natgillin/translations-raw huggingface dataset:
If you have pre-existing hypocalcaemia, it must be corrected before initiating the first dose of Zoledronic Acid Accord. 
Ako već imate hipokalcemiju, ona se mora korigirati prije uvođenja prve doze Zoledronatne kiseline Accord.
For instructions on the dilution of zoledronic acid before administration, see section 6.6. 
Za upute o razrjeđivanju zoledronatne kiseline prije primjene vidjeti dio 6.6.
Zoledronic Acid Accord 4 mg concentrate for solution for infusion, further diluted in 100 ml (see section 6.6), should be given as a single intravenous infusion in no less than 15 minutes. 
Zoledronatnu kiselinu Accord 4 mg koncentrat za otopinu za infuziju, dodatno razrijeđen u 100 ml (vidjeti dio 6.6), treba dati kao jednokratnu intravensku infuziju u trajanju od najmanje 15 minuta.
In long-term animal studies, zoledronic acid inhibits bone resorption without adversely affecting the formation, mineralization or mechanical properties of bone. 
U dugotrajnim ispitivanjima na životinjama, zoledronatna kiselina inhibirala je resorpciju kosti bez štetnog djelovanja na stvaranje, mineralizaciju ili mehanička svojstva kosti.
• Painful redness and/or swelling of the eye. 
• bolno crvenilo i/ili oticanje oka.
The diluted Zoledronic Acid Accord infusion solution should be used immediately in order to avoid microbial contamination. 
• Razrijeđenu otopinu Zoledronatne kiseline Accord za infuziju treba primijeniti odmah kako bi se izbjegla mikrobiološka kontaminacija.
Median time to onset of the first SRE was not reached in the zoledronic acid-treated arm at the end of the study and was significantly prolonged compared to placebo (p=0.007). 
Medijan vremena do nastupa prvog koštanog događaja nije dosegnut u skupini liječenoj zoledronatnom kiselinom do kraja ispitivanja i bio je značajno dulji u usporedbi s placebom (p=0,007).
• Severe kidney impairment (will normally be determined by your doctor with certain specific blood tests). 
• teško oštećenje funkcije bubrega (obično će ga utvrditi liječnik pomoću određenih specifičnih krvnih pretraga)
No pharmacokinetic data for zoledronic acid are available in patients with hypercalcaemia or in patients with hepatic insufficiency. 
Nema dostupnih farmakokinetičkih podataka za zoledronatnu kiselinu u bolesnika s hiperkalcemijom ili bolesnika sa insuficijencijom jetre.
• Thalidomide (a medicine used to treat a certain type of blood cancer involving the bone) or any other medicines which may harm your kidneys. 
• talidomid (lijek za liječenje određenih vrsta raka krvi koji zahvaća kost) ili neke druge lijekove koji mogu oštetiti bubrege
• Anti-angiogenic medicines (used to treat cancer), since the combination of these with zoledronic acid has been associated with an increased risk of osteonecrosis of the jaw (ONJ). 
• antiangiogene lijekove (primjenjuju se za liječenje raka), budući da je kombinacija ovih lijekova sa zoledronatnom kiselinom povezana s povećanim rizikom od osteonekroze čeljusti.
• Sudden coldness with fainting, limpness or collapse. 
• iznenadan osjećaj hladnoće s nesvjesticom, posrtanjem ili kolapsom.
The plasma protein binding is low, with the unbound fraction ranging from 60% at 2 ng/ml to 77% at 2000 ng/ml of zoledronic acid 
Vezanje za proteine plazme je nisko, s nevezanom frakcijom u rasponu od 60% kod 2 ng/ml do 77% kod 2000 ng/ml zoledronatne kiseline.
In the clinical studies, zoledronic acid treatment was resumed only when the creatinine level returned to within 10% of the baseline value (see section 4.4). 
U kliničkim je ispitivanjima liječenje zoledronatnom kiselinom nastavljeno tek kad se kreatinin vratio na vrijednosti unutar 10% početne vrijednosti (vidjeti dio 4.4).
Dyspnoea, cough, bronchoconstriction 
dispneja, kašalj, bronhokonstrikcija
Thrombocytopenia, leukopenia 
trombocitopenija, leukopenija
Patients received either 4 mg zoledronic acid or placebo every four weeks for one year. 
Bolesnici su primali zoledronatnu kiselinu u dozi od 4 mg ili placebo svaka četiri tjedna tijekom jedne godine.
- Hypersensitivity to the active substance, to other bisphosphonates or to any of the excipients listed in section 6.1 - Breast-feeding (see section 4.6) 
- Preosjetljivost na djelatnu tvar, druge bisfosfonate ili neku od pomoćnih tvari navedenih u dijelu 6.1 - Dojenje (vidjeti dio 4.6)
• If you are being treated to reduce the amount of calcium in your blood, you will normally only be given one infusion of Zoledronic Acid Accord. 
• Ako se liječite radi snižavanja količine kalcija u krvi, obično ćete dobiti samo jednu infuziju
• Aminoglycosides (medicines used to treat severe infections), calcitonin (a type of medicine used to treat post-menopausal osteoporosis and hypercalcaemia), loop diuretics (a type of medicine to treat high blood pressure or oedema) or other calcium-lowering medicines, since the combination of these with bisphosphonates may cause the calcium level in the blood to become too low. 
• aminoglikozide (lijekovi za liječenje teških infekcija), kalcitonin (vrsta lijeka za liječenje postmenopauzalne osteoporoze i hiperkalcemije), diuretici Henleove petlje (vrsta lijekova za liječenje visokog krvnog tlaka ili edema) ili drugi lijekovi koji snizuju razinu kalcija, budući da kombinacija ovih lijekova s bisfosfonatima može dovesti do preniskih razina kalcija u krvi
Aseptic techniques must be followed during the preparation of the infusion. 
Tijekom pripreme infuzije moraju se koristiti aseptičke tehnike.
Blood creatinine and blood urea increased, hypocalcaemia 
povišeni kreatinin i urea u krvi, hipokalcemija
Adverse reactions, such as dizziness and somnolence, may have influence on the ability to drive or use machines, therefore caution should be exercised with the use of Zoledronic Acid Accord along with driving and operating of machinery. 
Nuspojave poput omaglice i pospanosti mogu utjecati na sposobnost upravljanja vozilima i rada na strojevima te je stoga potreban oprez kad se tijekom primanja Zoledronatne kiseline Accord upravlja vozilima i radi sa strojevima.
Very common Hypocalcaemia Common: 
Vrlo često: hipokalcemija Često:
• Since no data are available on the compatibility of Zoledronic Acid Accord with other intravenously administered substances, Zoledronic Acid Accord must not be mixed with other medications/substances and should always be given through a separate infusion line. 
• Budući da nema dostupnih podataka o kompatibilnosti Zoledronatne kiseline Accord s drugim tvarima za intravensku primjenu, Zoledronatna kiselina Accord se ne smije miješati s drugim lijekovima/tvarima i uvijek se mora primjenjivati kroz zasebnu infuzijsku liniju.
After initiating the infusion of zoledronic acid, the plasma concentrations of zoledronic acid rapidly increased, achieving their peak at the end of the infusion period, followed by a rapid decline to < 10% of peak after 4 hours and < 1% of peak after 24 hours, with a subsequent prolonged period of very low concentrations not exceeding 0.1% of peak prior to the second infusion of zoledronic acid on day 28. 
Nakon početka infuzije zoledronatne kiseline, koncentracija zoledronatne kiseline u plazmi brzo se povisila i postigla vršnu vrijednost na kraju razdoblja infuzije, nakon čega je uslijedilo brzo sniženje na < 10% vršne vrijednosti nakon 4 sata te < 1% vršne vrijednosti nakon 24 sata, a potom produljeno razdoblje vrlo niskih koncentracija koje nisu prelazile 0,1% vršne vrijednosti prije druge infuzije zoledronatne kiseline 28. dana.
Zoledronic Acid Accord contains the same active substance as found in Aclasta (zoledronic acid). 
Zoledronatnom kiselinom Accord sadrži istu djelatnu tvar koja se nalazi u Aclasti (zoledronatna kiselina).
Zoledronic acid is not recommended for patients presenting with severe renal impairment prior to initiation of therapy, which is defined for this population as CLcr < 30 ml/min. 
Zoledronatna kiselina ne preporučuje se u bolesnika koji prije početka liječenja imaju teško oštećenje funkcije bubrega, koje se u ove populacije definira kao klirens kreatinina < 30 ml/min.
• Other medicines that also contain zoledronic acid and are used to treat osteoporosis and other non-cancer diseases of the bone, or any other bisphosphonate, since the combined effects of these medicines taken together with Zoledronic Acid Accord are unknown. 
• druge lijekove koji također sadrže zoledronatnu kiselinu i koriste se za liječenje osteoporoze i drugih bolesti kostiju koje nisu uzrokovane rakom ili bilo koji drugi bisfosfonat, budući da kombinirani učinci ovih lijekova kad se uzimaju zajedno sa Zoledronatnom kiselinom Accord nisu poznati
Animal reproduction studies with zoledronic acid have shown reproductive toxicity (see section 5.3). 
Ispitivanja zoledronatne kiseline na životinjama pokazala su da postoji reproduktivna toksičnost (vidjeti dio 5.3).
The European Medicines Agency has waived the obligation to submit the results of studies with the reference product containing zoledronic acid in all subsets of the paediatric population in the treatment of tumour-induced hypercalcaemia and prevention of skeletal-related events in patients with advanced malignancies involving bone (see section 4.2 for information on paediatric use). 
Europska agencija za lijekove je izuzela obvezu podnošenja rezultata ispitivanja referentnog lijeka koji sadrži zoledronatnu kiselinu u svim podskupinama pedijatrijske populacije u liječenju hiperkalcemije izazvane tumorom i sprječavanju događaja povezanih s koštanim sustavom u bolesnika s uznapredovalom zloćudnom bolešću koja zahvaća kosti (vidjeti dio 4.2 za informacije o pedijatrijskoj primjeni).
Following initiation of therapy, serum creatinine should be measured prior to each dose of zoledronic acid and treatment should be withheld if renal function has deteriorated. 
Nakon početka liječenja kreatinin u serumu treba mjeriti prije primjene svake doze zoledronatne kiseline, a liječenje treba obustaviti ako se funkcija bubrega pogorša.
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 
UVJETI ILI OGRANIČENJA VEZANI ZA SIGURNU I UČINKOVITU PRIMJENU LIJEKA
• Irregular heart rhythm (atrial fibrillation) has been seen in patients receiving zoledronic acid for postmenopausal osteoporosis. 
• nepravilan srčani ritam (fibrilacija atrija) opažen je u bolesnica koje su primale zoledronatnu kiselinu zbog postmenopauzalne osteoporoze.
Within three days after zoledronic acid administration, an acute phase reaction has commonly been reported, with symptoms including bone pain, fever, fatigue, arthralgia, myalgia, rigors and arthritis with subsequent joint swelling; these symptoms usually resolve within a few days (see description of selected adverse reactions). 
Tijekom tri dana nakon primjene zoledronatne kiseline često je zabilježena reakcija akutne faze sa simptomima koji uključuju bol u kostima, vrućicu, umor, artralgiju, mialgiju, tresavicu i artritis s posljedičnim oticanjem zglobova; ti se simptomi obično povuku u roku od nekoliko dana (vidjeti opis odabranih nuspojava).
The recommended dose in hypercalcaemia (albumin-corrected serum calcium ≥12.0 mg/dl or 3.0 mmol/l) is a single dose of 4 mg zoledronic acid. 
Preporučena doza kod hiperkalcemije (serumski kalcij korigiran za albumin ≥ 12,0 mg/dl ili 3,0 mmol/l) je jednokratna doza od 4 mg zoledronatne kiseline.
Additionally, there have been sporadic reports of osteonecrosis of other sites, including the hip and femur, reported predominantly in adult cancer patients treated with Zoledronic Acid . 
Dodatno, bilo je sporadičnih prijava osteonekroze drugih anatomskih mjesta, uključujući kuk i bedrenu kost, koje su bile prijavljene pretežno u odraslih bolesnika oboljelih od raka liječenih Zoledronatnu kiselina.
The onset time is ≤ 3 days post-zoledronic acid infusion, and the reaction is also referred to using the terms “flu-like” or “post-dose” symptoms. 
Vrijeme nastupa je ≤3 dana nakon infuzije Zomete, a reakcija se još zove “sindrom sličan gripi” ili simptomi “nakon doziranja”.
Hypophosphataemia 1 Adverse events occurring with frequencies < 5% were medically assessed and it was shown that these cases are consistent with the well established safety profile of zoledronic acid (see section 4.8) 
hipofosfatemija 1 Nuspojave koje nastaju učestalošću < 5% bile su medicinski procijenjene i pokazalo se da su u skladu s dobro utvrđenim sigurnosnim profilom zoledronatne kiseline (vidjeti dio 4.8).
Hypersensitivity reaction 
reakcija preosjetljivosti
Intravenous use after dilution. 
Primjena u venu nakon razrjeđenja.
In clinical studies, zoledronic acid has been administered concomitantly with commonly used anticancer agents, diuretics, antibiotics and analgesics without clinically apparent interactions occurring. 
U kliničkim se ispitivanjima zoledronatna kiselina primjenjivala istodobno s često davanim antitumorskim lijekovima, diureticima, antibioticima i analgeticima bez klinički vidljivih interakcija.
Intravenously administered zoledronic acid is eliminated by a triphasic process: rapid biphasic disappearance from the systemic circulation, with half-lives of t½α 0.24 and t½β 1.87 hours, followed by a long elimination phase with a terminal elimination half-life of t½γ 146 hours. 
Intravenski primijenjena zoledronatna kiselina eliminira se procesom u tri faze: brzim bifazičnim nestankom iz sistemskog krvotoka, uz poluvijek t1/2α od 0,24 sata i t1/2β od 1,87 sati, za kojim slijedi dugotrajna faza eliminacije uz terminalni poluvijek eliminacije t1/2γ od 146 sati.
The imbalance observed in this trial has not been observed in other trials with zoledronic acid, including those with zoledronic acid 4 mg every 3-4 weeks in oncology patients. 
Opažena neravnoteža u ovom ispitivanju nije bila primijećena u drugim ispitivanjima zoledronatne kiseline, uključujući ispitivanja zoledronatne kiseline u dozi od 4 mg primijenjene svaka 3-4 tjedna u onkoloških bolesnika.
5-ml plastic vial made of clear, cycloolefine copolymer with chlorobutyl rubber stopper and aluminium cap with flip-off component. 
Plastična bočica od 5 ml izrađena od prozirnog cikloolefinskog kopolimera s čepom od klorobutilne gume i aluminijskim poklopcem s „flip-off“ dijelom.
During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture. 
Bolesnicima treba savjetovati da tijekom liječenja bisfosfonatima prijave svaki bol u natkoljenici, kuku ili preponama, i svakog bolesnika s takvim simptomima treba pregledati na nepotpuni prijelom bedrene kosti.
In the clinical programme patients aged 1 to < 3 years received 0.025 mg/kg zoledronic acid (up to a maximum single dose of 0.35 mg) every 3 months and patients aged 3 to 17 years received 0.05 mg/kg zoledronic acid (up to a maximum single dose of 0.83 mg) every 3 months. 
Bolesnici uključeni u klinički program u dobi od 1 do < 3 godine primali su 0,025 mg/kg zoledronatne kiseline (do najveće jednokratne doze od 0,35 mg) svaka 3 mjeseca, a bolesnici u dobi od 3 do 17 godina primali su 0,05 mg/kg zoledronatne kiseline (do najviše jednokratne doze od 0,83 mg) svaka 3 mjeseca.
• if you are allergic to zoledronic acid, another bisphosphonate (the group of substances to which Zoledronic Acid Accord belongs), or any of the other ingredients of this medicine 
• ako ste alergični (preosjetljivi) na zoledronatnu kiselinu, drugi bisfosfonat (skupina tvari kojoj pripada Zoledronatna kiselina Accord) ili neki drugi sastojak ovog lijeka (naveden u dijelu 6).
• The active substance is zoledronic acid. 
• Djelatna tvar je zoledronatna kiselina.
Statistically significant differences are marked (*p< 0.05) for between treatment comparisons (4 mg zoledronic acid vs. 
Označene su statistički značajne razlike (*p<0,05) između dvije terapije (zoledronatna kiselina u dozi od 4 mg nasuprot placebu)
• Zoledronic Acid Accord must only be given by healthcare professionals trained in administering bisphosphonates intravenously, i.e. through a vein. 
• Zoledronatnu kiselinu Accord smije davati samo zdravstveni djelatnici iskusni u davanju bisfosfonata intravenskim putem, tj. u venu.
4.1 ml for 3.3 mg dose 
- 4,1 ml za dozu od 3,3 mg
Median time to SRE (days) 
Vrijeme u ispitivanju (tjedni)
Zoledronic acid 4 mg was also studied in a double-blind, randomised, placebo-controlled trial in 228 patients with documented bone metastases from breast cancer to evaluate the effect of 4 mg zoledronic acid on the skeletal related event (SRE) rate ratio, calculated as the total number of SRE events (excluding hypercalcaemia and adjusted for prior fracture), divided by the total risk period. 
Zoledronatna kiselina od 4 mg također se ispitivala u dvostruko slijepom, randomiziranom, placebom kontroliranom ispitivanju u 228 bolesnika s potvrđenim koštanim metastazama karcinoma dojke da bi se procijenio učinak zoledronatne kiseline u dozi od 4 mg na omjer stope koštanih događaja izračunatog kao ukupni broj koštanih događaja (bez hiperkalcemije i prilagođen s obzirom na prethodne prijelome) podijeljen s ukupnim rizičnim razdobljem.
Zoledronic acid has been associated with reports of renal dysfunction. 
Zoledronatna kiselina povezuje se s prijavama poremećaja funkcije bubrega.
MARKETING AUTHORISATION NUMBER(S) EU/1/13/834/001- 1vial pack EU/1/13/834/002- 4 vial pack EU/1/13/834/003- 10 vial pack 
EU/1/13/834/001- pakiranje s 1 bočicom EU/1/13/834/002- pakiranje sa 4 bočice EU/1/13/834/003- pakiranje s 10 bočica
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 16.01.2014 
DATUM PRVOG ODOBRENJA/DATUM OBNOVE ODOBRENJA
The active substance in Zoledronic Acid Accord is zoledronic acid, which belongs to a group of substances called bisphosphonates. 
Djelatna tvar u Zoledronatnoj kiselini Accord je zoledronatna kiselina, koja pripada skupini tvari koje se zovu bisfosfonati.
Zoledronic acid treatment should be resumed at the same dose as that given prior to treatment interruption. 
Liječenje zoledronatnom kiselinom treba nastaviti istom dozom koja se davala prije prekida liječenja.
In patients with bone metastases presenting with mild to moderate renal impairment prior to initiation of therapy, which is defined for this population as CLcr 30-60 ml/min, the following zoledronic acid dose is recommended (see also section 4.4): 
U bolesnika s metastazama u kostima koji prije početka liječenja imaju blago do umjereno oštećenje funkcije bubrega, koje se u ove populacije definira kao klirens kreatinina od 30 do 60 ml/min, preporučuje se sljedeća doza zoledronatne kiseline (vidjeti također dio 4.4):
Reduced levels of calcium in the blood (hypocalcaemia), sometimes leading to muscle cramps, dry skin, burning sensation, have been reported in patients treated with Zoledronic Acid Accord. 
Smanjene razine kalcija u krvi (hipokalcemija), što ponekad dovodi do mišićnih grčeva, suhe kože, osjećaja peckanja, zabilježene su u bolesnika koji su liječeni Zoledronatnom kiselinom Accord.
The following are the important identified risks with zoledronic acid in the approved indications: Renal function impairment, osteonecrosis of the jaw, acute phase reaction, hypocalcaemia, atrial fibrillation, anaphylaxis, interstitial lung disease. 
Utvrđeni su sljedeći važni rizici primanja zoledronatne kiseline u odobrenim indikacijama: oštećenje funkcije bubrega, osteonekroza čeljusti, reakcija akutne faze, hipokalcemija, fibrilacija atrija, anafilaksija, intersticijska bolest pluća.
Based on the review of both clinical trial and post-marketing cases, there is sufficient evidence to support an association between zoledronic acid therapy, the reported event of hypocalcaemia, and the secondary development of cardiac arrhythmia. 
Na osnovu ocjenjivanja kliničkog ispitivanja i slučajeva nakon stavljanja lijeka na tržište postoji dovoljno dokaza koji ukazuju na povezanost između terapije zoledronatnom kiselinom, prijavljenih slučajeva hipokalcemije i posljedičnog razvoja srčane aritmije.
Caution is advised when Zolendronc Acid Accord is administered with medicinal products known to cause hypocalcaemia, as they may have a synergistic effect resulting in severe hypocalcaemia (see section 4.5). 
Savjetuje se oprez kod primjene Zoledronatne kiseline Accord s lijekovima za koje je poznato da uzrokuju hipokalcemiju budući da mogu imati sinergistički učinak s posljedičnom teškom hipokalcemijom (vidjeti dio 4.5).
Excipients: mannitol (E421), sodium citrate and water for injections. 
Pomoćne tvari: manitol (E421), natrijev citrat i voda za injekcije.
Convulsions, hypoaesthesia and tetany (secondary to hypocalcaemia) 
konvulzije, hipoestezija, tetanija (uzrokovana hipokalcemijom)
Pain in extremities, arthralgia, musculoskeletal pain 
bol u ekstremitetima, artralgija, mišićno-koštana bol
What Zoledronic Acid Accord looks like and contents of the pack Zoledronic Acid Accord is supplied as a liquid concentrate in a vial. 
Kako Zoledronatna kiselina Accord izgleda i sadržaj pakiranja Zoledronatna kiselina Accord isporučuje se kao tekući koncentrat u bočici.
From a microbiological point of view, the diluted solution for infusion should be used immediately. 
S mikrobiološkog stajališta, razrijeđena otopina za infuziju treba se odmah primijeniti.
Increases in serum creatinine also occur in some patients with chronic administration of zoledronic acid at recommended doses for prevention of skeletal related events, although less frequently. 
U nekih bolesnika dolazi do povišenja kreatinina u serumu i kod kronične primjene zoledronatne kiseline u dozama koje se preporučuju za sprječavanje koštanih događaja, iako manje često.
3.8 ml for 3.0 mg dose 
- 3,8 ml za dozu od 3,0 mg
Median time to relapse (re-increase of albumin-corrected serum calcium ≥ 2.9 mmol/l) was 30 to 40 days for patients treated with zoledronic acid versus 17 days for those treated with pamidronate 90 mg (p-values: 0.001 for 4 mg and 0.007 for 8 mg zoledronic acid). 
Medijan vremena do relapsa (ponovnog povišenja kalcija u serumu korigiranog za albumin ≥ 2,9 mmol/l) iznosio je 30 do 40 dana u bolesnika liječenih zoledronatnom kiselinom za razliku od 17 dana u onih liječenih pamidronatom u dozi od 90 mg (p-vrijednosti: 0,001 za 4 mg i 0,007 za 8 mg zoledronatne kiseline).
In view of the potential impact of zoledronic acid on renal function, the lack of clinical safety data in patients with severe renal impairment (in clinical trials defined as serum creatinine ≥ 400 µmol/l or ≥ 4.5 mg/dl for patients with TIH and ≥ 265 µmol/l or ≥ 3.0 mg/dl for patients with cancer and bone metastases, respectively) at baseline and only limited pharmacokinetic data in patients with severe renal impairment at baseline (creatinine clearance < 30 ml/min), the use of zoledronic acid is not recommended in patients with severe renal impairment. 
S obzirom na mogući utjecaj zoledronatne kiseline na funkciju bubrega, nedostatak kliničkih podataka o sigurnosti primjene u bolesnika s teškim oštećenjem funkcije bubrega (u kliničkim ispitivanjima definiranim kao kreatinin u serumu ≥ 400 μmol/l ili ≥ 4,5 mg/dl u bolesnika s hiperkalcemijom izazvanom tumorom, odnosno ≥ 265 μmol/l ili ≥ 3,0 mg/dl u bolesnika s rakom i metastazama u kostima) na početku liječenja i ograničene farmakokinetičke podatke u bolesnika s teškim oštećenjem funkcije bubrega (klirens kreatinina <30 ml/min) na početku liječenja, ne preporučuje se primjena zoledronatne kiseline u bolesnika s teškim oštećenjem funkcije bubrega.
• Difficulty in breathing with wheezing or coughing. 
• otežano disanje uz piskanje u plućima ili kašljanje.
The safety margins relative to renal effects were narrow in the long-term repeat-dose parenteral animal studies but the cumulative no adverse event levels (NOAELs) in the single dose (1.6 mg/kg) and multiple dose studies of up to one month (0.06-0.6 mg/kg/day) did not indicate renal effects at doses equivalent to or exceeding the highest intended human therapeutic dose. 
Dugotrajna ispitivanja ponovljene parenteralne doze u životinja pokazala su uzak raspon sigurnosti s obzirom na učinke na bubrege, ali najviša kumulativna doza koja ne uzrokuje oštećenje (NOAEL) u ispitivanjima jednostruke doze (1,6 mg/kg) i višestrukih doza u trajanju do jednog mjeseca (0,060,6 mg/kg na dan) nije imala učinke na bubrege pri dozama jednakima ili višima od najviše terapijske doze namijenjene ljudima.