natgillin/translations-raw huggingface dataset:
Enviage er kontraindikeret under 2. og 3. trimester af graviditeten.
As for any medicine that acts directly on the RAS, Enviage should not be used during the first trimester of pregnancy or in women planning to become pregnant and is contraindicated during the second and third trimesters (see section 4.3).
Amning Det vides ikke, om aliskiren udskilles i human modermælk.
Lactation It is not known whether aliskiren is excreted in human milk.
Enviage er evalueret med henblik på sikkerhed hos mere end 7. 800 patienter, herunder over 2. 300, som var i behandling i mere end 6 måneder, og mere end 1. 200, som var i behandling i over 1 år.
Enviage has been evaluated for safety in more than 7,800 patients, including over 2,300 treated for over 6 months, and more than 1,200 for over 1 year.
For patienter, der blev behandlet med placebo (0, 6%) svarede incidensen af hoste til incidensen for patienter, der blev behandlet med Enviage (0, 9%).
The incidence of cough was similar in placebo (0.6%) and Enviage treated (0.9%) patients.
Meget almindelig (≥1/ 10); almindelig (≥1/ 100 til, < 1/ 10); ikke almindelig (≥1/ 1. 000 til, < 1/ 100); sjælden (≥1/ 10. 000 til, < 1/ 1. 000); meget sjælden (< 1/ 10. 000), inklusive enkeltstående rapporter.
The adverse drug reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (< 1/ 10,000), including isolated reports.
5 Tabel 1
5 Table 1
I tilfælde af tegn tydende på en allergisk reaktion (særligt besvær med vejrtrækning eller synkning, hævelse i ansigtet, ekstremiteterne, øjne, læber og/ eller tunge), bør patienten afbryde behandlingen og kontakte lægen.
In the event of any signs suggesting an allergic reaction (in particular difficulties in breathing, or swallowing, or swelling of the face, extremities, eyes, lips and/ or tongue) patients should discontinue treatment and contact the physician.
Laboratoriefund I kontrollerede kliniske forsøg blev klinisk relevante ændringer i standardlaboratorieparametre i få tilfælde associeret med administration af Enviage.
Laboratory findings In controlled clinical trials, clinically relevant changes in standard laboratory parameters were uncommonly associated with the administration of Enviage.
I kliniske studier af hypertensive patienter havde Enviage ingen klinisk signifikant virkning på total kolesterol, HDL- kolesterol, fastende triglycerider, fastende glukose eller urinsyre.
In clinical studies in hypertensive patients, Enviage had no clinically important effects on total cholesterol, high density lipoprotein cholesterol (HDL-C), fasting triglycerides, fasting glucose or uric acid.
Hæmoglobin og hæmatokritværdi:
Haemoglobin and haematocrit:
0, 05 mmol/ l og 0, 16 volumenprocent).
Small decreases in haemoglobin and haematocrit (mean decreases of approximately 0.05 mmol/ l and 0.16 volume percent, respectively) were observed.
ACE- hæmmere og angiotensin- II- antagonister.
This effect is also seen with other agents acting on the renin- angiotensin system, such as angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers.
Serumkalium:
Serum potassium:
Stigningerne i serumkalium var minimale og ikke hyppige hos patienter med essentiel hypertension, som blev behandlet med Enviage alene (0, 9% kontra 0, 6% med placebo).
Increases in serum potassium were minor and infrequent in patients with essential hypertension treated with Enviage alone (0.9% compared to 0.6% with placebo).
I et studie, hvor Enviage blev anvendt sammen med en ACE- hæmmer i en diabetisk population, var stigningerne i serumkalium dog mere hyppige (5, 5%).
However, in one study where Enviage was used in combination with an ACEI in a diabetic population, increases in serum potassium were more frequent (5.5%).
Derfor er rutinemæssig monitorering af elektrolytter og nyrefunktion som ved andre stoffer, der virker på RAS- systemet, indiceret i patienter med diabetes mellitus, nyresygdom eller hjertesvigt.
Therefore as with any agent acting on the RAS system, routine monitoring of electrolytes and renal function is indicated in patients with diabetes mellitus, kidney disease, or heart failure.
Reninhæmmer, ATC- kode:
Renin inhibitor, ATC code:
Aliskiren er en oral aktiv, non- peptid, potent og selektiv direkte hæmmer af humant renin.
Aliskiren is an orally active, non-peptide, potent and selective direct inhibitor of human renin.
Ved at hæmme enzymet renin hæmmer aliskiren RAS- systemets aktiveringspunkt og blokerer konverteringen af angiotensinogen til angiotensin I og mindsker niveauet af angiotensin I og angiotensin II.
By inhibiting the enzyme renin, aliskiren inhibits the RAS at the point of activation, blocking the conversion of angiotensinogen to angiotensin I and decreasing levels of angiotensin I and angiotensin II.
50- 80%.
Whereas other agents that inhibit the RAS (ACEI and angiotension II receptor blockers (ARB)) cause a compensatory rise in plasma renin activity (PRA), treatment with aliskiren decreases PRA in hypertensive patients by approximately 50 to 80%.
Forhøjet PRA er uafhængigt associeret med øget kardiovaskulær risiko hos hypertensive og normotensive patienter.
Elevated PRA has been independently associated with increased cardiovascular risk in hypertensive and normotensive patients.
6 Hypertension Hos hypertensive patienter gav administration af Enviage en gang dagligt i doser på 150 mg og 300 mg dosisafhængige reduktioner i både det systoliske og det diastoliske blodtryk, som blev opretholdt over hele dosisintervallet på 24 timer (med vedvarende gavnlig virkning tidligt om morgenen) med en gennemsnitlig peak/ trough ratio for diastolisk respons på op til 98% for 300- mg - dosen.
6 Hypertension In hypertensive patients, once-daily administration of Enviage at doses of 150 mg and 300 mg provided dose-dependent reductions in both systolic and diastolic blood pressure that were maintained over the entire 24-hour dose interval (maintaining benefit in the early morning) with a mean peak to trough ratio for diastolic response of up to 98% for the 300 mg dose.
85- 90% af den maksimale blodtrykssænkende effekt blev observeret efter 2 uger.
85 to 90% of the maximal blood- pressure-lowering effect was observed after 2 weeks.
Enviage er undersøgt i 1. 864 patienter i alderen 65 år eller derover og i 426 patienter i alderen 75 år eller derover.
Enviage has been studied in 1,864 patients aged 65 years or older, and in 426 patients aged 75 years or older.
Undersøgelser af Enviage- monoterapi har vist en blodtrykssænkende effekt, som er sammenlignelig med andre klasser af antihypertensiva, herunder ACE- hæmmere og angiotension- II- antagonister.
Enviage monotherapy studies have shown blood pressure lowering effects comparable to other classes of antihypertensive agents including ACEI and ARB.
Sammenlignet med et diuretikum (hydrochlortiazid – HCTZ) sænkede Enviage 300 mg det systoliske/ diastoliske blodtryk med 17, 0/ 12, 3 mmHg sammenlignet med 14, 4/ 10, 5 mmHg for HCTZ 25 mg efter 12 ugers behandling.
Compared to a diuretic (hydrochlorothiazide - HCTZ), Enviage 300 mg lowered systolic/ diastolic blood pressure by 17.0/ 12.3 mmHg, compared to 14.4/ 10.5 mmHg for HCTZ 25 mg after 12 weeks of treatment.
Der er undersøgelser af kombinationsbehandling tilgængelige hvor Enviage er kombineret med diuretikaet hydrochlorthiazid, ACE- hæmmeren ramipril, calciumkanal- blokkeren amlodipin og angiotensinreceptor- antogonisten valsartan og betablokeren atenolol.
Combination therapy studies are available for Enviage added to the diuretic hydrochlorothiazide, the ACEI ramipril, the calcium channel blocker amlodipine, the angiotensin receptor antagonist valsartan, and the beta blocker atenolol.
Hos patienter, som ikke responderede tilstrækkeligt på 5 mg af calciumantagonisten amlodipin, havde kombinationen med Enviage 150 mg en blodtrykssænkende virkning, som svarede til den opnåede virkning ved at amlodipindosen blev øget til 10 mg, men med en lavere incidens af ødem (aliskiren 150 mg/ amlodipin 5 mg 2, 1% kontra amlodipin 10 mg 11, 2%).
In patients who did not adequately respond to 5 mg of the calcium channel blocker amlodipine, the addition of Enviage 150 mg had a blood-pressure-lowering effect similar to that obtained by increasing amlodipine dose to 10 mg, but had a lower incidence of oedema (aliskiren 150 mg/ amlodipine 5 mg 2.1% vs. amlodipine 10 mg 11.2%).
Enviage i kombination med angiotensinreceptor- antagonisten valsartan viste en additiv blodtrykssænkende effekt i et studie specifikt designet til at undersøge effekten af kombinationsterapien.
Enviage in combination with the angiotensin receptor antagonist valsartan showed an additive antihypertensive effect in the study specifically designed to investigate the effect of the combination therapy.
Hos hypertensive patienter med diabetes gav Enviage en additiv blodtryksreduktion, når det blev kombineret med ramipril, mens kombination af Enviage og ramipril havde en lavere incidens af hoste (1, 8%) end ramipril (4, 7%).
In diabetic hypertensive patients, Enviage provided additive blood pressure reductions when added to ramipril, while the combination of Enviage and ramipril had a lower incidence of cough (1.8%) than ramipril (4.7%).
Kraftig hypotension var usædvanlig (0, 1%) hos patienter med ukompliceret hypertension, som blev behandlet med Enviage alene.
Excessive hypotension was uncommonly (0.1%) seen in patients with uncomplicated hypertension treated with Enviage alone.
Hypotension var også usædvanlig (< 1%) under kombinationsbehandling med andre antihypertensiva.
Hypotension was also uncommon (< 1%) during combination therapy with other antihypertensive agents.
I et 3- måneders studie med 302 patienter med let stabilt hjertesvigt, som alle var i standardbehandling for stabilt hjertesvigt blev tillæg af Enviage 150 mg godt tolereret.
In a 3-month study of 302 patients with mild stable heart failure, all of whom were receiving standard therapy for stable heart failure, addition of Enviage 150 mg was well tolerated.
Type B natriuretisk peptid (BNP) - niveauet blev nedsat med 25% i Enviage- armen sammenlignet med placebo.
B-type natriuretic peptide (BNP) levels were reduced by 25% in the Enviage arm compared to placebo.
I et 6 måneders studie med 599 hypertensionspatienter med type 2 diabetes mellitus og nefropati, der alle fik 100 mg losartan sammen med optimal antihypertensiv standardbehandling, opnåede ved tillæg af Enviage 300 mg en 20% reduktion i forhold til placebo i urin- albumin- kreatininforholdet (UACR), dvs. fra 58 mg/ mmol til 46 mg/ mmol.
In a 6-month study of 599 patients with hypertension, type 2 diabetes mellitus, and nephropathy, all of whom were receiving losartan 100 mg and optimised antihypertensive background therapy, addition of Enviage 300 mg achieved a 20% reduction versus placebo in urinary albumin: creatinine ratio (UACR), i. e. from 58 mg/ mmol to 46 mg/ mmol.
Andelen af patienter, som fik UACR reduceret med mindst 50% fra baseline ved forsøgets slutning var henholdsvis 24, 7% for Enviage og 12, 5% for placebo.
The proportion of patients who had UACR reduced at least 50% from baseline to endpoint was 24.7% and 12.5% for Enviage and placebo, respectively.
Enviage påvirkede ikke serumkoncentrationen af kreatinin men blev forbundet med en øget frekvens (4, 2% vs.
Enviage did not affect the serum concentration of creatinine but was associated with an increased frequency (4.2% vs.
1, 9% for placebo) af serum- kaliumkoncentrationen (≥ 6, 0 mmol), selvom det ikke var statistisk signifikant.
1.9% for placebo) of serum potassium concentration (≥ 6.0 mmol/ l), although this was not statistically significant.
7 Gavnlige virkninger af Enviage med hensyn til mortalitet, kardiovaskulær morbiditet og organskade er for nærværende ikke kendt.
7 Beneficial effects of Enviage on mortality and cardiovascular morbidity and target organ damage are currently unknown.
Kardiel elektrofysiologi Ingen effekt på QT- intervallet blev rapporteret i et randomiseret, dobbeltblindet, placebo og aktivt kontrolleret studie ved anvendelse af standard og Holter elektrokardiografi.
Cardiac electrophysiology No effect on QT interval was reported in a randomised, double-blind, placebo, and active-controlled study using standard and Holter electrocardiography.
Absorption Efter oral absorption nås de maksimale plasmakoncentrationer af aliskiren efter 1- 3 timer.
Absorption Following oral absorption, peak plasma concentrations of aliskiren are reached after 1-3 hours.
2- 3%.
The absolute bioavailability of aliskiren is approximately 2-3%.
Måltider med højt fedtindhold reducerer Cmax med 85% og AUC med 70%.
Meals with a high fat content reduce Cmax by 85% and AUC by 70%.
2 gange større end ved initialdosen.
Steady-state-plasma concentrations are reached within 5-7 days following once-daily administration and steady-state levels are approximately 2-fold greater than with the initial dose.
Fordeling Efter intravenøs administration er det gennemsnitlige distributionsvolumen omkring 135 liter, hvilket indikerer, at aliskiren distribueres omfattende i det ekstravaskulære rum.
Distribution Following intravenous administration, the mean volume of distribution at steady state is approximately 135 litres, indicating that aliskiren distributes extensively into the extravascular space.
Aliskirens plasmaproteinbinding er moderat (47- 51%) og uafhængig af koncentrationen.
Aliskiren plasma protein binding is moderate (47-51%) and independent of the concentration.
40 timer (interval 34- 41 timer).
Metabolism and elimination The mean half-life is about 40 hours (range 34-41 hours).
Aliskiren udskilles hovedsageligt som et uændret stof i fæces (78%).
Aliskiren is mainly eliminated as unchanged compound in the faeces (78%).
Cirka 1, 4% af den totale orale dosis bliver metaboliseret.
Approximately 1.4% of the total oral dose is metabolised.
Omkring 0, 6% af dosis genfindes i urinen efter oral administration.
Approximately 0.6% of the dose is recovered in urine following oral administration.
9 l/ time.
Following intravenous administration, the mean plasma clearance is approximately 9 l/ h.
Linearitet/ non- linearitet Eksponeringen med aliskiren øgedes mere end proportionelt sammenlignet med stigningen i dosis.
Linearity/ non-linearity Exposure to aliskiren increased more than in proportion to the increase in dose.
Efter administration af en enkelt dosis i intervallet 75 til 600 mg, resulterede en fordobling i dosis i en ~2, 3 og 2, 6 fold stigning i respektivt AUC og Cmax.
After single dose administration in the dose range of 75 to 600 mg, a 2-fold increase in dose results in a ~2.3 and 2.6- fold increase in AUC and Cmax, respectively.
Ved steady state kan non- linearitet være mere udtalt.
At steady state the non-linearity may be more pronounced.
Patientkarakteristika Aliskiren er en effektiv en gang daglig antihypertensiv behandling til voksne patienter uanset køn, alder, BMI og etnicitet.
Characteristics in patients Aliskiren is an effective once-a-day antihypertensive treatment in adult patients, regardless of gender, age, body mass index and ethnicity.
AUC er 50% højere hos ældre (> 65 år) end hos yngre individer.
The AUC is 50% higher in elderly (> 65 years) than in young subjects.
Den relative AUC og Cmax for aliskiren hos personer med nedsat nyrefunktion lå på mellem 0, 8 og 2 gange niveauet hos raske personer efter administration af en enkelt dosis og ved steady state.
Relative AUC and Cmax of aliskiren in subjects with renal impairment ranged between 0.8 to 2 times the levels in healthy subjects following single dose administration and at steady state.
Det karcinogene potentiale blev vurderet i et 2- årigt rottestudie og i et 6- måneders studie af transgene mus.
Carcinogenic potential was assessed in a 2-year rat study and a 6-month transgenic mouse study.
Der er registreret et tilfælde af adenom i kolon og et tilfælde af adenocarcinom i coecum hos rotter ved dosen 1. 500 mg/ kg/ dag, hvilket ikke var statistisk signifikant.
One colonic adenoma and one caecal adenocarcinoma recorded in rats at the dose of 1,500 mg/ kg/ day were not statistically significant.
Selvom aliskiren har et kendt irritationspotentiale blev de opnåede sikkerhedsmargener i et studie på raske frivillige forsøgspersoner hos mennesker ved en dosis på 300 mg anset for at være passende ved 9- 11 gange baseret på fækale koncentrationer eller 6 gange baseret på koncentrationerne i mucosa, sammenlignet med 250 mg/ kg/ dag i karcinogenitetsstudiet hos rotter.
Although aliskiren has known irritation potential, safety margins obtained in humans at the dose of 300 mg during a study in healthy volunteers were considered to be appropriate at 9-11-fold based on faecal concentrations or 6-fold based on mucosa concentrations in comparison with 250 mg/ kg/ day in the rat carcinogenicity study.
Aliskiren havde ikke noget mutagent potentiale i in vitro - og in vivo- mutagenicitetsstudierne.
Aliskiren was devoid of any mutagenic potential in the in vitro and in vivo mutagenicity studies.
Analyserne omfattede in vitro- analyser af bakterie - og pattedyrsceller og in vivo- vurderinger hos rotter.
The assays included in vitro assays in bacterial and mammalian cells and in vivo assessments in rats.
Studier af aliskirens reproduktive toksicitet viste ingen tegn på embryoføtal toksicitet eller teratogenicitet ved doser på op til 600 mg/ kg/ dag hos rotter eller 100 mg/ kg/ dag hos kaniner.
Reproductive toxicity studies with aliskiren did not reveal any evidence of embryofoetal toxicity or teratogenicity at doses up to 600 mg/ kg/ day in rats or 100 mg/ kg/ day in rabbits.
Fertiliteten og den præ - og postnatale udvikling blev ikke påvirket hos rotter ved doser på op til 250 mg/ kg/ dag.
Fertility, pre-natal development and post-natal development were unaffected in rats at doses up to 250 mg/ kg/ day.
Doserne hos rotter og kaniner gav en systemisk eksponering, der var henholdsvis 1- 4 og 5 gange højere end den maksimale anbefalede humane dosis (300 mg).
The doses in rats and rabbits provided systemic exposures of 1 to 4 and 5 times higher, respectively, than the maximum recommended human dose (300 mg).
Hændelser under gentagen- dosis toksicitetsstudier i dyr var i overensstemmelse med det kendte potentiale for lokalirritation eller de forventede farmakologiske effekter af aliskiren.
Findings during repeat-dose toxicity studies in animals were consistent with the known local irritation potential or the expected pharmacological effects of aliskiren.
Crospovidon Magnesiumstearat Cellulose, mikrokrystallinsk Povidon Silica, kolloid vandfri Hypromellose Macrogol Talcum Jernoxid, sort (E172) Jernoxid, rød (E172) Titandioxid (E171)
Crospovidone Magnesium stearate Cellulose, microcrystalline Povidone Silica, colloidal anhydrous Hypromellose Macrogol Talc Iron oxide, black (E 172) Iron oxide, red (E 172) Titanium dioxide (E 171)
9 6. 5 Emballagetype og pakningsstørrelser
9 6.5 Nature and contents of container
PA/ Alu/ PVC blister.
PA/ Alu/ PVC blisters
Lyserød, udadbuet, oval tablet, præget med ” IU ” på den ene side og ” NVR ” på den anden side.
Light-red, biconvex, ovaloid tablet, imprinted “ IU ” on one side and “ NVR” on the other side.
4. 3 Kontraindikationer
11 4.3 Contraindications
4. 6).
Second and third trimesters of pregnancy (see section 4.6).
Patienter, som anvender andre lægemidler, der hæmmer renin- angiotensin systemet (RAS), og/ eller har nedsat nyrefunktion og/ eller diabetes mellitus, har en øget risiko for hyperkalæmi under behandling med aliskiren.
Patients receiving other medicinal products inhibiting the renin-angiotensin system (RAS), and/ or those with reduced kidney function and/ or diabetes mellitus are at an increased risk of hyperkalaemia during aliskiren therapy.
Samtidig administration af Enviage havde ingen signifikant indvirkning på atorvastatins, valsartans, metformins eller amlodipins farmakokinetik.
Co- administration of Enviage had no significant impact on atorvastatin, valsartan, metformin or
12 Foreløbige data tyder på at irbesartan kan nedsætte AUC og Cmax for Enviage.
Preliminary data suggest that irbesartan may decrease Enviage AUC and Cmax.
Kalium og kaliumbesparende diuretika Baseret på erfaringer med andre stoffer, som påvirker renin- angiotensin- systemet kan samtidig brug af kaliumbesparende diuretika, kaliumtilskud, kaliumholdige salterstatninger eller andre stoffer, som kan
13 Potassium and potassium-sparing diuretics Based on experience with the use of other substances that affect the renin-angiotensin system, concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other substances that may increase serum potassium levels (e. g. heparin) may lead to increases in serum potassium.
14 Tabel 1
14 Table 1
15 Hypertension Hos hypertensive patienter gav administration af Enviage en gang dagligt i doser på 150 mg og 300 mg dosisafhængige reduktioner i både det systoliske og det diastoliske blodtryk, som blev opretholdt over hele dosisintervallet på 24 timer (med vedvarende gavnlig virkning tidligt om morgenen) med en gennemsnitlig peak/ trough ratio for diastolisk respons på op til 98% for 300- mg - dosen.
15 Hypertension In hypertensive patients, once-daily administration of Enviage at doses of 150 mg and 300 mg provided dose-dependent reductions in both systolic and diastolic blood pressure that were maintained over the entire 24-hour dose interval (maintaining benefit in the early morning) with a mean peak to trough ratio for diastolic response of up to 98% for the 300 mg dose.
16 Gavnlige virkninger af Enviage med hensyn til mortalitet, kardiovaskulær morbiditet og organskade er for nærværende ikke kendt.
16 Beneficial effects of Enviage on mortality and cardiovascular morbidity and target organ damage are currently unknown.
17 5. 3 Prækliniske sikkerhedsdata
17 5.3 Preclinical safety data
18 6. 5 Emballagetype og pakningsstørrelser
18 6.5 Nature and contents of container
Via Provinciale Schito 131 I- 80058 Torre Annunziata/ NA Italien
Via Provinciale Schito 131 I-80058 Torre Annunziata/ NA Italy
Pharmacovigilancesystem Indehaveren af markedsføringstilladelsen skal sikre at pharmacovigilancesystemet, som beskrevet i version 2 (dateret 5. juli 2006) præsenteret i modul 1. 8. 1 af ansøgningen om markedsføringstilladelse, er på plads og operativt før og mens produktet er på markedet.
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 2 (dated 5 July 2006) presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Risk ManagementPlan Indehaveren af markedsføringstilladelsen forpligter sig til at udføre studier og yderligere pharmacovigilance- aktiviteter som beskrevet i pharmacovigilance- planen, som aftalt i versionen af 30. maj 2007 af risk management planen (RMP), præsenteret i modul 1. 8. 2 af ansøgningen om markedsførringstilladelse og enhver efterfølgende opdatering af RMP aftalt af CHMP.
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 30 May 2007 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
I henhold til CHMPs ” Guideline on Risk Management Systems for medicinal products for human use ”, bør den opdaterede RMP indsendes samtidig som den næste Periodic Safety Update Report (PSUR).
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).