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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.
WARNINGS/PRECAUTIONS
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 as 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.
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, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline.
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 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.
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.
Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
Lithium generally should not be given with thiazides.
In the controlled trials of various doses of Valsartan and Hydrochlorothiazide the incidence of hypertensive patients who developed hypokalemia (serum potassium < 3.5 mEq/L) was 3%; 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, 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 preexisting renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or valsartan may be required.
Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Untreated acute angle-closure glaucoma can lead to permanent vision loss. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.
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.
DRUG INTERACTIONS
Valsartan
The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1 and the hepatic efflux transporter MRP2. Coadministration of inhibitors of the uptake transporter (rifampin, cyclosporine) or efflux transporter (ritonavir) may increase the systemic exposure to valsartan.
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of non-steroidal anti-inflammatory drugs (NSAIDs), including selective Cyclooxygenase-2 inhibitors (COX-2), with angiotensin II receptor antagonists, including valsartan, may result in deterioration of renal function, including possible acute renal failure. The antihypertensive effect of angiotensin II receptor antagonists, including valsartan may be attenuated by NSAIDs including selective COX-2 inhibitors.
Potassium: Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine. If co-medication is considered necessary, monitoring of serum potassium is advisable.
Hydrochlorothiazide
When administered concurrently, the following drugs may interact with thiazide diuretics: antidiabetic drugs (oral agents and insulin), lithium, NSAIDS and COX-2 selective inhibitors, carbamazepine, cyclosporine and ion exchange resins.
ADVERSE EVENTS
The most common reasons for discontinuation for therapy with Valsartan and Hydrochlorothiazide were headache and dizziness.
The only adverse reaction that occurred in controlled clinical trials in at least 2% of patients treated with valsartan and hydrochlorothiazide and at a higher incidence in Valsartan and Hydrochlorothiazide (n = 4,372) than placebo (n = 262) patients was nasopharyngitis (2.4% vs. 1.9%).
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