qanastek/EMEA-V3 huggingface dataset:
This overfill ensures that after dilution with the entire contents of the accompanying solvent for Docetaxel Winthrop vial, there is a minimal extractable premix volume of 8 ml containing 10 mg/ ml docetaxel which corresponds to the labelled amount of 80 mg per vial.
Din iż- żieda fil- volum tiżgura li, wara li ssir it- taħlita tal- kontenut sħiħ tal- kunjett tas - solvent mal- kontenut tal- kunjett ta’ Docetaxel Winthrop, ikun hemm ammont minimu li jista ’ jittella ’ ta ’ 8 ml, li għandu 10 mg/ ml docetaxel, li jikkorrispondi għall- ammont indikat fuq it - tabella ta ’ 80 mg kull fjala.
2.2 Solvent for Docetaxel Winthrop 80 mg vial
2. 2 Solvent għall- kunjett ta ’ Docetaxel Winthrop 80 mg:
• The solvent for Docetaxel Winthrop 80 mg vial is a 15 ml clear glass vial with a transparent colourless flip-off cap.
• Is- solvent għal Docetaxel Winthrop 80 mg huwa f’ kunjett tal- ħġieġ ċar ta ’ 15 ml u li għandu tapp trasparenti u mingħajr kulur, li jinfetaħ billi tgħollih.
105 3.
105 • Kull kunjett tas- solvent, li tmur ma ’ kunjett ta ’ Docetaxel Winthrop 80 mg, fiha 7. 33 ml.
4.1.4 Remove the syringe and needle and mix manually by repeated inversions for at least 45 seconds.
106 4. 1. 4 Neħħi s- siringa u l- labra u ħawwad b’ idejk billi ddawwar repetutament il- kunjett għal mhux anqas minn 45 sekonda.
106 4.1.5 Allow the premix vial to stand for 5 minutes at room temperature (below 25 °C) and then check that the solution is homogenous and clear (foaming is normal even after 5 minutes due to the presence of polysorbate 80 in the formulation).
4. 1. 5 Ħalli il- kunjett, li issa fih is- soluzzjoni inizjali, joqgħod għal 5 minuti f’ temperatura ambjentali (taħt 25 °Ċ) u ara li t- taħlita hija omoġenja u ċara (il- formazzjoni tar- ragħwa hija ħaġa normali u tista ’ tibqa ’ anke wara 5 minuti dovuta għall - preżenza tal- polysorbate 80 fil- formulazzjoni).
If you want more information on the basis of the CHMP recommendations, read the Scientific Discussion (also part of the EPAR).
Jekk trid aktar informazzjoni abbażi tar- rakkomandazzjonijiet tas- CHMP, aqra d - Diskussjoni Xjentifika (ukoll parti mill- EPAR).
What is Doribax?
X’ inhu Doribax?
Doribax is a medicine containing the active substance doripenem.
Doribax hija mediċina li fiha s- sustanza attiva doripenem.
It is available as a powder to be made up into a solution for infusion (drip into a vein).
Jiġi bħala trab li jitħallat f’ soluzzjoni għall - infużjoni (drip ġol- vina).
What is Doribax used for?
Għalxiex jintuża Doribax?
Doribax is an antibiotic.
Doribax huwa antibijotiku.
It is used to treat the following infections in adults: • nosocomial pneumonia (an infection of the lungs). ‘ Nosocomial ’ means that the infection was caught in hospital, including pneumonia caused by the use of a ventilator (a machine that helps a patient to breathe); • complicated infections in the abdomen (tummy). ‘ Complicated ’ means that the infection is difficult to treat; • complicated infections of the urinary tract (the structures that carry urine).
Huwa jintuża biex jikkura l- infezzjonijiet li ġejjin fl- adulti: • pnewmonja nożokomjali (infezzjoni tal- pulmuni). ‘ Nożokomjali ’ tfisser li l- infezzjoni ttieħdet fi sptar, inkluża pnewmonja ikkaġunata permezz ta ’ l- użu ta ’ ventilatur (magna li tgħin pazjent biex jieħu n- nifs); • infezzjonijiet ikkumplikati fl- addome (iż- żaqq). ‘ Ikkumplikata ’ tfisser li l- infezzjoni hija diffiċli biex tkun ikkurata; • infezzjonijiet ikkumplikati tal- passaġġi awrinarji (l- istrutturi li jġorru l- awrina).
Before using Doribax, doctors should consider official guidance on the use of antibiotics.
Qabel jintuża Doribax, it- tobba għandhom jikkunsidraw il- gwida uffiċjali fuq l- użu ta ’ l- antibijotiċi.
How is Doribax used?
Kif jintuża Doribax?
The standard dose of Doribax is 500 mg every eight hours.
Id- doża standard ta ’ Doribax hija ta ’ 500 mg kull tmien sigħat.
Each infusion lasts for one hour, although some patients with pneumonia may need infusions lasting four hours.
Kull infużjoni ddum siegħa, għalkemm xi pazjenti bi pnewmonja jista ’ jkollhom bżonn infużjonijiet li jdumu erba ’ sigħat.
Treatment usually continues for between five and 14 days, depending on the type and severity of the infection and the patient’ s response.
Il- kura ġeneralment tkompli għal bejn ħames u 14- il jum, jiddependi fuq it- tip u s- severità ta ’ l- infezzjoni u r- reazzjoni tal - pazjent.
Because the medicine is removed from the body by the kidneys, the dose of Doribax should be reduced in patients who have moderate or severe problems with their kidneys.
Peress li l- mediċina titneħħa mill- ġisem permezz tal- kliewi, id- doża ta ’ Doribax għandha titnaqqas f’ pazjenti li għandhom problemi moderati jew severi fil- kliewi.
Doribax is not recommended for use in children under 18 years of age because of a lack of information on safety and effectiveness in this age group.
Doribax mhuwiex irrakkomandat għall- użu fi tfal taħt it- 18- il sena minħabba nuqqas ta ’ tagħrif dwar is- sigurtà u l- effikaċja f’ dan il- grupp ta ’ età.
How does Doribax work?
Kif jaħdem Doribax?
The active substance in Doribax, doripenem, is an antibiotic that belongs to the group ‘ carbapenems’.
Is- sustanza attiva f’ Doribax, doripenem, hija antibijotiku li jappartieni għall- grupp ta ’ ‘ carbapenems ’.
It works by attaching to certain types of protein on the surface of the bacteria cells.
Taħdem billi torbot ma ’ ċerti tipi ta ’ proteina fuq il- wiċċ ta ’ ċelloli tal- batterji.
This prevents the bacteria from building the walls that surround their cells, which kills the bacteria.
Dan jimpedixxi l - batterji milli jibnu l- ħitan li jiċċirkondaw iċ- ċelloli tagħhom, li joqtlu lill- batterji.
The list of bacteria against which Doribax is active can be found in the Summary of Product Characteristics (also part of the EPAR).
Il- lista ta ’ batterji kontra liema huwa attiv Doribax tista ’ tinstab fis- Sommarju tal- Karatteristiċi tal- Prodott (ukoll parti mill- EPAR).
How has Doribax been studied?
Kif ġie studjat Doribax?
The effects of Doribax were first tested in experimental models before being studied in humans.
L- effetti ta ’ Doribax għall- ewwel ġew ittestjati fuq mudelli sperimentali qabel ma ġew studjati fuq il - bniedem.
Doribax has been studied in five main studies that compared Doribax with other antibiotics: • two studies compared Doribax with piperacillin/ tazobactam or imipenem in a total of 979 patients with nosocomial pneumonia; • two studies compared Doribax with meropenem in a total of 962 patients with complicated infections in the abdomen; • one study compared Doribax with levofloxacin in 753 patients with complicated urinary tract infections.
Doribax ġie studjat f’ ħames studji ewlenin li qabblu Doribax ma ’ antibijotiċi oħrajn: • żewġ studji qabblu Doribax ma ’ piperacillin/ tazobactam jew ma ’ imipenem f’ total ta ’ 979 pazjent bi pnewmonja nażokomjali; • żewġ studji qabblu Doribax ma ’ meropenem f’ total ta ’ 962 pazjent b’ infezzjonijiet ikkumplikati fl- addome; • studju wieħed qabbel Doribax ma ’ levofloxacin f’ 753 pazjent b’ infezzjonijiet ikkumplikati tal - passaġġi awrinarji.
In all of the studies, the main measure of effectiveness was the number of patients whose infection was cured after treatment.
Fl- istudji kollha, il- miżura ewlenija ta ’ l- effikaċja kienet in- numru ta ’ pazjenti li fiequ mill- infezzjoni wara l- kura.
What benefit has Doribax shown during the studies?
Liema benefiċċju wera Doribax waqt l- istudji mwettqa?
Doribax was as effective as the other antibiotics in treating the infections: • looking at the results of the two studies in nosocomial pneumonia taken together, 75% of the patients receiving Doribax were cured (195 out of 260), compared with 72% of the patients taking piperacillin/ tazobactam or imipenem (174 out of 241); • looking at the results of the two studies of complicated abdominal infections taken together, 85% of the patients receiving Doribax were cured (275 out of 325), compared with 84% of the patients receiving meropenem (260 out of 309); • in complicated urinary tract infections, 82% of the patients receiving Doribax were cured (230 out of 280), compared with 83% of the patients receiving levofloxacin (221 out of 265).
Doribax kien effettiv daqs l- antibijotiċi l- oħrajn fil- kura ta ’ l- infezzjonijiet: • meta wieħed iħares lejn ir- riżultati taż- żewġ studji fi pnewmonja nażokomjali meħudin flimkien, fiequ 75% tal- pazjenti li kienu qegħdin jirċievu Doribax (195 minn 260), meta mqabbla ma ’ 72% ta ’ pazjenti li kienu qegħdin jieħdu piperacillin/ tazobactam jew imipenem (174 minn 241); • meta wieħed iħares lejn ir- riżultati taż- żewġ studji ta ’ infezzjonijiet addominali kkumplikati meħudin flimkien, fiequ 85% tal- pazjenti li kienu qegħdin jirċievu Doribax (275 minn 325), meta mqabbla ma ’ 84% tal- pazjenti li kienu qegħdin jirċievu meropenem (260 minn 309); • f’ infezzjonijiet tal- passaġġi awrinarji, fiequ 82% tal- pazjenti li kienu qegħdin jirċievu Doribax (230 minn 280), meta mqabbla ma ’ 83% tal- pazjenti li kienu qegħdin jirċievu levofloxacin (221 minn 265).
What is the risk associated with Doribax?
X’ inhu r- riskju assoċjat ma ’ Doribax?
The most common side effect with Doribax (seen in more than 1 patient in 10) is headache.
L- iktar effett sekondarju komuni b’ Doribax (li deher f' iktar minn pazjent 1 minn kull 10) huwa uġigħ ta ’ ras.
For the full list of all side effects reported with Doribax, see the Package Leaflet.
Għal- lista sħiħa ta ’ effetti sekondarji kollha rrappurtata b’ Doribax, ara l- Fuljett ta ’ Tagħrif.
Doribax should not be used in people who may be hypersensitive (allergic) to doripenem or to other carbapenems.
Doribax m’ għandux jintuża f’ nies li huma ipersensittivi (allerġiċi) għal doripenem jew għal xi carbapenems.
It must not be used in patients who are severely allergic to other ‘ beta-lactam’ antibiotics, such as penicillins or cephalosporins.
Huwa m’ għandux jintuża f’ pazjenti li huma severament allerġiċi għal antibijotiċi ‘ beta - lactam ’ oħrajn, bħalma huma peniċillini u kefalosporini.
Why has Doribax been approved?
Għaliex ġie approvat Doribax?
The Committee for Medicinal Products for Human Use (CHMP) decided that Doribax’ s benefits are greater than its risks for the treatment of nosocomial pneumonia, complicated intra-abdominal infections and complicated urinary tract infections in adults.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) iddeċieda li l- benefiċċji ta ’ Doribax huma ikbar mir- riskji tiegħu għall- kura ta ’ pnewmonja nożokomjali, infezzjonijiet intra - addominali kkumplikati u infezzjonijiet tal- passaġġi awrinarji kkumplikati fl- adulti.
The Committee recommended that Doribax be given marketing authorisation.
Il- Kumitat irrakkomanda li Doribax jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Other information about Doribax:
Informazzjoni oħra dwar Doribax:
The European Commission granted a marketing authorisation valid throughout the European Union for Doribax to Janssen-Cilag International NV on 25 July 2008.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fuq is- suq madwar l- Unjoni Ewropea, għal Doribax lil Janssen- Cilag International NV fl- 25 ta ’ Lulju 2008.
The full EPAR for Doribax can be found here.
L- EPAR sħiħ għal Doribax jista ’ jinstab hawn.
This summary was last updated in 06-2008.
Dan is- sommarju ġie aġġornat l- aħħar fi 06- 2008.
Route of EU number
Numru ta ’ Proċedura ta ’ l- EU
Powder for solution for infusion
Trab għal soluzzjoni għall - infużjoni
Intravenous use
Użu għal ġol- vina
Vial (glass)
Kunjett ta ’ 10ml
Doribax 500 mg powder for solution for infusion
Doribax 500 mg trab għal soluzzjoni għall- infużjoni
Each vial contains doripenem monohydrate equivalent to 500 mg doripenem.
Kull kunjett fih doripenem monohydrate ekwivalenti għal 500 mg doripenem
The medicinal product does not contain any excipients.
Il- prodott mediċinali ma fih l- ebda sustanzi mhux attivi.
Powder for solution for infusion (Powder for infusion)
(Trab għal infużjoni)
A white to slightly yellowish off-white crystalline powder
Trab kristallin abjad sa abjad jagħti ftit fl- isfar
Doribax is indicated for the treatment of the following infections in adults (see sections 4.4 and 5.1):
Doribax huwa indikat għall- kura ta ’ l- infezzjonijiet li ġejjin fl- adulti (ara sezzjonijiet 4. 4 u 5. 1):
• Nosocomial pneumonia (including ventilator– associated pneumonia) • Complicated intra-abdominal infections • Complicated urinary tract infections
• Pulmonite li tittieħed minn ġo sptar (inkluż pulmonite assoċjata ma ’ apparat li jagħti r - respirazzjoni artifiċjali) • Infezzjonijiet intra- addominali kkumplikati • Infezzjonijiet ikkumplikati fl- apparat ta ’ l- awrina
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Għandha tingħata konsiderazzjoni lill- gwida uffiċjali dwar l- użu xieraq ta ’ sustanzi antibatteriċi.
The recommended dosage and administration by infection is shown in the following table:
Id- dożaġġ irrakkomandat u l- amministrazzjoni skond l- infezzjoni huma murija fit- tabella hawn taħt:
Nosocomial pneumonia including ventilator– associated pneumonia
Infezzjoni Pulmonite li tittieħed minn ġo sptar, inkluż pulmonite assoċjata ma ’ apparat li jagħti r - respirazzjoni artifiċjali
500 mg
Dożaġġ 500 mg
every 8 hours
Frekwenza kull 8 sigħat
1 or 4 hours*
Ħin ta ’ l- infużjoni Siegħa jew 4 sigħat *
Complicated intra-abdominal infection Complicated UTI, including pyelonephritis
Infezzjonijiet UTI ikkumplikati, inkluż pajelonefrite
every 8 hours every 8 hours
kull 8 sigħat
1 hour 1 hour
siegħa
*Based mainly on PK/ PD considerations, a 4-hour infusion time may be more suitable for infection with less susceptible pathogens (see section 5.1).
* Ibbażat l- aktar fuq kunsiderazzjonijiet PK/ PD, infużjoni li tieħu 4 sigħat tista ’ tkun aktar xierqa għall - infezzjoni b’ patoġeni anqas suxxettibbli (ara sezzjoni 5. 1).
This dosing regimen should also be considered in particularly severe infections.
Din is- sistema ta ’ dożaġġ għandha tiġi kkunsidrata f’ infezzjonijiet partikolarment severi.
For infusion solution shelf life see section 6.3.
Għaż- żmien kemm iddum tajba s- soluzzjoni għall- infużjoni ara sezzjoni 6. 3.
The usual treatment duration of doripenem therapy is 5-14 days and should be guided by the severity, site of the infection and the patient’ s clinical response.
It- tul ta ’ kura b’ terapija ta ’ doripenem is- soltu jdum bejn 5- 14- il ġurnata u għandu jkun iggwidat mill - qawwa u s- sit ta ’ l- infezzjoni u r- rispons kliniku tal- pazjent.
Doripenem was given for up to 14 days in clinical studies and the safety of longer durations of therapy has not been established.
Wara li tinbeda kura
After commencing treatment with intravenous doripenem, a switch to appropriate oral therapy to complete the treatment course is possible once clinical improvement has been establised.
2 b’ doripenem fil- vina, bidla għal kura xierqa mill- ħalq biex jitkompla l- kors ta ’ kura huwa possibbli ladarba jkun stabbilit titjib kliniku.
Dosage in paediatric patients Doribax is not recommended for use in children below 18 years of age due to a lack of safety and efficacy data.
Dożaġġ f’ pazjenti pedjatriċi Doribax m’ huwiex rakkomandat għall- użu fi tfal taħt it- 18- il sena minħabba nuqqas ta ’ dejta dwar sigurtà u effikaċja.
2 Dosage in patients with impaired renal function In patients with mild renal impairment (i. e. creatinine clearance (CrCl) is 51-79 ml/ min), no dosage adjustment is necessary.
Dożaġġ f’ pazjenti b’ indeboliment fil- funzjoni tal- kliewi F’ pazjenti b’ indeboliment ħafif tal- kliewi (jiġifieri t- tneħhija tal- kreatinina (CrCl) hija minn 51- 79 ml/ min), l- ebda aġġustament tad- doża ma huwa meħtieġ.
In patients with moderate renal impairment (CrCl 30 to < 50 ml/ min), the dosage of Doribax should be 250 mg every 8 hours.
F’ pazjenti b’ indeboliment tal- kliewi moderat (CrCl 30 sa < 50 ml/ min), id- doża ta ’ Doribax għandha tkun ta ’ 250 mg kull 8 sigħat.
In patients with severe renal impairment (CrCl < 30 ml/ min), the dosage of Doribax should be 250 mg every 12 hours.
F’ pazjenti b’ indeboliment tal- kliewi qawwi (CrCl < 30 ml/ min), id- dożaġġ ta ’ Doribax għandu jkun ta ’ 250 mg kull 12- il siegħa.
Due to limited clinical data and an expected increased exposure of doripenem and its metabolite, Doribax should be used with caution in patients with severe renal impairment (see section 5.2).
Minħabba dejta klinika limitata u żieda mistennija fl- esponiment għal doripenem u l- metabolit tiegħu, Doribax għandu jintuża b’ attenzjoni f’ pazjenti b’ indeboliment qawwi tal- kliewi (ara sezzjoni 5. 2).
Dosage in patients on dialysis Doribax is haemodialyzable; however, there is insufficient information to make dose adjustment recommendations in patients on dialysis.
Dożaġġ f’ pazjenti fuq id- dijaliżi Doribax jitneħħa bid- dijaliżi tad- demm; madankollu m’ hemmx informazzjoni biżżejjed biex isiru rakkomandazzjonijiet dwar aġġustament tad- doża f’ pazjenti li qegħdin fuq id- dijaliżi tad- demm.
Therefore, Doribax is not recommended for patients on any type of dialysis (see section 5.2).
Għalhekk, Doribax m’ huwiex rakkomandat għall- pażjenti li qegħdin fuq kwalunkwe tip ta ’ dijaliżi (ara sezzjoni 5. 2).
Dosage in elderly patients (≥ 65 years of age) No dosage adjustment is necessary in elderly patients, except in cases of moderate to severe renal insufficiency (see Dosage in patients with impaired renal function above and section 5.2).
Dożaġġ f’ pazjenti anzjani (età ta ’ 65 sena jew aktar) L- ebda aġġustament tad- doża ma huwa meħtieġ f’ pazjenti anzjani, minbarra f’ każijiet ta ’ insuffiċjenza moderata jew qawwija tal- kliewi (ara Dożaġġ f’ pazjenti b’ indeboliment fil- funzjoni tal - kliewi hawn fuq u sezzjoni 5. 2).
Dosage in patients with impaired hepatic function No dosage adjustment is necessary.
Dożaġġ f’ pazjenti b’ indeboliment fil- funzjoni tal- fwied L- ebda aġġustament tad- doża ma huwa meħtieġ.
Method for administration Doribax is to be reconstituted and then further diluted (see section 6.6) prior to administration by intravenous infusion over a period of one or four hours.
Metodu ta ’ kif jingħata Doribax għandu jiġi rikostitwit imbagħad iddilwit aktar (ara sezzjoni 6. 6) qabel ma ’ jingħata permezz ta ’ infużjoni ġol- vina fuq perjodu ta ’ siegħa jew erba ’ sigħat.
Hypersensitivity to the active substance Hypersensitivity to any other carbapenem antibacterial agent Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of beta-lactam antibacterial agent (e.g. penicillins or cephalosporins).
Sensittività eċċessiva għas- sustanza attiva Sensittività eċċessiva għal kwalunkwe sustanza antibatterjali carbapenem oħra Sensittività eċċessiva qawwija (eż. reazzjoni anafilattika, reazzjoni qawwija fil- ġilda) għal kull tip ieħor ta ’ sustanza antibatterjali beta- lactam (eż. penicillins jew cephalosporins).
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have occurred in patients receiving beta-lactam antibiotics.
Reazzjonijiet ta ’ sensittività eċċessiva (anafilattiċi) serji u xi kultant fatali ġraw f’ pazjenti li kienu qed jirċievu antibijotiċi beta- lactam.
Before therapy with Doribax is started, careful inquiry should be made concerning a previous history of hypersensitivity reactions to other active substances in this class or to beta-lactam antibiotics.
Qabel ma tinbeda kura b’ Doribax, għandu jsir studju bir- reqqa dwar storja fil- passat ta ’ reazzjonijiet ta ’ sensittività eċċessiva għal sustanzi attivi oħra f’ din il- klassi jew għal antibijotiċi beta- lactam.
Doribax should be used with caution in patients with such a history.
Doribax għandu jintuża b’ attenzjoni f’ pazjenti bi storja bħal din.
Should a hypersensitivity reaction to Doribax occur, it should be discontinued immediately and appropriate measures taken.
Kieku kellha sseħħ reazzjoni ta ’ sensittività eċċessiva għal Doribax, dan għandu jitwaqqaf minnufiħ u għandhom jittieħdu l- miżuri xierqa.
Serious acute hypersensitivity (anaphylactic) reactions require immediate emergency treatment.
Reazzjonijiet ta ’ sensittività eċċessiva serji u akuti (anafilattiċi) jinħtieġu kura ta ’ emerġenza immedjata.
Seizures have infrequently been reported during treatment with other carbapenems.
Aċċessjonijiet ġew irrappurtati b’ mod mhux frekwenti waqt kura b’ carbapenems oħra.
Pseudomembranous colitis due to Clostridium difficile has been reported with Doribax as with nearly all anti-bacterial agents and may range in severity from mild to life-threatening.
Kolite psewdomembranuża minħabba Clostridium difficile kienet irrappurtata b’ Doribax bħall- kważi għal kull sustanza oħra antibatterika u l- qawwa tagħha tista ’ tkun minn dik ħafifa sa waħda ta ’ periklu
Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of Doribax (see section 4.8).
Għalhekk, huwa importanti li tkun ikkunsidrata din id- dijanjosi f’ pazjenti li jkollhom dijarea waqt jew wara l- amministrazzjoni ta ’ Doribax (ara sezzjoni 4. 8).
Administration of doripenem, like other antibiotics, has been associated with emergence and selection of strains with reduced susceptibility.
L- amministrazzjoni ta ’ doripenem, bħal b' antibijotiċi oħra, ġiet assoċjata ma ’ tfaċċar u għażla ta ’ razez b’ suxxettibiltà imnaqqsa.
Patients should be carefully monitored during therapy.
Il- pazjenti għandhom jiġu mmonitorjati b’ attenzjoni waqt il- kura.
If superinfection occurs, appropriate measures should be taken.
Jekk isseħħ superinfezzjoni, għandhom jittieħdu miżuri xierqa.
Prolonged use of Doribax should be avoided.
L- użu fit- tul ta ’ Doribax għandu jiġi evitat.
When Doribax was used investigationally via inhalation, pneumonitis occurred.
Meta Doribax kien użat b’ mod investigattiv permezz ta ’ teħid man- nifs, seħħet pulmonite.
Therefore, Doribax should not be administered by this route.
Għalhekk, Doribax m’ għandux jingħata permezz ta ’ din ir- rotta.
3 Description of the patient population treated in clinical studies In two clinical trials of patients with nosocomial pneumonia (N=979), 60% of the clinically-evaluable Doribax-treated patients had ventilator-associated pneumonia (VAP).
Deskrizzjoni tal- popolazzjoni tal- pazjenti kkurati fi studji kliniċi F’ żewġ provi kliniċi fuq pazjenti b’ pulmonite li tittieħed minn ġo sptar (N=979), 60% tal- pazjenti li seta ’ jkollhom evalwazzjoni klinika, ikkurati b’ Doribax, kellhom pulmonite assoċjata ma ’ l- apparat li jagħti r- respirazzjoni artifiċjali (VAP).
Of these, 50% had late-onset VAP (defined as that occurring after five days of mechanical ventilation), 54% had an APACHE (Acute Physiology And Chronic Health Evaluation) II score > 15 and 32% received concomitant aminoglycosides (76% for more than 3 days).
Minn dawn 50% kellhom VAP li seħħet tard (definita bħala dik li tiġri wara ħamest ijiem fuq apparat li jagħti respirazzjoni artifiċjali), 54% kellhom punteġġ APACHE (Evalwazzjoni ta ’ Fiżjoloġija Akuta U Saħħa Kronika) II ta ’ > 15 u 32% flimkien mal- kura rċievew aminoglycosides (76% għal- aktar minn 3 ijiem).
In two clinical trials of patients with complicated intra-abdominal infections (N=962) the most common anatomical site of infection in microbiologically-evaluable Doribax-treated patients was the appendix (62%).
F’ żewġ provi kliniċi fuq pazjenti b’ infezzjonijiet intra- addominali kkumplikati (N=962) l- aktar sit anatomiku komuni ta ’ infezzjoni f’ pazjenti kkurati b’ Doribax li seta ’ jkollhom evalwazzjoni mikrobijoloġika kien l- appendiċi (62%).
Of these, 51% had generalised peritonitis at baseline.
Minn dawn, 51% kellhom peritonite mifruxa fil- linja bażi.
Other sources of infection included colon perforation (20%), complicated cholecystitis (5%) and infections at other sites (14%).
Sorsi oħra ta ’ infezzjoni kienu jinkludu titqib tal- musrana l- ħoxna (20%), koleċistite kkumplikata (5%) u infezzjonijiet f’ siti oħra (14%).
Eleven percent had an APACHE II score of > 10, 9.5% had post-operative infections, 27% had single or multiple intra-abdominal abscesses and 4% had concurrent bacteraemia at baseline.
Ħdax fil- mija kellhom punteġġ APACHE II ta ’ > 10, 9. 5% kellhom infezzjonijiet wara operazzjoni, 27% kellhom axxess intra- addominali wieħed jew aktar u 4% fl- istess ħin kellhom batterimja fil- linja bażi.
In two clinical trials of patients with complicated urinary tract infections (N=1179), 52% of microbiologically-evaluable Doribax-treated patients had complicated lower urinary tract infections and 48% had pyelonephritis, of which 16% were complicated.
F’ żewġ provi kliniċi fuq pazjenti b’ infezzjonijiet kkumplikati fl- apparat ta ’ l- awrina (N=1179), 52% ta ’ pazjenti kkurati b’ Doribax li seta ’ jkollhom evalwazzjoni mikrobijoloġika kellhom infezzjonijiet ikkumplikati fil- parti t’ isfel ta ’ l- apparat ta ’ l- awrina u 48% kellhom pajelonefrite li minnhom 16% kienu ikkumplikati.
Overall, 54% of patients had a persistent complication, 9% had concurrent bacteraemia and 23% were infected with a levofloxacin resistant uropathogen at baseline.
Fuq kollox 54% tal- pazjenti kellhom kumplikazzjoni persistenti, 9% fl- istess ħin kellhom batterijmja u 23% kienu infettati b’ patoġenu ta ’ l- awrina reżistenti għal levofloxacin fil- linja bażi.
The experience in patients who are severely immunocompromised, receiving immunosuppressive therapy, and patients with severe neutropenia is limited since this population was excluded from phase 3 trials.
L- esperjenza f’ pazjenti li huma immunokompromessi ħafna, qed jirċievu kura immunosoppressiva, u pazjenti b’ newtropenja qawwija hija limitata minħabba li din il- popolazzjoni ġiet eskluża mill- provi tal- fażi 3.
Doripenem undergoes little to no Cytochrome P450 (CYP450) mediated metabolism.
Doripenem jgħaddi minn ftit li xejn jew ma jgħaddi mill- ebda metaboliżmu medjat miċ- Ċitokroma P450 (CYP450).
Based on in vitro studies it is not expected that doripenem will inhibit or induce the activities of CYP450.
Fuq bażi ta ’ studji in vitro m’ huwiex mistenni li doripenem jimpedixxi jew jinduċi l - attivitajiet ta ’ CYP450.
Therefore, no CYP450-related drug interactions are to be expected (see section 5.2).
Għalhekk, ma huma mistennija l- ebda interazzjonijiet ma mediċini relatati ma ’ CYP450 (ara sezzjoni 5. 2).
Carbapenem antibacterial agents may reduce serum valproic acid concentrations.
Sustanzi antibatteriċi carbapenem jistgħu jnaqqsu l- konċentrazzjonijiet ta ’ valproic acid fis- serum.
Serum concentrations of valproic acid should be monitored if Doribax is administered concomitantly with valproic acid.
Konċentrazzjonijiet ta ’ valproic acid fis- serum għandhom jkunu osservati mill- qrib jekk Doribax jingħata flimkien ma ’ valproic acid.
Probenecid competes with doripenem for renal tubular secretion and reduces the renal clearance of doripenem.
Probenecid jikkompeti ma ’ doripenem għas- sekrezzjoni tubulari tal- kliewi u jnaqqas it- tneħħija ta ’ doripenem mill- kliewi.
In an interaction study, the mean doripenem AUC increased by 75% following co-administration with probenecid.
Fi studju ta ’ interazzjoni, il- medja AUC ta ’ doripenem żdiedet b’ 75% wara amministrazzjoni flimkien ma ’ probenecid.
Therefore, co-administration of probenecid with Doribax is not recommended.
Għalhekk, l- amministrazzjoni ta ’ probenecid flimkien ma ’ Doribax m’ hijiex rakkommandata.
An interaction with other drugs eliminated by renal tubular secretion cannot be excluded.
Ma jistax jiġi eskluż li mediċini oħra li jiġu mneħħija permezz ta ’ sekrezzjoni tubulari tal- kliewi ma jaqblux ma dan il- prodott mediċinali.
4.6 Pregnancy and lactation
4 4. 6 Tqala u Treddigħ
For doripenem, limited clinical data on exposed pregnancies are available.
Għal doripenem, huwa disponibbli tagħrif kliniku limitat dwar tqaliet esposti.
Animal studies are insufficient with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).
Studji fuq l- annimali m’ humiex biżejjed rigward l- effetti fuq it- tqala, l- iżvilupp ta ’ l- embriju/ l- fetu, il- ħlas jew l- iżvilupp wara t- twelid (ara sezzjoni 5. 3).
The potential risk for humans is unknown.
Ir- riskju li jista ’ jkun hemm għan- nies m’ hux magħruf.
Doribax should not be used during pregnancy unless clearly necessary.
Doribax m’ għandux jintuża waqt it- tqala jekk m’ hemmx bżonn ċar.
It is unknown whether doripenem is excreted in human breast milk.
M’ huwiex magħruf jekk doripenem jitneħħiex mal- ħalib uman.
A study in rats has shown that doripenem and its metabolite are transferred to milk.
Studju fil- firien wera li doripenem u l - metabolit tiegħu jiġu trasferiti fil- ħalib.
A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Doribax should be made taking into account the benefit of breast-feeding to the child and the benefit of Doribax therapy to the woman.
Deċiżjoni dwar jekk jitkompla/ ma jitkompliex it- treddigħ jew titkompliex/ ma titkompliex kura b’ Doribax għandha tittieħed wara li jiġi kkunsidrat il- benefiċcju tat - treddigħ għat- tarbija u l- benefiċċju tal- kura b’ Doribax għall- mara.
No studies on the effects of Doribax on the ability to drive and use machines have been performed.
Ma saru l- ebda studji dwar l- effetti ta ’ Doribax fuq il- ħila biex issuq u tħaddem magni.
Based on reported adverse drug reactions, it is not anticipated that Doribax will affect the ability to drive and use machines.
Fuq bażi tar - reazzjonijiet avversi għall- mediċina rrappurtati, m’ huwiex antiċipat li Doribax jaffettwa l- ħila biex issuq u tħaddem magni.
4 4.8 Undesirable effects
4. 8 Effetti mhux mixtieqa
In 3,142 adult patients (1817 of which received Doribax) evaluated for safety in phase 2 and phase 3 clinical trials, adverse reactions due to Doribax 500 mg every 8 hours occurred at rate of 32%.
F’ 3142 pazjenti adulti (li minnhom 1817 rċievew Doribax) li kienu evalwati għas- sigurtà fi provi kliniċi fil- fażi 2 u l- fażi 3, reazzjonijiet avversi minħabba Doribax 500 mg kull 8 sigħat seħħew b’ rata ta ’ 32%.
Doribax was discontinued because of adverse drug reactions in 0.1% of patients overall.
Doribax twaqqaf minħabba f’ reazzjonijiet avversi tal- mediċina f’ 0. 1% tat- total tal- pazjenti.
Adverse drug reactions that led to Doribax discontinuation were nausea (0.1%), diarrhoea (0.1%), pruritus (0.1%), vulvomycotic infection (0.1%), hepatic enzyme increased (0.2%) and rash (0.2%).
Reazzjonijiet avversi tal- mediċina li wasslu biex ma titkompliex il- kura b’ Doribax kienu tqalligħ (0. 1%), dijarea (0. 1%), ħakk (0. 1%), infezzjoni bil- moffa fil- vulva (0. 1%), żieda fl- enzimi tal- fwied (0. 2%) u raxx (0. 2%).
The most common adverse reactions were headache (10%), diarrhoea (9%) and nausea (8%).
L- aktar reazzjonijiet avversi komuni kienu uġigħ ta ’ ras (10%), dijarea (9%) u tqalligħ (8%).
Adverse drug reactions due to Doribax 500 mg are listed below by frequency category.
Reazzjonijiet avversi għall- mediċina minħabba Doribax 500 mg huma elenkati hawn taħt skond il - kategorija ta ’ frekwenza.
Frequency categories are defined as follows:
Il- kategoriji ta ’ frekwenza huma definiti kif ġej:
Very common (≥ 1/10); Common (≥1/100 to < 1/10); Uncommon (≥1/1,000 to < 1/100).
Komuni ħafna (≥ 1/ 10); Komuni (≥ 1/ 100 sa < 1/ 10); Mhux komuni (≥ 1/ 1, 000 sa < 1/ 100).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull grupp ta ’ frekwenza, l- effetti mhux mixtieqa huma ppreżentati skond is- serjetà dejjem tonqos tagħhom.
Adverse Drug Reactions Identified During Clinical Trials with Doribax Infections and infestation Immune system disorders Nervous system disorders Vascular disorders Gastrointestinal disorders
Reazzjonijiet Avversi għall- Mediċina Identifikati Waqt Provi Kliniċi b’ Doribax Infezzjonijiet u infestazzjonjiet Disturbi fis- sistema immuni
Common: oral candidiasis, vulvomycotic infection Uncommon: hypersensitivity reactions (see section 4.4) Very common: headache Common: phlebitis Common: nausea, diarrhoea Uncommon:
Komuni: kandidjażi orali, infezzjoni bil- moffa fil- vulva Mhux komuni: reazzjonijiet ta ’ sensittiività eċċessiva (ara sezzjoni 4. 4)
C. difficile colitis (see section 4.4)
Kolite permezz ta ’ C. difficile (ara sezzjoni 4. 4)
Hepato-biliary disorders Skin and subcutaneous tissue disorders
Disturbi fil- fwied u fil- marrara Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Common: hepatic enzyme increased Common: pruritus, rash
Komuni: żieda fl- enzimi tal- fwied Komuni: ħakk, raxx
Adverse Drug Reactions Identified During Post-marketing Experience with Doribax Blood and the lymphatic system disorders
Reazzjonijiet Avversi għall- Mediċina Suq b’ Doribax
Frequency not known: neutropenia
Disturbi tad- demm u tas- sistema limfatika
Frequency not known: anaphylaxis (see section 4.4)
Il- frekwenza m’ hijiex magħrufa: anafilassi (ara sezzjoni 4. 4)
4.9 Overdose
5 4. 9 Doża eċċessiva
In the event of overdose, Doribax should be discontinued and general supportive treatment given until renal elimination takes place.
F’ każ ta ’ doża eċċessiva, Doribax għandu jitwaqqaf u kura ġenerali ta ’ sapport għandha tingħata sakemm ikun hemm eliminazzjoni mill- kliewi.
Doribax can be removed by haemodialysis (see section 5.2); however, no information is available on the use of haemodialysis to treat overdose.
Doribax jista ’ jitneħħa permezz ta ’ dijaliżi tad- demm (ara sezzjoni 5. 2); madankollu, l- ebda informazzjoni ma hija disponibbli dwar l- użu tad- dijaliżi tad- demm biex tikkura doża eċċessiva.
Carbapenems, ATC code:
Antibijotiku carbapenems, Kodiċi ATC:
Mode of action Doripenem is a synthetic carbapenem antibacterial agent.
Kif jaħdem Doripenem huwa sustanza anti- batterika carbapenem sintetika.
Doripenem exerts its bactericidal activity by inhibiting bacterial cell wall biosynthesis.
Doripenem jagħmel użu mill- attività batteriċidjali tiegħu billi jimpedixxi l- biosinteżi tal- ħajt taċ - ċellula tal- batterju.
Doripenem inactivates multiple essential penicillin-binding proteins (PBPs) resulting in inhibition of cell wall synthesis with subsequent cell death.
Doripenem iwaqqaf proteini multipli essenzjali li jintrabtu mal- penicillin (PBP) milli jaħdmu li jirriżulta fl- impedimet tas- sinteżi tal- ħajt taċ- ċellula u sussegwentement il- mewt taċ - ċellula.
In vitro doripenem showed little potential to antagonize or be antagonized by other antibacterial agents.
In vitro doripenem wera li ftit li xejn għandu potenzjal li jantagonizza jew jiġi antagonizzat minn sustanzi antibatteriċii oħra.
Additive activity or weak synergy with amikacin and levofloxacin has been seen for Pseudomonas aeruginosa and for gram-positive bacteria with daptomycin, linezolid, levofloxacin, and vancomycin.
Attività addittiva jew sinerġija dgħajfa b’ amikacin u levofloxacin intweriet għal Pseudomonas aeruginosa u għal batterji gram- pożittivi b’ daptomycin, linezolid, levofloxacin, u vancomycin.
5 Pharmacokinetic/pharmacodynamic relationship Similar to other beta-lactam antimicrobial agents, the time that the plasma concentration of doripenem exceeds the MIC (%T > MIC) of the infecting organism has been shown to best correlate with efficacy in pre-clinical pharmacokinetic/pharmacodynamic (PK/PD) studies.
Relazzjoni farmakokinetika/ farmakodinamika Bħal sustanzi oħra beta- lactam kontra l- mikrobi, il- ħin li l- konċentrazzjoni ta ’ doripenem fil- plażma taqbeż l- MIC (% T > MIC) ta ’ l- organiżmu infettiv intweriet li taqbel l- aktar ma ’ l- effikaċja ta ’ qabel l - istudji farmakokinetiċi u farmakodinamiċi (PK/ PD) kliniċi.
Monte Carlo simulations using pathogen susceptibility results from completed phase 3 trials and population PK data indicated that the %T > MIC target of 35% was achieved in greater than 90% of patients with nosocomial pneumonia, complicated urinary tract infections and complicated intra-abdominal infections, for all degrees of renal function.
Simulazzjonijiet Monte Carlo bl- użu ta’ riżultati minn patoġeni suxxettibbli minn provi tal- fażi 3 kompluti u data PK tal- poplazzjoni indikaw li l- mira% T > MIC ta ’ 35% inkisbet f’ aktar minn 90% tal- pazjenti b' pulmonite li tittieħed minn ġo sptar, infezzjonijiet ikkumplikati intra- addominali u infezzjonijiet ikkumplikati fl- apparat ta ’ l- awrina, għal kull grad ta ’ funzjoni tal- kliewi.
Extending the infusion time of Doribax to 4 hours maximizes the %T > MIC for a given dose and is the basis for the option to administer 4-hour infusions in patients with nosocomial pneumonia including ventilator-associated pneumonia.
L- estensjoni tal- ħin ta ’ l- infużjoni ta ’ Doribax għal- 4 sigħat tkabbar il -% T > MIC għad- doża partikolari u hija l- bażi għall- għażla biex jiġu amministrati infużjonijiet fuq 4 sigħat lill- pazjenti b' pulmonite li tittieħed minn ġo sptar inkluż pulmonite assoċjata ma ’ l- apparat li jagħti r- respirazzjoni artifiċjali.
In seriously ill patients or those with an impaired immune response, a 4-hour infusion time may be more suitable when the MIC of doripenem for the known or suspected pathogen(s) has been shown or is expected to be > 0.5 mg/l, in order to reach a target attainment of 50% T > MIC in at least 95% of the patients (see section 4.2).
F’ pazjenti morda serjament jew dawk b’ indeboliment fir- rispons immuni, ħin ta ’ infużjoni ta ’ 4 sigħat jista ’ jkun aktar xieraq meta l- MIC ta ’ doripenem għal patoġenu( i) magħruf( a) jew issuspettat( i) intweriet jew hija mistennija li tkun > 0. 5 mg/ l, sabiex tintlaħaq il- mira ta ’ kisba ta ’ 50% T > MIC f’ mill- anqas 95% tal- pazjenti (ara sezzjoni 4. 2).
Monte Carlo simulations supported the use of 500 mg 4-hour infusions every 8 hours in subjects with normal renal function for target pathogens with doripenem MICs ≤ 4 mg/l.
Simulazzjonijiet Monte Carlo appoġġjaw l- użu ta ’ infużjonijiet ta ’ 500 mg fuq 4 sigħat kull 8 sigħat f’ individwi b’ funzjoni normali tal- kliewi għall - patoġeni fil- mira b’ MICs ≤ 4 mg/ l ta ’ doripenem.
Mechanisms of resistance Bacterial resistance mechanisms that effect doripenem include active substance inactivation by carbapenem-hydrolyzing enzymes, mutant or acquired PBP’s, decreased outer membrane permeability and active efflux.
Mekkaniżmi ta ’ reżistenza Mekkaniżmi ta ’ reżistenza tal- batterji li jaffettwaw doripenem jinkludu l- inattivazzjoni tas- sustanza attiva permezz ta ’ enzimi li jidrolizzaw il- carbapenem, PBP’ s mutant jew akkwiżiti, tnaqqis fil - permeabbiltà tal- membrana ta ’ barra u effluss attiv.
Doripenem is stable to hydrolysis by most beta-lactamases, including penicillinases and cephalosporinases produced by gram-positive and gram-negative bacteria, with the exception of relatively rare carbapenem hydrolyzing beta-lactamases.
Doripenem huwa stabbli għal idrolisi mill - maġġoranza ta ’ beta- lactamases, inkluż penicillinases u cephalosporinases li jipproduċuhom batterji gram- pożittivi u gram- negattivi, bl- eċċezzjoni tal- beta- lactamases relattivament rari li jidrolizzaw il - carbapenems.
Species resistant to other carbapenems do generally express co-resistance to doripenem.
Speċji reżistenti għal carbapenems oħrajn ġeneralment jesprimu ko- reżistenza għal doripenem.
Methicillin-resistant staphylococci should always be considered as resistant to doripenem.
Staphylococci reżistenti għal methicillin għandhom dejjem jiġu kkunsidrati bħala reżistenti għal doripenem.
As with other antimicrobial agents, including carbapenems, doripenem has been shown to select for resistant bacterial strains.
Bħal sustanzi oħrajn kontra l- batterji, inkluż carbapenems, doripenem intwera li juri preferenza għal razez ta ’ batterji reżistenti.
Breakpoints Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows:
6 Breakpoints Breakpoints fil- konċentrazzjoni impeditorja minima (MIC) stabbiliti mill- Kumitat Ewropew dwar Ittestjar ta ’ Suxxettibilità Kontra l- Mikrobi (EUCAST) huma kif ġej:
Enterobacteriaceae Acinetobacter spp.
Mhux relatat ma ’ l- ispeċi Staphylococci Enterobacteriaceae Acinetobacter spp.
Streptococcus spp. other than S. pneumoniae S. pneumoniae Enterococci Haemophilus spp.
Streptococcus spp. ħlief S. pneumoniae S. pneumoniae Enterococci Haemophilus spp.
S ≤1 mg/l and R > 4 mg/l S ≤1 mg/l and R > 4 mg/l S ≤1 mg/l and R > 4 mg/l S ≤1 mg/l and R > 1 mg/l S ≤ 1 mg/l and R > 1 mg/l “inappropriate target” S ≤ 1 mg/l and R > 1 mg/l IE (insufficient evidence) S ≤1 mg/l and R > 1 mg/l
S ≤ 1 mg/ l u R > 4 mg/ l inferita mill- breakpoint ta ’ methicillin S ≤ 1 mg/ l u R > 4 mg/ l S ≤ 1 mg/ l u R > 4 mg/ l ≤ 1 mg/ l u R > 4 mg/ l S ≤ 1 mg/ l u R > 1 mg/ l S ≤ 1 mg/ l u R > 1 mg/ l “ mira mhix xierqa ” S ≤ 1 mg/ l u R > 1 mg/ l IE (evidenza insuffiċjenti) S ≤ 1 mg/ l u R > 1 mg/ l
Susceptibility
Suxxettibiltà
local information on resistance is desirable, particularly when treating severe infections.
Il- prevalenza ta ’ reżistenza miksuba tista ’ tvarja ġeografikament u biż- żmien fi speċi magħżula, u informazzjoni lokali fuq ir- rezistenza hija mixtieqa, b’ mod partikolari meta jkunu qegħdin jiġu kkurati infezzjonijiet serji.
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.
Għandu jiġi mfittex parir ta ’ espert, skond il- ħtieġa, meta l- prevalenza lokali ta ’ reżistenza hija tali li l- użu tas- sustanza f’ ta ’ l- anqas ċerti tipi ta ’ infezzjonijiet hija dubjuża.
Localized clusters of infections due to carbapenem-resistant organisms have been reported in the European Union.
Ġemgħat lokalizzati ta ’ infezzjonijiet permezz ta ’ organiżmi reżistenti għall- carbapenems ġew irrappurtati fl- Unjoni Ewropea.
The information below gives only approximate guidance on the probability as to whether the micro-organism will be susceptible to doripenem or not.
L- informazzjoni li ġejja tagħti biss indikazzjoni approssimattiva tal - probabbiltà ta ’ jekk il- mikro- organiżmu hux se jkun suxxettibbli għal doripenem jew le.
6 Commonly Susceptible Species:
Speċi Komunement Suxxettibbli:
Gram Positive Aerobes Enterococcus faecalis*$ Staphylococcus aureus (methicillin susceptible strains only)*^ Staphylococcus spp.
Aerobi Gram Pożittivi Enterococcus faecalis* $Staphylococcus aureus (razez suxxettibbli għal methicillin biss) * ^ Staphylococcus spp.
(methicillin susceptible strains only)^ Streptococcus pneumoniae* Streptococcus spp.
(razez suxxettibbli għal methicillin biss) ^ Streptococcus pneumoniae * Streptococcus spp.
Gram Negative Aerobes Citrobacter diversus Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae* Haemophilus influenzae* Escherichia coli Klebsiella pneumoniae* Klebsiella oxytoca Morganella morganii Proteus mirabilis* Proteus vulgaris Providencia rettgeri Providencia stuartii Salmonella species Serratia marcescens Shigella species
Aerobi Gram Negattivi Citrobacter diversus Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae * Haemophilus influenzae * Escherichia coli Klebsiella pneumoniae * Klebsiella oxytoca Morganella morganii Proteus mirabilis * Proteus vulgaris Providencia rettgeri Providencia stuartii
Anaerobes Bacteroides fragilis* Bacteroides caccae* Bacteroides ovatus Bacteroides uniformis* Bacteroides thetaiotaomicron* Bacteroides vulgatus* Bilophila wadsworthia Peptostreptococcus magnus Peptostreptococcus micros* Porphyromonas spp.
7 Anaerobi Bacteroides fragilis * Bacteroides caccae * Bacteroides ovatus Bacteroides uniformis * Bacteroides thetaiotaomicron * Bacteroides vulgatus * Bilophila wadsworthia Peptostreptococcus magnus Peptostreptococcus micros * Porphyromonas spp.
Species for which acquired resistance may be a problem:
Speċi li għalihom reżistenza akkwiżita tista ’ tkun problema:
Inherently resistant organisms:
Organiżmi reżistenti b’ mod inerenti:
Gram Positive Aerobes Enterococcus faecium Gram Negative Aerobes Stenotrophomonas maltophilia Legionella spp. * species against which activity has been demonstrated in clinical studies $species that show natural intermediate susceptibility + species with > 50% acquired resistance in one or more Member State ^all methicillin-resistant staphylococci should be regarded as resistant to doripenem
Aerobi Gram Pożittivi Enterococcus faecium Aerobi Gram Negattivi Stenotrophomonas maltophila Legionella spp. * speċi li intweriet attività kontrihom fil- provi kliniċi $speċi li juru suxxettibilità intermedja naturali + speċi b ’ > 50% reżistenza akkwiżita f’ wieħed mill- Istati Membri jew aktar ^l- istaphylococci kollha li huma reżistenti għall- methicillin għandhom jiġu meqjusa bħala reżistenti għal- doripenem
7 5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku
The mean Cmax and AUC0-∞ of doripenem in healthy subjects across studies following administration of 500 mg over 1 hour are approximately 23 µg/ml and 36 µg.h/ml, respectively.
Il- medja tas- Cmax u l - AUC0- ∞ ta ’ doripenem f’ individwi f’ saħħithom fi studji wara l- amministrazzjoni ta ’ 500 mg fuq perjodu ta ’ siegħa huma bejn wieħed u ieħor 23 µg/ ml u 36 µg. h/ ml, rispettivament.
The mean Cmax and AUC0-∞ of doripenem in healthy subjects across studies following administration of 500 mg and 1 g over 4 hours are approximately 8 µg/ml and 17 µg/ml, and 34 µg.h/ml and 68 µg.h/ml, respectively.
Il - medja tas- Cmax u l - AUC0- ∞ ta ’ doripenem f’ individwi f’ saħħithom fi studji wara l- amministrazzjoni ta ’ 500 mg u gramma fuq perjodu ta ’ erba ’ sigħat huma bejn wieħed u ieħor 8 µg/ ml u 17 µg/ ml, u 34 µg. h/ ml u 68 µg. h/ ml, rispettivament.
There is no accumulation of doripenem following multiple intravenous infusions of either 500 mg or 1 g administered every 8 hours for 7 to 10 days in patients with normal renal function.
M’ hemmx akkumulazzjoni ta ’ doripenem wara infużjonijiet multipli kemm ta ’ 500 mg kif ukoll ta ’ gramma doripenem mogħtija kull 8 sigħat għal bejn 7 u 10 ijiem f’ pazjenti b’ funzjoni tal- kliewi normali.
Distribution The average binding of doripenem to plasma proteins was approximately 8.1% and is independent of plasma concentrations.
Distribuzzjoni Il- medja ta ’ l- irbit ta ’ doripenem mal- proteini tal- plasma kienet bejn wieħed u ieħor 8. 1% u hija indipendenti mill- konċentrazzjonijiet fil- plażma.
The volume of distribution at steady state is approximately 16.8 L, similar to extracellular fluid volume in man.
Il- volum ta ’ distribuzzjoni fl- istat fiss huwa bejn wieħed u ieħor 16. 8 L, li jixbaħ lill- volum ta ’ fluwidu ekstraċellulari fil- bniedem.
Doripenem penetrates well into several body fluids and tissues, such as uterine tissue, retroperitoneal fluid, prostatic tissue, gallbladder tissue and urine.
Doripenem jippenetra tajjeb f’ diversi fluwidi u tessuti tal- ġisem, bħat- tessut ta ’ l- utru, il- fluwidu ta ’ wara l - peritonew, it- tessut tal- prostata, it- tessut tal- marrara u l- awrina.
Metabolism Metabolism of doripenem to a microbiologically inactive ring-opened metabolite occurs primarily via dehydropeptidase-I.
Metaboliżmu Il- metaboliżmu ta ’ doripenem f’ metabolit ċirku miftuħ li huwa mikrobijoloġikament inattiv iseħħ primarjament permezz ta ’ dehydropeptidase- I.
In vitro studies have determined that doripenem does not inhibit or induce the activities of CYP isoforms 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 or 3A4.
Studji in vitro ddeterminaw li doripenem ma jimpedixxix jew jinduċi l- attivitajiet ta ’ l- isoforms CYP 1A2, 2A6, 2C9, 2C19, 2D6, 2E1jew 3A4.
Elimination Doripenem is primarily eliminated unchanged by the kidneys.
8 Eliminazzjoni Doripenem huwa primarjament eliminat mhux mibdul permezz tal- kliewi.
Mean plasma terminal elimination half- life of doripenem in healthy young adults is approximately 1-hour and plasma clearance is approximately 15.9 l/hour.
Il- medja tal- half- life ta ’ l - eliminazzjoni terminali ta ’ doripenem fil- plażma f’ adulti żgħażagħ f’ saħħithom hija bejn wieħed u ieħor ta ’ siegħa u t- tneħħija mill- plażma hija ta ’ bejn wieħed u ieħor 15. 9 l/ siegħa.
Mean renal clearance is 10.3 l/hour.
It- tneħħija medja mill- kliewi hija ta ’ 10. 3 l/ siegħa.
The magnitude of this value, coupled with the significant decrease in the elimination of doripenem seen with concomitant probenecid administration, suggests that doripenem undergoes glomerular filtration, tubular secretion and re- absorption.
Il- kobor ta ’ dan il- valur, flimkien ma ’ tnaqqis sinifikanti fl - eliminazzjoni ta ’ doripenem li tidher meta jingħata flimkien ma ’ probenecid, jissuġġerixxi li doripenem ikollu kemm filtrazzjoni glomerulari, sekrezzjoni tubulari kif ukoll rijassorbiment.