qanastek/EMEA-V3 huggingface dataset:
The effect of the combination of irbesartan and hydrochlorothiazide on morbidity and mortality has not been studied.
Ma ġiex studjat l- effett tal- kombinazzjoni ta ’ irbesartan u hydrochlorothiazide fuq il- morbidità u l - imwiet.
Epidemiological studies have shown that long term treatment with hydrochlorothiazide reduces the risk of cardiovascular mortality and morbidity.
Studji epidemjoloġiċi wrew li kura fit- tul b’ hydrochlorothiazide tnaqqas ir- riskju ta ’ mwiet u morbidità kardjovaskulari.
There is no difference in response to CoAprovel, regardless of age or gender.
Ir- rispons għal CoAprovel ma jiddependix mill- età u lanqas mis- sess.
As is the case with other medicinal products that affect the renin-angiotensin system, black hypertensive patients have notably less response to irbesartan monotherapy.
Bħal fil- każ ta ’ prodotti mediċinali oħra li jaffetwaw is- sistema renin- angiotensin, pazjenti suwed bi pressjoni għolja għandhom rispons notevolment anqas għal terapija bi ibersartan waħdu.
12.5 mg daily), the antihypertensive response in black patients approaches that of non-black patients.
Meta irbesartan jingħata flimkien ma ’ doża baxxa ta ’ hydrochlorothiazide (p. e 12. 5 mg kuljum), ir- rispons kontra il- pressjoni għolja f’ pazjenti suwed javviċina lil dak f’ pazjenti mhux suwed.
Efficacy and safety of CoAprovel as initial therapy for severe hypertension (defined as SeDBP ≥ 110 mmHg) was evaluated in a multicenter, randomized, double-blind, active-controlled, 8-week, parallel-arm study.
L- effikaċja u s- sigurtà ta ’ CoAprovel bħala terapija inizjali għal pressjoni għolja severa (definita bħala SeDBP ≥ 110 mmHg) ġew evalwati fi studju b’ aktar minn ċentru wieħed, b’ mod każwali, double - blind, ikkontrollat b’ mod attiv ta ’ 8 ġimgħat, parallel- arm.
A total of 697 patients were randomized in a 2:1 ratio to either irbesartan/ hydrochlorothiazide 150 mg/ 12.5 mg or to irbesartan 150 mg and systematically force- titrated (before assessing the response to the lower dose) after one week to irbesartan/ hydrochlorothiazide 300 mg/ 25 mg or irbesartan 300 mg, respectively.
B’ kollox 697 pazjent intagħżlu b’ mod każwali fi proporzjon ta ’ 2: 1 jew għal irbesartan/ hydrochlorothiazide 150 mg/ 12. 5 mg jew għal irbesartan 150 mg u ġew titrati bil- forza b’ mod sistematiku (qabel ma r- rispons tagħhom għal doża iktar baxxa ġie vvalutat) wara ġimgħa għal irbesartan/ hydrochlorothiazide 300 mg/ 25 mg jew irbesartan 300 mg, rispettivament.
The study recruited 58% males.
L- istudju kien magħmul minn 58% irġiel.
The mean age of patients was 52.5 years, 13% were ≥ 65 years of age, and just 2% were ≥ 75 years of age.
L- età medja tal- pazjenti kienet ta ’ 52. 5 sena, 13% kienu ≥ 65 sena, u 2% biss kienu ≥ 75 sena.
Twelve percent (12%) of patients were diabetic, 34% were hyperlipidemic and the most frequent cardiovascular condition was stable angina pectoris in 3.5% of the participants.
Tnax fil- mija (12%) tal- pazjenti kienu dijabetiċi, 34% kienu iperlipidemiċi u l- aktar kundizzjoni kardjovaskulari frekwenti kienet anġina pectoris stabbli fi 3. 5% tal- parteċipanti.
Forty-seven percent (47.2%) of patients on
L- għan ewlieni ta ’ dan l- istudju kien li jqabbel il- proporzjon ta ’ pazjenti li l- SeDBP tagħhom kien ikkontrollat (SeDBP < 90 mmHg) f’ Ġimgħa 5 tat- trattament.
10 the combination achieved trough SeDBP < 90 mmHg compared to 33.2% of patients on irbesartan (p = 0.0005).
Erbgħa u sebgħin fil- mija (47. 2%) tal - pazjenti fuq il- kombinazzjoni laħqu livell minimu ta ’ SeDBP < 90 mmHg meta mqabbel ma ’ 33. 2% tal- pazjenti fuq irbesartan (p = 0. 0005).
The mean baseline blood pressure was approximately 172/ 113 mmHg in each treatment group and decreases of SeSBP/ SeDBP at five weeks were 30.8/ 24.0 mmHg and 21.1/ 19.3 mmHg for irbesartan/ hydrochlorothiazide and irbesartan, respectively (p < 0.0001).
Il- pressjoni tad- demm medja fil- linja bażi kienet bejn wieħed u ieħor 172/ 113 mmHg f’ kull grupp ta ’ trattament u t- tnaqqis ta ’ SeSBP/ SeDBP wara ħames ġimgħat kien 30. 8/ 24. 0 mmHg u 21. 1/ 19. 3 mmHg għal irbesartan/ hydrochlorothiazide u irbesartan, rispettivament (p < 0. 0001).
The types and incidences of adverse events reported for patients treated with the combination were similar to the adverse event profile for patients on monotherapy.
It- tipi u l- inċidenzi ta ’ episodji avversi rrapportati għal pazjenti ttrattati bil- kombinazzjoni kienu simili għall- profil ta ’ l- episodju avvers għal pazjenti fuq monoterapija.
During the 8-week treatment period, there were no reported cases of syncope in either treatment group.
Matul il- perjodu ta ’ trattament ta ’ 8 ġimgħat, ma kien hemm ebda każ ta ’ sinkope rrapportat f’ xi grupp tat- trattament.
There were 0.6% and 0% of patients with hypotension and 2.8% and 3.1% of patients with dizziness as adverse reactions reported in the combination and monotherapy groups, respectively.
Kien hemm 0. 6% u 0% ta ’ pazjenti bi pressjoni baxxa u 2. 8% u 3. 1% ta ’ pazjenti bi sturdament bħala reazzjonijiet avversi rrapportati fil- gruppi ta ’ kombinazzjoni u ta ’ monoterapija, rispettivament.
Concomitant administration of hydrochlorothiazide and irbesartan has no effect on the pharmacokinetics of either medicinal product.
L- użu flimkien ta ’ hydrochlorothiazide u irbesartan m’ għandu l- ebda effett fuq il- farmakoniteċi taż - żewġ mediċini.
Irbesartan and hydrochlorothiazide are orally active agents and do not require biotransformation for their activity.
Irbesartan u hydrochlorothiazide huma attivi mill- ħalq u m’ għandhomx bżonn biotransformazzjoni biex ikunu attivi.
Following oral administration of CoAprovel, the absolute oral bioavailability is 60-80% and 50-80% for irbesartan and hydrochlorothiazide, respectively.
Wara li jingħata mill- ħalq CoAprovel il- biodisponibilità assoluta orali hija 60 - 80% u 50 - 80% għal irbesartan u hydrochlorothiazide, rispettivament.
Food does not affect the bioavailability of CoAprovel.
L- ikel ma jaffettwax il - biodisponibilità ta ’ CoAprovel.
Peak plasma concentration occurs at 1.5-2 hours after oral administration for irbesartan and 1-2.5 hours for hydrochlorothiazide.
Il- konċentrazzjoni fil- plażma tilħaq l- ogħla livell 1. 5 - 2 sigħat wara li tingħata mill- ħalq għal irbesartan u 1 - 2. 5 sigħat għal hydrochlorothiazide.
Plasma protein binding of irbesartan is approximately 96%, with negligible binding to cellular blood components.
Irbesartan jeħel mal- proteina tal- plażma b’ madwar 96%, u l- għaqda mal- komponenti taċ- ċelluli tad - demm hija negliġibbli.
The volume of distribution for irbesartan is 53-93 litres.
Il- volum ta ’ distribuzzjoni għal irbesartan huwa 53 - 93 litru.
Hydrochlorothiazide is 68% protein-bound in the plasma, and its apparent volume of distribution is 0.83-1.14 l/ kg.
11 Hydrochlrothiazide jeħel mal- proteini tal- plażma bi 68%, u l- volum ta ’ distibuzzjoni apparenti huwa 0. 83 - 1. 14 l/ kg.
Irbesartan exhibits linear and dose proportional pharmacokinetics over the dose range of 10 to 600 mg.
Irbesartan juri farmakokinetiċi linjari u proporzjonati mad- doża meta jingħata fuq il- firxa tad- doża ta ’ 10 sa 600 mg.
A less than proportional increase in oral absorption at doses beyond 600 mg was observed; the mechanism for this is unknown.
Ġiet osservata żieda mhux proporzjonali, fl- assorbiment mill- ħalq meta tingħata doża iktar minn 600 mg; dan il- mekkaniżmu għadu mhux magħruf.
The total body and renal clearance are 157-176 and 3.0-3.5 ml/ min, respectively.
It- tneħħija mill- ġisem kollu u renali hija 157 - 176 u 3. 0 - 3. 5 ml/ min, rispettivament.
The terminal elimination half-life of irbesartan is 11-15 hours.
Il- half- life ta ’ l- eliminazzjoni terminali ta ’ irbesartan hija 11 - 15- il siegħa.
Steady-state plasma concentrations are attained within 3 days after initiation of a once-daily dosing regimen.
Il- konċentrazzjoni fissa fil- plażma tintlaħaq wara 3 ijiem minn meta tinbeda l- kura ta ’ darba kuljum.
Limited accumulation of irbesartan (< 20%) is observed in plasma upon repeated once-daily dosing.
Kienet osservata akkumulazzjoni limitata ta ’ irbesartan (< 20%) fil- plażma meta ngħatat doża darba kuljum repetuta.
In a study, somewhat higher plasma concentrations of irbesartan were observed in female hypertensive patients.
Fi studju ġew osservati konċentrazzjonijiet ta ’ irbesartan fil - plażma xi ftit ogħla fil- pazjenti nisa bi pressjoni għolja.
However, there was no difference in the half-life and accumulation of irbesartan.
Madankollu ma kienx hemm differenza fil - half- life u fl- akkumulazzjoni ta ’ irbesartan.
No dosage adjustment is necessary in female patients.
M’ hemmx bżonn aġġustar tad- doża f’ pazjenti nisa.
Irbesartan AUC and Cmax values were also somewhat greater in elderly subjects (≥ 65 years) than those of young subjects (18-40 years).
Il - valuri ta ’ irbesartan AUC u Cmax kienu wkoll xi ftit iktar fil- pazjenti anzjani (≥ 65 sengħa) milli fil - pazjenti żgħar (18- 40 sena).
However the terminal half-life was not significantly altered.
Madankollu il- half- life terminali ma tbiddlitx b’ mod sinifikanti.
No dosage adjustment is necessary in elderly patients.
M’ hemmx bżonn aġġustar ta ’ doża f’ pazjenti anzjani.
The mean plasma half-life of hydrochlorothiazide reportedly ranges from 5-15 hours.
Il- medja tal- half life tal- plażma ta ’ hydrochlorothiazide ġiet irrapportata li tvarja minn 5- 15- il siegħa.
Following oral or intravenous administration of 14C irbesartan, 80-85% of the circulating plasma radioactivity is attributable to unchanged irbesartan.
Wara li 14C irbesartan jingħata mill- ħalq jew ġol- vini, 80 - 85% tar- radjuattività li tiċċirkola fil- plażma hi attribwita għal irbesartan mhux mibdul.
Irbesartan is metabolised by the liver via glucuronide conjugation and oxidation.
Irbesartan jiġi metabolizzat fil- fwied permezz tal - konjugazzjoni mal- glucuronide u l- ossidazzjoni.
The major circulating metabolite is irbesartan glucuronide (approximately 6%).
Il- metabolit maġġuri li jiċċirkola huwa irbesartan glucuronide (bejn wieħed u ieħor 6%).
In vitro studies indicate that irbesartan is primarily oxidised by the cytochrome P450 enzyme CYP2C9; isoenzyme CYP3A4 has negligible effect.
Studji in vitro jindikaw li irbesartan huwa primarjament ossidat bl- enzima cytochrome P450 CYP2C9; l- isoenzima CYP3A4 għandha effett negliġibbli.
Irbesartan and its metabolites are eliminated by both biliary and renal pathways.
Irbesartan u l - metaboliti tiegħu huma eliminati kemm permezz tas- sistema biljari kif ukoll permezz ta ’ dik renali.
After either oral or intravenous administration of 14C irbesartan, about 20% of the radioactivity is recovered in the urine, and the remainder in the faeces.
Wara li 14C irbesartan jingħata jew mill- ħalq jew ġol- vini, madwar 20% tar- radjuattività tiġi rkuprata fl- awrina, u l- kumplament fl- ippurgar.
Less than 2% of the dose is excreted in the urine as unchanged irbesartan.
Inqas minn 2% tad- doża toħroġ fl- awrina bħala irbesartan mhux mibdul.
Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidneys.
Hydrochlorothiazide ma jiġix metabolizzat iżda jiġi eliminat malajr permezz tal- kliewi.
At least 61% of the oral dose is eliminated unchanged within 24 hours.
Għall- inqas 61% tad- doża meħuda mill- ħalq tiġi eliminata mingħajr tibdil wara 24 siegħa.
Hydrochlorothiazide crosses the placental but not the blood-brain barrier, and is excreted in breast milk.
Hydrochlorothiazide jgħaddi mill- plaċenta iżda mhux mill- barriera bejn il- moħħ u d- demm, u jitneħħa fil- ħalib tas- sider.
Renal impairment: in patients with renal impairment or those undergoing haemodialysis, the pharmacokinetic parameters of irbesartan are not significantly altered.
Indeboliment Renali: f’ pazjenti b’ indeboliment renali jew li qed jagħmlu l- emodijalisi, il- parametri farmakokinetiċi ta ’ irbesartan ma tbiddlux b’ mod sinifikanti.
Irbesartan is not removed by haemodialysis.
Irbesartan ma jitneħħiex bl- emodijalisi.
In patients with creatinine clearance < 20 ml/ min, the elimination half-life of hydrochlorothiazide was reported to increase to 21 hours.
F’ pazjenti bi tneħħija ta ’ krejatinina < 20 ml/ min, l- half- life ta ’ l- eliminazzjoni ta ’ hydrochlorothiaze ġiet irrapportata li tiżdied għal 21 siegħa.
11 Hepatic impairment: in patients with mild to moderate cirrhosis, the pharmacokinetic parameters of irbesartan are not significantly altered.
Indeboliment epatiku: f’ pazjenti b’ ċirrożi, minn ħafifa għal moderata, il- parametri farmakokinetiċi ta ’ irbesartan ma jitbiddlux b’ mod sinifikanti.
Studies have not been performed in patients with severe hepatic impairment.
Ma sarux studji f’ pazjenti b’ indeboliment epatiku sever.
5.3 Preclinical safety data
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- siġurtà tal- mediċina
Irbesartan/ hydrochlorothiazide: the potential toxicity of the irbesartan/ hydrochlorothiazide combination after oral administration was evaluated in rats and macaques in studies lasting up to 6 months.
Irbesartan/ hydrochlorothiazide: it- tossiċità potenzjali tal- kombinazzjoni ta ’ irbesartan / hydrochlorothiazide wara li tingħata mill- ħalq ġiet evalwata f’ firien u f’ makakki (macaques) waqt studji li damu sa 6 xhur.
There were no toxicological findings observed of relevance to human therapeutic use.
Ma ġewx osservati sejbiet tossikoloġiċi, ta ’ relevanza, waqt l- użu terapewtiku fil- bniedem.
The following changes, observed in rats and macaques receiving the irbesartan/ hydrochlorothiazide combination at 10/ 10 and 90/ 90 mg/ kg/ day, were also seen with one of the two medicinal products alone and/ or were secondary to decreases in blood pressure (no significant toxicologic interactions were observed): kidney changes, characterized by slight increases in serum urea and creatinine, and hyperplasia/ hypertrophy of the juxtaglomerular apparatus, which are a direct consequence of the interaction of irbesartan with the renin-angiotensin system; slight decreases in erythrocyte parameters (erythrocytes, haemoglobin, haematocrit); stomach discoloration, ulcers and focal necrosis of gastric mucosa were observed in few rats in a 6 months toxicity study at irbesartan 90 mg/ kg/ day, hydrochlorothiazide 90 mg/ kg/ day, and irbesartan/ hydrochlorothiazide 10/ 10 mg/ kg/ day.
It- tibdiliet li ġejjin, osservati f’ firien u f’ makakki li rċevew il- kombinazzjoni ta ’ irbesartan / hydrochlorothiazide f’ dożi ta ’ 10/ 10 u 90/ 90 mg/ kg/ jum, dehru wkoll b’ wieħed minn dawn iż- żewġ mediċini waħidhom u/ jew kienu sekondarji għal tnaqqis tal- pressjoni (ma ġewx osservati interazzjonijiet tossikoloġiċi sinifikanti): tibdil fil- kliewi, ikkaratterizzat minn żidiet ħfief fl- urea fis- serum u tal- krejatinina, u iperplażja / ipertrofija ta ’ l- apparat jukstaglomerulari, li huma konsegwenza diretta ta ’ l- interazzjoni ta ’ irbesartan mas- sistema renin- angiotensin; tnaqqis żgħir fil- parametri ta ’ l- eritroċiti (eritroċiti, emoglobina, ematokrit); telf ta ’ kulur fl- istonku, ulċeri, nekrożi fokali tal- mukoża gastrika ġew osservati fi ftit firien fi studju ta ’ 6 xhur fuq it- tossiċita` b’ irbesartan 90 mg/ kg/ jum, hydrochlorothiazide 90 mg/ kg/ jum u irbesratan/ hydrochlorothiazide 10/ 10 mg/ kg/ jum.
These lesions were not observed in macaques; decreases in serum potassium due to hydrochlorothiazide and partly prevented when hydrochlorothiazide was given in combination with irbesartan.
Dawn il- leżjonijiet ma ġewx osservati fil - makakki; tnaqqis tal- potassium fis- serum minħabba hydrochlorothiazide u mfixkla parzjalment meta hydrochlorothiazide ingħata flimkien ma ’ irbesartan.
Most of the above mentioned effects appear to be due to the pharmacological activity of irbesartan (blockade of angiotensin-II-induced inhibition of renin release, with stimulation of the renin-producing cells) and occur also with angiotensin converting enzyme inhibitors.
12 Il- parti l- kbira mill- effetti msemmija hawn fuq jidhru li ġraw minħabba l- attivita` farmakoloġika ta ’ irbesartan (imblokk ta ’ l- inibizzjoni stimulata minn angiotensin II tal- ħelsien ta ’ renin, b’ stimulazzjoni ta ’ ċelluli li jipproduċu renin) u jseħħu wkoll b’ impedituri ta ’ enzimi li jikkonvertu angiotensin.
These findings appear to have no relevance to the use of therapeutic doses of irbesartan/ hydrochlorothiazide in humans.
Dawn is- sejbiet jidhru li m’ għandhomx rilevanza għall- użu ta ’ dożi terapewtiċi ta ’ irbesartan/ hydrochlorothiazides fil- bnedmin.
No teratogenic effects were seen in rats given irbesartan and hydrochlorothiazide in combination at doses that produced maternal toxicity.
Ma deherx li kien hemm effetti teratoġeniċi f’ firien li ngħataw irbesartan u hydrochlorothiazide flimkien b’ dożi li jipproduċu tossiċità materna.
The effects of the irbesartan/ hydrochlorothiazide combination on fertility have not been evaluated in animal studies, as there is no evidence of adverse effect on fertility in animals or humans with either irbesartan or hydrochlorothiazide when administered alone.
L- effetti tal- kombinazzjoni ta ’ irbesartan/ hydrocholorhiazide fuq il- fertilitàgħadhom ma ġewx evalwati fi studji fl- annimali, għax m’ hemmx evidenza ta ’ effetti avversi fuq il- fertilità fl- annimali jew fil- bnedmin b’ irbesartan jew b’ hydrochlorothiazide meta jingħataw waħidhom.
However, another angiotensin-II antagonist affected fertility parameters in animal studies when given alone.
Madankollu, antagonist ieħor ta ’ l - angiotensin- II affetwa l- parametri tal- fertilità waqt studji fuq l- annimali meta ngħata waħdu.
These findings were also observed with lower doses of this other angiotensin-II antagonist when given in combination with hydrochlorothiazide.
Dawn is- sejbiet ġew ukoll osservati b’ dożi aktar baxxi ta ’ dan l- antagonista ieħor ta ’ l- angiotensin- II meta ngħata flimkien ma ’ hydrochlorothiazide.
There was no evidence of mutagenicity or clastogenicity with the irbesartan/ hydrochlorothiazide combination.
Ma kienx hemm evidenza ta ’ mutaġeniċità jew klasroġenitiċità bil- kombinazzjoni ta ’ irbesartan/ hydrochlorothiazide.
The carcinogenic potential of irbesartan and hydrochlorothiazide in combination has not been evaluated in animal studies.
Il- potenzjal karċinoġeniku tal- kombinazzjoni ta ’ irbesartan u hydrochlorothiazide għadu ma ġiex evalwat bi studji fuq l- annimali.
Irbesartan: there was no evidence of abnormal systemic or target organ toxicity at clinically relevant doses.
Irbesartan: ma kienx hemm evidenza ta ’ anormalità sistemika jew tossiċità li tattakka l- organu immirat b’ dożi klinikament rilevanti.
In non-clinical safety studies, high doses of irbesartan (≥ 250 mg/ kg/ day in rats and ≥ 100 mg/ kg/ day in macaques) caused a reduction of red blood cell parameters (erythrocytes, haemoglobin, haematocrit).
Fi studji mhux kliniċi ta ’ sigurta`, dożi għoljin ta ’ irbesartan (≥ 250 mg/ kg/ jum f’ firien u ≥ 100 mg/ kg/ jum f’ makakki) ikkawżaw tnaqqis fil- parametri taċ- ċelluli ħomor tad- demm (eritroċiti, emoglobina, ematokrit).
At very high doses (≥ 500 mg/ kg/ day) degenerative changes in the kidneys (such as interstitial nephritis, tubular distention, basophilic tubules, increased plasma concentrations of urea and creatinine) were induced by irbesartan in the rat and the macaque and are considered secondary to the hypotensive effects of the medicinal product which led to decreased renal perfusion.
B’ dożi għoljin ħafna (≥ 500 mg/ kg/ jum) tibdil diġenerattiv fil- kliewi (bħal nefrite interstizjali, nefħa tubulari, tubi bażofiliċi, żidiet fil - konċentrazjonijiet ta ’ l- urea u tal- krejatinina fil- plażma) ġew stimulati b’ irbesartan f’ firien u f’ makakki u huma meqjusa bħala sekondarji għall- effetti ipotensivi tal- mediċina li waslet għal tnaqqis fil- perfużjoni renali.
Furthermore, irbesartan induced hyperplasia/ hypertrophy of the juxtaglomerular cells (in rats at ≥ 90 mg/ kg/ day, in macaques at ≥ 10 mg/ kg/ day).
Iktar minn hekk irbesartan ikkaġuna iperplasja/ ipertrofija taċ- ċelluli jukstaglomerulari (f’ firien b’ ≥ 90 mg/ kg/ jum, f’ makakki b ’ ≥ 10 mg/ kg/ jum).
All of these changes were considered to be caused by the pharmacological action of irbesartan.
Dan it- tibdil kollu kien ikkonsidrat li seħħ bl- azzjoni farmakoloġika ta ’ irbesartan.
For therapeutic doses of irbesartan in humans, the hyperplasia/ hypertrophy of the renal juxtaglomerular cells does not appear to have any relevance.
Għall- dożi terapewtiċi ta ’ irbesartan fil - bnedmin, ma jidhirx li l- iperplażja/ ipertrofija taċ- ċelluli renali jukstaglomerulari għandha xi rilevanza.
There was no evidence of mutagenicity, clastogenicity or carcinogenicity.
Ma kienx hemm evidenza ta ’ mutaġeniċita, klastoġeniċita` jew karċinoġeniċita`.
Animal studies with irbesartan showed transient toxic effects (increased renal pelvic cavitation, hydroureter or subcutaneous oedema) in rat foetuses, which were resolved after birth.
Studji fuq annimali b’ irbesartan urew effetti tossiċi li jgħaddu (żieda fil- formazzjoni tal- ħofor fil- pelvi renali, hydroureter, edema ta ’ taħt il- ġilda) fil- feti tal- firien, li ġew risolvuti wara t- twelid.
In rabbits, abortion or early resorption was noted at doses causing significant maternal toxicity, including mortality.
Fil- fniek, abort jew reassorbiment kmieni ta ’ l- embriju ġie nnotat b’ dożi li kkaġunaw tossiċita` sinifikanti fl - omm, li nkludew mwiet.
No teratogenic effects were observed in the rat or rabbit.
Ma ġewx osservati effetti teratoġeniċi fil- far jew fil- fenek.
12 Hydrochlorothiazide: although equivocal evidence for a genotoxic or carcinogenic effect was found in some experimental models, the extensive human experience with hydrochlorothiazide has failed to show an association between its use and an increase in neoplasms.
Hydrochlorothiazide: għalkemm instabet evidenza ekwivoka għall- effett ġenotossiku u karċinoġeniku f’ xi mudelli esperimentali, l- esperjenza estensiva fil- bniedem b’ hydrochlorothiazide ma rnexxilhiex turi assoċjazzjoni bejn l- użu tagħha u żieda fin- neoplażmi.
Microcrystalline cellulose Croscarmellose sodium Lactose monohydrate Magnesium stearate Colloidal hydrated silica Pregelatinised maize starch Red and yellow ferric oxides (E172)
Microcrystalline cellulose Croscarmellose sodium Lactose monohydrate Magnesium stearate Colloidal hydrated silica Pregelatinised maize starch Ferric oxide aħmar u isfar (E172)
Not applicable.
Ma jgħoddux f’ dan il- każ.
3 years.
snin.
Store in the original package in order to protect from moisture.
Aħżen fil- pakkett oriġinali biex tilqa ’ mill- umdità.
Cartons of 14 tablets; 1 blister card of 14 tablets in PVC/ PVDC/ Aluminium blisters.
Pakketti ta ’ 14- il pillola; strixxa ta ’ 14- il pillola f’ folji al- PVC/ PVDC/ Aluminju.
Cartons of 28 tablets; 2 blister cards of 14 tablets in PVC/ PVDC/ Aluminium blisters.
Pakketti ta ’ 28 pillola; 2 strixxi ta ’ 14- il pillola f’ folji tal- PCV/ PVDC/ Aluminju.
Cartons of 56 tablets; 4 blister cards of 14 tablets in PVC/ PVDC/ Aluminium blisters.
Pakketti ta ’ 56 pillola; 4 strixxi ta ’ 14- il pillola f’ folji tal- PVC/ PVDC/ Aluminju.
Cartons of 98 tablets; 7 blister cards of 14 tablets in PVC/ PVDC/ Aluminium blisters.
Pakketti ta ’ 98 pillola; 7 strixxi ta ’ 14- il pillola f’ folji tal- PVC/ PVDC/ Aluminju.
Cartons of 56 x 1 tablets; 7 blister cards of 8 x 1 tablets each in PVC/ PVDC/ Aluminium perforated unit dose blisters.
Pakketti ta ’ 56 x 1 pillola; 7 strixxi ta ’ 8 x 1 pillola kull waħda f’ folji tal- PVC/ PVDC/ Aluminju perforati ta ’ doża waħda.
Any unused product or waste material should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jiġix użat jew skart li jibqa 'wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
SANOFI PHARMA BRISTOL-MYERS SQUIBB SNC 174 avenue de France F-75013 Paris - France
SANOFI PHARMA BRISTOL- MYERS SQUIBB SNC 174 avenue de France F- 75013 Paris - Franza
MARKETING AUTHORISATION NUMBERS
NUMRU( I) TA 'L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
15 October 1998 Date of last renewal:
15 ta ’ Ottubru 1998 Data ta ’ l- aħħar tiġdid:
1 October 2008
1 ta ’ Ottubru 2008
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /.
CoAprovel 300 mg/ 12.5 mg tablets.
CoAprovel 300 mg/ 12. 5 mg pilloli.
Each tablet contains 300 mg of irbesartan and 12.5 mg of hydrochlorothiazide.
Kull pillola fiha 300 mg ta ’ irbesartan u 12. 5 mg ta ’ hydrochlorothiazide.
Each tablet contains 65.8 mg of lactose (as lactose monohydrate).
Kull pillola miksija b’ rita fiha 65. 8 mg ta ’ lactose (bħala lactose monohydrate).
Peach, biconvex, oval-shaped, with a heart debossed on one side and the number 2776 engraved on the other side.
Lewn il- ħawħa, ibbuzzata fuq iż- żewġ naħat, ovali, b’ qalb ibbuzzata fuq naħa waħda u numru 2776 mnaqqax fuq in- naħa l- oħra.
15 Elderly patients: no dosage adjustment of CoAprovel is necessary in elderly patients.
15 Pazjenti anzjani: m’ hemmx bżonn aġġustar fid- doża ta ’ CoAprovel f’ pazjenti anzjani.
Increases in cholesterol and triglyceride levels have been associated with thiazide diuretic therapy; however at the 12.5 mg dose contained in CoAprovel, minimal or no effects were reported.
16 Żidiet fil- livelli tal- kolesterol u tat- trigliċeridi ġew assoċjati mat- terapija dijuretika thiazide; madankollu b’ doża ta ’ 12. 5 mg ta ’ CoAprovel, l- effetti li ġew irrapportati kienu minimi jew xejn.
16 Hyperuricaemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
Tista ’ sseħħ iperuriċemija jew tiħrax gotta ċara f’ xi pazjenti li jirċievu it- terapija thiazide.
17 Lactose: this medicinal product contains lactose.
17 Lactose: dan il- prodott mediċinali fih il- lactose.
Additional information on hydrochlorothiazide interactions: when administered concurrently, the following medicinal products may interact with thiazide diuretics:
18 Tagħrif addizzjonali dwar l- effetti ta ’ hydrochlorothiazide ma ’ mediċini oħra: meta jingħataw flimkien, il- prodotti mediċinali segwenti jistgħu jinteraġixxu ma ’ dijuretiċi thiazide:
18 Alcohol: potentiation of orthostatic hypotension may occur;
Alkoħol: jista ’ jkun hemm żieda fil- pressjoni baxxa ortostatika;
(see section 5.3).
19 Espożizzjoni għal terapija AIIRAs matul it- tieni u t- tielet trimestri hija magħrufa li twassal għal tossiċità tal- fetu uman (tnaqqis fil- funzjoni tal- kliewi, oligohydramnios, tnaqqis fl- ossifikazzjoni tal - għadam tar- ras) u tossiċità neonatali (nuqqas fil- funzjoni tal- kliewi, pressjoni baxxa, iperkalemija) (ara sezzjoni 5. 3).
19 Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Jekk seħħet espożizzjoni għall- AIIRAs mit- tieni trimestru tat- tqala, huwa rrakkomandat kontroll bl - ultrasound tal- funzjoni renali u tal- kranju.
21 The dose dependent adverse events of hydrochlorothiazide (particularly electrolyte disturbances) may increase when titrating the hydrochlorothiazide.
L- episodji avversi dipendenti fuq id- doża ta 'hydrochlorothiazide (b' mod partikolari disturbi elettrolitiċi) jistgħu jiżdiedu meta jkun qed jiġi ttitrat il- hydrochlorothiazide.
CoAprovel is a combination of an angiotensin-II receptor antagonist, irbesartan, and a thiazide diuretic, hydrochlorothiazide.
22 CoAprovel huwa kombinazzjoni ta ’ antagonist ta ’ riċettur angiotensin- II, irbesartan u dijuretiku thiazide, hydrochlorothiazide.
22 The combination of hydrochlorothiazide and irbesartan produces dose-related additive reductions in blood pressure across their therapeutic dose ranges.
Il- kombinazzjoni ta ’ hydrochlorothiazide u irbesartan tipproduċi tnaqqis addittiv relatat mad- doża fil - pressjoni tad- demm tul il- firxa terapewtika tad- doża.
The blood pressure lowering effect of irbesartan in combination with hydrochlorothiazide is apparent after the first dose and substantially present within 1-2 weeks, with the maximal effect occurring by 6-8 weeks.
23 L- effett li għandu irbesartan f’ kombinazzjoni ma ’ hydrochlorothiazide fit- tnaqqis tal- pressjoni jitfaċċa wara l- ewwel doża u jibqa ’ preżenti sostanzjalment f’ 1- 2 ġimgħat, bl- effett massimu jseħħ fi żmien 6 - 8 ġimgħat.
23 the combination achieved trough SeDBP < 90 mmHg compared to 33.2% of patients on irbesartan (p = 0.0005).
Erbgħa u sebgħin fil- mija (47. 2%) tal - pazjenti fuq il- kombinazzjoni laħqu livell minimu ta ’ SeDBP < 90 mmHg meta mqabbel ma ’ 33. 2% tal- pazjenti fuq irbesartan (p = 0. 0005).
Hydrochlorothiazide is 68% protein-bound in the plasma, and its apparent volume of distribution is 0.83-1.14 l/ kg.
24 Hydrochlrothiazide jeħel mal- proteini tal- plażma bi 68%, u l- volum ta ’ distibuzzjoni apparenti huwa 0. 83 - 1. 14 l/ kg.
24 Hepatic impairment: in patients with mild to moderate cirrhosis, the pharmacokinetic parameters of irbesartan are not significantly altered.
Indeboliment epatiku: f’ pazjenti b’ ċirrożi, minn ħafifa għal moderata, il- parametri farmakokinetiċi ta ’ irbesartan ma jitbiddlux b’ mod sinifikanti.
Most of the above mentioned effects appear to be due to the pharmacological activity of irbesartan (blockade of angiotensin-II-induced inhibition of renin release, with stimulation of the renin-producing cells) and occur also with angiotensin converting enzyme inhibitors.
25 Il- parti l- kbira mill- effetti msemmija hawn fuq jidhru li ġraw minħabba l- attivita` farmakoloġika ta ’ irbesartan (imblokk ta ’ l- inibizzjoni stimulata minn angiotensin II tal- ħelsien ta ’ renin, b’ stimulazzjoni ta ’ ċelluli li jipproduċu renin) u jseħħu wkoll b’ impedituri ta ’ enzimi li jikkonvertu angiotensin.
25 Hydrochlorothiazide: although equivocal evidence for a genotoxic or carcinogenic effect was found in some experimental models, the extensive human experience with hydrochlorothiazide has failed to show an association between its use and an increase in neoplasms.
Hydrochlorothiazide: għalkemm instabet evidenza ekwivoka għall- effett ġenotossiku u karċinoġeniku f’ xi mudelli esperimentali, l- esperjenza estensiva fil- bniedem b’ hydrochlorothiazide ma rnexxilhiex turi assoċjazzjoni bejn l- użu tagħha u żieda fin- neoplażmi.
6.3 Shelf life
26 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
CoAprovel 150 mg/ 12.5 mg film-coated tablets.
CoAprovel 150 mg/ 12. 5 mg pilloli miksijin b' rita.
Each film-coated tablet contains 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide.
Kull pillola miksija b' rita fiha 150 mg ta ’ irbesartan u 12. 5 mg ta ’ hydrochlorothiazide.
Each film-coated tablet contains 38.5 mg of lactose (as lactose monohydrate).
Kull pillola miksija b’ rita fiha 38. 5 mg ta ’ lactose (bħala lactose monohydrate).
Film-coated tablet.
Pillola miksija b' rita.
Peach, biconvex, oval-shaped, with a heart debossed on one side and the number 2875 engraved on the other side.
Lewn il- ħawħa, ibbuzzata fuq iż- żewġ naħat, ovali, b’ qalb ibbuzzata fuq naħa waħda u numru 2875 mnaqqax fuq in- naħa l- oħra.
Hepatic impairment:
28 Indeboliment epatiku:
28 Elderly patients: no dosage adjustment of CoAprovel is necessary in elderly patients.
Pazjenti anzjani: m’ hemmx bżonn aġġustar fid- doża ta ’ CoAprovel f’ pazjenti anzjani.
Metabolic and endocrine effects: thiazide therapy may impair glucose tolerance.
29 Effetti metaboliċi u endokrinali: it- terapija bit- thiazide tista ’ tfixkel it- tolleranza tal- glucose.
Increases in cholesterol and triglyceride levels have been associated with thiazide diuretic therapy; however at the 12.5 mg dose contained in CoAprovel, minimal or no effects were reported.
Żidiet fil- livelli tal- kolesterol u tat- trigliċeridi ġew assoċjati mat- terapija dijuretika thiazide; madankollu b’ doża ta ’ 12. 5 mg ta ’ CoAprovel, l- effetti li ġew irrapportati kienu minimi jew xejn.
29 Hyperuricaemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
Tista ’ sseħħ iperuriċemija jew tiħrax gotta ċara f’ xi pazjenti li jirċievu it- terapija thiazide.
When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).
Meta tiġi ddijanjostikata tqala, trattament b’ AIIRAs
30 Lactose: this medicinal product contains lactose.
Lactose: dan il- prodott mediċinali fih il- lactose.
The effects of CYP2C9 inducers such as rifampicin on the pharmacokinetic of irbesartan have not been evaluated.
L- effetti ta ’ indutturi ta ’ CYP2C9 bħal rifampicin fuq il -
Additional information on hydrochlorothiazide interactions: when administered concurrently, the following medicinal products may interact with thiazide diuretics:
Tagħrif addizzjonali dwar l- effetti ta ’ hydrochlorothiazide ma ’ mediċini oħra: meta jingħataw flimkien, il- prodotti mediċinali segwenti jistgħu jinteraġixxu ma ’ dijuretiċi thiazide:
31 Alcohol: potentiation of orthostatic hypotension may occur;
Alkoħol: jista ’ jkun hemm żieda fil- pressjoni baxxa ortostatika;
Unless continued AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy.
32 għandhom jinqalbu għal trattamenti alternattivi ta ’ kontra l- pressjoni għolja li għandhom profil ta ’ sigurtà stabbilit għal użu waqt tqala.
(see section 5.3).
Espożizzjoni għal terapija AIIRAs matul it- tieni u t- tielet trimestri hija magħrufa li twassal għal tossiċità tal- fetu uman (tnaqqis fil- funzjoni tal- kliewi, oligohydramnios, tnaqqis fl- ossifikazzjoni tal - għadam tar- ras) u tossiċità neonatali (nuqqas fil- funzjoni tal- kliewi, pressjoni baxxa, iperkalemija) (ara sezzjoni 5. 3).
32 Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Jekk seħħet espożizzjoni għall- AIIRAs mit- tieni trimestru tat- tqala, huwa rrakkomandat kontroll bl - ultrasound tal- funzjoni renali u tal- kranju.
Cardiac disorders:
Mhux komuni:
Common:
sturdament ortostatiku
Not known:
uġigħ ta ’ ras
syncope, hypotension, tachycardia, oedema dizziness orthostatic dizziness headache
Disturbi fil- widnejn u fis- sistema labirintika:
Ear and labyrinth disorders:
Mhux magħrufa:
Respiratory, thoracic and mediastinal disorders:
Disturbi respiratorji, toraċiċi u
Not known:
sogħla
tinnitus cough
medjastinali:
nausea/ vomiting diarrhoea dyspepsia, dysgeusia
Disturbi fil- kliewi u fis- sistema
Renal and urinary disorders:
tneħħi l- awrina b’ mod anormali
Common:
urinarja:
abnormal urination impaired renal function including isolated cases of renal failure in patients at risk (see section 4.4)
funzjoni renali indebolita inkluż każijiet iżolati ta ’ kollass renali f’ pazjenti f’ riskju (ara sezzjoni 4. 4)
Musculoskeletal and connective tissue disorders:
Disturbi muskolu- skeltrali u tal - connective tissue:
Not known:
artralġija, mijalġija
swelling extremity arthralgia, myalgia hyperkalaemia
Disturbi fil- metaboliżmu u n - nutrizzjoni:
Vascular disorders:
Mhux magħruf:
Uncommon:
iperkalemja
flushing
Mhux komuni:
33
fwawar
fatigue
għeja kbira
Not known:
magħrufa:
hepatitis, abnormal liver function sexual dysfunction, libido changes
eċċessiva bħal anġjoedema, raxx, urtikarja epatite, funzjoni anormali tal- fwied
Adverse reactions (regardless of relationship to medicinal product) reported with the use of hydrochlorothiazide alone Investigations:
Reazzjonijiet avversi (minkejja r- relazzjoni mal- prodott mediċinali) rapportati ma ’ l- użu ta ’ hydrochlorothiazide waħdu Mhux magħrufa: żbilanċ fl- elettroliti (li tinkludi l- ipokalemija u l - Investigazzjonijiet: iponatremja, ara sezzjoni 4. 4), iperuriċemija glikożurja, ipergliċemija, żieda fil- kolesterol u trigliċeridi Mhux magħrufa: arritmji kardijaċi Disturbi fil- qalb:
electrolyte imbalance (including hypokalaemia and hyponatraemia, see section 4.4), hyperuricaemia, glycosuria, hyperglycaemia, increases in cholesterol and triglycerides
Disturbi tad- demm u tas - Mhux magħrufa: anemija aplastika, dipressjoni tal- mudullun ta ’ l - għadam, newtropenja/ agranuloċitożi, anemija sistema limfatika: emolitika, lewkopenja, tromboċitopenja Mhux magħrufa:
Cardiac disorders:
Vertigo, parasteżija, sturdament, irrekwitezza Disturbi fis- sistema nervuża:
Blood and lymphatic system disorders:
Mhux magħrufa: vista mċajpra li tgħaddi, xanthopsia Disturbi fl- għajnejn:
Not known:
34 Disturbi gastro - intestinali:
cardiac arrhythmias aplastic anaemia, bone marrow depression, neutropenia/ agranulocytosis, haemolytic anaemia, leucopenia, thrombocytopenia
pankrejatite, anoressja, dijarea, stitikezza, irritazzjoni fl- istonku, sijaladenite, nuqqas ta ’ aptit
Nervous system disorders:
Disturbi fil- kliewi u fis - sistema urinarja:
vertigo, paraesthesia, light-headedness, restlessness
nefrite interstizjali, disfunzjoni renali
Respiratory, thoracic and mediastinal disorders:
Disturbi fil- ġilda u fit - tessuti ta ’ taħt il- ġilda:
transient blurred vision, xanthopsia respiratory distress (including pneumonitis and pulmonary oedema)
reazzjonijiet anafilattiċi, nekroliżi epidermali tossika, anġite nekrotizzanti (vaskulite, vaskulite kutanja), reazzjonijiet tal- ġilda bħal lupus eritematożi, riattivazzjoni tal- lupus eritematożi kutanja, reazzjonijiet fotosensittivi, raxx, urtikarja
Gastrointestinal disorders:
Disturbi muskolu - skeltrali u tal- connective tissue:
pancreatitis, anorexia, diarrhoea, constipation, gastric irritation, sialadenitis, loss of appetite
għeja, spażmu tal- muskoli
Renal and urinary disorders:
Disturbi vaskulari:
interstitial nephritis, renal dysfunction anaphylactic reactions, toxic epidermal necrolysis, necrotizing angitis (vasculitis, cutaneous vasculitis), cutaneous lupus erythematosus-like reactions, reactivation of cutaneous lupus erythematosus, photosensitivity reactions, rash, urticaria
pressjoni baxxa tal- qagħda
Musculoskeletal and connective tissue disorders:
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata:
weakness, muscle spasm
deni
Vascular disorders:
Disturbi fil- fwied u fil - marrara:
postural hypotension fever
suffejra (suffejra intraepatika kolestatika)
jaundice (intrahepatic cholestatic jaundice) depression, sleep disturbances
dipressjoni, disturbi fl- irqad
The dose dependent adverse events of hydrochlorothiazide (particularly electrolyte disturbances) may increase when titrating the hydrochlorothiazide.
L- episodji avversi dipendenti fuq id- doża ta 'hydrochlorothiazide (b' mod partikolari disturbi elettrolitiċi) jistgħu jiżdiedu meta jkun qed jiġi ttitrat il- hydrochlorothiazide.
34 4.9 Overdose
4. 9 Doża eċċessiva
CoAprovel is a combination of an angiotensin-II receptor antagonist, irbesartan, and a thiazide diuretic, hydrochlorothiazide.
CoAprovel huwa kombinazzjoni ta ’ antagonist ta ’ riċettur angiotensin- II, irbesartan u dijuretiku thiazide, hydrochlorothiazide.
It is expected to block all actions of angiotensin-II mediated by the AT1 receptor, regardless of the source or route of synthesis of angiotensin-II.
Huwa mistenni li jimblokka l- azzjonijiet kollha ta ’ l- angiotensin- II medjati mir- riċettur AT1,
The combination of hydrochlorothiazide and irbesartan produces dose-related additive reductions in blood pressure across their therapeutic dose ranges.
Il- kombinazzjoni ta ’ hydrochlorothiazide u irbesartan tipproduċi tnaqqis addittiv relatat mad- doża fil - pressjoni tad- demm tul il- firxa terapewtika tad- doża.
The addition of 12.5 mg hydrochlorothiazide to 300 mg irbesartan once daily in patients not adequately controlled on 300 mg irbesartan alone resulted in further placebo-corrected diastolic blood pressure reductions at trough (24 hours post-dosing) of
Iż- żieda ta ’ 12. 5 mg hydrochlorothiazide ma ’ 300 mg ta ’ irbesartan darba waħda kuljum f’ pazjenti li ma kinux ikkontrollati sew meta ħadu 300 mg irbesartan waħdu irriżulta f’ aktar tnaqqis fil- pressjoni dijastolika korreta bil- plaċebo fl- inqas livelli (24 siegħa wara li tingħata d- doża) ta ’ 6. 1 mmHg.
The blood pressure lowering effect of irbesartan in combination with hydrochlorothiazide is apparent after the first dose and substantially present within 1-2 weeks, with the maximal effect occurring by 6-8 weeks.
L- effett li għandu irbesartan f’ kombinazzjoni ma ’ hydrochlorothiazide fit- tnaqqis tal- pressjoni jitfaċċa wara l- ewwel doża u jibqa ’ preżenti sostanzjalment f’ 1- 2 ġimgħat, bl- effett massimu jseħħ fi żmien 6 - 8 ġimgħat.
The effect of the combination of irbesartan and hydrochlorothiazide on morbidity and mortality has not been studied.
36 Ma ġiex studjat l- effett tal- kombinazzjoni ta ’ irbesartan u hydrochlorothiazide fuq il- morbidità u l - imwiet.
A total of 697 patients were randomized in a 2:1 ratio to either irbesartan/ hydrochlorothiazide 150 mg/ 12.5 mg or to irbesartan 150 mg and systematically force- titrated (before assessing the response to the lower dose) after one week to irbesartan/ hydrochlorothiazide 300 mg/ 25 mg or irbesartan 300 mg, respectively.
B’ kollox, 697 pazjent intagħżlu b’ mod każwali fi proporzjon ta ’ 2: 1 jew għal irbesartan/ hydrochlorothiazide 150 mg/ 12. 5 mg jew għal irbesartan 150 mg u ġew titrati bil- forza b’ mod sistematiku (qabel ma r- rispons tagħhom għal doża iktar baxxa ġie vvalutat) wara ġimgħa għal irbesartan/ hydrochlorothiazide 300 mg/ 25 mg jew irbesartan 300 mg, rispettivament.
The primary objective of this study was to compare the proportion of patients whose SeDBP was controlled (SeDBP < 90 mmHg) at Week 5 of treatment.
L- għan ewlieni ta ’ dan l- istudju kien li jqabbel il- proporzjon ta ’ pazjenti li l- SeDBP tagħhom kien ikkontrollat (SeDBP < 90 mmHg) f’ Ġimgħa 5 tat- trattament.
Forty-seven percent (47.2%) of patients on the combination achieved trough SeDBP < 90 mmHg compared to 33.2% of patients on irbesartan (p = 0.0005).
Sebgħa u ergħin fil- mija (47. 2%) tal - pazjenti fuq il- kombinazzjoni laħqu livell minimu ta ’ SeDBP < 90 mmHg meta mqabbel ma ’ 33. 2% tal- pazjenti fuq irbesartan (p = 0. 0005).
36 The types and incidences of adverse events reported for patients treated with the combination were similar to the adverse event profile for patients on monotherapy.
It- tipi u l- inċidenzi ta ’ episodji avversi rrapportati għal pazjenti ttrattati bil- kombinazzjoni kienu simili għall- profil ta ’ l- episodju avvers għal pazjenti fuq monoterapija.
Hydrochlorothiazide is 68% protein-bound in the plasma, and its apparent volume of distribution is 0.83-1.14 l/ kg.
Hydrochlrothiazide jeħel mal- proteini tal- plażma bi 68%, u l- volum ta ’ distibuzzjoni apparenti huwa 0. 83 - 1. 14 l/ kg.
The terminal elimination half-life of irbesartan is 11-15 hours.
Il- half- life ta ’ l- eliminazzjoni terminali ta ’ irbesartan hija
Hepatic impairment: in patients with mild to moderate cirrhosis, the pharmacokinetic parameters of irbesartan are not significantly altered.
Indeboliment epatiku: f’ pazjenti b’ ċirrożi, minn ħafifa għal moderata, il- parametri farmakokinetiċi ta ’ irbesartan ma jitbiddlux b’ mod sinifikanti.
37 5.3 Preclinical safety data
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Most of the above mentioned effects appear to be due to the pharmacological activity of irbesartan (blockade of angiotensin-II-induced inhibition of renin release, with stimulation of the renin-producing cells) and occur also with angiotensin converting enzyme inhibitors.
Il- parti l- kbira mill- effetti msemmija hawn fuq jidhru li ġraw minħabba l- attivita` farmakoloġika ta ’ irbesartan (imblokk ta ’ l- inibizzjoni stimulata minn angiotensin II tal- ħelsien ta ’ renin, b’ stimulazzjoni ta ’ ċelluli li jipproduċu renin) u jseħħu wkoll b’ impedituri ta ’ enzimi li jikkonvertu angiotensin.
No teratogenic effects were seen in rats given irbesartan and hydrochlorothiazide in combination at doses that produced maternal toxicity.
38 Ma deherx li kien hemm effetti teratoġeniċi f’ firien li ngħataw irbesartan u hydrochlorothiazide flimkien b’ dożi li jipproduċu tossiċità materna.
Hydrochlorothiazide: although equivocal evidence for a genotoxic or carcinogenic effect was found in some experimental models, the extensive human experience with hydrochlorothiazide has failed to show an association between its use and an increase in neoplasms.
Hydrochlorothiazide: għalkemm instabet evidenza ekwivoka għall- effett ġenotossiku u karċinoġeniku f’ xi mudelli esperimentali, l- esperjenza estensiva fil- bniedem b’ hydrochlorothiazide ma rnexxilhiex turi assoċjazzjoni bejn l- użu tagħha u żieda fin- neoplażmi.
Lactose monohydrate Microcrystalline cellulose Croscarmellose sodium Hypromellose Silicon dioxide Magnesium stearate
Lactose monohydrate Microcrystalline cellulose Croscarmellose sodium Hypromellose Silicon dioxide Magnesium stearate
Film-coating:
Kisja b' rita:
Lactose monohydrate Hypromellose Titanium dioxide Macrogol 3000 Red and yellow ferric oxides Carnauba wax
Lactose monohydrate Hypromellose Titanium dioxide Macrogol 3000 Ferric oxides ħomor u sofor Carnauba wax
6.2 Incompatibilities
39 6. 2 Inkompatibilitajiet
Cartons of 28 film-coated tablets; 2 blister cards of 14 film-coated tablets in PVC/ PVDC/ Aluminium blisters.
Pakketti ta ’ 14- il pillola miksija b' rita; strixxa ta ’ 14- il pillola miksija b' rita f’ folji tal - PVC/ PVDC/ Aluminju Pakketti ta ’ 28 pillola miksija b' rita; 2 strixxi ta ’ 14- il pillola miksija b' rita f’ folji tal - PCV/ PVDC/ Aluminju.
Cartons of 30 film-coated tablets; 2 blister cards of 15 film-coated tablets in PVC/ PVDC/ Aluminium blisters.
Pakketti ta ’ 30 pillola miksija b' rita; 2 strixxiet ta ’ 15- il pillola miksija b' rita f’ folji tal - PCV/ PVDC/ Aluminju.
Cartons of 56 film-coated tablets; 4 blister cards of 14 film-coated tablets in PVC/ PVDC/ Aluminium blisters.
Pakketti ta ’ 56 pillola miksija b' rita; 4 strixxi ta ’ 14- il pillola miksija b' rita f’ folji tal - PVC/ PVDC/ Aluminju.
Cartons of 84 film-coated tablets; 6 blister cards of 14 film-coated tablets in PVC/ PVDC/ Aluminium blisters.
Pakketti ta ’ 84 pillola miksija b' rita; 6 strixxi ta ’ 14- il pillola miksija b' rita f’ folji tal - PVC/ PVDC/ Aluminju.
Cartons of 90 film-coated tablets; 6 blister cards of 15 film-coated tablets in PVC/ PVDC/ Aluminium blisters.
Pakketti ta ’ 90 pillola miksija b' rita; 6 strixxiet ta ’ 15- il pillola miksija b' rita f’ folji tal - PCV/ PVDC/ Aluminju.
Cartons of 98 film-coated tablets; 7 blister cards of 14 film-coated tablets in PVC/ PVDC/ Aluminium blisters.
Pakketti ta ’ 98 pillola miksija b' rita; 7 strixxi ta ’ 14- il pillola miksija b' rita f’ folji tal - PVC/ PVDC/ Aluminju.
Cartons of 56 x 1 film-coated tablets; 7 blister cards of 8 x 1 film-coated tablets each in PVC/ PVDC/ Aluminium perforated unit dose blisters.
Pakketti ta ’ 56 x 1 pillola miksija b' rita; 7 strixxi ta '8 x 1 pillola miksija b' rita kull waħda f’ folji tal - PVC/ PVDC/ Aluminju perforati ta' doża waħda.
CoAprovel 300 mg/ 12.5 mg film-coated tablets.
CoAprovel 300 mg/ 12. 5 mg pilloli miksijin b' rita.
Each film-coated tablet contains 300 mg of irbesartan and 12.5 mg of hydrochlorothiazide.
Kull pillola miksija b' rita fiha 300 mg ta ’ irbesartan u 12. 5 mg ta ’ hydrochlorothiazide.
Each film-coated tablet contains 89.5 mg of lactose (as lactose monohydrate).
Kull pillola miksija b’ rita fiha 89. 5 mg ta ’ lactose (bħala lactose monohydrate).
Peach, biconvex, oval-shaped, with a heart debossed on one side and the number 2876 engraved on the other side.
Lewn il- ħawħa, ibbuzzata fuq iż- żewġ naħat, ovali, b’ qalb ibbuzzata fuq naħa waħda u numru 2876 mnaqqax fuq in- naħa l- oħra.
Hepatic impairment:
42 Indeboliment epatiku:
41 Elderly patients: no dosage adjustment of CoAprovel is necessary in elderly patients.
Pazjenti anzjani: m’ hemmx bżonn aġġustar fid- doża ta ’ CoAprovel f’ pazjenti anzjani.
Metabolic and endocrine effects: thiazide therapy may impair glucose tolerance.
43 Effetti metaboliċi u endokrinali: it- terapija bit- thiazide tista ’ tfixkel it- tolleranza tal- glucose.
42 Hyperuricaemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
Tista ’ sseħħ iperuriċemija jew tiħrax gotta ċara f’ xi pazjenti li jirċievu it- terapija thiazide.
43 Lactose: this medicinal product contains lactose.
Lactose: dan il- prodott mediċinali fih il- lactose.
44 Alcohol: potentiation of orthostatic hypotension may occur;
Alkoħol: jista ’ jkun hemm żieda fil- pressjoni baxxa ortostatika;