When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
Warnngs and precautions concerning use in pregnancy and lactation have been updated and the name of the MAH has changed to reflect new ownership.
In particular, in section 4.3 the product is no longer contra-indicated in lactation although in section 4.6 it is recommended that patients are switched to products with a better established safety profile especially when nursing newborn or preterm infants. The information on the use during pregnancy (sections 4.4 and 4.6) has been revised by including more detail of the possible risk to the foetus to enable prescribers to make a better informed treatment decision. In section 7, the name of the MAH has been changed to Abbott Healthcare Products Ltd.
The information on the use during pregnancy (sections 4.4 and 4.6) has been revised by including more detail of the possible risk to the foetus to enable prescribers to make a better informed treatment decision. In section 7, the name of the MAH has been changed to Abbott Healthcare Products Ltd.
In section 7, the name of the MAH has been changed to Abbott Healthcare Products Ltd.
For excipients see section 6.1. sec. 2 propsed
Each film-coated tablet contains eprosartan mesylate equivalent to 400 mg eprosartan.
For a full list of excipients, see section 6.1.
sec. 3 present
Film-coated tablet.
Teveten 400 is an oval light pink film-coated tablet imprinted 5044 on one side and SOLVAY on the other sec. 3 propsed
Oval, light to moderately pink film-coated tablet marked "5044" on one side and "SOLVAY" on the other side.
sec. 4.2 present
The recommended dose is 600 mg Eprosartan once daily.
Achievement of maximal blood pressure reduction in most patients may take 2 to 3 weeks of treatment.
Eprosartan may be used alone or in combination with other anti-hypertensives. In particular, addition of a thiazide-type diuretic such as hydrochlorothiazide or a calcium channel blocker such as sustained release nifedipine has been shown to have an additive effect with Eprosartan.
Elderly
No dose adjustment is required in the elderly.
Dosage in Hepatically Impaired Patients
There is limited experience in patients with hepatic insufficiency (see Section 4.3 Contraindications).
Dosage in Renally Impaired Patients
In patients with moderate or severe renal impairment (creatinine clearance <60 ml/min), the daily dose should not exceed 600 mg.
Children
As safety and efficacy in children have not been established, treatment of children is not recommended.
Eprosartan may be taken with or without food.
Duration of treatment is not limited. sec. 4.2 proposed
The recommended dose is 600 mg eprosartan once daily.
Eprosartan may be used alone or in combination with other anti-hypertensives. In particular, addition of a thiazide-type diuretic such as hydrochlorothiazide or a calcium channel blocker such as sustained release nifedipine has been shown to have an additive effect with eprosartan.
Duration of treatment is not limited.
Geriatric patients
There is limited experience in patients with hepatic insufficiency (see section 4.3).
Paediatric patients
Teveten is not recommended for use in children and adolescents due to lack of data on safety and efficacy.
sec. 4.3 present
Known hypersensitivity to eprosartan or to any of the excipients.
Severe hepatic impairment.
Pregnancy and lactation (see Section 4.6 Pregnancy and Lactation). sec. 4.3 proposed
Pregnancy and lactation (see section 4.6).
Hemodynamically significant bilateral renovascular disease or severe stenosis of a solitary functioning kidney.
sec. 4.4 present
Hepatic Impairment
Renal Impairment
No dose adjustment is required in patients with mild to moderate renal insufficiency (creatinine clearance 30 ml/min). Caution is recommended for use in patients with creatinine clearance < 30 ml/min or in patients undergoing dialysis.
Coronary Heart Disease
There is limited experience in patients with coronary heart disease at this time.
Sodium and/or volume depletion
Symptomatic hypotension may occur in patients with severe volume and/or salt depletion (e.g. high dose diuretic therapy). These conditions should be corrected prior to commencing therapy.
The following precautions have been included based on experience with other agents in this class and also ACE inhibitors:
Hyperkalaemia
During treatment with other medicinal products which affect the renin-angiotensin-aldosterone system hyperkalaemia may occur, especially in the presence of renal impairment and/or heart failure. Adequate monitoring of serum potassium in patients at risk is recommended.
Based on experience with the use of other medicinal products which affect the renin-angiotensin-aldosterone system, concomitant use with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products which may increase the potassium level (e.g. heparin) may lead to an increase in serum potassium and should therefore be co-administered cautiously with Teveten.
General information (for patients with renal impairment and/or severe cardiac insufficiency)
Patients whose renal function is dependent on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe cardiac insufficiency, bilateral renal artery stenosis, or renal artery stenosis of a solitary kidney) have developed oliguria and/or progressive azotaemia and rarely acute renal failure during therapy with angiotensin converting enzyme (ACE) inhibitors. Since there is currently inadequate therapeutic experience in patients with severe cardiac insufficiency or renal artery stenosis, it cannot be ruled out that renal function in these patients may be impaired with Eprosartan due to inhibition of the renin-angiotensin-aldosterone system. When Eprosartan is 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.
Primary Hyperaldosteronism
Patients with primary hyperaldosteronism are not recommended to be treated with Eprosartan.
Aortic and Mitral Valve Stenosis / Hypertrophic Cardiomyopathy
As with all vasodilators, Eprosartan should be used with caution in patients with aortic and mitral valve stenosis or hypertrophic cardiomyopathy.
Renal Transplantation
There is no experience in patients with recent kidney transplantation.
Other warnings and precautions
As observed for angiotensin converting enzyme inhibitors, eprosartan and the other angiotensin antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. sec. 4.4 proposed Hepatic Impairment
No dose adjustment is required in patients with mild to moderate renal insufficiency (creatinine clearance ³ 30 ml/min). Caution is recommended for use in patients with creatinine clearance < 30 ml/min or in patients undergoing dialysis.
Renin-angiotensin-aldosterone system dependent patients (see section 4.3)
Patients whose renal function is dependent on the activity of the renin-angiotensinaldosterone system (e.g. patients with severe cardiac insufficiency (NYHA-classification: class IV), bilateral renal artery stenosis, or renal artery stenosis of a solitary kidney) have developed oliguria and/or progressive azotaemia and rarely acute renal failure during therapy with angiotensin converting enzyme (ACE) inhibitors. Since there is currently inadequate therapeutic experience in patients with severe cardiac insufficiency or renal artery stenosis, it cannot be ruled out that renal function in these patients may be impaired with eprosartan due to inhibition of the renin-angiotensin-aldosterone system. When eprosartan is 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.
During treatment with other medicinal products which affect the renin-angiotensinaldosterone system hyperkalaemia may occur, especially in the presence of renal impairment and/or heart failure. Adequate monitoring of serum potassium in patients at risk is recommended.
Based on experience with the use of other medicinal products which affect the reninangiotensin-aldosterone system, concomitant use of with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products which may increase the potassium level (e.g. heparin) may lead to an increase in serum potassium and should therefore be co-administered cautiously with Teveten.
Patients with primary hyperaldosteronism are not recommended to be treated with eprosartan.
As with all vasodilators, eprosartan should be used with caution in patients with aortic and mitral valve stenosis or hypertrophic cardiomyopathy.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
sec. 4.5 present Since in placebo-controlled clinical studies significantly elevated serum potassium concentration were observed, and based on experience with the use of other drugs that affect the renin-angiotensin-aldosterone system, concomitant use of K-sparing diuretics, K-supplements, salt substitutes containing potassium or other drugs that may increase serum potassium levels (e.g. heparin) may lead to increase in serum potassium.
The antihypertensive effect may be potentiated by other antihypertensives.
Toxicity and a reversible increase in serum lithium concentrations have been reported during concurrent therapy with lithium preparations and ACE inhibitors. The possibility of a similar effect after the use of eprosartan
cannot be excluded and careful monitoring of serum lithium levels is recommended during concomitant use. sec. 4.5 proposed No effect on the pharmacokinetics of digoxin and the pharmacodynamics of warfarin or glyburide (glibenclamide) has been shown with eprosartan. Similarly no effect on eprosartan pharmacokinetics has been shown with ranitidine, ketoconazole or fluconazole.
Eprosartan can be used concomitantly with thiazide diuretics (e.g. hydrochlorothiazide) and calcium channel blockers (e.g. sustained-release nifedipine) without evidence of clinically significant adverse interactions.
Since in placebo-controlled clinical studies significantly elevated serum potassium concentration were observed, and based on experience with the use of other drugs that affect the renin-angiotensin-aldosterone system, concomitant use of K-sparing diuretics, Ksupplements, salt substitutes containing potassium or other drugs that may increase serum potassium levels (e.g. heparin) may lead to increase in serum potassium.
Toxicity and a reversible increase in serum lithium concentrations have been reported during concurrent therapy with lithium preparations and ACE inhibitors. The possibility of a similar effect after the use of eprosartan can not 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.
sec. 4.8 present
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 frequencies indicated in the text are based on the non-corrected numbers in placebo-controlled clinical trials.
In clinical trials following adverse events were reported:
Body as a whole
Common: viral infection, injury and pain.
Cardiovascular system
Common: chest pain and palpitation.
Gastrointestinal system
Common: Abdominal pain and dyspepsia.
Respiratory system
Common: Rhinitis, pharyngitis, dyspnoea, upper respiratory tract infection and coughing.
Nervous system
Common: headache, dizziness, fatigue and depression
Musculoskeletal system
Common: Back pain and arthralgia.
Urogenital system
Common: Urinary tract infections.
Metabolic system
Common: Hypertriglyceridaemia.
A relationship with eprosartan treatment could not always be established.
The following adverse events were reported by the market:
Rare: Asthenia.
Rare: Headache and dizziness.
Very rare: Hypotension, including postural hypotension
Skin and appendages
Rare: Skin reactions (rash, pruritis, urticaria).
Very rare: Facial swelling and/or angioedema.
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. sec. 4.8 proposed
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).
ADVERSE EXPERIENCES BY EPROSARTAN-TREATED PATIENTS PARTICIPATING IN CLINICAL TRIALS MedDRA system organ class Common ³1/100, <1/10 Uncommon ³1/1,000, <1/100 Rare ³1/10,000 <1/1,000 Very rare ≤1/10,000 incl. isolated reports Unknown Infections and infestations Viral infection Metabolism and nutrition disorders Hyper- triglyceridaemia Hyperkalaemia Nervous system disorders Headache, dizziness, fatigue, depression Cardiac disorders Chest pain, palpitation Vascular disorders Hypotension, including postural hypotension Respiratory, thoracic and mediastinal disorders Rhinitis, pharyngitis, dyspnoe, upper respiratory tract infection, cough Skin and subcutaneous tissue disorders Allergic skin reaction (e.g. rash, pruritus, urticaria) facial swelling, angioedema Musculoskeletal and connective tissue disorders Back pain, arthralgia Renal and urinary disorders Urinary tract infections Gastrointestinal disorders Nausea, vomiting, diarrhoea, abdominal pain, unspecific gastrointestinal complaints, dyspepsia General disorders and administration site reactions Asthenia, injury, pain Investigations Haemoglobin decreased, blood urea increased
ADVERSE EXPERIENCES BY EPROSARTAN-TREATED PATIENTS PARTICIPATING IN CLINICAL TRIALS
MedDRA
system organ
class
Common
³1/100, <1/10
Uncommon
³1/1,000,
<1/100
Rare
³1/10,000
<1/1,000
Very rare
≤1/10,000
incl.
isolated
reports
Unknown
Infections and
infestations
Viral infection
Metabolism and
nutrition
disorders
Hyper-
triglyceridaemia
Headache,
dizziness,
fatigue,
depression
Cardiac
Chest pain,
palpitation
Vascular
Hypotension,
including
postural
hypotension
Respiratory,
thoracic and
mediastinal
Rhinitis,
pharyngitis,
dyspnoe, upper
respiratory
tract infection,
cough
Skin and
subcutaneous
tissue disorders
Allergic skin
reaction (e.g.
rash,
pruritus,
urticaria)
facial
swelling,
angioedema
Musculoskeletal
and connective
Back pain,
arthralgia
Renal and
urinary
Urinary tract
infections
Gastrointestinal
Nausea,
vomiting,
diarrhoea,
abdominal pain,
unspecific
gastrointestinal
complaints, dyspepsia
General
disorders and
administration
site reactions
Asthenia,
injury, pain
Investigations
Haemoglobin
decreased,
blood urea
increased
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 (e.g. renal artery stenosis).
sec. 4.9 present
Limited data are available in regard to overdose in humans. The most likely manifestation of overdose would be hypotension. If symptomatic hypotension should occur, supportive treatment should be instituted. sec. 4.9 proposed
Limited data are available in regard to overdose in humans. Eprosartan was well tolerated after oral dosing (maximum unit dose taken to date in humans 1200 mg). The most likely manifestation of overdose would be hypotension. If symptomatic hypotension should occur, supportive treatment should be instituted. sec. 5.1 present Pharmacotherapeutic class: Antihypertensive agent: ATC-code: C09CA02. (...) sec. 5.1 proposed Pharmacotherapeutic class: Eprosartan, ATC-code: C09CA02. (...) sec. 5.3 present (...) c) Reproduction toxicity (...) sec. 5.3 proposed (...) c) Reproductive and developmental toxicity (...) sec. 6.1 present Tablet cores Lactose monohydrate Microcrystalline cellulose Pregelatinised starch Croscarmellose sodium Magnesium stearate Film-coat Titanium dioxide Hypromellose 3CP Hypromellose 6CP Macrogol 400 Polysorbate 80 Iron oxide yellow Iron oxide red sec. 6.1 proposed Tablet Core: Lactose monohydrate Microcrystalline cellulose Pregelatinised starch Croscarmellose sodium Magnesium stearate Purified water. Film-coat: Hypromellose (E464) Titanium dioxide (E171) Macrogol 400 Polysorbate 80 (E433) Iron oxide yellow (E172) Iron oxide red (E172). sec. 6.5 present Opaque PVC/Aclar blister packs or HDPE bottles with polypropylene caps. Blister packs: 14 film-coated tablets 28 film-coated tablets 56 film-coated tablets 98 film-coated tablets 280 (10 x 28) film-coated tablets 400 mg tablets are also available in blister packs: 4 film coated tablets 7 film coated tablets 50 (5 x 10) film coated tablets Bottle packs: 100 film coated tablets Not all pack sizes may be marketed. sec. 6.5 proposed Opaque PVC/Aclar/Al blister packs or HDPE bottles with polypropylene caps. Blister packs: 4 film coated tablets 7 film coated tablets 14 film-coated tablets 28 film-coated tablets 50 (5 x 10) film coated tablets 56 film-coated tablets 98 film-coated tablets 280 (10 x 28) film-coated tablets Bottle packs: 100 film coated tablets Not all pack sizes may be marketed. sec. 10 present January 2005 sec. 10 proposed October 2007
Pharmacotherapeutic class: Antihypertensive agent: ATC-code: C09CA02. (...) sec. 5.1 proposed
Pharmacotherapeutic class: Eprosartan, ATC-code: C09CA02.
(...) sec. 5.3 present (...) c) Reproduction toxicity (...) sec. 5.3 proposed (...)
c) Reproductive and developmental toxicity (...) sec. 6.1 present
Tablet cores
Lactose monohydrate
Microcrystalline cellulose
Pregelatinised starch
Croscarmellose sodium
Magnesium stearate
Film-coat
Titanium dioxide
Hypromellose 3CP
Hypromellose 6CP
Macrogol 400
Polysorbate 80
Iron oxide yellow
Iron oxide red
sec. 6.1 proposed
Tablet Core:
Purified water.
Film-coat:
Hypromellose (E464)
Titanium dioxide (E171)
Polysorbate 80 (E433)
Iron oxide yellow (E172)
Iron oxide red (E172).
sec. 6.5 present
Opaque PVC/Aclar blister packs or HDPE bottles with polypropylene caps.
Blister packs: 14 film-coated tablets
28 film-coated tablets
56 film-coated tablets
98 film-coated tablets
280 (10 x 28) film-coated tablets
400 mg tablets are also available in blister packs:
4 film coated tablets
7 film coated tablets
50 (5 x 10) film coated tablets
Bottle packs: 100 film coated tablets
Not all pack sizes may be marketed.
sec. 6.5 proposed
Opaque PVC/Aclar/Al blister packs or HDPE bottles with polypropylene caps.
Blister packs:
14 film-coated tablets
sec. 10 present January 2005 sec. 10 proposed
October 2007