qanastek/EMEA-V3 huggingface dataset:
This is supported by two similar fed studies using the same reference drug and the same test drug with the same batch number when entirely different results are obtained and which confidence intervals were within conventionally acceptable limits.
Dan huwa imwieżen minn żewġ studji bl- ikel simili, bl- użu ta ’ l- istess mediċina ta ’ referenza u l- istess mediċina tat- test bl- istess numru tal- lott meta riżultati kompletament differenti huma miksuba u liema intervalli ta ’ kunfidenza kienu fi ħdan limiti konvenzjonalment aċċettabbli.
The results of these fed studies demonstrate that Lansoprazole’ s bioavailability is not only markedly reduced when taken with food, but that its absorption, in the presence of food, can be very erratic.
Ir- riżultati ta ’ l- istudji bl- ikel juru li l- bijodisponibbiltà tal- Lansoprazole mhix biss imnaqqsa b’ mod sinjifikanti meta jittieħed ma ’ l- ikel, iżda li l- assorbiment tiegħu, fil- preżenza ta ’ l- ikel, jista ’ jkun erratiku ħafna.
This is a known pharmacokinetic characteristic of Lansoprazole, particularly when taken with high fat and calorie meal as in the current case.
Din hija karatteristika farmakokinetika magħrufa tal- Lansoprazole, partikolarment meta jittieħed ma ’ ikla b’ xaħam u kaloriji għoljin kif inhu fil- każ kurrenti.
Lansoprazole has a wide therapeutic window regarding its clinical efficacy and safety.
Lansoprazole għandu tieqa terapewtika wiesa ’ fir- rigward ta ’ l- effikaċja klinika u s- sigurtà klinika tiegħu.
It also has a flat dose/ response curve i. e. its efficacy is largely independent of the dose.
Huwa għandu ukoll kurva doża/ reazzjoni ċatta i. e. l- effikaċja tiegħu hija fil- parti l- kbira indipendenti mid- doża.
This means that the small difference in blood levels between the reference and test products shown under fed conditions is of no clinical significance.
Dan ifisser li d- differenza żgħira fil- livelli tad- demm bejn il- prodotti ta ’ referenza u tat- test murija taħt kondizzjonijiet mitmugħa ma hija ta ’ l- ebda sinjifikat kliniku.
In conclusion, the questions have been addressed satisfactorily by the applicant.
Bħala konkluzjoni, il- mistoqsijiet ġew indirizzati b’ mod sodisfaċjenti mill- applikant.
The Applicant has provided sufficient data to support that the outcome of the fed study does not lead to a potential risk to public health.
L- Applikant ipprovda tagħrif suffiċjenti biex jappoġġja li r- riżultat ta ’ l- istudju bl- ikel ma jwassalx għal riskju potenzjali għas- saħħa pubblika.
The CHMP has recommended the granting of the Marketing Authorisation(s).
6 Is- CHMP irrakkomanda l- għoti ta ’ l- Awtorizzazzjoni( jiet) għat- Tqegħid fis- Suq.
The valid Summary of Product Characteristics, labelling and package leaflet are the final versions achieved during the Coordination group procedure as mentioned in Annex III.
Is- Sommarju tal - Karatteristiċi tal- Prodott, it- Tikketta u l- Fuljett ta ’ tagħrif validi huma l- verżjonijiet miksuba waqt il - proċedura ta ’ Koordinazzjoni tal- grupp kif imsemmija f’ Anness III.
SUMMARY OF PRODUCT CHARACHTERITICS, LABELLING AND PACKAGE LEAFLET
KARATTERISTIĊI TAL- PRODOTT FIL- QOSOR, TIKKETTA U L- FULJETT TA ’ TAGĦRIF FIL- PAKKETT
8 The valid Summary of Product Characteristics, labelling and package leaflet are the final versions achieved during the Coordination group procedure.
8 Is- Sommarju tal- Karatteristiċi tal- Prodott, l- ittikkettar u l- fuljett ta ’ tagħrif validi huma l- verżjonijiet finali miksuba waqt il- proċedura tal- Grupp tal- Koordinazzjoni.
LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTH OF THE MEDICINAL PRODUCT, ROUTE OF ADMINISTRATION, APPLICANTS / MARKETING AUTHORISATION HOLDERS IN THE MEMBER STATES
LISTA TAL- ISMIJIET, L- GĦAMLIET FARMAĊEWTIĊI, IL- QAWWIET TAL- PRODOTT MEDIĊINALI, MNEJN JINGĦATA, APPLIKANTI / DETENTURI TAL - AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ FL- ISTATI MEMBRI
Marketing Authorisation Holder
Id- Detentur tal- Awtorizzazzjoni għat- Tqegħid fis- Suq
tablets
pilloli
oral use
Użu orali
Hungary.
L- Ungerija.
oral use
pilloli
1 Name approval pending
1 L- approvazzjoni tal- isem għadha pendenti
Lisonorm 10mg/ 5mg
Ir- Repubblika Slovakka
3 ANNEX II
3 ANNESS II
SCIENTIFIC CONCLUSIONS AND GROUNDS PRESENTED BY THE EMEA
KONKLUŻJONIJIET XJENTIFIĊI U RAĠUNIJIET IPPREŻENTATI MILL- EMEA
4 SCIENTIFIC CONCLUSIONS
4 KONKLUŻJONIJIET XJENTIFIĊI
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF LISONORM AND ASSOCIATED NAMES (SEE ANNEX I)
SOMMARJU ĠENERALI TAL- EVALWAZZJONI XJENTIFIKA TA 'LISONORM U ISMIJIET ASSOĊJATI (ARA ANNESS I)
Lisonorm is a new fixed-dose combination containing 10mg lisinopril (an ACE inhibitor) and 5mg amlodipine (a calcium antagonist), indicated for patients with blood pressure adequately controlled with lisinopril and amlodipine given concurrently at the same dose level.
Lisonorm huwa kombinazzjoni ġdida ta 'doża fissa li fih 10mg lisinopril (inibitur ta' ACE) u 5mg amlodipina (amlodipine, antagonista tal- kalċju), indikat għal pazjenti bi pressjoni tad- demm ikkontrollata b' mod adegwat b' lisinopril u amlodipina mogħtijin fl- istess ħin fl- istess dożaġġ.
The applicant, Gideon Richter, sought a Marketing Authorisation in several member states (CZ, EE, LT, LV, PL, RO, and SK,) through the Mutual Recognition Procedure with Hungary acting as the reference member state.
L - applikant, Gideon Richter, ippreżenta applikazzjoni għal Awtorizzazzjoni għat- Tqegħid fis- Suq f' bosta Stati Membri (CZ, EE, LT, LV, PL, RO, u SK,) permezz tal- Proċedura ta 'Rikonoxximent Reċiproku bl- Ungerija taġixxi bħala l- Istat Membru ta' referenza.
An Article 29 referral procedure was initiated due to concerns raised by the CZ and LV on the potential serious risk to public health regarding insufficient proof of bioequivalence since the Applicant did not use the originator´s products (Aulin Gel) as reference treatments but used monocomponent-containing generics in the originally submitted bioequivalence study.
Minħabba tħassib imqajjem minn CZ u LV fir - rigward tar- riskji gravi potenzjali għas- saħħa pubblika relatati ma 'prova insuffiċjenti ta' bijoekwivalenza minħabba li l- Applikant, fl- istudju ta 'bijoekwivalenza sottomessi oriġinarjament, ma użax il- prodotti tal- oriġinatur (Aulin Gel) bħala trattament ta' referenza iżda uża mediċini ġeneriċi li fihom monokomponenti, inbdiet proċedura ta 'referenza skont l- Artikolu 29.
In line with the regulatory requirements (CHMP/ EWP/ 191583/ 2005), a formal proof of bioequivalence, evidence of a wide therapeutic experience, and an adequately established benefit/ risk ratio should be demonstrated for new fixed dose combination products claiming substitution indication.
Għall- prodotti ġodda ta 'kombinazzjoni ta' doża fissa li juru l- indikazzjoni bħala terapija sostituttiva, ir- rekwiżiti regolatorji (CHMP/ EWP/ 191583/ 2005) jipprevedu li l- bijoekwivalenza tkun formalment ppruvata, li jiġu ppreżentati provi ta 'esperjenza terapewtika mifruxa u murija l- eżistenza ta' relazzjoni ta 'riskju/ benefiċċju stabbilita adegwatament.
For Lisonorm (new lisinopril 10mg/ amlodipine 5mg combination), a positive benefit/ risk ratio had not been established given that the initial bioequivalence study submitted was not conducted with the appropriate control, and that preliminary results of a new bioequivalence study (No.67289) did not allow a full assessment of the benefit risk ratio.
Għal Lisonorm (kombinazzjoni ġdida ta 'lisinopril 10mg / amlodipina 5mg), ma kinitx ġiet stabbilita relazzjoni ta' riskju/ benefiċċju favorevoli meta wieħed jikkunsidra li l- istudju ta 'bijoekwivalenza inizjalment ippreżentat ma sarx b' kontroll xieraq, u r - riżultati preliminari ta' studju ta 'bijoekwivalenza ġdid (Nru 67289) ma ppermettewx valutazzjoni sħiħa tar- relazzjoni riskju/ benefiċċju.
Therefore, the Applicant acknowledged the limitations arising from the product selection in the initial pivotal BE study and performed a study (Protocol No 67289) to investigate bioequivalence of LISONORM FORTE (fixed-combination of amlodipine 10 mg and lisinopril 20 mg), co-administration of NORVASC 10 mg (containing amlodipine 10 mg) and PRINIVIL 20 mg (containing lisinopril 20 mg), and LISONORM (fixed-combination of amlodipine 5 mg and lisinopril 10 mg) under fasting conditions.
Għaldaqstant, l- Applikant għaraf il- limiti li jirriżultaw mill- għażla tal- prodotti fl- istudju BE inizjali ta 'importanza fundamentali u wettaq studju (Protokoll Nru 67289) sabiex jeżamina l- bijoekwivalenza ta' LISONORM FORTE (kombinazzjoni fissa ta 'amlodipina 10 mg u lisinopril 20 mg), amministrazzjoni fl- istess ħin ta' NORVASC 10 mg (li fih amlodipina 10 mg) u PRINIVIL 20 mg (li fih lisinopril 20 mg), u LISONORM (kombinazzjoni fissa ta 'amlodipina 5 mg u lisinopril 10 mg) taħt kundizzjonijiet ta' sawm.
Pharmacokinetic parameters were calculated for amlodipine and lisinopril by the means of Bioequiv 3.5 software using a model independent approach.
Il- parametri farmakokinetiċi ġew ikkalkolati għal amlodipina u lisinopril permezz ta 'softwer Bioequiv 3. 5 li juża approċċ mudell- indipendenti.
The Applicant provided these pharmacokinetic results for amlodipine and lisinopril along with semi-logarithmic mean plasma concentration-time curves.
L- Applikant ipprovda dawn ir- riżultati dwar il - farmakokinetika ta 'amlodipina u lisinopril flimkien ma' kurvi semilogaritmiċi tal- konċentrazzjoni tal - plażma/ ħin medja.
The geometric mean ratios, 90% confidence intervals and corresponding intra-individual CVs for Cmax, AUC0-t and AUC0-∞ for amlodipine and lisinopril were also presented.
Ġew ippreżentati wkoll il- proporzjonijiet medji ġeometriċi, l- intervalli ta 'kunfidenza ta' 90% u CVs intraindividwi korrispondenti għal Cmax, AUC0- t u AUC0- ∞ ta 'amlodipina u lisinopril.
Overall, the CHMP considered that the applicant had responded adequately by providing the results of an additional study, BES No.67289, and had demonstrated formal proof of bioequivalence.
Kumplessivament, is- CHMP ikkunsidra li l- Applikant wieġeb b' mod adegwat billi pprovda r- riżultati ta 'studju addizzjonali, BES Nru 67289, u wera prova formali ta' bijoekwivalenza.
The overall design of the study was adequately pre-specified in the protocol and was considered acceptable.
Id- disinn kumplessiv tal- istudju kien prespeċifikat b' mod adegwat fil- protokoll u kien ikkunsidrat aċċettabbli.
Subjects were selected by appropriate inclusion criteria and the regimen was standardized, excluding factors influencing pharmacokinetic interactions.
Is- suġġetti ntgħażlu skoni kriterji ta 'inklużjoni xierqa, b' reġim standardizzat li kien jeskludi fatturi li jinfluwenzaw l- interazzjonijiet farmakokinetiċi.
The sampling interval and wash-out period were considered long enough and the statistical evaluation was also appropriate.
L- intervall ta 'teħid ta' kampjuni u l- perjodu ta 'wash - out tqiesu twal biżżejjed u l- evalwazzjoni statistika kienet xierqa wkoll.
LC-MS/ MS methods were validated for analysis of both compounds, and the stability of the samples was documented over the period of sample storage.
Ġew ivvalidati l- metodi ta 'LC- MS/ MS għall- analiżi taż- żewġ komposti, u ġiet iddokumentata l- istabbiltà tal- kampjuni fuq il - perjodu tal- ħżin tal- kampjuni.
Based on the data provided, bioequivalence for both amlodipine 10 mg and lisinopril 20 mg after administration of single oral doses of LISONORM FORTE, co-administration of NORVASC 10 mg and PRINIVIL 20 mg, or administration of LISONORM (fixed-combination of amlodipine 5 mg and lisinopril 10 mg) could be concluded.
Abbażi tad- dejta pprovduta, kien possibbli li jiġi konkluż favur il- bijoekwivalenza kemm għal amlodipina 10 mg kif ukoll għal lisinopril 20 mg wara l- għoti ta 'dożi orali singoli ta' LISONORM FORTE, l- għoti fl- istess ħin ta 'NORVASC 10 mg u PRINIVIL 20 mg, jew l- għoti ta' LISONORM (kombinazzjoni fissa ta 'amlodipina 5 mg u lisinopril 10 mg).
The 90% confidence intervals calculated for AUC(0-t), AUC(0-inf) and Cmax were within the range of 0.8-1.25 for both components (lisinopril and amlodipine).
L- intervalli ta 'kunfidenza ta' 90% ikkalkolati għal AUC( 0- t), AUC( 0- inf) u Cmax kienu fil- medda ta '0. 8- 1. 25 għaż- żewġ komponenti (lisinopril u amlodipina).
With regards to safety, there were 3 drop-out subjects.
5 Fir- rigward tas- sigurtà, kien hemm 3 suġġetti li rtiraw.
As expected in this type of
Total ta '96 episodju avvers ta' wara d- doża ġew irrapportati minn 35 mit- 48 suġġett li rċevew għall- inqas doża waħda tal- mediċina tal- istudju.
5 medicinal product, headache was the most commonly reported adverse event.
Kif mistenni f' dan it- tip ta 'prodott mediċinali, l- uġigħ ta' ras kien l- aktar episodju avvers irrapportat b' mod komuni.
Additionally, there was a high incidence of QT prolongation observed in 16.7% subjects (n=8).
Barra minn hekk, kien hemm inċidenza għolja ta 'prolungament tal- QT osservat f' 16. 7% tas- suġġetti (n=8).
The appearance of QT prolongation was similar in all 3 different treatment options, and there were no statistically significant differences between pre- dose and post-dose QTc values.
Il- feġġa tal- prolungament tal- QT irriżultat simili fit- 3 għażliet ta 'trattament differenti kollha, u ma kien hemm ebda differenza statistikament sinifikanti bejn il- valuri tal- QTc ta' qabel id- doża u ta 'wara d- doża.
In summary, there were no differences with respect to adverse events associated with the administration of amlodipine and lisinopril between the three investigated treatments, and no additional safety issues were raised by the results of the study.
Fil- qosor, ma kien hemm ebda differenza bejn it- tliet trattamenti eżaminati fir- rigward tal- episodji avversi assoċjati mat- teħid ta 'amlodipina u lisinopril, u ebda kwistjoni addizzjonali fir - rigward tas- sigurtà ma tqajmet mir- riżultati tal- istudju.
GROUNDS
RAĠUNIJIET
67289, which shows that the test product induces
- l- Applikant ippreżenta studju ta 'bijoekwivalenza, Nru 67289, li juri li l- prodott prova jwassal għal
comparable PK profiles for amlodipine and lisinopril in the fixed dose combination to those of the reference products (monocomponents).
profili farmakokinetiċi komparabbli għal amlodipina u lisinopril fil- kombinazzjoni ta 'doża fissa għal dawk tal- prodotti ta' referenza (monokomponenti);
- bioequivalence with the monocomponent products has been adequately demonstrated.
- il- bijoekwivalenza mal- prodotti monokomponenti ntweriet b' mod adegwat;
- the safety profile of the test product shows no differences with respect to adverse events associated with the
- il- profil tas- sigurtà tal- prodott tal- prova ma juri ebda differenza fir- rigward tal- episodji avversi
administration of amlodipine and lisinopril compared to either reference treatments.
assoċjati mat- teħid ta 'amlodipina u lisinopril meta mqabbla mat- trattament ta' referenza rispettivi;
the CHMP has recommended the granting of the Marketing Authorisation(s) for which the Summary of Product Characteristics, labelling and package leaflet are set out in Annex III for Lisonorm and associated names (see Annex I).
is- CHMP irrakkomanda l- għoti tal- Awtorizzazzjoni( jiet) għat- Tqegħid fis- Suq li għalih, is- Sommarju tal- Karatteristiċi tal- Prodott, it- tikketta u l- fuljett ta 'tagħrif huma stabbiliti fl- Anness III għal Lisonorm u l- ismijiet assoċjati (ara l- Anness I).
7 ANNEX III
7 SOMMARJU TAL- KARATTERISTIĊI TAL- PRODOTT
Lisonorm and associated names (see Annex I) 10/ 5 mg tablets [See Annex I - To be completed nationally]
Lisonorm u ismijiet assoċjati (ara Anness I) 10/ 5 mg pilloli [Ara Anness I - Għandu jitlesta fil- pajjiż stess]
Each tablet contains 10 mg lisinopril (as dihydrate) and 5 mg amlodipine (as besilate).
Kull pillola fiha 10 mg lisinopril (bħala dihydrate) u 5 mg amlodipine (bħala besilate).
White or off-white, round, flat, bevel-edged tablet with a score line on one side and with an engraving „ A+L” on the reverse side.
Pillola tonda bajda jew ofwajt, ċatta, b’ tarf imċanfar b’ sinjal imnaqqax fuq naħa waħda u b ’ “ A+L ” imnaqqax fuq in- naħa l- oħra.
Diameter: about 8 mm.
Dijametru: madwar 8 mm.
The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
Is- sinjal imnaqqax qiegħed hemm biss biex tkun tista ’ taqsamha sabiex tkun tista ’ tiblagħha mingħajr tbatija u mhux biex taqsamha f’ dożi indaqs.
Treatment of essential hypertension.
Trattament għal pressjoni għolja essenzjali.
Lisonorm is indicated as substitution therapy of patients with blood pressure adequately controlled with lisinopril and amlodipine given concurrently at the same dose level.
Lisonorm hu indikat bħala terapija ta ’ sostituzzjoni għal pazjenti bil- pressjoni tad- demm ikkontrollata b’ mod adegwat b’ lisinopril u amlodipine mogħtija flimkien fl- istess livell ta ’ doża.
The recommended dose is one tablet daily.
Id- doża rakkomandata hi ta ’ pillola waħda kuljum.
The maximum daily dose is one tablet.
L- ogħla doża li tista ’ tingħata kuljum hi ta ’ pillola waħda.
Since food does not affect absorption, Lisonorm may be taken irrespective of meals.
Peress li l- assorbiment mhux affettwat bl- ikel, Lisonorm jista ’ jittieħed irrispettivament mill - ikel.
Patients with renal impairment To find the optimal starting dose and maintenance dose of patients with renal impairment, the patients should be individually titrated using the individual components of lisinopril and amlodipine.
Pazjenti b’ indeboliment Renali Sabiex tingħata l- aħjar doża tal- bidu u dik ta ’ manteniment għal pazjenti b’ indebolment renali, il - pazjenti għandhom jiġu ttitrati individwalment bl- użu tal- komponenti individwali ta ’ lisinopril u amlodipine.
Lisonorm is indicated only for patients in whom the optimal maintenance dose of lisinopril and amlodipine has been titrated to 10 mg and 5 mg, respectively.
Lisonorm hu indikat biss għal pazjenti li għalihom l- aħjar doża ta ’ manteniment ta ’ lisinopril u amlodipine ġiet ittittrata għal 10 mg u 5 mg, rispettivament.
Renal function, serum potassium and sodium levels should be monitored during therapy with Lisonorm.
Il- funzjoni renali, il- livelli ta ’ potassju u sodju fis- serum għandhom jiġu mmonitorati waqt it- terapija b’ Lisonorm.
In the case of renal function deterioration, the use of Lisonorm should be discontinued and replaced by the individual components adequately adjusted.
F’ każ li l- funzjoni renali tmur għall- agħar, l- użu ta ’ Lisonorm għandu jitwaqqaf u jiġi mibdul ma ’ komponenti individwali aġġustati b’ mod xieraq.
Patients with hepatic impairment The elimination of amlodipine may be prolonged in patients with impaired liver function.
Pazjenti b’ indeboliment tal- fwied L- eliminazzjoni ta ’ amlodipine tista ’ titwal f’ pazjenti li għandhom funzjoni tal- fwied indebolita.
No precise dosage recommendations have been established for such cases and, therefore, this medicinal product should be administered with caution to patients with hepatic impairment.
Ma ġewx stabbiliti rakkomandazzjonijiet għal doża preċiża għal każijiet bħal dawn u, għalhekk, dan il - prodott mediċinali għandu jingħata b’ kawtela lil pazjenti li għandhom indeboliment epatiku.
Children and adolescents Lisonorm is not recommended for use in children below age 18 due to a lack of data on safety and efficacy.
Tfal u adoloxxenti Lisonorm mhux rakkomandat għal użu fi tfal taħt l- età ta ’ 18- il sena minħabba n- nuqqas ta ’ tagħrif dwar is- sigurtà u l- effikaċja.
Elderly (> 65 years)
Anzjani (> 65 sena)
10 In clinical studies, there was no age-related change in the efficacy or safety profile of amlodipine or lisinopril.
9 Fi studji kliniċi, ma kienx hemm bidla relatata ma ’ l- età fl- effikaċja jew il- profil tas- sigurtà ta ’ amlodipine jew lisinopril.
To find the optimal maintenance dose for elderly patients they should be individually titrated using the free combination of lisinopril and amlodipine.
Sabiex wieħed isib l- aħjar doża ta ’ manteniment għal pazjenti anzjani dawn għandhom jiġu ttittrati individwalment billi tintuża l- kombinazzjoni libera ta ’ lisinopril u amlodipine.
Lisonorm is indicated only for patients in whom the optimal maintenance dose of lisinopril and amlodipine has been titrated to 10 mg and 5 mg, respectively (see section 4.4).
Lisonorm hu indikat biss għal pazjenti li għalihom l- aħjar doża ta ’ manteniment ta ’ lisinopril u amlodipine ġiet ittittrata għal 10 mg u 5 mg, rispettivament (ara sezzjoni 4. 4).
• Hypersensitivity to lisinopril or to any other angiotensin converting enzyme (ACE) inhibitor. • Hypersensitivity to amlodipine or to any other dihydropyridine derivatives. • Hypersensitivity to any of the excipients. • Severe hypotension. • A history of angioedema relating to previous ACE inhibitor therapy. • Hereditary or idiopathic angioedema (see section 4.4). • Haemodynamically significant obstruction in the outflow tract of the left ventricle (aortic stenosis, hypertrophic cardiomyopathy), mitral stenosis or cardiogenic shock. • Heart failure after acute myocardial infarction (during the first 28 days). • Unstable angina pectoris (excluding Prinzmetal’ s angina). • Pregnancy and lactation (see section 4.6).
• Sensittività eċċessiva għal lisinopril jew għal kull impeditur ieħor għal enżimi li jikkonvertu angiotensin (ACE). • Sensittività eċċessiva għal amlodipine jew kull derivat ieħor ta ’ dihydropyridine. • Sensittività eċċessiva għal xi wieħed mis- sustanzi mhux attivi. • Pressjoni baxxa qawwija. • Storja ta ’ anġjoedema relatata ma ’ terapija ta ’ impedituri ta ’ ACE. • Anġjoedema ereditarja jew idjopatika (ara sezzjoni 4. 4). • Imblukkar emodinamiku sinifikanti fil- passaġġ tal- iżbokk tal- ventrikola tax- xellug (stenosi aortika, kardjomijopatija ipertrofika), stenosi mitrali jew xokk kardjoġeniku. • Insuffiċjenza kardijaka wara infart mijokardijaku akut (matul l- ewwel 28 jum). • Anġina pectoris instabbli (li teskludi l- anġina ta ’ Prinzmetal). • Tqala u treddigħ (ara sezzjoni 4. 6).
Symptomatic hypotension Substantial decrease in blood pressure and hence symptomatic hypotension can occur in patients with volume and/ or sodium depletion resulting from diuretic therapy, fluid loss of other origin such as excessive diaphoresis, prolonged vomiting and/ or diarrhoea (see section 4.2).
Pressjoni baxxa sintomatika Tnaqqis sostanzjali fil- pressjoni tad- demm u minhekk tista ’ sseħħ pressjoni baxxa sintomatika f’ pazjenti li għandhom żvojtjar volumetriku u/ jew tas- sodju li jirriżulta minn terapija dijuretika, telf ta ’ fluwidi ta ’ oriġini oħra bħal dijaforesi eċessiva, rimettar u/ jew dijarea fit- tul (ara sezzjoni 4. 2).
If hypotension occurs, the patient should be placed in a supine position and intravenous fluid replacement (intravenous infusion of physiologic saline) should be administered if necessary.
Jekk ikun hemm pressjoni baxxa, il- pazjent għandu jitqiegħed wiċċu ’ l fuq, u jekk meħtieġ għandu jingħata fluwidu ta ’ sostituzzjoni ġol- vina (infużjoni ta ’ salina fiżjoloġika fil- vina).
Preferably, sodium and/ or volume depletion should be corrected before treatment with Lisonorm is started.
Preferibbilment, in- nuqqas ta ’ sodju u/ jew ta ’ fluwidi għandu jiġi kkorreġut qabel ma jibda t- trattament b’ Lisonorm.
The magnitude of antihypertensive effect should be closely monitored after administering the initial dose.
Il- qawwa tal- effett ta ’ kontra l- pressjoni għolja għandu jiġi mmonitorat mill- qrib wara li tingħata d- doża inizjali.
Aortic and mitral stenosis, obstructive hypertrophic cardiomyopathy As with all vasodilators, Lisonorm should be administered with caution to patients with obstruction in the outflow tract of the left ventricle and with stenosis of mitral valve.
Stenosi aortika u mitrali, kardjomijopatija ipertrofika osstruttiva Bħal fil- każ tal- vażodilaturi kollha, Lisonorm għandu jingħata b’ kawtela lil pazjenti b’ imblukkar fil- passaġġ ta ’ l- iżbokk tal- ventrikola tax- xellug u bi stenosi tal- valv mitrali.
Renal function impairment Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when angiotensin converting enzyme inhibitors has been given concomitantly with a diuretic.
Indeboliment fil- funzjoni renali Xi pazjenti bil- pressjoni baxxa li ma deherx li kellhom mard vaskulari eżistenti fil- kliewi qabel żviluppaw żidiet fil- livelli ta ’ urea fid- demm u tal- kreatinina fis- serum, ġeneralment minuri u mhux permanenti, speċjalment meta impedituri għal enżimi li jikkonvertu angiotensin ingħataw flimkien ma ’ dijuretiku.
This is more likely to occur in patients with pre-existing renal impairment.
Dan għandu aktar ċans li jseħħ f’ pazjenti li għandhom indeboliment renali li kien jeżisti minn qabel.
In some patients with bilateral renal artery stenosis or with a stenosis of the artery to a solitary kidney, who have been treated with angiotensin converting enzyme inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy, have been seen.
F’ xi pazjenti bi stenosi bilaterali tal- arterja renali jew bi stenosi tal- arterja għal kilwa solitarja, li ġew ittrattati b’ impedituri għal enżimi li jikkonvertu angiotensin, dehru żidiet fil- livelli ta ’ urea fid- demm u ta ’ kreatinina fis- serum, ġeneralment riversibbli malli twaqqfet it- terapija.
This is especially likely in patients with renal insufficiency.
Dan għandu aktar ċans li jseħħ f’ pazjenti b’ insuffiċjenza renali.
To find the optimal maintenance dose of patients with renal impairment, the patients should individually be titrated using the individual components of lisinopril and amlodipine, with close monitoring of renal function.
Sabiex tinsab l- aħjar doża ta ’ manteniment ta ’ pazjenti b’ impediment renali, il- pazjenti għandhom jiġu ttittrati individwalment billi jintużaw il- komponenti individwali ta ’ lisinopril u amlodipine, b’ monitoraġġ mill- qrib tal- funzjoni renali.
Lisonorm is indicated only for patients with titrated optimal maintenance dose of lisinopril and amlodipine of 10 mg and 5 mg, respectively.
Lisonorm hu indikat biss għal pazjenti li għalihom l- aħjar doża ta ’ manteniment ta ’ lisinopril u amlodipine ġiet ittittrata għal 10 mg u 5 mg, rispettivament.
In the case of renal function deterioration, Lisonorm should be withdrawn and replaced by the therapy with individual components adequately adjusted.
Fil- każ ta ’ peġġorament tal- funzjoni renali, Lisonorm għandu jitwaqqaf u minflok jingħataw terapija tal- komponenti individwali aġġustati kif jixraq.
Dose reduction and/ or discontinuation of the diuretic may also be required.
Tnaqqis tad- doża u/ jew twaqqif tad- dijuretiku jista ’ jkun meħtieġ ukoll.
11 Angioedema of the face, extremities, lips, tongue, glottis and/ or larynx has been reported in patients treated with angiotensin converting enzyme inhibitors, including lisinopril.
Anġjoedema Anġjoedema tal- wiċċ, ta ’ l- estremitajiet, tax- xofftejn, ta ’ l- ilsien, tal- glottide u/ jew tal- larinġi ġew rapportati f’ pazjenti trattati b’ impedituri għal enżimi li jikkonvertu angiotensin, li jinkludu lisinopril.
In such cases, Lisonorm should be discontinued immediately and the patient kept under close medical supervision until complete and sustained resolution of symptoms has occurred.
10 F’ każijiet bħal dawn, Lisonorm għandu jitwaqqaf minnufih u l- pazjent jinżamm taħt superviżjoni medika attenta sakemm jiġu sollevati s- sintomi b’ mod komplut u sostnut.
Where swelling is confined to the face, lips and extremities, it usually resolves spontaneously; nevertheless, antihistamines may be useful in relieving symptoms.
Meta n- nefħa ħi ristretta għal wiċċ, ix- xofftejn u l- estremitajiet, ġeneralment tirriżolvi ruħha b’ mod spontaneju; madankollu, antistamini jistgħu jkunu utli biex jissolevaw is- sintomi.
Angioedema accompanied by laryngeal oedema is potentially fatal.
Anġjoedema akkumpanjata minn edema larinġeali hi potenzjalment fatali.
If the oedematous swelling involves the tongue, glottis or larynx, or it is likely to cause airway obstruction; emergency treatment should be initiated promptly.
Jekk in- nefħa edematuża tinvolvi l- ilsien, il- glottide jew il- larinġi, jew x’ aktarx toħloq imblokk fil- passaġġ ta ’ l- arja; trattament ta ’ emerġenza għandu jiġi mibdi minnufih.
Appropriate measures include the subcutaneous administration of 0.3-0.5 mg adrenaline epinephrine or the slow intravenous administration of 0.1 mg adrenaline, followed by glucocorticoids and antihistamines, with simultaneous monitoring of vital functions.
Miżuri xierqa jinkludu l- għoti taħt il- ġilda ta ’ 0. 3- 0. 5 mg adrenaline epinephrine jew l- għoti bil- mod fil- vina ta ’ 0. 1 mg adrenaline, segwita b’ glukokortikojdi u antistamini, b’ monitoraġġ simultaneju tal- funzjonijiet vitali.
Angiotensin converting enzyme inhibitors cause a higher rate of angioedema in black patients than in non- black patients.
Impedituri għal enżimi li jikkonvertu angiotensin jikkaġunaw rata ogħla ta ’ anġjoedema f’ pazjenti suwed milli f’ dawk li mhumiex suwed.
Intestinal oedema has been reported rarely in patients treated with ACE inhibitors.
Edema intestinali ġiet rapportata rarement f’ pazjenti ttrattati b’ impedituri ta ’ l- ACE.
These patients presented with abdominal pain (with or without nausea and vomiting); in some cases there was no prior facial angioedema and C-1 esterase levels were normal.
Dawn il- pazjenti ppreżentaw rwieħom b’ uġigħ addominali (bi jew mingħajr tqalliegħ u rimettar); f’ xi wħud mill - każijiet ma ’ kienx hemm anġjoedema tal- wiċċ qabel u l- livelli ta ’ C- 1 esterase kienu normali.
The angioedema was diagnosed by procedures including CT scan, or ultrasound or at surgery and symptoms resolved after stopping the ACE inhibitor.
L - anġjoedema kienet dijanjonizzata bi proċeduri li kienu jinkludu CT scan, jew ultrasawnd jew waqt kirurġija u s- sintomi rriżolvew wara t- twaqqif ta ’ l- impeditur ta ’ l- ACE.
Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Anġjoedema intestinali għandha tiġi inkluża fid- dijanjosi divrenzjali ta ’ pazjenti fuq impedituri ta ’ l- ACE li jippreżentaw rwieħom b’ uġigħ addominali.
Anaphylactoid reactions in haemodialysis patients Anaphylactic shock has been reported in patients dialysed with polyacrylonitrile (e. g.
Reazzjonijiet anafilattojdi f’ pazjenti b’ emodijalisi Xokk anafilattiku ġie rapportat f’ pazjenti dijalizzati b’ membrana ta ’ polyacrylonitrile (eż.
AN 69) membrane and treated concomitantly with an ACE inhibitor, therefore, this combination must be avoided.
AN 69) u trattati fl- istess ħin b’ impeditur ta ’ l- ACE, u għalhekk, din il- kombinazzjoni għandha tiġi evitata.
In these patients, it is recommended to use a different type of dialysis membrane or a different class of antihypertensive agent.
F’ dawn il- pazjenti, hu rakkomandat li tintuża tip differenti ta ’ membrana ta ’ dijalisi jew klassi differenti ta ’ mediċina li taġixxi kontra l- pressjoni għolja.
Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis Rarely, patients receiving ACE inhibitors during low-density lipoproteins (LDL) apheresis with dextran sulphate have experienced life-threatening anaphylactoid reactions.
Reazzjonijiet anafilattojdi waqt aferesi ta ’ liunpoproteini ta ’ densità baxxa (LDL)) F’ każijiet rari, pazjenti li rċevew impedituri ta ’ l- ACE waqt aferesi ta ’ lipoproteini ta ’ densità baxxa (LDL) b’ dextran sulphate kellhom reazzjonijiet anafilattojdi li kienu ta ’ periklu għal ħajja.
These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.
Dawn ir - reazzjonijiet kienu evitati billi t- terapija b’ impeditur ta ’ l- ACE ġiet temporanjament miżmuma qabel kull aferesi.
Bee/ wasp venom desensitization Occasionally, patients receiving ACE inhibitors during desensitization with Hymenoptera (e. g. wasp, bee) venom have experienced anaphylactoid reactions.
Desensitizzazzjoni tal- velenu tan- naħal jew taż- żunżan Xi minn daqqiet, pazjenti li kienu qed jirċievu impedituri ta ’ l- ACE waqt desensitizzazzjoni minn velenu ta ’ Hymenoptera (eż. żunżan, naħal) esperjenzaw reazzjonijiet anafilattojdi.
These life-threatening reactions can be avoided by temporary withdrawal of ACE inhibitor therapy.
Dawn ir - reazzjonijiet li huma ta ’ periklu għal ħajja jistgħu jiġu evitati b’ waqfien temporanju tat- terapija b’ impedituri ta ’ l- ACE.
Hepatotoxicity Very rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant necrosis and (sometimes) death.
Tossiċita epatika B’ mod rari ħafna, l- impedituri ta ’ l- ACE ġew assoċjati ma ’ sindromu li jibda bħala suffejra kolestatika jew epatite u jiżviluppa għal nekrosi fulminanti u (xi kultant) mewt.
The mechanism of this syndrome is not understood.
Il- mekkaniżmu ta ’ dan is - sindromu għadu mhux mifhum.
Patients receiving Lisonorm tablets who develop jaundice or marked elevations of hepatic enzymes should discontinue Lisonorm and receive appropriate medical follow-up.
Pazjenti li jirċievu l- pilloli Lisonorm li jiżviluppaw suffejra jew ikollhom żieda sostanzjali fil- livelli tal- enżimi epatiċi għandhom iwaqqfu Lisonorm u jieħdu follow- up mediku xieraq.
Hepatic impairment The half-life of amlodipine is prolonged in patients with impaired liver function.
Indeboliment epatiku Il- half- life ta ’ amlodipine hu mtawwal f’ pazjenti b’ funzjoni tal- fwied indebolita.
Since no dose recommendations have been established, this medicinal product should therefore be administered with caution, weighing individually the expected benefits and potential risks of the treatment.
Peress li l- ebda rakkomandazzjonijiet għad- doża ma ġew stabbiliti, dan il- prodott mediċinali għandu għalhekk jingħata b’ kawtela, billi jiġu mwieżna individwalment l- benefiċċji mistennija u r- riskji potenzjali tat - trattament.
Haematological toxicity Very rarely, neutropenia, agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors (see section 4.8).
Tossiċità ematoloġika B’ mod rari ħafna, newtropenja, agranuloċitosi u anemija ġew rapportati f’ pazjenti li qed jieħdu impedituri ta ’ l- ACE (ara sezzjoni 4. 8).
In patients with normal renal function and no other complicating
F’ pazjenti li għandhom funzjoni renali normali u mingħajr
12 factors, neutropenia occurs rarely.
11 fatturi oħra li jistgħu jikkomplikaw l- affarijiet, in- newtropenja tista ’ sseħħ b’ mod rari.
Neutropenia and agranulocytosis are reversible after discontinuation of the ACE inhibitor.
In- newtropenja u l- agranuloċitosi huma riversibbli wara li l- impeditur ta ’ l- ACE jitwaqqaf.
Lisonorm should be used with extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing impaired renal function.
Lisonorm għandu jintuża b’ kawtela estrema f’ pazjenti b’ mard vaskulari tal- kollaġen, terapija ta ’ immunosuppressjoni, trattament b’ allupurinol jew procainamide, jew kombinazzjoni ta ’ dawn il- fatturi li jistgħu jikkomplikaw l- affarijiet, speċjalment jekk hemm indeboliment tal- kliewi li kien jeżisti qabel.
Some of these patients developed serious infections, which in a few instances did not respond to intensive antibiotic therapy.
Xi wħud minn dawn il- pazjenti żviluppaw infezzjonijiet serji, li f’ xi każijiet ma rrispondewx għal terapija intensiva ta ’ antibijotiċi.
If Lisonorm is used in such patients, periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection.
Jekk Lisonorm jintuża f’ pazjenti bħal dawn, monitoraġġ perijodiku tal- għadd taċ- ċelluli tad- demm bojod hu rakkomandat u pazjenti għandhom jingħataw struzzjonijiet biex jirraportaw kull sinjal ta ’ infezzjoni.
Cough Commonly, cough has been reported with the use of ACE inhibitors.
Sogħla B’ mod komuni, is- sogħla ġiet rapportata bl- użu ta ’ impedituri ta ’ l- ACE.
Characteristically, the cough is non- productive, persistent and resolves after discontinuation of therapy.
Karatteristikament, is- sogħla mhix produttiva, persistenti u tirriżolvi ruħha wara il- waqfien tat- terapija.
ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.
Sogħla indotta minn impedituri ta ’ l- ACE għandha tiġi kkonsidrata bħala parti mid- dijanjosi divrenzjali ta ’ sogħla.
Surgery/ general anaesthesia In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, lisinopril may block angiotensin II formation secondary to compensatory renin release.
Kirurġija/ loppju ġenerali F’ pazjenti li tkun ser isirilhom operazzjoni maġġuri jew waqt il- loppju b’ sustanzi li jipproduċu pressjoni baxxa, lisinopril jista ’ jimblokka l- formazzjoni ta ’ angiotensin II b’ mod sekondarju għal rilaxx kompensatorju ta ’ renin.
If hypotension occurs, probably as a consequence of this mechanism, it can be corrected by volume expansion
Jekk isseħħ pressjoni baxxa, probabbilment bħala konsegwenza ta ’ dan il- mekkaniżmu, dan jista ’ jiġi kkoreġut b’ espansjoni tal- volum.
Elderly When advanced age is associated with decrease in renal function Lisonorm dose adjustments for patients with renal impairment apply (see section 4.2).
Anzjani Meta età avvanzata hija assoċjata ma ’ tnaqqis fil- funzjoni renali, tibdiliet fid- doża ta ’ Lisonorm għal pazjenti b’ indeboliment tal- kliewi għandhom jiġu fis- seħħ (ara sezzjoni 4. 2).
Hyperkalaemia Elevations in potassium serum levels have been observed in some patients treated with ACE inhibitors.
Iperkalemja Żidiet fil- livelli ta ’ potassju fis- serum ġew osservati f’ xi pazjenti trattati b’ impedituri ta ’ l- ACE.
Patients at risk for the development of hyperkalaemia include those with renal impairment, diabetes mellitus, acute cardiac decompensation, dehydration, metabolic acidosis, or concomitant use of potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes, or any medicinal products associated with increases in potassium serum levels (e. g. heparin).
Pazjenti f’ riskju li jistgħu jiżviluppaw iperkalemja jinkludu dawk b’ indeboliment renali, dijabete mellitus, dekompensazzjoni kardijata akuta, deidrazzjoni, aċidosi metabolika, jew l- użu konkomitanti ta ’ dijuretiċi li ma jħallux il- potassju joħroġ fl- awrina, supplimenti tal- potassju jew mluħa sostituti li jkun fihom il- potassju, jew kull prodott mediċinali ieħor assoċjat ma żidiet fil- livell ta ’ potassju fis - serum (eż. heparin).
If concomitant use of the abovementioned substances is needed, regular monitoring of potassium serum levels is recommended (see section 4.5).
Jekk użu konkomitanti tas- sustanzi msemmija hawn fuq hi meħtieġa, monitoraġġ regolari tal- livelli ta ’ potassju fis- serum hu meħtieġ (ara sezzjoni 4. 5).
Potassium-sparing diuretics (e. g. spironolactone, amiloride, and triamterene), potassium supplements, or potassium-containing salt substitutes and other substances that may increase potassium levels (e. g. heparin) can lead to hyperkalaemia in combination with ACE inhibitors, particularly in patients with renal impairment and other pre-existing conditions (see section 4.4).
Interazzjonijiet relatati ma ’ lisinopril Sustanzi li jaffettwaw il- livelli ta ’ potassju: dijuretiċi li ma jħallux il- potassju joħroġ fl- awrina (eż. spironolactone, amiloride, u triamterene), supplimenti tal- potassju, jew mluħa sostituti li jkun fihom il- potassju u sustanzi oħra li jistgħu jżidu l- livelli ta ’ potassju (eż. heparin) jistgħu jwasslu għal iperkalemja f’ kombinazzjoni mal- impedituri ta ’ l- ACE, b’ mod partikolari f’ pazjenti b’ indeboliment fil- kliewi u kundizzjonijiet oħra li kienu jeżistu qabel (ara sezzjoni 4. 4).
If a medicinal product that affects potassium levels is to be prescribed in combination with lisinopril, monitoring of potassium serum levels is advised.
Jekk prodott mediċinali li jaffettwa l- livelli ta ’ potassju jiġi preskritt f’ kombinazzjoni ma ’ lisinopril, hu rakkomandat li jkun hemm monitoraġġ tal- livelli ta ’ potassju fis- serum.
Therefore, concomitant administration should be carefully considered and only undertaken with increased caution and regular monitoring of both serum potassium levels and renal function.
Għalhekk, l- għoti konġunt għandu jiġi kkonsidrat b’ attenzjoni u għandu jsir b’ kawtela akbar b’ monitoraġġ regolari kemm tal- livelli ta ’ potassju fis - serum u tal- funzjoni renali.
Diuretics:
Dijuretiċi:
When a diuretic is added to the therapy of a patient receiving Lisonorm the antihypertensive effect is usually additive (see section 4.4).
Meta dijuretiku jiġi miżjud mat- terapija ta ’ pazjent li qed jirċievi Lisonorm l- effett kontra l- pressjoni għolja huwa ġeneralment magħdud (ara sezzjoni 4. 4).
Lisinopril mitigates the kaliuretic effect of diuretics.
Lisinopril jimmitiga l- effetti kaliuretiċi tad- dijuretiċi.
Other antihypertensives:
Mediċini ta ’ kontra l- pressjoni għolja oħra:
Concomitant use of these agents may increase the hypotensive effects of Lisonorm.
Użu konkomitanti ta ’ dawn il- mediċini jista ’ jżid l- effetti li jbaxxu l- pressjoni ta ’ Lisonorm.
Concomitant use with glyceryl trinitrate and other nitrates, or other vasodilators, may further reduce blood pressure.
L- użu konkomitanti ta ’ glyceryl trinitrate u nitrati oħra, jew vażodilaturi oħra, jista ’ jnaqqas aktar il- pressjoni tad- demm.
Tricyclic antidepressants/ antipsychotics/ anaesthetics/ narcotics:
12 Antidipressanti triċikliċi/ antipsikotiċi/ anestetiċi/ narkotiċi:
Concomitant use with ACE inhibitors may result in further reduction of blood pressure (see section 4.4).
L- użu konkomitanti ta ’ impedituri ta ’ l - ACE jista ’ jirriżulta f’ aktar tnaqqis fil- pressjoni tad- demm (ara sezzjoni 4. 4).
13 Alcohol enhances the hypotensive effect.
Alkoħol iħarrex l- effett li jbaxxi l- pressjoni.
Allopurinol, procainamide, cytostatics or immunosuppressive agents (systemic corticosteroids) may lead to an increased risk of leukopenia when administered concomitantly with ACE inhibitors.
Allopurinol, procainamide, ċitostatiċi jew sustanzi immunosuppressivi (kortikosterojdi sistemiċi) jistgħu jwasslu għal riskju ogħla ta ’ lewkopenja meta jingħataw flimkien ma ’ impedituri ta ’ l- ACE.
Antacids decrease the bioavailability of the concomitant use of ACE inhibitors.
Antaċidi nnaqqsu l- bijodisponibilità ta ’ l- użu konkomitanti ta ’ impedituri ta ’ l- ACE.
Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors; patients should be carefully monitored to confirm that the desired effect is being obtained.
Simpatomimetiċi għandhom mnejn inaqqsu l- effetti ta ’ kontra l- pressjoni għolja ta ’ impedituri ta ’ l - ACE; Il- pazjenti għandhom jiġu mmonitorati b’ attenzjoni sabiex jikkonfermaw li l- effett mixtieq qed jintlaħaq.
Antidiabetics:
Mediċini kontra d- dijabete:
Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic medicinal products (insulins, oral hypoglycaemic agents) may cause an increased blood glucose lowering effect with risk of hypoglycaemia.
Studji epidemjoloġiċi ssuġġerew li l- għoti ta ’ impedituri ta ’ l- ACE flimkien ma ’ prodotti mediċinali li jaħdmu kontra d- dijabete (insulini, sustanzi ipogliċemiċi orali) jistgħu jikkawżaw żieda fl- effett li jitnaqqas il- livell ta ’ żokkor fid- demm li jista ’ jwassal għal riskju ta ’ ipogliċemija.
This phenomenon appeared to be more likely to occur during the first weeks of combined treatment and in patients with renal impairment.
Dan il- fenomenu deher li kien aktar probabbli li jseħħ fl- ewwel ġimgħat ta ’ trattament ikkombinat u f’ pazjenti b’ indeboliment tal- kliewi.
Chronic administration of NSAIDs, including high-dosed acetylsalicylic acid ≥ 3 g/ day, may reduce the antihypertensive effect of an ACE inhibitor.
L- għoti b’ mod kroniku ta ’ NSAIDs, li jinkludu dożi għoljin ta ’ acetylsalicylic acid ≥ 3 g/ kuljum, jista ’ jnaqqas l- effett ta ’ kontra l- pressjoni għolja ta ’ impeditur ta ’ l- ACE.
NSAIDs and ACE inhibitors exert an additive effect on the increase in serum potassium and may result in a deterioration of renal function.
Mediċini NSAIDs u impedituri ta ’ l- ACE jeżerċitaw effett addittiv fuq iż- żieda fil- livell ta ’ potassju fis- serum u jista ’ jirriżulta f’ peġġorament fil- funzjoni renali.
Rarely, acute renal failure may occur, especially in patients with compromised renal function such as the elderly or dehydrated.
Bi frekwenza rari, falliment renali akut jista ’ jseħħ, speċjalment f’ pazjenti li għandhom il - funzjoni renali tagħhom kompromessa bħall- anzjani jew deidrati.
Lithium elimination may be reduced during concomitant use of ACE inhibitor and therefore, serum lithium levels should be monitored.
L- eliminazzjoni ta ’ Lithium tista ’ titnaqqas meta jingħata flimkien ma ’ impedituri ta ’ l- ACE u għalhekk, il- livell ta ’ Lithium fis- serum għandu jiġi mmonitorat.
Interactions related to amlodipine CYP3A4 inhibitors:
Interazzjonijiet relatati ma ’ amlodipine Impedituri ta ’ CYP3A4:
A study in elderly patients has shown that diltiazem inhibits the metabolism of amlodipine, probably via CYP3A4 (plasma concentration increases by approximately 50% and the effect of amlodipine is increased).
Studju f’ pazjenti anzjani wera li diltiazem jimpedixxi l- metaboliżmu ta ’ amlodipine, probabilment permezz ta ’ CYP3A4 (il- konċentrazzjoni fil- plażma tiżdied b’ madwar 50% u jiżdied ukoll l- effett ta ’ amlodipine).
The possibility that more potent inhibitors of CYP3A4 (i. e. ketoconazole, itraconazole, ritonavir) may increase the plasma concentration of amlodipine to a greater extent than diltiazem cannot be excluded.
Il- possibilità li impedituri aktar potenti ta ’ CYP3A4 (i. e. ketoconazole, itraconazole, ritonavir) jistgħu jżidu l- konċentrazzjoni fil- plażma ta ’ amlodipine aktar minn diltiazem ma jistax jiġi eskluż.
Caution is required with concomitant use.
Kawtela hi meħtieġa waqt t- teħid konġunt.
CYP3A4 inducers:
Indutturi ta ’ CYP3A4:
Co-administration with anticonvulsant agents (e. g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, herbal preparations containing St.
It- teħid konġunt ta ’ sustanzi antikonvulsanti (eż. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, preparazzjonijiet bil- ħxejjex li fihom St.
John’ s wort/ Hypericum perforatum) may lead to reduced plasma concentrations of amlodipine.
John’ s wort/ Hypericum perforatum) jista ’ jwassal għal tnaqqis fil- konċentrazzjonijiet ta ’ amlodipine fil - plażma.
Clinical monitoring is indicated, with possible dosage adjustment of amlodipine during the treatment with the inducer and after its withdrawal.
Monitoraġġ kliniku hu indikat, b’ possibilità ta ’ tibdil fid- doża ta ’ amlodipine waqt it - trattament bl- induttur u wara l- waqfien tiegħu.
In monotherapy, amlodipine has been safely administered with thiazide diuretics, beta blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, anti- acid medicines (aluminium hydroxide gel, magnesium hydroxide, simeticone), cimetidine, non-steroidal anti- inflammatory medicines, antibiotics and oral hypoglycaemic medicines.
Fil- monoterapija, amlodipine ngħata b’ mod sikur ma ’ dijuretiċi ta ’ thiażide, imblokkaturi tar - riċetturi beta, impedituri tal- ACE, nitrati li jaġixxu fuq perijodu ta ’ żmien twil, nitrogliċerina għal taħt l- ilsien, digoxin, warfarina, atorvastatin, sildenafil, mediċini kontra l- aċidu (ġel ta ’ aluminium hydroxide, magnesium hydroxide, simeticone), cimetidine, mediċini anti- infjammatorji mhux sterojdi, antibijotiċi u mediċini ipogliċemiċi li jittieħdu mill- ħalq.
Pregnancy The use of ACE inhibitors is not recommended during the first trimester of pregnancy and they are contra- indicated in the second and third trimester.
Tqala L- użu ta ’ impedituri ta ’ l- ACE mhux rakkomandat waqt l- ewwel trimestru ta ’ tqala u huma kontra - indikati fit- tieni u t- tielet trimestru.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded.
13 Evidenza epidemjoloġika dwar ir- riskju ta ’ teratoġeniċita wara espożizzjoni għal impedituri ta ’ l- ACE waqt l- ewwel trimestru tat- tqala ma kinetx konklużiva; madankollu żieda żgħira fir- riskju ma tistax tiġi eskluża.