In section 4.1 (therapeutic indications),
adult patients have been added.
In section 4.2 (posology and administration),
Method of administration: The tablet should be swallowed with a sufficient amount of fluid (e.g. one glass of water). The tablet should not be chewed and should be taken at the same time each day, has been deleted and placed at the end of the section.
Children and adolescents have been deleted,
Paediatric population added.
Sevikar is not recommended for use has been deleted,
The safety and efficacy of Sevikar has been added.
of age due to lack of has been deleted,
has not been established has been added.
Data on safety and efficacy (see scetion 5.2) has been deleted,
No data are available has been added.
In section 4.3 (contraindications),
Cardiogenic shock has been deleted,
severe hypotension has been added.
shock (including cardiogenic shock), has been added
Acute obstruction has been deleted,
obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis) has been added.
Haemodynamically unstable heart failure after acute myocardial infarction has been added,
(within the first 4 weeks) has been deleted.
Unstable angina pectoris has been deleted.
In section 4.4 (special warnings and precautions),
Elderly patients: In the elderly, increase of the dosage should take place with care (see section 5.2), has been added.
In section 4.5 (Interaction other medicinal products).
Concomitant use requiring action, has been deleted
Effects of other medicinal products on amlodipine - has been added.
CYP3A4 inhibitors: A study in elderly patients showed that diltiazem inhibits the metabolism of amlodipine, probably via CYP3A4, since plasma concentrations of amlodipine increased by approximately 50% and its effect was increased. The possibility that more potent CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir) may increase the plasma concentration of amlodipine to a greater extent than diltiazem cannot be excluded - has been deleted.
With concomitant use of CYP3A4 inhibitor erythromycin in young patients and diltiazem in elderly patients respectively the plasma concentration of amlodipine increased by 22% and 50 % respectively. However, the clinical relevance of this finding is uncertain. It cannot be ruled out that strong inhibitors of CYP3A4 (i.e. ketoconazole, itraconazole, ritonavir) may increase the plasma concentrations of amlodipine to a greater extent than diltiazem. Amlodipine should be used with caution together with CYP3A4 inhibitors. However, no adverse events attributable to such interaction have been reported - has been added.
CYP3A4 inducers:
(anticonvulsants [e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone], rifampicin, Hypericum perforatum): - has been deleted.
There is no data available regarding the effect of CYP3A4 inducers on amlodipine. The concomitant use of CYP3A4 inducers (i.e. rifampicin, hypericum perforatum) may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers. - has been added.
Concomitant administration may decrease the plasma concentration of amlodipine. Clinical monitoring is indicated, with possible adjustment of amlodipine dosage during treatment with the CYP3A4 inducer and after its withdrawal. Sildenafil: When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect. Additional information: Concomitant administration of 240 ml of grapefruit juice with a single oral dose of 10 mg amlodipine in 20 healthy volunteers did not show a significant effect on the pharmacokinetic properties of amlodipine. Co-administration of amlodipine with cimetidine had no significant effect on the pharmacokinetics of amlodipine. Co-administration of amlodipine with atorvastatin, digoxin, warfarin or ciclosporin had no significant effect on the pharmacokinetics or pharmacodynamics of these agents - has been deleted
In clinical interaction studies, grapefruit juice, cimetidine, aluminium/ magnesium (antacid) and sildenafil did not affect the pharmacokinetics of amlodipine.
Effects of amlodipine on other medicinal products
The blood pressure lowering effects of amlodipine adds to the blood pressure-lowering effects of other antihypertensive agents.
In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, ethanol (alcohol), warfarin or cyclosporin.
There is no effect of amlodipine on laboratory parameters. - has been added.
In section 4.7 (effects on ability to drive and use machines),
No studies on the effects - has been deleted
can have minor or moderate influence - has been added
have been performed. However, it should be borne in mind that dizziness - has been deleted
Dizziness, headache, nausea - has been added
which may impair the ability to react - has been added
In section 4.8 (undesirable effects),
The most commonly reported adverse reactions during treatment with Sevikar are peripheral oedema (11.3%), headache (5.3%) and dizziness (4.5%). - has been added
Adverse reactions from - has been added
The safety of - has been deleted
was investigated - has been deleted
controlled - has been deleted
clinical trials, post-authorisation safety studies and spontaneous reporting are summarised - has been added
2892 patients receiving - has been deleted
the below table as well as adverse reactions from the individual components - has been added
in combination with - has been deleted
and - has been added
based on the known safety profile of these substances. - has been added
undesirable effects - has been deleted
adverse reactions - has been added
System organ class table updated - added
Additional information on the individual components
Adverse reactions previously reported with one of the individual components may be potential adverse reactions with Sevikar, even if not observed in clinical trials with this product.
Olmesartan medoxomil (active ingredient of Sevikar)
Further adverse events reported in clinical studies with olmesartan medoxomil monotherapy in hypertension were as follows: Angina pectoris, bronchitis, pharyngitis, rhinitis, abdominal pain, gastroenteritis, arthritis, skeletal pain, haematuria, urinary tract infection, chest pain, influenza-like symptoms, pain.
Further laboratory adverse events reported in clinical studies with olmesartan medoxomil monotherapy (irrespective of causality) were: Increased creatine phosphokinase, hypertriglyceridaemia, liver enzyme elevations.
In post-marketing experience with olmesartan medoxomil, additional adverse reactions reported, all at very rare frequency, were as follows: Thrombocytopenia, pruritus, exanthema, angioneurotic oedema, face oedema, allergic dermatitis, myalgia, acute renal failure, renal insufficiency, blood urea increased, malaise. - has been deleted.
A causal relationship, however, has not been established.
Additional information on special populations
In elderly patients the frequency of hypotension is slightly increased from rare to uncommon.
Amlodipine (active ingredient of Sevikar)
Further adverse reactions reported with amlodipine monotherapy were as follows:
Common additional adverse reactions are facial flushing and abdominal pain. Less common adverse reactions include: Leukocytopenia, thrombocytopenia, gynaecomastia, hyperglycaemia, sleep disorder, irritability, depression, confusion, mood changes including anxiety, malaise, tremor, increased sweating, taste changes, peripheral neuropathy, visual disturbances, tinnitus, chest pain, aggravation of angina pectoris, vasculitis, rhinitis, gingival hyperplasia, gastritis, elevated liver enzymes, jaundice, hepatitis, pancreatitis, increased micturition frequency, impotency, exanthema, pruritus, alopecia, skin discolouration, purpura, isolated cases of allergic reactions (pruritus, rash, angio-oedema, erythema exsudativum multiforme, exfoliative dermatitis, Stevens Johnson syndrome, Quincke oedema), myalgia, arthralgia, increase or decrease in weight. Isolated cases of myocardial infarction and arrhythmias (including extrasystole, ventricular tachycardia, bradycardia and atrial arrhythmias) and angina pectoris have been reported in patients with coronary artery disease, but a clear association with amlodipine has not been established. - has been deleted
In section 5.1 (Pharmacodynamic properties),
Mechanism of action - has been added
Clinical efficacy and safety - has been added
In a - has been deleted
A - has been added
treated with - has been deleted
receiving - has been added
amlodipine was - has been deleted
Has - has been added
not to cause any - has been deleted
that amlodipine did not lead to an - has been added
the , death or in the combined risk of- has been deleted
or combined mortality - has been added
A follow-up study (PRAISE 2) showed that amlodipine did not have an effect on the total or cardiovascular mortality of decompensatio cordis class III-IV patients without ischemic origin. In this study treatment with amlodipine was associated with an increase in pulmonary oedema, although this could not be related to an increase in symptoms. - has been deleted
In a follow-up, long-term, placebo controlled study (PRAISE-2) of amlodipine in patients with NYHA III and IV heart failure without clinical symptoms or objective findings suggestive of underlying ischaemic disease, on stable doses of ACE inhibitors, digitalis, and diuretics, amlodipine had no effect on total or cardiovascular mortality. In this same population amlodipine was associated with increased reports of pulmonary oedema despite no significant difference in the incidence of worsening heart failure as compared to placebo. - has been added
In section 5.2, (pharmacokinetic properties),
patients - has been deleted
population - has been added
Following oral intake of amlodipine, the time to peak plasma concentration is comparable in young and in elderly patients. In elderly patients, the clearance of amlodipine tends to decline, resulting in increases in AUC and in elimination half-life. - has been deleted
The time to reach peak plasma concentrations of amlodipine is similar in elderly and younger subjects. Amlodipine clearance tends to be decreased with resulting increases in AUC and elimination half life in elderly patients. Increases in AUC and elimination half life in patients with congestive heart failure were as expected for the patient age group in this study (see Section 4.4). - has been added
In section 5.3, (Preclinical safety data),
programme - has been deleted
program - has been added
programme -
programme -
programme -
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