Valsartan And Hydrochlorothiazide

2 DOSAGE AND ADMINISTRATION Dose once daily. Titrate as needed to a maximum dose of 320 mg/25 mg. (2) May be used as add-on/switch therapy for patients not adequately controlled on any of the components (valsartan or HCTZ). (2) May be substituted for titrated components.

5 mg once daily. 2) ]. Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose. 2 Add-On Therapy 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 valsartan and hydrochlorothiazide tablets.

A patient who experiences dose-limiting adverse reactions on either component alone may be switched to valsartan and hydrochlorothiazide tablets containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions.

The clinical response to valsartan and hydrochlorothiazide tablets 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 mg/25 mg.

3 Replacement Therapy Valsartan and hydrochlorothiazide tablets may be substituted for the titrated components. 2) ]. 5 Use with Other Antihypertensive Drugs Valsartan and hydrochlorothiazide tablets may be administered with other antihypertensive agents.

6 ADVERSE REACTIONS The most common reasons for discontinuation of therapy with valsartan and hydrochlorothiazide were headache and dizziness. 4% vs. 9%). gov/medwatch. 1 Clinical Trials Experience 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 Valsartan and hydrochlorothiazide 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 valsartan and hydrochlorothiazide was comparable to placebo.

The overall frequency of adverse reactions was neither dose-related nor related to gender, age, or race. 1% of placebo patients. The most common reasons for discontinuation of therapy with valsartan and hydrochlorothiazide were headache and dizziness.

4% vs. 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 valsartan and hydrochlorothiazide. 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 mg/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. 2) , Drug Interactions (7) ]. 5%). 001). 2 Postmarketing Experience The following additional adverse reactions have been reported in valsartan or valsartan/hydrochlorothiazide postmarketing experience.

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.

Hypersensitivity:

Angioedema has been reported. Some of these patients previously experienced angioedema with other drugs including ACE inhibitors. Valsartan and hydrochlorothiazide should not be re-administered to patients who have had angioedema.

Digestive:

Elevated liver enzymes and reports of hepatitis Musculoskeletal: Rhabdomyolysis Renal: Impaired renal function Dermatologic: Alopecia, bullous dermatitis Vascular: Vasculitis Nervous System: Syncope Hydrochlorothiazide: The following additional adverse reactions have been reported in postmarketing experience with hydrochlorothiazide: Acute renal failure, renal disorder, aplastic anemia, erythema multiforme, pyrexia, muscle spasm, asthenia, acute angle-closure glaucoma, bone marrow failure, worsening of diabetes control, hypokalemia, blood lipids increased, hyponatremia, hypomagnesemia, hypercalcemia, hypochloremic alkalosis, impotence, and visual impairment.

Pathological changes in the parathyroid gland of patients with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy. If hypercalcemia occurs, further diagnostic evaluation is necessary.

Non-melanoma Skin Cancer:

Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses.

The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥ 50,000 mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.

5 WARNINGS AND PRECAUTIONS Hypotension: Correct volume depletion prior to initiation. 2) Observe for signs of fluid or electrolyte imbalance. 9) Monitor renal function and potassium in susceptible patients. 7) Exacerbation or activation of systemic lupus erythematosus.

5) Acute angle-closure glaucoma. 1 Fetal Toxicity Valsartan and hydrochlorothiazide can cause fetal harm when administered to a pregnant woman. 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. Thiazides cross the placenta, and use of thiazides during pregnancy is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

1) ]. 7%) in patients with uncomplicated hypertension treated with valsartan and hydrochlorothiazide 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 and hydrochlorothiazide, or the treatment should start under close medical supervision. If hypotension occurs, place the patient in the supine position and, if necessary, give intravenous 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. 3 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 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 and hydrochlorothiazide. 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 and hydrochlorothiazide [see Drug Interactions (7) ] . 4 Hypersensitivity Reaction 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.

5 Systemic Lupus Erythematosus Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus. 6 Lithium Interaction Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of valsartan or thiazide diuretics.

Monitor lithium levels in patients receiving valsartan and hydrochlorothiazide tablets and lithium [see Drug Interactions (7) ]. 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. , muscular weakness, paresis, or ECG alterations), valsartan and hydrochlorothiazide 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 valsartan therapy. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment. 1) ] . 8 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 angle-closure glaucoma may include a history of sulfonamide or penicillin allergy. 9 Metabolic Disturbances 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 and hydrochlorothiazide tablets.

4 CONTRAINDICATIONS 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 [see Drug Interactions (7) ] . Anuria; Hypersensitivity to any sulfonamide-derived drugs or any component; Do not co-administer aliskiren with valsartan and hydrochlorothiazide tablets in patients with diabetes.

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