qanastek/EMEA-V3 huggingface dataset:
Refludan is used to prevent blood clotting in adult patients with heparin-induced thrombocytopenia (HIT, a certain type of allergy to heparin which causes a lack of platelets in the blood or clots in the blood vessels) and who have thromboembolic disease (abnormal development of blood clots) that needs injected antithrombotic treatment, usually heparin.
Refludan jintuża sabiex jimpedixxi t- tagħqid tad- demm f’ pazjenti adulti bi tromboċitopenija indotta mill- eparina (HIT, ċertu tip ta ’ allerġija għall- eparina li tikkawża nuqqas ta ’ pjastrini (platelets) fid - demm jew emboli fil- vini u l- arterji) u li għandhom mard trombo- emboliku (żvilupp anormali ta ’ emboli) li jeħtieġ trattament anti- trombotiku injettat, ġeneralment eparina.
The diagnosis must be confirmed using specific tests, such as the heparin induced platelet aggregation assay (HIPAA) test.
Id- dijanjosi trid tiġi kkonfermata bl- użu ta ’ testijiet speċifiċi, bħall- heparin induced platelet aggregation assay (HIPAA) test.
How is Refludan used?
Kif jintuża Refludan?
Refludan is given by injection and intravenous infusion (drip into a vein).
Refludan jingħata b’ injezzjoni u infużjoni fil- vini (dripp ġo vina).
A doctor who has experience in the treatment of coagulation (clotting) disorders should initiate treatment with Refludan.
Il- kura b’ Refludan għandha tinbeda minn tabib li jkollu esperjenza fit- trattament ta ’ disturbi tal- koagulazzjoni (tagħqid tad- demm).
The recommended dose is 0.4 mg/ kg body weight as a single intravenous injection followed by 0.15 mg/ kg body weight per hour as a continuous intravenous infusion for 2 to 10 days, or longer if needed.
Id - doża rakkomandata hija 0. 4 mg/ kilogramm ta ’ piż tal- ġisem bħala injezzjoni waħda fil- vini segwita minn 0. 15 mg/ kilogramm ta ’ piż tal- ġisem kull siegħa bħala infużjoni kontinwa fil- vini għal 2 sa 10 ijiem, jew itwal jekk ikun meħtieġ.
The doses need to be reduced in patients with kidney problems.
Id- dożi jeħtieġ li jitnaqqsu f’ pazjenti bi problemi tal- kliewi.
How does Refludan work?
Kif jaħdem Refludan?
Refludan is an antithrombotic medicine.
Refludan huwa mediċina anti- trombotika.
It prevents the blood from coagulating (clotting).
Huwa jimpedixxi lid- demm milli jikkoagula (jagħqad).
Lepirudin, the active substance in Refludan, is nearly identical to hirudin, the anticoagulant substance produced by leeches.
Lepirudin, is- sustanza attiva f’ Refludan, huwa kważi identiku għal hirudin, is- sustanza anti- koagulanti prodotta mis- sangisugi.
Lepirudin is made by a cell that has received a gene (DNA), which makes it able to produce the substance.
Lepirudin isir minn ċellola li tkun irċeviet ġene (DNA), li jagħmilha kapaċi li tipproduċi s- sustanza.
Lepirudin specifically blocks one of the substances involved in the clotting process, thrombin.
Lepirudin jimblokka speċifikament waħda mis- sustanzi involuti fil- proċess tal - koagulazzjoni, thrombin.
Thrombin is central for the complete process of blood clotting.
Thrombin huwa fundamentali għall- proċess sħiħ tal- koagulazzjoni tad - demm.
Refludan greatly reduces the risk of blood clots forming, preventing subsequent damage.
Refludan inaqqas ħafna r- riskju li jiffurmaw emboli, u b’ hekk jevita ħsara suċċessiva.
How has Refludan been studied?
Kif ġie studjat Refludan?
Refludan has been studied in 198 patients in two trials.
Refludan ġie studjat fuq 198 pazjent f’ żewġ provi.
The studies examined death, amputations, and new thromboembolic (clotting) complications.
L- istudji eżaminaw mewt, amputazzjonijiet, u kumplikazzjonijiet trombo- emboliċi (tagħqid tad- demm) ġodda.
The trials did not include a comparison treatment so the results were judged against historical controls (expected results without treatment based on past studies).
Il- provi ma inkludewx kura ta ’ tqabbil u għalhekk ir- riżultati ġew iġġudikati fuq kontrolli li saru maż- żmien (ir- riżultati mistennija mingħajr il- kura fuq il- bażi ta ’ studji preċedenti).
(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 What benefit has Refludan shown during the studies?
(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 X’ benefiċċju wera Refludan matul l- istudji?
The overall mortality (death rate) during the study period was 9%.
Il- mortalità globali (rata ta ’ mwiet) matul il- perjodu ta ’ l- istudju kienet ta ’ 9%.
Six per cent of the patients had amputations and 10% had new thromboembolic complications.
Sitta fil- mija tal - pazjenti kellhom amputazzjonijiet u 10% kellhom kumplikazzjonijiet trombo- emboliċi ġodda.
In the comparison with historical controls, the 2 trials taken together showed a significant benefit of Refludan on the rate of new thromboembolic complications and a trend towards increased survival.
Fit - tqabbil mal- kontrolli li saru maż- żmien, iż- żewġ provi meħudin flimkien urew benefiċċju sinifikanti ta ’ Refludan fuq ir- rata ta ’ kumplikazzjonijiet trombo- emboliċi ġodda u tendenza favur sopravivenza akbar.
What is the risk associated with Refludan?
X’ inhu r- riskju assoċjat ma ’ Refludan?
As with other antithrombotic drugs, the most common side effect of Refludan (seen in more than 1 patient in 10) is bleeding.
Bħal fil- każ ta ’ mediċini anti- trombotiċi oħra, l- aktar effett sekondarju komuni ta ’ Refludan (jidher f’ aktar minn 1 minn kull 10 pazjenti) huwa fsada.
Bleeding leading to death occurs in around 1 patient in 100.
Fsada li twassal għall- mewt isseħħ f’ madwar pazjent wieħed minn kull 100.
For the full description of the side effects reported with Refludan, see the Package Leaflet.
Għal deskrizzjoni sħiħa ta ’ l- effetti sekondarji rrapportati b’ Refludan, ara l- Fuljett ta ’ Tagħrif.
Refludan should not be used in people who may be hypersensitive (allergic) to lepirudin, any other hirudin derivative, or any of the other ingredients, or who are currently bleeding.
Refludan m’ għandux jintuża f’ nies li jista ’ jkollhom sensittività eċċessiva (allerġiċi) għal lepirudin, kull derivattiv ieħor ta ’ hirudin, għal xi sustanza oħra tiegħu, jew li jkollhom fsada.
This bleeding can be because the patient has recently had a biopsy, a stroke, major surgery, or is over the age of 65, among other reasons.
Din il- fsada tista ’ tkun minħabba li l- pazjent dik il- ħabta jkun għamel bijopsija, tatu puplesija, għamel operazzjoni maġġuri, jew ikollu aktar minn 65 sena, fost raġunijiet oħra.
See the Package Leaflet for the full list of restrictions.
Ara l- Fuljett ta ’ Tagħrif għal- lista sħiħa ta ’ restrizzjonijiet.
Some patients can have a serious allergic shock when they receive Refludan for a second time.
Xi pazjenti jista ’ jkollhom xokk allerġiku serju meta jirċievu Refludan għat- tieni darba.
Doctors should be very careful when re- exposing a patient to the medicine.
It- tobba għandhom joqogħdu attenti ħafna meta jerġgħu jesponu pazjent għall- mediċina.
Why has Refludan been approved?
Għaliex ġie approvat Refludan?
As the disease is very severe, and there is no other effective treatment approved, the Committee for Medicinal Products for Human Use (CHMP) decided that Refludan’ s benefits are greater than its risks for the treatment of patients with heparin-induced thrombocytopenia and thromboembolic disease.
Billi l- marda hija serja ħafna, u ma hemmx kura effettiva oħra approvata, il- Kumitat dwar il- Prodotti Mediċinali għal Użu mill- Bniedem (CHMP) iddeċieda li l- benefiċċji ta ’ Refludan huma akbar mir - riskji tiegħu għall- kura ta ’ pazjenti bi tromboċitopenija indotta mill- eparina u mard trombo- emboliku.
They recommended that Refludan be given marketing authorisation.
Huma rrikkmandaw li Refludan jingħata l- awtorizzazzjoni għat- tqegħid fis- suq.
Other information about Refludan:
Aktar tagħrif dwar Refludan:
The European Commission granted a marketing authorisation valid throughout the European Union, for Refludan on 13 March 1997.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha, għal Refludan fit- 13 ta ’ Marzu 1997.
The marketing authorisation was renewed on 13 March 2002 and 13 March 2007.
L- awtorizzazzjoni għat- tqegħid fis- suq ġiet mġedda fit - 13 ta ’ Marzu 2007.
The marketing authorisation holder is Pharmion Ltd.
Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq huwa Pharmion Ltd.
The full EPAR for Refludan is available here.
L- EPAR sħiħ għal Refludan jista ’ jinstab hawnhekk.
This summary was last updated in 03-2007.
Dan is- sommarju kien aġġornat l- aħħar f’ 03- 2007.
EU/ 1/ 97/ 035/ 001
Numru ta ’ l- UE EU/ 1/ 97/ 035/ 001
Refludan
Isem ivvintat Refludan
Powder for solution for injection or infusion
Għamla Farmaċewtika Trab għal soluzzjoni għall - injezzjoni jew infużjoni
Intravenous use
Mnejn jingħata Użu għal ġol - vini
Powder for solution for injection or infusion
Trab għal soluzzjoni għall - injezzjoni jew infużjoni
Refludan 20 mg powder for solution for injection or infusion
Refludan 20 mg trab għal soluzzjoni għall- injezzjoni jew infużjoni
Each vial contains 20 mg lepirudin.
Kull fjala fiha 20 mg lepirudin.
(Lepirudin is a recombinant DNA product derived from yeast cells)
(Lepirudin huwa prodott ta ’ DNA rikombinat li ġej minn ċellolli tal- ħmira)
Powder for solution for injection or infusion.
Trab għal soluzzjoni għall- injezzjoni jew infużjoni.
White to almost white lyophilised powder.
Trab lajofilizzat abjad għal kważi abjad.
Anticoagulation in adult patients with heparin-induced thrombocytopenia (HIT) type II and thromboembolic disease mandating parenteral antithrombotic therapy.
Antikoagulazzjoni f’ pazjenti adulti b’ tromboċitopenija indotta mill- eparina (HIT) tat- tip II u mard tromboembolitiku li jeħtieġ terapija antitrombolitika parenterali.
The diagnosis should be confirmed by the HIPAA (heparin induced platelet activation assay) or an equivalent test.
Id- dijanjożi trid tiġi kkonfermata minn HIPAA (heparin induced platelet activation assay) jew test ekwivalenti.
Treatment with Refludan should be initiated under the guidance of a physician with experience in coagulation disorders.
Kura b’ Refludan għandha tinbeda taħt il- gwida ta ’ tabib b’ esperjenza fil- mard tal- koagulazzjoni.
Initial dosage
Doża tal- bidu
Anticoagulation in adult patients with HIT type II and thromboembolic disease:
Antikoagulazzjoni f’ pazjenti adulti b’ HIT tat- tip II u mard tromboembolitiku:
– 0.4 mg / kg body weight intravenously as a bolus dose – followed by 0.15 mg / kg body weight / hour as a continuous intravenous infusion for 2 - 10 days or longer if clinically needed.
– 0. 4 mg / kg piż tal- ġisem ġol- vina bħala doża bolus – segwit minn 0. 15 mg / kg piż tal- ġisem / siegħa bħala infużjoni kontinwa ġol- vina għal 2 – 10 ġurnata jew aktar jekk klinikament meħtieġ.
Normally, the dosage depends on the patient's body weight.
Normalment, id- dożaġġ jiddependi fuq il- piż tal- ġisem tal- pazjent.
This is valid up to a body weight of 110 kg.
Dan huwa validu sa piż tal- ġisem ta ’ 110 kg.
In patients with a body weight exceeding 110 kg the dosage should not be increased beyond the 110 kg body weight dose (see also tables 2 and 3, below).
F’ pazjenti b’ piż tal- ġisem aktar minn 110 kg id- dożaġġ m’ għandux jiġi miżjud aktar mid- doża ta ’ 110 kg piż tal- ġisem (ara wkoll tabelli 2 u 3, isfel).
Monitoring and modification of the Refludan dosage regimen
Sorveljanza u modifikazzjoni tal- kors ta ’ dożaġġ ta ’ Refludan
Standard recommendations
Rakkomandazzjonijiet stàndard
Monitoring: – In general, the dosage (infusion rate) should be adjusted to the activated partial thromboplastin time, aPTT. – The first aPTT determination should be done 4 hours after start of Refludan therapy.
Sorveljanza: – Ġeneralment, id- dożaġġ (rata ta ’ infużjoni) għandu tiġi aġġustat għall- ħin ta ’ thromboplastin parzjali attivat, aPTT. – L- ewwel determinazzjoni ta ’ aPTT għandha ssir 4 siegħat wara l- bidu ta ’ terapija b’ Refludan. – L’ aPTT għandu jiġi sorveljat ta ’ l- inqas darba kuljum.
2 – The aPTT should be monitored at least once daily.
2 – Firxa mmirata (tieqa terapewtika) għal aPTT:
- Using "Actin FS" or "Neothromtin" on automated coagulometers the target range for the
- Bl- użu ta ’ "Actin FS" jew "Neothromtin" f’ koagulometri awtomati il- firxa mmirata għal aPTT
aPTT is 1.5 fold to 3 fold prolongation of the normal control value.
hija titwil ta ’ 1. 5 drabi sa 3 darbiet aktar mill- valur normali ta ’ kontroll.
- With other reagents, the upper limit of the therapeutic aPTT window should be reduced to
- B’ reaġents oħra, il- limitu ta ’ fuq tat- tieqa terapewtika ta ’ aPTT għandha titnaqqas għal titwil ta ’
2.5 fold prolongation of the normal control value.
2. 5 drabi aktar mill- valur normali ta ’ kontroll.
- To obtain specific and exact aPTT limits, the laboratory equipment / test reagent used may
- Sabiex jinkiżbu limiti speċifiċi u eżatti ta ’ aPTT, l- apparat tal- laboratorju / reaġent tat- test użati
be calibrated by spiking standardised human plasma with 0.15 μ g/ ml lepirudin (lower limit) and 1.5 μ g/ ml lepirudin (upper limit).
jistgħu jiġu kkalibrati billi tintuża plażma uman standardizzata miżjuda ma ’ 0. 15 μg/ ml lepirudin (limitu baxx) u 1. 5 μg/ ml lepirudin (limitu għoli).
Dose modifications: – Any aPTT value out of the target range is to be confirmed at once before drawing conclusions with respect to dose modifications, unless there is a clinical need to react immediately. – If the confirmed aPTT value is above the target range, the infusion should be stopped for two hours.
Modifikazzjoni tad- doża: – Kull valur ta ’ aPTT li jkun barra mill- firxa mmirata għandu jiġi kkonfermat minnufih qabel ma jsiru konklużjonijiet dwar modifikazzjonijiet tad- doża, sakemm ma hemmx ħtieġa klinika biex tirreaġixxi minnufih. – Jekk il- valur ikkonfermat ta ’ aPTT huwa għola mill- firxa mmirata, l- infużjoni għandha titwaqqaf għal sagħtejn.
At restart, the infusion speed should be decreased by 50% (no additional intravenous bolus should be administered).
Meta terġa ’ tinbeda, il- veloċità ta ’ l- infużjoni għandha titnaqqas b’ 50% (m’ għandu jingħata l’ ebda bolus addizzjonali ġol- vina).
The aPTT should be determined again 4 hours later. – If the confirmed aPTT value is below the target range, the infusion speed should be increased by 20%.
L’ aPTT għandu jerġa ’ jiġi ddeterminat 4 sigħat wara. – Jekk il- valur ikkonfermat ta ’ aPTT huwa anqas mill- firxa mmirata, il- veloċità ta ’ l- infużjoni għandha tiżdied b’ 20%.
The aPTT should be determined again 4 hours later. – In general, an infusion rate of 0.21 mg/ kg/ hour should not be exceeded without checking for coagulation abnormalities which might be preventing an appropriate aPTT response.
L- aPTT għandu jerġa ’ jiġi ddeterminat 4 sigħat wara. – Ġeneralment, rata ta ’ infużjoni ta ’ 0. 21 mg/ kg/ siegħa m’ għandiex tinqabeż mingħajr ma jsir kontroll għall- abnormalitajiet fil- koagulazzjoni li jistgħu jkunu qed jipprevjenu rispons xieraq ta ’ aPTT.
Recommendations for use in patients scheduled for a switch to oral anticoagulation
Rakkomandazzjonijiet għall- użu f’ pazjenti ppjanati li jibdlu l- kura tagħhom għal antikoagulanti mill- ħalq
If a patient is scheduled to receive coumarin derivatives (vitamin K antagonists) for oral anticoagulation after Refludan therapy, the following should apply:
Jekk pazjenti huwa ppjanat li jirċievi derivattivi ta ’ coumarin (antagonisti ta ’ vitamina K) għall - antikoagulazzjoni mill- ħalq wara terapija b’ Refludan, li ġej għandu japplika:
Coumarin derivatives should be initiated only when platelet counts are normalising.
Derivati ta ’ coumarin għandhom jinbdew biss meta l- għadd ta ’ plejtlets qed jinnormalizzaw.
The intended maintenance dose should be started with no loading dose.
Id- doża ta ’ manteniment maħsuba għandha tinbeda mingħajr doża għola tal- bidu.
To avoid prothrombotic effects when initiating coumarin, continue parenteral anticoagulation for 4 to 5 days (see oral anticoagulant package insert for information).
Sabiex jiġu evitati effeti protrombotiċi meta jinbeda coumarin, l- antikoagulazzjoni parenterali għandha titkompla għal 4 sa 5 ijiem (ara l- fuljett ta ’ tagħrif ta ’ l - antikoagulant mill- ħalq għal aktar informazzjoni).
The parenteral agent can be discontinued when the International Normalised Ratio (INR) stabilises within the desired target range.
L- aġent parenterali jista ’ jitwaqqaf meta l- International Normalised Ratio (INR) jistabilizza fil- firxa mmirata mixtieqa.
Recommendations for use in patients with renal impairment
Rakkomandazzjonijiet għall- użu f’ pazjenti b’ indeboliment tal- kliewi
As lepirudin is almost exclusively excreted and metabolised renally (see also section 5.2), the patient’ s renal function should be considered prior to administration.
Minħabba li lepirudin jintrema u jiġi metabolizzat kważi esklussivament mill- kliewi (ara wkoll sezzjoni 5. 2), il- funżjoni tal- kliewi tal- pazjent għandha tiġi kkunsidrata qabel l- amministrazzjoni.
In case of renal impairment relative overdose might occur even under standard dosage regimen.
F’ kaz ta ’ indeboliment tal- kliewi, doża eċċessiva relattiva tista ’ sseħħ anki taħt kors ta ’ dożaġġ stàndard.
Therefore, the bolus dose and infusion rate must be reduced in case of known or suspected renal insufficiency (creatinine clearance below 60 ml/ min or creatinine value above 15 mg/ l [133 μ mol/ l]).
Għalhekk, id- doża bolus u r- rata ta ’ infużjoni iridu jitnaqqsu f’ każ ta ’ insuffiċjenza tal- kliewi magħrufa jew issuspettata (tneħħija ta ’ kreatinina taħt 60 ml/ min jew valur ta ’ kreatinina aktar minn 15 mg/ l [133 μmol/ l]).
In clinical trials, Refludan was not therapeutically administered to HIT type II patients with significant renal impairment.
Fi studji kliniċi, Refludan ma ngħatax terapewtikament lill- pazjenti b’ HIT tat- tip II li kellhom indeboliment tal- kliewi sinifikanti.
The following dosage recommendations are based on single-dose studies in a small number of patients with renal impairment.
Ir- rakkomandazzjonijiet ta ’ dożaġġ li ġejjin huma bbażati fuq studji ta ’ doża waħda f’ numru żgħir ta ’ pazjenti b’ indeboliment tal- kliewi.
Therefore, these recommendations are only tentative.
Għalhekk, dawn ir- rakkomandazzjonijiet huma biss tentattiv.
Whenever available, dose adjustments should be based on creatinine clearance values as obtained from a reliable method (24 h urine sampling).
Meta disponibbli, aġġustamenti fid- doża għandhom jiġu bbażati fuq il- valuri ta ’ tneħħija ta ’ kreatinina hekk kif miksuba minn methodu affidabbli (kampjun ta ’ l- urina fuq 24 h).
In all other cases the dose adjustment is based on the creatinine value.
Fil- każijiet l- oħra kollha l - aġġustament tad- doża huwa bbażat fuq il- valur ta ’ kreatinina.
In any case, the bolus dose must be reduced to 0.2 mg / kg body weight.
F’ kull każ, id- doża bolus għandha tiġi mnaqqsa għal 0. 2 mg / kg piż tal- ġisem.
The infusion rate must be reduced according to table 1.
Ir- rata ta ’ infużjoni għandha tiġi mnaqqsa skond tabella 1.
Additional aPTT monitoring is mandatory.
Sorveljanza addizzjonali ta ’ aPTT hija obligatorja.
Reduction of infusion rate in patients with renal impairment
Tnaqqis tar- rata ta ’ infużjoni f’ pazjenti b’ indeboliment tal- kliewi
45 – 60 30 – 44 15 – 29
Tneħħija ta ’ keatinina [ml/ min] 45 – 60 30 – 44 15 – 29
16 – 20 (141 - 177) 21 – 30 (178 - 265) 31 - 60 (266 - 530)
Valur ta ’ kreatinina [mg/ l (μmol/ l)] 16 – 20 (141 - 177) 21 – 30 (178 - 265) 31 - 60 (266 - 530)
50% 30% 15%
ta ’ infużjoni aġġustata [% tad- doża oriġinali] 50% 30% 15%
below 15*
taħt 15 *
above 60 (530)*
’ l fuq minn 60 (530) *
avoid or STOP infusion! *
Evita jew WAQQAF l- infużjoni! *
* In haemodialysis patients or in case of acute renal failure (creatinine clearance below 15 ml/ min or creatinine value above 60 mg/ l [530 μ mol/ l]), infusion of Refludan is to be avoided or stopped.
* F’ pazjenti b’ emodijalisi jew f’ każ ta ’ insuffiċjenza akuta tal- kliewi (tneħħija ta ’ kreatinina taħt 15 ml/ min jew valur ta ’ kreatinina l’ fuq minn 60 mg/ l [530 μmol/ l]), infużjoni ta ’ Refludan għandha tiġi evitata jew titwaqqaf.
Only if aPTT values have fallen below the lower therapeutic limit (see Monitoring: target range), further intravenous bolus doses of 0.1 mg / kg body weight may be considered every other day.
Aktar dożi bolus ġol- vina ta ’ 0. 1 mg / kg ta ’ piz tal- ġisem jistgħu jiġu kkunsidrati ġurnata iva u oħra le biss jekk il- valuri ta ’ aPTT waqgħu taħt il- limitu terapewtiku ta ’ taħt.
Reconstitute the lyophilisate as described in section 6.6.
Irrikostitwixxi il- lijofilizzat kif deskritt f’ sezzjoni 6. 6.
Initial intravenous bolus:
Bolus tal- bidu ġol- vina:
For intravenous bolus injection, a solution with a concentration of 5 mg/ ml is needed.
Għall- injezzjoni bolus ġol- vina, soluzzjoni b’ konċentrazzjoni ta ’ 5 mg/ ml hija meħtieġa.
Intravenous injection is to be carried out slowly.
L- injezzjoni ġol- vina għandha tingħata bil- mod.
Examples for standard injection volume according to body weight
Eżempji ta ’ volum stàndard ta ’ injezzjoni skond il- piż tal- ġisem
Body weight
Piż tal- ġisem
Injection volume [ml]
Volum ta ’ l- injezzjoni [ml]
Dosage 0.4 mg / kg body weight 4.0 4.8 5.6 6.4 7.2 8.0
Dożaġġ 0. 4 mg / kg piż tal- ġisem 4. 0 4. 8 5. 6 6. 4 7. 2 8. 0
Dosage 0.2 mg / kg body weight 2.0 2.4 2.8 3.2 3.6 4.0
Dożaġġ 0. 2 mg / kg piż tal- ġisem 2. 0 2. 4 2. 8 3. 2 3. 6 4. 0
Intravenous infusion:
Infużjoni ġol- vina:
For continuous intravenous infusion, a solution with a concentration of 2 mg/ ml is needed.
Għall- infużjoni kontinwa ġol- vina, soluzzjoni b’ konċentrazzjoni ta ’ 2 mg/ ml hija meħtieġa.
The speed of the perfusor automate [ml per hour] is to be set in a body weight dependent fashion.
Il- veloċità tal- perfusor awtomat [ml kull siegħa] għandha tiġi ssettjata skond il- piż tal- ġisem.
Examples for standard infusion speed according to body weight
Eżempji ta ’ veloċità ta ’ infużjoni standard skond il- piż tal- ġisem
Infusion speed [ml/ h]
Veloċità ta ’ infużjoni [ml/ h]
Dosage 0.15 mg
Dożaġġ 0. 15 mg
weight / h Dosage 0.1 mg / kg body weight / h 2.5 3.0 3.5 4.0 4.5 5.0 5.5
/ kg piż tal- ġisem / h Dożaġġ 0. 1 mg / kg piż tal- ġisem / h 3. 8 2. 5 4. 5 3. 0 5. 3 3. 5 6. 0 4. 0 6. 8 4. 5 7. 5 5. 0
4 4.3 Contraindications
4 4. 3 Kontra- indikazzjonijiet
– Known hypersensitivity to lepirudin, to hirudins or to any of the excipients – Pregnancy and lactation (see section 4.6)
– Sensittività eċċessiva magħrufa għal lepirudin, hirudins jew xi wieħed mis- sustanżi l- oħra – Tqala u treddigħ (ara sezzjoni 4. 6)
Where there is active bleeding or bleeding tendency it is generally not advisable to administer Refludan.
Ġeneralment mhux rakkomandat li jingħata Refludan meta jkun hemm fsada attiva jew tendenza ta ’ fsada.
The physician should carefully weigh the risk of Refludan administration versus its anticipated benefit, taking into account possible measures to control bleeding.
It- tabib għandu jqis b’ attenzjoni ir- riskju ta ’ għotja ta ’ Refludan mal- benefiċċji mistennija, bi ħsieb għall - miżuri possibbli biex tiġi kkontrollata fsada.
This particularly includes the following situations with increased bleeding risk: – Recent puncture of large vessels or organ biopsy – Anomaly of vessels or organs – Recent cerebrovascular accident, stroke, or intracerebral surgery – Severe uncontrolled hypertension – Bacterial endocarditis – Advanced renal impairment – Haemorrhagic diathesis – Recent major surgery – Recent bleeding (e. g. intracranial, gastrointestinal, intraocular, pulmonary) – Overt signs of bleeding – Recent active peptic ulcer – Age > 65 years.
Dan jinkludi b’ mod speċjali s- sitwazzjonijiet b’ riskju miżjud ta ’ fsada li ġejjin: – Titqib riċenti tal- kanali l- kbar tad- demm jew bijopsija ta ’ organu – Anomalija tal- kanali l- kbar tad- demm jew organi – Aċċident ċerebrovaskulari reċenti, puplesija, jew kirurġija intraċerebrali – Pressjoni għolja severa mhux ikkontrollata – Endokardite kkawżata minn batterja – Indeboliment avvanzat tal- kliewi – Dijateżi emorraġika – Kirurġija maġġuri reċenti – Fsada reċenti (e. ż. intrakranjali, gastro- intestinali, intraokulari, pulmonari) – Sinjali viżibbli ta ’ fsada – Ulċera peptika attiva reċenti – Età > 65 sena.
– Anaphylaxis:
– Anafilassi:
Refludan may cause allergic reactions including anaphylaxis and shock (see section 4.8).
Refludan jista ’ jikkawża reazzjonijiet allerġiċi inklż anafilassi u xokk (ara sezzjoni 4. 8).
Fatal anaphylactic reactions have been reported in patients re-exposed to Refludan in a second or subsequent treatment course.
Reazzjonijiet anafilattiċi fatali ġew irrappurtati f’ pazjenti li reġgħu kienu esposti għal Refludan fit - tieni kors ta ’ kura jew kors ta ’ kura sussegwenti.
Therefore, alternative treatment options must be considered before the decision to re-expose a patient to Refludan.
Għalhekk, forom alternattivi ta ’ kura iridu jiġu kkunsidrati qabel id- deċiżjoni li pazjent jiġi espost mill- ġdid għal Refludan.
As these reactions are immune-mediated, patients with recent exposure to hirudin or hirudin analog may be at an increased risk.
Minħabba li dawn ir - reazzjonijiet huma medjati mis- sistema immunitarja, pazjenti li kienu esposti reċentament għal hirudin jew analogi ta ’ hirudin jistgħu jkunu f’ riskju akbar.
Treatment initiation with Refludan should be undertaken only in a setting where medical assistance is readily available and where there is access to treatment for anaphylactic reactions. – Patients should be informed that they have received Refludan. – In case of renal impairment relative overdose may occur even under a standard dosage regimen.
Bidu ta ’ kura b’ Refludan għandu jinbeda biss f’ post fejn assistenza medika hija faċilment miksuba u fejn hemm aċċess għall- kura ta ’ reazzjonijiet anafilattiċi. – Il- pazjenti għandhom jiġu nfurmati li rċevew Refludan. – F’ każ ta ’ indeboliment tal- kliewi, doża eċċessiva relattiva tista ’ sseħħ anke f’ kors ta ’ dożaġġ stàndard.
Therefore, the treating physician should carefully weigh the risk of administration versus its anticipated benefit.
Għalhekk, it- tabib li qed jikkura għandu jiżen b’ attenzjoni ir- riskji ta ’ għotja kontra il - benefiċċji mistennija.
It may be necessary to exclude patients with renal impairment from treatment with lepirudin regimen.
Jista ’ jkun neċessarju li pazjenti b’ indeboliment tal- kliewi jiġu esklużi mill - kura b’ kors ta ’ lepirudin.
The rate of infusion must be reduced in case of known or suspected renal insufficiency (see sections 4.2, and 5.2). – There is no experience with lepirudin in patients with significant liver impairment.
Ir- rata ta ’ infużjoni għandha tiġi mnaqqsa f’ każ ta ’ insuffiċjenza tal- kliewi magħrufa jew issuspettata (ara sezzjoni 4. 2 u 5. 2). – Ma hemm l- ebda esperjenza b’ lepirudin f’ pazjenti b’ indeboliment sinifikanti tal- fwied.
Liver cirrhosis may also affect the renal excretion of lepirudin.
Ċirrożi tal - fwied tista ’ taffettwa wkoll it- tneħħija mill- kliewi ta ’ lepirudin.
Serious liver injury (e. g. liver cirrhosis) may enhance the anticoagulant effect of lepirudin due to coagulation defects secondary to reduced generation of vitamin K-dependent coagulation factors. – Formation of anti-hirudin antibodies was observed in about 40% of HIT type II patients and have been reported especially with a treatment period exceeding five days.
Korriment serju tal- fwied (e. ż. ċirrożi tal- fwied) jista ’ jsaħħaħ l- effett antikoagulanti ta ’ lepirudin minħabba diffetti ta ’ koagulazzjoni sekondarji għall- ġenerazzjoni mnaqqsa ta ’ fatturi ta ’ koagulazzjoni dipendenti mill - vitamina K. – Formazzjoni ta ’ antikorpi anti- hirudin ġew osservati f’ madwar 40% tal- pazjenti b’ HIT tat- tip II u ġew irrappurtati speċjalment meta l- perjodu ta ’ kura qabeż ħamest ijiem.
This may result in an enhanced anticoagulant effect of lepirudin, possibly due to delayed renal elimination of active lepirudin-antihirudin complexes.
Dan jista ’ jwassal għall - effetti antikoagulanti msaħħa ta ’ lepirudin, possibilment minħabba dewmien fl- eliminazzjoni mill - kliewi ta ’ kumplessi attivi ta ’ lepirudin- antihirudin.
Therefore, strict monitoring of aPTT is necessary also during prolonged therapy.
Għalhekk, sorveljanża stretta ta ’ aPTT hija neċessarja anke waqt terapija mtawwla.
No evidence of a neutralisation of lepirudin or of an allergic reaction associated with the positive antibody test results was found. – Experience of combined therapy with thrombolytic agents in patients with HIT type II is very limited.
Esperjenza ta ’ terapija kombinata ma ’ aġenti trombolitiċi f’ pazjenti b’ HIT tat- tip II hija limitata – ħafna.
Since the risk of serious bleeding is considerable in this situation, the dosage of Refludan should be substantially reduced.
Minħabba li r- riskju ta ’ fsada serja hija konsiderevoli f’ din is- sitwazzjoni, id- dożaġġ ta ’ Refludan għandu jiġi mnaqqas b’ mod sostanzjali.
The optimal dose regimen of Refludan in these circumstances is not known. – Paediatric Use:
Il- kors ta ’ dożaġġ ottimu f’ dawn iċ - ċirkostanzi mhux magħruf. – Użu pedjatriku:
Safety and effectiveness in paediatric patients have not been established. – Elderly:
Is- sigurtà u l- effettività f’ pazjenti pedjatriċi għandhom ma ġewx stabbiliti. – Anzjani:
Patients of advanced age have an increased risk of bleeding complications with anticoagulation.
Pazjenti b’ età avvanzata għandhom riskju akbar ta ’ kumplikazzjonijiet ta ’ fsada b’ antikoagulazzjoni.
With respect to lepirudin dosage the potential of renal impairment in elderly
F’ dak li għandu x’ jaqsam mad- dożaġġ ta ’ lepirudin, il- potenzjal ta ’
No specific dosage adjustment is made for elderly patients.
5 indeboliment tal- kliewi f’ pazjenti anzjani trid tingħata konsiderazzjoni Ma hemm l- ebda aġġustament speċifiku tad- dożaġġ f’ pazjenti anzjani.
Dosing adjustments are based on renal function, weight, and aPTT (see section 4.2).
Aġġustamenti fid- dożaġġ huma bbażati fuq il - funzjoni tal- kliewi, piż u aPTT (ara sezzjoni 4. 2).
Concomitant treatment with thrombolytics (e. g. rt-PA or streptokinase) may – increase the risk of bleeding complications – considerably enhance the effect of Refludan on aPTT prolongation.
Kura flimkien ma ’ trombolitiċi (e. ż. rt- PA jew streptokinase) jistgħu – jżidu r- riskju ta ’ kumplikazzjonijiet ta ’ fsada – jsaħħu sew l- effett ta ’ Refludan fuq it- titwil ta ’ aPTT.
Concomitant treatment with coumarin derivatives (vitamin K antagonists) and drugs that affect platelet function may also increase the risk of bleeding.
Kura flimkien ma ’ derivati ta ’ coumarin (antagonisti tal- vitamina K) u mediċini li jaffettwaw il- funzjoni tal- plejtlets jistgħu wkoll jżidu ir- riskju ta ’ fsada.
Concomitant use with – antiplatelet agents other than acetylsalicylic acid, such as ticlopidine or clopidogrel, – GpIIb/ IIIa receptor antagonists such as eptifibatide, tirofiban, or abciximab, – other thrombin inhibitors such as low molecular weight heparins has not been assessed.
L- użu flimkien ma ’ – aġenti antiplejtlet minbarra acetylsalicylic acid, bħal ticlopidine jew clopidogrel, – antagonisti tar- riċetturi GpIIb/ IIIa bħal eptifibatide, tirofiban, jew abciximab, – inibituri ta ’ thrombin oħra bħall- eparins ta ’ piż molekolari baxx Ma ġiex studjat.
The safety of Refludan for use in human pregnancy or lactation has not been established.
Is- sigurtà ta ’ Refludan għall- użu fit- tqala u treddigħ fil- bniedem ma ġietx stabbilita.
In a standard embryo-foetal toxicity trial, decreased pup and maternal survival was observed.
Fi prova stàndard ta ’ tossiċità fuq l- embriju/ fetu, kien osservat tnaqqis fis- sopravvivenza tal- ferħ u tal - omm.
There is currently no information available on the use of Refludan during lactation.
Bħalissa ma hemmx tagħrif disponibbli fuq l- użu ta ’ Refludan waqt it- treddigħ.
Refludan should therefore not be administered to pregnant women or nursing mothers.
Għalhekk, Refludan m’ għandux jingħata lill- nisa tqal jew ommijiet li qed ireddgħu.
Not relevant.
Mhux relevanti.
The majority of undesirable effects experienced by patients treated with Refuldan were generally related to bleeding (> 1/ 10).
Il- maġġoranza ta ’ effetti mhux mixtieqa li esperjenzaw il- pazjenti kkurati b’ Refuldan kienu ġeneralment relatati ma ’ fsada (> 1/ 10).
Life-threatening bleeding events (including intracranial bleeding) were uncommonly reported (≥ 1/ 1,000 to < 1/ 100) in patients with acute coronary syndrome included in clinical studies.
Episodji ta ’ fsada li jistgħu jikkawżaw il- mewt (inkluż fsada intrakranjali) kienu irrappurtati b’ mod mhux komuni (≥1/ 1, 000 to < 1/ 100) f’ pazjenti bis- sindromu koronarju akut li kienu inkużi fl- istudji kliniċi.
In intensified post-marketing surveillance in HIT type II, fatal bleeding was reported in 1% and intracranial bleeding in 0.2% of patients
F’ sorveljanza intensifikata ta ’ wara t- tqegħid fis- suq f’ HIT tat- tip II, fsada fatali ġiet irrappurtata f’ 1% u fsada intrakranjali f’ 0. 2% tal- pazjenti.
Adverse events reported on Refuldan are shown in the table below:
Effetti avversi rrappurtati fuq Refuldan huma mniżżla fit- tabella hawn taħt:
6 Very common (> 1/ 10); Common (> 1/ 100 ,< 1/10); Uncommon (> 1/1 ,000 < 1/100); Rare (> 1/10,000 < 1/ 1,000); Very Rare (< 1/10,000)
6 Komuni Ħafna (> 1/ 10); Komuni (> 1/ 100, < 1/ 10); Mhux Komuni (> 1/ 1, 000 < 1/ 100); Rari (> 1/ 10, 000 < 1/ 1, 000); Rari Ħafna (< 1/ 10, 000)
System Organ Class Immune System Disorders
Sistema tal- Klassifika tal - Organi
Rare Anaphylactic/ oid reactions
Reazzjonijiet anafilattiċi/ ojdi
Vascular Disorders
Mard Vaskulari
Anemia or drop in the haemoglobin value without obvious source of bleeding Haematoma Bleeding from puncture sites Epistaxis Haematuria Gastrointestinal bleeding Vaginal bleeding Rectal bleeding Pulmonary haemorrhage Postoperative haemothorax Haemopericardium Intracranial bleeding
Anemija jew tnaqqis qawwi fil- valur ta ’ emoglobina mingħajr sors ovvju ta ’ fsada Ematoma Fsada minn postijiet ta ’ titqib Epistassi Ematuria Fsada gastro- intestinali Fsada mill- vaġina Fsada mir- rektum Emorraġijja pulmonari Emothorax wara kirurġija Emopericardium Fsada intrakranjali
Hot flushes Shock including fatal shock
Fwawar Xokk inkluż xokk fatali
Respiratory, thoracic and mediastinal disorders
Mard respiratorju, toraċiku u medjastinali
Cough Stridor Dyspnea
Sogħla Stridor Qtugħ ta ’ Nifs
Skin and Subcutaneous Tissue Disorders
Mard tal- Ġilda u tat- Tessuti ta ’ Taħt il- Ġilda
Allergic Skin Reactions (including rash) Pruritus Urticaria Angio-oedema (including: face oedema, tongue oedema, larynx oedema)
Reazzjonijiet Allerġiċi tal- Ġilda (inkluż raxx) Ħakk Urtikarja Angjo- edema (inkluż: edema fil - wiċċ, edema fl- ilsien, edema fil - larinġi)
General Disorders and Administration Site Conditions
Mard Ġenerali u Kondizzjonijiet ta 'Mnejn Jingħata
Fever Chills Injection site reactions including pain.
Deni Tertir Reazzjonijiet fil- post ta ’ l - injezzjoni inkluż uġigħ.
In case of overdose the risk of bleeding may be increased.
F’ każ ta ’ doża eċcessiva ir- riskju ta ’ fsada jista ’ jiżdied.
Currently, no specific antidote against lepirudin is available.
Bħalissa, mhux disponibbli antidotu speċifiku kontra lepirudin.
If life-threatening bleeding occurs and excessive plasma levels of lepirudin are suspected, the following recommendations should be followed: – Immediately STOP Refludan administration – Determine aPTT and other coagulation parameters as appropriate – Determine haemoglobin and prepare for blood transfusion – Follow the current guidelines for shock-therapy.
Jekk fsada li tista ’ tikkawża l- mewt iseħħ u hemm suspett ta ’ livelli eċċessivi ta ’ lepirudin fil- plażma, ir- rakkomandazzjonijiet li ġejjin għanhom jiġu segwiti: – WAQQAF minnufih l- amministrazzjoni ta ’ Refludan – Iddetermina l- aPTT u parametri oħra ta ’ koagulazzjoni kif xieraq – Iddetermina l- emoglobina u pprepara għall- trasfużjoni tad- demm – Segwi il- linji gwida kurrenti għall- kura ta ’ xokk.
Additionally, individual case reports and in-vitro data suggest that either haemofiltration or haemodialysis (using high flux dialysis membranes with a cut-off point of 50,000 Dalton) may be useful in this situation.
Barra minn hekk, rapporti ta ’ każi individwali u tagħrif in- vitro jissuġġerixxu li emofiltrazzjoni jew emodijaliżi (bl- użu ta ’ membrani tad- dijaliżi high flux b’ cut- off point ta ’ 50, 000 Dalton) jistgħu jkunu ta ’ għajnuna f’ din is- sitwazzjoni.
7 Results from studies in pigs showed that the application of von Willebrand Factor (vWF, 66 I. U. / kg body weight) markedly reduced the bleeding time.
Riżultati minn studji fil- ħnieżer urew li applikazzjoni tal- Fattur von Willebrand (vWF, 66 I. U. / kg piż tal - ġisem) naqqas ħafna il- ħin ta ’ fsada.
Antithrombotic agent - direct thrombin inhibitor, ATC Code:
Aġent antitrombotiku – inibitur dirett ta ’ thrombin, Kodiċi ATC:
Lepirudin ([Leu1, Thr2]-63-desulfohirudin) is a recombinant hirudin derived from yeast cells.
Lepirudin ([Leu1, Thr2] - 63- desulfohirudin) huwa hirudin rikombinat derivat minn ċellolli tal- ħmira.
The polypeptide composed of 65 amino acids has a molecular weight of 6979.5 Dalton.
Il - polypeptide huwa kompost minn 65 aċidi amminiċi u għandu piż molekolari ta ’ 6979. 5 Dalton.
Natural hirudin is produced in trace amounts as a family of highly homologous iso-polypeptides by the leech Hirudo medicinalis.
Hirudin naturali huwa prodott f’ ammonti żgħar ħafna bħala familja ta ’ iso- polipetids omologa ħafna minn sangisuga Hirudo medicinalis.
Lepirudin is a highly specific direct inhibitor of thrombin.
Lepirudin huwa inibitur dirett speċifiku ħafna ta ’ thrombin.
Its activity is measured in a chromogenic assay.
L- attività tiegħu hija mkejjla minn assay kromoġeniku.
One anti-thrombin unit (ATU) is the amount of hirudin that neutralises one unit of WHO preparation 89/ 588 of thrombin.
Unita waħda anti- thrombin (ATU) hija l- ammont ta ’ hirudin li tinnewtralizza unita waħda ta ’ preparazzjoni 89/ 588 ta ’ WHO ta ’ thrombin.
The specific activity of lepirudin is approximately 16,000 ATU/ mg.
L- attività speċifika ta ’ lepirudin hija ta ’ madwar 16, 000 ATU/ mg.
Its mode of action is independent of antithrombin III.
Il- mod kif jaħdem huwa indipendenti minn antithrombin III.
Platelet factor 4 does not inhibit lepirudin.
Platelet factor 4 ma jinibixxix lepirudin.
One molecule of hirudin binds to one molecule of thrombin and thereby blocks the thrombogenic activity of thrombin.
Molekola waħda ta ’ hirudin teħel ma ’ molekola waħda ta ’ thrombin u b’ hekk iwaqqaf l- attività tromboġenika ta ’ thrombin.
As a result all thrombin dependent coagulation assays are affected, e. g. the aPTT values increase in a dose-dependent fashion.
Bħala riżultat, kull assay ta ’ koagulazzjoni li tiddependi fuq thrombin huma affettwati, e. ż. l- valuri ta ’ aPTT jiżdiedu b’ mod dipendenti mid- doża.
The clinical information on HIT type II in this SPC is based upon the data of two prospective trials comprising a total of 198 HIT type II patients treated with Refludan.
L- informazzjoni klinika fuq HIT tat- tip II f’ dan l- SPC huwa bbażat fuq it- tagħrif ta ’ żewġ provi prospettivi li għandhom total ta ’ 198 pazjent b’ HIT tat- tip II kkurati b’ Refludan.
In the indication HIT type II with thromboembolic disease (125 patients) the overall mortality during the study period was approximately 9% while amputations and new thromboembolic complications were recorded in 6% and 10%, respectively.
Fl- indikazzjoni ta ’ HIT tat- tip II b’ mard tromboembolitiku (125 pazjent) il- mortalità globali waqt il- perjodu ta ’ studju kienet ta ’ madwar 9% waqt li amputazzjonijiet u kumplikazzjonijiet tromboembolitiċi ġodda kienu rreġistrati f’ 6% u 10%, rispettivament.
The pharmacokinetic properties of lepirudin following intravenous administration are well described by a two-compartment model.
Il- proprjetajiet farmakokinetiċi ta ’ lepirudin wara amministrazzjoni ġol- vina huma deskritti sew minn mudell b’ żewġ kumpartimenti.
Distribution is essentially confined to extra-cellular fluids and is characterised by an initial half-life of approximately 10 minutes.
Distribuzzjoni hija essenzjalment ristretta għall- fluwidi extra- ċellolari u hija kkaratterizzata minn half- life inizjali ta ’ madwar 10 minuti.
Elimination follows a first order process and is characterised by a terminal half-life of about 1.3 hours in young healthy volunteers.
Eliminazzjoni ssegwi proċess ta ’ l - ewwel ordni u hija kkaratterizzata minn half- life terminali ta ’ madwar 1. 3 sigħat f’ volontiera żagħżugħa b’ saħħithom.
Both, excretion and metabolism take place in the kidney, and about 45% of the dose administered is detectable in the urine.
Kemm it- tneħħija kif ukoll l- metaboliżmu jseħħu fil- kilwa u madwar 45% tad- doża amministrata tista ’ tinstab fl- awrina.
About 35% of the dose is excreted as unchanged compound.
Madwar 35% tad- doża tintrema bħala prodott mhux mibdul.
The systemic clearance of lepirudin decreases in proportion to the existing glomerular filtration rate.
It- tneħħija sistemika ta ’ lepirudin tonqos f’ proporzjon mar- rata ta ’ filtrazzjoni glomerulari eżistenti.
In female patients the systemic clearance is about 25% lower as compared to male patients.
F’ pazjenti nisa, it- tneħħija sistemika hija madwar 25% inqas meta mqabbla ma ’ pazjenti rġiel.
In elderly patients the systemic clearance of lepirudin is about 25% lower as compared to younger patients.
F’ pazjenti anzjani it- tneħħija sistemika ta ’ lepirudin hija madwar 25% inqas meta mqabbla ma ’ dik f’ pazjenti iżgħar.
Age alone causes a 7% reduction in clearance from the age of 30 to 70 years.
L- età waħedha tikkawża tnaqqis ta ’ 7% fit- tneħħija minn età ta ’ 30 sa 70 sena.
The majority of the difference in clearance between young and elderly patients is due to the differences in renal function.
Il - maġġoranża tad- differenza fit- tneħħija bejn pażjenti żagħżugħa u anzjani hija minħabba id- differenzi fil- funzjoni tal- kliewi.
In patients with terminal renal insufficiency prolonged elimination half-lives of about 2 days were observed.
F’ pazjenti b’ insuffiċjenza tal- kliewi terminali kienu osservati half- lives ta ’ eliminazzjoni mtawwla ta ’ madwar jumejn.
General toxicity Single and repeat-dose toxicity studies in mice, rats and monkeys showed the adverse responses that could be expected from an exaggerated pharmacodynamic impact of lepirudin.
Tossiċità ġenerali Studji tat- tossiċità ta ’ doża waħda u ta ’ doża ripetuta fi ġrieden, firien u xadini wrew reazzjonijiet avversi li jistgħu jkunu mistennija minn impatt farmakodinamiku esaġerat ta ’ lepirudin.
In monkeys retinal haemorrhages occurred.
Fix- xadini kien hemm emorraġijji fir- retina.
Moreover, in rats slight to moderate sinushistiocytosis of the regional lymph
Antikorpi kontra
Antibodies against hirudin which appeared in several of the treated monkeys resulted in prolongation of the terminal half-life and an increase in systemic exposure to lepirudin.
8 hirudin li dehru f’ ħafna mix- xadini kkurati wassal għal titwil tal- half- life terminali u żieda fl - espożizzjoni sistemika għal lepirudin.
Mutagenicity Lepirudin was not mutagenic or clastogenic in standard assays for such effects.
Mutaġeniċità Lepirudin ma kienx mutaġeniku jew klastoġeniku f’ analiżi stàndard għal dawn l- effetti.
– Mannitol – Sodium hydroxide for adjustment to pH 7
– Mannitol – Sodium hydroxide għall- aġġustament sa pH 7
After reconstitution: use immediately.
Wara rikostituzzjoni: uża immedjatament.
Do not freeze.
Tiffiżax.
Injection vial:
Kunjett ta ’ injezzjoni:
Colourless glass vial (glass type I) sealed with bromobutyl rubber infusion stopper, plastic flip-off cap and aluminium cap.
Kunjett tal- ħġieġ bla kulur (ħġieġ tat- tip I) issiġillat b’ tapp ta ’ l- infużjoni tal- lasktu bromobutyl, għatu flip- off tal- plastik u għatu ta ’ l- aluminju.
Presentations: – Pack with 1 vial – Pack with 10 vials
Preżentazzjonijiet: – Pakkett b’ kunjett wieħed – Pakkett b’ 10 kunjetti
General recommendations – Reconstitution and further dilution must be carried out under sterile conditions. – For reconstitution water for injections or sodium chloride 9 mg/ ml (0.9%) solution are to be used. – For further dilution, sodium chloride 9 mg/ ml (0.9%) or glucose 5% solutions are suitable. – For rapid, complete reconstitution, inject 0.4 ml of diluent into the vacuum vial and shake it gently.
Rakkomandazzjonijiet ġenerali – Rikostituzzjoni u aktar dilwazzjoni iridu jsiru taħt kondizzjonijiet sterili. – Għar- rikostituzzjoni għandhom jintużaw ilma għall- injezzjoni jew soluzzjoni ta ’ sodium chloride 9 mg/ ml (0. 9%). – Għal aktar dilwazzjoni, soluzzjonijiet ta ’ sodium chloride 9 mg/ ml (0. 9%) jew glucose 5% huma tajbin. – Għar- rikostituzzjoni ta ’ malajr u kompluta, injetta 0. 4 ml tad- dilwent ġol- kunjett mingħajr arja u ħawwad bil- mod.
On reconstitution a clear, colourless solution is usually obtained within less than 3 minutes. – Do not use solutions which are cloudy or contain particles. – The reconstituted solution is to be used immediately. – The preparation should be warmed to room temperature before administration.
Wara r- rikostituzzjoni, soluzzjoni ċara u bla kulur ġeneralment tinkiseb f’ inqas minn 3 minuti. – Tużax soluzzjonijiet li huma mdardra jew fihom xi frak. – Is- soluzzjoni rikostitwita għandha tintuża immedjatament. – Il- preparazzjoni għandha tissaħħan sat- temperatura tal- kamra qabel l- amministrazzjoni. – Kull soluzzjoni li ma tintużax għandha tintrema kif xieraq.
9 – Any unused solution must be discarded appropriately. – For injection only polypropylene syringes may be used.
9 – Għall- injezzjoni, jistgħu jintużaw biss siringi ta ’ polypropylene.
Preparation of a Refludan solution with a concentration of 5 mg/ ml For intravenous bolus injection a solution with a concentration of 5 mg/ ml is needed: – Reconstitute one vial (20 mg of lepirudin) with 0.4 ml of either water for injections or sodium chloride 9 mg/ ml (0.9%) solution. – The final concentration of 5 mg/ ml is obtained by transfer into a sterile, single-use syringe (of at least 5 ml capacity) and further dilution to a total volume of 4 ml using sodium chloride 9 mg/ ml (0.9%) or glucose 5% solution. – The final solution is to be administered in a body weight-dependent fashion (see section 4.2).
Preparazzjoni ta ’ soluzzjoni ta ’ Refludan b’ konċetrazzjoni ta ’ 5 mg/ ml Għall- injezzjoni bolus ġol- vina, hija meħtieġa soluzzjoni b’ konċetrazzjoni ta ’ 5 mg/ ml: – Irrikostitwixxi kunjett wieħed (20 mg ta ’ lepirudin) b’ 0. 4 ml ta ’ imla għall- injezzjoni jew soluzzjoni ta ’ sodium chloride 9 mg/ ml (0. 9%). – Il- konċentrazzjoni finali ta ’ 5 mg/ ml hija miksuba billi jiġi trasferit ġo siringa sterili, li tintuża darba (b’ kapaċità mill- inqas ta ’ 5 ml) u aktar dilwazzjoni sa volum totali ta ’ 4 ml bl- użu ta ’ soluzzjoni ta ’ sodium chloride 9 mg/ ml (0. 9%) jew glucose 5%. – Is- soluzzjoni finali trid tiġi amministrata b’ mod dipendenti mill- piż tal- ġisem (ara sezzjoni 4. 2).