Hydrochlorothiazide
Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. Hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion. It accumulates in the amniotic fluid, with reported concentrations up to 19 times higher than in umbilical vein plasma. Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. Since they do not prevent or alter the course of EPH (Edema, Proteinuria, Hypertension) gestosis (pre-eclampsia), these drugs should not be used to treat hypertension in pregnant women. The use of hydrochlorothiazide for other indications (e.g., heart disease) in pregnancy should be avoided.

Nursing Mothers
It is not known whether valsartan is excreted in human milk. Valsartan was excreted into the milk of lactating rats; however, animal breast milk drug levels may not accurately reflect human breast milk levels. Hydrochlorothiazide is excreted in human breast milk. Because many drugs are excreted into human milk and because of the potential for adverse reactions in nursing infants from Valsartan-HCTZ, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use
Safety and effectiveness of Valsartan-HCTZ in pediatric patients have not been established. 

Neonates with a history of in utero exposure to Valsartan-HCTZ:
If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.

Geriatric Use
In the controlled clinical trials of Valsartan-HCTZ, 764 (17.5%) patients treated with valsartan-hydrochlorothiazide were >65 years and 118 (2.7%) were >75 years. No overall difference in the efficacy or safety of valsartan-hydrochlorothiazide was observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment
Safety and effectiveness of Valsartan-HCTZ in patients with severe renal impairment (CrCl ≤ 30 mL/min) have not been established. No dose adjustment is required in patients with mild (CrCl 60-90 mL/min) or moderate (CrCl 30-60) renal impairment.

Hepatic Impairment
Valsartan
No dose adjustment is necessary for patients with mild-to-moderate liver disease. No dosing recommendations can be provided for patients with severe liver disease.

Hydrochlorothiazide
Minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.

Storage

Store between 15-30°C.

Pharmacology

Mechanism of Action
Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Valsartan
blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis. There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Valsartan has much greater affinity (about 20000-fold) for the AT1 receptor than for the AT2 receptor. The
primary metabolite of valsartan is essentially inactive with an affinity for the AT1 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.

Valsartan is an angiotensin II receptor antagonist and reduces blood pressure by blocking the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Hydrochlorothiazide is a thiazide diuretic. Onset: Hyopotensive effect of valsartan: 2hr. Diuresis effect of hydrochlorothiazide: 2 hr. Duration: Hypotensive effect of valsartan: 24 hr. Diuresis effect of hydrochlorothiazide: 6-12 hr. Absorption: Valsartan: Rapidly absorbed, bioavailability 23%, peak plasma concentration occur 2-4 hr. Hydrochlorothiazide: Rapidly absorbed, bioavailability: 65-70%. Distribution: Valsartan: Protein binding 94-97%, mainly to serum albumin, volume of distribution: 17 L. Hydrochlorothiazide: Preferentially bound to red blood cells, crosses placenta and excreted into breast milk. Metabolism: Valsartan: Not significantly metabolised. Excretion: Valsartan: Excreted mainly as unchanged drug in faeces  and urine, terminal half life 5-9 hr. Hydrochlorthiazide: Excreted mainly unchanged in urine, plasma half life 5-15 hr.

ATC Classification

C09CA03 - valsartan; Belongs to the class of angiotensin II antagonists. Used in the treatment of cardiovascular disease. C03AA03 - hydrochlorothiazide; Belongs to the class of low-ceiling thiazide diuretics. Used to promote excretion of urine.

Brand/Product Info


Total Products : 10          
Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price
CARDIVAL Plus-160 Drug International Ltd Valsartan INN USP 1600mg+ Hydrochlorothiazide BP 12.5mg Tablet (film-coated) 10's: 160.00 MRP
CARDIVAL Plus-80 Drug International Ltd Valsartan INN USP 80mg+ Hydrochlorothiazide BP 12.5mg Tablet (film-coated) 20's: 160.00 MRP
CO-DIOVAN 160/12.5 Novartis (Bangladesh) Ltd. Valsartan INN USP 160mg + Hydrochlorothiazide 12.5mg Film Coated Tablet 28's: MRP 1848.00
CO-DIOVAN 80/12.5 Novartis (Bangladesh) Ltd. Valsartan INN USP 80mg + Hydrochlorothiazide 12.5mg Film Coated Tablet 28's: MRP 1344.00
DISYS PLUS Healthcare Pharmacuticals Ltd. Valsartan 80mg + Hydrochlorothiazide 12.5mg Tablet 30's MRP 300 Tk
REOVAN H R A K Pharmaceuticals Pvt. Ltd. Valsartan INN USP 80mg+ Hydrochlorothiazide BP 12.5mg Tablet (film-coated) 30's: 360.00 MRP
Valsartil 160 Plus Incepta Pharmaceuticals Limited Valsartan 160mg + Hydrochlorothiazide 25mg Tablet 10x3's:MRP 480 Tk
Valsartil 80 Plus Incepta Pharmaceuticals Limited Valsartan 80mg + Hydrochlorothiazide 12.5mg Tablet 10x3's:MRP 270 Tk
VALZIDE 160/12.5 Renata Limited Valsartan INN USP 1600mg+ Hydrochlorothiazide BP 12.5mg Tablet (film-coated) 20's: 321.20 MRP
VALZIDE 80/12.5 Renata Limited Valsartan INN USP 80mg+ Hydrochlorothiazide BP 12.5mg Tablet (film-coated) 20's: 180.00 MRP
 | See Brand Manufacturer's Prescribing Information | | Back to top |
Simple Breath Test Might Diagnose Heart Failure An experimental breath test, designed to quickly identify patients suffering from heart failure simply by analyzing the contents of a...
Osteoporosis drug stops Breast cancer growth   News & Events News & Events     HIGHLIGHTS Osteoporosis drug stops growth of breast cancer...
Generic drug safety info loophole FDA plans to close generic drug safety info loophole The US Food and Drug Administration has announced plans to speed up the dissemination of...
Large trials unpublished   News & Events News & Events   HIGHLIGHTS Almost 1 in 3 of large clinical trials unpublished after...
TB activists boo Indian minister News & Events News & Events   HIGHLIGHTS TB activists at world conference boo Indian minister off...
Key bone marrow protein identified News & Events News & Events   HIGHLIGHTS Key bone marrow protein identified as potential new leukemia...