qanastek/EMEA-V3 huggingface dataset:
Sodium and/ or volume depleted patients In patients with marked volume- and/ or salt-depletion (e. g. those receiving high doses of diuretics) symptomatic hypotension could occur after initiation of treatment with Enviage.
Pazjenti li għandhom nuqqas ta ’ sodium u/ jew volum F’ pazjenti li jkollhom nuqqas serju ta ’ volum u/ jew melħ (eż dawk li qed jingħataw dożi għoljin ta ’ dijuretiċi) jista ’ jkun hemm sintomi ta ’ pressjoni baxxa wara li tibda l- kura b’ Enviage.
This condition should be corrected prior to administration of Enviage, or the treatment should start under close medical supervision.
Din il - kundizzjoni għandha tiġi korretta qabel ma jingħata Enviage, jew il- kura għandha tinbeda taħt superviżjoni medika stretta.
Renal impairment In clinical studies Enviage has not been investigated in hypertensive patients with severe renal impairment (serum creatinine ≥ 150 μ mol/ l or 1.70 mg/ dl in women and ≥ 177 μ mol/ l or 2.00 mg/ dl in men and/ or estimated glomerular filtration rate (GFR) < 30 ml/ min), history of dialysis, nephrotic syndrome or renovascular hypertension.
Indeboliment renali Fil- provi kliniċi, Enviage ma ġiex investigat f’ pazjenti li għandhom il- pressjoni għolja u li jbatu minn indeboliment renali sever (krejatinina fis- serum ≥ 150 μmol/ l jew 1. 70 mg/ dl fin- nisa u ≥ 177 μmol/ l jew 2. 00 mg/ dl fl- irġiel u/ jew rata ta ’ filtrazzjoni fil- glomeruli (GFR) stmata < 30 ml/ min), li kellhom dijalisi fil- passat, sindrome nefrotika jew pressjoni għolja renovaskulari.
Caution should be exercised in hypertensive patients with severe renal impairment due to the lack of safety information for Enviage.
Għandu jkun hemm kawtela f’ pazjenti bil- pressjoni għolja b’ indeboliment renali sever minħabba n- nuqqas ta ’ tagħrif dwar is - sigurtà li hemm għal Enviage.
Renal artery stenosis No data are available on the use of Enviage in patients with unilateral or bilateral renal artery stenosis, or stenosis to a solitary kidney.
Stenożi ta ’ l- arterja renali M’ hemmx tagħrif dwar l- użu ta ’ Enviage f’ pazjenti bi stenożi ta ’ l- arterja renali unilaterali jew bilaterali, jew fi stenożi f’ kilwa waħda.
Moderate P-gp inhibitors Co-administration of aliskiren 300 mg with ketoconazole 200 mg resulted in a 76% increase in aliskiren AUC but P-gp inhibitors such as ketoconazole are expected to increase tissue concentrations more than plasma concentrations.
Inibituri moderati ta ’ P- gp L- għotja fl- istess ħin ta ’ aliskiren 300 mg ma ’ ketoconazole 200 mg wasslet għal żieda ta ’ 76% fl - AUC ta ’ aliskiren iżda inibituri ta ’ P- gp bħal ketoconazole huma mistennija li jgħollu l - konċentrazzjonijiet fit- tessuti aktar milli fil- plażma.
Therefore caution should be exercised when aliskiren is administered with moderate P-gp inhibitors such as ketoconazole (see section 4.5).
Għalhekk, għandha ssir kawtela meta aliskiren jingħata ma ’ inibituri ta ’ P- gp moderati bħal ketoconazole (ara sezzjoni 4. 5).
Enviage has no known clinically relevant interactions with medicinal products commonly used to treat hypertension or diabetes.
Enviage mhux magħruf li jagħmel interazzjonijiet li għandhom rilevanza klinika ma ’ prodotti mediċinali li jintużaw għall- kura ta ’ pressjoni għolja jew dijabete.
Compounds that have been investigated in clinical pharmacokinetic studies include acenocoumarol, atenolol, celecoxib, pioglitazone, allopurinol, isosorbide-5-mononitrate, ramipril and hydrochlorothiazide.
Komposti kimiċi li kienu investigati fi studji ta ’ farmakokinetika klinika kienu jinkludu acenocoumarol, atenolol, celecoxib, pioglitazone, allopurinol, isosorbide- 5- mononitrate, ramipril u hydrochlorothiazide.
No interactions have been identified.
L- ebda interazzjonijiet ma ġew identifikati.
Co-administration of aliskiren with either valsartan (↓ 28%), metformin (↓ 28%), amlodipine (↑ 29%) or cimetidine (↑ 19%) resulted in between 20% and 30% change in Cmax or AUC of Enviage.
Meta aliskiren jingħata ma ’ valsartan (↓28%), metformin (↓28%), amlodipine (↑29%) jew cimetidine (↑19%) is- Cmax jew AUC ta ’ Enviage inbidlu b’ bejn 20% u 30%.
When administered with atorvastatin, steady-state Enviage AUC and Cmax increased by 50%.
Meta ngħata ma ’ atorvastatin, l- AUC u Cmax fi stat fiss ta ’ Enviage żdiedu b’ 50%.
Co- administration of Enviage had no significant impact on atorvastatin, valsartan, metformin or amlodipine pharmacokinetics.
Meta Enviage ingħata ma ’ atorvastatin, valsartan, metformin jew amlodipine dan ma kellux impatt sinifikanti fuq il- farmakokinetika tagħhom.
As a result no dose adjustment for Enviage or these co-administered medicinal products is necessary.
Għalhekk, m’ hemmx bżonn ta ’ aġġustar tad- doża għal Enviage jew ta ’ dawn il- prodotti mediċinali li jingħataw miegħu.
Digoxin bioavailability may be slightly decreased by Enviage.
3 Il- biodisponibilità ta ’ digoxin tista ’ titnaqqas xi ftit b’ Enviage.
3 Preliminary data suggest that irbesartan may decrease Enviage AUC and Cmax.
Tagħrif preliminari jindika li irbesartan jista ’ jnaqqas xi ftit l- AUC u s- Cmax ta ’ Enviage.
In experimental animals, it has been shown that P-gp is a major determinant of Enviage bioavailability.
F’ annimali esperimentali, intwera li P- gp jiddetermina bil- kbir il- biodisponibilità ta ’ Enviage.
Inducers of P-gp (St.
Indutturi ta ’ P- gp (St.
John’ s wort, rifampicin) might therefore decrease the bioavailability of Enviage.
John’ s wort, rifampicin) għalhekk jistgħu jnaqqsu l- biodisponibilità ta ’ Enviage.
CYP450 interactions Aliskiren does not inhibit the CYP450 isoenzymes (CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A).
Interazzjonijiet ma ’ CYP450 Aliskiren ma jinibixxix l- iżoenzimi CYP450 (CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1 u 3A).
Aliskiren does not induce CYP3A4.
Aliskiren ma jinduċix CYP3A4.
Therefore aliskiren is not expected to affect the systemic exposure of substances that inhibit, induce or are metabolised by these enzymes.
Għalhekk aliskiren mhux mistenni li jeffettwa l- esponiment sistemiku ta ’ sustanzi li jinibixxu, jinduċu jew jiġu metabolizzati b’ dawn l- enzimi.
Aliskiren is metabolised minimally by the cytochrome P450 enzymes.
Aliskiren jiġi metabolizzat mill - anqas mill- enzimi cytochrome P450.
Hence, interactions due to inhibition or induction of CYP450 isoenzymes are not expected.
Għalhekk, interazzjonijiet minħabba l- inibizzjoni jew l - induzzjoni ta ’ l- isoenzimi CYP450 mhumiex mistennija.
However, CYP3A4 inhibitors often also affect P-gp.
Madankollu, inibituri ta ’ CYP3A4 ta ’ spiss jeffettwaw ukoll P- gp.
Increased aliskiren exposure during co-administration of CYP3A4 inhibitors that also inhibit P-gp can therefore be expected (see P-glycoprotein interactions below).
Żieda fl- esponiment għal aliskiren waqt l- għotja fl- istess ħin ta ’ inibituri ta ’ CYP3A4 li jimpedixxu wkoll P- gp tista ’ għalhekk tkun mistennija (ara interazzjonijiet ma ’ glikoproteina- P hawn taħt).
P-glycoprotein interactions MDR1/ Mdr1a/ 1b (P-gp) was found to be the major efflux system involved in intestinal absorption and biliary excretion of aliskiren in preclinical studies.
Interazzjonijiet ma ’ glikoproteina P Fi studji ta ’ qabel l- użu kliniku instab li MDR1/ Mdr1a/ 1b (P- gp) hija s- sistema ta ’ effluss li hi l- aktar involuta fl- assorbiment mill- imsaren u tneħħija mill- marrara ta ’ aliskiren.
John’ s wort, rifampicin) might therefore decrease the bioavailability of Enviage.
John’ s Wort, rifampicin) għalhekk jistgħu jnaqqsu l- bijodisponibilità ta ’ Enviage.
Although this has not been investigated for aliskiren, it is known that P-gp also controls tissue uptake of a variety of substrates and P-gp inhibitors can increase the tissue-to-plasma concentration ratios.
Għalkemm din ma ġietx investigata għal aliskiren, huwa magħruf li P- gp jikkontrolla wkoll it- teħid ta ’ varjetà ta ’ sottostrati mit- tessuti u inibituri ta ’ P- gp jistgħu jżidu l- proporzjon tal- konċentrazzjoni tat- tessuti mal- plażma.
Therefore, P-gp inhibitors may increase tissue levels more than plasma levels.
Għalhekk inibituri ta ’ P- gp jistgħu iżidu l- livelli fit- tessuti aktar mill- livelli fil- plażma.
The potential for drug interactions at the P-gp site will likely depend on the degree of inhibition of this transporter.
Il- potenzjal ta ’ interazzjonijiet fis- sit P- gp x’ aktarx li jkunu jiddependu mill- grad ta ’ inibizzjoni tat- trasportatur.
P-gp substrates or weak inhibitors No relevant interactions with atenolol, digoxin, amlodipine or cimetidine have been observed.
Sottostrati ta ’ P- gp jew inibituri dgħajfa Ma dehru l- ebda interazzjonijiet rilevanti ma ’ atenolol, digoxin, amlodipine jew cimetidine.
When administered with atorvastatin (80 mg), steady-state aliskiren (300 mg) AUC and Cmax increased by 50%.
Meta ingħata ma ’ atorvastatin (80 mg), l- AUC u Cmax ta ’ aliskiren (300 mg) fi stat fiss żdiedu b’ 50%.
Moderate P-gp inhibitors Co-administration of ketoconazole (200 mg) with aliskiren (300 mg) resulted in an 80% increase in plasma levels of aliskiren (AUC and Cmax).
Inibituri moderati ta ’ P- gp L- għoti ta ’ ketoconazole (200 mg) ma ’ aliskiren (300 mg) irriżulta f’ żieda ta ’ 80% fil- livelli tal - plażma ta ’ aliskiren (AUC u Cmax).
Preclinical studies indicate that aliskiren and ketoconazole co-administration enhances aliskiren gastrointestinal absorption and decreases biliary excretion.
Studji prekliniċi jindikaw li l- għoti ta ’ aliskiren ma ’ ketoconazole jtejjeb l- assorbiment gastrointestinali ta ’ aliskiren u jnaqqas l- eskrezzjoni biljari.
The change in plasma levels of aliskiren in the presence of ketoconazole is expected to be within the range that would be achieved if the dose of aliskiren were doubled; aliskiren doses of up to 600 mg, or twice the highest recommended therapeutic dose, have been found to be well tolerated in controlled clinical trials.
Il- bidla fil- livelli tal - plażma ta ’ aliskiren fil- preżenza ta ’ ketoconazole hija mistennija li tkun fil- medda li tintlaħaq li kieku d- doża ta ’ aliskiren kellha tiġi rduppjata; id- dożi ta ’ aliskiren ta ’ mhux aktar minn 600 mg, jew darbtejn l- ogħla d- doża terapewtika rakkomandata, instabu li jkunu ttollerati sewwa fi provi kliniċi kkontrollati.
Yet, P-gp inhibitors are expected to increase tissue concentrations more than plasma concentrations.
Madankollu, inibituri ta ’ P- gp huma mistennija li jgħollu l- konċentrazzjonijiet fit- tessuti aktar milli fil- plażma.
Therefore, caution should be exercised when aliskiren is administered with ketoconazole or other moderate pgp inhibitors (itraconazol, clarithromycin, telithromycin, erythromycin, amiodarone).
Għalhekk għandha issir kawtela meta aliskiren jingħata ma ’ ketoconazole jew inibituri moderati oħrajn ta ’ P- gp (itraconazol, clarithromycin, telithromycin, erythromycin, amiodarone).
P-gp potent inhibitors A single dose drug interaction study in healthy subjects has shown that ciclosporin (200 and 600 mg) increases Cmax of aliskiren 75 mg approximately 2.5-fold and AUC approximately 5-fold.
Inibituri potenti ta ’ P- gp Studju dwar interazzjoni b’ doża waħda f’ individwi b’ saħħithom wera li ciclosporin (200 u 600 mg) iżid is- Cmax ta ’ aliskiren 75 mg b’ madwar 2. 5 drabi u l- AUC b’ madwar 5 darbiet.
The increase may be higher with higher aliskiren doses.
Iż- żiediet jistgħu jkunu ogħla b’ dożi ogħla ta ’ aliskiren.
Therefore, concomitant use of aliskiren and P-gp potent inhibitors is contraindicated (see section 4.3).
Għalhekk, l- użu ta ’ aliskiren u inibituri potenti ta ’ P- gp f’ daqqa huwa kontra- indikat (ara sezzjoni 4. 3).
Furosemide When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide were reduced by 28% and 49% respectively.
Furosemide Meta aliskiren ingħata ma ’ furosemide, l- AUC u Cmax ta ’ furosemide tnaqqsu b’ 28% u 49% rispettivament.
It is therefore recommended that the effects be monitored when initiating and adjusting furosemide therapy to avoid possible under-utilisation in clinical situations of volume overload.
Għalhekk huwa irrakkomandat li l- effetti jkunu monitorati meta tinbeda u tkun qed tiġi aġġustata t- terapija ta ’ furosemide biex dan ma jkunx sotto- utilizzat f’ sitwazzjonijiet kliniċi ta ’ volum żejjed.
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 u dijuretiċi li ma jħallux il- potassium jintilef Minn esperjenza b’ sustanzi oħrajn li jeffettwaw is- sistema renin- angiotensin, l- użu ta ’ dijuretiċi li ma jħallux il- potassium jintilef, supplimenti tal- potassium, sostituti tal- melħ li fihom il- potassium jew
4 potassium or other substances that may increase serum potassium levels (e. g. heparin) may lead to increases in serum potassium.
4 sustanzi oħra li jistgħu jżidu l- livelli ta ’ potassium fis- serum (eż heparin) jistgħu jwasslu għal żidied tal- potassium fis- serum.
If co-medication is considered necessary, caution is advisable.
Jekk ikun meħtieġ li jingħataw f’ daqqa, huwa xieraq li tittieħed il- kawtela
Grapefruit juice Due to the lack of data a potential interaction between grapefruit juice and aliskiren cannot be excluded.
Meraq tal- grejpfrut Minħabba nuqqas ta ’ dejta interazzjonijiet li jista ’ jkun hemm bejn il- meraq tal- grejpfrut u aliskiren ma jistgħux jiġu esklużi.
Grapefruit juice should not be taken together with Enviage.
Il- meraq tal- grejpfrut m’ għandux jittieħed flimkien ma ’ Enviage.
Warfarin The effects of Enviage on warfarin pharmacokinetics have not been evaluated.
Warfarin L- effetti ta ’ Enviage fuq il- farmakokinetika ta ’ warfarin ma kienux evalwati.
Food intake Meals with a high fat content have been shown to reduce the absorption of Enviage substantially.
It- teħid ta ’ l- ikel Ikliet b’ kontenut ta ’ xaħam għoli ntwerew li jnaqqsu l- assorbiment ta ’ Enviage b’ mod sostanzjali.
Pregnancy There are no data on the use of aliskiren in pregnant women.
Tqala M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ aliskiren waqt it- tqala.
Enviage was not teratogenic in rats or rabbits (see section 5.3).
Enviage ma kienx teratoġeniku fi frien jew fniek (ara sezzjoni 5. 3).
Other substances that act directly on the RAS have been associated with serious foetal malformations and neonatal death.
Sustanzi oħra li jaħdmu direttament fuq RAS kienu assoċjati ma ’ malformazzjonijiet tal- feti u mwiet tal- frieħ.
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).
Bħal kull mediċina oħra li taħdem direttament fuq ir - RAS, Enviage m’ għandux jintuża waqt l- ewwel trimestru tat- tqala jew f’ nisa li qed jippjanaw biex joħorġu tqal u huwa kontraindikat waqt it- tieni u t- tielet trimestri (ara sezzjoni 4. 3).
Healthcare professionals prescribing any agents acting on the RAS should counsel women of childbearing potential about the potential risk of these agents during pregnancy.
Professjonisti fil - kura tas- saħħa li jkunu qed jordnaw xi aġenti li jaħdmu fuq RAS għandhom jagħtu parir lil nisa li qieghdin f’ età li jista ’ jkollhom it- tfal dwar ir- riskju li jista ’ jkun hemm b’ dawn l- aġenti waqt it- tqala.
If pregnancy is detected during therapy, Enviage should be discontinued accordingly.
Jekk jinsab li hemm tqala waqt it- terapija, Enviage għandu jitwaqqaf kemm jista ’ jkun malajr kif ikun xieraq.
Lactation It is not known whether aliskiren is excreted in human milk.
Treddigħ Mhux magħruf jekk aliskiren jgħaddix fil- ħalib tal- mara.
Enviage was secreted in the milk of lactating rats.
Enviage għadda fil- ħalib ta ’ firien li kienu qed ireddgħu.
Its use is therefore not recommended in women who are breast-feeding.
Għalhekk l- użu tiegħu mhux irrakkomandat f’ nisa waqt it- treddigħ.
However, when driving vehicles or operating machinery it must be borne in mind that dizziness or weariness may occasionally occur when taking any antihypertensive therapy.
Madankollu, waqt is- sewqan jew tħaddim ta ’ magni għandu jkun meqjus il- fatt li jista ’ jkun hemm, xi kultant, sturdament jew għeja bl- użu ta ’ terapija kontra l- pressjoni għolja.
Enviage has negligible influence on the ability to drive and use machines.
Enviage ftit li xejn għandu influwenza fuq il- ħila biex issuq u tħaddem magni.
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.
Enviage ġie evalwat għas- sigurtà f’ aktar minn 7, 800 pazjent, li kienu jinkludu aktar minn 2, 300 li ingħataw kura għal aktar minn 6 xhur, u aktar minn 1, 200 għal aktar minn sena.
The incidence of adverse reactions showed no association with gender, age, body mass index, race or ethnicity.
L- inċidenza ta ’ reazzjonijiet avversi ma wrietx assoċjazzjoni mas- sess, età, indiċi tal- massa tal- ġisem, razza jew etniċità.
Treatment with Enviage resulted in an overall incidence of adverse reactions similar to placebo up to 300 mg.
Kura b’ Enviage wasslet għal inċidenza globali ta ’ reazzjonijiet avversi simili għal plaċebo sa ’ 300 mg.
Adverse reactions have generally been mild and transient in nature and have only infrequently required discontinuation of therapy.
Reazzjonijiet avversi kienu ħfief b’ mod ġenerali u ta ’ natura li jgħaddu u ma kienux frekwenti l- każijiet fejn kellha titwaqqaf il- kura.
The most common adverse drug reaction is diarrhoea.
L- aktar reazzjoni avversa komuni għall- mediċina hija dijarrea.
The incidence of cough was similar in placebo (0.6%) and Enviage treated (0.9%) patients.
L- inċidenza tas- sogħla kienet simili f’ pazjenti ikkurati bi plaċebo (0. 6%) u b’ Enviage (0. 9%).
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.
Ir- reazzjonijiet avversi għall- mediċina (Tabella 1) huma elenkati taħt it- titlu tal- frekwenza, l- aktar frekwenti l- ewwel, bil- konvenzjoni li ġejja: komuni ħafna (≥1/ 10); komuni (≥1/ 100, < 1/ 10); mhux komuni (≥1/ 1, 000, < 1/ 100); rari (≥1/ 10, 000, < 1/ 1, 000); rari ħafna (< 1/ 10, 000), inklużi rapporti iżolati.
Angioedema has occurred during treatment with Enviage.
Anġjoedema seħħet waqt il- kura b’ Enviage.
In controlled clinical trials, angioedema occurred rarely during treatment with Enviage with rates comparable to treatment with placebo or hydrochlorothiazide.
Fi provi kliniċi kkontrollati, anġjoedema seħħet b’ mod rari waqt il- kura b’ Enviage b’ rati li setgħu jitqabblu mal- kura bi plaċebo jew hydrochlorthiazide.
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.
F’ każ ta ’ kwalunkwe sinjali li jindikaw reazzjoni allerġika (l- aktar tbatija biex tieħu n- nifs jew tibla ’, jew nefħa tal- wiċċ, fl- idejn u s- saqajn, għajnejn, xofftejn u/ jew ilsien), il- pazjenti għandhom iwaqqfu l- kura u jgħamlu kuntatt mat- tabib.
Laboratory findings In controlled clinical trials, clinically relevant changes in standard laboratory parameters were uncommonly associated with the administration of Enviage.
Sejbiet tal- laboratorju Fi provi kliniċi kkontrollati, bidliet klinikament rilevanti f’ parametri standard tal- laboratorju kienu assoċjati b’ mod mhux komuni ma ’ l- għoti ta ’ Enviage.
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.
Fi studji kliniċi f’ pazjenti bi pressjoni għolja, Enviage ma kellux effetti klinikament importanti fuq il- kolesterol totali, lipoproteina tal- kolesterol ta ’ densità għolja (HDL- C), trigliċeridi ta ’ waqt is- sawm, glucose ta ’ waqt is- sawm jew uric acid.
Haemoglobin and haematocrit:
Emoglobina u ematokrit:
Small decreases in haemoglobin and haematocrit (mean decreases of approximately 0.05 mmol/ l and 0.16 volume percent, respectively) were observed.
Deher tnaqqis żgħir fl- emoglobina u ematokrit (medja ta ’ tnaqqis b’ madwar 0. 05 mmol/ l u 0. 16 perċentwali tal- volum, rispettivament).
No patients discontinued therapy due to anaemia.
Ħadd mill- pazjenti ma waqqaf it- terapija minħabba anemija.
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.
Dan l- effett jidher ukoll b’ aġenti oħra li jaħdmu fuq is- sistema renin- angiotensin, bħall- inibituri ta ’ l- enzimi li jikkonvertu l- angiotensin (ACEI) u imblukkaturi tar- riċettur ta ’ angiotensin.
Serum potassium:
Potassium fis- serum:
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).
Żiediet tal- potassium fis- serum kienu minuri u mhux frekwenti f’ pazjenti bil - pressjoni għolja naturali kkurata b’ Enviage waħdu (0. 9% imqabbla ma ’ 0. 6% bil- plaċebo).
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%).
Madankollu, fi studju wieħed fejn Enviage intuża ma ’ ACEI f’ popolazzjoni ta ’ pazjenti dijabetiċi iż - żiediet tal- potassium fis- serum kienu aktar frekwenti (5. 5%).
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.
Għalhekk bħal ma jsir ma ’ kull aġent li jaħdem fuq is- sistema RAS, monitoraġġ ta ’ rutina ta ’ l- elettroliti u l- funzjoni renali huma indikati għall- pazjenti b’ dijabete mellitus, mard tal- kliewi, jew insuffiċjenza tal- qalb.
Limited data are available related to overdose in humans.
Hemm tagħrif limitat dwar l- użu eċċessiv fil- bniedem.
The most likely manifestations of overdosage would be hypotension, related to the antihypertensive effect of aliskiren.
L- aktar ħaga li x’ aktarx tidher b’ doża eċċessiva ta ’ Enviage tkun pressjoni baxxa, relatata ma ’ l- effett ta ’ aliskiren li jbaxxi l- pressjoni.
If symptomatic hypotension should occur, supportive treatment should be initiated.
Jekk jidhru sintomi ta ’ pressjoni baxxa, kura ta ’ support għandha tinbeda.
Renin inhibitor, ATC code:
Inibitur tar- renin, Kodiċi ATC:
Aliskiren is an orally active, non-peptide, potent and selective direct inhibitor of human renin.
Aliskiren huwa inibitur dirett tar- renin tal- bniedem, attiv b’ mod orali, selettiv u potenti, mhux peptajd.
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.
Bl- inibizzjoni ta ’ l- enzima renin, aliskiren jinibixxi ir- RAS fil- punt ta ’ l- attivazzjoni, u b’ hekk jimblokka l- konverżjoni ta ’ angiotensin f’ angiotensin I u jnaqqas il- livell ta ’ angiotensin I u angiotensin II.
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%.
Filwat li aġenti oħrajn li jinibixxu r- RAS (ACEI u imblukkaturi tar- riċetturi ta ’ angiotensin II (ARB)) jikkawżaw żieda ta ’ kumpens fl- attività ta ’ renin fil- plażma (PRA), il- kura b’ aliskiren tnaqqas il- PRA f’ pazjenti bil- pressjoni għolja b’ madwar 50 sa 80%.
Similar reductions were found when aliskiren was combined with other antihypertensive agents.
Tnaqqis simili deher meta aliskiren ingħata ma ’ aġenti kontra l- pressjoni għolja oħrajn.
Elevated PRA has been independently associated with increased cardiovascular risk in hypertensive and normotensive patients.
PRA elevat kien assoċjat b’ mod indipendenti ma ’ żiediet fir- riskju kardjovaskulari f’ pazjenti bi pressjoni għolja u pazjenti bi pressjoni normali.
The clinical implications of the differences in effect on PRA are not known at the present time.
L- implikazzjonijiet kliniċi tad- differenzi fl- effett fuq il- PRA mhux magħrufin sa ’ issa.
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.
6 Pressjoni għolja F’ pazjenti bil- pressjoni għolja, l- għotja darba kuljum ta ’ Enviage b’ dożi ta ’ 150 mg u 300 mg ikkawżaw tnaqqis dipendenti mid- doża fil- pressjoni tad- demm sistolika u dijastolika li nżammu fuq perijodu sħiħ ta ’ 24 siegħa ta ’ l- intervall bejn id- dożi (b’ hekk żammew il- benefiċċju ta ’ kmieni filgħodu) b’ medja fil- proporzjon bejn l- ogħla u l- anqas għar- rispons dijastoliku sa ’ 98% għad- doża ta ’ 300 mg.
85 to 90% of the maximal blood- pressure-lowering effect was observed after 2 weeks.
85 sa 90% ta ’ l- effett massimu li jbaxxi l- pressjoni deher wara ġimgħatejn.
The blood-pressure-lowering effect was sustained during long-term treatment, and was independent of age, gender, body mass index and ethnicity.
L- effett li jbaxxi l - pressjoni inżamm waqt kura li ngħatat fit- tul, u ma kienetx tiddependi mill- età, sess, indiċi tal- massa tal- ġisem u razza.
Enviage has been studied in 1,864 patients aged 65 years or older, and in 426 patients aged 75 years or older.
Enviage kien studjat f’ 1, 864 pazjent ta ’ etajiet minn 65 sena ’ l fuq, u f’ 426 pazjent ta ’ etajiet minn 75 sena ’ l fuq.
Enviage monotherapy studies have shown blood pressure lowering effects comparable to other classes of antihypertensive agents including ACEI and ARB.
Studji b’ monoterapija b’ Enviage urew li l- effetti li jbaxxi l- pressjoni kienu jitqabblu ma ’ klassijiet oħra ta ’ aġenti li jbaxxu l- pressjoni inklużi ACEI u ARB.
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.
Meta mqabbel ma ’ dijuretiku (hydrochlorothiazide - HCTZ), Enviage 300 mg naqqas il- pressjoni sistolika/ dijastolika tad- demm b’ 17. 0/ 12. 3 mmHg, imqabbel ma ’ 14. 2/ 10. 5 mmHg għal HCTZ 25 mg wara 12- il ġimgħa ta ’ kura.
In diabetic hypertensive patients, Enviage monotherapy was safe and effective.
F’ pazjenti dijabetiċi bil- pressjoni għolja, monoterapija ta ’ Enviage kienet sigura u effettiva.
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.
Hemm studji b’ terapija ta ’ kombinazzjoni għal Enviage miżjud mad- dijuretiku hydrochlorthiazide, l - ACEI ramipril, l- imblukkatur tal- kanali tal- calcium amlodipine, l- antagonist tar- riċettur ta ’ l - angiotensin valsartan, u l- imblukkatur beta atenolol.
These combinations were well tolerated.
Dawn il- kombinazzjonijiet kienu tollerati sew.
Enviage induced an additive blood-pressure-lowering effect when added to hydrochlorothiazide and to ramipril.
Enviage ikkawża tnaqqis fil- pressjoni tad- demm akbar meta żdied ma ’ hydrochlorthiazide u ma ’ ramipril.
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%).
F’ pazjenti li ma kellhomx rispons xieraq għall- 5 mg ta ’ l- imblokkatur tal- kanali tal- calcium amlodipine, iż- żieda ta ’ Enviage 150 mg kellu effett li jbaxxi l- pressjoni simili għal dak miksub meta d- doża ta ’ amlodopine tiżdied għal 10 mg iżda kien hemm anqas każijiet ta ’ edema (aliskiren 150 mg/ amlodipine 5 mg 2. 1% vs amlodipine 10 mg 11. 2%).
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.
Enviage flimkien ma ’ l- antagonist tar - riċettur ta ’ angiotensin valsartan wera effett ta ’ tnaqqis fil- pressjoni akbar fl- istudju li kien imfassal apposta sabiex jiġi mistħarreġ l- effett tat- terapija kombinata.
In obese hypertensive patients who did not adequately respond to HCTZ 25 mg, add-on treatment with Enviage 300 mg provided additional blood pressure reduction that was comparable to add-on treatment with irbesartan 300 mg or amlodipine 10 mg.
F’ pazjenti obeżi li għandhom il- pressjoni għolja li ma wrewx rispons xieraq għal HCTZ 25 mg, kura bl- inklużjoni ta ’ Enviage 300 mg ipprovdiet tnaqqis addizzjonali fil- pressjoni tad- demm li seta ’ jitqabbel ma ’ kura bl- inklużjoni ta ’ irbesartan 300 mg jew amlodipine 10 mg.
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%).
F’ pazjenti dijabetiċi li għandhom il- pressjoni għolja, Enviage ipprovda tnaqqis addittiv tal- pressjoni tad- demm meta ngħata ma ’ ramipril, filwaqt li l- kombinazzjoni ta ’ Enviage u ramipril kellha anqas każijiet ta ’ sogħla (1. 8%) minn ramipril (4. 7%).
There has been no evidence of first-dose hypotension and no effect on pulse rate in patients treated in controlled clinical studies.
Ma kienx hemm evidenza ta ’ pressjoni baxxa bl- ewwel doża u l- ebda effett fuq r- rata tal- polz f’ pazjenti ikkurati fi studji kliniċi kkontrollati.
Excessive hypotension was uncommonly (0.1%) seen in patients with uncomplicated hypertension treated with Enviage alone.
Pressjoni baxxa żżejjed kienet mhux komuni (0. 1%) f’ pazjenti bi pressjoni għolja mingħajr komplikazzjoni li kienu kkurati b’ Enviage waħdu.
Hypotension was also uncommon (< 1%) during combination therapy with other antihypertensive agents.
Pressjoni baxxa kienet ukoll mhux komuni (< 1%) waqt terapija kombinata b’ aġenti kontra l- pressjoni għolja oħrajn.
With cessation of treatment, blood pressure gradually returned towards baseline levels over a period of several weeks, with no evidence of a rebound effect for blood pressure or PRA.
Meta twaqqfet it- terapija, l- pressjoni reġgħet lura għall- livelli tal- linja bażi fuq perijodu ta ’ numru ta ’ ġimgħat, mingħajr ma kien hemm effett rebound għall- pressjoni tad- demm jew PRA.
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.
Fi studju ta ’ 3 xhur fuq 302 pazjenti b’ insuffiċjenza tal- qalb stabbli u mhux severa (Klassi funzjonali NYHA II u III), li kollha kemm huma kienu qed jirċievu terapija standard għall- insuffiċjenza tal- qalb iż- żieda ta ’ Rasliez 150 mg kienet tollerata sew.
However the clinical significance of this reduction is unknown.
Il- livelli ta ’ peptajd natrijuretiku tat- tip- B (BNP) kienu mnaqqsa b’ 25% fil- fergħa ta ’ Enviage meta mqabbla mal- plaċebo għalkemm is- sinifikat kliniku għadu mhux magħruf.
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.
Fi studju ta ’ 6 xhur ta ’ 599 pazjent bi pressjoni għolja, dijabete mellitus tat- tip 2, u nefropatija, li kollha kemm huma kienu qed jingħataw losartan 100 mg u terapija ta ’ sfond adattata għal kontra l - pressjoni għolja, iż- żieda ta ’ Enviage 300 mg kisbet tnaqqis ta ’ 20% kontra plaċebo, i. e. minn 58 mg/ mmol għal 46 mg/ mmol, fil- proporzjon ta ’ l- albumina mal- krejatina fl- awrina (UACR).
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.
Il - proporzjon tal- pazjenti li kellhom tnaqqis fil- UACR b’ mill- anqas 50% mill- linja bażi sat- tragward finali kien ta ’ 24. 7% u 12. 5% għal Enviage u l- plaċebo, rispettivament.
The clinical relevance of a reduction in UACR is not established in the absence of an effect on blood pressure.
Ir- rilevanza klinika tat- tnaqqis fl- UACR mhux stabbilit fl- assenza ta ’ effett fuq il- pressjoni tad- demm.
Enviage did not affect the serum concentration of creatinine but was associated with an increased frequency (4.2% vs.
Enviage ma effettwax il - konċentrazzjoni fis- serum tal- krejatinina iżda kien assoċjat ma ’ żieda fil- frekwenza (4. 2% vs 1. 9%
1.9% for placebo) of serum potassium concentration (≥ 6.0 mmol/ l), although this was not statistically significant.
7 għal plaċebo) tal- konċentrazzjoni tal- potassium fis- serum (≥ 6. 0 mmol/ l), għalkemm dan ma kienx statistikament sinifikanti.
7 Beneficial effects of Enviage on mortality and cardiovascular morbidity and target organ damage are currently unknown.
L- effetti benefiċi ta ’ Enviage fuq il- mortalità jew morbidità kardjovaskulari u l- ħsara fl- organu milqut bħalissa mhumhiex magħrufa.
Cardiac electrophysiology No effect on QT interval was reported in a randomised, double-blind, placebo, and active-controlled study using standard and Holter electrocardiography.
Elettrofiżjoloġija tal- qalb Ma ġiex irrappurtat l- ebda effett fi studju randomized, double- blind, kontrollat bi plaċebo u bis - sustanza attiva b’ elettrokardjografija standard u Holter.
Absorption Following oral absorption, peak plasma concentrations of aliskiren are reached after 1-3 hours.
Assorbiment Wara assorbiment orali, il- konċentrazzjonijiet ta ’ aliskiren fil- plażma laħqu l- quċċata wara 1- 3 siegħat.
The absolute bioavailability of aliskiren is approximately 2-3%.
Il- biodisponibilità assoluta ta ’ aliskiren hija madwar 2- 3%.
Meals with a high fat content reduce Cmax by 85% and AUC by 70%.
Ikliet b’ kontenut għoli ta ’ xaħam naqqsu is- Cmax b ’ 85% u l- AUC b’ 70%.
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.
Konċentrazzjonijiet fil- plażma fi stat fiss jintlaħqu fi żmien 5- 7 ijiem wara li jingħata darba kuljum u l- livelli ta ’ stat fiss huma darbtejn ogħla minn dik li tintlaħaq bl- ewwel doża.
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.
Distribuzzjoni Wara li jingħata minn ġol- vina, il- medja tal- volum ta ’ distribuzzjoni fi stat fss hija madwar 135 litru, li jindika li aliskiren jinfirex b’ mod estensiv fl- ispazju extravaskulari.
Aliskiren plasma protein binding is moderate (47-51%) and independent of the concentration.
Ir- rabta mal- proteini fil- plażma ta ’ alsikiren hija moderata (47- 51%) u ma tiddependix fuq il- konċentrazzjoni.
Metabolism and elimination The mean half-life is about 40 hours (range 34-41 hours).
Metaboliżmu u eliminazzjoni Il- medja tal- half- life hija madwar 40 siegħa (medda bejn 34- 41 siegħa).
Aliskiren is mainly eliminated as unchanged compound in the faeces (78%).
Aliskiren jiġi eliminat bħala kompost kimiku mhux mibdul fl- ippurgar (78%).
Approximately 1.4% of the total oral dose is metabolised.
Madwar 1. 4% tad- doża orali totali tiġi metabolizzata.
The enzyme responsible for this metabolism is CYP3A4.
L- enzima responsabbli għal dan il- metaboliżmu hija CYP3A4.
Approximately 0.6% of the dose is recovered in urine following oral administration.
Madwar 0. 6% tad- doża tiġi rkuprata mill- awrina wara doża li tingħata mill- ħalq.
Following intravenous administration, the mean plasma clearance is approximately 9 l/ h.
Wara l- għotja minn ġol- vina, it- tneħħija medja mill- plażma hija madwar 9 l/ h.
Linearity/ non-linearity Exposure to aliskiren increased more than in proportion to the increase in dose.
Linejarità/ nuqqas ta ’ linejarità L- esponiment għal aliskiren żdied b’ mod aktar minn proporzjonali għaż- żieda fid- doża.
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.
Wara li tingħata doża waħda fil- medda ta ’ dożi bejn 75 u 600 mg, meta d- doża tiġi rduppjata jkun hemm żieda ta ’ ~2. 3 u 2. 6- il darba fl- AUC u s- Cmax rispettivament.
At steady state the non-linearity may be more pronounced.
Fi stat fiss in- nuqqas ta ’ linejarità tista ’ tkun tidher aktar.
Mechanisms responsible for deviation from linearity have not been identified.
Mekkaniżmi responsabbli għad- devjazzjoni mill- linejarità ma ġewx identifikati.
A possible mechanism is saturation of transporters at the absorption site or at the hepatobiliary clearance route.
Mekkaniżmu possibli huwa s- saturazzjoni tat- trasportaturi fis- sit ta ’ l- assorbiment jew fir- rotta ta ’ tneħħija mill- fwied u mill- marrara.
Characteristics in patients Aliskiren is an effective once-a-day antihypertensive treatment in adult patients, regardless of gender, age, body mass index and ethnicity.
Karatteristiċi f’ pazjenti Aliskiren huwa kura effettiva kontra l- pressjoni għolja f’ pazjenti aduti, ikun x’ ikun is- sess, l- età, l - indiċi tal- massa tal- ġisem u l- etniċità.
The AUC is 50% higher in elderly (> 65 years) than in young subjects.
L- AUC huwa 50% ogħla fl- anzjani (> 65 sena) milli f’ individwi żgħażagħ.
Gender, weight and ethnicity have no clinically relevant influence on aliskiren pharmacokinetics.
Is- sess, piż u etniċità m’ għandhomx influwenza klinikament rilevanti fuq il- farmakokinetika ta ’ aliskiren.
The pharmacokinetics of aliskiren were evaluated in patients with varying degrees of renal insufficiency.
Il- farmakokinetika ta ’ aliskiren kienetevalwata f’ pazjenti bi gradi varji ta ’ insuffiċjenza renali.
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.
AUC u Cmax relattivi ta ’ aliskiren f’ individwi b’ indeboliment renali kellhom medda ta ’ bejn 0. 8 sa darbtejn il - livelli f’ individwi b’ saħħithom wara li ngħatat doża waħda u fi stat fiss.
These observed changes, however, did not correlate with the severity of renal impairment.
Dawn il- bidliet li dehru, madankollu, ma kienux jikkorrelataw mas- severità ta ’ l- indeboliment renali.
No adjustment of the initial dosage of Enviage is required in patients with mild to severe renal impairment, however caution should be exercised in patients with severe renal impairment.
Mhux meħtieġ bdil tad - doża tal- bidu ta ’ Enviage f’ pazjenti b’ indeboliment renali ħafif għal sever, iżda għandha tingħata attenzjoni f’ pazjenti b’ indeboliment renali sever.
The pharmacokinetics of aliskiren were not significantly affected in patients with mild to severe liver disease.
Il- farmakokinetika ta ’ aliskiren ma nbidlitx b’ mod sinifikanti f’ pazjenti b’ mard tal- fwied ħafif għal sever.
Consequently, no adjustment of the initial dose of aliskiren is required in patients with mild to severe hepatic impairment.
Għalhekk, mhux meħtieġ li d- doża tal- bidu ta ’ aliskiren tinbidel f’ pazjenti b’ indeboliment epatiku ħafif għal sever.
8 5.3 Preclinical safety data
8 5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Carcinogenic potential was assessed in a 2-year rat study and a 6-month transgenic mouse study.
Il- potenzjal karċinoġenu kien evalwat fi studju fuq firien li dam sentejn u fi studju fuq ġrieden transġeniċi li dam 6 xhur.
No carcinogenic potential was detected.
Ma nstabx potenzjal karċinoġenu.
One colonic adenoma and one caecal adenocarcinoma recorded in rats at the dose of 1,500 mg/ kg/ day were not statistically significant.
Każ ta ’ adenoma fil- kolon u każ ta ’ adenokarċinoma fil- musrana l- għamja li kien reġistrat fi firien b’ doża ta ’ 1, 500 mg/ kg/ jum ma kienux statistikament sinifikanti.
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.
Għalkemm huwa magħruf li aliskiren jista ’ jikkawża irritazzjoni, il- marġini ta ’ sigurtà miksuba fil- bniedem b’ doża ta ’ 300 mg waqt studju f’ voluntiera b’ saħħithom kienu meqjusa xierqa b’ 9- 11- il darba ibbażat fuq konċentrazzjonijiet fl- ippurgar jew 6 darbiet fuq konċentrazzjonijiet fil- mukuża meta mqabbla ma ’ 250 mg/ kg/ jum fl- istudju dwar il- karċinoġeniċità fil- far.
Aliskiren was devoid of any mutagenic potential in the in vitro and in vivo mutagenicity studies.
Aliskiren kien nieqes minn kull potenzjal mutaġeniku fl- istudji dwar il- mutaġeniċità in vitro u in vivo.
The assays included in vitro assays in bacterial and mammalian cells and in vivo assessments in rats.
L- essejs kienu jinkludu essejs in vitro f’ ċelluli batteriċi u mammiferi u f’ evalwazzjonijiet in vivo fi firien.
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.
Studji dwar it- tossiċità fuq is- sistema riproduttiva b’ aliskiren ma wrew l- ebda evidenza ta ’ tossiċità għall- embriju/ fetu jew teratoġeniċità b’ dożi sa 600 mg/ kg/ jum fil- firien jew 100 mg/ kg/ jum fil- fniek.
Fertility, pre-natal development and post-natal development were unaffected in rats at doses up to 250 mg/ kg/ day.
Il- fertilità, l- iżvilupp ta ’ qabel u wara t- twelid ma kienux effettwati fil- firien b’ dożi sa 250 mg/ kg/ jum.
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).
Id- dożi fil- firien u fniek kienu jipprovdu esponimenti sistemiċi ta ’ 1 sa 4 darbiet ogħla, rispettivament, mill- għola doża rrakkomandata fil- bniedem (300 mg).
Safety pharmacology studies did not reveal any adverse effects on central nervous, respiratory or cardiovascular function.
Studji dwar is- sigurtà farmakoloġika ma wrew l- ebda effetti avversi fuq is- sistema nervuża ċentrali, respiratorja jew funzjoni kardjovaskulari.
Findings during repeat-dose toxicity studies in animals were consistent with the known local irritation potential or the expected pharmacological effects of aliskiren.
Is- sejbiet waqt studji ta ’ tossiċità minn dożi ripetuti kienu konsistenti ma ’ l- irritazzjoni lokali li hi magħrufa jew ma ’ l- effetti farmakoloġiċi mistennija ta ’ aliskiren.
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)
6. 1 Lista ta ’ sustanzi mhux attivi 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 Nature and contents of container
9 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
PA/ Alu/ PVC blisters
Folji PA/ Alu/ PVC
Packs containing 7, 14, 28, 30, 50, 56, 84, 90, 98 or 280 tablets.
Pakketti li jkun fihom 7, 14, 28, 30, 50, 56, 84, 90, 98 jew 280 pillola.
Packs containing 84 (3x28), 98 (2x49) or 280 (20x14) tablets are multi-packs.
Pakketti li jkun fihom 84 (3x28), 98 (2x49) jew 280 (20x14) pillola huma pakketti b’ ħafna.
Enviage 300 mg film-coated tablets
Enviage 300 mg pilloli miksijin b’ rita
Each film-coated tablet contains 300 mg aliskiren (as hemifumarate).
Kull pillola miksija b’ rita fiha 300 mg aliskiren (bħala hemifumarate)..
Light-red, biconvex, ovaloid tablet, imprinted “ IU ” on one side and “ NVR” on the other side.
Pillola ħamra ċar, konvessa miż- żewġ naħat, f’ għamla ovali, ittimbrata ‘ IU ’ fuq naħa u ‘ NVR ’ fuq in - naħa l- oħra.
11 4.3 Contraindications
11 4. 3 Kontra- indikazzjonijiet
Second and third trimesters of pregnancy (see section 4.6).
It- tieni u t- tielet trimestri tat- tqala (ara sezzjoni 4. 6).
When administered with atorvastatin, steady-state Enviage AUC and Cmax increased by 50%.
Meta ngħata ma ’ atorvastatin, l- AUC
12 amlodipine pharmacokinetics.
12 u Cmax fi stat fiss ta ’ Enviage żdiedu b’ 50%.
Digoxin bioavailability may be slightly decreased by Enviage.
Il- biodisponibilità ta ’ digoxin tista ’ titnaqqas xi ftit b’ Enviage.
Preliminary data suggest that irbesartan may decrease Enviage AUC and Cmax.
Tagħrif preliminari jindika li irbesartan jista ’ jnaqqas xi ftit l- AUC u s- Cmax ta ’ Enviage.
It is therefore recommended that the effects be monitored when initiating and adjusting furosemide therapy to avoid possible under-utilisation in clinical situations of volume overload.
13 aġġustata t- terapija ta ’ furosemide biex dan ma jkunx sotto- utilizzat f’ sitwazzjonijiet kliniċi ta ’ volum żejjed.
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.
Potassium u dijuretiċi li ma jħallux il- potassium jintilef Minn esperjenza b’ sustanzi oħrajn li jeffettwaw is- sistema renin- angiotensin, l- użu ta ’ dijuretiċi li ma jħallux il- potassium jintilef, supplimenti tal- potassium, sostituti tal- melħ li fihom il- potassium jew sustanzi oħra li jistgħu jżidu l- livelli ta ’ potassium fis- serum (eż heparin) jistgħu jwasslu għal żidied tal- potassium fis- serum.
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.
Ir- reazzjonijiet avversi għall- mediċina (Tabella 1) huma elenkati taħt it- titlu tal- frekwenza, l- aktar frekwenti l- ewwel, bil- konvenzjoni li ġejja: komuni ħafna (≥1/ 10); komuni (≥1/ 100, < 1/ 10); mhux
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
14 komuni (≥1/ 1, 000, < 1/ 100); rari (≥1/ 10, 000, < 1/ 1, 000); rari ħafna (< 1/ 10, 000), inklużi rapporti iżolati.
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.
Għalhekk bħal ma jsir ma kull aġent li jaħdem fuq is- sistema RAS, monitoraġġ ta ’ rutina ta ’ l- elettroliti u l- funzjoni renali huma indikati għall- pazjenti b’ dijabete mellitus, mard tal- kliewi, jew insuffiċjenza tal- qalb.
Elevated PRA has been independently associated with increased cardiovascular risk in hypertensive and normotensive patients.
15 indipendenti ma ’ żiediet fir- riskju kardjovaskulari f’ pazjenti bi pressjoni għolja u pazjenti bi pressjoni normali.
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.
Pressjoni għolja F’ pazjenti bil- pressjoni għolja, l- għotja darba kuljum ta ’ Enviage b’ dożi ta ’ 150 mg u 300 mg ikkawżaw tnaqqis dipendenti mid- doża fil- pressjoni tad- demm sistolika u dijastolika li nżammu fuq perijodu sħiħ ta ’ 24 siegħa ta ’ l- intervall bejn id- dożi (b’ hekk żammew il- benefiċċju ta ’ kmieni filgħodu) b’ medja fil- proporzjon bejn l- oghla u l- anqas għar- rispons dijastoliku sa ’ 98% għad- doża ta ’ 300 mg.
Enviage did not affect the serum concentration of creatinine but was associated with an increased frequency (4.2% vs.
Enviage ma effettwax il -