qanastek/EMEA-V3 huggingface dataset:
Ceplene maintenance therapy should be administered following completion of consolidation therapy in patients concomitantly treated with IL-2 under the supervision of a physician experienced in the management of acute myeloid leukaemia.
Ceplene għandu jingħata bħala terapija ta 'manteniment wara t- tkomplija ta' terapija ta 'konsolidament f' pazjenti ttrattati b' IL- 2 taħt sorveljanza ta' tabib espert fil- ġestjoni ta 'lewċemija mjelojde akuta.
For dosing instructions for Ceplene in combination with IL-2, see posology below.
Għall- istruzzjonijiet ta 'dożaġġ għal Ceplene li jingħata flimkien ma' IL- 2, ara l- pożoloġija hawn taħt.
Interleukin-2 (IL-2) IL-2 is administered twice daily as a subcutaneous injection 1 to 3 minutes prior to the administration of Ceplene; each dose of IL-2 is 16 400 IU/ kg.
Interleukin- 2 (IL- 2) IL- 2 jingħata darbtejn kuljum bħala injezzjoni taħt il- ġilda minn minuta sa 3 minuti qabel l- għoti ta 'Ceplene; kull doża ta' IL- 2 hija 16 400 IU/ kg.
Ceplene 0.5 ml solution is sufficient for a single dose (see section 6.6).
Ceplene Soluzzjoni ta '0. 5 ml hija biżżejjed għal doża waħda (ara sezzjoni 6. 6).
Ceplene is administered 1 to 3 minutes after each injection of IL-2.
Ceplene jingħata minn minuta sa 3 minuti wara kull injezzjoni ta 'IL- 2.
Each 0.5 ml Ceplene dose is injected slowly, over 5-15 minutes.
Kull doża ta '0. 5 ml ta ’ Ceplene tiġi injettata bil- mod, fuq perjodu minn 5 sa 15- il minuta.
Treatment cycles Ceplene and IL-2 are administered for 10 treatment cycles: each cycle consists of a treatment period of 21 days (3 weeks) followed by a three-week or six-week treatment-free period.
Ċikli ta 'trattament Ceplene u IL- 2 jingħataw għal 10 ċikli ta' trattament: kull ċiklu jikkonsisti minn perjodu ta 'trattament ta' 21 jum (3 ġimgħat) segwiti minn perjodu mingħajr trattament ta 'tliet ġimgħat jew sitt ġimgħat.
For cycles 1-3, each cycle consists of 3 weeks of treatment, followed by a 3-week treatment free period.
Għaċ- ċikli 1- 3, kull ċiklu jikkonsisti minn 3 ġimgħat trattament, segwit minn perjodu mingħajr trattament ta '3 ġimgħat.
For cycles 4-10, each cycle consists of 3 weeks of treatment, followed by a 6-week treatment- free period.
Għaċ- ċikli 4- 10, kull ċiklu jikkonsisti minn 3 ġimgħat ta 'trattament, segwiti minn perjodu mingħajr trattament ta' 6 ġimgħat.
The recommended dosing regimen is presented in Tables 1 and 2.
Ir- reġim tad- dożaġġ irrakkomandat huwa ppreżentat fit- Tabelli 1 u 2.
2 Table 1:
Għaċ- ċikli ta 'trattament b' Ceplene u IL- 2
For treatment cycles 1-3 with Ceplene and IL-2
Ġimgħa numru (ġ) *
Cycle 1
Trattament *
Week
Ċiklu 1
number (w)* Cycle 2
Ċiklu 2
Cycle 3
Ċiklu 3
Treatment*
ġ. 13 sa ġ. 15 IL- 2 16 400 IU/ kg segwit b' 0. 5 ml Ceplene.
w.1 to w.3
ġ. 1 sa ġ. 3
w.7 to w.9
ġ. 7 sa ġ. 9
(Days 1-21)
(Jiem 1- 21)
(Days 1-21) Twice daily.
(Jiem 1- 21) Darbtejn kuljum.
Treatment-free (3 weeks)
Mingħajr trattament (3 ġimgħat)
*see dose modification for provisions for the modification to dose and dosage schedule
* ara modifika tad- doża għall- proviżjoni għall- modifika tad- doża u l- iskeda tad- dożaġġ
For treatment cycles 4-6 with Ceplene and IL-2, same as for Table 1 above, with the exception of number of cycles and duration of rest periods
Għal ċikli ta 'trattament b' Ceplene u IL- 2, l- istess bħal għat- Tabella 1 hawn fuq, bl - eċċezzjoni ta' numru ta 'ċikli u tul ta' żmien ta 'perjodi ta' mistrieħ
Week number (w)* Cycles
Ġimgħa numru (ġ) * Ċikli
Treatment*
Trattament *
w.1 w.2 w.3 w.4 w.55 w.6 w.7 IL-2 16 400 IU/ kg followed by 0.5 ml
IL- 2 16 400 IU/ kg
9 to 8 to 7 to 6 to w.2 w.3 w.3 w.4 w.57 w.6 w.7
ġ. 19 sa
- to
ġ.
4 to 3 to Ceplene.
ġ. 46 sa ġ.
Twice daily
ġ. 64 sa
1 0 9 8 w.2 w.3 w.4 w.4 w.58 w.6 w.7
ġ. 73 sa
6 5 Treatment-free (6 weeks)
Mingħajr trattament
2 to 1 to 0 to 9 to w.2 w.3 w.4 w.5 w.63 w.7 w.8
ġ. 40 sa
to
ġ. 49 sa
7 to 6 to
ġ. 58 sa
7 6 5 4
ġ. 67 sa
2 1
ġ. 76 sa
*see dose modification for provisions for the modification to dose and dosage schedule
* ara modifika tad- doża għad- dispożizzjonijiet għall- modifika tad- doża u tal- programm tad - dożaġġ
Dose modification Patients should be monitored for the expected symptomatic adverse reactions and laboratory changes associated with this treatment.
Modifika tad- doża Il- pazjenti għandhom ikunu sorveljati għar- reazzjonijiet sintomatiċi avversi u bidliet tal- laboratorju mistennija assoċjati ma 'dan it- trattament.
Doses of Ceplene and IL-2 should be modified as necessary based on individual patient tolerance to treatment.
Dożi ta 'Ceplene u IL- 2 għandhom ikunu modifikati kif meħtieġ abbażi tat- tolleranza individwali għat- trattament tal- pazjent.
It is recommended that dose modifications be addressed early in treatment.
Huwa rakkomandat li modifiki tad- doża jkunu indirizzati kmieni waqt it- trattament.
The dose reductions can be temporary or permanent.
It- tnaqqis fid- doża jista 'jkun temporanju jew permanenti.
Should Ceplene related toxicities occur (such as hypotension, headache), the injection time can be increased from 5 minutes to a maximum of duration of 15 minutes.
Jekk iseħħu tossiċitajiet relatati ma 'Ceplene (bħalma huma ipotensjoni, uġigħ ta' ras), il- ħin għall - injezzjoni jista 'jiżdied minn 5 minuti sa tul massimu ta' 15- il minuta.
For patients experiencing grade 1 toxicity events:
Għall- pazjenti li qegħdin jesperjenzaw episodju ta 'tossiċità ta' grad 1:
No altered dose recommendations with the exception of grade 1 neurologic toxicity and grade 1 generalised toxic dermatitis.
L- ebda tibdil fir- rakkomandazzjonijiet tad- doża ħlief għal tossiċità newroloġika ta 'grad 1 u dermatite tossika ġeneralizzata ta' grad 1.
For the dose recommendations for these grade 1 toxicity events refer to the relevant sections below:
Għar- rakkomandazzjonijiet fid- doża għal dawn l- episodji tossiċi ta 'grad 1 irreferi għas- sezzjonijiet rilevanti hawn taħt:
For patients experiencing grade 1-4 neurologic toxicity -for grade 1 to 3 toxicity, treatment should be discontinued until grade 0 toxicity event has been achieved.
- għal tossiċità minn grad 1 sa 3, it- trattament għandu jieqaf sakemm jinkiseb episodju ta '
Treatment should then be resumed at a 20% dose reduction for both Ceplene and IL-2. -for grade 4 toxicity, discontinuation of treatment should be considered.
It- trattament għandu jerġa 'jinbeda bi tnaqqis fid- doża ta' 20% kemm għal Ceplene kif ukoll għal IL- 2.
For patients experiencing grade 1-4 generalised toxic dermatitis -for grade 1 toxicity, the treatment should be delayed for 48 hours or until all symptoms have been resolved.
It- trattament għandu mbagħad jitkompla bl- użu ta 'doża sħiħa ta' Ceplene, iżda bi tnaqqis tad- doża ta 'IL- 2 b' 20%.
Treatment should then be resumed using the full dose of Ceplene, but reducing the IL-2 dose by 20%. -for grade 2 toxicity, the IL-2 dose should be reduced 50% and only increased to full dose if the symptoms do not reappear.
- għal tossiċità ta 'grad 2, id- doża ta' IL- 2 għandha titnaqqas b' 50% u tiżdied għal doża
Ceplene and IL-2 doses should be separated by 60 minutes, which should be maintained throughout treatment. -for grade 3 and 4 toxicity, treatment should be discontinued and not resumed until events have been resolved.
- għal tossiċità ta 'grad 3 u 4, it- trattament għandu jieqaf u ma jerġax jinbeda sakemm
Treatment should only be resumed after consideration of risk – benefit to the patient.
It- trattament għandu jitkompla biss wara kunsiderazzjoni tar- riskju – benefiċċju għall- pazjent.
3 For patients experiencing grade 2 (including cardiac function, renal, hepatic) toxicity:
3 Għal pazjenti li qegħdin jesperjenzaw tossiċità ta 'grad 2 (inklużi funzjoni kardijaka, renali, epatika)
- treatment should be discontinued until the event has returned to grade 1
- it- trattament għandu jieqaf sakemm l- episodju jirritorna għal grad 1
- the time of injection of the dose of Ceplene should be extended to a maximum of 15
- il- perjodu tal- injezzjoni tad- doża ta 'Ceplene għandu jittawwal sa massimu ta' 15- il
minutes.
minuta.
- for cardiac, hepatic or renal toxicities the dose should be reduced by 20% for both Ceplene
- għal tossiċitajiet kardijaċi, epatiċi jew renali, id- doża għandha titnaqqas b' 20% kemm għal
and IL-2.
Ceplene kif ukoll għal IL- 2.
For patients experiencing grade 3 and 4 (including hypotension, arrhythmia) toxicities:
Għal pazjenti li qegħdin jesperjenzaw tossiċitajiet ta 'grad 3 u 4 (inklużi ipotensjoni, aritmija):
- treatment should be discontinued until the event is resolved.
- it- trattament għandu jieqaf sakemm l- episodju jkun ġie solvut.
A maximum delay of one
Ittardjar massimu ta 'ċiklu
treatment cycle can be considered for the resolution of grade 3 and 4 events.
wieħed ta 'trattament jista' jiġi kkunsidrat għar- riżoluzzjoni ta 'episodji ta' grad 3 u 4.
For persistent hypotension, headache, arrhythmia, cardiac, hepatic and renal toxicities:
Għall- ipotensjoni persistenti, l- uġigħ ta 'ras, l- aritmija, it- tossiċitajiet kardijaċi, epatiċi u renali:
- the dose amount of both Ceplene and IL-2 should be reduced by 20%.
- l- ammont tad- doża kemm ta 'Ceplene u kemm ta' IL- 2 għandha titnaqqas b' 20%.
Fever
Deni
- IL-2 can be discontinued for 24 hours and then restarted at a 20% dose reduction level.
IL- 2 jista 'jiġi sospiż għal 24 siegħa u mbagħad jerġa' jinbeda f' livell ta 'tnaqqis ta' 20% tad- doża.
Abnormal WBC counts
Għadd anormali ta 'WBC
- the dose of IL-2 can be reduced by 20% for the remaining duration of the treatment course
- id- doża ta 'IL- 2 tista' titnaqqas b' 20% għall- kumplament taż- żmien tal- kors ta 'trattament u
and if abnormal WBC counts re-occur during the following cycle a permanent IL-2 reduction is recommended.
jekk jerġgħu jseħħu għadd ta 'WBC anormali waqt iċ- ċiklu li jmiss, huwa rrakkomandat tnaqqis permanenti ta' IL- 2.
Localised toxic dermatitis
Dermatite tossika lokalizzata
- treatment should be discontinued until symptoms resolved.
- it- trattament għandu jieqaf sakemm is- sintomi jkunu ġew solvuti.
Treatment can be resumed by
It- trattament jista '
administering Ceplene at the full dose and IL-2 at 50%.
jinbeda bl- għoti ta 'Ceplene fid- doża sħiħa u IL- 2 f' 50%.
Special populations
Popolazzjonijiet speċjali
Renal impairment:
Insuffiċjenza renali:
Patients with renal impairment may be more sensitive to the blood pressure lowering effects of Ceplene.
Pazjenti b' insuffiċjenza renali jistgħu jkunu iktar sensittivi għall- effetti ta 'Ceplene li jbaxxu l - pressjoni tad- demm.
Although the degree of renal impairment has no demonstrable effect on the pharmacokinetic disposition of Ceplene, caution is warranted when Ceplene is administered to patients with severe renal impairment.
Għalkemm il- grad ta 'insuffiċjenza renali m' għandu l- ebda effett li jidher fuq id - dispożizzjoni farmakokinetika ta' Ceplene, meta Ceplene tingħata lil pazjenti b' insuffiċjenza renali severa, dan għandu jsir b' kawtela.
However, no Ceplene dose reduction is normally required in renally impaired patients.
Madankollu, l- ebda tnaqqis tad- doża ma huwa normalment meħtieġ f' pazjenti b' insuffiċjenza renali.
Hepatic impairment:
Insuffiċjenza epatika:
Ceplene should be used with caution in patients with moderate to severe hepatic impairment (see section 5.2).
Ceplene għandu jintuża b' kawtela f' pazjenti b' insuffiċjenza epatika minn moderata għal severa (ara sezzjoni 5. 2).
Plasma Ceplene levels are higher in patients with moderate and severe liver impairment, and these patient groups tend to experience more tachycardia and lower blood pressure after Ceplene dosing than do patients with normal or mildly affected liver function.
Il- livelli ta 'Ceplene fil- plażma huma ogħla f' pazjenti b' insuffiċjenza epatika moderata u severa, u dawn il- gruppi ta' pazjenti għandhom it- tendenza li jesperjenzaw iktar takikardija u pressjoni tad- demm iktar baxxa wara dożaġġ b' Ceplene milli pazjenti b' funzjoni tal- fwied normali jew affettwata b' mod ħafif.
Plasma drug levels were not predictive of adverse effects, however, and effects did not correlate closely with drug exposure.
Madankollu, il- livelli ta 'mediċini fil- plażma ma kinux ta' tbassir għal effetti avversi, u l- effetti ma kkorrelatawx mill- qrib mal- esponiment għall- mediċina.
Dose reduction of Ceplene is normally not required in hepatically impaired patients, but caution should be used in these patients.
Normalment mhuwiex meħtieġ tnaqqis fid- doża f' pazjenti b' insuffiċjenza epatika, iżda għandha tintuża l- kawtela f' dawn il - pazjenti.
Paediatric Population:
Popolazzjoni pedjatrika:
Ceplene is not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy in this age group (see section 5.1 and 5.2).
Ceplene mhuwiex rakkomandat għall- użu fi tfal taħt l- età ta '18- il sena minħabba nuqqas ta' tagħrif ta 'sigurtà u effikaċja f' dan il- grupp ta' età (ara sezzjoni 5. 1 u 5. 2).
Method of administration
Metodu ta 'għoti
For subcutaneous use only.
Għal użu taħt il- ġilda biss.
4 One to 3 minutes after the subcutaneous administration of IL-2 has been completed, Ceplene should be administered by slow subcutaneous injection at a rate not to exceed 0.1 ml (0.1 mg histamine dihydrochloride) per minute.
4 Minuta sa 3 minuti wara li jintemm l- għoti taħt il- ġilda ta 'IL- 2, Ceplene għandu jingħata bil- mod b' injezzjoni taħt il- ġilda f' rata li ma taqbiżx 0. 1 ml (0. 1 ml ta ’ istamina dikloridrat) kull minuta.
The usual time for administering a 0.5 ml Ceplene dose is 5 minutes.
Il- ħin normalment meħtieġ biex tingħata doża ta '0. 5 ml ta ’ Ceplene huwa ta' 5 minuti.
To reduce potential adverse reactions, the administration time may be lengthened to a maximum of 15 minutes, see below.
Biex tnaqqas reazzjonijiet avversi potenzjali, iż- żmien tal- għoti jista 'jittawwal b' massimu ta' 15- il minuta, ara hawn taħt.
Ceplene can be administered via an ambulatory infusion syringe pump or by controlled manual subcutaneous injection by syringe with a timer.
Ceplene jista 'jingħata permezz ta' siringa bil- pompa għal infużjoni ambulatorja jew permezz ta 'injezzjoni taħt il- ġilda manwali kkontrollata permezz ta' timer.
The first dose of Ceplene and IL-2 on day 1 of the initiation of the first cycle of treatment should be administered in the clinic under direct supervision by a physician.
L- ewwel doża ta 'Ceplene u IL- 2 fl- ewwel jum tal- bidu tal- ewwel ċiklu ta' trattament għandha tingħata fi klinika taħt sorveljanza diretta ta 'tabib.
Patient monitoring on day 1 should include vital signs, including pulse, blood pressure and respiratory rate.
Monitoraġġ tal- pazjent fl- ewwel jum għandha tinkludi sinjali vitali, inklużi l- polz, il- pressjoni tad- demm u r- rata respiratorja.
If the patient experiences a significant change in vital signs, the physician should evaluate the status of the patient and continue to monitor vital signs; these patients should be monitored during subsequent treatments.
Jekk il- pazjent jesperjenza bidla sinifikanti fis- sinjali vitali, it- tabib għandu jevalwa l- istatus tal- pazjent u jkompli jissorvelja s- sinjali vitali; dawn il- pazjenti għandhom ikunu sorveljati waqt trattamenti sussegwenti.
Subsequent injections of Ceplene may be self-administered at home by a patient who demonstrates a good understanding of necessary precautions and who has demonstrated adequate injection skills.
Injezzjonijiet sussegwenti ta 'Ceplene jistgħu jingħataw, mill- pazjent innifsu li juri li jifhem tajjeb il - prekawzjonijiet meħtieġa u li juri kapaċità adegwata li jagħti injezzjoni hu stess.
Injections should be preferably administered in a supervised setting in the presence of an adult family member, friend, or other care provider who is capable of responding appropriately should signs or symptoms of hypotension occur.
L- injezzjonijiet għandhom preferibbilment jingħataw f' sitwazzjoni sorveljata fil- preżenza ta 'membru tal- familja adult, ħabib, jew xi ħaddieħor li jagħti t- trattament li huwa kapaċi jirreaġixxi b' mod adegwat jekk iseħħu sinjali jew sintomi ta' ipotensjoni.
The preferred injection areas are the thighs and the abdomen.
Iż- żoni ppreferuti tal- injezzjoni huma l- koxxtejn u l- addome.
Ceplene should not be injected into the same anatomic region as IL-2.
Ceplene ma għandu jiġi injettat fl- istess żona anatomika bħalma jkun ġie injettat IL- 2.
The twice daily dosing of IL-2 and Ceplene should be separated by a minimum of 6 hours.
Id- dożaġġ ta 'darbtejn kuljum ta' IL- 2 u Ceplene għandu jkun separat permezz ta 'intervall minimu ta' 6 sigħat.
Patients should remain at rest for 20 minutes after injection of Ceplene.
Il- pazjenti għandhom jibqgħu mistrieħa għal 20 minuta wara injezzjoni ta 'Ceplene.
4.3 Contraindications
4. 3 Kontraindikazzjonijiet
• Hypersensitivity to the active substance or to any of the excipients. • Patients with significantly compromised cardiac function, e. g., NYHA Class III/ IV. • Patients receiving systemic steroid therapy, clonidine and H2 blocking agents. • Patients who have received an allogenic stem cell transplant. • During pregnancy. • During breast feeding.
NYHA Klassi III/ IV. • Pazjenti li qegħdin jirċievu terapija sistemika bi sterojdi, klonidina (clonidine) u mediċini li jimblokkaw H2. • Pazjenti li rċievew trapjant alloġenu ta 'ċelloli staminali. • Waqt it- tqala. • Waqt it- treddigħ.
4.4 Special warnings and special precautions for use
Ceplene għandu jingħata minn minuta sa 3 minuti wara għoti ta 'IL- 2, u mhux b' mod konkomittanti.
Ceplene should be administered 1 to 3 minutes after IL-2 administration, and not concomitantly. • Rapid subcutaneous injection or injection into a vascular space may result in severe hypotension, tachycardia, or syncope.
• Injezzjoni taħt il- ġilda rapida jew injezzjoni ġewwa spazju vaskulari tista 'tirriżulta f' ipotensjoni severa, takikardija, jew sinkope.
Treatment with Ceplene in conjunction with IL-2 should be used with caution in patients with poorly compensated cardiac function.
It- trattament b' Ceplene flimkien ma 'IL- 2 għandu jingħata bil- kawtela f' pazjenti b' funzjoni kardijaka mhux ikkompensata tajjeb.
Patients with cardiac disease should be evaluated for ventricular ejection fraction and wall function by echocardiography or nuclear medicine stress test and then treated with caution. • Patients should be monitored during treatment for possible clinical complications due to hypotension or hypovolaemia.
Pazjenti b' mard kardijaku għandhom jiġu evalwati għal frazzjoni ta 'tfigħ' il barra (ejection fraction) ventrikolari u l- funzjoni parjetali (wall function) permezz ta 'ekokardjografija jew test ta' stress bil- mediċina nukleari u mbagħad ittrattati b' kawtela. • Il- pazjenti għandhom jiġu sorveljati waqt it- trattament għal kumplikazzjonijiet kliniċi possibbli minħabba ipotensjoni jew ipovolemija.
Ceplene should be administered in the clinic under supervision of the physician on day 1 of the initial treatment cycle.
Ceplene għandu jingħata fi klinika taħt sorveljanza ta 'tabib f' jum 1 taċ- ċiklu ta' trattament inizjali.
Patient monitoring on day 1 should include vital signs, including pulse, blood pressure and respiratory rate. • Patient monitoring during subsequent treatment days or cycles should be performed as long as the patient continues to experience significant changes in vital signs during administration of Ceplene.
Sorveljanza tal- pazjent fl- ewwel jum għandha tinkludi sinjali vitali, inklużi polz, pressjoni tad- demm u rata respiratorja. • Għandha ssir sorveljanza waqt jiem ta 'trattament jew ċikli ta' trattament sussegwenti sakemm il- pazjent ikompli jesperjenza bidliet sinifikattivi fis- sinjali vitali waqt l- għoti ta 'Ceplene.
If significant hypotension or related symptoms are observed in subsequent treatment cycles, dose reduction should be initiated and if required, administered in hospital until responses to treatment allow for home administration.
Jekk ikunu osservati ipotensjoni jew sintomi relatati f' ċikli ta 'trattament sussegwenti, għandu jinbeda tnaqqis fid- doża u jekk meħtieġ, tingħata fi sptar sakemm ir- reazzjonijiet jagħtu lok għal għoti mid- dar.
5 • Caution should be used for patients with any of the following: symptomatic peripheral arterial disease, past or present peptic or oesophageal ulcer disease with a history of bleeding, clinically significant renal disease and stroke within the last 12 months.
5 • Għandha tintuża l- kawtela għall- pazjenti b' xi waħda minn dawn li ġejjin: mard sintomatiku tal - arterji periferali, ulċera peptika jew tal- esofagu bi storja ta 'fsada passata jew preżenti, nefropatija klinikament sinifikattiva jew puplesija fi żmien l- aħħar 12- il xahar.
Where appropriate, consideration should be made to providing concomitant treatment with a proton pump inhibitor. • Patients with clinically significant infection requiring the use of antibiotics, antifungals, or antivirals, or who have completed prior anti-infectious therapy within 14 days of starting treatment should be treated with caution unless the use of antibiotics and antivirals were for prophylaxis purposes. • Patients with a prior history of autoimmune disease (including systemic lupus, inflammatory bowel disease, psoriasis and rheumatoid arthritis) should be treated with caution. • Monitoring of laboratory test results is recommended including standard haematological and blood chemistry tests. • Patients receiving the following medicinal products should be treated with caution (see section 4.5) -Beta-blockers or other anti-hypertensive agents. -H1 blocking agents and neuroleptics (anti-psychotics) with H1 receptor blocking properties. -Tricyclic anti-depressants that may have H1 and H2 receptor blocking properties. -Monoamine oxidase inhibitors and anti-malarial and anti-trypanosomal agents. -Neuromuscular blocking agents, narcotic analgesics, and various contrast media.
Fejn approprjat, għandu jiġi kkunsidrat li tiġi pprovduta trattament konkomittanti b' inibitur tal- pompa protonika. • Pazjenti b' infezzjoni klinikament sinifikanti li teħtieġ l- użu ta 'antibijotiċi, antifungali, jew antivirali, jew li temmew terapija preċedenti kontra l- infezzjoni fi żmien 14- il jum mill- bidu tat - trattament għandhom ikunu ttrattati bil- kawtela sakemm l- antibijotiċi jew l- antivirali ma kinux biss għal skopijiet ta' profilassi. • Pazjenti bi storja preċedenti ta 'mard awtoimmunitarju (inkluż lupus sistemiku, marda infjammatorja intestinali, psorijażi u artrite rewmatojde) għandhom ikunu ttrattati b' kawtela. • Hija rrakkomandata sorveljanza ta' riżultati ta 'testijiet tal- laboratorju inklużi testijiet standard ematoloġiċi u ematokimiċi. • Pazjenti li qegħdin jirċievu l- prodotti mediċinali li ġejjin għandhom jiġu ttrattati bil- kawtela (ara sezzjoni 4. 5)
4.5 Interaction with other medicinal products and other forms of interaction
- Imblokkaturi Beta jew mediċini antipertensivi oħrajn.
While posology differs, when Ceplene is used in conjunction with IL-2, physicians should also refer to the SmPC for IL-2 and observe the respective medical product interactions.
Waqt li l- pożoloġija hija differenti, meta Ceplene jintuża flimkien ma 'IL- 2, it- tobba għandhom jirreferu wkoll għall- SPC għal IL- 2 u josservaw l- interazzjonijiet tal- prodott mediku rispettiv.
H2 receptor antagonists with imidazole structures similar to histamine, e. g., cimetidine, systemic steroids and clonidine, must not be used during treatment with Ceplene (see section 4.3).
Antagonisti tar- riċetturi H2 bi strutturi imidazole simili għall- istamina, pereżempju, ċimetidina (cimetidine), sterojdi sistemiċi u klonidina, ma għandhomx jintużaw waqt trattament b' Ceplene (ara sezzjoni 4. 3).
Beta-blockers and other anti-hypertensive agents should be used with caution during treatment with Ceplene.
Imblokkaturi Beta u antipertensivi oħrajn għandhom jintużaw b' kawtela waqt trattament b' Ceplene.
Concurrent administration of medicinal products with cardiotoxicity or blood pressure lowering effects may increase the toxicity of Ceplene.
Għoti komkomitanti ta 'prodotti mediċinali b' effetti ta' kardjotossiċità jew li jbaxxu l- pressjoni tad - demm jistgħu jżidu t- tossiċità ta 'Ceplene.
H1 receptor blocking antihistamines or neuroleptics (anti-psychotics) with H1 receptor blocking properties that might decrease efficacy of Ceplene should be avoided.
Antistaminiċi li jimblokkaw ir- riċettur H1 jew newrolettiċi (antipsikotiċi) b' karatteristiċi li jimblokkaw ir- riċetturi H1 li jistgħu jnaqqsu l- effikaċja ta 'Ceplene għandhom jiġu evitati.
Tricyclic anti-depressants may have H1 and H2 receptor blocking properties and should be avoided.
Antidepressivi triċikliċi jistgħu jkollhom karatteristiċi li jimblokkaw ir- riċetturi H1 u H2 u għandhom jiġu evitati.
Monoamine oxidase inhibitors, anti-malarial, and anti-trypanosomal active substances may alter the metabolism of Ceplene and should be avoided (see section 4.4).
Inibituri ta ’ monoamine oxidase u sustanzi attivi kontra l- malarja u antitripanosomiċi jistgħu jbiddlu l - metaboliżmu ta 'Ceplene u għandhom jiġu evitati (ara sezzjoni 4. 4).
It has been noted that neuromuscular blocking agents, narcotic analgesics, and various contrast media can induce the release of endogenous histamine; therefore in patients undergoing diagnostic or surgical procedures, the additive effect of Ceplene treatment should be considered prior to the procedure (see section 4.4).
Ġie nnotat li aġenti imblokkaturi newromuskolari, analġeżiċi narkotiċi, u diversi mezzi ta 'kuntrast jistgħu jinduċu t- tnixxija ta' istamina endoġena; għaldaqstant f' pazjenti li qegħdin isirulhom proċeduri dijanjostiċi jew kirurġiċi, l- effett addittiv tat- trattament b' Ceplene għandu jkun ikkunsidrat qabel il - proċedura (ara sezzjoni 4. 4).
For Ceplene, no clinical data on exposed pregnancies are available.
L- ebda dejta ma hija disponibbli fuq każijiet ta 'tqala esposti għal Ceplene.
Animal studies showed reproductive toxicity but only at maternotoxic doses, and did not indicate direct harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development (see Section 5.3).
Studji fl- annimali juru tossiċità riproduttiva biss f' dożi maternotossiċi, u ma jindikawx effetti ta 'ħsara diretta fir- rigward tat - tqala, żvilupp embrijonali, fetali, ħlas jew żvilupp ta' wara t- twelid (ara sezzjoni 5. 3).
Ceplene in conjunction with IL-2 must not be used during pregnancy.
Ceplene flimkien ma 'IL- 2 ma għandhiex tintuża waqt it- tqala.
It is unknown whether histamine is excreted in human breast milk.
6 Mhuwiex magħruf jekk l- istamina hijiex eliminata fil- ħalib tas- sider tal- bniedem.
The excretion of histamine in milk has not been studied in animals, but at maternotoxic doses in rats, offspring showed slight toxicity during early lactation (see Section 5.3).
L- eskrezzjoni tal - istamina fil- ħalib ma ġietx studjata fl- annimali, iżda f' dożi maternotossiċi fil- firien, il- frieħ urew xi ftit tossiċità waqt treddigħ bikri (ara sezzjoni 5. 3).
Ceplene in conjunction with IL-2 must not be used during breast-feeding.
Waqt it- treddigħ, Ceplene ma għandux jintuża flimkien ma 'IL- 2.
6 No clinical data are available on the effects of Ceplene on fertility.
Ma hemm l- ebda dejta klinika dwar l- effetti ta 'Ceplene fuq il- fertilità.
Animal studies revealed no adverse effects on fertility apart from a slight reduction in implantations and viable foetuses (see section 5.3).
Studji fl- annimali ma wrew l - ebda effett avvers fuq il- fertilità apparti tnaqqis żgħir fl- impjanti u l- feti vijabbli (ara sezzjoni 5. 3).
Women of childbearing potential and sexually active men must use effective methods of contraception during treatment with Ceplene and IL-2.
Nisa f' età fertili u rġiel sesswalment attivi għandhom jużaw metodi effikaċi ta 'kontraċezzjoni waqt it - trattament b' Ceplene u IL- 2.
Refer to the IL-2 SmPC for information on pregnancy and lactation with IL-2.
Għal tagħrif fuq tqala u treddigħ b' IL- 2 irreferi għall- SmPC ta 'IL- 2.
Ceplene has minor or moderate influence on the ability to drive and use machines.
Ceplene għandu influwenza minuri jew moderata fuq il- ħila biex issuq u tħaddem magni.
Administration of Ceplene can cause hypotension and may result in dizziness, light-headedness and blurred vision.
L- għoti ta 'Ceplene jista' jikkaġuna ipotensjoni u jista 'jirriżulta fi sturdament, ras mhux f' sikkitha u vista mċajpra.
Patients should not drive or operate machines for at least 1 hour after receiving Ceplene.
Il- pazjenti ma għandhomx isuqu jew iħaddmu magni sa tal- anqas siegħa wara li jirċievu Ceplene.
Acute Myeloid Leukaemia
Lewċemija mjelojde akuta
Adverse reactions were reported to be at least possibly related to IL-2 and Ceplene treatment in almost all patients in studies in acute myeloid leukaemia (AML).
Reazzjonijiet avversi li kienu tal- inqas possibbilment relatati mat- trattament b' IL- 2 u Ceplene kienu rrapportati kważi fil- pazjenti kollha fi studji f' lewċemija mjelojde akuta (AML).
The most common adverse reactions experienced by 30% or more of patients receiving IL-2 and Ceplene (listed in descending order of frequency) were: flushing, headache, fatigue, injection site granuloma, pyrexia and injection site erythema.
L- iktar effetti avversi komuni esperjenzati minn 30% jew iktar ta 'pazjenti li kienu qegħdin jirċievu IL- 2 u Ceplene (elenkati f' ordni ta' frekwenza li tonqos) kienu: fwawar, uġigħ ta 'ras, għeja, granuloma fis- sit tal- injezzjoni, piressija u eritema fis- sit tal- injezzjoni.
The adverse reactions occurring in at least 5% of patients considered at least possibly related to the treatment of low-dose IL-2 with Ceplene in AML studies (n=196 for the IL-2 and Ceplene treatment arm) are listed below by body system organ, class and frequency.
Ir- reazzjonijiet avversi li seħħew f' għall- inqas 5% tal- pazjenti kkunsidrati tal- inqas possibbilment relatati ma 'trattament b' IL- 2 f' doża baxxa ma' Ceplene fi studji AML (n=196 għall- fergħa tat - trattament IL- 2 u Ceplene) huma elenkati hawn taħt skont is- sistema ta 'klassifikazzjoni tal- organi tal - ġisem, klassi u frekwenza.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Għal kull grupp ta 'frekwenza, l- effetti mhux mixtieqa l- aktar serji jitniżżlu qabel dawk inqas serji.
Frequencies are defined as very common (≥ 1/ 10) and common (≥ 1/ 100 to < 1/ 10).
Il- frekwenzi huma ddefiniti bħala komuni ħafna (≥ 1/ 10) u komuni (≥ 1/ 100 sa < 1/ 10).
Blood and lymphatic system disorders Very common: eosinophilia, thrombocytopenia
Disturbi fid- demm u fis- sistema linfatika Komuni ħafna: eosinofilija, tromboċitopenija
Metabolism and nutrition disorders Common: anorexia
Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni: anoressija
Psychiatric disorders Common: insomnia
Disturbi psikjatriċi Komuni: insonnja
Nervous system disorders Very common: headache, dizziness, dysgeusia
Disturbi fis- sistema nervuża Komuni ħafna: uġigħ ta 'ras, sturdament, disġewsija
Cardiac disorders Very common: tachycardia Common: palpitations
Disturbi kardijaċi Komuni ħafna: takikardija Komuni: palpitazzjonijiet
Vascular disorders Very common: flushing, hypotension
7 Komuni ħafna: fwawar, ipotensjoni
Respiratory, thoracic, and mediastinal disorders Very common: cough, dyspnoea Common: nasal congestion
Disturbi respiratorji, toraċiċi u medjastiniċi Komuni ħafna: sogħla, dispnea Komuni: konġestjoni nażali
Gastrointestinal disorders Very common: nausea, dyspepsia, diarrhoea.
Disturbi gastrointestinali Komuni ħafna: nawżea, dispepsija, dijarrea.
Common: vomiting, upper abdominal pain, dry mouth
Komuni: remettar, uġigħ addominali fin- naħa ta 'fuq, ħalq xott
7 Skin and subcutaneous tissue disorders Very common: rash Common: erythema, increased sweating, night sweats, pruritus
Disturbi fil- ġilda u fit- tessuti ta 'taħt il- ġilda Komuni ħafna: raxx Komuni: eritema, żieda fil- ħruġ tal- għaraq, ħruġ tal- għaraq bil- lejl, ħakk
Musculoskeletal and connective tissue disorders Very common: arthralgia, myalgia Common: limb pain, back pain
Disturbi muskoluskeletriċi u tat- tessut konnettiv Komuni ħafna: artralġija, mijalġija Komuni: uġigħ fid- dirgħajn u r- riġlejn, uġigħ fid- dahar
General disorders and administration site conditions Very common: injection site granuloma, fatigue, pyrexia, injection site erythema, feeling hot, injection site reaction, injection site pruritus, influenza like illness, rigors, injection site inflammation, injection site pain Common: injection site urticaria, injection site bruising, injection site rash, injection site swelling, weakness, chest pain
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni ħafna: granuloma fis- sit tal- injezzjoni, għeja kbira, piressija, eritema fis- sit tal- injezzjoni, sensazzjoni ta' sħana, reazzjoni fis- sit tal- injezzjoni, ħakk fis- sit tal- injezzjoni, marda simili għall - influwenza, tkexkix ta 'bard, infjammazzjoni fis- sit tal- injezzjoni, uġigħ fis- sit tal- injezzjoni Komuni: urtikarja fis- sit tal- injezzjoni, tbenġil fis- sit tal- injezzjoni, raxx fis- sit tal- injezzjoni, dgħufija, uġigħ fis- sider
Other oncology (advanced tumour) studies
Studji onkoloġiċi (tumuri avvanzati) oħrajn
Ceplene and low dose IL-2 have been investigated in other clinical studies at different doses (1.0 mg histamine dihydrochloride twice a day) and with different dose regimens of low-dose IL-2 and interferon-alfa.
Ceplene u doża baxxa ta 'IL- 2 ġew investigati fi studji kliniċi oħrajn f' dożi differenti (1. 0 mg ta ’ istamina dikloridrat darbtejn kuljum) u b' reġim ta' dożi differenti ta 'doża baxxa ta' IL- 2 u interferon - alfa.
The following adverse events, not listed above, were reported in at least 5% of patients and as at least possibly related to the study medicine:
L- effetti avversi li ġejjin, mhux elenkati hawn fuq, kienu rrapportati f' mhux inqas minn 5% tal - pazjenti u għall- inqas possibbilment relatati mal- mediċina tal- istudju:
Blood and lymphatic system disorders Common: anaemia
Disturbi fid- demm u fis- sistema linfatika Komuni: anemija
Skin and subcutaneous tissue disorders Very common: dry skin
Disturbi fil- ġilda u fit- tessuti ta 'taħt il- ġilda Komuni ħafna: ġilda xotta
Ear and labyrinth disorders Common: vertigo
Disturbi fil- widnejn u fis- sistema labirintika Komuni: vertigo
Endocrine disorders Common: acquired hypothyroidism
Disturbi fil- kliewi u fis- sistema urinarja Komuni: ipotirojdiżmu akkwiżit
Metabolism and nutrition disorders Very common: decreased appetite Common: dehydration
Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni ħafna: nuqqas ta 'aptit Komuni: diżidratazzjoni
Psychiatric disorders Very common: anxiety Common: depression
Disturbi psikjatriċi Komuni ħafna: ansjetà Komuni: depressjoni
Nervous system disorders Common: paraesthesia
Disturbi fis- sistema nervuża Komuni: parestesija
Vascular disorders Common: hot flushes
Disturbi vaskulari
8 Common: injection site fibrosis, pain
8 Komuni: fwawar
Administration of Ceplene or IL-2 by rapid infusion or into vascular spaces, at higher doses than the approved ones, may exaggerate the adverse reactions associated with Ceplene.
Għoti ta 'Ceplene jew IL- 2 permezz ta' infużjoni rapida jew ġewwa l- ispazji vaskulari, f' dożi ogħla minn dawk approvati, jista 'jesaġera l- effetti avversi assoċjati ma' Ceplene.
Other cytokines and immunomodulators; ATC code:
Kodiċi ATC:
Ceplene/ IL-2 is an immunotherapy which aims to induce immune-mediated destruction of residual myeloid leukaemic cells and thereby to prevent relapse of leukaemia.
Ceplene/ IL- 2 huwa immunoterapija li jimmira li jinduċi qerda immuno- medjata ta 'ċelloli residwi tal - lewċemija mjelojde u permezz ta' dan jimpedixxi rikaduta tal- lewċemija.
The role of Ceplene is to protect lymphocytes, in particular NK cells and T cells, which are responsible for the immune- mediated destruction of residual leukaemic cells.
Ir- rwol ta 'Ceplene huwa li jipproteġi l- linfoċiti, b' mod partikolari ċelloli NK u ċelloli T, li huma responsabbli għall- qerda immuno- medjata ta' ċelloli lewċemiċi residwi.
The role of IL-2 is to promote the functions of NK cells and T cells by activating the anti-leukaemic properties of these cells and by expanding these cell populations by inducing cell cycle proliferation.
Ir- rwol ta 'IL- 2 huwa li jippromovi l- funzjonijiet ta' ċelloli NK u ċelloli T billi jattiva l- proprjetajiet antilewċemiċi ta 'dawn iċ- ċelloli u billi jespandi dawn il- popolazzjonijiet ta' ċelloli billi jinduċi proliferazzjoni taċ- ċiklu taċ- ċellola.
The mechanism by which Ceplene improves the anti- leukaemic function of lymphocytes in AML is not completely established; it is considered to be by inhibition of reactive oxygen species (ROS or “ oxygen free radicals”), which are synthesised by monocytes/ macrophages and granulocytes.
Il- mekkaniżmu li bih Ceplene itejjeb il- funzjoni antilewċemika tal- linfoċiti f' AML mhuwiex kompletament stabbilit; huwa kkunsidrat li jsir permezz ta 'inibizzjoni ta' speċijiet reattivi tal- ossiġenu (ROS jew "radikali liberi tal - ossiġenu"), li huma sintetizzati mill- monoċiti/ makrofaġi u granuloċiti.
ROS are known to limit the anti-leukaemic effects of lymphocyte activators such as IL-2, by triggering dysfunction and death by apoptosis in NK cells and T cells.
Ir- ROS huma magħrufin li jillimitaw l- effetti antilewċemiċi ta 'attivaturi ta' linfoċiti bħalma huwa IL- 2, billi jikkawżaw disfunzjoni u mewt permezz ta 'apoptożi f' ċelloli NK u ċelloli T.
Ceplene inhibits NAPDH oxidase which initiates the formation and release of ROS from phagocytes.
Ceplene jinibixxi NAPDH oxidase li tagħti bidu għall- formazzjoni u r- rilaxx ta 'ROS mill- fagoċiti.
By inhibiting oxidase function and reducing ROS production, Ceplene protects IL-2- activated NK cells and T cells from oxygen free radical-induced inhibition and apoptosis.
Billi jinibixxi l- funzjoni ta ’ oxidase u jnaqqas il- produzzjoni tar- ROS, Ceplene jipproteġi ċ- ċelloli NK u ċ- ċelloli T attivati minn IL- 2 mill - inibizzjoni indotta mir- radikali liberi mill- ossiġenu u mill- apoptożi.
The concomitant administration of Ceplene and IL-2 therefore aims to optimise the anti-leukaemic functions of NK cells and T cells.
L- għoti ta 'Ceplene flimkien ma ’ IL- 2 għaldaqstant jimmira għall- ottimizzazzjoni tal- funzjonijiet antilewċemiċi ta' ċelloli NK u ċelloli T.
There have been 2 clinical studies to evaluate the use of Ceplene in the maintenance of remission in adult AML patients.
Twettqu żewġ studji kliniċi biex jevalwaw l- użu ta 'Ceplene fil- manteniment ta' remissjoni f' pazjenti adulti b' AML.
Study AML-1 was exploratory, enrolling 39 AML patients in remission to determine the dose and feasibility of Ceplene administered together with IL-2.
L- istudju AML- 1 kien wieħed esploratorju, li daħħal 39 pazjenti b' AML f' remissjoni biex jiddetermina d- doża u jekk Ceplene jistax jingħata flimkien ma 'IL- 2.
Results of this pilot study were used to design and implement a multi-national phase 3 trial.
Ir- riżultati ta 'dan l- istudju pilota ntużaw biex ifasslu u jimplimentaw prova tal- fażi 3 multinazzjonali.
The randomised phase 3 trial (0201) compared Ceplene+IL-2 treatment to no treatment in 261 patients in first remission (CR1) and in another 59 patients in subsequent remission after relapse (CR > 1).
Il- prova tal- fażi 3 randomizzata (0201) qabblet it- trattament b' Ceplene+IL- 2 ma 'ebda trattament f' 261 pazjent fl- ewwel remissjoni (CR1) u 59 pazjent oħra f' remissjoni wara rikaduta sussegwenti (CR > 1).
For CR1 patients, the median duration of leukaemia-free survival increased from 291 days (9.7 months) to 450 days (15 months) after Ceplene/ IL-2 versus no maintenance treatment (ITT, p=0.01. n=261).
Għal pazjenti CR1, it- tul ta 'żmien medjan ta' sopravivenza mingħajr lewċemija żdied minn 291 jum (9. 7 xhur) għal 450 jum (15- il xahar) wara Ceplene/ IL- 2 meta mqabbal ma 'ebda trattament ta' manteniment (ITT, p=0. 01. n=261).
The number of CR1 patients remaining leukaemia-free for 3 years was 40% after Ceplene+IL-2 versus 26% in patients not receiving this treatment (p=0.01).
In- numru ta 'pazjenti CR1 li baqgħu mingħajr lewċemija għal 3 snin kien ta' 40% wara Ceplene+IL- 2 meta mqabbel 26% f' pazjenti li ma kinux qegħdin jirċievu dan it- trattament (p=0. 01).
This medicinal product has been authorised under “ Exceptional circumstances”.
Dan il- prodott mediċinali ġie awtorizzat f ''Ċirkostanzi Eċċezzjonali '.
This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.
Kull
The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.
9 sena, l- Aġenzija Ewropea għall- Mediċini (l- EMEA) tirrevedi kwalunkwe tagħrif ġdid li jista 'jinkiseb u dan is- sommarju sejjer jiġi aġġornat kif meħtieġ.
Histamine is rapidly absorbed after subcutaneous injection.
L- istamina hija assorbita rapidament wara injezzjoni taħt il- ġilda.
Maximum plasma concentration is reached approximately 10 minutes after end of subcutaneous infusion.
Il- konċentrazzjoni massima fil - plażma tintlaħaq f' madwar 10 minuti wara t- tmiem ta 'infużjoni taħt il- ġilda.
Histamine concentrations and PK were highly variable across studies, as well as within the normal volunteer and patient groups.
Konċentrazzjonijiet ta 'istamina u PK huma ferm varjabbli matul l- istudji, kif ukoll fi gruppi ta' voluntiera normali u pazjenti.
Patients showed a higher degree of variability with respect to systemic exposure as compared to healthy subjects.
Il- pazjenti wrew grad ogħla ta 'varjabbilità fir- rigward tal- esponiment sistemiku kif imqabbel ma' suġġetti f' saħħithom.
Histamine is eliminated by metabolism in kidney, liver and other tissues.
Histamine huwa eliminat permezz ta 'metaboliżmu fil- kilwa, fwied u tessuti oħrajn.
The main enzymes involved in the metabolism of histamine are HNMT (histamine-N-methyltransferase) and DAO (diamine
L- enzimi ewlenin involuti fil- metaboliżmu ta ’ histamine huma HNMT (histamine- N- methyltransferase) u DAO (diamine- oxidase).
The metabolites are mainly excreted in urine.
Il- metaboliti huma eliminati prinċiplament fl- awrina.
The mean half-life was 0.75 to 1.5 hours in patients.
F' pazjenti, il- half- life medja kienet 0. 75 sa 1. 5 sigħat.
There are no significant effects of age or weight on the pharmacokinetic properties of histamine.
Ma hemm l- ebda effett sinifikanti relatat mal- età jew piż fuq il- proprjetajiet farmakokinetiċi tal - istamina.
Clearance of Ceplene is almost twice as high in females resulting in considerably lower systemic exposure than in males.
Ir- rata ta 'eliminazzjoni ta' Ceplene hija kważi darbtejn ogħla fin- nisa li tirriżulta f' esponiment sistemiku ferm ogħla milli fl- irġiel.
It is not known whether histamine crosses the placenta.
Mhuwiex magħruf jekk l- istamina tgħaddix mill- plaċenta.
Renal impairment The pharmacokinetics of histamine are similar in healthy volunteers with normal renal function compared to volunteers with mild, moderate, or severe renal impairment.
Insuffiċjenza renali Il- farmakokinetika tal- istamina hija simili f' voluntiera f' saħħithom b' funzjoni renali normali meta mqabbla ma 'voluntiera b' insuffiċjenza renali, ħafifa, moderata, jew severa.
In subjects with severe renal impairment, there were decreases in systolic and diastolic blood pressure at plasma histamine concentrations which caused no appreciable decrease in blood pressure in other subjects.
F' suġġetti b' insuffiċjenza renali gravi, kien hemm tnaqqis fil- pressjoni tad- demm sistolika u dijastolika f' konċentrazzjoniet tal - plażma li ma kkaġunaw l- ebda tnaqqis apprezzabbli fil- pressjoni tad- demm f' suġġetti oħrajn.
Thus, subjects with severe renal impairment may be more sensitive to the blood pressure lowering effects of exogenously administered histamine than subjects with normal renal function or subjects with mild or moderate renal impairment.
Għalhekk, suġġetti b' insuffiċjenza renali gravi jistgħu jkunu iktar sensittivi għall- effetti ta 'tnaqqis fil - pressjoni tad- demm tal- istamina mogħtija eżoġenament milli suġġetti b' funzjoni renali normali jew suġġetti b' insuffiċjenza renali minn ħafifa għal moderata.
Although the degree of renal impairment has little effect on the PK disposition of histamine, caution should be used in the administration of histamine to patients with severe renal impairment.
Għalkemm il- grad ta 'insuffiċjenza renali kellu ftit effett fuq id- dispożizzjoni PK tal- istamina, għandha tintuża l- kawtela fl- għoti tal- istamina lill- pazjenti b' insuffiċjenza renali gravi.
Hepatic impairment A study was performed to measure the PK of histamine in normal volunteers compared to patients with mild, moderate, and severe hepatic impairment.
Insuffiċjenza epatika Sar studju biex ikejjel il- PK tal- istamina f' voluntiera normali meta mqabbla ma 'pazjenti b' insuffiċjenza epatika ħafifa, moderata jew gravi.
There were no clinically significant differences in safety parameters or in pharmacodynamics.
Ma kien hemm l- ebda differenza sinifikanti fil - parametri ta 'sigurtà jew fil- farmakodinamika.
Plasma histamine concentrations were highly variable and were considerably higher in the groups of patients with moderate or severe hepatic impairment (medians 10 and 5 times the normal volunteers respectively).
Konċentrazzjonijiet tal- istamina fil- plażma kienu ferm varjabbli u kienu konsiderevolment ogħla fi gruppi ta 'pazjenti b' insuffiċjenza epatika ħafifa, moderata jew gravi (medjani 10 u 5 darbiet il- voluntiera normali, rispettivament).
Patients with all degrees of hepatic impairment may have tachycardia or hypotension for 30-60 minutes after Ceplene+IL-2 administration.
Il- pazjenti bil- gradi kollha ta 'insuffiċjenza epatika jista' jkollhom takikardija jew ipotensjoni għal 30- 60 minuta wara għoti ta 'Ceplene+IL- 2.
5.3 Preclinical safety data
5. 3 Tagħrif prekliniku tas- sigurtà
Non-clinical data reveal no special hazard for humans based on conventional studies of repeated-dose toxicity, local tolerance and genotoxicity.
Tagħrif mhux kliniku ma juri l- ebda periklu speċjali għall- bnedmin abbażi ta 'studji konvenzjonali ta' tossiċità ta 'doża ripetuta, tolleranza lokali u ġenotossiċità.
Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure, indicating little relevance to clinical use.
Effetti fi studji mhux kliniċi kienu osservati f' esponimenti kkunsidrati suffiċjentement f' eċċess tal- esponiment massimu tal- bniedem, li jindikaw ftit rilevanza għal użu kliniku.
No carcinogenicity studies have been performed on Ceplene.
Ma sar l- ebda studju tal- karċinoġeniċità fuq Ceplene.
Histamine dihydrochloride was not teratogenic in rats or rabbits at doses resulting in several hundred- fold greater systemic exposures than the clinical exposure.
L- istamina dikloridrat ma kinitx teratoġena fil- firien jew fniek f' dożi li jirriżultaw f' esponimenti diversi mitt darba ikbar mill- esponiment kliniku.
In female rats dosed before mating to gestation day 7, slightly reduced numbers of implantations and viable foetuses were found, but without any dose-response and within the range of historical control data.
F' firien nisa ddożati qabel it- tgħammir sa jum 7 tal - ġestazzjoni, instab xi tnaqqis żgħir ta 'impjanti u feti vijabbli, iżda mingħajr xi doża- reazzjoni u fi ħdan il- medda ta' dejta storika ta 'kontroll.
In the peri-post natal development study, high doses of histamine dihydrochloride caused maternal toxicity, and the offspring showed toxicity during lactation (fewer live pups at day 21 compared to lactation at day 4) but not after weaning.
Fl- istudju ta 'żvilupp matul u wara t- twelid, dożi għoljin ta' istamina dikloridrat ikkaġunaw tossiċità materna, u l- frieħ urew tossiċità waqt it- treddigħ (inqas frieħ ħajjin f' jum 21 meta mqabblin ma 'treddigħ f' jum 4) iżda mhux wara li jinfatmu.
Sodium chloride Sodium hydroxide (for pH adjustment) Hydrochloric acid (for pH adjustment) Water for injections
Klorur tas- sodju Idrossidu tas- sodju (għal aġġustament tal- pH) Aċidu idrokloriku (għal aġġustament tal- pH) Ilma għall- injezzjonijiet
10 In the absence of compatibility studies this medicinal product should not be mixed with other medicinal products, diluents or infusion solutions.
Fin- nuqqas ta 'studji tal- kompatibbilità dan il- prodott mediċinali ma għandux jitħallat ma' prodotti mediċinali oħrajn, dilwenti jew soluzzjonijiet tal- infużjoni.
Unopened vials:
Kunjetti mhux miftuħin:
6.5 Nature and contents of container
6. 5 Natura tal- kontenitur u tal- kontenut