natgillin/translations-raw huggingface dataset:
Therefore, the potential benefit and risks associated with continued therapy in patients who do not show haematological and/or clinical improvement after 2 treatment cycles should be assessed by the treating physician (see section 4.4).
Stoga nadležni liječnik treba procijeniti moguće koristi i rizike povezane s nastavkom liječenja u onih bolesnika u kojih nakon 2 ciklusa liječenja ne dođe do hematološkog i/ili kliničkog poboljšanja (vidjeti dio 4.4).
The concomitant use of medicinal products that have been associated with renal toxicity and those eliminated by tubular secretion such as NSAIDs, amphotericin B, methotrexate, aminosides, organoplatines, foscarnet, pentamidine, cyclosporin, tacrolimus, acyclovir and valganciclovir, should be avoided particularly during the 5 day clofarabine administration period; preference should be given to those medicinal products that are not known to be nephrotoxic (see sections 4.5 and 4.8).
metotreksat, aminozidi, spojevi platine, foskarnet, pentamidin, ciklosporin, takrolimus, aciklovir i valganciklovir, naročito tijekom petodnevnog razdoblja primjene klofarabina; prednost treba dati onim lijekovima za koje se zna da nisu nefrotoksični (vidjeti dijelove 4.5 i 4.8).
ORPHELIA Pharma
DRUGO ORPHELIA
If a patient experiences one or more severe toxicities (US National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Grade 3 toxicities excluding nausea and vomiting), treatment should be delayed until the toxicities resolve to baseline parameters or to the point where they are no longer severe and the potential benefit of continued treatment with clofarabine outweighs the risk of such continuation.
Common Toxicity Criteria, CTC) Američkog nacionalnog instituta za rak (NCI), izuzev mučnine i povraćanja), liječenje treba odgoditi sve dok se parametri toksičnosti ne vrate na početne vrijednosti ili dok se njihova težina ne ublaži do te mjere da moguća korist nastavka liječenja klofarabinom nadilazi rizik.
Occurrences of enterocolitis, including neutropaenic colitis, caecitis, and C. difficile colitis, have been reported during treatment with clofarabine.
Pojave enterokolitisa, uključujući neutropenijski kolitis, tiflitis i kolitis uzrokovan bakterijom C. difficile prijavljeni su tijekom liječenja klofarabinom.
200 ml *Each ml of concentrate contains 1 mg of clofarabine.
200 ml *Jedan ml koncentrata sadrži 1 mg klofarabina.
Haemorrhage, including cerebral, gastrointestinal and pulmonary haemorrhage, has been reported and may be fatal.
Prijavljena su krvarenja, uključujući cerebralno, gastrointestinalno i plućno krvarenje, koja mogu imati smrtni ishod.
Any patient who experiences a severe toxicity on a third occasion, a severe toxicity that does not recover within 14 days (see above for exclusions), or a life-threatening or disabling toxicity (US NCI CTC Grade 4 toxicity) should be withdrawn from treatment with clofarabine (see section 4.4).
U svih bolesnika u kojih se teška toksičnost pojavi po treći put, u kojih se teška toksičnost ne povuče u roku od 14 dana (vidjeti gore za iznimke) ili u slučaju pojave po život opasne ili onesposobljavajuće toksičnosti (toksičnost NCI CTC stupnja 4), mora se u potpunosti obustaviti liječenje klofarabinom
Common: Respiratory distress, epistaxis, dyspnoea, tachypnoea, cough
Poremećaji dišnog sustava, prsišta i sredoprsja često: respiratorni distres, epistaksa, dispneja, tahipneja, kašalj
(7.0 to -)
(7,0 do -)
Haemorrhage, including cerebral, gastrointestinal and pulmonary haemorrhage, has been reported and may be associated with a fatal outcome (see section 4.4).
Prijavljena su krvarenja, uključujući cerebralno, gastrointestinalno i plućno krvarenje, koja mogu biti povezana sa smrtnim ishodom (vidjeti dio 4.4).
Therefore, the potential benefit and risks associated with continued therapy in patients who do not show haematological and/or clinical improvement after 2 treatment cycles should be assessed by the treating physician.
Stoga nadležni liječnik treba procijeniti moguće koristi i rizike povezane s nastavkom liječenja u onih bolesnika u kojih nakon 2 ciklusa liječenja ne dođe do hematološkog i/ili kliničkog poboljšanja.
Ivozall is used to treat children (≥ 1 year old), teenagers and young adults up to 21 years old with acute lymphoblastic leukaemia (ALL) when previous treatments have not worked or have stopped working.
Ivozall se koristi za liječenje djece (u dobi ≥ 1 godine), tinejdžera i mladih odraslih ljudi u dobi do 21
Dosing commenced at 11.25 with escalation to 15, 30, 40, 52 and 70 mg/m2/day by intravenous infusion for 5 days every 2 to 6 weeks depending on toxicity and response.
15, 30, 40, 52 i 70 mg/m2 na dan, a primjenjivala se intravenskom infuzijom tijekom 5 dana svakih
The limited data available indicate that clofarabine may accumulate in patients with decreased creatinine clearance (see sections 4.4 and 5.2).
Oštećenje bubrežne funkcije Ograničeni dostupni podaci ukazuju na mogućnost akumulacije klofarabina u bolesnika sa smanjenim klirensom kreatinina (vidjeti dijelove 4.4 i 5.2).
Clofarabine should be discontinued immediately if patients show early signs or symptoms of SIRS, capillary leak syndrome or substantial organ dysfunction and appropriate supportive measures instituted.
Ako se u bolesnika pojave rani znakovi ili simptomi SIRS-a, sindroma povećane propusnosti kapilara ili značajnog poremećaja funkcije organa, mora se odmah prekinuti primjenu klofarabina i primijeniti odgovarajuće potporne mjere.
There are currently insufficient data to establish the safety and efficacy of clofarabine in adult patients (see section 5.2).
Odrasli bolesnici (uključujući starije osobe) Trenutno nema dovoljno podataka za utvrđivanje sigurnosti i djelotvornosti klofarabina u odraslih bolesnika (vidjeti dio 5.2).
The active substance is clofarabine.
Djelatna tvar je klofarabin.
Very common: Fatigue, pyrexia, mucosal inflammation Common: Multi-organ failure, systemic inflammatory response syndrome*, pain, chills, irritability, oedema, peripheral oedema, feeling hot, feeling abnormal
Opći poremećaji i reakcije na mjestu primjene vrlo često: umor, pireksija, upala sluznice često: višeorgansko zatajenje, sindrom sistemskog upalnog odgovora*, bol, zimica, razdražljivost, edem, periferni edem, osjećaj vrućine, neuobičajeno osjećanje
Very common (may affect more than 1 in 10 people): - anxiety, headache, fever, tiredness; - feeling and being sick, diarrhoea (loose bowels); - flushing, itching and inflamed skin, inflammation of mucus (moist) linings such as the mouth and other areas; - you may have more infections than normal because Ivozall can lower the number of certain types of blood cells in your body; - skin rashes which may be itchy, red, painful or peeling skin including palms of the hands and soles of the feet, or small reddish or purple spots underneath the skin.
- navale crvenila, svrbež i upaljena koža, upala sluznice poput usta i drugih područja; - možete imati više infekcija nego obično jer Ivozall može sniziti broj nekih vrsta krvnih stanica u tijelu; - kožni osip koji može svrbjeti, biti crven ili bolan, ljuštenje kože, uključujući dlanove i tabane, male crvenkaste ili ljubičaste mrlje ispod kože.
Each 20 ml vial contains 20 mg of clofarabine.
Jedna bočica od 20 ml sadrži 20 mg klofarabina.
Instructions for handling
15. UPUTE ZA UPORABU
How to store Ivozall
Kako čuvati lijek Ivozall
Overall remission (OR) Rate
Stopa ukupne remisije (UR)
Responses were seen in different immunophenotypes of ALL, including pre-B cell and T-cell.
Odgovori su primijećeni u različitim imunofenotipovima ALL-a,
How to use Ivozall
Kako primjenjivati lijek Ivozall
The use of disposable gloves and protective garments is recommended when handling clofarabine.
Pri rukovanju klofarabinom preporučuje se uporaba jednokratnih rukavica i zaštitne odjeće.
Your doctor will work out the dose that is right for you depending on your height, weight and how well you are.
Liječnik će odrediti dozu prikladnu za Vas na temelju
Ivozall 1 mg/ml concentrate for solution for infusion clofarabine
Ivozall 1 mg/ml koncentrat za otopinu za infuziju klofarabin
Capillary leak syndrome cases reported during the post-marketing period have been associated with a fatal outcome (See section 4.4).
Slučajevi sindroma kapilarne propusnosti prijavljeni nakon stavljanja lijeka u promet povezani su sa smrtnim ishodom (vidjeti dio 4.4)
Therefore, clofarabine should be used with caution in patients with mild to moderate hepatic impairment (see sections 4.2 and 4.3).
Stoga klofarabin treba primjenjivati uz oprez u bolesnika s blagim do umjerenim oštećenjem jetrene funkcije (vidjeti dijelove 4.2 i 4.3).
CRp
KRt
(6.1 to -)
(6,1 do -)
Thus, the concomitant use of medicinal products that have been associated with hepatic toxicity should be avoided wherever possible (see sections 4.4 and
Stoga istodobnu primjenu lijekova povezanih s hepatotoksičnošću treba izbjegavati kad god je to moguće (vidjeti dijelove 4.4 i 4.8).
breathlessness, cough; - vomiting blood, stomach ache, pain in the bottom; - bleeding inside the head, stomach, intestine or lungs, mouth or gums, mouth ulcers, inflamed mouth lining; - yellowing of the skin and eyes (also called jaundice), or other liver disorders; - bruising, hair loss, changes to skin colour, increased sweating, dry skin, or other skin problems; - pain in the chest wall or bones, neck or back pain, pain in limbs, muscles, or joints; - blood in urine; - failure of organs, pain, increased muscle tension, water retention and swelling in parts of the body, including the arms and legs, changes in mental state, feeling hot, cold or abnormal; - clofarabine may affect the levels of certain substances in the blood.
- bol u stjenci prsnog koša ili kostima, bol u vratu ili leđima, bol u udovima, mišićima ili zglobovima; - krv u mokraći; - zatajenje organa, bol, pojačana napetost u mišićima, zadržavanje vode i oticanje određenih dijelova tijela, uključujući ruke i noge, promjene duševnog stanja, osjećaj vrućine, hladnoće ili neuobičajeno osjećanje; - klofarabin može utjecati na razine određenih tvari u krvi.
A multi-centre, phase II, open-label, non-comparative study of clofarabine was conducted to determine the overall remission (OR) rate in heavily pretreated patients (≤ 21 years old at initial diagnosis) with relapsed or refractory ALL defined using the French-American-British classification.
≤ 21 godine kod početne dijagnoze) s relapsnom ili refraktornom ALL definiranim prema francusko američko-britanskoj klasifikaciji provedeno je multicentrično, otvoreno, nekomparativno ispitivanje klofarabina faze II.
Clofarabine may cause harm to unborn babies when used by pregnant women.
Kad se primjenjuje u trudnica, klofarabin može naškoditi nerođenu djetetu.
Very common: Vomiting, nausea, diarrhoea Common: Mouth haemorrhage, gingival bleeding, haematemesis, abdominal pain, stomatitis, upper abdominal pain, proctalgia, mouth ulceration Frequency not known: Pancreatitis elevations in serum amylase and lipase, enterocolitis, neutropenic colitis, caecitis
Poremećaji probavnog sustava vrlo često: povraćanje, mučnina, proljev često: krvarenje u ustima, krvarenje iz desni, hematemeza, bol u abdomenu, stomatitis, bol u gornjem dijelu abdomena, proktalgija, ulceracije usne šupljine učestalost nepoznata: pankreatitis, povišene vrijednosti amilaza i lipaza u serumu, enterokolitis, neutropenijski kolitis, tiflitis
NAME OF THE MEDICINAL PRODUCT Ivozall 1 mg/ml concentrate for solution for infusion
NAZIV LIJEKA Ivozall 1 mg/ml koncentrat za otopinu za infuziju
Twenty-one (18.3%) events were considered to be related to clofarabine of which catheter related infection (1 event), sepsis (2 events) and septic shock (2 events; 1 patient died (see above)) were considered to be serious.
S klofarabinom se smatrao povezanim 21 (18,3%) događaj, od kojih su se ozbiljnima smatrali infekcija povezana s kateterom (1 događaj), sepsa (2 događaja) i septički šok
Tell your doctor if you are using or have recently used: - medicines for heart disease (e.g. amiodarone, valsartan); - any medicine that changes your blood pressure (e.g. captopril, propranolol); - medicines that affect your liver (e.g. paracetamol, diclofenac) or kidneys (e.g. ibuprofen,
- lijekove za liječenje bolesti srca (npr. amiodaron, valsartan); - bilo koji lijek koji utječe na krvni tlak (npr. kaptopril, propranolol);
Dose reduction for patients experiencing non-haematological toxicities
Smanjenje doze u bolesnika u kojih je došlo do nehematološke toksičnosti Infektivni događaji
Forty-eight percent of patients had one or more ongoing infections prior to receiving treatment with clofarabine.
Infekcije i infestacije Prije liječenja klofarabinom u 48% bolesnika bila je prisutna jedna ili više infekcija.
Common: Maculo-papular rash, petechiae, erythema, pruritic rash, skin exfoliation, generalised rash, alopecia, skin hyperpigmentation, generalised erythema, erythematous rash, dry skin, hyperhidrosis Frequency not known: Stevens Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN)
Poremećaji kože i potkožnog tkiva vrlo često: sindrom palmarno-plantarne eritrodizestezije, pruritus često: makulopapularni osip, petehije, eritem, osip sa svrbežom, ljuštenje kože, generalizirani osip, alopecija, hiperpigmentacija kože, generalizirani eritem, osip s crvenilom, suha koža, hiperhidroza učestalost nepoznata: Stevens-Johnsonov sindrom (SJS),
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE Name and address of the manufacturer responsible for batch release
Naziv i adresa proizvođača odgovornog za puštanje serije lijeka u promet
Patients with advanced stages of ALL or AML may have confounding medical conditions that make causality of adverse events difficult to assess due to the variety of symptoms related to the underlying disease, its progression and the co-administration of numerous medicinal products.
U bolesnika s uznapredovalim stadijima akutne limfoblastične leukemije ili akutne mijeloične leukemije mogu istodobno postojati različite popratne bolesti koje otežavaju procjenu uzročno-posljedične povezanosti između lijeka i štetnog događaja, zbog raznih simptoma povezanih s podležećom bolešću,
A 25% dose reduction may be warranted in patients experiencing significant toxicities (see below).
U bolesnika u kojih se jave značajni toksični učinci možda će biti potrebno smanjenje doze za 25% (vidjeti u nastavku).
The use of disposable gloves and protective garments is recommended when handling Ivozall.
Pri rukovanju lijekom Ivozall preporučuje se uporaba jednokratnih rukavica i zaštitne odjeće.
Clofarabine AUC0-24 hours by baseline estimated creatinine clearance in patients aged between 2 to 19 years old with relapsed or refractory ALL or AML (n = 11 / n = 12) following administration of multiple doses of clofarabine by intravenous infusion (creatinine clearance estimated using Schwartz formula)
19 godina s relapsnom ili refraktorom ALL ili AML (n = 11 / n = 12) nakon primjene višekratnih doza klofarabina intravenskom infuzijom (klirens kreatinina procijenjen primjenom Schwartzove formule)
STATEMENT OF ACTIVE SUBSTANCE(S) Each 20 ml vial contains 20 mg of clofarabine
NAVOĐENJE DJELATNE(IH) TVARI Jedna bočica od 20 ml sadrži 20 mg klofarabina.
Therefore, clofarabine is contraindicated in patients with severe hepatic impairment (see section 4.3) and should be used with caution in patients with mild to moderate hepatic impairment (see section 4.4).
Stoga je klofarabin kontraindiciran u bolesnika s teškim oštećenjem jetrene funkcije (vidjeti dio 4.3), a u bolesnika s blagim do umjerenim oštećenjem jetrene funkcije mora se primjenjivati uz oprez (vidjeti dio 4.4).
Ivozall is a potent antineoplastic agent with potentially significant haematological and non-haematological adverse reactions (see section 4.8).
Ivozall je snažan antineoplastik koji može izazvati značajne hematološke i nehematološke nuspojave
Ivozall contains the active substance clofarabine.
Što je Ivozall i za što se koristi Ivozall sadrži djelatnu tvar klofarabin.
Very common: Flushing* Common: Hypotension*, capillary leak syndrome, haematoma
često: hipotenzija*, sindrom povećane propusnosti kapilara,
Clofarabine is contraindicated in patients with severe renal insufficiency (see section 4.3) and should be used with caution in patients with mild to moderate renal insufficiency (see section 4.4).
Klofarabin je kontraindiciran u bolesnika s teškim zatajivanjem bubrega (vidjeti dio 4.3), a u bolesnika s blagim do umjerenim zatajivanjem bubrega mora se primjenjivati uz oprez (vidjeti dio 4.4).
Do not use Ivozall - - if you are allergic to clofarabine or any of the other ingredients of this medicine (listed in section 6); - if you are breast-feeding (please read the section “Pregnancy and breast-feeding” below); - if you have severe kidney or liver problems.
Nemojte primjenjivati lijek Ivozall: - ako ste alergični na klofarabin ili neki drugi sastojak ovog lijeka (naveden u dijelu 6.);
Special precautions for administration
Posebne mjere opreza za primjenu lijeka
Clofarabine should be discontinued immediately if substantial increases in creatinine, liver enzymes and/or bilirubin are observed.
Ako dođe do značajnih povećanja vrijednosti kreatinina, jetrenih enzima i/ili bilirubina, liječenje klofarabinom mora se odmah prekinuti.
What Ivozall is and what it is used for 2.
Pogledajte dio 4. Što se nalazi u ovoj uputi: Što je Ivozall i za što se koristi
Your doctor will carry out regular blood tests to check whether your body is working properly; - liver damage (liver failure).
Liječnik će redovito provoditi krvne pretrage kako bi provjerio stanje Vašeg organizma.
Increases in postimplantation loss, reduced foetal body weights and decreased litter sizes together with increases in the number of malformations (gross external, soft tissue) and skeletal alterations (including retarded ossification) were reported in rats receiving doses which produced approximately 2 to 3 fold the clinical exposure (54 mg/m2/day) and in rabbits receiving 12 mg/m2/day clofarabine.
U štakora koji su primali doze koje su dovele do izloženosti približno 2 do 3 puta veće od one kliničke (54 mg/m2 na dan) te u kunića koji su primali dozu klofarabina od 12 mg/m2 na dan prijavljena je povećana učestalost gubitka ploda nakon implantacije, smanjena tjelesna težina ploda i smanjena veličina legla, uz povećanje broja malformacija (velike vanjske, meko tkivo) i koštanih promjena (uključujući zastoj u osifikaciji).
Tell your doctor or carer immediately if you experience any of the following as you may need to stop treatment: - if you get a fever or high temperature - because clofarabine reduces the number of blood cells made in the bone marrow, you may be more likely to catch infections; - if you have breathing difficulties, rapid breathing, or breathlessness; - if you feel a change in your heart rate; - if you suffer from dizziness (light-headedness) or fainting - it may be a symptom of low blood pressure; - if you feel sick or have diarrhoea (loose bowels); - if your urine is darker than usual - it is important to drink plenty of water to avoid dehydration; - if you get a rash with blisters or mouth ulcers; - if you lose your appetite, have nausea (feeling sick), vomiting, diarrhea, dark-colored urine and light-coloured stools, stomach pain, jaundice (yellowing of the skin and eyes), or if you feel generally unwell, these could be symptoms of an inflammation of the liver (hepatitis), or liver damage (hepatic failure); - if you pass little or no urine, or experience drowsiness, nausea, vomiting, breathlessness, loss of appetite and / or weakness (these may be signs of acute kidney failure / kidney failure).
- ako izgubite apetit, imate mučninu, povraćanje, proljev, tamno obojenu mokraću i svijetlo obojenu stolicu, bol u trbuhu, žuticu (žuto obojenje kože i očiju) ili ako se općenito loše osjećate, to mogu biti simptomi upale jetre (hepatitisa) ili oštećenja jetre (zatajenje jetre); - ako mokrite malo ili nimalo mokraće, ili osjetite omamljenost, mučninu, povraćanje, nedostatak zraka, gubitak apetita i/ili slabost (ovo mogu biti znakovi akutnog zatajenja bubrega/zatajenja bubrega).
For storage conditions after dilution of the medicinal product, see section 6.3
Uvjete čuvanja nakon razrjeđivanja lijeka vidjeti u dijelu 6.3. 6.5 Vrsta i sadržaj spremnika
Pharmacokinetics in patients aged between 2 to 19 years old with relapsed or refractory ALL or AML following administration of multiple doses of clofarabine by intravenous infusion
Farmakokinetika u bolesnika u dobi između 2 i 19 godina s relapsnom ili refraktornom ALL
This means that due to the rarity of the disease it has not been possible to obtain complete information on the reference medicinal product.The European Medicines Agency will review any new information which may become available every year and this SmPC will be updated as necessary accordingly to the reference medicinal product SmPC.
Europska agencija za lijekove svake će godine procjenjivati sve nove informacije koje postanu dostupne te će se tekst sažetka opisa svojstava lijeka ažurirati prema potrebi, u skladu s tekstom sažetka opisa svojstava referentnog lijeka.
Therefore, clofarabine should be used with caution in patients with mild to moderate renal insufficiency (see section 4.2 for dose adjustments).
Stoga klofarabin treba primjenjivati uz oprez u bolesnika s blagim do umjerenim zatajivanjem bubrežne funkcije (vidjeti dio 4.2. za prilagodbu doze).
Response category
Način primjene
Eleven events in 115 patients were considered to be related to clofarabine, none of which were serious and the most frequently reported cardiac disorder was tachycardia (35%) (see section 4.4); 6.1% (7/115) patient's tachycardia were considered to be related to clofarabine.
Jedanaest događaja prijavljenih u 115 bolesnika smatralo se povezanima s klofarabinom; nijedan nije bio ozbiljan, a najčešće je prijavljivana tahikardija (35%) (vidjeti dio 4.4).
Cases of hepatitis and hepatic failure, including fatal outcomes, have been reported with clofarabine treatment (see section 4.8).
Prilikom liječenja klofarabinom prijavljeni su slučajevi hepatitisa i zatajenja jetre, uključujući smrtne ishode (vidjeti dio 4.8).
• Patients should receive intravenous fluids throughout the 5 day clofarabine administration period to reduce the effects of tumour lysis and other events.
• Radi ublažavanja učinaka lize tumora i drugih događaja, bolesnicima je tijekom petodnevnog razdoblja primjene klofarabina potrebna intravenska hidracija.
Common: Hypersensitivity
Poremećaji imunološkog sustava često: preosjetljivost
OTHER
Ako
Systemic inflammatory response syndrome (SIRS) or capillary leak syndrome SIRS, capillary leak syndrome (signs and symptoms of cytokine release, e.g., tachypnea, tachycardia, hypotension, pulmonary oedema) were reported as an adverse reaction in 5% (6/115) of paediatric patients (5 ALL, 1 AML) (see section 4.4).
Sindrom sistemskog upalnog odgovora (SIRS) ili sindrom povećane propusnosti kapilara Sindrom sistemskog upalnog odgovora, sindrom povećane propusnosti kapilara (znakovi i simptomi otpuštanja citokina, npr. tahnipneja, tahikardija, hipotenzija, plućni edem) prijavljeni su kao nuspojave u
Clofarabine may cause serious birth defects when administered during pregnancy.
Ako se primjenjuje tijekom trudnoće, klofarabin može prouzročiti ozbiljne prirođene mane.
Stevens - Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal cases, have been reported in patients who were receiving or had recently been treated with clofarabine.
U bolesnika koji su primali klofarabin ili su nedavno njim bili liječeni, prijavljeni su Stevens-Johnsonov sindrom (SJS) i toksična epidermalna nekroliza (TEN), uključujući i smrtne slučajeve.
Neoplasms benign and malignant (including cysts and polyps) and Immune systems disorders Administration of clofarabine results in a rapid reduction in peripheral leukaemia cells.
Dobroćudne i zloćudne novotvorine (uključujući ciste i polipe) i poremećaji imunološkog sustava
Very common: Febrile neutropenia Common: Neutropenia
Poremećaji krvi i limfnog sustava vrlo često: neutropenijska vrućica često: neutropenija