Amlodipine And Valsartan

Dual blockade of the renin-angiotensin system is associated with increased risks of hypotension, hyperkalemia, and changes in renal function.

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

Increases in serum lithium levels and potential lithium toxicity may occur with valsartan.

In elderly, volume-depleted, or renally impaired patients, coadministration may result in deterioration of renal function including possible acute renal failure. May attenuate antihypertensive effect. Monitor renal function.

In elderly, volume-depleted, or renally impaired patients, coadministration may result in deterioration of renal function including possible acute renal failure. NSAIDs may attenuate antihypertensive effect. Monitor renal function.

Potassium-sparing diuretic that may increase serum potassium when combined with valsartan. Monitor serum potassium levels.

7 DRUG INTERACTIONS No drug interaction studies have been conducted with amlodipine and valsartan tablets and other drugs, although studies have been conducted with the individual amlodipine and valsartan components. 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. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment [see Clinical Pharmacology (12.3) ] .

Amlodipine may increase systemic exposure of cyclosporine. Frequent monitoring of trough blood levels and dose adjustment recommended.

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers due to potential decreased amlodipine efficacy.

Coadministration results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for hypotension and edema symptoms.

May increase serum potassium levels when combined with valsartan. Monitor serum potassium levels.

Concomitant use with valsartan may increase serum potassium levels. Monitor potassium concentration.

May lead to increases in serum potassium when combined with valsartan. Monitor serum potassium levels.

CYP3A inducer that may reduce amlodipine effectiveness. Blood pressure should be closely monitored when coadministered.

Monitor for hypotension when 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 ) • Non-Steroidal Anti-Inflammatory Drug (NSAID) use may lead to increased risk of renal impairment and loss of anti-hypertensive effect ( 7 ) • Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia ( 7 ) • Lithium: Increases in serum lithium level and lithium toxicity ( 7 ) Drug Interactions Sildenafil When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect [see Drug Interactions (7) ] .

Potassium-sparing diuretic that may increase serum potassium when combined with valsartan. Monitor serum potassium levels.

CYP3A inducer that may reduce amlodipine effectiveness. Blood pressure should be closely monitored when coadministered.

Amlodipine may increase systemic exposure of tacrolimus. Frequent monitoring of trough blood levels and dose adjustment recommended.

Potassium-sparing diuretic that may increase serum potassium when combined with valsartan. Monitor serum potassium levels.

7 DRUG INTERACTIONS If simvastatin is coadministered with amlodipine, do not exceed doses greater than 20 mg daily of simvastatin ( 7 ) Non-Steroidal Anti-Inflammatory Drug (NSAID) use may lead to increased risk of renal impairment and loss of anti-hypertensive effect ( 7 ) Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia ( 7 ) Lithium: Increases in serum lithium level and lithium toxicity ( 7 ) No drug interaction studies have been conducted with Amlodipine and Valsartan Tablets and other drugs, although studies have been conducted with the individual amlodipine and valsartan components. 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. Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including valsartan, may result in deterioration of renal function, including possible acute renal failure.

Valsartan No clinically significant pharmacokinetic interactions were observed when valsartan was coadministered with amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide, hydrochlorothiazide, or indomethacin. The valsartan-atenolol combination was more antihypertensive than either component, but it did not lower the heart rate more than atenolol alone.

Impact of Amlodipine on Other Drugs Coadministered amlodipine does not affect the exposure to atorvastatin, digoxin, ethanol and the warfarin prothrombin response time.

However, strong inhibitors of CYP3A (e.g., itraconazole, clarithromycin) may increase the plasma concentrations of amlodipine to a greater extent [see Drug Interactions (7) ] .

Erythromycin coadministration in healthy volunteers did not significantly change amlodipine systemic exposure.

Valsartan No clinically significant pharmacokinetic interactions were observed when valsartan was coadministered with amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide, hydrochlorothiazide, or indomethacin.

Valsartan No clinically significant pharmacokinetic interactions were observed when valsartan was coadministered with amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide, hydrochlorothiazide, or indomethacin.

However, strong inhibitors of CYP3A (e.g., itraconazole, clarithromycin) may increase the plasma concentrations of amlodipine to a greater extent [see Drug Interactions (7) ] .

Coadministration of inhibitors of the uptake transporter (rifampin, cyclosporine) or efflux transporter (ritonavir) may increase the systemic exposure to valsartan.