natgillin/translations-raw huggingface dataset:
The recommended dose in paediatric patients is 100 mg/m2 larotrectinib twice daily with a maximum of 100 mg per dose until disease progression or until unacceptable toxicity occurs.
Preporučena doza u pedijatrijskih bolesnika je 100 mg/m2 larotrektiniba dvaput na dan, uz maksimalno 100 mg po dozi, do progresije bolesti ili do pojave neprihvatljive toksičnosti.
How VITRAKVI works
Kako VITRAKVI djeluje
Fill the syringe with a small amount of solution by pulling the plunger down, then push the plunger upwards to remove any large bubbles that are in the syringe.
Napunite štrcaljku malom količinom otopine tako što ćete povući klip prema dolje, a zatim ga potisnite prema gore da uklonite eventualne veće mjehuriće iz štrcaljke.
In rats, severe toxicity (STD10) was observed at doses corresponding to 1- to 2-times the human AUC at the recommended clinical dose.
Na štakorima je bila opažena jaka toksičnost (STD10) pri dozama koje odgovaraju 1 do 2 puta većem AUC-u od onog kod ljudi pri preporučenoj kliničkoj dozi.
In vitro studies indicate that larotrectinib does not inhibit the transporters BCRP, P-gp, OAT1, OAT3, OCT1, OCT2, OATP1B3, BSEP, MATE1 and MATE2-K at clinically relevant concentrations and is unlikely to affect clearance of substrates of these transporters.
In vitro ispitivanja pokazuju da larotrektinib ne inhibira prijenosnike BCRP, P-gp, OAT1, OAT3, OCT1, OCT2, OATP1B3, BSEP, MATE1 i MATE2-K u klinički važnim koncentracijama i vjerojatno neće utjecati na klirens supstrata ovih prijenosnika.
Permanent discontinuation of VITRAKVI for treatment emergent adverse reactions, regardless of attribution occurred in 3% of patients (one case each of ALT increase, AST increase, intestinal perforation, jaundice, small intestinal obstruction).
Liječenje lijekom VITRAKVI trajno je prekinuto zbog nuspojava nastalih tijekom liječenja, neovisno o pripisivanju ispitivanom lijeku, u 3 % bolesnika (po jedan slučaj povišenja ALT-a, povišenja AST-a, perforacije crijeva, žutice, opstrukcije tankog crijeva).
Tube length (cm)
Duljina sonde (cm)
Typical tube diameter, tube lengths and derived prime volumes are presented in Table 7.
Uobičajen promjer sonde, duljina sonde i izvedeni volumeni punjenja navedeni su u tablici 7.
Tell your doctor, pharmacist or nurse if you notice any of the following side effects: Very common (may affect more than 1 in 10 people): - you may look pale and feel your heart pumping, which could be symptoms of low red blood cells (anaemia) - flu like symptoms including fever, which could be symptoms of low white blood cells
Obavijestite liječnika, ljekarnika ili medicinsku sestru ako primijetite bilo koju od sljedećih nuspojava: Vrlo često (mogu se javiti u više od 1 na 10 osoba): - možete izgledati blijedo i osjećati pojačan rad srca, što mogu biti simptomi sniženog broja crvenih krvnih stanica (anemije) - simptomi nalik gripi, uključujući vrućicu, što mogu biti simptomi sniženog broja bijelih krvnih stanica („neutropenija“, „leukopenija“) - mučnina ili povraćanje - zatvor - bol u mišićima (mialgija) - mišićna slabost - osjećaj umora - povišena razina jetrenih enzima u krvnim pretragama - povećanje tjelesne težine.
VITRAKVI is for oral use.
VITRAKVI je namijenjen za peroralnu primjenu.
Co-administration of larotrectinib with CYP2C8, CYP2C9 or CYP2C19 substrates (e.g. repaglinide, warfarin, tolbutamide or omeprazole) may decrease their exposure.
Istodobna primjena larotrektiniba sa supstratima CYP2C8, CYP2C9 ili CYP2C19 (npr. repaglinid, varfarin, tolbutamid ili omeprazol) može smanjiti njihovu izloženost.
Table 5: Pooled efficacy results in solid tumours including and excluding primary CNS tumours Efficacy parameter
Tablica 5: Objedinjeni rezultati djelotvornosti u solidnih tumora uključujući ili izostavljajući primarne tumore SŽS-a
How to take this medicine
Koliko lijeka uzeti
Use a 5 mL syringe with 0.2 mL marks for doses of 1 mL or more.
Upotrijebite štrcaljku od 5 ml s oznakama od 0,2 ml za doze od 1 ml ili veće.
Patients enrolled to Study 2 (“NAVIGATE”) were required to have TRK fusion-positive cancer.
Bolesnici uključeni u ispitivanje 2 („NAVIGATE“) morali su imati tumor pozitivan na fuzijski gen TRK.
Grade 3 ALT and AST increases in 3 (2%) and 2 (2%) patients, respectively.
3. stupanj povišenja ALT-a pojavio se u 3 (2 %), a AST-a u 2 (2 %) bolesnika.
Table 1: Recommended dose modifications for VITRAKVI for adverse reactions Dose modification
Tablica 1: Preporučene prilagodbe doze lijeka VITRAKVI zbog nuspojava Prilagodba doze
VITRAKVI may make you feel dizzy or tired.
VITRAKVI Vam može izazvati omaglicu ili umor.
There was a median of 1 prior systemic treatment regimen received.
Prethodno su primili medijan od 1 sistemskog terapijskog protokola.
Larotrectinib was not teratogenic and embryotoxic when dosed daily during the period of organogenesis to pregnant rats and rabbits at maternotoxic doses, i.e. corresponding to 32-times (rats) and 16-times (rabbits) the human AUC at the recommended clinical dose.
Larotrektinib nije bio ni teratogen ni embriotoksičan kad se svakodnevno davao u razdoblju organogeneze gravidnim ženkama štakora i kunića u dozama toksičnima za majku, tj. onima koje su 32 puta (štakor) i 16 puta (kunići) veće od AUC-a kod ljudi pri preporučenoj kliničkoj dozi.
VITRAKVI should be permanently discontinued in patients who are unable to tolerate VITRAKVI after three dose modifications.
Primjenu lijeka VITRAKVI u bolesnika koji ne mogu tolerirati lijek nakon tri prilagodbe doze potrebno je trajno prekinuti.
If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse.
Ako se nešto od gore navedenog odnosi na Vas (ili niste sigurni), obratite se liječniku, ljekarniku ili medicinskoj sestri.
Larotrectinib had no effect on respiratory function in rats; at exposures (Cmax) at least 8-times the human therapeutic exposure.
Larotrektinib nije imao učinak na respiratornu funkciju kod štakora; pri izloženostima (Cmax) koje su barem 8 puta veće od terapijske izloženosti u ljudi.
Grade 2 ALT and AST increases were observed in 9 (7%) and 6 (5%) of patients, respectively, and Grade 1 ALT and AST increases were observed in 26 (21%) and 28 (22%) of patients, respectively.
Povišenja ALT-a i AST-a 2. stupnja bila su opažena u 9 (7 %), odnosno 6 (5%) bolesnika, a povišenja ALT-a i AST-a 1. stupnja bila su opažena u 26 (21 %), odnosno 28 (22 %) bolesnika.
Effect of larotrectinib on CYP3A substrates
Učinak larotrektiniba na supstrate CYP3A
The oral solution should be administered by mouth using an oral syringe of 1 mL or 5 mL volume or enterally by using a nasogastric feeding tube.
Oralnu otopinu treba primijeniti kroz usta pomoću štrcaljke za usta volumena 1 ml ili 5 ml ili enteralno putem nazogastrične sonde.
Due to the rarity of TRK fusion-positive cancer, patients were studied across multiple tumour types with a limited number of patients in some tumour types, causing uncertainty in the ORR estimate per tumour type.
Zbog male učestalosti tumora pozitivnog na fuzijski gen TRK ispitivani su bolesnici s različitim vrstama tumora s tim da je u skupinama s nekim vrstama tumora broj bolesnika bio ograničen, uzrokujući nesigurnu procjenu ukupne stope odgovora (engl. overall response rate, ORR) prema vrsti tumora.
Table 3: Adverse drug reactions reported in TRK fusion-positive paediatric cancer patients treated with VITRAKVI at recommended dose (n=37); all Grades System organ class
Tablica 3: Nuspojave prijavljene uz lijek VITRAKVI u preporučenoj dozi u pedijatrijskih bolesnika s tumorom pozitivnim na fuzijski gen TRK (n = 37); svi stupnjevi Klasifikacija organsik sustava
Acquired resistance mutations after progression on TRK inhibitors have been observed.
Nakon progresije su uočene stečene mutacije koje uzrokuju rezistenciju na TRK inhibitore.
No relevant effects on fertility were observed in repeat-dose toxicity studies (see section 5.3).
U ispitivanjima toksičnosti ponovljene doze nisu opaženi relevantni učinci na plodnost (vidjeti dio 5.3).
Baseline characteristics for the 9 patients with primary CNS tumours with an NTRK gene fusion assessed by investigator were as follows: median age 12 years (range 2-79 years); 6 patients
Početne značajke 9 bolesnika s primarnim tumorom SŽS-a s fuzijskim genom NTRK prema procjeni ispitivača bile su sljedeće: medijan dobi 12 godina (raspon: 2-79 godina), 6 bolesnika u dobi
The highest reported grade was Grade 3 for adverse reactions anaemia, weight increased, fatigue, increased AST, dizziness, paraesthesia, nausea, myalgia, and leukocyte count decreased.
Treći stupanj bio je najviši prijavljeni stupanj nuspojava koje uključuju anemiju, povećanje tjelesne težine, umor, povišenje AST-a, omaglicu, paresteziju, mučninu, mialgiju i smanjen broj leukocita.
The active substance is larotrectinib.
Djelatna tvar je larotrektinib.
• Adult patients (≥ 18 years) with advanced solid tumours with an NTRK gene fusion
• odrasli bolesnici (≥ 18 godina) s uznapredovalim solidnim tumorima s fuzijskim genom NTRK
In particular, tell your doctor, pharmacist or nurse if you are taking any of the following medicines: - medicines used to treat fungal or bacterial infections called itraconazole, voriconazole,
Osobito obavijestite liječnika, ljekarnika ili medicinsku sestru ako uzimate neke od sljedećih lijekova: - lijekovi koji se primjenjuju za liječenje gljivičnih ili bakterijskih infekcija kao što su itrakonazol, vorikonazol, klaritromicin, telitromicin, troleandomicin
The adverse drug reactions are classified according to the System Organ Class.
Nuspojave su kategorizirane prema klasifikaciji organskih sustava.
If necessary, VITRAKVI may be administered via a nasogastric feeding tube.
Po potrebi, VITRAKVI se može primijeniti putem nosno-želučane sonde.
The target for larotrectinib is the TRK family of proteins inclusive of TRKA, TRKB, and TRKC that are encoded by NTRK1, NTRK2 and NTRK3 genes, respectively.
Ciljna molekula za larotrektinib je obitelj TRK proteina koja se sastoji od TRKA, TRKB i TRKC kodiranih genima NTRK1, NTRK2 odnosno NTRK3.
NOTE: See exceptions regarding neonates and patients with fluid restrictions in the sub-point directly below.
Vidjeti točku direktno dolje za iznimke za novorođenčad i bolesnike s ograničenim unosom tekućine.
Larotrectinib was not mutagenic in bacterial reverse mutation (Ames) assays and in in vitro mammalian mutagenesis assays.
Larotrektinib nije imao mutageno djelovanje na testovima reverznih mutacija u bakterijama (Amesov test) i u in vitro testovima mutageneze kod sisavaca.
If you are giving this medicine to your child, please replace “you” with “your child” throughout.
Ako lijek dajete djetetu, molimo da ono što piše za Vas primijenite na Vaše dijete.
All patients had received prior treatment for their cancer, defined as surgery, radiotherapy, or systemic therapy.
Svi su bolesnici prethodno primili terapiju za liječenje karcinoma, definiranu kao kirurški zahvat, radioterapija ili sistemska terapija.
Exercise caution with concomitant use of CYP3A substrates with narrow therapeutic range (e.g. alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, or tacrolimus) in patients taking VITRAKVI.
Nužan je oprez kod istodobne primjene supstrata CYP3A uskog terapijskog indeksa (npr. alfentanila, ciklosporina, dihidroergotamina, ergotamina, fentanila, pimozida, kinidina, sirolimusa ili takrolimusa) u bolesnika koji uzimaju lijek VITRAKVI.
Mean clearance (CL) of larotrectinib was approximately 34 L/h following intravenous administration of an IV microtracer in conjunction with a 100 mg oral dose of VITRAKVI.
Srednja vrijednost klirensa (CL) larotrektiniba iznosila je približno 34 l/h nakon intravenske primjene mikroobilježivača zajedno s oralnom dozom od 100 mg lijeka VITRAKVI.
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Of 125 patients in the overall safety population who received VITRAKVI, 28 (22%) patients were 65 years or older and 8 (6%) patients were 75 years or older.
Od 125 bolesnika u cjelokupnoj populaciji u ispitivanju sigurnosti primjene koja je primala lijek VITRAKVI, 28 (22 %) bolesnika bilo je u dobi od 65 godina ili stariji, a 8 (6 %) bolesnika bilo je u dobi od 75 godina ili stariji.
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Effect of larotrectinib on substrates of PXR regulated enzymes In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT).
In vitro ispitivanja ukazuju na to da larotrektinib može inducirati PXR regulirane enzime (npr. CYP2C skupinu i UGT).
Put the bottle adapter into the bottle neck and make sure it is well fixed.
Umetnite adapter za bocu u grlo boce i provjerite je li dobro pričvršćen.
% with duration ≥ 6 months % with duration ≥ 12 months
Trajanje odgovora (medijan, mjeseci) [raspon] % s trajanjem ≥ 6 mjeseci % s trajanjem
Effect of larotrectinib on CYP2B6 substrates
Učinak larotrektiniba na supstrate CYP2B6
The mean volume of distribution of larotrectinib in healthy adult subjects was 48 L following intravenous administration of an IV microtracer in conjunction with a 100 mg oral dose, indicating moderate distribution into tissues from the plasma.
Srednja vrijednost volumena distribucije larotrektiniba u zdravih odraslih ispitanika iznosila je 48 l nakon intravenske primjene mikroobilježivača zajedno s oralnom dozom od 100 mg, pokazujući umjerenu distribuciju iz plazme u tkiva.
ALT and AST increases leading to dose modifications occurred in 7 (6%) patients and 6 (5%) patients, respectively (see section 4.4).
Povišenja ALT-a i AST-a koja su dovela do prilagodbi doza nastala su u 7 (6 %), odnosno 6 (5 %) bolesnika (vidjeti dio 4.4).
Baseline characteristics for the pooled 93 patients with solid tumours with an NTRK gene fusion were as follows: median age 41 years (range 0.1-78 years); 30% < 18 years of age, and 70% ≥ 18 years;
Početne značajke sva 93 bolesnika sa solidnim tumorima s fuzijskim genom NTRK bile su sljedeće: medijan dobi 41 godina (raspon 0,1-78 godina); 30 % u dobi < 18 godina, a 70 % u dobi od
The most common adverse drug reactions (≥ 20%) of VITRAKVI in order of decreasing frequency were fatigue (32%), increased ALT (31%), dizziness (30%), increased AST (29%), constipation (29%), nausea (26%), anaemia (24%), and vomiting (20%).
Najčešće nuspojave (≥ 20 %) na lijek VITRAKVI prema sve manjoj učestalosti bile su umor (32 %), povišen ALT (31%), omaglica (30 %), povišen AST (29%), konstipacija (29 %), mučnina (26 %), anemija (24 %) i povraćanje (20 %).
Following oral administration of 100 mg radiolabeled larotrectinib to healthy adult subjects, 58% of the administered radioactivity was recovered in faeces and 39% was recovered in urine and when an IV microtracer dose was given in conjunction with a 100 mg oral dose of larotrectinib, 35% of the administered radioactivity was recovered in faeces and 53% was recovered in urine.
Nakon oralne primjene 100 mg radioaktivno obilježenog larotrektiniba zdravim odraslim ispitanicima, 58 % primijenjene radioaktivnosti otkriveno je u stolici, a 39 % u mokraći, a kad se intravenska doza mikroobilježivača dala zajedno sa 100 mg oralne doze larotrektiniba, 35 % primijenjene radioaktivnosti otkriveno je u stolici, a 53 % u mokraći.
Each carton contains 1 child-resistant plastic bottle containing 56 hard gelatine capsules.
Jedna kutija sadrži jednu plastičnu bocu sa zatvaračem sigurnim za djecu sa 56 tvrdih želatinoznih kapsula.
VITRAKVI 20 mg/mL oral solution larotrectinib
VITRAKVI 20 mg/ml oralna otopina larotrektinib
- Insert the bottle adapter into the bottle neck and ensure it is well fixed.
- Umetnite adapter za bocu u grlo boce i provjerite je li dobro pričvršćen.
- Open the bottle: press the bottle cap and turn it counter clockwise.
- Otvorite bocu: pritisnite zatvarač boce i zakrenite ga u smjeru suprotnom od kazaljke na satu.
- The maximum recommended dose is 100 mg (5 mL), two times a day.
- Maksimalna preporučena doza je 100 mg (5 ml), dvaput na dan.
If concomitant use of these CYP3A substrates with narrow therapeutic range is required in patients taking VITRAKVI, dose reductions of the CYP3A substrates may be required due to adverse reactions.
Ako je u bolesnika koji uzimaju VITRAKVI potrebna istodobna primjena tih supstrata CYP3A s uskim terapijskim indeksom, možda će biti potrebno sniziti doze supstrata CYP3A zbog nuspojava.
No effects on female reproductive organs were seen in the 3-months toxicity studies in rats and monkeys at doses corresponding to approximately 3-times (female rats) and 17-times (female monkeys) the human AUC at the recommended clinical dose.
Nisu bili opaženi učinci na reproduktivne organe ženki u 3-mjesečnim ispitivanjima toksičnosti na štakorima i majmunima pri dozama koje su bile približno 3 puta (ženke štakora) i približno 17 puta (ženke majmuna) veće od AUC-a kod ljudi pri preporučenoj kliničkoj dozi.
[range]
(neutropenija).
Table 7: Recommended tube dimensions per age group Patient
Tablica 7: Preporučene dimenzije sonde prema dobnoj skupini Bolesnici
In 3-months toxicity studies, larotrectinib had no histological effect on the male reproductive organs in rats and monkeys at the highest tested doses corresponding to approximately 7-times (male rats) and 10-times (male monkeys) the human AUC at the recommended clinical dose.
U 3-mjesečnim ispitivanjima toksičnosti, larotrektinib nije imao histološki učinak na reproduktivne organe mužjaka kod štakora i majmuna pri najvišim ispitanim dozama koje su bile približno 7 puta (mužjaci štakora) i 10 puta (mužjaci majmuna) veće od AUC-a kod ljudi pri preporučenoj kliničkoj dozi.
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SD: stable disease + denotes ongoing response a independent review committee analysis by RECIST v1.1 b patients with a primary CNS tumour were evaluated per investigator assessment using either RANO or RECIST v1.1
+ označava odgovor koji još traje a Analiza neovisnog stručnog povjerenstva prema kriterijima RECIST v1.1 b Bolesnici s primarnim tumorom SŽS-a ocijenjeni su procjenom ispitivača prema kriterijima RANO ili RECIST v1.1 c Nesekretorni
Carcinogenicity studies have not been performed with larotrectinib.
Nisu provedena ispitivanja kancerogenosti larotrektiniba.
Use a 1 mL syringe with 0.1 mL marks for doses less than 1 mL.
Upotrijebite štrcaljku od 1 ml s oznakama od 0,1 ml za doze manje od 1 ml.
Tube prime volume (mL)
Volumen punjenja sonde (ml)
- The maximum recommended dose is 100 mg (1 capsule of 100 mg or 4 capsules of 25 mg), two times a day.
- Maksimalna preporučena doza je 100 mg (1 kapsula od 100 mg ili 4 kapsule od 25 mg), dvaput na dan.
Effect of CYP3A, P-gp and BCRP inhibitors on larotrectinib Larotrectinib is a substrate of cytochrome P450 (CYP) 3A, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).
Larotrektinib je supstrat citokroma P450 (CYP) 3A, P-glikoproteina (P-gp) i proteina rezistencije raka dojke (engl. breast cancer resistance protein, BCRP).
Second
Druga
A pharmacokinetic study was conducted in subjects with mild (Child-Pugh A), moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment, and in healthy adult control subjects with normal hepatic function matched for age, body mass index and sex. All subjects received a single 100 mg dose of larotrectinib.
Farmakokinetičko ispitivanje provedeno je u ispitanika s blagim (Child-Pugh A), umjerenim (Child-Pugh B) i teškim (Child-Pugh C) oštećenjem funkcije jetre te u zdravih odraslih kontrolnih ispitanika s normalnom funkcijom jetre koji su po dobi, indeksu tjelesne mase i spolu odgovarali bolesnicima.
< 18 years of age, and 3 patients ≥ 18 years, and 8 patients white and 5 patients male; and ECOG PS 0-1 (8 patients), or 2 (1 patient).
≥ 18 godina, 8 bolesnika bili su bijelci, 5 bolesnika bili su muškog spola, a ECOG status bio je 0-1 (8 bolesnika) ili 2 (1 bolesnik).
• Phase 1, open-label, dose escalation and expansion study; expansion phase required tumours with an NTRK gene fusion
• otvoreno ispitivanje faze 1 povišenja doze s proširenjem; faza proširenja zahtijevala je tumore s fuzijskim genom NTRK
Co-administration of VITRAKVI with strong CYP3A inhibitors, P-gp and BCRP inhibitors (e.g. atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole or grapefruit) may increase larotrectinib plasma concentrations (see section 4.2).
Istodobna primjena lijeka VITRAKVI s jakim inhibitorima CYP3A, P-gp-a i BCRP-a (npr. atazanavirom, klaritromicinom, indinavirom, itrakonazolom, ketokonazolom, nefazodonom, nelfinavirom, ritonavirom, sakvinavirom, telitromicinom, troleandomicinom, vorikonazolom ili grejpom) može povećati koncentracije larotrektiniba u plazmi (vidjeti dio 4.2).
First
Prva
- VITRAKVI 25 mg is supplied as white opaque hard gelatine capsule, (18 mm long x 6 mm wide), with blue printing of BAYER-cross and “LARO 25 mg” on the body of the capsule - VITRAKVI 100 mg is supplied as white opaque hard gelatine capsule, (22 mm long x 7 mm wide), with blue printing of BAYER-cross and “LARO 100 mg” on the body of the capsule
Kako VITRAKVI izgleda i sadržaj pakiranja - VITRAKVI 25 mg isporučuje se kao bijela neprozirna tvrda želatinozna kapsula (18 mm dugačka x 6 mm široka), s plavo otisnutim križem „BAYER“ i „LARO 25 mg“ na tijelu kapsule - VITRAKVI 100 mg isporučuje se kao bijela neprozirna tvrda želatinozna kapsula (22 mm dugačka x 7 mm široka), s plavo otisnutim križem „BAYER“ i „LARO 100 mg“ na tijelu kapsule
For Grade 3 or 4 adverse reactions: - VITRAKVI should be withheld until the adverse reaction resolves or improves to baseline or
Kod nuspojava 3. ili 4. stupnja: - Primjenu lijeka VITRAKVI potrebno je prekinuti do povlačenja nuspojave ili njezina poboljšanja do početnog stanja ili 1. stupnja.
Larotrectinib had no neurobehavioural findings in adult animals (rats, mice, cynomolgus monkeys) at exposure (Cmax) at least 7-fold higher than the human exposure.
Larotrektinib nije imao neurobihevioralne učinke u odraslih životinja (npr. štakora, miševa, makaki majmuna) pri izloženosti (Cmax) koja je najmanje 7 puta veća od one u ljudi.
At the time of data cut-off, 8 of 9 enrolled patients with primary CNS tumours were evaluable for response by investigator assessment.
U vrijeme prestanka prikupljanja podataka, ispitivač je mogao procijeniti terapijski odgovor u 8 od 9 uključenih bolesnika s primarnim tumorom SŽS-a.
• Adult and paediatric patients ≥ 12 years with advanced solid tumours with an NTRK gene fusion
• odrasli i pedijatrijski bolesnici u dobi od ≥ 12 godina s uznapredovalim solidnim tumorima s fuzijskim genom
The recommended dose modifications for VITRAKVI for adverse reactions are provided in Table 1.
Preporučene prilagodbe doze lijeka VITRAKVI zbog nuspojava prikazane su u tablici 1.
Patients with primary CNS tumours
Bolesnici s primarnim tumorom SŽS-a
Larotrectinib had no adverse effect on haemodynamic parameters and ECG intervals in telemetered monkeys at exposures (Cmax) which are approximately 6-fold the human therapeutic exposures.
Larotrektinib nije imao štetan učinak na hemodinamičke parametre i EKG intervale na telemetrijski praćenim majmunima pri izloženosti (Cmax) koja je bila približno 6 puta veća od terapijske izloženosti u ljudi.
Co-administration with strong CYP3A4 inhibitors If co-administration with a strong CYP3A4 inhibitor is necessary, the VITRAKVI dose should be reduced by 50%.
Ako je potrebna istodobna primjena s jakim inhibitorom CYP3A4, dozu lijeka VITRAKVI treba sniziti za 50 %.
High density polyethylene (HDPE)-bottles with a child-resistant polypropylene (PP) cap with a polyethylene (PE) heat seal layer.
Boce od polietilena visoke gustoće (HDPE) s polipropilenskim (PP) zatvaračem sigurnim za djecu i termički zapečaćene polietilenskom (PE) folijom.
Co-administration of larotrectinib with CYP2B6 substrates (e.g. bupropion, efavirenz) may decrease their exposure.
Istodobna primjena larotrektiniba sa supstratima CYP2B6 (npr. bupropionom, efavirenzom) može smanjiti izloženost tim supstratima.
No relevant systemic toxicity was observed in monkeys at doses which correspond to > 10-times the human AUC at the recommended clinical dose.
Nije opažena značajna sistemska toksičnost na majmunima pri dozama koje odgovaraju onima > 10 puta većima od AUC-a kod ljudi pri preporučenoj kliničkoj dozi.