Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Generics [UK] Limited t/a Mylan, Station Close, Potters Bar, Hertfordshire, EN6 1TL
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Second and third trimester of pregnancy (see sections 4.4 and 4.6).
Severe hepatic impairment.
Haemodynamically significant bilateral renovascular disease or severe stenosis of a single functioning kidney.
The concomitant use of Eprosartan Mylan with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR<60 ml/min/1.73m²) (see sections 4.5 and 5.1).
When eprosartan is used in patients with mild to moderate hepatic impairment, special care should be exercised due to the fact that there is limited experience in this patient population.
No dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance ≥30 ml/min). Caution is recommended for use in patients with creatinine clearance <30 ml/min or in patients undergoing dialysis.
Some patients whose renal function is dependent on the continued inherent activity of the renin-angiotensin-aldosterone system (e.g. patients with severe cardiac insufficiency (NYHA class IV), bilateral renal artery stenosis, or renal artery stenosis of a solitary kidney) have risks of developing oliguria and/or progressive azotaemia and in rare cases acute renal failure during treatment with an angiotensin converting enzyme inhibitor (ACE-inhibitors). These events are more likely to occur in patients treated concomitantly with a diuretic. Angiotensin II receptor blockers, such as eprosartan, have not had adequate therapeutic experience to determine if there is a similar risk of developing renal function compromise in these susceptible patients. When eprosartan is to be used in patients with renal impairment, renal function should be assessed before starting treatment with eprosartan and regularly during treatment. If worsening of renal function is observed during therapy, treatment with eprosartan should be reassessed.
The following precautions are based on experience from other drugs belonging to the same class and ACE-inhibitors.
There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).
If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Symptomatic hypotension may occur in patients with severe volume depletion and/or salt depletion (e.g. high dose diuretic therapy). These conditions should be corrected before commencing therapy.
During treatment with other drugs affecting the renin-angiotensin-aldosterone system, hyperkalaemia may occur, especially in patients with impaired renal function and/or cardiac failure. Regular monitoring for serum potassium levels is recommended in risk patients.
Based on experience with the use of other medicinal products which affect the renin-angiotensin- aldosterone system concomitant administration with potassium-sparing diuretics, potassium-supplements, salt replacing preparations containing potassium or other drug which may elevate potassium levels (e.g. heparin) may lead to increased serum potassium levels and should therefore be administered cautiously with eprosartan.
Treatment with eprosartan is not recommended for these patients.
There is limited experience of treatment of patients with coronary heart disease.
As with all vasodilators caution should be exercised in patients with aortic and mitral valve stenosis or hypertrophic cardiomyopathy.
There is no experience from treatment with eprosartan in patients that have had a recent kidney transplantation.
Angiotensin II Receptor Blockers should not be initiated during pregnancy. Unless continued Angiotensin II Receptor Blocker 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 Angiotensin II Receptor Blockers should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).
As observed for ACE inhibitors, eprosartan and other Angiotensin II Receptor Blockers are apparently less effective in lowering the blood pressure in black people than in non-blacks, possibly because of higher prevalence of low renin status in the black hypertensive population.
This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Elevated serum potassium levels have been observed in placebo controlled clinical trials. Experience from other drugs affecting the renin-angiotensin-aldosterone system indicate that concomitant use of potassium sparing diuretics, potassium supplements, salt replacing agents containing potassium or other drugs which may elevate serum potassium levels (e.g. heparin) may cause an increase in serum potassium.
The blood pressure lowering effect may be enhanced during concomitant treatment with other blood pressure lowering drugs.
Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 4.3, 4.4 and 5.1).
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. While this is not documented with eprosartan, the possibility of a similar effect cannot be excluded and careful monitoring of serum lithium levels is recommended during concomitant use.
Eprosartan has been shown not to inhibit human cytochrome P450 enzymes CYP1A, 2A6, 2C9/8, 2C19, 2D6, 2E and 3A in vitro.
As with ACE inhibitors, concomitant use of Angiotensin II Receptor Blockers and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.
Concomitant use of losartan with the NSAID indometacin led to a decrease in efficacy of the angiotensin II receptor blocker; a class effect cannot be excluded.
The use of AIIRAs is not recommended during the first trimester of pregnancy (see section 4.4). The use of AIIRAs is contra-indicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4).
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Blockers, similar risks may exist for this class of drugs. Unless continued Angiotensin II Receptor Blocker 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 Angiotensin II Receptor Blockers should be stopped immediately and, if appropriate, alternative therapy should be started.
Exposure to Angiotensin II Receptor Blocker therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).
Should exposure to Angiotensin II Receptor Blockers have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken Angiotensin II Receptor Blockers should be closely observed for hypotension (see also sections 4.3 and 4.4).
Because no information is available regarding the use of eprosartan during breast-feeding, eprosartan is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
No studies on the effects on the ability to drive and use machines has been performed. Based on its pharmacodynamic properties, eprosartan is unlikely to affect this ability. When driving vehicles or operating machines, it should be taken into account, that occasionally dizziness or weariness may occur during treatment of hypertension.
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 reactions have been ranked under headings of frequency 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 (cannot be estimated from the available data).
Adverse experiences by erposartan-treated patients participating in clinical trials (n=2316):
Uncommon: Hypersensitivity*
Very common: Headache*
Common: Dizziness*
Uncommon: Hypotension
Common: Rhinitis
Common: Unspecific gastrointestinal complaints (e.g. nausea, vomiting, diarrhoea)
Common: Allergic skin reactions (e.g. rash, pruritus)
Uncommon: Angioedema*
Not known: Arthralgia
Common: Asthenia
* Did not occur in a higher frequency than in placebo.
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 available data (not known).
Impaired renal function including renal failure in patients at risk (e.g. renal artery stenosis).
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Not applicable.
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