Valsartan And Hydrochlorothiazide

Dual blockade of RAS associated with increased risks of hypotension, hyperkalemia, and renal failure. Contraindicated in patients with diabetes and should be avoided in renal impairment.

Dual blockade of RAS with ACE inhibitors and valsartan is associated with increased risks of hypotension, hyperkalemia, and acute renal failure. Avoid combined use.

Potassium-sparing diuretic may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine when used with valsartan.

Dual blockade of RAS is associated with increased risks of hypotension, hyperkalemia, and changes in renal function including acute renal failure.

May lead to symptomatic hyponatremia when administered concurrently with hydrochlorothiazide.

May increase serum potassium levels when used concomitantly with valsartan, potentially leading to increased serum creatinine in heart failure patients.

NSAIDs may result in deterioration of renal function including possible acute renal failure in vulnerable patients. May attenuate antihypertensive effect of valsartan.

Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration with valsartan and hydrochlorothiazide. Monitor lithium levels.

NSAIDs may result in deterioration of renal function including possible acute renal failure, especially in elderly, volume-depleted, or renal-compromised patients. May attenuate antihypertensive effect.

NSAIDs with valsartan may result in deterioration of renal function including possible acute renal failure, especially in elderly, volume-depleted, or renal-compromised patients. Antihypertensive effect may be attenuated.

May lead to increases in serum potassium and in heart failure patients to increases in serum creatinine when used with valsartan.

Potassium-sparing diuretic may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine when used with valsartan.

Potassium-sparing diuretic may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine when used with valsartan.

Hydrochlorothiazide may increase blood glucose; dosage adjustment of antidiabetic drug may be required.

7 DRUG INTERACTIONS No drug interaction studies have been conducted with amlodipine/valsartan/hydrochlorothiazide and other drugs, although studies have been conducted with the individual components. A pharmacokinetic drug-drug interaction study has been conducted to address the potential for pharmacokinetic interaction between the triple combination, amlodipine/valsartan/hydrochlorothiazide, and the corresponding 3 double combinations. Amlodipine Impact of Other Drugs on Amlodipine CYP3A Inhibitors Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction.

Ion exchange resin may interact with hydrochlorothiazide; dosage staggering is recommended.

Ion exchange resin may interact with hydrochlorothiazide; dosage staggering is recommended.

Co-administration of cyclosporine (uptake transporter inhibitor) may increase systemic exposure to valsartan.

CYP3A inducers may decrease amlodipine efficacy. Blood pressure should be closely monitored when coadministered.

Coadministration with CYP3A inhibitors increases systemic exposure to amlodipine and may require dose reduction. Monitor for hypotension and edema.

7 DRUG INTERACTIONS Valsartan-Hydrochlorothiazide: Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or thiazides. Monitor lithium levels in patients taking valsartan and hydrochlorothiazide tablets. Hydrochlorothiazide: When administered concurrently, the following drugs may interact with thiazide diuretics: Antidiabetic Drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.

Dosage adjustment may be required when hydrochlorothiazide is administered concurrently.

Dosage of hydrochlorothiazide and ion exchange resins should be staggered to avoid interaction.

Co-administration of rifampin (uptake transporter inhibitor) may increase systemic exposure to valsartan.

Co-administration of ritonavir (efflux transporter inhibitor) may increase systemic exposure to valsartan.

Monitor for hypotension when sildenafil is coadministered with amlodipine.

Impact of Amlodipine on Other Drugs Simvastatin: Coadministration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily [ see Clinical Pharmacology ( 12.3 ) ]. If simvastatin is coadministered with amlodipine, do not exceed doses greater than 20 mg daily of simvastatin ( 7 ) Antidiabetic drugs: Dosage adjustment of antidiabetic may be required ( 7 ) Cholestyramine and colestipol: Reduced absorption of thiazides ( 12.3 ) Lithium: Increased risk of lithium toxicity.

CYP3A inducer that may decrease amlodipine efficacy. Blood pressure should be closely monitored when amlodipine is coadministered with St. John's Wort.

Amlodipine may increase the systemic exposure of tacrolimus. Frequent monitoring of trough blood levels is recommended and adjust dose when appropriate.

7 DRUG INTERACTIONS Valsartan-Hydrochlorothiazide: Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or thiazides. Monitor lithium levels in patients taking valsartan and hydrochlorothiazide tablets. Valsartan: Agents Increasing Serum Potassium: Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium or other drugs that may increase potassium levels (e.g., heparin) may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine.

No clinically significant pharmacokinetic interactions observed; combination was more antihypertensive than either component alone.

No clinically significant pharmacokinetic interactions were observed when coadministered with valsartan.

No clinically significant pharmacokinetic interactions were observed when coadministered with valsartan.

No clinically significant pharmacokinetic interactions were observed when coadministered with valsartan.

No clinically significant pharmacokinetic interactions were observed when coadministered with valsartan.

No clinically significant pharmacokinetic interactions were observed when coadministered with valsartan.

Coadministration of valsartan and warfarin did not change the pharmacokinetics of valsartan or the time-course of warfarin's anticoagulant properties.

Antineoplastic Agents (e.g., Cyclophosphamide, Methotrexate) Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance their myelosuppressive effects.