natgillin/translations-raw huggingface dataset:
Reduction of risk of cardiac events in patients with a history of myocardial infarction and/ or revascularisation”.
Zmanjševanje tveganja za srčne zaplete pri bolnikih, ki so v preteklosti že imeli miokardni infarkt in/ ali revaskularizacijo «.
An official referral for arbitration was notified by the Netherlands to the CHMP on 17.03.2005.
17. 03. 2005 je Nizozemska CHMP prijavila uradno napotitev na arbitražo.
1. - The Applicant should justify the proposed indication based on the results of the EUROPA trial and relevant published literature on other ACE-Is in terms of patients to be included and goals of therapy.
1. - Vlagatelj mora utemeljiti predlagano indikacijo, temelječo na rezultatih študije EUROPA in z zadevnimi navedbami v literaturi o drugih ACE- I- jih, z vidika bolnikov, ki bi jih naj vključevala, ter ciljev zdravljenja.
2. - The second issue addresses the question whether the beneficial effect may extend beyond a mere reduction of MI to a reduction of cardiac events.
2. - Drugi predmet razprave se tiče vprašanja, ali je mogoče koristnost z zgolj zmanjševanja pogostosti MI razširiti na zmanjševanje srčnih zapletov.
Consistency was noted between the various components of the primary endpoint although significance was only reached for prevention of MI.
Med posameznimi elementi primarnega izida so ugotovili konsistentnost rezultatov, vendar pa so bili ti statistično značilni zgolj pri preprečevanju MI.
A significant effect was noted on the occurrence of heart failure.
Pomemben učinek je bil ugotovljen pri pojavljanju srčne odpovedi.
5  EMEA 2005 Evaluation of Clinical Efficacy The indication under review is based on the results of the EUROPA study, a trial designed to evaluate the ability of Perindopril to reduce the risk of the combined endpoint of cardiovascular death, non-fatal acute MI and cardiac arrest with successful resuscitation in patients with stable coronary heart disease, without evidence of heart failure.
5 EMEA 2005 Ocena klinične učinkovitosti Ponovno obravnavana indikacija temelji na rezultatih študije EUROPA, ki je bila načrtovana s ciljem ovrednotenja zmožnosti perindoprila, da zmanjša tveganje za kombinirani izid kamor spadajo kardiovaskularna smrt, nesmrtni akutni miokardni infarkt in zaustavitev srca z uspešnim oživljanjem, pri bolnikih s stabilno koronarno arterijsko boleznijo, brez dokazov srčne odpovedi.
60.5%) would reflect serious coronary lesions in the group of patients with a history of revascularisation and with no history of MI.
Višji delež bolnikov z vsaj 70% zožitvijo ene od glavnih arterij (82, 4% napram 60, 5%) v skupini bolnikov z v preteklosti izvedeno revaskularizacijo, ki pa v preteklosti niso imeli MI, bi naj odražal resne koronarne lezije.
The Applicant was also requested to justify the indication based on the results of relevant published literature on other ACE-Is in terms of patients to be included and goals of therapy.
Od vlagatelja je bilo nadalje zahtevano, da utemelji indikacijo, temelječo na zadevnih navedbah v literaturi o drugih ACE- I- jih, z vidika bolnikov, ki naj bi jih vključevala, ter ciljev zdravljenja.
As further consistency is shown for the secondary variables, it is reasonable to extend the indication from “ reduction of MI” to “ reduction of cardiac events”, a term that includes patients with a history of MI and/ or a history of revascularisation.
Glede na to, da je nadaljnja konsistentnost dokazana za sekundarne spremenljivke, je indikacijo smiselno razširiti z » zmanjševanja pojavnosti MI « na » zmanjševanje pojavnosti srčnih zapletov «, torej na termin, ki vključuje bolnike, ki so v preteklosti že imeli miokardni infarkt in/ ali revaskularizacijo.
In the light of the above the CHMP concludes that the proposed indication for Coversyl “ Stable coronary artery disease:
V skladu z zgoraj navedenim CHMP zaključuje, da je predlagana indikacija za zdravilo Coversyl » Stabilna koronarna arterijska bolezen:
Reduction of risk of cardiac events in patients with a history of myocardial infarction and/ or revascularisation” is adequately supported by the information provided.
Zmanjševanje tveganja za srčne zaplete pri bolnikih, ki so v preteklosti že imeli miokardni infarkt in/ ali revaskularizacijo « s predloženimi informacijami ustrezno podprta.
Overall conclusion on benefit/ risk
Celostni sklep glede razmerja med koristmi in tveganji
At its meeting of 25-28 July 2005, the CHMP considered the data on efficacy presented by the MAHs and concluded that it had been shown that Coversyl and associated names was effective in the reduction of risk of cardiac events in patients with stable coronary artery disease with a history of myocardial infarction and/ or revascularisation.
Na svojem sestanku v dneh od 25. do 28. julija 2005 je CHMP pretehtal podatke o učinkovitosti, ki so jih predložili imetniki dovoljenja za promet z zdravilom, ter sklenil, da je bilo dokazano, da je zdravilo Coversyl in z njim povezana imena učinkovito pri zmanjševanju tveganja za srčne zaplete pri bolnikih
6  EMEA 2005 GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS
7 EMEA 2005 PODLAGA ZA DOPOLNILO POVZETKA GLAVNIH ZNAČILNOSTI ZDRAVILA
Whereas, • the CHMP considered the referral made under article 6.12 of Commission Regulation (EC) No 1084/ 2003, for Coversyl and associated names (see Annex I), • The MAH has implemented the text proposed by the CHMP in the SPC: • It is proposed to add the following indication in section 4.1: “ Stable coronary artery disease:
1084/ 2003 za zdravilo Coversyl in z njim povezana imena (glej Dodatek I), • je imetnik dovoljenja za promet z zdravilom v Povzetek glavnih značilnosti vključil besedilo, ki ga je predlagal CHMP:
Reduction of risk of cardiac events in patients with a history of myocardial infarction and/ or revascularisation .”
Zmanjševanje tveganja za srčne zaplete pri bolnikih, ki so v preteklosti že imeli miokardni infarkt in/ ali revaskularizacijo. «
• The posology in Section 4.2 has been updated as follows:
Odmerjanje v poglavju 4. 2 je bilo posodobljeno kot sledi:
Elderly patients should receive 2 mg once daily for one week, then 4 mg once daily the next week, before increasing the dose up to 8 mg once daily depending on renal function (see Table 1 “ Dosage adjustment in renal impairment”).
Starejši bolniki naj dobivajo 2 mg enkrat dnevno v obdobju enega tedna, nato 4 mg enkrat dnevno naslednji teden, preden se odmerek poveča na 8 mg enkrat dnevno, v odvisnosti od ledvične funkcije (glej tabelo 1 » Prilagajanje odmerka v primeru prizadetosti ledvic «).
• A warning has been introduced in Section 4.4:
V poglavju 4. 4 je bilo dodano opozorilo:
Stable coronary artery disease:
Stabilna arterijska koronarna bolezen:
If an episode of unstable angina pectoris (major or not) occurs during the first month of perindopril treatment, a careful appraisal of the benefit/ risk should be performed before treatment continuation.
V primeru epizode nestabilne angine pektoris (večje ali manjše) v prvem mesecu zdravljenja s perindoprilom je potrebno pred nadaljevanjem zdravljenja skrbno pretehtati koristi in tveganja.
• The following description of the observed side-effects has been added in Section 4.8:
V poglavju 4. 8 je bil dodan naslednji opis opaženih neželenih stranskih učinkov:
Clinical trials:
Klinična preizkušanja:
During the randomised period of the EUROPA study, only serious adverse events were collected.
V randomiziranem obdobju študije EUROPA so beležili le resne neželene stranske učinke.
16 (0.3%) of the 6122 perindopril patients and 12 (0.2%) of the 6107 placebo patients.
Pri maloštevilnih bolnikih je prišlo do resnih neželenih stranskih učinkov: pri 16 (0, 3%) med 6122 bolniki, ki so prejemali perindopril, in pri 12 (0, 2%) med 6107 bolniki, ki so prejemali placebo.
More patients withdrew for cough, hypotension or other intolerance on perindopril than on placebo, 6.0% (n=366) versus 2.1% (n=129) respectively.
6, 0% (n=366) proti 2, 1% (n=129).
• Section 5.1 has been updated to include the results of the EUROPA trial as follows:
Poglavje 5. 1 je bilo posodobljeno tako, da vključuje rezultate študije EUROPA kot sledi:
The EUROPA study was a multicentre, international, randomised, double-blind, placebo- controlled clinical trial lasting 4 years.
Študija EUROPA je bilo mednarodno multicentrično, randomizirano, dvojno slepo klinično preizkušanje, nadzorovano s placebom, ki je trajalo 4 leta.
Overall, 90% of the patients had a previous myocardial infarction and/ or a previous coronary revascularisation.
Celotno gledano je 90% bolnikov v preteklosti že imelo miokardni infarkt in/ ali koronarno revaskularizacijo.
Most of the patients received the study medication on top of conventional therapy including platelet inhibitors, lipid lowering agents and beta-blockers.
Večina bolnikov je prejemala v študiji obravnavano zdravilo poleg klasične terapije, ki je vključevala zaviralce agregacije trombocitov, zdravila za zmanjšanje ravni serumskih lipidov ter zaviralce beta.
The main efficacy criterion was the composite of cardiovascular mortality, non fatal myocardial infarction and/ or cardiac arrest with successful resuscitation.
Glavni kriterij učinkovitosti je bila pojavnost kardiovaskularne smrtnosti, nesmrtnega miokardnega infarkta in/ ali zaustavitev srca z uspešnim oživljanjem.
The treatment with perindopril 8 mg once daily resulted in a significant absolute reduction in the primary endpoint of 1.9% (relative risk reduction of 20%, 95%CI [9.4; 28.6] – p < 0.001).
Zdravljenje s perindoprilom v odmerku 8 mg enkrat dnevno je privedlo do pomembnega absolutnega zmanjšanja pogostosti primarnega izida za 1, 9% (relativno zmanjšanje tveganja za 20%, 95% interval zaupanja [9. 4; 28. 6] – p < 0. 001).
In patients with a history of myocardial infarction and/ or revascularisation, an absolute reduction of 2.2% corresponding to a RRR of 22.4% (95%CI [12.0; 31.6] – p < 0.001) in the primary endpoint was observed by comparison to placebo.
zmanjšanju tveganja za 22, 4% (95% interval zaupanja [12. 0; 31. 6] – p < 0. 001), v primerjavi s placebom.
7  EMEA 2005 • no untoward safety findings related to the extension of the indication have been identified.
• ugotovljene niso bile nikakršne neugodne ugotovitve v zvezi z varnostjo, povezane z razširitvijo indikacije,
• the CHMP, as a consequence, considered the benefit/ risk balance for the above-mentioned extension of indication to be favourable,
• je CHMP posledično menil, da je razmerje med tveganji in koristmi za zgoraj omenjeno razširitev indikacije ugodno.
8  EMEA 2005 ANNEX III
9 EMEA 2005 DODATEK III
< COVERSYL and associated names (see Annex I) > ,< strength >, tablets
< COVERSYL in sorodna imena (glejte dodatek I) >, < jakost >, tablete
< [See Annex I - to be completed nationally] >
< [Glejte dodatek I – izpolniti nacionalno] >
< COVERSYL and associated names > 2 mg:
KAKOVOSTNA IN KOLIČINSKA SESTAVA
2 mg perindopril tert-butylamine salt, equivalent to 1.669 mg perindopril
2 mg terc- butilaminijevega perindoprilata, kar ustreza 1, 669 mg perindoprila.
2 mg perindopril tert-butylamine salt, equivalent to 1.669 mg perindopril< [To be completed nationally] >
2 mg terc- butilaminijevega perindoprilata, kar ustreza 1, 669 mg perindoprila. < [Izpolniti nacionalno] >
< [To be completed nationally] >
< [Izpolniti nacionalno] >
Treatment of hypertension
Zdravljenje hipertenzije.
Treatment of symptomatic heart failure
Zdravljenje simptomatičnega srčnega popuščanja.
Reduction of risk of cardiac events in patients with a history of myocardial infarction and/ or revascularisation.
Zmanjševanje tveganja za srčnožilne dogodke pri bolnikih z miokardnim infarktom ali revaskularizacijo ali obema v anamnezi.
It is recommended that< COVERSYL and associated names > is taken once daily in the morning before a meal.
< COVERSYL in sorodna imena > je priporočljivo jemati enkrat na dan zjutraj pred obrokom.
The dose should be individualised according to the patient profile (see 4.4 “ Special warnings and special precautions for use”) and blood pressure response.
Odmerek prilagodite bolnikovemu profilu (glejte poglavje 4. 4 Posebna opozorila in previdnostni ukrepi) in odzivu krvnega tlaka.
Hypertension :< COVERSYL and associated names > may be used in monotherapy or in combination with other classes of antihypertensive therapy.
Hipertenzija: < COVERSYL in sorodna imena > lahko uporabljate v monoterapiji ali kombinaciji z drugimi razredi antihipertenzivnih zdravljenj.
Patients with a strongly activated renin-angiotensin-aldosterone system (in particular, renovascular hypertension, salt and/ or volume depletion, cardiac decompensation or severe hypertension) may experience an excessive drop in blood pressure following the initial dose.
Bolnikom z močno aktiviranim renin- angiotenzin- aldosteronskim sistemom (zlasti z renovaskularno hipertenzijo, izgubo soli ali hipovolemijo ali obema, dekompenzacijo srca ali hudo hipertenzijo) se lahko preveč zniža krvni tlak po prvem odmerku.
10  EMEA 2005 The dose may be increased to 8 mg once daily after one month of treatment.
11 EMEA 2005 Po enem mesecu zdravljenja lahko odmerek povečate na 8 mg enkrat na dan.
Symptomatic hypotension may occur following initiation of therapy with< COVERSYL and associated names >; this is more likely in patients who are being treated concurrently with diuretics.
Verjetnejša je pri bolnikih, ki sočasno jemljejo diuretike.
Caution is therefore recommended since these patients may be volume and/ or salt depleted.
Priporočljiva je previdnost, saj imajo lahko tovrstni bolniki izgubo volumna ali soli ali obeh.
If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with< COVERSYL and associated names > (see section 4.4 “Special warnings and special precautions for use”).
Če je mogoče, diuretik ukinite 2 do 3 dni pred začetkom zdravljenja z zdravilom < COVERSYL in sorodna imena > (glejte poglavje 4. 4 Posebna opozorila in previdnostni ukrepi).
In hypertensive patients in whom the diuretic cannot be discontinued, therapy with< COVERSYL and associated names > should be initiated with a 2 mg dose.
Bolnikom s hipertenzijo, pri katerih diuretika ne morete ukiniti, zdravljenje z zdravilom < COVERSYL in sorodna imena > uvedite z odmerkom po 2 mg.
The subsequent dosage of< COVERSYL and associated names > should be adjusted according to blood pressure response.
Nadaljnje odmerjanje zdravila < COVERSYL in sorodna imena > prilagajajte glede na odziv krvnega tlaka.
It is recommended that< COVERSYL and associated names >, generally associated with a non- potassium-sparing diuretic and/or digoxin and/or a beta blocker, be introduced under close medical supervision with a recommended starting dose of 2 mg taken in the morning.
Simptomatično srčno popuščanje: < COVERSYL in sorodna imena > je priporočljivo uvajati pod strogim zdravniškim nadzorom in v priporočenem začetnem odmerku 2 mg zjutraj, in sicer običajno ob diuretikih, ki ne zadržujejo kalija, digoksinu, blokatorjih beta receptorjev ali vseh.
In severe heart failure and in other patients considered to be at high risk (patients with impaired renal function and a tendency to have electrolyte disturbances, patients receiving simultaneous treatment with diuretics and/ or treatment with vasodilating agents), treatment should be initiated under careful supervision (see 4.4 “ Special warnings and special precautions for use”).
Pri bolnikih s hudim srčnim popuščanjem in pri drugih zelo rizičnih skupinah (ledvično popuščanje in nagnjenost k motnjam ravnovesja elektrolitov; sočasno jemanje diuretikov, vazodilatatorjev ali obojih) mora uvedba zdravljenja potekati pod strogim zdravniškim nadzorom (glejte poglavje 4. 4 Posebna opozorila in previdnostni ukrepi).
Patients at high risk of symptomatic hypotension e. g. patients with salt depletion with or without hyponatraemia, patients with hypovolaemia or patients who have been receiving vigorous diuretic therapy should have these conditions corrected, if possible, prior to therapy with< COVERSYL and associated names >.
Bolnikom, ki jih spremlja veliko tveganje za simptomatično hipotenzijo (z izgubo soli s hiponatremijo ali brez nje), hipovolemija ali intenzivno jemljejo diuretike, morate tovrstna stanja odpraviti pred uvedbo zdravila < COVERSYL in sorodna imena >, če je mogoče.
Blood pressure, renal function and serum potassium should be monitored closely, both before and during treatment with< COVERSYL and associated names > (see section 4.4 “Special warnings and special precautions for use”).
Pozorno morate spremljati krvni tlak, ledvično delovanje in raven kalija v serumu že pred zdravljenjem z zdravilom < COVERSYL in sorodna imena > in med njim (glejte poglavje 4. 4 Posebna opozorila in previdnostni ukrepi).
Stable coronary artery disease :< COVERSYL and associated names > should be introduced at a dose of 4 mg once daily for two weeks, then increased to 8 mg once daily, depending on renal function and provided that the 4 mg dose is well tolerated.
Bolnikom s stabilno koronarno arterijsko boleznijo uvedite zdravilo < COVERSYL in sorodna imena > po 4 mg enkrat na dan za dva tedna, nato odmerek povečajte na 8 mg enkrat na dan, odvisno od delovanja ledvic in če bolniki odmerek po 4 mg dobro prenašajo.
The dose should be increased only if the previous lower dose is well tolerated.
Starejši bolniki naj jemljejo odmerek 2 mg enkrat na dan en teden, nato 4 mg enkrat na dan naslednji teden, potem pa odmerek povečajte do 8 mg enkrat na dan, odvisno od delovanja ledvic (glejte preglednico 1 Prilagajanje odmerka pri bolnikih z ledvičnim popuščanjem).
Table 1: dosage adjustment in renal impairment
12 EMEA 2005 Preglednica 1.
creatinine
Prilagajanje odmerka pri bolnikih z ledvičnim popuščanjem
clearance (ml/ min) ClCR ≥ 60
Očistek kreatinina (ml/ min) očistek kreatinina ≥ 60 30 < očistek kreatinina < 60 15 < očistek kreatinina < 30 bolniki na hemodializi *
recommended dose 4 mg per day
Priporočeni odmerek 4 mg na dan 2 mg na dan 2 mg vsak drug dan
ClCR < 15
očistek kreatinina < 15
2 mg on the day of dialysis
2 mg na dan dialize
* Dialysis clearance of perindoprilat is 70 ml/ min.
* Dializni očistek perindoprilata je 70 ml/ min.
11  EMEA 2005 Dosage adjustment in hepatic impairment:
Prilagajanje odmerka pri bolnikih z jetrnim popuščanjem:
No dosage adjustment is necessary in patients with hepatic impairment (see sections 4.4 “ Special warnings and special precautions for use” and 5.2 “ Pharmacokinetic properties”) Paediatric use:
Bolnikom z jetrnim popuščanjem ni potrebno prilagajati odmerka (glejte poglavji 4. 4 Posebna opozorila in previdnostni ukrepi in 5. 2 Farmakokinetične lastnosti).
• Hypersensitivity to perindopril, to any of the excipients or to any other ACE inhibitor; • History of angioedema associated with previous ACE inhibitor therapy; • Hereditary or idiopathic angioedema; • Second and third trimesters of pregnancy (see 4.6 “ Pregnancy and lactation”).
• Preobčutljivost za perindopril, katero od pomožnih snovi ali katerikoli drug zaviralec angiotenzinske konvertaze. • Angioedem v anamnezi, povezan s predhodnim zdravljenjem z zaviralci angiotenzinske konvertaze. • Dedni ali idiopatični angioedem. • Drugo in tretje trimesečje nosečnosti (glejte poglavje 4. 6 Nosečnost in dojenje).
If an episode of unstable angina pectoris (major or not) occurs during the first month of perindopril treatment, a careful appraisal of the benefit/ risk should be performed before treatment continuation.
Če bolnik v prvem mesecu zdravljenja s perindoprilom doživi epizodo nestabilne angine pektoris (hujšo ali ne), morate pred nadaljevanjem zdravljenja pazljivo oceniti razmerje med koristnostjo in tveganjem.
Symptomatic hypotension is seen rarely in uncomplicated hypertensive patients and is more likely to occur in patients who have been volume- depleted e. g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting, or who have severe renin-dependent hypertension (see sections 4.5 “ Interaction with other medicaments and other forms of interaction” and 4.8 “ Undesirable effects”).
Simptomatična hipotenzija je redka pri bolnikih s hipertenzijo brez zapletov, verjetnejša pa pri tistih s hipovolemijo, na primer zaradi zdravljenja z diuretiki, omejitve soli v prehrani, dialize, driske ali bruhanja, ali pri vseh s hudo reninsko odvisno hipertenzijo (glejte poglavji 4. 5 Medsebojno delovanje z drugimi zdravili in druge oblike interakcij in 4. 8 Neželeni učinki).
In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustment should be closely monitored (see 4.2 “ Posology and method of administration” and 4.8 “ Undesirable effects”).
Pri bolnikih s povečanim tveganjem za simptomatično hipotenzijo morate uvedbo zdravljenja in prilagajanje odmerka pazljivo nadzorovati (glejte poglavji 4. 2 Odmerjanje in način uporabe in 4. 8 Neželeni učinki).
In some patients with congestive heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with< COVERSYL and associated names >.
Pri nekaterih bolnikih s kongestivnim srčnim popuščanjem, ki imajo normalen ali nizek krvni tlak, lahko < COVERSYL in sorodna imena > dodatno zniža sistemski krvni tlak.
If hypotension becomes symptomatic, a reduction of dose or discontinuation of< COVERSYL and associated names > may be necessary.
Če hipotenzija postane simptomatična, je lahko potrebno zmanjšanje odmerka ali prekinitev zdravljenja z zdravilom < COVERSYL in sorodna imena >.
Aortic and mitral valve stenosis/ hypertrophic cardiomyopathy:
13 EMEA 2005 Bolniki z zožitvijo aorte in mitralne zaklopke ter hipertrofično kardiomiopatijo:
As with other ACE inhibitors ,< COVERSYL and associated names > should be given with caution to patients with mitral valve stenosis and obstruction in the outflow of the left ventricle such as aortic stenosis or hypertrophic cardiomyopathy.
Kot velja tudi za druge zaviralce angiotenzinske konvertaze, morate biti previdni pri predpisovanju zdravila < COVERSYL in sorodna imena > bolnikom z zožitvijo mitralne zaklopke in zaporo v iztočnem delu levega prekata, na primer z zožitvijo aorte, ali hipertrofično kardiomiopatijo.
Renal impairment:
Bolniki z ledvičnim popuščanjem:
In cases of renal impairment (creatinine clearance < 60 ml/ min) the initial perindopril dosage should be adjusted according to the patient’ s creatinine clearance (see 4.2 “ Posology and method of administration”) and then as a function of the patient’ s response to treatment.
Pri bolnikih z ledvičnim popuščanjem (očistek kreatinina < 60 ml/ min) morate začetni odmerek perindoprila prilagajati glede na bolnikov očistek kreatinina (glejte poglavje 4. 2 Odmerjanje in način uporabe) in nato kot funkcijo bolnikovega odziva na zdravljenje.
Routine monitoring of potassium and creatinine are part of normal medical practice for these patients (see 4.8 “ Undesirable effects”).
Rutinsko spremljanje ravni kalija in kreatinina je del običajne medicinske prakse pri tovrstnih bolnikih (glejte poglavje 4. 8 Neželeni učinki).
12  EMEA 2005 In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, who have been treated with ACE inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy, have been seen.
Pri nekaterih bolnikih z obojestransko zožitvijo ledvične arterije ali zožitvijo arterije v solitarno ledvico, ki so jemali zaviralce angiotenzinske konvertaze, so opazili povečanje vrednosti sečnine v krvi in kreatinina v serumu, ki je običajno izginilo po prekinitvi zdravljenja.
Since treatment with diuretics may be a contributory factor to the above, they should be discontinued and renal function should be monitored during the first weeks of< COVERSYL and associated names > therapy.
Ker lahko zdravljenje z diuretiki navedena stanja poslabša, jih morate ukiniti in spremljati delovanje ledvic v prvih tednih zdravljenja z zdravilom < COVERSYL in sorodna imena >.