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Dual blockade of the Renin-Angiotensin-System (RAS) with ARBs, ACEIs, or aliskerin: The concomitant use of ARBs, including Valsartan, with other agents acting on the RAS is associated with an increased incidence of hypotension, hyperkalemia, and changes in renal function compared to monotherapy. It is recommended to monitor blood pressure, renal function and electrolytes in patients on valsartan and other agents that affect the RAS.
The concomitant use of ARBs - including valsartan or of ACEIs with aliskerin, should be avoided in patients with severe renal impairment (GFR <30 mL/min).
The concomitant use of ARBs - including valsartan or ACEIs with aliskerin is contraindicated in patients with Type 2 diabetes.
Potassium: Concomitant use of potassium-sparing diuretics (eg. 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.
Non-Steroidal Anti-Inflammatory Agents (NSAIDS) including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): When angiotensin II antagonists are administered simultaneously with NSAIDS, attenuation of the antihypertensive effect may occur. Furthermore, in patients who are elderly, volume-depleted (including those on diuretic therapy), or have compromised renal function, concomitant use of angiotensin II antagonists and NSAIDS may lead to an increased risk of worsening of renal function. Therefore, monitoring of renal function is recommended when initiating or modifying the treatment in patients on valsartan who are taking NSAIDS concomitantly.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors or angiotensin II receptor antagonists, including valsartan. Therefore, careful monitoring of serum lithium level is recommended during concomitant use. If a diuretic is also used, the risk of lithium toxicity may presumably be increased further with valsartan.
Transporters: Co-administration of inhibitor of the uptake transporter (rifampicin, ciclosporin) or efflux transporter (ritonavir) may increase the systemic exposure to valsartan.
No drug interactions of clinical significance have been found. Compounds which have been studied in clinical trials include, cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorthiazide, amlodipine and glibenclamide.
As valsartan is not metabolized to significant extent, clinically relevant drug-drug interactions in the form of metabolic induction or inhibition of the cytochrome P450 system are not expected with valsartan. Although valsartan is highly bound to plasma proteins, in vitro studies have not shown any interaction at this level with a range of molecules which are also highly protein bound, such as diclofenac, furosemide and warfarin.
Pediatric Population: In hypertension in children and adolescents, where underlying renal abnormalities are common, caution is recommended with the concomitant use of valsartan and other substances that inhibit the renin angiotensin aldosterone system which may increase serum potassium. Renal function and serum potassium should be closely monitored in these patients.
