Abbott Healthcare Products Limited

4.3.      Contraindications

Known hypersensitivity to components of the product.

Pregnancy and lactation.

Severe hepatic impairment.

4.3.      Contraindications

Hypersensitivity to the active substance or to any of the excipients. 

Second and third trimester of pregnancy (see sections 4.4 and 4.6).

Severe hepatic impairment.

4.4. Special warnings and precautions for use

Risk of renal impairment

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function including renal failure have been reported with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor antagonists in susceptible individuals. Such changes in renal function may be reversible upon discontinuation of therapy.

As clinical experience is limited in patients with creatinine clearance <60 ml/min and in patients undergoing dialysis, caution is recommended.

As with other angiotensin II antagonists, pre-treatment and periodic monitoring of serum potassium and creatinine levels is recommended in patients with impaired renal function.

Sodium and/or volume depletion

At the start of therapy, symptomatic hypotension may occur in patients with severe sodium depletion and/or volume depletion (e.g. high dose diuretic therapy). Sodium and/or volume depletion should be corrected before commencing therapy or existing diuretic therapy should be reduced.

Hyperkalaemia

Although eprosartan has no significant effect on serum potassium there is no experience of concomitant administration with K-sparing diuretics or K-supplements. Consequently, as with other angiotensin II antagonists, the risk of hyperkalaemia when taken with K-sparing diuretics or K-supplements cannot be excluded. Regular monitoring for serum potassium levels is recommended when drugs that may increase potassium are administered with eprosartan in patients with renal impairment.

4.4. Special warnings and precautions for use

Renal impairment

Patients whose renal function is dependent predominantly on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe cardiac insufficiency [NYHA-classification: class IV], bilateral renal artery stenosis, or renal artery stenosis of a solitary kidney) are at increased risk of developing oliguria and/or progressive azotaemia and rarely acute renal failure during therapy with an angiotensin converting enzyme (ACE) inhibitor. These events are more likely to occur in patients treated concomitantly with a diuretic. The possibility of similar effects cannot be excluded with angiotensin II receptor antagonists. When eprosartan is to be used in patients with renal impairment, renal function should be assessed before starting treatment with eprosartan and at intervals during the course of therapy. If worsening of renal function is observed during therapy, treatment with eprosartan should be reassessed.

As clinical experience is limited in patients with creatinine clearance <60 ml/min and in patients undergoing dialysis, caution is recommended.

Hypotension

Symptomatic hypotension may occur in patients with severe sodium depletion and/or volume depletion (e.g. high dose diuretic therapy).  These conditions should be corrected before commencing therapy. There is an increased risk of severe hypotension when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with medical products that affect the renin-angiotensin-aldosterone system.

Aortic and mitral valve stenosis or obstructive hypertrophic cardiomyopathy.

As with other vasodilators, special caution is indicated in patients suffering from haemodynamically relevant aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism will not generally respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin-aldosterone system. Therefore, the use of Teveten is not recommended.

Hyperkalaemia

Although eprosartan has no significant effect on serum potassium there is no experience of concomitant administration with K-sparing diuretics or K-supplements.  Consequently, as with other angiotensin II antagonists, the risk of hyperkalaemia when taken with K-sparing diuretics or K-supplements cannot be excluded.  Regular monitoring for serum potassium levels is recommended when drugs that may increase potassium are administered with eprosartan in patients with renal impairment.

Pregnancy

Eprosartan should not be initiated during pregnancy. Unless continued Eprosartan 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. When pregnancy is diagnosed, treatment with Eprosartan should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

Other conditions

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.8       Undesirable effects

Clinical Trials

In placebo-controlled clinical trials, the overall incidence of adverse experiences reported with eprosartan was comparable to placebo.  Adverse experiences have usually been mild and transient in nature and have only required discontinuation of therapy in 4.1% of patients treated with eprosartan in placebo-controlled studies (6.5% for placebo).

The following table shows the adverse experiences, regardless of causality, reported by patients with hypertension in placebo controlled studies of up to 13 weeks duration.  It includes all adverse experiences occurring on eprosartan 600 - 800 mg once daily with an incidence at least 1% higher than placebo.

Angioedema has been infrequently reported.

Market Experience

The following adverse reactions have been reported during post-marketing experience with the following frequencies: very common ( >1/10); common ( >1/100, <1/10); uncommon ( >1/1000, <1/100); rare  ( >1/10,000, <1/1000); very rare  ( <1/10,000).

Laboratory Findings

In placebo-controlled clinical studies, significantly elevated serum potassium concentrations were observed in 0.9% of patients treated with eprosartan and 0.3% of patients who received placebo.

Significantly low values of haemoglobin were observed in 0.1% and 0% patients treated with eprosartan and placebo respectively.

In rare cases elevations of BUN values were reported in patients treated with eprosartan.  In rare cases increases in liver function values were also observed but were not considered to be causally related to eprosartan treatment.

4.8       Undesirable effects

Clinical Trials

The most commonly reported adverse drug reactions of patients treated with eprosartan are headache and unspecific gastrointestinal complaints, occurring in approximately 11% and 8%, respectively, of patients.

ADVERSE EVENTS  REPORTED DURING CLINICAL TRIALS IN PATIENTS TREATED WITH EPROSARTAN (n = 2316)

Postmarketing experience

In addition to those adverse events reported during clinical trials, the following side effects have been reported spontaneously during postmarketing use of eprosartan. A frequency cannot be estimated from the available data (not known).

Renal and urinary disorders  

Impaired renal function including renal failure in patients at risk.

Laboratory Findings

In placebo-controlled clinical studies, significantly elevated serum potassium concentrations were observed in 0.9% of patients treated with eprosartan and 0.3% of patients who received placebo.

Significantly low values of haemoglobin were observed in 0.1% and 0% patients treated with eprosartan and placebo respectively.

In rare cases elevations of BUN values were reported in patients treated with eprosartan.  In rare cases increases in liver function values were also observed but were not considered to be causally related to eprosartan treatment.