VALSARTAN/HYDROCHLOROTHIAZIDE

5 mg is one film-coated tablet once daily. Dose titration with the individual components is recommended. In each case, up- titration of individual components to the next dose should be followed in order to reduce the risk of hypotension and other adverse events.

When clinically appropriate direct change from monotherapy to the fixed combination may be considered in patients whose blood pressure is not adequately controlled on valsartan or hydrochlorothiazide monotherapy, provided the recommended dose titration sequence for the individual components is followed.

The clinical response to Valsartan/Hydrochlorothiazide should be evaluated after initiating therapy and if blood pressure remains uncontrolled, the dose may be increased by increasing either one of the components to a maximum dose of Valsartan/Hydrochlorothiazide 320 mg/25 mg.

The antihypertensive effect is substantially present within 2 weeks. In most patients, maximal effects are observed within 4 weeks. However, in some patients 4-8 weeks treatment may be required. This should be taken into account during dose titration.

Special populations Renal impairment No dose adjustment is required for patients with mild to moderate renal impairment (Glomerular Filtration Rate (GFR) ≥30 ml/min). 2). 4). No adjustment of the hydrochlorothiazide dose is required for patients with mild to moderate hepatic impairment.

2). Elderly No dose adjustment is required in elderly patients. Paediatric population Valsartan/Hydrochlorothiazide is not recommended for use in children below the age of 18 years due to a lack of data on safety and efficacy. Method of administration Valsartan/Hydrochlorothiazide can be taken with or without food and should be administered with water.

Adverse drug reactions reported in clinical trials and laboratory findings occurring more frequently with valsartan plus hydrochlorothiazide versus placebo and individual postmarketing reports are presented below according to system organ class.

Adverse drug reactions known to occur with each component given individually but which have not been seen in clinical trials may occur during treatment with valsartan/hydrochlorothiazide. Adverse drug reactions are ranked by frequency, the most frequent first, using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (frequency cannot be estimated from the available data).

Within each frequency grouping, adverse drug reactions are ranked in order of decreasing seriousness. Table 1. Frequency of adverse reactions with valsartan/hydrochlorothiazide Metabolism and nutrition disorders Uncommon Dehydration Nervous system disorders Uncommon Paraesthesia Very rare Dizziness Not known Syncope Eye disorders Uncommon Vision blurred Ear and labyrinth disorders Uncommon Tinnitus Vascular disorders Uncommon Hypotension Respiratory, thoracic and mediastinal disorders Uncommon Cough Not known Non cardiogenic pulmonary oedema Gastrointestinal disorders Very rare Diarrhoea Musculoskeletal and connective tissue disorders Uncommon Myalgia Very rare Arthralgia Renal and urinary disorders Not known Impaired renal function General disorders and administration site conditions Uncommon Fatigue Investigations Not known Serum uric acid increased, serum bilirubin and serum creatinine increased, hypokalaemia, hyponatraemia, elevation of blood urea nitrogen, neutropenia Additional information on the individual components Adverse reactions previously reported with one of the individual components may be potential undesirable effects with Valsartan/Hydrochlorothiazide as well, even if not observed in clinical trials or during postmarketing period.

) is not recommended. Monitoring of potassium should be undertaken as appropriate. Hydrochlorothiazide Hypokalaemia has been reported under treatment with thiazide diuretics, including hydrochlorothiazide. Frequent monitoring of serum potassium is recommended.

Treatment with thiazide diuretics, including hydrochlorothiazide, has been associated with hyponatraemia and hypochloraemic alkalosis. Thiazides, including hydrochlorothiazide, increase the urinary excretion of magnesium, which may result in hypomagnesaemia.

Calcium excretion is decreased by thiazide diuretics. This may result in hypercalcaemia. As for any patient receiving diuretic therapy, periodic determination of serum electrolytes should be performed at appropriate intervals. Sodium and/or volume-depleted patients Patients receiving thiazide diuretics, including hydrochlorothiazide, should be observed for clinical signs of fluid or electrolyte imbalance.

In severely sodium-depleted and/or volume-depleted patients such as those receiving high doses of diuretics, symptomatic hypotension may occur in rare cases after initiation of therapy with Valsartan/Hydrochlorothiazide. Sodium and/or volume depletion should be corrected before starting treatment with Valsartan/Hydrochlorothiazide.

g. patients with severe congestive heart failure), treatment with angiotensin converting enzyme (ACE) inhibitors has been associated with oliguria and/or progressive azotaemia, and in rare cases with acute renal failure and/or death.

Evaluation of patients with heart failure or post-myocardial infarction should always include assessment of renal function. The use of Valsartan / Hydrochlorothiazide in patients with severe chronic heart failure has not been established.

Hence it cannot be excluded that because of the inhibition of the renin-angiotensin- aldosterone system the application of Valsartan/Hydrochlorothiazide as well may be associated with impairment of the renal function. Valsartan/Hydrochlorothiazide should not be used in these patients.

1. 6). − Severe hepatic impairment, biliary cirrhosis and cholestasis. − Severe renal impairment (creatinine clearance < 30 ml/min), anuria. − Refractory hypokalaemia, hyponatraemia, hypercalcaemia and symptomatic hyperuricaemia. 1).