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.

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

CYP   450 Interactions : In vitro metabolism studies indicate that CYP 450 mediated drug interactions between valsartan and co-administered drugs are unlikely because of low extent of metabolism [see Pharmacokinetics (12.3)].

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, cyclosporine) or efflux transporter (ritonavir) may increase the systemic exposure to valsartan.

Hydrochlorothiazide : When administered concurrently, the following drugs may interact with thiazide diuretics:

Alcohol, Barbiturates, or N arcotics - Potentiation of orthostatic hypotension may occur.

Antidiabetic D rugs (oral agents and insulin) - Dosage adjustment of the antidiabetic drug may be required.

Other Antihypertensive D rugs - Additive effect or potentiation.

Cholestyramine and Colestipol R esins - Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43% respectively.

Corticosteroids, ACTH - Intensified electrolyte depletion, particularly hypokalemia.

Pressor A mines (e.g., norepinephrine) - Possible decreased response to pressor amines but not sufficient to preclude their use.

Skeletal Muscle Relaxants, N ondepolarizing (e.g., tubocurarine) - Possible increased responsiveness to the muscle relaxant.

Lithium - Should not generally be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with Diovan HCT.

Non steroidal A nti -inflammatory Drugs - In some patients, the administration of a nonsteroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when Diovan HCT and nonsteroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

Carbamazepine – May lead to symptomatic hyponatremia.

In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of Diovan HCT.

Creatinine /Blood Urea N itrogen (BUN) : Minor elevations in creatinine and BUN occurred in 2% and 15% respectively, of patients taking Diovan HCT and 0.4% and 6% respectively, given placebo in contr