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 adult patients presenting with symptomatic heart failure in case of intolerance to angiotensin-converting enzyme (ACE) inhibitors or in case of intolerance to beta-blockers, as add-on treatment to an ACE inhibitor 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 RAAS by the concomitant use of ACEIs, ARBs or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and impairment of renal function (including acute renal failure) compared to the use of a single drug acting on the RAAS (see sections 4.3, 4.4 and 5.1).

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 TAREG. 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, potassium-containing salt substitutes 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 for which precautions for use are required

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

An attenuation of the antihypertensive effect may occur in case of concomitant administration of angiotensin II antagonists and NSAIDs; 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 appropriate hydration status of the patient should be maintained.

Transporters

The results of an in vitro study conducted on human hepatic tissue indicate that valsartan is a substrate of the hepatic influx transporter OATP1B1 /OATP1B3 and the hepatic efflux transporter MRP2. The clinical relevance of this information is unknown. Co-administration of influx transporter inhibitors (e.g. rifampicin, cyclosporine) or efflux transporter inhibitors (e.g. ritonavir) may increase the systemic exposure of valsartan. Appropriate attention should be paid when initiating or discontinuing concomitant treatment with such drugs.

Other

In drug interaction studies with valsartan, no clinically significant interaction was observed with valsartan or any of the following substances: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.

Pediatric population

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