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Valsartan / Hydrochlorothiazide

Pronunciation

Pronunciation: val-SAR-tan/HYE-droe-KLOR-oh-THYE-a-zide
Class: Antihypertensive combination

Trade Names

Diovan HCT
- Tablets, oral valsartan 80 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral valsartan 160 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral valsartan 160 mg/hydrochlorothiazide 25 mg
- Tablets, oral valsartan 320 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral valsartan 320 mg/hydrochlorothiazide 25 mg

Pharmacology

Valsartan

Antagonizes the effect of angiotensin II (vasoconstriction and aldosterone secretion) by blocking the angiotensin II receptor (AT 1 receptor subtype) in vascular smooth muscle and the adrenal gland, producing decreased BP.

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Hydrochlorothiazide

Increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium.

Indications and Usage

For the treatment of hypertension.

Contraindications

Hypersensitivity to any component of this product or to sulfonamide-derived drugs; anuria.

Dosage and Administration

Adults

PO Dosage must be individualized. The usual starting dosage is 160 mg/12.5 mg once daily. Increase after 1 to 2 wk to a max dosage of 320 mg/25 mg once daily.

Renal Function Impairment (CrCl 30 mL/min or less)

Use is not recommended.

Hepatic Function Impairment

Start with a low dose and titrate slowly.

General Advice

  • May be taken with or without food.
  • May be administered with other antihypertensives.
  • The combination may be substituted for the titrated components.
  • Patients whose BP is not controlled on valsartan or hydrochlorothiazide alone may be switched to combination therapy with valsartan/hydrochlorothiazide.

Storage/Stability

Store at 59° to 86°F. Protect from moisture.

Drug Interactions

No drug interaction studies have been conducted between valsartan/hydrochlorothiazide and other drugs. The following interactions are based on drug interactions involving each component of the valsartan/hydrochlorothiazide combination.

ACE inhibitors (eg, captopril, ramipril)

Concurrent use may be associated with an increased risk of renal dysfunction and hyperkalemia. Consider monotherapy. Coadministration with ramipril is not recommended.

Alcohol, barbiturates, narcotics

Potentiation of orthostatic hypotension may occur.

Aliskiren

Renal excretion of potassium may be decreased, resulting in hyperkalemia. Coadministration is contraindicated in diabetic patients because of an increased risk of renal impairment, hypotension, and hyperkalemia. Avoid coadministration in patients with moderate or severe renal impairment (glomerular filtration rate less than 60 mL/min).

Antihypertensives (eg, propranolol)

Additive or potentiation of hypotensive effects may occur.

Antineoplastic agents (eg, cyclophosphamide)

Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. If coadministration cannot be avoided, use with caution.

Carbamazepine

Coadministration of carbamazepine with hydrochlorothiazide may lead to symptomatic hyponatremia.

Cholestyramine, colestipol resins

Hydrochlorothiazide absorption may be impaired. Single doses of either cholestyramine or colestipol resins bind hydrochlorothiazide, reducing GI absorption up to 85% and 43%, respectively. Separate the administration times by at least 4 hours. Adjust diuretic dose as needed.

COX-2 inhibitors (eg, celecoxib), NSAIDs (eg, ibuprofen, indomethacin, ketorolac [nasal])

The diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide and the antihypertensive effects of valsartan may be reduced. In addition, concomitant use may further deteriorate renal function, especially in volume-depleted, renally impaired, or elderly patients. Monitor BP and renal function. If an interaction is suspected, it may be necessary to discontinue the NSAID.

Cyclosporine, rifampin, ritonavir

Coadministration of inhibitors of the organic anion–transporting polypeptide (OATP1B1) uptake transporter (rifampin, cyclosporine) or multidrug resistance protein 2 efflux transporter (ritonavir) may increase the systemic exposure to valsartan. Concomitant treatment with cyclosporine may increase the risk of hyperuricemia and gout-type complications.

Diazoxide

The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood glucose, and serum uric acid.

Digoxin

Hydrochlorothiazide-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Closely monitor plasma concentrations of potassium and magnesium, and monitor patients for signs of digoxin toxicity.

Dofetilide

Plasma concentrations of dofetilide may be increased; prolongation of the QT interval may occur, increasing the risk of torsades de pointes. Coadministration is contraindicated.

Insulin

Insulin requirements may increase or decrease, or remain unchanged. Monitor blood glucose and adjust the insulin dose as needed.

Lithium

Lithium clearance may be decreased, increasing lithium concentrations and the risk of lithium toxicity. Avoid coadministration. If coadministration cannot be avoided, closely monitor serum lithium levels and adjust the dose of lithium as needed.

Loop diuretics (eg, furosemide)

Loop diuretics and hydrochlorothiazide have synergistic effects that may result in profound diuresis and electrolyte abnormalities. Monitor fluid status and electrolytes.

Nondepolarizing muscle relaxants (eg, tubocurarine)

A possible increase in responsiveness to the muscle relaxant due to diuretic-induced hypokalemia may occur. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.

Potassium preparations (eg, potassium-sparing diuretics [eg, amiloride, spironolactone], potassium supplements, salt substitutes containing potassium)

Serum potassium concentrations may be increased, decreased, or unchanged. Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur. Closely monitor serum potassium concentrations. Adjust treatment as needed.

Sulfonylureas (eg, glyburide)

Hydrochlorothiazide may increase fasting blood glucose and decrease the hypoglycemic action of sulfonylureas. Closely monitor blood glucose and adjust therapy as needed.

Tretinoin

The risk of phototoxicity may be increased if these agents are coadministered. Avoid coadministration.

Trimethoprim

Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur, especially in elderly patients. Closely monitor serum potassium. Adjust therapy as needed.

Laboratory Test Interactions

Hydrochlorothiazide may decrease serum protein-bound iodine levels without signs of thyroid disturbance. Interrupt therapy for a few days before carrying out tests of parathyroid function.

Adverse Reactions

Cardiovascular

Hypotension (1%); palpitations, syncope, tachycardia; vasculitis (postmarketing).

CNS

Dizziness (6%); anxiety, asthenia, depression, fatigue, insomnia, paresthesia, postural dizziness, somnolence, vertigo.

Dermatologic

Hyperhidrosis, pruritus, rash, sunburn; alopecia (postmarketing).

GI

Abdominal pain, constipation, diarrhea, dry mouth, dyspepsia, flatulence, gastroenteritis, nausea, upper abdominal pain, vomiting.

Genitourinary

Dysuria, erectile dysfunction, pollakiuria, UTI; impaired renal function (postmarketing).

Hepatic

Elevated liver enzymes, hepatitis (postmarketing).

Lab Tests

Increased BUN (15%); increased creatinine (2%).

Metabolic

Dehydration, increased appetite, peripheral edema; hyperkalemia (postmarketing).

Musculoskeletal

Arthralgia, back pain, gout, muscle cramps, muscle weakness, myalgia, pain in extremity; rhabdomyolysis (postmarketing).

Respiratory

Nasopharyngitis (2%); acute bronchitis, bronchitis, cough, dyspnea, epistaxis, nasal congestion, pharyngitis, pharyngolaryngeal pain, sinus congestion, sinusitis, upper respiratory tract infection.

Special Senses

Abnormal vision, tinnitus.

Miscellaneous

Anaphylaxis, chest pain, decreased libido, influenza, pyrexia, viral infection; angioedema (postmarketing).

Precautions

Warnings

Fetal toxicity

When pregnancy is detected, discontinue therapy as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.


Monitor

Observe patients for clinical signs of fluid or electrolyte imbalance. Monitor BP and electrolytes at regular intervals.


Pregnancy

Category D . Can cause reduced fetal renal function and increased fetal and neonatal morbidity and death.

Lactation

Valsartan

Undetermined.

Hydrochlorothiazide

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Greater sensitivity of some older individuals cannot be ruled out.

Hypersensitivity

May occur in patients with or without history of allergy or bronchial asthma; cross-sensitivity with sulfonamides may also occur.

Renal Function

Decreases in renal function may occur in patients whose renal function is dependent on the renin-angiotensin system; patients with renal artery stenosis may experience acute renal failure. Use caution in treating patients whose renal function may depend on the activity of renin-angiotensin-aldosterone system (eg, severe CHF). In addition, hydrochlorothiazide may precipitate azotemia, and cumulative effects of the drug may develop in patients with renal function impairment.

Hepatic Function

Use with caution. Minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Fluid/Electrolyte imbalance

May occur. Electrolyte abnormalities may include hypercalcemia, hyperkalemia, hypochloremic alkalosis, hypokalemia, hypomagnesemia, and hyponatremia.

Hyperuricemia

May occur, or acute gout may be precipitated in thiazide therapy.

Hyperglycemia

May occur; latent diabetes may become manifest during thiazide therapy.

Hypotension/Volume-depleted patients

Symptomatic hypotension may occur after initiation of valsartan therapy in patients who are intravascularly volume depleted (eg, those treated with diuretics). Correct these conditions prior to administration of valsartan or start treatment under close medical supervision.

Lipids

Increases in cholesterol and triglycerides may occur.

Ophthalmic effects

Hydrochlorothiazide can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma.

Systemic lupus erythematosus

Exacerbation or activation may occur.

Overdosage

Symptoms

Bradycardia, circulatory collapse, dehydration, depressed consciousness, electrolyte depletion (eg, hypochloremia, hypokalemia, hyponatremia), hypotension, shock, tachycardia.

Patient Information

  • Advise patients to take once daily as prescribed without regard to meals, but to take with food if GI upset occurs.
  • Inform patients that drug controls but does not cure hypertension and to continue taking drug as prescribed even when BP is not elevated.
  • Caution patients not to change the dose or stop taking unless advised by health care provider.
  • Instruct patients to continue taking other BP medications as prescribed by health care provider.
  • Advise patients to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted.
  • Caution patients to avoid sudden position changes to prevent orthostatic hypotension.
  • Caution patients that light-headedness can occur, especially during the first few days of therapy, and to report it to their health care provider.
  • Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, resulting in light-headedness or fainting.
  • Instruct patients with diabetes to monitor blood glucose more frequently when drug is started or dose is changed, and to inform health care provider of significant changes in readings.
  • Caution patients to avoid unnecessary exposure to UV light (sunlight, tanning booths), and to use sunscreen and wear protective clothing when exposed to UV light to avoid a photosensitivity reaction.
  • Instruct patients to stop taking drug and immediately report any of the following symptoms to health care provider: fainting; swelling of the face, lips, eyelids, or tongue.
  • Advise patients not to use salt substitutes containing potassium or potassium supplements without consulting their prescribing health care provider.
  • Caution patients not to take any prescription or OTC medications or dietary supplements unless advised by their health care provider.
  • Advise female patients of childbearing age that use of valsartan/hydrochlorothiazide during pregnancy can cause serious problems in the fetus and infant. Inform women of childbearing age to report pregnancy to their health care provider as soon as possible.
  • Advise women not to breast-feed while taking this medication.

Copyright © 2009 Wolters Kluwer Health.

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