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 : The enzyme(s) responsible for valsartan metabolism have not been identified but do not seem to be CYP 450 isozymes. The inhibitory or induction potential of valsartan on CYP 450 is also unknown.
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.
Clinical Laboratory Test Findings
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 controlled clinical trials.
Hemoglobin and Hematocrit : Greater than 20% decreases in hemoglobin and hematocrit were observed in less than 0.1% of Diovan HCT patients, compared with 0.0% in placebo-treated patients.
Liver Function Tests : Occasional elevations (greater than 150%) of liver chemistries occurred in Diovan HCT-treated patients.
Neutropenia : Neutropenia was observed in 0.1% of patients treated with Diovan HCT and 0.4% of patients treated with placebo.
Serum Electrolytes : [ See W arnings and Precautions ( 5.7) ].