qanastek/EMEA-V3 huggingface dataset:
Which measures are being taken to ensure the safe use of Cubicin?
X’ miżuri qed jittieħdu biex ikun żgurat l- użu sigur ta ’ Cubicin?
The company that makes Cubicin will carry out further studies with Cubicin to investigate whether it has an effect on the muscle, and to look at its safety and effectiveness in patients with kidney disease and in the elderly.
Il- kumpanija li tagħmel Cubicin se tagħmel iktar studji fuq Cubicin biex tistħarreġ jekk għandux effett fuq il- muskoli, u biex tiġi studjata s- sigurtà u l- effettività tiegħu f’ pazjenti b’ mard tal- kliewi u fl - anzjani.
Other information about Cubicin:
Tagħrif ieħor dwar Cubicin:
The European Commission granted a marketing authorisation valid throughout the European Union for Cubicin on 23 January 2006.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Cubicin fit- 23 ta ’ Jannar 2006.
The marketing authorisation holder is Novartis Europharm Limited.
Id- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq huwa Novartis Europharm Limited.
The full EPAR for Cubicin can be found here.
L- EPAR sħiħ għal Cubicin jista ’ jinstab minn hawn.
Cubicin 350 mg powder for concentrate for solution for infusion
Cubicin 350 mg trab għall- konċentrat għal soluzzjoni għall- infużjoni
Each vial contains 350 mg daptomycin.
Kull kunjett fih 350 mg daptomycin.
One ml provides 50 mg of daptomycin after reconstitution with 7 ml of sodium chloride 9 mg/ ml (0.9%) solution or water for injections.
Millilitru wieħed jipprovdi 50 mg daptomycin wara li jkun imħallat ma ’ 7 ml ta ’ sodium chloride 9 mg/ ml (0. 9%) soluzzjoni jew ilma għall- injezzjonijiet.
Powder for concentrate for solution for infusion.
Trab għall - konċentrat għal soluzzjoni għall- infużjoni
A pale yellow to light brown lyophilised powder.
Trab lajofilizzat minn isfar ċar għall- kannella ċar.
Cubicin is indicated for the treatment of the following infections in adults (see sections 4.4 and 5.1).
Cubicin huwa indikat għall- kura ta ’ infezzjonijiet li ġejjin (ara sezzjonijiet 4. 4 u 5. 1).
- Complicated skin and soft-tissue infections (cSSTI).
- Infezzjonijiet kumplikati tal- ġilda u tat- tessuti rotob (cSSTI).
- Right-sided infective endocarditis (RIE) due to Staphylococcus aureus.
- Endokardite fin- naħa tal- lemin (RIE) minn Staphylococcus aureus.
It is recommended that
Huwa rrakkomandat li d -
the decision to use daptomycin should take into account the antibacterial susceptibility of the organism and should be based on expert advice.
deċiżjoni li jintuża daptomycin għandha ssir wara li tkun ikkunsidrata s- suxxettibilità antibatterika ta ’ l- organiżmu u għandha tkun ibbażata fuq parir ta ’ espert.
See sections 4.4 and 5.1.
Ara sezzjonijiet 4. 4 u 5. 1.
- Staphylococcus aureus bacteraemia (SAB) when associated with RIE or with cSSTI.
- Batterimja minn Staphylococcus aureus (SAB) meta tkun assoċjata ma ’ RIE jew ma ’ cSSTI.
Daptomycin is active against Gram positive bacteria only (see section 5.1).
Daptomycin huwa attiv kontra batteri tat- tip Gram posittivi biss (ara sezzjoni 5. 1).
In mixed infections where Gram negative and/ or certain types of anaerobic bacteria are suspected, Cubicin should be co- administered with appropriate antibacterial agent(s).
F’ każijiet ta ’ taħlita ta ’ infezzjonijiet meta jkun hemm suspett li hemm batteri tat- tip Gram negattivi u/ jew ċerti tipi ta ’ batteri anerobiċi, Cubicin għandu jingħata flimkien ma ’ s- sustanza( i) antibatteriku( ċi) xieraq( qa).
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Għandhom jitqiesu il- linja gwida uffiċjali dwar l- użu xieraq ta ’ sustanzi antibatteriċi.
Posology
Pożoloġija
- cSSTI without concurrent Staphylococcus aureus bacteraemia:
- cSSTI mingħajr batterimja bi Staphylococcus aureus fl- istess ħin:
The recommended dose is
Id- doża rakkomandata hija
4 mg/ kg administered once every 24 hours for 7-14 days or until the infection is resolved (see section 5.1).
4 mg/ kg mogħtija darba kull 24 siegħa għal 7- 14- il ġurnata jew sakemm l- infezzjoni tfieq (ara sezzjoni 5. 1).
- cSSTI with concurrent Staphylococcus aureus bacteraemia:
- cSSTI b’ batterimja bi Staphylococcus aureus fl- istess ħin:
The recommended dose is 6 mg/ kg
Id- doża rakkomadata hija 6 mg/ kg
administered once every 24 hours.
mogħtija darba kull 24 siegħa.
See below for dose adjustments in patients with renal insufficiency.
Ara hawn taħt għal aġġustamenti tad- doża f’ pazjenti b’ insuffiċjenza renali.
The duration of therapy may need to be longer than 14 days in accordance with the perceived risk of complications in the individual patient.
It- tul tat- terapija tista ’ tkun teħtieġ li tkun aktar minn 14- il jum skond kif ikun perċepit ir- riskju ta ’ kumplikazzjonijiet fil- pazjent individwali.
The
- Meta jkun magħruf jew suspettat li jkun hemm endokardite infettiva fin- naħa tal- lemin
recommended dose is 6 mg/ kg administered once every 24 hours.
Id- doża rakkomandata hija 6 mg/ kg mogħtija darba kull 24 siegħa.
The duration of therapy should be in accordance with available official recommendations.
It- tul tat - terapija għandu jkun skond ir- rakkomandazzjonjiet uffiċjali disponibbli.
Renal insufficiency Daptomycin is eliminated primarily by the kidney.
Insuffiċjenza renali Daptomycin huwa eliminat l- aktar mill- kilwa.
2 Due to limited clinical experience (see table and footnotes below) Cubicin should only be used in patients with any degree of renal insufficiency (Cr Cl < 80 ml/ min) when it is considered that the expected clinical benefit outweighs the potential risk.
2 Minħabba esperjenza klinika limitata (ara t- tabella u n- noti f’ qiegħ it- tabella hawn taħt) Cubicin għandu jintuża biss f’ pazjenti bi kwalunkwe grad ta ’ insuffiċjenza renali (Cr Cl < 80 ml/ min) meta jkun ikkunsidrat li l- benefiċċju kliniku mistenni ikun akbar mir- riskju li jista ’ jkun hemm.
The response to treatment and renal function should be closely monitored in all patients with some degree of renal insufficiency (see also sections 4.4 and 5.2).
Ir- respons għat- trattament u l- funzjoni renali għandhom ikunu segwiti mill- qrib fil- pazjenti kollha li għandhom xi grad ta ’ insuffiċjenza renali (ara wkoll sezzjonijiet 4. 4 u 5. 2).
Dose adjustments in patients with renal insufficiency by indication and creatinine clearance
Aġġustamenti tad- doża f’ pazjenti b’ insuffiċjenza renali skond l- indikazzjoni u t- tneħħija tal - krejatinina
Indication for use (1) cSSTI without S.
Indikazzjoni għall- użu (1) cSSTI mingħajr
Creatinine clearance (1)
Tneħħija tal- krejatinina (1) ≥30 ml/ min
Dose recommendation (1)
Rakkomandazzjoni tad - doża (1)
Comments
Kummenti
aureus bacteraemia
batterimja b’ S. aureus
4 mg/ kg once daily
4 mg/ kg darba kuljum
See section 5.1
Ara sezzjoni 5. 1
4
4 mg/ kg kull 48 siegħa
RIE or cSSTI
RIE jew cSSTI assoċjata
≥ 50 ml/ min
≥50 ml/ min
6 mg/ kg once daily
6 mg/ kg darba kuljum
(1) The safety and efficacy of the dose interval adjustment has not been clinically evaluated and the recommendation is based on pharmacokinetic modelling data (see sections 4.4 and 5.2).
(1) Is- sigurtà u l- effikaċja ta ’ l- aġġustament ta ’ l- intervall ta ’ bejn id- dożi ma ġiex evalwat klinikament u r- rakkomandazzjoni hija bbażata fuq dejta ta ’ mudell farmakokinetiku (ara sezzjonijiet 4. 4 u 5. 2).
(2) The same dose adjustments, which are also based solely on modelling are recommended for patients on haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
(2) L- istess aġġustamenti tad- dożi, li huma wkoll ibbażati biss fuq mudellar huma rakkomandati għall - pazjenti li qed jagħmlu l- emodijalisi jew dijalisi peritonali ambulatorja kontinwa (CAPD).
Whenever possible, Cubicin should be administered following the completion of dialysis on dialysis days (see section 5.2).
Kull meta jkun possibbli, Cubicin għandu jiġi amministrat wara li titlesta d- dijalisi fil- ġranet tad- dijalisi (ara sezzjoni 5. 2).
(3) There are insufficient data to support a dose recommendation for patients with RIE or cSSTI associated with Staphylococcus aureus bacteraemia who have a creatinine clearance < 50 ml/ min.
(3) M’ hemmx dejta biżżejjed li ssostni rakkomandazzjoni tad- doża għall- pazjenti li għandhom RIE jew cSSTI assoċjata ma ’ batterimja bi Staphylococcus aureus li t- tneħħija tal- krejatinina tagħhom hija < 50 ml/ min.
There are no data available to support the efficacy of 4 mg/ kg daily in patients with RIE or cSSTI associated with Staphylococcus aureus bacteraemia whose creatinine clearance is between 30-49 ml/ min or to support the use of 4 mg/ kg every 48 hours in such patients whose creatinine clearance is < 30 ml/ min.
M’ hemm l- ebda dejta disponibbli li ssostni l- effikaċja ta ’ 4mg/ kg kuljum f’ pazjenti li għandhom RIE jew cSSTI assoċjata ma ’ batterimja bi Staphylococcus aureus li t- tneħħija tal - kreatinina tagħhom hija bejn 30- 49 ml/ min jew li ssostni l- użu ta ’ 4mg/ kg kull 48 siegħa f’ dawn il - pazjenti li t- tneħħija tal- kreatinina tagħhom hija < 30 ml/ min.
Hepatic insufficiency No dose adjustment is necessary when administering Cubicin to patients with mild or moderate hepatic insufficiency (Child-Pugh Class B) (see section 5.2).
Insuffiċjenza epatika M’ hemmx bżonn ta ’ aġġustament tad- doża meta jingħata Cubicin lill- pazjenti b’ insuffiċjenza epatika ħafifa jew moderata (klassifika Child- Pugh B) (ara sezzjoni 5. 2).
No data are available in patients with severe hepatic insufficiency (Child-Pugh Class C).
M’ hemmx dejta dwar pazjenti b’ insuffiċjenza tal- fwied severa (klassifika Child- Pugh C).
Therefore caution should be exercised if Cubicin is given to such patients.
Għalhekk għandu jkun hemm kawtela jekk Cubicin jingħata lil dawn il- pazjenti.
Elderly patients The recommended doses should be used in elderly patients except those with severe renal insufficiency (see above and section 4.4).
Pazjenti anzjani Id- dożi rakkomandati għandhom jintużaw f’ pazjenti anzjani ħlief f’ dawk li jkollhom insuffiċjenza renali severa (ara hawn fuq sezzjoni 4. 4).
However, there are limited data on the safety and efficacy of daptomycin in patients aged > 65 years and caution should be exercised if Cubicin is given to such patients.
Madankollu, hemm dejta limitata dwar is- sigurtà u l - effikaċja ta ’ daptomycin f’ pazjenti li għandhom > 65 sena u għandu jkun hemm kawtela jekk Cubicin jingħata lil dawn il- pazjenti.
Children and adolescents (< 18 years old) Due to the lack of data on safety and efficacy Cubicin is not recommended for use in children and adolescents (< 18 years of age).
Tfal u adolexxenti (< 18– il sena) Peress li m’ hemmx biżżejjed informazzjoni dwar is- sigurtà u l- effikaċja Cubicin mhux irrakkomandat għall- użu fit- tfal u fl- adolexxenti (età < 18- il sena).
See also section 5.2.
Ara wkoll sezzjoni 5. 2.
Method of administration Cubicin is given by intravenous infusion (see section 6.6) and administered over a 30 minute period.
Metodu ta ’ kif jingħata Cubicin jingħata permezz ta ’ infużjoni fil- vina (ara sezzjoni 6. 6) u jingħata fuq perijodu ta ’ 30 minuta.
Hypersensitivity to the active substance or excipient.
Sensittività eċċessiva għas- sustanza attiva jew għas- sustanza mhux attiva.
If a focus of infection other than cSSTI or RIE is identified after initiation of Cubicin therapy consideration should be given to instituting alternative antibacterial therapy that has been demonstrated to be efficacious in the treatment of the specific type of infection(s) present.
Jekk jiġi identifikat fokus ta ’ infezzjoni li ma jkunx cSSTI jew RIE wara li tinbeda terapija bi Cubicin, għandu jiġi kkunsidrat li tingħata terapija antibatterika oħra li jkun intwera li hi effikaċi fil- kura tat- tip ta ’ infezzjoni( jiet) speċifika( ċi) li jkun hemm.
It has been demonstrated in clinical studies that Cubicin is not effective in the treatment of pneumonia.
Intwera fi provi kliniċi li Cubicin m’ huwiex effettiv għall- kura ta ’ pulmonite.
Clinical data on the use of Cubicin to treat RIE due to Staphylococcus aureus are limited to 19 patients (see “ Information from clinical trials” in section 5.1).
Dejta klinika dwar l- użu ta ’ Cubicin għall- kura ta ’ RIE minn Staphylococcus aureus hija limitata għall- 19- il pazjent (ara “ Tagħrif minn provi kliniċi ” f’ sezzjoni 5. 1).
The efficacy of Cubicin in patients with prosthetic valve infections or with left-sided infective endocarditis due to Staphylococcus aureus has not been demonstrated.
L- effikaċja ta ’ Cubicin f’ pazjenti b’ infezzjonijiet tal- valv prostetiku jew b’ endokardite infettiva fin - naħa tax- xellug minn Staphylococcus aureus ma ntwerietx.
Patients with deep-seated infections should receive any required surgical interventions (e. g. debridement, removal of prosthetic devices, valve replacement surgery) without delay.
Pazjenti b’ infezzjonijiet li jkunu daħlu fil- fond għandhom jagħmlu kwalunkwe intervent kirurġiku meħtieġ (eż debrajdment, tneħħija ta ’ apparat prostetiku, operazzjoni ta ’ tibdil tal- valvs) mingħajr dewmien.
There is insufficient evidence to be able to draw any conclusions regarding the possible clinical efficacy of Cubicin against infections due to enterococci, including Enterococcus faecalis and Enterococcus faecium.
M’ hemmx biżżejjed evidenza sabiex wieħed jasal għal xi konklużjonijiet fir- rigward ta ’ l- effikaċja klinika ta ’ Cubicin għall- infezzjonijiet ġejjin min enterokokki, inklużi Enterococcus faecalis u Enterococcus faecium.
In addition, dose regimens of daptomycin that might be appropriate for the treatment of enterococcal infections, with or without bacteraemia, have not been identified.
Minbarra hekk, il- kors tad- dożi għal daptomycin li jistgħu jgħoddu għall- kura ta ’ infezzjonijiet b’ enterokokki, bil- batterimja jew mingħajrha, ma ġewx identifikati.
Failures with daptomycin in the treatment of enterococcal infections that were mostly accompanied by bacteraemia have been reported.
Fallimenti b’ daptomycin fil- kura ta ’ infezzjonijiet b’ enterokokki li ħafna minnhom kellhom ukoll batterimja kienu rrappurtati.
In some instances treatment failure has been associated with the selection of organisms with reduced susceptibility or frank resistance to daptomycin (see section 5.1).
Kultant il- falliment tal- kura kien assoċjat ma ’ l- għażla ta ’ organiżmi b’ suxxettibilità mnaqqsa jew reżistanza dgħajfa għal daptomycin (ara sezzjoni 5. 1).
Creatine phosphokinase and myopathy Increases in plasma creatine phosphokinase (CPK; MM isoenzyme) levels associated with muscular pains and/ or weakness and cases of myositis, myoglobinaemia and rhabdomyolysis have been reported during therapy with Cubicin (see also sections 4.5, 4.8 and 5.3).
Creatine phosphokinase u mijopatija Żieda fil- livelli ta ’ creatine phosphokinase (CPK; iżoenzima MM) assoċjati ma ’ uġigħ muskolari u/ jew dgħjufija u każijiet ta ’ majosite, majoglobinimja u rabdomajolożi kienu rappurtati waqt terapija bi Cubicin (ara wkoll sezzjonijiet 4. 4, 4. 8 u 5. 3).
In clinical studies, marked increases in plasma CPK to > 5x Upper Limit of Normal (ULN) without muscle symptoms occurred more commonly in Cubicin-treated patients (1.9%) than in those that received comparators (0.5%).
Fil- provi kliniċi, żidiet konsiderevoli fis- CPK fil - plażma sa > 5x Il- Limitu ta ’ Fuq tan- Normali (ULN) mingħajr sintomi muskolari seħħew b’ mod aktar komuni f’ pazjenti kkurati bi Cubicin (1. 9%) milli f’ dawk li rċevew sustanzi għat- tqabbil (0. 5%).
Therefore, it is recommended that: • Plasma CPK should be measured at baseline and at regular intervals (at least once weekly) during therapy in all patients. • It cannot be ruled out that those patients with CPK greater than 5 times upper limit of normal at baseline may be at increased risk of further increases during daptomycin therapy.
Għalhekk huwa rakkomandat li: • Is- CPK fil- plażma għandu jitkejjel fil- linja bażi u f’ intervalli regolari (mill- anqas darba fil - ġimgħa) waqt it- terapija fil- pazjenti kollha. • Ma jistax jiġi eskluż li pazjenti li jkollhom CPK ogħla minn 5 darbiet il- limitu ta ’ fuq tan - normali fil- linja bażi jista ’ jkollhom riskju akbar ta ’ aktar żidiet waqt it- terapija b’ daptomycin.
This should be taken into account when initiating daptomycin therapy and, if daptomycin is given, these patients should be monitored more frequently than once weekly. • CPK should be measured more frequently than once weekly in patients who are at higher risk of developing myopathy.
Dan għandu jitqies meta tinbeda terapija b’ daptomycin, u jekk jingħata daptomycin, dawn il - pazjenti għandhom ikunu mmonitorjati aktar ta ’ spiss minn darba f’ ġimgħa. • CPK għandu jitkejjel aktar ta ’ spiss minn darba fil- ġimgħa f’ pazjenti li għandhom riskju akbar li jiżviluppaw mijopatija.
HMG-CoA reductase inhibitors, fibrates and ciclosporin). • Cubicin should not be administered to patients who are taking other medications associated with myopathy unless it is considered that the benefit to the patient outweighs the risk. • Patients should be reviewed regularly while on therapy for any signs or symptoms that might represent myopathy. • Any patient that develops unexplained muscle pain, tenderness, weakness or cramps should have CPK levels monitored every 2 days.
Dawn il- pazjenti jinkludu dawk li jkollhom insuffiċjenza renali severa (tneħħija tal- krejatinina < 30 ml/ min; ara wkoll sezzjoni 4. 2) u pazjenti li jkunu qed jieħdu mediċini oħrajn magħrufa li huma assoċjati ma ’ majopatija (eż impedituri ta ’ HMG- CoA reductase, fibrati u ciclosporin). • Cubicin m’ għandux jingħata lill- pazjenti li jkunu qed jieħdu mediċini oħrajn li huma assoċjati ma ’ majopatija sakemm ma jitqiesx li l- benefiċċju għal pazjent jegħleb ir- riskju. • Il- pazjenti għandhom ikunu invistati b’ mod regolari waqt li jkunu fuq it- terapija, għal sinjali jew sintomi li jindikaw li hemm majopatija. • Kull pazjenti li jiżviluppa uġigħ fil- muskoli, tenerezza, dgħjufija jew bugħawwieġ mingħajr spjegazzjoni għandu jkollhom il- livelli ta ’ CPK immonitorjat kull jumejn.
Cubicin should be discontinued in the presence of unexplained muscle symptoms if the CPK level reaches greater than 5 times upper limit of normal.
Cubicin għandu jitwaqqaf fil- preżenza ta ’ sintomi tal- muskoli mingħajr spjegazzjoni jekk il- livelli ta ’ CPK jilħqu livell ogħla minn 5 darbiet il- limitu ta ’ fuq tan- normali.
4 Peripheral Neuropathy Patients who develop signs or symptoms that might represent a peripheral neuropathy during therapy with Cubicin should be investigated and consideration should be given to discontinuation of daptomycin (see sections 4.8 and 5.3).
4 Newropatija periferali Pazjenti li jkollhom sinjali jew sintomi li jistgħu jindikaw newropatija periferali waqt it- terapija bi Cubicin għandhom jiġu eżaminati u għandu jiġi kkonsidrat li jitwaqqaf daptomycin (ara sezzjonijiet 4. 8 u 5. 3).
Renal Insufficiency Renal insufficiency has been reported during treatment with Cubicin.
Insuffiċjenza renali Insuffiċjenza renali kienet rappurtata waqt kura bi Cubicin.
Severe renal insufficiency may in itself also pre-dispose to elevations in daptomycin levels which may increase the risk of development of myopathy (see above).
Insuffiċjenza renali severa tista ’, fiha nfisha, twassal għal predispożizzjoni sabiex il- livelli ta ’ daptomycin jogħlew u dawn jistgħu jżidu r - riskju ta ’ l- iżvilupp ta ’ majopatija (ara hawn fuq).
Dose adjustment is needed for patients with cSSTI without bacteraemia whose creatinine clearance is < 30 ml/ min (see sections 4.2 and 5.2).
Aġġustament tad- doża huwa meħtieġ għal pazjenti b’ cSSTI mingħajr batterimja li t- tneħħija tal - krejatinina tagħhom hija < 30 ml/ min (ara sezzjonijiet 4. 2 u 5. 2).
The safety and efficacy of the dose interval adjustment guidelines provided in section 4.2 are based on pharmacokinetic modelling and have not been clinically evaluated.
Is- sigurtà u l- effikaċja tal- linji gwida dwar l- aġġustament ta ’ l- intervall ta ’ bejn id- dożi mogħtija f’ sezzjoni 4. 2 huma bażati fuq mudelli farmakokinetiċi u ma ġewx evalwati b’ mod kliniku.
In addition there are no data to support the use of 6 mg/ kg daptomycin once daily in patients with RIE or with cSSTI associated with bacteraemia whose creatinine clearance is < 50 ml/ min.
Flimkien ma ’ dan m’ hemm l- ebda dejta li ssostni l- użu ta ’ 6 mg/ kg daptomycin darba kuljum f’ pazjenti b’ RIE jew b’ cSSTI assoċjata ma ’ batterimja li t - tneħħija tal- krejatinina tagħhom hija < 50 ml/ min.
Cubicin should only be used in such patients when it is considered that the expected clinical benefit outweighs the potential risk.
Cubicin għandu jintuża f’ dawn il- pazjenti biss meta jkun meqjus li l- benefiċċju kliniku mistenni jegħleb ir- riskju potenzjali.
Caution is advised when administering Cubicin to patients who already have some degree of renal insufficiency (creatinine clearance < 80 ml/ min) before commencing therapy with Cubicin.
Il- kawtela hi meħtieġa meta jingħata Cubicin lill- pazjenti li diġà għandhom xi grad ta ’ insuffiċjenza renali (tneħħija tal- krejatinina < 80 ml/ min) qabel ma tibda t- terapija bi Cubicin.
Regular monitoring of renal function is advised (see also section 5.2).
Monitoraġġ regolari tal- funzjoni renali huwa kkunsiljat (ara wkoll sezzjoni 5. 2).
In addition, regular monitoring of renal function is advised during concomitant administration of potentially nephrotoxic agents, regardless of the patient’ s pre-existing renal function (see also section 4.5).
(ara wkoll sezzjoni 4. 5).
In obese subjects with Body Mass Index (BMI) > 40 kg/ m2 but with creatinine clearance > 70 ml/ min, the AUC0-∞ daptomycin was significantly increased (mean 42% higher) compared with non-obese matched controls.
F’ individwi obeżi b’ Indiċi tal- Piż tal- Ġisem (BMI) > 40 kg/ m2 iżda bi tneħħija tal- krejatinina > 70 ml/ min, l- AUC0- ∞ ta ’ daptomycin għoliet b’ mod sinifikanti (medja ta ’ 42% ogħla) meta mqabbla ma ’ kontrolli mhux obeżi ppariġġati magħhom.
There is limited information on the safety and efficacy of daptomycin in the very obese and so caution is recommended.
Hemm tagħrif limitat dwar is- sigurtà u l- effikaċja ta ’ daptomycin f’ individwi li jkunu obeżi ħafna u għalhekk hija rakkomandata l- kawtela.
However, there is currently no evidence that a dose reduction is required (see section 5.2).
Madankollu, s’ issa m’ hemmx evidenza li tnaqqis fid- doża huwa meħtieġ (ara sezzjoni 5. 2).
The use of antibiotics may promote the overgrowth of non-susceptible micro-organisms.
L- użu ta ’ antibijotiċi jista ’ jiffavorixxi t- tkabbir żejjed ta ’ mikro- organiżmi li ma jkunux suxxettibli.
If superinfection occurs during therapy, appropriate measures should be taken.
Jekk ikun hemm sopra- infezzjoni waqt it- terapija, għandhom jittieħdu miżuri xierqa.
Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening.
Kolite assoċjata ma ’ l- antibijotiċi u kolite sewdomembranika kienu rappurtati kważi bl- antibatteriċi kollha u jistgħu jvarjaw fis- severità tagħhom minn ħfief għal li jkunu ta ’ theddida għall- ħajja.
Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or shortly following treatment.
Għalhekk, huwa importanti li tkun kkunsidrata din id- dijanjożi f’ pazjenti li taqbadhom dijarrea waqt jew ftit wara l- kura.
Daptomycin undergoes little to no Cytochrome P450 (CYP450) mediated metabolism.
Daptomycin ikollu ftit li xejn jew l- ebda metaboliżmu permezz ta ’ cytochrome P450 (CYP450).
In vitro studies have determined that daptomycin does not inhibit or induce the activities of clinically significant human CYP isoforms (1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4).
Studji in vitro stabilixxew li daptomycin la jinibixxi u l- anqas jinduċi l- attivitajiet ta ’ iżoformi ta ’ CYP uman klinikament sinifikanti (1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4).
Therefore, no CYP450-related drug interactions are to be expected.
Għalhekk mhux mistennija interazzjonijiet relatati ma ’ CYP450.
There is limited experience regarding concomitant administration of daptomycin with other medicinal products that may trigger myopathy.
Hemm esperjenza limitata dwar l- għoti fl- istess ħin ta ’ daptomycin ma ’ prodotti mediċinali oħrajn li jistgħu jqanqlu majopatija.
However, some cases of marked rises in CPK levels and cases of rhabdomyolysis occurred in patients taking one of these medications at the same time as Cubicin.
Madankollu, xi każijiet ta ’ żidiet fil- livelli ta ’ CPK u każijiet ta ’ rabdomajelożi seħħew f’ pazjenti li kienu qed jieħdu wieħed minn dawn il- mediċini fl- istess ħin ma Cubicin.
It is recommended that other medications associated with myopathy should if possible be temporarily discontinued during treatment with Cubicin unless the benefits of concomitant administration outweigh the risk.
Huwa rakkomandat li medikazzjonijiet oħrajn li huma assoċjati ma ’ majopatija jekk jista ’ jkun, għandhom jitwaqqfu b’ mod temporanju waqt kura bi Cubicin sakemm il- benefiċċji tal- kura fl - istess ħin ma jegħlbux ir- riskju.
If co-administration cannot be avoided, CPK levels should be measured more frequently than once weekly and patients should be closely monitored for any signs or symptoms that might represent myopathy.
Jekk l- għoti fl- istess ħin ma jistax jiġi evitat, il- livelli ta ’ CPK għandhom jitkejjlu aktar ta ’ spiss minn darba f’ ġimgħa u għandhom jiġu mmonitorjati mill- qrib għal xi sinjali jew sintomi li jistgħu jirrappreżentaw majopatija.
See sections 4.4, 4.8 and 5.3.
Ara sezzjonijiet 4. 4, 4. 8 u 5. 3.
NSAIDs and COX-2 inhibitors).
5 Daptomycin jitneħħa l- aktar b’ filtrazzjoni renali u għalhekk il- livelli fil- plażma jistgħu jiżdiedu meta jingħata flimkien ma ’ mediċini li jnaqqsu l- filtrazzjoni renali (eż NSAID’ s u inibituri ta ’ COX- 2).
In addition, there is a potential for a pharmacodynamic interaction to occur during co- administration due to additive renal effects.
Minbarra hekk, hemm potenzjal ta ’ interazzjoni farmakodinamika meta jingħataw flimkien minħabba effetti renali addizzjonali.
Therefore, caution is advised when daptomycin is co- administered with any other medicinal product known to reduce renal filtration.
Għalhekk, hija kkunsiljata l- kawtela meta daptomycin jingħata ma ’ kwalunkwe mediċina oħra li tnaqqas il- filtrazzjoni renali.
During post– marketing surveillance, cases of interference between daptomycin and particular reagents used in some assays of Prothrombin Time/ International Normalised Ratio (PT/ INR) have been reported.
Waqt sorveljanza ta ’ wara t- tqegħid fis- suq, każijiet ta ’ interferenza bejn daptomycin u kimiċi partikulari li jintużaw f’ xi analiżi tal- Ħin ta ’ Protrombin/ Proporzjon Internazzjonali Normalizzat (PT/ INR) kienu rappurtati.
This interference led to an apparent prolongation of PT and elevation of INR.
Din l- interferenza wasslet għal PT itwal u ta ’ INR ogħla.
If unexplained abnormalities of PT/ INR are observed in patients taking daptomycin, consideration should be given to a possible in vitro interaction with the laboratory test.
Jekk ikun hemm anormalitajiet bla spjegazzjoni fil- PT/ INR ta ’ pazjenti fuq daptomycin, għandha tkun ikkunsidrata interazzjoni in vitro mat- test tal- laboratorju.
The possibility of erroneous results may be minimised by drawing samples for PT or INR testing near the time of trough plasma concentrations of daptomycin.
Il- possibilità li r- riżultati jiġu żbaljati tista ’ titnaqqas billi jittieħdu kampjuni għall- ittestjar ta ’ PT u INR fil- ħin meta l- livelli ta ’ daptomycin fil- plażma jkunu l - aktar baxxi.
No clinical data on pregnancies are available for daptomycin.
Għal daptomycin m’ hemmx tagħrif kliniku dwar l- użu waqt it- tqala.
Animal studies do not indicate direct or indirect harmful effects with respect to fertility, pregnancy, embryonal/ fetal development, parturition or postnatal development (see section 5.3).
Studji fuq il- bhejjem ma jurux effetti ħżiena diretti jew indiretti fuq il- fertilità, it- tqala, fuq l- iżvilupp ta 'l- embriju/ fetu, ħlas jew żvilupp wara t- twelid (ara sezzjoni 5. 3).
Cubicin should not be used during pregnancy unless clearly necessary i. e., only if the potential benefit outweighs the possible risk.
Cubicin m’ għandux jintuża waqt it- tqala ħlief meta jkun hemm bżonn speċifiku i. e., biss jekk il - benefiċċju potenzjali jegħleb ir- riskju possibli.
It is not known whether daptomycin is excreted in human milk.
Mhux magħruf jekk daptomycin joħroġx fil- ħalib tas- sider tal- bniedem.
Therefore, breastfeeding should be discontinued during treatment with Cubicin.
Għalhekk, it- treddigħ għandu jitwaqqaf waqt il- kura bi Cubicin.
On the basis of reported adverse drug reactions, Cubicin is presumed to be unlikely to produce an effect on the ability to drive or use machinery.
Mir- reazzjonijiet avversi rrappurtati, Cubicin huwa meqjus li mhux probabbli li jkollu effett fuq il- ħila biex issuq jew tħaddem makkinarju.
Clinical Studies In clinical studies, 2,011 subjects received Cubicin.
Studji kliniċi Fi studji kliniċi, aktar minn 2, 011 individwu rċevew Cubicin.
Within these trials, 1,221 subjects received a daily dose of 4 mg/ kg, of whom 1,108 were patients and 113 were healthy volunteers; 460 subjects received a daily dose of 6 mg/ kg, of whom 304 were patients and 156 were healthy volunteers.
Reazzjonijiet avversi (ie.
Adverse reactions (i. e. considered by the investigator to be possibly, probably, or definitely related to the medicinal product) were reported at similar frequencies for Cubicin and comparator regimens.
Dawk meqjusa mill- investigatur bħala possibiliment, probabbilment jew bla ebda dubju relatati mal- prodott mediċinali) kienu rappurtati bi frekwenzi simili għal Cubicin u l- korsijet li ngħataw għat- tqabbil.
For subjects who received Cubicin, the adverse reactions that were most frequently reported during therapy plus follow-up were: headache, nausea, vomiting, diarrhoea, fungal infections, rash, infusion site reaction, increased Creatine phosphokinase (CPK) and abnormal liver enzymes; Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase.
Għal dawk li rċevew Cubicin, ir- reazzjonijiet avversi li kienu rappurtati l- aktar ta ’ spiss waqt il- kura kif ukoll waqt il- follow- up kienu: uġigħ ta ’ ras, dardir, rimettar, dijarrea, infezzjonijiet tal- moffa, raxx, reazzjonijiet fil- post mnejn tingħata l- infużjoni, żieda fil- Creatine phosphokinase (CPK) u enzimi tal - fwied anormali; Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase.
The following adverse reactions were reported during therapy and during follow-up with frequencies corresponding to Common = ≥ 1/ 100 ,< 1/10; Uncommon = > 1/1 ,000, < 1/100; Rare = > 1/10,000, < 1/ 1,000, Very rare = ≤ 1/10 ,000:
Ir- reazzjonijiet avversi li ġejjin kienu rappurtati waqt t- terapija u waqt il- follow- up bi frekwenzi li jikkorrispondu għal Komuni ≥1/ 100, < 1/ 10; Mhux komuni ≥1/ 1, 000, < 1/ 100; Rari ≥1/ 10, 000, < 1/ 1, 000, Rari ħafna ≤1/ 10, 000.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
L - effetti li huma l- aktar serji mniżżlin l- ewwel, segwiti minn dawk anqas serji.
6 Infections and Infestations Common:
6 Infezzjonijiet u infestazzjonijiet Komuni:
Fungal infections Uncommon:
Infezzjonijiet tal- moffa Mhux komuni:
Urinary tract infection
Infezzjoni tas- sistema awrinarja
Blood and lymphatic system disorders Uncommon:
Disturbi tad- demm u tas- sistema limfatika Mhux komuni:
Thrombocythaemia, anaemia, eosinophilia
Tromboċitemja, anemija, eżinofilja
Metabolism and nutrition disorders Uncommon:
Disturbi fil- metaboliżmu u n- nutrizzjoni Mhux komuni:
Anorexia, hyperglycaemia
Anoressija, ipergliċemija
Psychiatric disorders Uncommon:
Disturbi psikjatriċi Mhux komuni:
Anxiety, insomnia
Ansjetà, nuqqas ta ’ rqad
Headache Uncommon:
Uġigħ ta ’ ras Mhux komuni:
Dizziness, paraesthesiae, taste disorder
Sturdament, parasteżiji, problemi biex ittiegħem
Cardiac disorders Uncommon:
Disturbi fil- qalb Mhux komuni:
Supraventricular tachycardia, extrasystole
Takikardija supraventrikolari, extrasystole
Vascular disorders Uncommon:
Disurbi vaskulari Mhux komuni:
Flushes, hypertension, hypotension
Fwawar, pressjoni għolja, pressjoni baxxa
Gastrointestinal disorders Common:
Disturbi gastro- intestinali Komuni:
Nausea, vomiting, diarrhoea Uncommon:
Dardir, rimettar, dijarrea Mhux komuni:
Constipation, abdominal pain, dyspepsia, glossitis
Stitikezza, uġigħ addominali, dispepsja, glossite
Hepatobiliary disorders Uncommon:
Disturbi fil- fwied u fil- marrara Mhux komuni:
Jaundice
Suffejra
Rash Uncommon:
Raxx Mhux komuni:
Pruritis, urticaria
Ħakk, urtikarja
Musculoskeletal, connective tissue and bone disorders Uncommon:
Mhux komuni:
Myositis, muscle weakness, muscle pain, arthralgia
Majożite, dgħjufija tal- muskoli, uġigħ fil- muskoli, artralġja
Renal and urinary disorders Uncommon:
Disturbi renali u awrinarji Mhux komuni:
Renal insufficiency, including renal impairment and renal failure
Insuffiċjenza renali, inkluż indeboliment renali u insuffiċjenza renali
Reproductive system and breast disorders Uncommon:
Disturbi fis- sistema riproduttiva u fis- sider Mhux komuni:
Vaginitis
Vaġinite
General disorders and administration site conditions Common:
Disturbi ġenerali u kundizzjonijiet ta 'mnejn jingħata Komuni:
Infusion site reactions Uncommon:
Reazzjonijiet fil- post ta ’ l- infużjoni Mhux komuni:
Pyrexia, weakness, fatigue, pain
Deni, dgħjufija, għeja, uġigħ
Liver function tests abnormal (increased AST, ALT and alkaline phosphatase), increased CPK Uncommon:
Testijiet tal- funzjoni tal- fwied anormali (żieda fl- AST, ALT u alkaline phosphatase) żieda fis- CPK Mhux komuni:
Electrolyte imbalance, increased serum creatinine, increased myoglobin, Lactic dehydrogenase (LDH) increased
Żbilanċ fl- elettroliti, żieda fil- krejatinina fis- serum, żieda fil- majoglobina, żieda fil - lactic dehydrogenase (LDH)
7 Post-Marketing Adverse reactions that have been reported Post-Marketing that are not listed above are:
Wara t- tqegħid fis- suq Reazzjonijiet avversi li kienu rappurtati wara t- tqegħid fis- suq li mhux imniżżla hawn fuq huma:
Immune system disorders Hypersensitivity, manifested by isolated spontaneous reports including, but not limited to; pulmonary eosinophilia, vesicobullous rash with mucous membrane involvement and sensation of oropharyngeal swelling.
7 Disturbi fis- sistema immuni Sensittività eċċessiva, li dehret f’ rapporti iżolati spontanji li jinkludu, iżda mhux limitati għall -; eżinofilja pulmonari, raxx b’ imsiemer bil- materja li jieħu wkoll fil- membrani mukożi u sensazzjoni ta ’ nefħa orofarinġali.
Anaphylaxis Infusion reactions including the following symptoms: tachycardia, wheezing, pyrexia, rigors, systemic flushing, vertigo, syncope and metallic taste.
Takikardja, tisfir man- nifs, deni, tertir, fawra mal- ġisem kollu, vertigo, sinkope u togħma tal- metall.
Musculoskeletal, connective tissue and bone disorders Rhabdomyolysis When clinical information on the patients was available to make a judgement, approximately 50% of the cases occurred in patients with pre-existing renal insufficiency, or in those receiving concomitant medications known to cause rhabdomyolysis.
Disturbi muskolu- skeletrali, tal- connective tissue u ta ’ l- għadam Rabdomajelożi Meta kien hemm tagħrif kliniku dwar il- pazjenti sabiex isir ġudizzju, madwar 50% tal- każijiet seħħew f’ pazjenti li kellhom minn qabel insuffiċjenza renali, jew dawk li kienu qed jieħdu fl- istess ħin mediċini magħrufin li jistgħu jikkawżaw rabdomajelożi.
Nervous system disorders Peripheral neuropathy
Disturbi fis- sistema nervuża Newroptija periferali
Investigations In some cases of myopathy involving raised CPK and muscle symptoms, the patients also presented with elevated transaminases.
Investigazzjonijiet F’ xi każijiet ta ’ majopatija li kienu jinvolvu żiediet fis- CPK u sintomi tal- muskoli, il- pazjenti kellhom ukoll żiediet fit- transaminases.
These transaminase increases were likely to be related to the skeletal muscle effects.
Dawn iż- żiediet fit- transaminases x’ aktarx kienu marbuta ma ’ l- effetti fuq il- muskoli skeletrali.
The majority of transaminase elevations were of Grade 1-3 toxicity and resolved upon discontinuation of treatment.
Il- maġġoranza taż- żiediet ta ’ transaminases kienu ta ’ Grad ta ’ tossiċità 1- 3 u marru lura għan- normal meta twaqqfet il- kura.
In the event of overdose, supportive care is advised.
F’ każ ta ’ doża eċċessiva, huwa kkonsiljat li jkun hemm kura ta ’ appoġġ.
Daptomycin is slowly cleared from the body by haemodialysis (approximately 15% of the administered dose is removed over 4 hours) or by peritoneal dialysis (approximately 11% of the administered dose is removed over 48 hours).
Daptomycin jitneħħa bil- mod mill- ġisem b’ emodijalisi (madwar 15% tad- doża mogħtija titneħħa fuq perijodu ta’ 4 sigħat) jew b’ dijalisi tal- peritonew (madwar 11% tad- doża mogħtija titneħħa fuq perijodu ta’ 48 siegħa).
Antibacterials for systemic use, Other antibacterials, ATC code:
Antibatteriċi għal użu sistemiku, Antibatteriċi oħrajn, Kodiċi ATC:
Mode of action Daptomycin is a cyclic lipopeptide natural product that is active against Gram positive bacteria only.
Mod kif jaħdem Daptomycin huwa prodott naturali lipopeptidu li jaħdem kontra il- batteri Gram posittivi biss.
The mechanism of action involves binding (in the presence of calcium ions) to bacterial membranes of both growing and stationary phase cells causing depolarisation and leading to a rapid inhibition of protein, DNA, and RNA synthesis.
Il- mekkaniżmu ta ’ kif jaħdem jinvolvi irbit (fil- preżenza ta ’ joni ta ’ Calcium) mal- membrani ta ’ ċelluli tal- batteri kemm dawk iċ- ċelloli li jkunu qegħdin fil- fażi ta ’ tkattir kif ukoll dawk fil- fażi stazzjonarja, li jikkawża dipolarizzazzjoni u li twassal għall- inibizzjoni tas- sintesi tal- proteini, tad- DNA u ta ’ l - RNA.
This results in bacterial cell death with negligible cell lysis.
Din twassal għall- mewt taċ- ċelluli batteriċi b’ numru żgħir minnhom li jinfaqaw.
PK/ PD relationship Daptomycin exhibits rapid, concentration dependent bactericidal activity against sensitive Gram positive organisms in vitro.
Relazzjoni PK/ PD Daptomycin juri attività batteriċida mgħaġġla, li tiddependi mill- konċentrazzjoni, kontra organiżmi Gram posittivi li huma sensittivi in vitro.
In animal models AUC/ MIC and Cmax/ MIC correlate with efficacy and predicted bacterial kill in vivo at single doses equivalent to human doses of 4 mg/ kg and 6 mg/ kg once daily.
F’ mudelli ta ’ annimali, l- AUC/ MIC u Cmax/ MIC jikkorelataw ma ’ l- effikaċja u l- qtil ta ’ batteri li jkun imbassar in vivo b’ dożi ta ’ darba ekwivalenti għal dożi fin - nies ta ’ 4 mg/ kg u 6 mg/ kg darba kuljum.
8 Mechanisms of resistance Strains with decreased susceptibility to daptomycin have been reported especially during the treatment of patients with difficult-to-treat infections and/ or following administration for prolonged periods.
Mekkaniżmi ta ’ reżistenza Razez b’ suxxettibilità mnaqqsa għal daptomycin kienu rrappurtati l- aktar waqt kura ta’ pazjenti b’ infezzjonijiet li huma diffiċli- biex- tikkurhom u/ jew wara amministrazzjoni għal perijodi twal.
In particular, there have been reports of treatment failures in patients infected with Staphylococcus aureus, Enterococcus faecalis or Enterococcus faecium, including bacteraemic patients, that have been associated with the selection of organisms with reduced susceptibility or frank resistance to daptomycin during therapy.
B’ mod partikolari, kien hemm rapporti ta ’ fallimenti ta ’ kura f’ pazjenti infettati b’ Staphylococcus aureus, Enterococcus faecalis jew Enterococcus faecium, inklużi pazjenti bil- batterimja, li kienet
The mechanism of resistance to daptomycin has not yet been identified.
8 assocata ma ’ l- għażla ta ’ l- organiżmi b’ suxxettibilità mnaqqsa jew reżistenza batuta għal daptomycin waqt it- terapija.
Breakpoints Minimum inhibitory concentration (MIC) breakpoint established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for Staphylococci and Streptococci (except S. pneumoniae) are Susceptible ≤ 1 mg/ l and Resistant > 1 mg/ l.
Pneumoniae) huma Suxxettibli ≤1 mg/ l u Resistenti > 1 mg/ l.
Susceptibility The prevalence of resistance may vary geographically and over time for selected species and local information on resistance is desirable, particularly when treating severe infections.
Suxxettibilità Il- prevalenza tar- reżistenza tista ’ tvarja ġejografikament u maż- żmien għall- speċi magħżula u għalhekk ikun xieraq li jinġabar tagħrif lokali fuq ir- reżistenza, l- aktar meta jkunu qed jiġu kkurati infezzjonijiet severi.
As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
Jekk ikun hemm bżonn, għandu jittieħed parir ta ’ l- esperti meta l- prevalenza lokali tar- reżistenza tkun tant li l- utilità tal- mediċina f’ għalmenu xi wħud mill- infezzjonijiet ma tkunx ċara.
Commonly Susceptible Species Staphylococcus aureus * Staphylococcus haemolyticus Coagulase negative staphylococci Streptococcus agalactiae* Streptococcus dysgalactiae subsp equisimilis* Streptococcus pyogenes* Group G streptococci Clostridium perfringens Peptostreptococcus spp Inherently resistant organisms Gram negative organisms * denotes species against which it is considered that activity has been satisfactorily demonstrated in clinical studies.
Speċi li ta ’ Spiss ikunu Suxxettibli Staphylococcus aureus * Staphylococcus haemolyticus Staphylococci negattivi għall- Coagulase Streptococcus agalactiae * Streptococcus dysgalactiae subsp equisimilis * Streptococcus pyogenes * Streptococci grupp G Clostridium perfringens Peptostreptococcus spp Organiżmi reżistenti b’ mod inerenti Organiżmi Gram negattivi * tindika speċi fejn hu meqjus li l- attività kontrihom ntweriet b’ mod sodisfaċenti fi studji kliniċi.
Information from clinical trials In two clinical trials in complicated skin and soft tissues infections, 36% of patients treated with Cubicin met the criteria for systemic inflammatory response syndrome (SIRS).
Tagħrif minn provi kliniċi F’ żewġ provi kliniċi ta ’ infezzjonijiet komplikati tal- ġilda u tat- tessuti rotob, 36% tal- pazjenti kkurati b’ Cubicin laħqu l- kriterju għal sindromu ta ’ respons infjammatorju sistemiku (SIRS).
The most common type of infection treated was wound infection (38% of patients), while 21% had major abscesses.
L- aktar tip ta ’ infezzjoni komuni li kienet ikkurata kienet infezzjoni ta ’ ferita (38% tal- pazjenti), filwaqt li 21% kellhom bżieżaq bil- materja.
These limitations of the patients population treated should be taken into account when deciding to use Cubicin.
Dawn il- limitazzjonijiet tal- popolazzjonijiet tal- pazjenti kkurati għandhom jitqiesu meta jiġi deċiż biex jintuża Cubicin.
In a randomised controlled open-label study in 235 patients with Staphylococcus aureus bacteraemia (i. e, at least one positive blood culture of Staphylococcus aureus prior to receiving the first dose) 19 of 120 patients treated with Cubicin met the criteria for RIE.
Fi studju randomised ikontrollat open- label ta ’ 235 pazjent b’ batterimja bi Staphylococcus aureus (jiġifieri mill- inqas koltura waħda tad- demm pożittiva bi Staphylococcus aureus qabel ma ’ rċievew l - ewwel doża) 19 mill- 120 pazjent ikkurati bi Cubicin issodisfaw il- kriterji għal RIE.
Of these 19 patients 11 were infected with methicillin-susceptible and 8 with methicillin-resistant Staphylococcus aureus.
Minn dawn id- 19 - il pazjent 11 kienu infettati bi Staphylococcus aureus suxxettibbli u 8 bi Staphylococcus aureus reżistenti għall- methicillin.
The success rates in RIE patients are shown in the table below.
Ir- rati ta ’ suċċess fil- pazjenti b’ RIE huma murija fit- tabella hawn taħt.
9 Differences in Population
Popolazzjoni Popolazzjoni ITT (intenzjoni li tiġi kkurata)
Daptomycin
Daptomycin n/ N (%)
n/ N (%) n/ N (%)
Kumparatur n/ N (%)
Rates (95% CI)
Differenzi fis- Suċċess Rates (95% CI)
RIE PP (per protocol) Population
RIE Popolazzjoni PP (għal kull protokol)
8/ 19 (42.1%)
8/ 19 (42. 1%)
7/ 16 (43.8%)
7/ 16 (43. 8%)
-1.6% (-34.6, 31.3)
- 1. 6% (- 34. 6, 31. 3)
6/ 12 (50.0%)
6/ 12 (50. 0%)
4/ 8 (50.0%)
4/ 8 (50. 0%)
0.0% (-44.7, 44.7)
0. 0% (- 44. 7, 44. 7)
Failure of treatment due to persisting or relapsing Staphylococcus aureus infections was observed in 19/ 120 (15.8%) patients treated with Cubicin, 9/ 53 (16.7%) patients treated with vancomycin and 2/ 62 (3.2%) patients treated with an anti-staphylococcal semi-synthetic penicillin.
Falliment tal- kura minħabba infezzjonijiet bi Staphylococcus aureus persistenti jew li jerġgħu joħorġu kienu osservati f’ 19/ 120 (15. 8%) pazjent ikkurati bi Cubicin, 9/ 53 (16. 7%) pazjent ikkurati b’ vancomycin u 2/ 62 (3. 2%) pazjent ikkurati b’ penicillin semi- sintetiku kontra l- istaphylococci.
Among these failures six patients treated with Cubicin and one patient treated with vancomycin were infected with Staphylococcus aureus that developed increasing MICs of daptomycin on or following therapy (see “ Mechanisms of resistance” above).
Fost 9 dawn il- fallimenti sitt pazjenti kkurati bi Cubicin u pazjent wieħed ikkurat b’ vancomycin kienu infettati bi Staphlococcus aureus li żviluppa żieda fl- MIC’ s ta ’ daptomycin waqt jew wara t- terapija (ara “ Mekkaniżmi ta ’ reżistenza ” hawn fuq).
Most patients who failed due to persisting or relapsing Staphylococcus aureus infection had deep-seated infection and did not receive necessary surgical intervention.
Il- parti l- kbira tal- pazjenti li fallew minħabba infezzjoni bi Staphylococcus aureus persistenti jew li terġa ’ toħroġ kellhom infezzjoni fil- fond u ma saritilhomx il- kirurġija li kienu jeħtieġu.
Daptomycin pharmacokinetics are generally linear and time-independent at doses of 4 to 12 mg/ kg administered as a single daily dose for up to 14 days in healthy volunteers.
Il- farmakokinetiċi ta ’ daptomycin normalment isegwu linja dritta u ma jiddependux mill- ħin f’ dożi ta ’ 4 sa 12 mg/ kg mogħtija bħala doża waħda kuljum għal mhux aktar minn 14- il jum f’ voluntiera b’ saħħithom.
Steady-state concentrations are achieved by the third daily dose.
Konċentrazzjonijiet fl- istat fiss jintlaħqu mat- tielet doża li tingħata kuljum.
Animal studies showed that daptomycin is not absorbed to any significant extent after oral administration.
Studji b’ annimali wrew li daptomycin ma jiġix assorbit b’ mod sinifikanti meta jittieħed b’ mod orali.
Distribution The steady state volume of distribution of daptomycin was approximately 0.1 l/ kg in healthy adult volunteers, consistent with distribution primarily within the extracellular space.
Distribuzzjoni Il- volum ta ’ distribuzzjoni ta ’ daptomycin fi stat fiss kien madwar 0. 1 l/ kg f’ voluntiera adulti b’ saħħithom, li hija konsistenti ma ’ distribuzzjoni primarja fl- ispazju ta ’ barra ċ- ċelluli.
Tissue distribution studies in animals have shown that daptomycin preferentially distributes into highly vascularised tissues and to a lesser degree penetrates the blood-brain barrier and the placental barrier following single and multiple doses.
Studji dwar kif jinfirex fit- tessuti f’ annimali wrew li daptomycin jinfirex l- aktar fit- tessuti vaskulari, u f’ ammonti iżgħar jidħol fil- barriera ta ’ bejn il- moħħ u d- demm u l- barriera tal- plaċenta wara doża b’ waħda jew ħafna dożi.
Daptomycin is reversibly bound to human plasma proteins in a concentration independent manner.
Daptomycin jintrabat b’ mod riversibli mal- proteini tal- plażma fil- bniedem b’ mod li ma jiddependix mill- konċentrazzjoni.
In healthy volunteers and patients treated with daptomycin, protein binding averaged about 90% including subjects with renal insufficiency.
F’ voluntiera b’ saħħithom u f’ pazjenti kkurati b’ daptomycin, l- irbit mal- proteini laħaq medja ta ’ 90% inklużi individwi b’ insuffiċjenza renali.
Metabolism In vitro studies have demonstrated that there is no or limited liver microsomal mediated metabolism of daptomycin in humans and that CYP450 involvement in daptomycin metabolism is minimal.
Metaboliżmu Studji in vitro wrew li m’ hemm l- ebda jew ftit li xejn metaboliżmu ta ’ daptomycin permezz ta ’ mikrosomi tal- fwied fil- bnedmin u li r- rwol ta ’ CYP450 fil- metaboliżmu ta ’ daptomycin huwa minimu.
Analysis of plasma samples from subjects who received a 6 mg/ kg dose of daptomycin did not show any trace of metabolism, suggesting little to no systemic metabolism.
Analiżi ta ’ kampjuni tal- plażma minn individwi li rċevew doża ta ’ 6 mg/ kg ta ’ daptomycin ma wriet l- ebda ħjiel ta ’ metaboliżmu, li tindika li hemm ftit jew l- ebda metaboliżmu sistemiku.