ZENOVAN

Hypertension

Treatment of essential arterial hypertension in adults, and hypertension in children and adolescents aged 6 years to less than 18 years.

Recent post-myocardial infarction

Treatment of clinically stable adult patients presenting with symptomatic heart failure or asymptomatic left ventricular systolic dysfunction post-recent myocardial infarction (between 12 hours and 10 days) (see sections 4.4 and 5.1).

Heart failure

Treatment of symptomatic heart failure in adults:

· in case of intolerance to ACE inhibitors (IEC),

· in case of intolerance to beta-blockers, as additional treatment to an ACE inhibitor (IEC) when mineralocorticoid receptor antagonists cannot be used (see sections 4.2, 4.4, 4.5 and 5.1).

+ Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with ARBs, ACEIs or aliskiren

Data from clinical trials have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) by concomitant use of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and impairment of renal function (including acute renal failure) in comparison to the use of a single drug acting on the RAAS (see sections 4.3, 4.4 and 5.1).

Caution is required in case of co-administration of ARBs, including valsartan, and other agents blocking the RAAS such as ACEIs or aliskiren (see section 4.4).

The association of angiotensin II receptor antagonists (ARBs) - including valsartan - or angiotensin-converting enzyme inhibitors (ACEIs) and aliskiren is contraindicated in diabetic patients or those presenting with renal impairment (GFR < 60 ml/min/1.73 m²) (see section 4.3).

Associations not recommended

+ Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACEIs or angiotensin II receptor antagonists, including valsartan. If this association is necessary, strict monitoring of lithiaemia is recommended. If a diuretic is also used, the risk of lithium toxicity may likely be increased.

+ Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that may increase potassium levels

Monitoring of plasma potassium concentrations is recommended in case of an association deemed necessary of valsartan with a drug acting on potassium levels.

Associations requiring precautions for use

+ Non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid at more than 3 g/day and non-selective NSAIDs

An attenuation of the antihypertensive effect may occur in case of concomitant administration of angiotensin II antagonists and NSAIDs. In addition, this association may lead to an increased risk of impairment/worsening of renal function and increase in serum potassium. Consequently, renal function should be monitored at the start of treatment and an appropriate hydration status of the patient should be maintained.

+ Transporters

In vitro data show that valsartan is a substrate of the hepatic uptake transporter OATP1B1/OATP1B3 and the hepatic efflux transporter MRP2. The clinical relevance of this observation is unknown. Co-administration of uptake transporter inhibitors (rifampicin, cyclosporine) or efflux transporter inhibitors (ritonavir) may increase the systemic exposure of valsartan. Appropriate attention should be paid when initiating or discontinuing concomitant treatment with such drugs.

+ Others

In drug interaction studies with valsartan, no clinically significant interaction was observed with valsartan or any of the following substances: cimétidine, warfarine, furosémide, digoxine, aténolol, indométacine, hydrochlorothiazide, amlodipine, glibenclamide.

Pediatric population

In hypertensive children and adolescents, in whom underlying renal disorders are frequent, the concomitant use of valsartan and other drugs inhibiting the renin-angiotensin-aldosterone system and which may increase kaliemia should be done with caution. Renal function and kaliemia should be closely monitored.

The effects on the ability to drive vehicles and use machines have not been studied. Particular caution should be observed in vehicle drivers and machine users, due to the risk of sensation of dizziness and fatigue.