qanastek/EMEA-V3 huggingface dataset:
Aliskiren Treatment with Aliskiren up to 300 mg resulted in an overall incidence of adverse reactions similar to placebo.
Aliskiren Kura b’ aliskiren sa 300 mg wasslet għal frekwenza ta ’ reazzjonijiet avversi simili għall- plaċebo.
Adverse reactions have generally been mild and transient in nature and have only infrequently required discontinuation of therapy.
Reazzjonijiet avversi ġeneralment kienu ħfief u mumentanji fin- natura u rari kienu jeħtieġu t- twaqqif tat- terapija.
The most common adverse drug reaction is diarrhoea.
L- aktar effett avvers tal- mediċina komuni huwa dijarea.
The known aliskiren adverse drug reactions are presented in the table below using the same convention as described previously for the fixed combination.
Ir- reazzjonijiet avversi tal- mediċina magħrufa għall- aliskiren huma ppreżentati fit- tabella hawn taħt bl - użu tal- istess konvenzjoni kif imfisser qabel għat- taħlita fissa.
Rash Angioedema
Raxx Anġjoedima
In controlled clinical trials, angioedema occurred rarely during treatment with aliskiren with rates comparable to treatment with placebo or hydrochlorothiazide.
Fi provi kliniċi kkontrollati, anġjoedima seħħet b’ mod rari waqt il- kura b’ aliskiren b’ rati li setgħu jitqabblu mal- kura bi plaċebo jew hydrochlorothiazide.
Cases of angioedema have also been reported in post-marketing experience (frequency unknown).
Każijiet ta ’ anġjoedima kienu wkoll irrappurtati fl- esperjenza ta ’ wara t- tqegħid fis- suq (frekwenza mhux magħrufa).
In the event of any signs suggesting an allergic reaction patients should discontinue treatment and contact the physician (see section 4.4).
F’ każ ta ’ kwalunkwe sinjali li jindikaw reazzjoni allerġika il- pazjenti għandhom iwaqqfu l- kura u jgħamlu kuntatt mat- tabib (ara sezzjoni 4. 4).
The incidence of cough was similar in placebo (0.6%) and aliskiren-treated (0.9%) patients.
L- inċidenza tas- sogħla kienet simili f’ pazjenti ikkurati bi plaċebo (0. 6%) u b’ aliskiren (0. 9%).
This effect is also seen with other agents acting on the RAS, such as ACEIs and angiotensin receptor blockers.
Dan l- effett jidher ukoll b’ aġenti oħra li jaħdmu fuq ir- RAS, bħall- ACEIs u imblukkaturi tar- riċettur ta ’ angiotensin.
Serum potassium:
9 Potassium fis- serum:
Increases in serum potassium were minor and infrequent in patients with essential hypertension treated with aliskiren 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’ aliskiren waħdu (0. 9% imqabbla ma ’ 0. 6% bil- plaċebo).
However, in one study where aliskiren 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 aliskiren 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, 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 tal- elettroliti u l- funzjoni renali huwa indikat għall - pazjenti b’ dijabete mellitus, mard tal- kliewi, jew insuffiċjenza tal- qalb.
In post-marketing experience, renal dysfunction and cases of acute renal failure have been reported in patients at risk (see section 4.4).
Fl- esperjenza ta ’ wara t- tqegħid fis- suq, kliewi li ma jaħdmux tajjeb u każi ta ’ insuffiċjenza akuta tal - kliewi kienu rrappurtati f’ pazjenti li kienu f’ riskju (ara sezzjoni 4. 4).
Hydrochlorothiazide Adverse events (regardless of relationship to medicinal product) reported with the use of hydrochlorothiazide alone include:
Hydrochlorothiazide Reazzjonijiet avversi (irrispettivament mir- relazzjoni mal- prodott mediċinali) irrappurtat bl- użu ta ’ hydrochlorothiazide waħdu jinkludu:
Aplastic anaemia, bone marrow depression, neutropenia/ agranulocytosis, haemolytic anaemia, leucopenia, thrombocytopenia
Anemija aplastika, dipressjoni tal- mudullun, newtropenija/ agranuloċitożi, anemija emolitika, lewkopenija, tromboċitopenija
Depression, sleep disturbances
Depressjoni, disturbi tal- irqad
Restlessness, light-headedness, vertigo, paraesthesia, dizziness
Irrikwietezza, ras ħafifa, vertigo, paraesteżija, sturdament
Transient blurred vision, xanthopsia
Vista mċajpra mumentanja, xantopsja
Cardiac arrhythmias
Arritemiji kardijaċi
Postural hypotension
Ipotensjoni tal- pożizzjoni
Respiratory distress (including pneumonitis and pulmonary oedema)
Distress respiratorju (inkluż pnewmonite u edima pulmonari).
Pancreatitis, anorexia, diarrhoea, constipation, gastric irritation, sialadenitis, loss of appetite
Pankrejatite, anoressija, dijarea, stitikezza, irritazzjoni fl- istonku, sijaldenite, telf tal- aptit
Jaundice (intrahepatic cholestatic jaundice)
Suffejra (suffejra kolestatika intra- epatika)
Anaphylactic reactions, toxic epidermal necrolysis, necrotising angiitis (vasculitis, cutaneous vasculitis), cutaneous lupus erythematosus-like reactions, reactivation of cutaneous lupus erythematosus, photosensitivity reactions, rash, urticaria
Reazzjonijiet anafilattiċi, nekroliżi tossika tal- ġilda, anġiite nekrolitika (vaskulite, vaskulite kutanja), reazzjonijiet li jixbhu l- lupus erythematosus kutanji, riattivazzjoni ta ’ lupus erythematosus kutanja, reazzjonijiet ta ’ fotosensittività, raxx, urtikarja
Musculoskeletal and connective tissue disorders
Disturbi muskolu- skeltrali u tat- tessut konnettiv
Weakness, muscle spasm
Dgħjufija, spażmi tal- muskoli
Interstitial nephritis, renal dysfunction
Nefrite interstizjali, funzjoni ħażina tal- kliewi
Electrolyte imbalance, including hypokalaemia and hyponatraemia (see section 4.4), hyperuricaemia, glycosuria, hyperglycaemia, increases in cholesterol and triglycerides
Żbilanċ tal- elettroliti, inklużi ipokalimja u iponatrimja (ara sezzjoni 4. 4), iperuriċemija, glikosurja, ipergliċemija, żiediet fil- kolesterol u trgliċeridi
No information is available on the treatment of overdose with Rasilez HCT.
M’ hemmx tagħrif dwar il- kura ta ’ doża eċċessiva b’ Rasilez HCT.
The most likely manifestation of overdose would be hypotension, related to the antihypertensive effect of aliskiren.
L- aktar ħaga li x’ aktarx tidher b’ doża eċċessiva tkun pressjoni baxxa, relatata mal- effett ta ’ aliskiren li jbaxxi l- pressjoni.
Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, hypochloraemia, hyponatraemia) and dehydration resulting from excessive diuresis.
10 Doża eċċessiva b’ hydrochlorothiazide hija assoċjata ma ’ nuqqas ta ’ elettroliti (ipokalimja, ipoklorimja, iponatrimja) u deidratazzjoni li tiġi minn dijureżi eċċessiva.
The most common signs and symptoms of overdose are nausea and somnolence.
L- aktar sinjali u sintomi komuni ta ’ doża eċċessiva huma dardir u ngħas.
Hypokalaemia may result in muscle spasms and/ or accentuate cardiac arrhythmias associated with the concomitant use of digitalis glycosides or certain antiarrhythmic medicinal products.
Ipokalimja tista ’ twassal għall spażmi tal- muskoli u/ jew arritmiji kardijaċi aktar evidenti assoċjati mal- użu fl- istess ħin ta ’ digitalis glycosides jew ċerti prodotti mediċinali kontra l- arritmiji.
If symptomatic hypotension should occur, supportive treatment should be initiated.
Għandu jinbeda trattament ta ’ sapport jekk jkun hemm ipotensjoni sintomatika.
Renin inhibitor (aliskiren) combinations with diuretics (hydrochlorothiazide), ATC code:
Inibitur tar- renin (aliskiren) f’ taħlita ma ’ dijuretiċi (hydrochlorothiazide), Kodiċi ATC:
10 Rasilez HCT combines two antihypertensive compounds to control blood pressure in patients with essential hypertension:
Rasilez HCT jikkombina żewġ sustanzi kontra l- pressjoni għolja biex jikkontrolla il- pressjoni tad - demm f’ pazjenti bi pressjoni għolja naturali:
Aliskiren belongs to the class of direct renin inhibitors and hydrochlorothiazide to the class of thiazide diuretics.
Aliskiren li jgħamel parti minn klassi ta ’ inibituri tar - renin diretti u hydrochlorothiazide minn klassi ta ’ dijuretiċi thiazide.
The combination of these substances with complementary mechanisms of action provides an additive antihypertensive effect, reducing blood pressure to a greater degree than either component alone.
It- taħlita ta ’ dawn iż- żewġ sustanzi b’ mekkaniżmi ta ’ azzjoni kumplimentari tipprovdi effett addittiv kontra l- pressjoni għolja, u jbaxxi l- pressjoni bi grad akbar minn kull wieħed mill- kompnenti meħudin waħidhom.
Aliskiren Aliskiren is an orally active, non-peptide, potent and selective direct inhibitor of human renin.
Aliskiren 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 renin-angiotensin system (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 tal- enzima renin, aliskiren jinibixxi s- sistema renin- anġjotensin (RAS) fil- punt tal - 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 (angiotensin converting enzyme inhibitors (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 (inibituri tal- enzimi li jikkonvertu l- enzimi (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.
The clinical implications of the effects on PRA are not known at the present time.
L- implikazzjonijiet kliniċi tad- differenzi fl- effett fuq il- PRA mhux magħrufin sa ’ issa.
In hypertensive patients, once-daily administration of aliskiren 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.
F’ pazjenti bil- pressjoni għolja, l- għotja darba kuljum ta ’ aliskiren 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 tal- 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% tal- effett massimu li jbaxxi l- pressjoni deher wara ġimgħatejn.
The blood-pressure-lowering effect was sustained during long-term treatment (12 months), and was independent of age, gender, body mass index and ethnicity.
L- effett li jbaxxi l- pressjoni inżamm waqt kura li ngħatat fit- tul (12- il xahar), u ma kienetx tiddependi mill- età, sess, indiċi tal - massa tal- ġisem u razza.
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 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 aliskiren 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 ’ aliskiren 300 mg kisbet tnaqqis ta ’ 20% kontra plaċebo fil- proporzjon tal - albumina: krejatina fl- awrina (UACR), i. e. minn 58 mg/ mmol għal 46 mg/ mmol.
The proportion of patients who had UACR reduced at least 50% from baseline to endpoint was 24.7% and 12.5% for aliskiren 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 aliskiren 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 mhijix stabbilita fl- assenza ta ’ effett fuq il- pressjoni tad- demm.
Aliskiren did not affect the serum concentration of creatinine but was associated with an increased frequency (4.2% vs.
Aliskiren ma effettwax il - konċentrazzjoni fis- serum tal- krejatinina iżda kien assoċjat ma ’ żieda fil- frekwenza (4. 2% vs.
1.9% for placebo) of serum potassium concentration (≥ 6.0 mmol/ l), although this was not statistically significant.
1. 9% għal plaċebo) tal- konċentrazzjoni tal- potassium fis- serum (≥ 6. 0 mmol/ l), għalkemm dan ma kienx statistikament sinifikanti.
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 aliskiren 150 mg was well tolerated.
11 Fi studju ta ’ 3 xhur fuq 302 pazjenti b’ insuffiċjenza tal- qalb stabbli u mhux severa, li kollha kemm huma kienu qed jirċievu terapija standard għall- insuffiċjenza tal- qalb stabbli, iż- żieda ta ’ aliskiren 150 mg kienet tollerata sew.
B-type natriuretic peptide (BNP) levels were reduced by 25% in the aliskiren arm compared to placebo.
Il- livelli ta ’ peptajd natrijuretiku tat- tip- B (BNP) kienu mnaqqsa b’ 25% fil- fergħa ta ’ aliskiren meta mqabbla mal- plaċebo.
However the clinical significance of this reduction is unknown.
Madankollu s- sinifikat kliniku għadu mhux magħruf.
Combination therapy studies are available for aliskiren added to the diuretic hydrochlorothiazide, the ACEI ramipril, the calcium channel blocker amlodipine, the ARB valsartan, and the beta blocker atenolol.
Hemm studji dwar terapija ikkombinata għal aliskiren miżjud ma ’ dijuretiku hydrochlorothiazide, l - ACEI ramipril, l- imblukkatur tal- kanali tal- calcium amlodipine, l- ARB valsartan, u l- l- imblukkatur beta atenolol.
These combinations were efficacious and well tolerated.
Dawn il- kombinazzjonijiet kienu effikaċji u tollerati sew.
Hydrochlorothiazide The site of action of thiazide diuretics is primarily in the renal distal convoluted tubule.
Hydrochlorothiazide Is- sit ta ’ fejn jaħdmu d- dijuretiċi thiazide huwa l- aktar it- tubu distali konvolut renali.
It has been shown that there is a high-affinity receptor in the renal cortex as the primary binding site for the thiazide diuretic action and inhibition of NaCl transport in the distal convoluted tubule.
Intwera li hemm riċettur li għandu affinità għolja fil- kortiċi renali bħala s- sit ewlieni fejn jeħel u jaħdem id- dijuretiku thiazide u jiġi inibit it- trasport ta ’ NaCl fit- tubu distali konvolut.
The mode of action of thiazides is through inhibition of the Na+Cl- symporter by competing for the Cl- site, thereby affecting electrolyte reabsorption mechanisms: directly increasing sodium and chloride excretion to an approximately equal extent, and indirectly by this diuretic action reducing plasma volume, with
Il- mod ta ’ kif jaħdmu d- dijuretiċi thiazide huwa permezz tal- inibizzjoni tas- simportatur Na+Cl - billi jikkompeti għas- sit tas- Cl -, b’ hekk jeffettwa il- mekkaniżmi li bihom jerġgħu jiġu assorbiti l- elettroliti: iżid direttament l- eskrezzjoni ta ’ sodium u chloride b’ madwar l- istess ammont, u indirettament b’ din l- azzjoni dijuretika billi jnaqqas il - volum tal- plażma, b’ konsegwenza ta ’ żidiet fl- attività tar- renin fil- plażma, sekrezzjoni ta ’ aldosterone u telf tal- potassium fl- awrina tnaqqis tal- potassium fis- serum.
Aliskiren/ hydrochlorothiazide Over 3,900 hypertensive patients received Rasilez HCT once daily in clinical trials.
Aliskiren/ hydrochlorothiazide ’ L fuq minn 3, 900 pazjent bil- pressjoni għolja irċievew Rasilez HCT darba kuljum fi provi kliniċi.
In hypertensive patients, once-daily administration of Rasilez HCT provided dose-dependent reductions in both systolic and diastolic blood pressure that were maintained over the entire 24-hour dose interval.
F’ pazjenti bil- pressjoni għolja, l- għotja ta ’ Rasilez HCT ipprovdiet tnaqqis dipendenti fuq id- doża kemm fil- pressjoni sistolika kif ukoll dijastolika li nżammu fuq il- perijodu kollu tal- 24 siegħa intervall bejn id- dożi.
The antihypertensive effect is largely manifested within 1 week and the maximum effect is generally seen within 4 weeks. 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 fit- tul, u ma kienx jiddependi fuq l- età, sess, indiċi tal- massa tal- ġisem jew etniċità.
The antihypertensive effect of a single dose of the combination persisted for 24 hours.
L- effett kontra l- pressjoni għolja ta ’ doża waħda tat- taħlita inżammet għal 24 siegħa.
Upon withdrawal of the aliskiren treatment (aliskiren with or without hydrochlorothiazide add-on), the return of blood pressure towards baseline was gradual (3-4 weeks) with no evidence of the rebound effect.
Meta twaqqfet il- kura b’ aliskiren (aliskiren b’ hydrochlorothiazide jew mingħajru miżjud), il- pressjoni tad- demm marret lura ghal- linja bażi b’ mod gradwali (3- 4 ġimgħat) mingħajr ma deher ebda effett rebound.
Rasilez HCT was studied in a placebo-controlled trial including 2,762 hypertensive patients with diastolic blood pressure ≥ 95 mmHg and < 110 mmHg (mean baseline blood pressure of 153.6/ 99.2 mmHg).
Rasilez HCT kien studjat fi prova ikkontrollata bi plaċebo li kienet tinkludi 2, 762 pazjent bil- pressjoni għolja bil- pressjoni dijastolika ≥ 95 mmHg u < 110 mmHg (pressjoni medja tal- linja bażi ta ’ 153. 6/ 99. 2 mmHg).
In this study, Rasilez HCT in doses from 150 mg/ 12.5 mg to 300 mg/ 25 mg produced dose-dependent blood pressure reductions (systolic/ diastolic) from 17.6/ 11.9 mmHg to 21.2/ 14.3 mmHg, respectively, compared to 7.5/ 6.9 mmHg with placebo.
F’ dan l- istudju, Rasilez HCT f’ dożi minn 150 mg/ 12. 5 mg sa 300 mg/ 25 mg ikkawżaw tnaqqis fil- pressjoni tad- demm (sistolika/ dijastolika) minn 17. 6/ 11. 9 mmHg sa 21. 2/ 14. 3 mmHg, rispettivament, imqabbla ma ’ 7. 5/ 6. 9 mmHg bil- plaċebo.
The greater blood pressure reductions with these combination doses were also significantly greater than the respective doses of aliskiren and hydrochlorothiazide when used alone.
L- akbar tnaqqis tal - pressjoni b’ dawn id- dożi imħalta kienu akbar b’ mod sinifikanti minn dawk miksuba bid- dożi rispettivi ta ’ aliskiren u hydrochlorothiazide użati waħidhom.
The combination of aliskiren and hydrochlorothiazide neutralised the reactive increase of PRA caused by hydrochlorothiazide.
It- taħlita ta ’ aliskiren u hydrochlorothiazide innewtralizzat iż- żieda reattiva ta ’ PRA ikkawzata minn hydrochlorothiazide.
When administered in hypertensive patients with markedly elevated blood pressure (systolic blood pressure ≥ 160 mmHg and/ or diastolic blood pressure ≥ 100 mmHg), Rasilez HCT in doses from 150 mg/ 12.5 mg to 300 mg/ 25 mg administered without up-titration from monotherapy demonstrated significantly greater systolic/ diastolic blood pressure control rates (< 140/ 90 mmHg) as compared to the respective monotherapies.
Meta tingħata f’ pazjenti li jsofru minn pressjoni għolja u li għandhom pressjoni għolja ħafna (pressjoni sistolika ≥ 160 mmHg u/ jew pressjoni dijastolika ≥ 100 mmHg), dożi ta ’ Rasilez HCT minn 150 mg/ 12. 5 mg sa 300 mg/ 25 mg mogħtija mingħajr titrazzjoni tad- doża aktar minn monoterapija wrew rati ta ’ kontroll tal- pressjoni sistolika/ dijastolika tad- demm (< 140/ 90 mmHg) meta imqabbla ma ’ monoterapiji rispettivi.
In this population, Rasilez HCT 150 mg/ 12.5 mg to 300 mg/ 25 mg provided dose-dependent systolic/ diastolic blood pressure reduction from 20.6/ 12.4 mmHg to 24.8/ 14.5 mmHg, which were significantly superior to the respective monotherapies.
F’ din il- popolazzjoni, Rasilez HCT 150 mg/ 12. 5 mg sa 300 mg/ 25 mg ipprovdiet tnaqqis fil- pressjoni sistolika/ dijastolika tad- demm minn 20. 6/ 12. 4 mmHg sa 24. 8/ 14. 5 mmHg, li kienu superjuri b’ mod sinifikanti għal monoterapiji rispettivi.
The safety of the combination therapy was similar to the respective monotherapies regardless of severity of hypertension or of the presence or absence of additional cardiovascular risk.
Is- sigurtà tat - terapija kombinata kienet simili għall- monoterapiji rispettivi kienet x’ kienet is- severità tal- pressjoni għolja u irrispettivament minn jekk kienx hemm ukoll riskji kardjovaskulari.
Hypotension and related adverse events were uncommon with the combination treatment, with no increased incidence in elderly patients.
Pressjoni baxxa u każijiet avversi relatati ma kienux komuni bil- kura kombinata bl- ebda żieda f’ pazjenti anzjani.
In a study in 880 randomised patients not adequately responsive to aliskiren 300 mg treatment, the combination of aliskiren/ hydrochlorothiazide 300 mg/ 25 mg produced systolic/ diastolic blood pressure reductions of 15.8/ 11.0 mmHg, which were significantly greater than aliskiren 300 mg monotherapy.
12 Fi studju fuq 880 pazjent randomized li ma wrewx rispons xieraq għal kura b’ aliskiren 300 mg, it - taħlita aliskiren/ hydrochlorothiazide 300 mg/ 25 mg ikkawżat tnaqqis fil- pressjoni sistolika/ dijastolika tad- demm ta ’ 15. 8/ 11. 0 mmHg, li kienet akbar b’ mod sinifikanti minn monoterapija b’ aliskiren 300 mg.
In a study in 722 randomised patients not adequately responsive to hydrochlorothiazide 25 mg treatment, the combination of aliskiren/ hydrochlorothiazide 300 mg/ 25 mg produced systolic/ diastolic blood pressure reductions of 16.78/ 10.7 mmHg, which were significantly greater than hydrochlorothiazide 25 mg monotherapy.
Fi studju b’ 722 pazjent randomized li ma wrewx rispons xieraq għal kura b’ hydrochlorothiazide 25 mg, it- taħlita ta ’ aliskiren/ hydrochlorothiazide 300 mg/ 25 mg ikkawżat tnaqqis fil pressjoni sistolika/ dijastolika tad- demm ta ’ 16. 78/ 10. 7 mmHg, li kienu akbar b’ mod sinifikanti mill- monoterapija b’ hydrochlorothiazide waħdu.
In another clinical trial, the efficacy and safety of Rasilez HCT were also assessed in 489 obese hypertensive patients who did not respond to hydrochlorothiazide 25 mg (baseline systolic/ diastolic blood pressure 149.4/ 96.8 mmHg).
Fi prova klinika oħra, l- effikaċja u s- sigurtà ta ’ Rasilez HCT ħċ kienet evalwata f’ 489 pazjent obeż bi pressjoni għolja li ma wrewx rispons għal hudrochlorothiazide 25 mg (linja bażi tal- pressjoni sistolika/ dijastolika tad- demm 149. 4/ 96. 8 mmHg).
In this difficult-to-treat population, Rasilez HCT provided a blood pressure reduction (systolic/ diastolic) of 15.8/ 11.9 mmHg compared to 15.4/ 11.3 mmHg for irbesartan/ hydrochlorothiazide, 13.6/ 10.3 mmHg for amlodipine/ hydrochlorothiazide and 8.6/ 7.9 mmHg for hydrochlorothiazide monotherapy, with similar safety to hydrochlorothiazide monotherapy.
F’ din il- popolazzjoni li hi diffiċli biex tikkura, Rasilez HCT ikkawza tnaqqis fil- pressjoni (sistolika/ dijastolika) ta ’ 15. 8/ 11. 9 mmHg imqabbel ma ’ 15. 4/ 11. 3 mmHg għal irbesartan/ hydrochlorothiazide, 13. 6/ 10. 3 mmHg għal amlodipine/ hydrochlorothiazide u 8. 6/ 7. 9 mmHg għal monoterapija b’ hydrochlorothiazide, b’ sigurtà simili għal monoterapija b’ hydrochlorothiazide.
In a study in 183 randomised patients with severe hypertension (mean sitting diastolic blood pressure ≥ 105 and < 120 mmHg), aliskiren treatment regimen with optional addition of hydrochlorothiazide 25 mg was shown to be safe and efficacious in reducing blood pressure.
Fi studju f’ 183 pazjent randomised bi pressjoni għolja severa (medja tal- pressjoni dijastolika bilqiegħda ta ’ ≥ 105 u < 120 mmHg), kura b’ kors ta ’ aliskiren bl- opżjon li jiżdied hydrochlorothiazide 25 mg deher li kien sigur u effikaċji biex ibaxxi l- pressjoni.
Aliskiren Absorption Following oral absorption, peak plasma concentrations of aliskiren are reached after 1-3 hours.
Aliskiren Assorbiment Wara assorbiment orali, il- konċentrazzjonijiet ta ’ aliskiren fil- plażma laħqu l- quċċata wara 1- 3 sigħat.
Aliskiren is mainly eliminated as unchanged compound in the faeces (oral radioactive dose recovery = 91%).
Aliskiren jiġi eliminat bħala kompost kimiku mhux mibdul fl- ippurgar (irkupru tad- doża orali radjuattiva = 91%).
Linearity Exposure to aliskiren increased slightly more than in proportion to the increase in dose.
Il- kwalità lineari L- esponiment għal aliskiren żdied ftit 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.
Mechanisms responsible for the deviation from dose proportionality have not been identified.
Mekkaniżmi responsabbli għad- devjazzjoni mill- proporzjon mad- doża 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 tal- assorbiment jew fir- rotta ta ’ tneħħija mill- fwied u mill- marrara.
Hydrochlorothiazide Absorption The absorption of hydrochlorothiazide, after an oral dose, is rapid (Tmax about 2 h), with similar absorption characteristics for both suspension and tablet formulations.
Hydrochlorothiazide Assorbiment L- assorbiment ta ’ hydrochlorothiazide, wara doża orali, huwa mgħaġġel (Tmax madwar 2 h), b’ karatteristiċi ta ’ assorbiment simili kemm għas- suspensjoni u formulazzjonijiet ta ’ pilloli.
Absolute bioavailability of hydrochlorothiazide is 60-80% after oral administration.
Biodisponibilità assoluta ta ’ hydrochlorothiazide hija 60- 80% wara għotja orali.
Concomitant administration with food has been reported to both increase and decrease the systemic availability of hydrochlorothiazide compared with the fasted state.
13 Kien irrappurtat li meta jingħata mal- ikel id- disponibilità ta ’ hydrochlorothiazide tiżdied kif ukoll tonqos meta mqabbla mal- istat sawmi.
The magnitude of these effects is small and has little clinical importance.
Id- daqs ta ’ dawn il- bidliet hija żgħira u ftit għandhom importanza klinika.
Distribution The apparent volume of distribution is 4-8 l/ kg.
Distribuzzjoni Il- volum ta ’ distribuzzjoni li jidher huwa minn 4- 8 l/ kg.
Circulating hydrochlorothiazide is bound to serum proteins (40-70%), mainly serum albumin.
Hydrochlorothiazide li jiċċirkola huwa mwaħħal ma ’ proteini tas- serum (40- 70%), l- aktar mal- albumina tas- serum.
Hydrochlorothiazide also accumulates in erythrocytes at approximately 3 times the level in plasma.
Hydrochlorothiazide jakkumula wkoll fl- eritroċiti f’ bejn wieħed u ieħor 3 darbiet aktar mill- livell li jkun hemm fil- plażma.
Metabolism and elimination After oral administration, > 95% of the absorbed dose being excreted as unchanged compound in the urine.
Metaboliżmu u eliminazzjoni Wara li jingħata mil- ħalq, > 95% tad- doża assorbita tiġi mneħħija bħala sustanza mhux mibdula fl - awrina.
The distribution and elimination kinetics have generally been described by a bi-exponential decay function, with a terminal half-life of 6-15 h.
Il- kinetika tad- distribuzzjoni u l- eliminazzjoni ġeneralment ġew deskritti b’ funzjoni ta ’ tnaqqis bi- esponentali fil- qawwa, b’ half- life terminali bejn 6- 15 s.
Linearity The increase in mean AUC is linear and dose proportional in the therapeutic range.
Il- kwalità lineari Iż- zieda fil- medja tal- AUC hija lineari u fi proporzjon mad- doża fil- medda terapewtika.
There is no change in the kinetics of hydrochlorothiazide on repeated dosing, and accumulation is minimal when dosed once daily.
M’ hemmx tibdil fil- kinetika ta ’ hydrochlorothiazide wara dożi ripetuti, u akkumulazzjoni hija minima meta d - doża tingħata darba kuljum.
13 Aliskiren/ hydrochlorothiazide Following oral administration of Rasilez HCT tablets, the median peak plasma concentration time is within 1 hour for aliskiren and 2.5 hours for hydrochlorothiazide.
Aliskiren/ hydrochlorothiazide Wara li jingħataw pilloli ta ’ Rasilez HCT, il- medji tal- ħin tal- quċċati tal- konċentrazzjoni huwa fi żmien siegħa għal aliskiren u 2. 5 siegħa għal hydrochlorothiazide.
The rate and extent of absorption of Rasilez HCT are equivalent to the bioavailability of aliskiren and hydrochlorothiazide when administered as individual monotherapies.
Ir- rata u l- livell ta ’ assorbiment ta ’ Rasilez HCT huma ekwivalenti għal biodisponibilità ta ’ aliskiren u hydrochlorothiazide meta jingħataw bħala monoterapiji individwali.
Similar food effect was observed for Rasilez HCT as for the individual monotherapies.
L- effett li deher bl- ikel kien simili għal Rasilez HCT bħal dak tal- monoterapiji individwali.
Characteristics in patients Rasilez HCT has been shown to be effective as a once-a-day antihypertensive treatment in adult patients, regardless of gender, age, body mass index and ethnicity.
Karatteristiċi f’ pazjenti Rasilez HCT intwera li huwa effettiv bħala kura li tingħata darba kuljum kontra l- pressjoni għolja f’ pazjenti aduti, ikun x’ ikun is- sess, l- età, l- indiċi tal- massa tal- ġisem u l- etniċità.
The pharmacokinetics of aliskiren and hydrochlorothiazide are not significantly affected in patients with mild to moderate liver disease.
Il- farmakokinetika ta ’ alisikiren u hydrochlorothiazide mhumiex effettwati b’ mod sinfikanti f’ pazjenti b’ mard tal- fwied ħafif għal moderat.
Consequently, no initial dose adjustment of Rasilez HCT is required in patients with mild to moderate hepatic impairment.
B’ hekk, mhux meħtieġ li jkun hemm aġġustar tad- doża tal- bidu f’ pazjenti b’ indeboliment tal- fwied ħafif għal moderat.
No data are available on patients with severe hepatic impairment treated by Rasilez HCT.
M’ hemmx dejta dwar pazjenti b’ indeboliment sever tal- fwied ikkurati b’ Rasilez HCT.
However, due to its hydrochlorothiazide component, Rasilez HCT is contraindicated in patients with severe hepatic impairment (see section 4.3).
Madankollu, minħabba l- komponent hydrochlorothiazide, Rasilez HCT huwa kontra- indikat f’ pazjenti b’ mard sever tal- fwied (ara sezzjoni 4. 3).
No adjustment of the initial dose is required for patients with mild to moderate renal impairment (see sections 4.4 and 4.2).
M’ hemmx bżonn ta ’ aġġustar tad- doża f’ pazjenti b’ indeboliment renali ħafif għal moderat (ara sezzjonijiet 4. 4 u 4. 2).
No data are available for Rasilez HCT in patients with severe renal impairment (GFR < 30 ml/ min/ 1.73 m2).
M’ hemmx dejta għal Rasilez HCT f’ pazjenti b’ indeboliment renali sever (GFR < 30 ml/ min/ 1. 73 m2).
However, as expected for a compound which is cleared almost exclusively via the kidneys, renal function has a marked effect on the kinetics of hydrochlorothiazide.
Madankollu, kif mistenni għal sustanza li hija imneħħija kważi esklużivament mill- kliewi, il- funzjoni renali għandha effett qawwi fuq il- kinetika ta ’ hydrochlorothiazide.
Therefore, Rasilez HCT is contraindicated in patients with severe renal impairment (GFR < 30 ml/ min/ 1.73 m2) (see section 4.3).
Għalhekk, Rasilez HCT huwa kontra- indikat f’ pazjenti li jbatu minn indeboliment renali sever (GFR < 30 ml/ min/ 1. 73 m2) (ara sezzjoni 4. 3).
No initial dose adjustment of Rasilez HCT is required in elderly patients.
M’ hemmx bżonn ta ’ aġġustar tad- doża tal- bidu għall- pazjenti anzjani.
No pharmacokinetic data are available in the paediatric population.
M’ hemmx dejta farmakokinetika għall- popolazzjoni pedjatrika.
Safety pharmacology studies with aliskiren did not reveal any adverse effects on central nervous, respiratory or cardiovascular function.
Studji b’ aliskiren 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 f’ annimali minn dożi ripetuti kienu konsistenti mal- irritazzjoni lokali li hi magħrufa jew mal- effetti farmakoloġiċi mistennija ta ’ aliskiren.
No carcinogenic potential for aliskiren was detected in a 2-year rat study and a 6-month transgenic mouse study.
Ma nstabx li kien hemm xi potenzjal karċinoenu għal aliskiren fi studju fuq firien li dam sentejn u fi studju fuq ġrieden transġeniċi li dam 6 xhur.
Aliskiren was devoid of any mutagenic potential, embryo-foetal toxicity or teratogenicity.
Aliskiren ma kellux potenzjal mutaġeniku, tossiċità fuq l- embriju -
Fertility, prenatal development and postnatal development were unaffected in rats.
Il- fertilità, żvilupp ta ’ qabel it- twelid u ta ’ wara t- twelid ma kienux effettwati fil- firien.
Preclinical evaluations to support the administration of hydrochlorothiazide in humans included in vitro genotoxicity assays and reproductive toxicity and carcinogenicity studies in rodents.
Evalwazzjonijiet ta ’ qabel l- użu kliniku biex jindikaw il- bżonn li jingħata hydrochlorothiazide fi bnedmin kienu jinkludu essejs ġenotossiċi u tossiċità riproduttiva u studji dwar kanċeroġeniċità f’ annimali gerriema.
Extensive clinical data are available for hydrochlorothiazide and these are reflected in the relevant sections.
Hemm dejta kliniċi estensivi għal hydrochlorothiazide u dawn kienu riflessi fis - sezzjonijiet rilevanti.
The findings observed in the 2-week and 13-week toxicity studies were consistent with those observed previously with aliskiren or hydrochlorothiazide monotherapies.
Is- sejbiet osservati fl- istudji ta ’ tossiċità ta ’ ġimagħtejn u 13- il ġimgħa kienu konsistenti ma ’ dawk osservati qabel b’ monoterapiji ta ’ aliskiren u hydrochlorothiazide.
There were no new or unexpected findings observed of relevance to human use.
Ma kienu osservati l- ebda sejbiet ġodda jew mhux mistennija ta ’ rilevanza għall- użu uman.
Increased cellular vacuolation of the adrenal gland zona glomerulosa was observed during the 13-week toxicity study in rats.
Żieda fil- vakwolazzjoni ċellulari taż- żona glomerulosa tal- glandola adrenali kienet osservata waqt l- istudju ta ’ tossiċità ta ’ 13- il ġimgħa fil - firien.
The finding was observed in animals treated with hydrochlorothiazide but not in those animals receiving aliskiren alone or vehicle.
Is- sejba kienet osservata f’ annimali kkurati b’ hydrochlorothiazide iżda mhux f’ dawk l- annimali li rċievew aliskiren waħdu jew sustanza mingħajr il- mediċina.
There was no evidence that this finding was enhanced in the aliskiren/ hydrochlorothiazide combination as it was only apparent at a minimal severity in all animals.
Ma kienx hemm evidenza li din is- sejba kienet akbar fit- taħlita aliskiren/ hydrochlorothiazide minħabba li dehret biss f’ qawwa minima fl - annimali kollha.
Cellulose microcrystalline Crospovidone Lactose monohydrate Wheat starch Povidone Magnesium stearate Silica colloidal anhydrous Talc
Cellulose microcrystalline Crospovidone Lactose monohydrate Wheat starch Povidone Magnesium stearate Silica colloidal anhydrous Talc
Talc Hypromellose Macrogol Titanium dioxide (E171)
Talc Hypromellose Macrogol Titanium dioxide (E171)
PA/ Alu/ PVC – Alu blisters:
Folji PA/ Alu/ PVC – Alu:
Single-packs containing 7, 14, 28, 30, 50 or 56 tablets.
Pakketti b’ wieħed li jkun fihom 7, 14, 28, 30, 50 jew 56 pillola.
Multi-packs containing 90, 98 or 280 tablets.
Pakketti b’ ħafna li jkun fihom 90, 98 jew 280 pillola.
PVC/ polychlorotrifluoroethylene (PCTFE) – Alu blisters:
Folji PVC / polychlorotrifluoroethylene (PCTFE) – Alu:
Single-packs containing 7, 14, 28, 30, 50, 56, 90 or 98 tablets.
Pakketti b’ wieħed li jkun fihom 7, 14, 28, 30, 50, 56, 90 jew 98 pillola.
Single-packs (perforated unit dose blister) containing 56 x 1 tablets.
Pakketti b’ wieħed (folja mtaqqba b’ doża waħda) li jkun fihom 56 x 1 pillola.
Multi-packs containing 280 tablets.
Pakketti b’ ħafna li fihom 280 pillola.
Multi-packs (perforated unit dose blister) containing 98 x 1 tablets.
Pakketti b’ ħafna (folja mtaqqba b’ doża waħda) li jkun fihom 98 x 1 pillola.
Not all pack sizes or strengths may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jew tal- qawwiet kollha jkunu għall- skop kummerċjali.
Rasilez HCT 150 mg/ 25 mg film-coated tablets
Rasilez HCT 150 mg/ 25 mg pilloli miksijin b’ rita
Each film-coated tablet contains 150 mg aliskiren (as hemifumarate) and 25 mg hydrochlorothiazide.
Kull pillola miksija b’ rita fiha 150 mg aliskiren (bħala hemifumarate) u 25 mg hydrochlorothiazide.
Each tablet contains 50 mg lactose monohydrate and 49 mg wheat starch.
Kull pillola fiha 50 mg lactose monohydrate u 49 mg wheat starch.
Pale yellow, biconvex, ovaloid film-coated tablet imprinted with “ CLL” on one side and “ NVR” on the other.
Pillola tagħti fl- isfar, konvessa miż- żewġ naħat, b’ għamla ovali miksija b’ rita stampata b ’ “ CLL ” fuq naħa u “ NVR ” fuq l- oħra.
Rasilez HCT 150 mg / 25 mg may be administered in patients whose blood pressure is not adequately controlled with aliskiren 150 mg or hydrochlorothiazide 25 mg alone or by Rasilez HCT 150 mg/ 12.5 mg.
Rasilez HCT 150 mg/ 25 mg jista ’ jingħata f’ pazjenti li jkollhom il- pressjoni tad- demm li ma tkunx ikkontrollata kif jixraq b’ aliskiren 150 mg jew hydrochlorothiazide 25 mg waħidhom jew b’ Rasilez HCT 150 mg/ 12. 5 mg.
17 Posology as substitution therapy For convenience, patients receiving aliskiren and hydrochlorothiazide from separate tablets may be switched to a fixed combination tablet of Rasilez HCT containing the same component doses.
17 Pożoloġija bħala terapija ta ’ sostituzzjoni Għall- konvenjenza, pazjenti li jkunu qed jirċievu aliskiren u hydrochlorothiazide minn pilloli separati jistgħu jinqalbu għall- pillola ta ’ taħlita fissa ta ’ Rasilez HCT li fiha l- istess dożi tal- komponenti.
Intravascular volume depletion Symptomatic hypotension may occur in patients who are volume and/ or sodium depleted as a result of vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting.
18 Tnaqqis tal- volum intravaskulari Ipotensjoni sintomatika tista ’ sseħħ f’ pazjenti li jkollhom nuqqas tal- volum u/ jew sodium b’ konsegwenza ta ’ terapija vigoruża b’ dijuretiċi, restrizzjoni tal- melħ mill- ikel, dijarea jew rimettar.
18 Electrolyte imbalance As for any patient receiving diuretic therapy, periodic determination of serum electrolytes should be performed at appropriate intervals.
Żbilanċ tal- elettroliti Bħal ma jsir għal kull pazjent li jkun qed jirċievi terapija dijuretika, determinazzjoni perjodika tal - elettroliti fis- serum għandha titwettaq f’ intervalli xierqa.
Hepatic impairment Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
19 Indeboliment epatiku Thiazides għandhom jintużaw b’ kawtela f’ pazjenti b’ funzjoni epatika indebolita jew mard tal- fwied li jkun qed javvanza, peress li tibdil żgħir tal- fluwidi u l- elettroliti jista ’ jippreċipita koma epatika.
There is no clinical experience with Rasilez HCT in patients with hepatic impairment.
M’ hemmx esperjenza klinika b’ Rasilez HCT f’ pazjenti b’ indeboliment epatiku.
19 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.
Stenożi tal- valv tal- aorta u mitrali, kardjomijopatija ipertrofika ostruttiva Bħal ma jseħħ b’ vażodilataturi oħrajn, hija indikata kawtela speċjali f’ pazjenti li jsofru minn stenożi tal- aorta jew mitrali, jew kardjomijopatija ipertrofika ostruttiva.
Conversely, based on experience with the use of other medicinal products that blunt the renin-angiotensin system (RAS), concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products that may increase serum potassium levels (e. g. heparin sodium) may lead to increases in serum potassium.
20 Bil- kontra, minn esperjenza bi prodotti mediċinali oħrajn li joħonqu s- sistema renin- angiotensin (RAS), l- użu ta ’ dijuretiċi li ma jħallux il- potassium jintilef, supplimenti tal- potassium, sostituti tal - melħ li fihom il- potassium jew prodotti mediċinali oħrajn li jistgħu jżidu l- livelli ta ’ potassium fis - serum (eż. heparin sodium) jistgħu jwasslu għal żidiet tal- potassium fis- serum.
20 Medicinal products affected by serum potassium disturbances:
Prodotti mediċinali effettwati minn disturbi tal- potassium fis- serum:
Other antihypertensive agents:
Sustanzi kontra l- pressjoni oħrajn:
Grapefruit juice:
21 Meraq tal- grejpfrut:
In some patients with compromised renal function (dehydrated patients or elderly patients) aliskiren given concomitantly
Bħal ma jiġri b’ sustanzi oħra li jaħdmu fuq is - sistema ta ’ renin- angiotensin, l- NSAIDs jistgħu jnaqqsu l- effett li għandu aliskiren kontra l- pressjoni għolja.
21 with NSAIDs may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible.
F’ xi pazjenti b’ funzjoni tal- kliewi kompromessa (pazjenti deidradati jew pazjenti anzjani) aliskiren mogħti flimkien ma ’ NSAIDs jista ’ jwassal għal funzjoni tal- kliewi li aktar tmur għall- agħar, inkluż il- possibiltà ta ’ insuffiċjenza tal- kliewi li s- soltu terġa ’ tmur lura għal dak li kienet.
Curare derivatives (e. g. tubocurarine):
22 Derivati curare (eż. tubocurarine):
22 4.6 Pregnancy and lactation
4. 6 Tqala u treddigħ
Prolonged exposure to thiazides during the third trimester of pregnancy can reduce maternal plasma volume as well as uteroplacental blood flow, which may cause a foeto-placental ischaemia and growth retardation.
Esponiment fit- tul għal thiazides waqt it- tielet trimestru tat- tqala jista ’ jnaqqas il- volum tal- plażma tal - omm kif ukoll il- passaġġ tad- demm bejn l- utru u l- plaċenta, li jista ’ jikkawża iskemija fetu- plaċentali u ittardjar tat- tkabbir.
The frequency of adverse reactions listed below is defined using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
23 Il- frekwenza tar- reazzjonijiet avversi elenkati hawn taħt hija definita permezz tal- konvenzjoni li ġejja: komuni ħafna (≥ 1/ 10); komuni (≥ 1/ 100 sa < 1/ 10); mhux komuni (≥ 1/ 1, 000 sa < 1/ 100); rari (≥ 1/ 10, 000 sa < 1/ 1, 000); rari ħafna (< 1/ 10, 000), mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
23 Serum potassium:
Potassium fis- serum:
Additional information on individual components Adverse reactions previously reported with one of the individual components may occur with Rasilez HCT even if not observed in clinical trials.
Tagħrif ieħor dwar il- komponenti individwali Reazzjonijiet avversi li kienu rrappurtati qabel b’ wieħed mill- komponenti individwali jistgħu jseħħu b’ Rasilez HCT anki jekk ma dehrux waqt provi kliniċi.
Serum potassium:
24 Potassium fis- serum:
24 Blood and lymphatic system disorders
Disturbi tad- demm u tas- sistema limfatika
Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, hypochloraemia, hyponatraemia) and dehydration resulting from excessive diuresis.
25 Doża eċċessiva b’ hydrochlorothiazide hija assoċjata ma ’ nuqqas ta ’ elettroliti (ipokalimja, ipoklorimja, iponatrimja) u deidratazzjoni li tiġi minn dijureżi eċċessiva.
25 Rasilez HCT combines two antihypertensive compounds to control blood pressure in patients with essential hypertension:
Rasilez HCT jikkombina żewġ sustanzi kontra l- pressjoni għolja biex jikkontrolla il- pressjoni tad - demm f’ pazjenti bi pressjoni għolja naturali:
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 aliskiren 150 mg was well tolerated.
26 Fi studju ta ’ 3 xhur fuq 302 pazjenti b’ insuffiċjenza tal- qalb stabbli u mhux severa, li kollha kemm huma kienu qed jirċievu terapija standard għall- insuffiċjenza tal- qalb stabbli, iż- żieda ta ’ aliskiren 150 mg kienet tollerata sew.
26 approximately equal extent, and indirectly by this diuretic action reducing plasma volume, with consequent increases in plasma renin activity, aldosterone secretion and urinary potassium loss, and a decrease in serum potassium.
Il- mod ta ’ kif jaħdmu d- dijuretiċi thiazide huwa permezz tal- inibizzjoni tas- simportatur Na+Cl - billi jikkompeti għas- sit tas- Cl -, b’ hekk jeffettwa il- mekkaniżmi li bihom jerġgħu jiġu assorbiti l- elettroliti: iżid direttament l- eskrezzjoni ta ’ sodium u chloride b’ madwar l- istess ammont, u indirettament b’ din l- azzjoni dijuretika billi jnaqqas il - volum tal- plażma, b’ konsegwenza ta ’ żidiet fl- attività tar- renin fil- plażma, sekrezzjoni ta ’ aldosterone u telf tal- potassium fl- awrina tnaqqis tal- potassium fis- serum.
In a study in 880 randomised patients not adequately responsive to aliskiren 300 mg treatment, the combination of aliskiren/ hydrochlorothiazide 300 mg/ 25 mg produced systolic/ diastolic blood pressure reductions of 15.8/ 11.0 mmHg, which were significantly greater than aliskiren 300 mg monotherapy.
27 Fi studju fuq 880 pazjent randomized li ma wrewx rispons xieraq għal kura b’ aliskiren 300 mg, it - taħlita aliskiren/ hydrochlorothiazide 300 mg/ 25 mg ikkawżat tnaqqis fil- pressjoni sistolika/ dijastolika tad- demm ta ’ 15. 8/ 11. 0 mmHg, li kienet akbar b’ mod sinifikanti minn monoterapija b’ aliskiren 300 mg.
27 5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku
Concomitant administration with food has been reported to both increase and decrease the systemic availability of hydrochlorothiazide compared with the fasted state.
28 Kien irrappurtat li meta jingħata mal- ikel id- disponibilità ta ’ hydrochlorothiazide tiżdied kif ukoll tonqos meta mqabbla mal- istat sawmi.
28 Aliskiren/ hydrochlorothiazide Following oral administration of Rasilez HCT tablets, the median peak plasma concentration time is within 1 hour for aliskiren and 2.5 hours for hydrochlorothiazide.
Aliskiren/ hydrochlorothiazide Wara li jingħataw pilloli ta ’ Rasilez HCT, il- medji tal- ħin tal- quċċati tal- konċentrazzjoni huwa fi żmien siegħa għal aliskiren u 2. 5 siegħa għal hydrochlorothiazide.
Talc Hypromellose Macrogol Titanium dioxide (E171) Red iron oxide (E172) Yellow iron oxide (E172)
Talc Hypromellose Macrogol Titanium dioxide (E171) Red iron oxide (E172) Yellow iron oxide (E172)
6.5 Nature and contents of container
30 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Rasilez HCT 300 mg/ 12.5 mg film-coated tablets
Rasilez HCT 300 mg/ 12. 5 mg pilloli miksijin b’ rita
Each film-coated tablet contains 300 mg aliskiren (as hemifumarate) and 12.5 mg hydrochlorothiazide.
Kull pillola miksija b’ rita fiha 300 mg aliskiren (bħala hemifumarate) u 12. 5 mg hydrochlorothiazide.
Violet white, biconvex, ovaloid film-coated tablet imprinted with “ CVI” on one side and “ NVR” on the other.
Pillola vjola bajda, konvessa miż- żewġ naħat, b’ għamla ovali miksija b’ rita stampata b ’ “ CVI ” fuq naħa u “ NVR ” fuq l- oħra.
Rasilez HCT 300 mg / 12.5 mg may be administered in patients whose blood pressure is not adequately controlled with aliskiren 300 mg or hydrochlorothiazide 12.5 mg alone or by Rasilez HCT 150 mg/ 12.5 mg.
Rasilez HCT 300 mg/ 12. 5 mg jista ’ jingħata f’ pazjenti li jkollhom il- pressjoni tad- demm li ma tkunx ikkontrollata kif jixraq b’ aliskiren 300 mg jew hydrochlorothiazide 12. 5 mg waħidhom jew b’ Rasilez HCT 150 mg/ 12. 5 mg.