Potassium: Concomitant use of 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.
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 with 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.
Transporters: 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. Co-administration of inhibitors of the uptake transporter (rifampin, 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, hydrochlorothiazide, amlodipine and glibenclamide.
As valsartan is not metabolized to a 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.