Hydrochlorothiazide : Other adverse reactions that have been reported with hydrochlorothiazide, without regard to causality, are listed below:

Body As A Whole : weakness;

Digestive : pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation;

Hematologic : aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia;

Hypersensitivity : purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions;

Metabolic : hyperglycemia, glycosuria, hyperuricemia;

Musculoskeletal : muscle spasm;

Nervous System/Psychiatric : restlessness;

Renal : renal failure, renal dysfunction, interstitial nephritis;

Skin : erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis;

Special Senses : transient blurred vision, xanthopsia.

Initial T herapy - Hypertension

In a clinical study in patients with severe hypertension (diastolic blood pressure less than 110 mmHg and systolic blood pressure less than 140 mmHg), the overall pattern of adverse reactions reported through six weeks of follow-up was similar in patients treated with Diovan HCT as initial therapy and in patients treated with valsartan as initial therapy. Comparing the groups treated with Diovan HCT (force-titrated to 320/25 mg) and valsartan (force-titrated to 320 mg), dizziness was observed in 6% and 2% of patients, respectively. Hypotension was observed in 1% of those patients receiving Diovan HCT and 0% of patients receiving valsartan. There were no reported cases of syncope in either treatment group. Laboratory changes with Diovan HCT as initial therapy in patients with severe hypertension were similar to those reported with Diovan HCT in patients with less severe hypertension [See Clinical Studies (14.2) and Drug Interactions   (7.3)].

The following additional adverse reactions have been reported in valsartan postmarketing experience:

Hypersensitivity : There are rare reports of angioedema;

Digestive : Elevated liver enzymes and very rare reports of hepatitis;

Renal : Impaired renal function;

Clinical Laboratory Tests : Hyperkalemia;

Dermatologic : Alopecia.

Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

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 met