VALSARTAN

Posology Hypertension The recommended starting dose of Valsartan is 80 mg once daily. The antihypertensive effect is substantially present within 2 weeks, and maximal effects are attained within 4 weeks. In some patients whose blood pressure is not adequately controlled, the dose can be increased to 160 mg and to a maximum of 320 mg.

Valsartan may also be administered with other antihypertensive agents. The addition of a diuretic such as hydrochlorothiazide will decrease blood pressure even further in these patients. Recent myocardial infarction In clinically stable patients, therapy may be initiated as early as 12 hours after a myocardial infarction.

After an initial dose of 20 mg twice daily, valsartan should be titrated to 40 mg, 80 mg, and 160 mg twice daily over the next few weeks. The starting dose is provided by the 40 mg divisible tablet. The target maximum dose is 160 mg twice daily.

In general, it is recommended that patients achieve a dose level of 80 mg twice daily by two weeks after treatment initiation and that the target maximum dose, 160 mg twice daily, be achieved by three months, based on the patient's tolerability.

If symptomatic hypotension or renal dysfunction occur, consideration should be given to a dosage reduction. g. thrombolytics, acetylsalicylic acid, beta blockers, statins, and diuretics. 1). Evaluation of post-myocardial infarction patients should always include assessment of renal function.

Heart failure The recommended starting dose of Valsartan is 40 mg twice daily. Uptitration to 80 mg and 160 mg twice daily should be done at intervals of at least two weeks to the highest dose, as tolerated by the patient. Consideration should be given to reducing the dose of concomitant diuretics.

The maximum daily dose administered in clinical trials is 320 mg in divided doses. Valsartan may be administered with other heart failure therapies. 1). Evaluation of patients with heart failure should always include assessment of renal function.

Method of administration Valsartan may be taken independently of a meal and should be administered with water. Additional information on special populations Elderly patients No dose adjustment is required in older people. 3). 3). Patients with hepatic impairment In patients with mild to moderate hepatic impairment without cholestasis, the dose of valsartan should not exceed 80 mg.

In controlled clinical studies in patients with hypertension, the overall incidence of adverse reactions (ADRs) was comparable with placebo and is consistent with the pharmacology of valsartan. The incidence of ADRs did not appear to be related to dose or treatment duration and also showed no association with gender, age or race.

The ADRs reported from clinical studies, post-marketing experience and laboratory findings are listed below according to system organ class. Adverse 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), including isolated reports.

Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. For all the ADRs reported from post-marketing experience and laboratory findings, it is not possible to apply any ADR frequency and therefore they are mentioned with a "not known" frequency.

Hypertension Blood and lymphatic system disorders Not known Decrease in haemoglobin, Decrease in haematocrit, Neutropenia, Thrombocytopenia Immune system disorders Not known Hypersensitivity including serum sickness Metabolism and nutrition disorders Not known Increase of serum potassium Not known Hyponatraemia Ear and labyrinth system disorders Uncommon Vertigo Vascular disorders Not known Vasculitis Respiratory, thoracic and mediastinal disorders Uncommon Cough Gastrointestinal disorders Uncommon Abdominal pain Very rare Intestinal angioedema Hepato-biliary disorders Not known Elevation of liver function values including increase of serum bilirubin Skin and subcutaneous tissue disorders Not known Angioedema, Dermatitis bullous, Rash, Pruritus Musculoskeletal and connective tissue disorders Not known Myalgia Renal and urinary disorders Not known Renal failure and impairment, Elevation of serum creatinine General disorders and administration site conditions Uncommon Fatigue The safety profile seen in controlled-clinical studies in patients with post-myocardial infarction and/or heart failure varies from the overall safety profile seen in hypertensive patients.

) is not recommended. Monitoring of potassium should be undertaken as appropriate. Sodium- and/or volume-depleted patients 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.

Sodium and/or volume depletion should be corrected before starting treatment with Valsartan, for example by reducing the diuretic dose. Renal artery stenosis In patients with bilateral renal artery stenosis or stenosis to a solitary kidney, the safe use of Valsartan has not been established.

Short-term administration of Valsartan to twelve patients with renovascular hypertension secondary to unilateral renal artery stenosis did not induce any significant changes in renal haemodynamics, serum creatinine, or blood urea nitrogen (BUN).

However, other agents that affect the renin-angiotensin system may increase blood urea and serum creatinine in patients with unilateral renal artery stenosis, therefore monitoring of renal function is recommended when patients are treated with valsartan.

Kidney transplantation There is currently no experience on the safe use of Valsartan in patients who have recently undergone kidney transplantation. Primary hyperaldosteronism Patients with primary hyperaldosteronism should not be treated with Valsartan as their renin-angiotensin system is not activated.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy As with all other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or hypertrophic obstructive cardiomyopathy (HOCM).

Impaired renal function No dosage adjustment is required for patients with a creatinine clearance >10 ml/min. 2). 5). 2). Pregnancy Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy.

1. - Severe hepatic impairment, biliary cirrhosis and cholestasis. 6). 1).