qanastek/EMEA-V3 huggingface dataset:
Instructions for use and handling
Struzzjonijiet dwar l- użu u l- imaniġġar
350 mg presentation: a 50 mg/ ml concentration can be achieved by reconstituting with 7 ml of 0.9% sodium chloride intravenous infusion.
Preparat tat- 350 mg: konċentrazzjoni ta ’ 50 mg/ ml tista ’ tinkiseb billi tħallat ma ’ 7 ml ta ’ 0. 9% sodium chloride infużjoni għal ġol- vina.
Vials of 350 mg/ vial can also be reconstituted with sterile water for injections.
Kunjetti ta ’ 350 mg/ kunjett jistgħu jiġu rikostitwiti wkoll b’ ilma sterili għall- injezzjonijiet.
Cubicin (daptomycin) is not physically or chemically compatible with glucose-containing solutions.
Cubicin (daptomycin) mhuwiex fiżikament jew kimikament kumpatibbli ma ’ soluzzjonijiet li fihom glucose.
The vial should be gently rotated to ensure complete wetting of the product and then allowed to stand for 10 minutes.
Il- kunjett għandu jiddawar bil- mod sabiex ikun żgurat li l- prodott kollu jixxarrab u imbagħad jitħalla joqgħod għal 10 minuti.
Finally the vial should be gently rotated/ swirled for a few minutes as needed to obtain a clear reconstituted solution.
Fl- aħħar, il- kunjett għandu jiddawwar/ jitbandal bil- mod b’ mod ċirkolari għal ftit minuti skond kemm ikun hemm bżonn sabiex tinkiseb taħlita ta ’ soluzzjoni ċara.
Vigorous shaking/ agitation should be avoided to prevent foaming of the product.
Evita li tħallat/ tħawwad bil- qawwi tevita li l- prodott itella ’ r- rawgħa.
The reconstituted solution should be checked carefully to ensure that the product is in solution and visually inspected for the absence of particulates prior to use.
Is- soluzzjoni rikostitwita għandha tiġi ċcekkjata bir- reqqa biex ikun żgurat li l- prodott ikun inħall u għandha tiġi miflija sabiex ikun aċċertat li m’ hemmx xi frak qabel l- użu.
The reconstituted solution should then be diluted with sodium chloride intravenous infusion (typical volume 50 ml) and infused over 30 minutes.
Is- soluzzjoni rikostitwita wara għandha tiġi dilwita b’ infużjoni għal ġol- vina ta ’ sodium chloride (bħala regola volum ta ’ 50 ml) u l- infużjoni għandha tingħata fuq medda ta ’ 30 minuta.
Chemical and physical in-use stability on the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to 48 hours if stored under refrigeration (2 to 8°C).
L- istabbiltà kimika u fiżika waqt l- użu tas- soluzzjoni mħallta fil- kunjett intweriet għal 12- il siegħa f’ 25°C u sa 48 siegħa jekk tinħażen fi friġġ (2°C - 8°C).
The combined time (vial and infusion bag) at 25°C should not exceed 12 hours (24 hours if refrigerated).
Il- ħin tal- ħażna kombinat (kunjett u borża ta ’ l- infużjoni) f’ 25°C m’ għandhiex taqbeż it- 12- il siegħa (jew 24 siegħa fil- friġġ).
Stability of the diluted solution in infusion bags is established as 12 hours at 25°C or 24 hours if stored under refrigeration at 2 to 8°C.
L- istabbiltà tas- soluzzjoni dilwita fil- boroż ta ’ l- infużjoni hija stabbilita bħala 12- il siegħa f’ 25°C jew 24 siegħa jekk tinħażen fi friġġ f’ 2°C - 8°C.
If not used immediately, in-use storage times are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C unless reconstitution / dilution has taken place in controlled and validated aseptic conditions.
Jekk ma jintużax mill- ewwel, il - ħinijiet tal- ħażna waqt l- użu huma r- responsabbiltà ta ’ min qed jużah u normalment ma jkunux aktar minn 24 siegħa f’ 2°C - 8°C, sakemm r- rikostituzzjoni/ dilwazzjoni ma tkunx saret f’ post kontrollat b’ kundizzjonijiet asettiċi validati.
Cubicin is not physically or chemically compatible with glucose-containing solutions.
Cubicin mhuwiex kompatibbli fiżikament jew kimikament ma ’ soluzzjonijiet li fihom glucose.
This medicinal product must not be mixed with other medicinal products except those mentioned above.
Dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħrajn ħlief dawk imsemmija hawn fuq.
Any unused portion remaining in the vial should be discarded.
Il- kunjetti ta ’ Cubicin huma għal użu ta ’ darba biss. Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa wara l- użu tal- prodott għandu jintrema.
INFORMATION FOR THE USER
42 FULJETT TA ’ TAGĦRIF:
45 Tell your doctor if you develop any of the following symptoms:
43 Għid lit- tabib tiegħek jekk tiżviluppa xi wieħed mis- sintomi li ġejjin:
If your kidneys do not work well, you may receive Cubicin less often, e. g. once every other day.
44 Jekk il- kliewi tiegħek mhux qed jaħdmu tajjeb, tista ’ tirċievi Cubicin anqas ta ’ spiss, eż. darba kull jumejn.
46 A course of treatment usually lasts for 1 to 2 weeks for skin infections.
Kors ta ’ kura normalment idum minn ġimgħa sa ġimgħatejn għal infezzjonijiet tal- ġilda.
Č eská republika Novartis s. r. o.
46 Česká republika Novartis s. r. o.
49 INFORMATION FOR THE HEALTHCARE PROFESSIONALS
47 TAGĦRIF GĦALL- PROFESSJONISTI FIL- KURA TAS- SAĦĦA
500 mg presentation: a 50 mg/ ml concentration can be achieved by reconstituting with 10 ml of 0.9% sodium chloride intravenous infusion.
Preparat tal- 500 mg: konċentrazzjoni ta ’ 50 mg/ ml tista ’ tinkiseb billi tħallat ma ’ 10 ml ta ’ 0. 9% sodium chloride infużjoni għal ġol- vina.
Vials of 500 mg/ vial can also be reconstituted with sterile water for injections.
Kunjetti ta ’ 500 mg/ kunjett jistgħu jiġu rikostitwiti wkoll b’ ilma sterili għall- injezzjonijiet.
This document is a summary of the European Public Assessment Report (EPAR).
Dan id- dokument huwa sommarju tar- Rapport tal- Valutazzjoni Pubblika Ewropew.
It explains how the Committee for Medicinal products for Human Use (CHMP) assessed the studies performed, to reach their recommendations on how to use the medicine.
L- għan tiegħu huwa li jispjega kif il- valutazzjoni mwettqa mill- Kumitat għall- Prodotti Mediċinali għal Użu Veterinarju (CVMP) abbażi tad- dokumentazzjoni pprovduta, wasslet għar- rakkomandazzjonijiet fuq il- kundizzjonijiet ta ’ l- użu.
If you need more information about your medical condition or your treatment, read the Package Leaflet (also part of the EPAR) or contact your doctor or pharmacist.
Jekk tixtieq iktar informazzjoni dwar il- kundizzjoni medika jew it- trattament mediku ta ’ l- annimal tiegħek, ikkuntattja lill- veterinarju tiegħek.
If you want more information on the basis of the CHMP recommendations, read the Scientific Discussion (also part of the EPAR).
Jekk tixtieq iktar informazzjoni abbażi tar - rakkomandazzjonijiet tal- CVMP, aqra d- Diskussjoni Xjentifika (parti wkoll mill- EPAR).
What is Cyanokit?
X’ inhu Cyanokit?
Cyanokit is a powder to be made up into a solution for infusion (drip into a vein).
Cyanokit huwa trab li jitħallat f’ soluzzjoni għal infużjoni (drip ġol- vina).
It contains the active substance hydroxocobalamin (vitamin B12a).
Huwa fih is- sustanza attiva hydroxocobalamin (vitamina B12a).
What is Cyanokit used for?
Għal xiex jintuża Cyanokit?
Cyanokit is used as an antidote to treat known or suspected poisoning with cyanide, a highly poisonous chemical.
Cyanokit jintuża bħala antidot biex jikkura avvelenament magħruf jew issuspettat biċ- ċjanur, kimika velenuża ħafna.
Cyanide poisoning usually results from exposure to smoke from fire, from breathing or swallowing cyanide, or from getting it on the skin or mucous membranes (moist body surfaces, such as the lining of the mouth).
Avvelenament biċ- ċjanur ġeneralment jirriżulta minn espożizzjoni għal duħħan minn nar, minn teħid man- nifs ta ’ ċjanur jew meta jinbela ċjanur, jew milli jmiss mal- ġilda jew mal - membrani mukużi (uċuh umidi, bħal ma hija l- inforra tal- ħalq).
How is Cyanokit used?
Kif jintuża Cyanokit?
Cyanokit is given as an emergency treatment as soon as possible after poisoning.
Cyanokit jintuża bħala kura ta ’ emerġenza kemm jista ’ jkun malajr wara l- avvelenament.
It is given as an intravenous infusion over 15 minutes.
Huwa jingħata bħal infużjoni intravenuża fuq 15- il minuta.
For adults, the initial dose is 5 g.
Għall- adulti, id- doża tal- bidu hija 5 g.
For children, it is 70 mg per kilogram body weight up to a maximum dose of 5 g.
Għat- tfal, hija 70 mg għal kull kilogramm tal- piż tal- ġisem sa doża massima ta ’ 5 g.
A second dose can be given, depending on how severe the poisoning is and how well the patient is responding.
Tista ’ tingħata t- tieni doża, jiddependi kemm ikun qawwi l- avvelenament u kemm ikun qed jirrispondi tajjeb il- pazjent.
The second dose is given over a period of between 15 minutes and two hours, depending on the patient’ s condition.
It- tieni doża tingħata fuq perijodu ta ’ bejn 15- il minuta u sagħtejn, jiddependi fuq il- kundizzjoni tal- pazjent.
The maximum dose is 10 g for adults, and 140 mg/ kg in children up to a maximum of 10 g.
Id- doża massima hija ta ’ 10 g għall- adulti, u 140 mg/ kg fit- tfal sa massimu ta ’ 10 mg.
Cyanokit is given along with appropriate measures to decontaminate and support the patient, including providing oxygen for the patient to breathe.
Cyanokit jingħata flimkien mal- miżuri adatti biex titneħħa l- kontaminazzjoni u bħala appoġġ lill - pazjent, inkluż l- għoti ta ’ l- ossiġnu biex il- pazjent jieħu n- nifs.
How does Cyanokit work?
Kif jaħdem Cyanokit?
The active substance in Cyanokit, hydroxocobalamin, reacts with cyanide in the body.
Is- sustanza attiva f’ Cyanokit, hydroxocobalamin, tirreaġixxi maċ- ċjanur fil- ġisem.
This reaction forms cyanocobalamin, a non-poisonous compound that is removed from the body in the urine.
Din ir- reazzjoni tifforma cyanocobalamin, taħlita mhux velenuża li titneħħa mill- ġisem fl- awrina.
This lowers cyanide levels in the body and stops the cyanide fixing itself to an enzyme in cells called cytochrome oxidase, which is important for providing energy in cells.
Din tbaxxi l- livelli taċ- ċjanur fil- ġisem u twaqqaf liċ- ċjanur milli jeħel ma ’ enzima fiċ- ċelloli msejjħa cytochrome oxidase, li hija importanti biex tipprovdi enerġija fiċ- ċelloli.
This helps to reduce the effects of cyanide poisoning.
Dan jgħin biex inaqqas l- effetti ta ’ avvelenament biċ- ċjanur.
Hydroxocobalamin (vitamin B12a) has been used as a vitamin supplement since the 1950s.
Hydroxocobalamin (vitamina B12a) ilha tintuża bħala vitamina supplimentari mill- ħamsinijiet.
How has Cyanokit been studied?
Kif ġie studjat Cyanokit?
The effects of Cyanokit were first tested in experimental models before being studied in humans.
L- effetti ta ’ Cyanokit ġew l- ewwel ittestjati f’ mudelli esperimentali qabel ma ġew studjati fil - bnedmin.
There have been no studies directly comparing the effectiveness of Cyanokit to any other treatment in humans.
Ma kien hemm l- ebda studju li qabbel direttament l- effikaċja ta ’ Cyanokit ma ’ xi kura oħra fil - bniedem.
Information on its effectiveness was obtained in 83 patients who had been admitted to 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
Tagħrif fuq l- effikaċja tiegħu kien miksub fi 83 pazjent li kienu mdaħħla l- isptar b’ suspett 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
(44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged hospital with suspected cyanide poisoning and who received Cyanokit.
(44- 20) 74 18 84 00 Fax (44- 20) 74 18 84 16 E- mail: mail@ emea. europa. eu http: // www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged ta ’ avvelenament biċ- ċjanur u li rċievew Cyanokit.
In one study of 69 patients, cyanide poisoning was due to exposure to smoke from fire.
Fi studju ta ’ 69 pazjent, l- avvelenament biċ- ċjanur kien minn espożizzjoni għad- duħħan minn nar.
In this study, the patients’ condition at the accident scene was compared with that at the end of the infusion of Cyanokit and over the following three days.
F’ dan l- istudju, il- kondizzjoni tal- pazjent fis- sit ta ’ l - aċċident kienet imqabbla ma ’ dik fit- tmiem ta ’ l- infużjoni b’ Cyanokit u fuq it- tlett- ijiem segwenti.
A further 14 patients were studied whose cyanide poisoning was due to something other than smoke inhalation; most of these patients had taken cyanide during a suicide attempt.
Kienu studjati 14- il pazjent oħra, f’ liema, l- avvelenament biċ- ċjanur kien minħabba xi ħaġa oħra u mhux minħabba inalazzjoni tad- duħħan; il- parti l- kbira ta ’ dawn il- pazjenti kienu ħadu ċjanur waqt tentattiv ta ’ suwiċidju.
The information on these patients was obtained from their medical notes, as recorded in databases at two French hospitals.
It- tagħrif fuq dawn il- pazjenti kien miksub min- noti mediċi tagħhom, kif iddokumentati f’ databases f’ żewġ sptarijiet Franċiżi.
What benefit has Cyanokit shown during the studies?
X’ benefiċċju wera Cyanokit waqt l- istudji?
In the study of smoke inhalation, the response to Cyanokit was assessed as ‘ positive ’ in 31 patients (45%), ‘ partial’ in 15 (22%) and ‘ absent’ in 10 (15%).
Fl- istudju ta ’ l- inalazzjoni bid- duħħan, ir- reazzjoni għal Cyanokit kienet stmata bħala ‘ pożittiva ’ f’ 31 pazjent (45%), ‘ parzjali ’ fi 15 (22%) u ‘ assenti ’ f’ 10 (15%).
The response was unknown in the remaining 13 patients.
Ir- reazzjoni ma kinitx magħrufa fil- bqija tat- 13- il pazjent.
Fifty of the patients in this study survived.
Ħamsin mill- pazjenti f’ dan l- istudju baqgħu ħajjin.
Survival was more likely in those who received Cyanokit before their hearts had stopped, who had less severe symptoms of brain damage and who had lower blood cyanide levels.
Is- sopravivenza kienet aktar probabbli f’ dawk li rċievew Cyanokit qabel ma waqfetilhom qalbhom, li kellhom sintomi ta ’ ħsara fil - moħħ inqas severi u li kellhom livelli aktar baxxi taċ- ċjanur fid- demm.
Two patients survived despite their hearts having stopped before receiving Cyanokit.
Żewġ pazjenti issopravivew minkejja li qalbhom kienet waqfetilhom qabel irċievew Cyanokit.
Symptoms of brain damage resolved in 38 of 66 patients.
Sintomi ta ’ ħsara fil- moħħ irrisolvew fi 38 minn 66 pazjent.
Of the 14 patients whose cyanide exposure was due to something other than smoke inhalation, 10 survived, including seven patients with ‘ lethal’ levels of cyanide in the blood.
Mill- 14- il pazjent li l- espożizzjoni tagħhom għaċ- ċjanur kien għal xi ħaġa oħra barra inalazzjoni tad- duħħan, 10 issopravivew, inklużi seba ’ pazjenti b’ livelli ‘ letali ’ taċ - ċjanur fid- demm.
The four who died had high blood levels of cyanide, and either their hearts had stopped or they had stopped breathing before receiving Cyanokit.
L- erbgħa li mietu kellhom livelli għolja taċ- ċjanur fid- demm, u jew kienet waqfetilhom qalbhom jew waqfu jieħdu n- nifs qabel ma rċievew Cyanokit.
What is the risk associated with Cyanokit?
X’ inhu r- riskju assoċjat ma ’ Cyanokit?
Because hydroxocobalamin has an intense red colour, most patients will have dark red discoloration of the skin and mucous membranes for up to 15 days and of the urine for up to 35 days after receiving Cyanokit.
Minħabba li hydroxocobalamin għandu kulur aħmar qawwi, l- parti l- kbira tal- pazjenti jkollhom tindis aħmar skur tal- ġilda u tal- membrani mukużi għal sa 15- il jum u ta ’ l- awrina għal sa 35 jum wara li jirċievu Cyanokit.
The frequency of the other side effects of Cyanokit cannot be estimated with the information currently available.
Il- frekwenza ta ’ effetti sekondarji oħra ta ’ Cyanokit ma jistgħux jiġu stmati bit - tagħrif attwalment disponibbli.
For the full list of all side effects reported with Cyanokit, see the Package Leaflet.
Għal- lista sħiħa ta ’ l- effetti sekondarji kollha irrapportati b’ Cyanokit, ara l- Fuljett ta ’ Tagħrif.
The use of Cyanokit can interfere with the assessment of burns and with laboratory test results.
L- użu ta ’ Cyanokit jista ’ jxekkel l- istima ta ’ ħruq u t- testijiet tal- laboratorju.
A sticker explaining this is supplied with every pack of Cyanokit.
Tikketta li tispjega dan tiġi ma ’ kull pakkett ta ’ Cyanokit.
This can be attached to the patient’ s notes so that hospital staff are made aware of these effects of the medicine.
Din tista ’ titwaħħal man- noti tal- pazjenti sabiex l- impjegati ta ’ l - isptar tinġibdilhom l- attenzjoni fuq l- effetti ta ’ din il- mediċina.
Why has Cyanokit been approved?
Għaliex ġie approvat Cyanokit?
The Committee for Medicinal Products for Human Use (CHMP) concluded that Cyanokit appeared to be a well-tolerated and efficient cyanide antidote, based on its effects on survival and the prevention of brain damage.
Il- Kumitat għal Prodotti Mediċinali għal Użu mill- Bniedem (CHMP) ikkonkluda li Cyanokit jidher li huwa antidot taċ- ċjanur ittolerat tajjeb u effiċjenti, abbażi ta ’ l- effetti tiegħu fuq is- sopravivenza u l - prevenzjoni ta ’ ħsara lill- moħħ.
There is no information available on success rates with other antidotes for cyanide poisoning, so it was not possible to carry out a comparison between the success rates seen with Cyanokit and with alternatives.
Ma hemm l- ebda tagħrif disponibbli fuq ir- rati ta ’ suċċess b’ antidoti oħra għal avvelenament biċ- ċjanur, għalhekk ma kienx possibbli li jsir tqabbil bejn ir- rati ta ’ suċċess li jidhru b’ Cyanokit u b’ alternattivi.
However, the Committee concluded that Cyanokit had advantages over alternative antidotes because it has a good safety profile in patients who have not been poisoned.
Madankollu, il- Kumitat ikkonkluda li Cyanokit għandu vantaġġi fuq antidoti alternattivi minħabba li għandu profil ta ’ sigurtà tajjeb f’ pazjenti li ma ġewx ivvelenati.
This makes it a useful option when cyanide poisoning is only suspected.
Dan jagħmlu għażla bżonnjuża meta avvelenament biċ- ċjanur huwa biss issuspettat.
Therefore, the CHMP decided that Cyanokit’ s benefits are greater than its risks for the treatment of known or suspected cyanide poisoning.
Għaldaqstant, is- CHMP iddeċieda li l- benefiċċji ta ’ Cyanokit huma akbar mir- riskji tiegħu għall- kura ta ’ avvelenament biċ- ċjanur magħruf jew issuspettat.
The Committee recommended that Cyanokit be given marketing authorisation.
Il- kumitat irrakomanda li Cyanokit jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Other information about Cyanokit:
Tagħrif ieħor dwar Cyanokit:
The European Commission granted a marketing authorisation valid throughout the European Union for Cyanokit to Merck Santé s. a. s. on 23 November 2007.
Il- Kummissjoni Ewropea tat l- awtorizzazzjoni għat- tqegħid fis- suq għal Cyanokit valida fl- Unjoni Ewropea kollha lil Merck Santé s. a. s. fil- 23 ta ’ Novembru 2007.
The full EPAR for Cyanokit can be found here.
L- EPAR sħiħ għal Cyanokit jista ’ jinstab minn hawnhekk.
This summary was last updated in 10-2007.
Dan is- sommarju ġie aġġornat l- aħħar f’ Ottubru 2007.
Strength 2.5 g
2. 5 g
Pharmaceutical form Powder for solution for infusion
Trab għal soluzzjoni għall - infużjoni
Route of administration Intravenous use
Użu għal ġol- vini
Packaging Vial (glass)
Kunjett (ħġieġ)
Package size 2 vials + 1 infusion set + 2 transfer devices + 1 short catheter
2 kunjetti + 1 sett ta ’ l- infużjoni + 2 strumenti tat- trasferiment + 1 kateter qasir
Cyanokit 2.5 g powder for solution for infusion
Cyanokit 2. 5 g trab għal soluzzjoni għall- infużjoni
Each vial contains 2.5 g of hydroxocobalamin.
Kull kunjett fih 2. 5 g ta ’ hydroxocobalamin.
After reconstitution with 100 ml of diluent, each ml of the reconstituted solution contains 25 mg of hydroxocobalamin.
Wara r- rikostituzzjoni b’ 100 ml ta ’ dilwent, kull millilitru tas- soluzzjoni rikostitwita jkun fih 25 mg ta ’ hydroxocobalamin.
Powder for solution for infusion.
Trab għal soluzzjoni għall- infużjoni.
Dark red crystalline powder.
Trab kristallin aħmar skur.
Treatment of known or suspected cyanide poisoning.
Trattament ta ’ avvelenament magħruf jew suspettat b’ cyanide.
Cyanokit is to be administered together with appropriate decontamination and supportive measures.
Cyanokit għandu jingħata flimkien ma ’ miżuri adegwati ta ’ dekontaminazzjoni u sapport.
Initial dose
Doża inizjali
Cyanokit is administered as an intravenous infusion over 15 minutes.
Cyanokit jingħata bħala infużjoni ġol- vini fuq perjodu ta ’ 15- il minuta.
The initial dose of Cyanokit is 5 g.
Id- doża inizjali ta ’ Cyanokit hi ta ’ 5 g.
In infants to adolescents, the initial dose of Cyanokit is 70 mg/ kg body weight not exceeding 5 g.
Fi tfal żgħar sa adolexxenti, id- doża inizjali ta ’ Cyanokit hi ta ’ 70 mg/ kg piż tal - ġisem, u ma taqbiżx 5 g.
Body weight in kg Initial dose
Piż tal- ġisem f’ kg Doża inizjali
in g in ml
fi g f’ ml
0.35 14
0. 35 14
0.70 28
0. 70 28
1.40 56
1. 40 56
2.10 84
2. 10 84
2.80 112
2. 80 112
3.50 140
3. 50 140
4.20 168
4. 20 168
Subsequent dose
Doża sussegwenti
Depending upon the severity of the poisoning and the clinical response (see section 4.4), a second dose may be administered by intravenous infusion.
Skond is- serjeta` ta ’ l- avvelenament u r- rispons kliniku (ara sezzjoni 4. 4), tista ’ tingħata t- tieni doża permezz ta ’ infużjoni ġol- vini.
The rate of infusion for the second dose ranges from 15 minutes (for patients extremely unstable) to 2 hours based on patient condition.
Ir- rata ta ’ l- infużjoni għat- tieni doża tvarja minn 15- il minuta (għal pazjenti li huma estremament instabbli) sa sagħtejn, skond il- kundizzjoni tal- pazjent.
The subsequent dose of Cyanokit is 5 g.
Id- doża sussegwenti ta ’ Cyanokit hi ta ’ 5 g.
In infants to adolescents, the subsequent dose of Cyanokit is 70 mg/ kg body weight not exceeding 5 g.
Fi tfal żgħar sa adolexxenti, id- doża sussegwenti ta ’ Cyanokit hi ta ’ 70 mg/ kg piż tal- ġisem, u ma taqbiżx 5 g.
2 Maximum dose
2 Doża massima
The maximum recommended dose is 10 g.
Id- doża massima rakkomandata hi ta ’ 10 g.
In infants to adolescents, the maximum recommended dose is 140 mg/ kg not exceeding 10 g.
Fi tfal żgħar sa adolexxenti, id- doża massima rakkomandata hi ta ’ 140 mg/ kg, u ma taqbiżx 10 g.
Renal and hepatic impairments Although the safety and efficacy of hydroxocobalamin have not been studied in renal and hepatic impairments, Cyanokit is administered as emergency therapy in an acute, life-threatening situation only and no dosage adjustment is required in these patients.
Indebolimenti renali u epatiku Għalkemm is- sigurtà u l- effikaċja ta ’ hydroxocobalamin ma kinux studjati f’ indebolimenti renali u epatiċi, Cyanokit jingħata bħala terapija ta ’ emerġenza f’ sitwazzjoni akuta u ta ’ periklu għall- ħajja biss, u l- ebda aġġustament fid- dożaġġ mhu meħtieġ f’ dawn il- pazjenti.
For instructions on preparation and handling, see section 6.6.
Għal struzzjonijiet fuq il- preparazzjoni u l- immaniġġjar, ara sezzjoni 6. 6.
None.
Xejn.
Treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of oxygenation and hydration, cardiovascular support, and management of seizures.
It- trattament ta ’ avvelenament b’ cyanide jrid jinkludi attenzjoni immedjata għall- ftuħ tal- passaġġ tan - nifs, ossiġinazzjoni u idratazzjoni adegwati, sapport kardjovaskulari u l- immaniġġjar tal- puplesiji.
Consideration must be given to decontamination measures based on the route of exposure.
Trid tingħata konsiderazzjoni għal miżuri ta ’ dekontaminazzjoni bbażati fuq ir- rotta ta ’ l- espożizzjoni.
Cyanokit does not substitute oxygen therapy and must not delay the set up of the above measures.
Cyanokit ma jissostitwixxix it- terapija bl- ossiġnu u ma jridx jittardja t- tħejjija tal- miżuri msemmija hawn fuq.
The presence and extent of cyanide poisoning are often initially unknown.
Il- preżenza u l- grad ta ’ avvelenament b’ cyanide ta ’ spiss ma jkunux magħrufa inizjalment.
There is no widely available, rapid, confirmatory cyanide blood test.
M’ hemm l - ebda test li hu komunement disponibbli, mgħaġġel u li jikkonferma l- preżenza ta ’ cyanide fid- demm.
Treatment decisions must be made on the basis of clinical history and/ or signs and symptoms of cyanide intoxication.
Id- deċiżjonijiet dwar it- trattament jridu jsiru abbażi ta ’ l- istorja klinika u/ jew sinjali u sintomi ta ’ intossikazzjoni ta ’ cyanide.
Cyanide poisoning may result from exposure to smoke from closed space fires, inhalation, ingestion, or dermal exposure.
L- avvelenament b’ cyanide jista ’ jkun ikkawżat minn espożizzjoni għal duħħan minn nar fi spazji magħluqa, ġbid man- nifs, bligħ jew espożizzjoni dermali.
Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogens, including cyanogenic plants, aliphatic nitriles, or prolonged exposure to sodium nitroprusside.
Sorsi ta ’ avvelenament b’ cyanide jinkludu hydrogen cyanide u l- imlieħi tiegħu, cyanogens, li jinkludu pjanti ċijanoġeniċi, aliphatic nitriles, jew espożizzjoni fit- tul għal sodium nitroprusside.
Signs and symptoms of cyanide poisoning
Sinjali u sintomi ta ’ avvelenament b’ cyanide
Common signs and symptoms of cyanide poisoning include: nausea, vomiting, headache, altered mental status (e. g. confusion, disorientation), chest tightness, dyspnoea, tachypnoea or hyperpnoea (early), bradypnoea or apnoea (late), hypertension (early) or hypotension (late), cardiovascular collapse, seizures or coma, mydriasis, and plasma lactate concentration > 8 mmol/ l.
Sinjali komuni u sintomi ta ’ avvelenament b’ cyanide jinkludu: nawsja, rimettar, uġigħ ta ’ ras, stat mentali mibdul (eż. konfużjoni, diżorjentament), tagħfis fis- sider, qtugħ ta ’ nifs, takipnea jew iperpnea (bikrija), bradipnea jew apnea (tardiva), pressjoni għolja (bikrija) jew pressjoni baxxa (tardiva), kollass kardjovaskulari, puplesiji jew koma, midrijasi, u konċentrazzjoni ta ’ plażma lactate ta ’ > 8 mmol/ l.
In the setting of multiple casualties such as terrorism or chemical disaster, panic symptoms including tachypnoea and vomiting may mimic early cyanide poisoning signs.
F’ każ ta ’ ħafna vittmi, bħal xi attakk terroristiku jew diżastru kimiku, sintomi ta ’ paniku li jinkludu takipnea u rimettar jistgħu jimitaw lis- sinjali bikrija ta ’ avvelenament b’ cyanide.
The presence of altered mental status (confusion and disorientation) and/ or mydriasis is suggestive of true cyanide poisoning.
Il- preżenza ta ’ stat mentali mibdul (konfużjoni u diżorjentament) u/ jew midrijasi, hija indikattiva ta ’ avvelenament reali b’ cyanide.
Smoke inhalation
Duħħan li jinġibed man- nifs
Not all smoke inhalation victims necessarily will have cyanide poisoning, but may present with burns, trauma, and exposure to additional toxic substances aggravating the clinical picture.
Mhux il- vittmi kollha tad- duħħan li jinġibed man- nifs neċessarjament ser ikunu avvelenati b’ cyanide, iżda dawn jista ’ jkollhom ħruq, trawma u espożizzjoni għal sustanzi tossiċi addizzjonali li jaggravaw il- kwadru kliniku.
Before Cyanokit is administered, it is recommended to check affected persons for the presence of the following: • exposure to fire smoke in an enclosed area • soot present around mouth, nose and/ or oropharynx • altered mental status
Qabel ma jingħata Cyanokit, hu rakkomandat li l- persuni affettwati jiġu ċċekkjati għal preżenza ta ’ dawn li ġejjin:
In this setting hypotension and/ or a plasma lactate concentration ≥ 10 mmol/ l (higher than the one mentioned under signs and symptoms due to the fact that carbon monoxide contributes to lactic
3 • espożizzjoni għal duħħan li jkun ġej minn nar f’ żona magħluqa • ġmied preżenti madwar il- ħalq, imnieħer u/ jew l- orofarinġi • stat mentali mibdul
3 acidaemia) are highly suggestive of cyanide poisoning.
F’ dan l- isfond, ipotensjoni u/ jew konċentrazzjoni ta ’ plażma lactate ta ’ ≥ 10 mmol/ l (ogħla minn dik imsemmija taħt ‘ sinjali u sintomi ’ minħabba l- fatt li carbon monoxide jikkontribwixxi għal lactic acidaemia) huma indikazzjoni ċara ħafna ta ’ avvelenament b’ cyanide.
In the presence of the above signs, treatment with Cyanokit must not be delayed to obtain a plasma lactate concentration.
Fil- preżenza tas- sinjali t’ hawn fuq, it- trattament b’ Cyanokit ma jridx jittardja biex tinkiseb konċentrazzjoni ta ’ plażma lactate.
Hypersensitivity reactions
Reazzjonijiet minħabba sensittività eċċessiva
Known hypersensitivity to hydroxocobalamin or vitamin B12 must be taken into benefit-risk consideration before administration of Cyanokit, since hypersensitive reactions may occur in patients receiving hydroxocobalamin (see section 4.8).
Sensittività eċċessiva magħrufa għal hydroxocobalamin jew vitamina B12 trid tkun ikkunsidrata fir - rigward tal- benefiċċju- riskju qabel l- għoti ta ’ Cyanokit, minħabba li jistgħu jseħħu reazzjonijiet minħabba sensittività eċċessiva f’ pazjenti li jkunu qed jirċievu hydroxocobalamin (ara sezzjoni 4. 8).
Increase in blood pressure
Żieda fil- pressjoni tad- demm
Transient, generally asymptomatic, increase in blood pressure may occur in patients receiving hydroxocobalamin.
Żieda temporanja u ġeneralment asintomatika fil- pressjoni tad- demm tista ’ sseħħ f’ pazjenti li jkunu qed jirċievu hydroxocobalamin.
The maximal increase in blood pressure has been observed toward the end of infusion.
Iż- żieda massima fil- pressjoni tad- demm kienet osservata lejn it - tmiem ta ’ l- infużjoni.
Effects on blood cyanide assay
L- effetti fuq l- assaġġ ta ’ cyanide fid- demm
Hydroxocobalamin will lower blood cyanide concentrations.
Hydroxocobalamin ser ibaxxi l- konċentrazzjonijiet ta ’ cyanide fid- demm.
While determination of blood cyanide concentration is not required and must not delay treatment with hydroxocobalamin, it may be useful for documenting cyanide poisoning.
Filwaqt li d- determinazzjoni tal- konċentrazzjoni fid- demm ta ’ cyanide mhijiex meħtieġa u m’ għandhux jittardja t- trattament b’ hydroxocobalamin, tista ’ tkun utili biex tiddokumenta l- avvelenament b’ cyanide.
If a cyanide blood level determination is planned, it is recommended to draw the blood sample before initiation of treatment with Cyanokit.
Jekk tkun ippjanata determinazzjoni tal- livell ta ’ cyanide fid- demm, hu rakkomandat li l- kampjun tad- demm jittieħed qabel il- bidu tat- trattament b’ Cyanokit.
Interference with burn assessment
Interferenza ma ’ l- evalwazzjoni ta ’ ħruq
Because of its deep red colour, hydroxocobalamin has the potential to induce a red colouration of the skin and therefore may interfere with burn assessment.
Minħabba l- kulur aħmar skur tiegħu, hydroxocobalamin għandu l- potenzjal li jikkaġuna ħmura tal - ġilda u għalhekk jista ’ jinterferixxi ma ’ l- evalwazzjoni tal- ħruq.
However, skin lesions, oedema, and pain are highly suggestive of burns.
Madankollu, leżjonijiet fil- ġilda, edema, u uġigħ, huma sewwasew indikazzjonijiet ta ’ ħruq.
Interference with laboratory tests
Interferenza ma ’ testijiet tal- laboratorju
Because of its deep red colour, hydroxocobalamin has the potential to interfere with determination of laboratory parameters (e. g. clinical chemistry, haematology, coagulation, and urine parameters).
Minħabba l- kulur aħmar skur tiegħu, hydroxocobalamin għandu l- potenzjal li jinterferixxi mad - determinazzjoni tal- parametri tal- laboratorju (eż. parametri ta ’ kimika klinika, ematoloġija, koagulazzjoni u awrina).
In vitro tests indicate that the extent and duration of the interference is dependant on numerous factors such as the dose of hydroxocobalamin, analyte, analyte concentration, methodology, analyser, concentrations of cobalamins-(III) including cyanocobalamin and partially the time between sampling and measurement.
Testijiet in vitro jindikaw li l- grad u t- tul ta ’ żmien ta ’ l- interferenza jiddependu fuq fatturi diversi bħad- doża ta ’ hydroxocobalamin, l- analyte, il- konċentrazzjoni ta ’ analyte, il- metodoloġija, l- analizzatur, il- konċentrazzjonijiet ta ’ cobalamins - (III) li jinkludu cyanocobalamin u parzjalment fuq il- ħin bejn meta jittieħed il- kampjun u l- kejl.
Based on in vitro studies and pharmacokinetic data obtained in healthy volunteers the following table describes interference with laboratory tests that may be observed following a 5 g dose of hydroxocobalamin.
Ibbażat fuq studji in vitro u informazzjoni farmakokinetika miksuba f’ voluntiera b’ saħħithom, it - tabella li ġejja tiddeskrivi l- interferenza mat- testijiet tal- laboratorju li tista ’ tkun osservata wara doża ta ’ 5 g ta ’ hydroxocobalamin.
Interference following a 10 g dose can be expected to last up to an additional 24 hours.
L- interferenza wara doża ta ’ 10 g tista ’ tkun mistennija li ddum sa 24 siegħa addizzjonali.
The extent and duration of interference in cyanide-poisoned patients may differ according to the severity of intoxication.
Il- grad u t- tul ta ’ żmien ta ’ interferenza f’ pazjenti li jkollhom avvelenament b’ cyanide jistgħu jvarjaw skond is- serjetà ta ’ l- intossikazzjoni.
Results may vary considerably from one analyser to another, therefore, caution is required when reporting and interpreting laboratory results.
Ir- riżultati jistgħu jvarjaw b’ mod konsiderevoli minn analizzatur wieħed għall- ieħor, għalhekk, attenzjoni hi meħtieġa fir- rappurtaġġ u fl- interpretazzjoni tar- riżultati tal- laboratorju.
Observed in vitro interferences of hydroxocobalamin with laboratory tests
4 Interferenzi osservata in vitro ta ’ hydroxocobalamin ma ’ testijiet tal- laboratorju
No interference
L- ebda interferenza osservata
Duration of
It- tul ta ’ żmien ta ’ l- interferenza
Laboratory parameter
Parametru tal -
observed
Imnaqqas
Artificially increased*
artifiċjalment *
Artificially decreased*
Artifiċjalment *
Unpredictable***
prevedibbli ***
interference after a 5 g dose
wara doża ta ’ 5 g
Clinical chemistry
Kimika klinika
Calcium Sodium Potassium Chloride Urea Gamma glutamyl transferase (GGT)
Kalċju Sodju Potassju Chloride Urea Gamma glutamyl transferase (GGT)
Creatinine Total and conjugate bilirubin** Triglycerides Cholesterol Total protein Glucose Albumin Alkaline
Krejatinina Bilirubina totali u konjugata ** Triglycerides Kolesterol Proteina totali Glukosju Albumina Alkaline phosphatase
Alanine aminotransferase (ALT) Amylase
Alanine aminotransferase (ALT) Amylase
Phosphate Uric acid Aspartate aminotransferase (AST) Creatine kinase (CK) Creatinine kinase isoenzym MB (CKMB) Lactate dehydrogenase
Phosphate Uric acid Aspartate aminotransferase (AST) Creatine kinase (CK) Creatinine kinase isoenzym MB (CKMB) Lactate dehydrogenase (LDH)
24 hours with the exception of bilirubin (up to 4 days)
24 siegħa bl - eċċezzjoni tal - bilirubina (sa 4 ijiem)
Haematology
Ematoloġija
Erythrocytes Haematocrit Mean corpuscular volume (MCV) Leucocytes Lymphocytes Monocytes Eosinophils Neutrophils Platelets
Eritroċiti Ematokrit Medja tal- volum korpuskolari (MCV) Lewkoċiti Limfoċiti Monoċiti Eosinofili Newtrofili Plejtlets
Haemoglobin (Hb) Mean corpuscular haemoglobin (MCH) Mean corpuscular haemoglobin concentration (MCHC)
Emoglobina (Hb) Medja ta ’ emoglobina korpuskolari (MCH) Medja tal - konċentrazzjoni ta ’ emoglobina korpuskolari (MCHC)
12-16 hours
12- 16- il siegħa
Coagulation * ≥ 10% interference observed on at least one analyser ** Artificially decreased using the diazo method *** Inconsistent results
Koagulazzjoni * ≥ 10% interferenza osservata fuq mill- inqas analizzatur wieħed ** Imnaqqas artifiċjalment bl- użu tal- metodu diazo *** Riżultati inkonsistenti
Activated partial thromboplastin time (aPTT) Prothrombin time (PT) Quick or INR
Ħin tat - tromboplastin parzjali attivat (aPTT) Ħin tal- protrombin (PT) Quick jew INR
24 hours
24 siegħa
Analysers used:
Analizzaturi użati:
Hydroxocobalamin may interfere with all urine colorimetric parameters.
Hydroxocobalamin jista ’ jinterferixxi mal- parametri kolorimetriċi ta ’ l- awrina.
The effects on these tests typically last 48 hours after a 5 g dose, but may persist for longer periods.
L- effetti fuq dawn it - testijiet tipikament idumu 48 siegħa wara doża ta ’ 5 g, iżda jistgħu jippersistu għal perjodi itwal.
Caution is required in the interpretation of urinary colorimetric tests for as long as chromaturia is present.
Attenzjoni hi meħtieġa fl- interpretazzjoni ta ’ testijiet kolorimetriċi ta ’ l- awrina sakemm il- kromaturja tkun preżenti.
Use with other cyanide antidotes
L- użu ma ’ antidoti oħrajn ta ’ cyanide
The safety of administering other cyanide antidotes simultaneously with Cyanokit has not been established (see section 6.2).
Is- sigurtà li tagħti antidoti oħrajn ta ’ cyanide fl- istess ħin ma ’ Cyanokit ma kinitx stabbilita (ara sezzjoni 6. 2).
If the decision is made to administer another cyanide antidote with Cyanokit, these medicinal products must not be administered concurrently in the same intravenous line (see section 6.2).
Jekk issir id- deċiżjoni li jingħata antidotu ieħor ta ’ cyanide ma ’ Cyanokit, dawn il - prodotti mediċinali ma jridux jingħataw fl- istess ħin ġo l- istess linja tal- vini (ara sezzjoni 6. 2).
Animal studies have shown teratogenic effects following daily exposure throughout organogenesis (see section 5.3).
Studji fuq l- annimali wrew effetti teratoġeniċi wara l- espożizzjoni ta ’ kuljum matul l- organoġenesi (ara sezzjoni 5. 3).
There are no adequate data from the use of hydroxocobalamin in pregnant women and the potential risk for humans is unknown.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ hydroxocobalamin waqt it- tqala u mhux magħruf ir- riskju potenzjali fuq in- nies.
However, taken into account:
Madankollu, jekk wieħed jikkunsidra li:
- that no more than two injections of hydroxocobalamin are to be administered,
- mhux iktar minn żewġ injezzjonijiet ta ’ hydroxocobalamin jistgħu jingħataw,
- the potentially life threatening condition,
- il- kundizzjoni li potenzjalment tista ’ tipperikola l- ħajja,
- the lack of alternative treatment,
- in- nuqqas ta ’ trattamenti alternattivi adegwati,
hydroxocobalamin may be given to a pregnant woman.
hydroxocobalamin jista ’ jingħata lil mara tqila.
In case of known pregnancy at the time of treatment with Cyanokit or in case that pregnancy becomes known after treatment with Cyanokit, health care professionals are requested to promptly report the exposure during pregnancy to the Market Authorisation Holder and to carefully follow-up on the pregnancy and its outcome.
F’ każ ta ’ tqala magħruf fiż- żmien tal- kura b’ Cyanokit jew f’ każ li t- tqala ssir magħrufa wara l- kura b’ Cyanokit, il- professjonisti fil- qasam tal- kura tas- saħħa huma mitluba biex jirrappurtaw malajr l - espożizzjoni matul it- tqala lid- Detentur tal- Awtorizzazzjoni għat- Tqegħid fis- Suq u biex isegwu bl - attenzjoni t- tqala u r- riżultat tagħha.
5 Because hydroxocobalamin will be administered in potentially life-threatening situations, breast- feeding is not a contraindication to its use.
Minħabba li hydroxocobalamin ser jingħata f’ sitwazzjonijiet li potenzjalment jistgħu jipperikolaw il - ħajja, it- treddigħ mhuwiex kontra- indikazzjoni għall- użu tiegħu.
No studies on the effects on the ability to drive or to use machines have been performed.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
A total of 347 subjects were exposed to hydroxocobalamin in clinical studies.
Totali ta ’ 347 pazjent kienu esposti għal hydroxocobalamin fi studji kliniċi.
Of these 347 subjects, 245 patients had suspected exposure to cyanide at the time of hydroxocobalamin administration.
Minn dawn it- 347 pazjent, 245 pazjent kellhom espożizzjoni suspettata għal cyanide fil- ħin ta ’ l- għoti ta ’ hydroxocobalamin.
The remaining 102 subjects were healthy volunteers who had not been exposed to cyanide at the time of hydroxocobalamin administration.
Il - bqija tal- 102 suġġetti kienu voluntiera b’ saħħithom li ma kinux esposti għal cyanide fil- ħin ta ’ l- għoti ta ’ hydroxocobalamin.
Most patients will experience a reversible red colouration of the skin and mucous membranes that may last up to 15 days after administration of Cyanokit.
Il- biċċa l- kbira tal- pazjenti ser ikollhom ħmura riversibbli fil- ġilda u fil- membrani mukużi, li tista ’ ddum sa 15- il jum wara l- għoti ta ’ Cyanokit.
All patients will show a dark red colouration of the urine quite marked during the three days following administration.
Il- pazjenti kollha ser ikollhom awrina kulur aħmar skur notevoli matul it- tlitt ijiem wara l- għoti.
Urine colouration may last up to 35 days after administration of Cyanokit.
Il- kulur fl- awrina jista ’ jdum sa 35 jum wara l- għoti ta ’ Cyanokit.
The following undesirable effects have been reported in association with Cyanokit use.
L- effetti mhux mixtieqa li ġejjin kienu rrappurtati b’ rabta ma ’ l- użu ta ’ Cyanokit.
However, because of the limitations of the available data, it is not possible to apply frequency estimations:
Madankollu, minħabba l- limitazzjonijiet ta ’ l- informazzjoni disponibbli, mhuwiex possibbli li jkunu applikati l - istimi tal- frekwenza:
Cyanokit may cause red discolouration of the plasma, which may cause artificial elevation or reduction in the levels of certain laboratory parameters (see section 4.5).
Cyanokit jista ’ jikkawża tibdil ħamrani tal- plażma, li jista ’ jikkawża żieda jew tnaqqis artifiċjali fil - livelli ta ’ ċerti parametri tal- laboratorju (ara sezzjoni 4. 4).
Cardiac disorders
Disturbi fil- kardiaċi
Ventricular extrasystoles.
Extrasystoles ventrikulari.
An increase in heart rate was observed in cyanide-poisoned patients.
Żieda fir- rata ta ’ taħbit tal- qalb kienet osservata f’ pazjenti li kienu avvelenati b’ cyanide.
Blood and lymphatic system disorders
Disturbi tad- demm u tas- sistema limfatika
Decrease in the percentage of lymphocytes.
Tnaqqis fil- perċentwali tal- limfoċiti.
Memory impairment; dizziness.
Indeboliment fil- memorja; sturdament.
Swelling, irritation, redness.
Nefħa, irritazzjoni, ħmura.
Pleural effusion, dyspnoea, throat tightness, dry throat, chest discomfort.
Ħruġ ta ’ likwidu mill- plewra, qtugħ ta ’ nifs, tagħfis fil- gerżuma, gerżuma xotta, skomdu fis- sider.
Gastrointestinal disorders
6 Disturbi gastro- intestinali
Abdominal discomfort, dyspepsia, diarrhoea, vomiting, nausea, dysphagia.
Skomdu addominali, dispepsja, dijarea, rimettar, nawsja, disfaġja.
Renal and urinary disorders
Disturbi renali u fis- sistema urinarja
Chromaturia (see above).
Kromaturja (ara hawn fuq).
6 Reversible red colouration of the skin and mucous membranes (see above).
Ħmura riversibbli fil- ġilda u fil- membrani mukużi (ara hawn fuq).
Pustular rashes, which may last for several weeks, affecting mainly the face and the neck.
Raxx bil- ponot, li jista ’ jdum għal diversi ġimgħat, li jaffettwa primarjament il- wiċċ u l- għonq.
Transient increase in blood pressure, usually resolving within several hours; hot flush.
Żieda temporanja fil- pressjoni tad- demm, li normalment tgħaddi fi żmien diversi sigħat; fwawar.
A decrease in blood pressure was observed in cyanide-poisoned patients.
Tnaqqis fil- pressjoni tad- demm kien osservat f’ pazjenti avvelenati b’ cyanide.
Headache; injection site reaction; peripheral oedema.
Uġigħ ta ’ ras; reazzjoni fil- post ta ’ l- injezzjoni; edema periferali.
Allergic reactions including angioneurotic oedema, skin eruption, urticaria and pruritus.
Reazzjonijiet allerġiċi li jinkludu edema anġjonewrotika, eruzzjoni fil- ġilda, urtikarja u ħakk.
Restlessness.
Nuqqas ta ’ kwiet.
Doses as high as 15 g have been administered without reported specific dose related adverse reactions.
Dożi sa 15 g ingħataw mingħajr ebda rapporti ta ’ reazzjonijiet avversi speċifiċi relatati mad- doża.
If overdose occurs, treatment is directed to the management of symptoms.
Jekk isseħħ doża eċċessiva, it- trattament hu dirett lejn l- immaniġġjar tas- sintomi.
Haemodialysis may be effective in such a circumstance, but is only indicated in the event of significant hydroxocobalamin- related toxicity.
L- emodijalisi tista ’ tkun effettiva f’ ċirkustanza bħal din, iżda hi indikata biss f’ każ ta ’ tossiċità sinjifikanti relatata ma ’ hydroxocobalamin.
PHARMACOLOGICAL PROPERTIES
PROPRJETAJIET FARMAKOLOĠIKU
5.1 Pharmacodynamic properties
5. 1 Proprjetajiet farmakodinamiki
Antidote, ATC code:
Antidotu, Kodiċi ATC:
The action of hydroxocobalamin in the treatment of cyanide poisoning is based on its ability to tightly bind cyanide ions.
L- azzjoni ta ’ hydroxocobalamin fit- trattament ta ’ avvelenament b’ cyanide hi bbażata fuq il- ħila tiegħu li jgħaqqad sewwa l- joni ta ’ cyanide.
Each hydroxocobalamin molecule can bind one cyanide ion by substituting the hydroxo ligand linked to the trivalent cobalt ion to form cyanocobalamin.
Kull molekula ta ’ hydroxocobalamin tista ’ tingħaqad ma ’ jone waħda ta ’ cyanide billi tissostitwixxi l- ligand hydroxo marbut mal- jone trivalenti tal- cobalt biex tifforma cyanocobalamin.
Cyanocobalamin is a stable, non-toxic compound that is excreted in the urine.
Cyanocobalamin hu kompost stabbli, mhux tossiku, li jitneħħa fl- awrina.
Due to ethical considerations, no controlled human efficacy studies have been performed.
Minħabba konsiderazzjonijiet etiċi, ma saru l- ebda studji kkontrollati dwar l- effikaċja fil- bniedem.
• Animal pharmacology
7 • Farmakoloġija fl- annimali
The effectiveness of hydroxocobalamin was examined in a controlled study in cyanide-poisoned adult dogs.
L- effettività ta ’ hydroxocobalamin kienet eżaminata fi studju kkontrollat fi klieb adulti li kienu avvelenati b’ cyanide.
Dogs were poisoned by intravenous administration of a lethal dose of potassium cyanide.
Il- klieb kienu avvelenati permezz ta ’ l- għoti ġol- vini ta ’ doża letali ta ’ potassium cyanide.
Dogs then received sodium chloride 9 mg/ ml, 75 mg/ kg or 150 mg/ kg hydroxocobalamin, administered intravenously over 7.5 minutes.
Il- klieb imbagħad irċivew 9 mg/ ml ta ’ sodium chloride, 75 mg/ kg jew 150 mg/ kg hydroxocobalamin, li ngħata minn ġol- vina fuq perjodu ta ’ 7. 5 minuti.
The 75 mg/ kg and 150 mg/ kg doses are approximately equivalent to 5 g and 10 g of hydroxocobalamin, respectively, in humans, not only on a body weight basis but also on Cmax basis of hydroxocobalamin [total cobalamins-(III), see section 5.2].
Id- dożi ta ’ 75 mg/ kg u 150 mg/ kg huma ekwivalenti bejn wieħed u ieħor għal 5 g u 10 g ta ’ hydroxocobalamin, rispettivament, fil- bnedmin, mhux biss fuq bażi ta ’ piż tal- ġisem iżda wkoll fuq bażi tas- Cmax ta ’ hydroxocobalamin [cobalamins - (III) totali, ara sezzjoni 5. 2].
Survival at hour 4 and at day 14 was significantly greater in 75 mg/ kg and 150 mg/ kg hydroxocobalamin dose groups compared with dogs receiving sodium chloride 9 mg/ ml alone:
Is- sopravivenza f’ siegħa 4 u f’ jum 14 kienet evidentement akbar fil- gruppi li ngħataw doża ta ’ 75 mg/ kg u 150 mg/ kg ta ’ hydroxocobalamin meta mqabbla ma ’ klieb li kienu qed jirċievu 9 mg/ ml ta ’ sodium chloride biss:
7 Survival of cyanide-poisoned dogs
Sopravivenza ta ’ klieb avvelenati b’ cyanide
Parameter Survival at Hour 4, N (%) Survival at Day 14, N (%)
Parametru Sopravivenza f’ Siegħa 4, N (%) Sopravivenza f’ Jum 14, N (%) < 0. 025
(N=19) 18 (95)* 15 (79)*
(N=19) 18 (95) * 15 (79) *
(N=18) 18 (100)* 18 (100)*
(N=18) 18 (100) * 18 (100) *
Histopathology revealed brain lesions that were consistent with cyanide-induced hypoxia.
L- istopatoloġija żvelat leżjonijiet fil- moħħ li kienu konsistenti ma ’ nuqqas ta ’ ossiġnu kkaġunati mic - cyanide.
The incidence of brain lesions was markedly lower in dogs having received 150 mg/ kg hydroxocobalamin than in dogs having received 75 mg/ kg hydroxocobalamin or sodium chloride 9 mg/ ml.
L- inċidenza ta ’ leżjonijiet fil- moħħ kienet notevolment iktar baxxa fi klieb li kienu rċivew 150 mg/ kg ta ’ hydroxocobalamin milli fi klieb li kienu rċivew 75 mg/ kg ta ’ hydroxocobalamin jew 9 mg/ ml ta ’ sodium chloride.
The rapid and complete recovery of haemodynamics and subsequently of blood gases, pH, and lactate after cyanide poisoning likely contributed to the better outcome of the hydroxocobalamin-treated animals.
L- irkuprar mgħaġġel u komplut ta ’ l- emodinamika u sussegwentement tal- gassijiet fid- demm, pH u lactate wara avvelenament b’ cyanide, x’ aktarx li kkontribwew għar- riżultat aħjar fl- annimali trattati bil- hydroxocobalamin.
Hydroxocobalamin reduced whole blood cyanide concentrations from about 120 nmol/ ml to 30-40 nmol/ ml by the end of the infusion compared with 70 nmol/ ml in dogs receiving sodium chloride 9 mg/ ml alone.
Hydroxocobalamin naqqas konċentrazzjonijiet sħaħ ta ’ cyanide fid- demm minn madwar 120 nmol/ ml sa 30- 40 nmol/ ml sat- tmiem ta ’ l- infużjoni meta mqabbel ma ’ 70 nmol/ ml fi klieb li kienu qed jirċievu 9 mg/ ml sodium chloride biss.
• Cyanide-poisoned patients
• Pazjenti avvelenati b’ cyanide
A total of 245 patients with suspected or known cyanide-poisoning were included in the clinical studies of the efficacy of hydroxocobalamin as an antidote.
Total ta ’ 245 pazjent b’ avvelenament suspettat jew magħruf ta ’ cyanide, kienu inklużi fl- istudji kliniċi dwar l- effikaċja ta ’ hydroxocobalamin bħala antidotu.