qanastek/EMEA-V3 huggingface dataset:
Predictive Value of Week 12 Virological Response at the Recommended Dosing Regimen while on Pegasys Combination Therapy Genotype
Valur Preditt għar- rispons Viroloġiku tat- 12- il Ġimgħa fil- Kors ta ’ Dożaġġ Rakkomandat waqt Terapija Kombinata ta ’ Pegasys
No
Ġenotip
Negative
Ebda
Positive
Negattiva Ebda
response
Figura
No
Rispons sat -
Response
Pożittiva Rispons
by
Figura
week 12
rispons sat -
sustained response
rispons
Predictive by week Value 12
mbassra
Sustained response
mbassra
Predictive Value
ġimgħa miksub 12- il ġimgħa
Genotype 1 (N= 569)
Ġenotip 1
Genotype 2 and 3
Ġenotip 2 u 3
The negative predictive value for sustained response in patients treated with Pegasys in monotherapy was 98%.
Il- valur preditt negattiv għal rispons sostenut f’ pazjenti kurati b’ monoterapija ta ’ Pegasys kien ta ’ 98%.
A similar negative predictive value has been observed in HIV-HCV co-infected patients treated with Pegasys monotherapy or in combination with ribavirin (100% (130/ 130) or 98% (83/ 85), respectively).
Figura mbassra negattiva simili kienet osservata f’ pazjenti b’ infezzjoni fl- istess waqt ta ’ HIV- HCV kkurati b’ monoterapija ta ’ Pegasys jew f’ taħlita ma ’ ribavirin (100% (130/ 130) jew 98% (83/ 85), rispettivament).
Positive predictive values of 45% (50/ 110) and 70% (59/ 84) were observed for genotype 1 and genotype 2/ 3 HIV-HCV co-infected patients receiving combination therapy.
Figuri mbassra pożittvi ta ’ 45% (50/ 110) u 70% (59/ 84) kienu osservati f’ pazjenti li kienu ko- infettati b’ HIV- HCV ta ’ ġenotip 1 u ġenotip 2/ 3 li kienu qed jirċievu terapija kombinata.
Predictability of response and non-response – treatment-experienced patients In non-responder patients re-treated for 48 or 72 weeks, viral suppression at week 12 (undetectable HCV RNA defined as < 50 IU/ mL) has been shown to be predictive for sustained virological response.
Tbassir ta ’ rispons u ta ’ nuqqas ta ’ rispons – pazjenti b’ esperjenza ta ’ kura F’ pazjenti li ma rrispondewx li kienu kkurati mill- ġdid għal 48 jew 72 ġimgħa, sopressjoni tal- virus fit - 12- il ġimgħa (HCV RNA li ma jistax jiġi osservat definit bħala < 50 IU/ mL) intweriet li hija tbassir għall- rispons viroloġiku sostenut.
The probabilities of not achieving a sustained virological response with 48 or 72 weeks of treatment if viral suppression was not achieved at week 12 were 96% (363 of 380) and 96% (324 of 339), respectively.
Il- probabbiltajiet li ma jintlaħaqx rispons viroloġiku sostenut b’ 48 jew 72 ġimgħa ta ’ kura jekk sopressjoni virali ma nlaħqitx fit- 12- il ġimgħa kienu 96% (363 minn 380) u 96% (324 minn 339), rispettivament.
The probabilities of achieving a sustained virological response with 48 or 72 weeks of treatment if viral suppression was achieved at week 12 were 35% (20 of 57) and 57% (57 of 100), respectively.
Il- probabbiltajiet li jintlaħaq rispons viroloġiku sostenut b’ 48 jew 72 ġimgħa ta ’ kura jekk tkun intlaħqet sopressjoni virali fit- 12- il ġimgħa kienu 35% (20 minn 57) u 57% (57 minn 100), rispettivament.
Dose adjustment for adverse reactions
Tibdil fid- doża minħabba reazzjonijiet avversi
General Where dose adjustment is required for moderate to severe adverse reactions (clinical and/ or laboratory) initial dose reduction to 135 micrograms is generally adequate.
Ġenerali Meta jkun hemm bżonn ta ’ tibdil fid- doża minħabba reazzjonijiet avversi moderati jew severi (kliniċi u/ jew fil- laboratorju) tnaqqis inizjali għal doża ta ’ 135 mikrogrammi ġeneralment hija adegwata.
However, in some cases, dose reduction to 90 micrograms or 45 micrograms is necessary.
Iżda, f’ xi każijiet, tnaqqis fid- doża għal 90 mikrogrammi jew 45 mikrogrammi huwa neċessarju.
Dose increases to or towards the original dose may be considered when the adverse reaction abates (see sections 4.4 and 4.8).
Żidiet fid - doża lejn jew għal dik oriġinali jistgħu jiġu konsidrati meta r- reazzjoni avversa tonqos (ara sezzjonijiet 4. 4 u 4. 8).
Haematological (see also Table 3) Dose reduction is recommended if the neutrophil count is < 750/ mm3.
Ematoloġiċi (ara wkoll Tabella 3) Tnaqqis fid- doża huwa rakkomandat jekk in- numru ta ’ newtrofili huwa < 750/ mm3.
For patients with Absolute Neutrophil Count (ANC )< 500/mm3 treatment should be suspended until ANC values return to > 1000/mm3.
Il- kura għandha titwaqqaf f’ pazjenti li għandhom Numru Assolut ta ’ Newtrofili (ANC) < 500/ mm3 sakemm il- valuri ta 'ANC jerġgħu jitilgħu għal > 1000/ mm3.
Therapy should initially be re-instituted at 90 micrograms Pegasys and the neutrophil count monitored.
Meta t- terapija terġa ’ tibda, għandha tingħata doża ta ’ 90 mikrogrammi ta ’ Pegasys u l- livelli ta ’ newtrofili għandhom jiġu sorveljati.
Dose reduction to 90 micrograms is recommended if the platelet count is < 50,000/ mm3.
Huwa rakkomandat li d- doża titnaqqas għal 90 mikrogramma jekk in- numru ta ’ plejtlits huwa < 50, 000/ mm3.
Cessation of therapy is recommended when platelet count decreases to levels < 25,000/ mm3.
Twaqqif tat- terapija huwa rakkomandat jekk in- numru ta ’ plejtlits jonqos għal < 25, 000/ mm3.
Specific recommendations for management of treatment-emergent anaemia are as follows: ribavirin should be reduced to 600 milligrams/ day (200 milligrams in the morning and 400 milligrams in the evening) if either of the following apply:
Dawn li jmiss huma rakkomandazzjonijiet speċifiċi għall- immaniġġar ta ’ anemija li tiżviluppa waqt il - kura: ribavirin għandu jitnaqqas għal 600 milligramma/ ġurnata (200 milligramma filgħodu u 400 milligramma filgħaxija) jekk xi waħda minn dawn li jmiss tapplika:
(1) a patient without significant cardiovascular disease experiences a fall in haemoglobin to < 10 g/ dl and ≥ 8.5 g/ dl, or (2) a patient with stable cardiovascular disease experiences a fall in haemoglobin by ≥ 2 g/ dl during any 4 weeks of treatment.
(1) pazjent mingħajr ebda mard kardjovaskulari sinifikanti li jkollu tnaqqis fil- livell ta ’ emoglobina għal < 10 g/ dl u ≥ 8. 5 g/ dl, jew (2) pazjent b’ mard kardjovaskulari stabbli li jkollu tnaqqis fil- livell ta ’ emoglobina b ’ ≥ 2 g/ dl waqt kwalunkwe 4 ġimgħat tal- kura.
A return to original dosing is not recommended.
Mhux rakkomandat li jerġa ’ jingħata mill- ġdid id- dożaġġ oriġinali.
Ribavirin should be discontinued if either of the following apply:
Ribavirin għandu jitwaqqaf jekk waħda minn dawn li jmiss tapplika:
(1) A patient without significant cardiovascular disease experiences a fall in haemoglobin confirmed to < 8.5 g/ dl; (2) A patient with stable cardiovascular disease maintains a haemoglobin value < 12 g/ dl despite 4 weeks on a reduced dose.
(1) pazjent mingħajr ebda mard kardjovaskulari sinifikanti li jkollu tnaqqis fil- livell ta ’ emoglobina konfermat għal < 8. 5 g/ dl; (2) pazjent b’ mard kardjovaskulari stabbli li jżomm livell ta ’ emoglobina ta ’ < 12 g/ dl avolja jkun għamel 4 ġimgħat fuq doża imnaqqsa.
If the abnormality is reversed, ribavirin may be restarted at 600 milligrams daily, and further increased to 800 milligrams daily at the discretion of the treating physician.
5 600 milligramma kuljum, u tiġi miżjuda għal 800 milligramma kuljum skond id- diskrezzjoni tat- tabib responsabbli.
Dose Adjustment for Adverse Reaction (For further guidance see also text above)
Tibdil fid- Doża għal Reazzjonijiet Avversi (Għal aktar tagħrif aqra il- kitba ta ’ hawn fuq)
Reduce
Naqqas
Withhold Reduce Withhold
Waqqaf Naqqas Waqqaf
Discontinue
Waqqaf it -
Ribavirin Ribavirin to 600 mg
Ribavirin għal Ribavirin 600 mg
Pegasys Pegasys 135/ 90/ 45
Pegasys għal 135/ 90/ 45 mikrogrammi
micrograms Absolute Neutrophil Count
Numru Assolut ta ’ Newtrofili
Platelet Count
Numru ta ’
< 50,000/mm3 > 25,000/ mm
< 50, 000/ mm3
< 25,000/ mm3
< 25, 000/ mm3
Haemoglobin - no cardiac disease
> 25, 000/ mm
< ≥
Emoglobina - ebda marda kardijaka Emoglobina
10 g/ dl, and < 8.5 g/ dl 8.5 g/ dl
< 10 g/ dl, and < 8. 5 g/ dl ≥ 8. 5 g/ dl < 12 g/ dl Tnaqqis ≥ 2
decrease < 12 g/ dl
avolja kkurat g/ dl waqt
stable cardiac disease
- marda
despite 4 weeks at reduced dose
għal 4 ġimgħat kwalunkwe 4 kardijaka b’ doża ġimgħat stabbli imnaqqsa
In case of intolerance to ribavirin, Pegasys monotherapy should be continued.
F’ każ ta ’ intolleranza għal ribavirin, monoterapija b’ Pegasys għandha titkompla.
Liver function Fluctuations in abnormalities of liver function tests are common in patients with chronic hepatitis C.
Funzjoni tal- fwied Varjazzjonijiet fl- anormalitajiet tat- testijiet tal- funzjoni tal- fwied huma komuni f’ pazjenti li għandhom l- epatite Ċ kronika.
As with other alpha interferons, increases in ALT levels above baseline (BL) have been observed in patients treated with Pegasys, including patients with a virological response.
Bħal fl- użu ta ’ alfa interferons oħra, żidiet fil- livelli ta ’ l- ALT ’ l fuq mill- linja bażi (BL) dehru f’ pazjenti kurati b' Pegasys, inklużi pazjenti b’ rispons viroloġiku.
In chronic hepatitis C clinical trials, isolated increases in ALT (≥ 10x ULN, or ≥ 2x BL for patients with a BL ALT ≥ 10x ULN) which resolved without dose-modification were observed in 8 of 451 patients treated with combination therapy.
Fi provi kliniċi b’ epatite Ċ kronika, żidiet iżolati fl- ALT (≥ 10x ULN, jew ≥ 2x BL għall- pazjenti li għandhom BL ALT ≥ 10x ULN) li waqfu mingħajr ebda tibdil fid- doża dehru fi 8 minn 451 pazjent ikkurati b’ terapija kombinata.
If ALT increase is progressive or persistent, the dose should be reduced initially to 135 micrograms.
Jekk iż- żieda fl- ALT hija waħda progressiva jew persitenti, id- doża għandha titnaqqas inizjalment għal 135 mikrogrammi.
When increase in ALT levels is progressive despite dose reduction, or is accompanied by increased bilirubin or evidence of hepatic decompensation, therapy should be discontinued (see section 4.4).
(ara sezzjoni 4. 4).
For chronic hepatitis B patients, transient flares of ALT levels sometimes exceeding 10 times the upper limit of normal are not uncommon, and may reflect immune clearance.
Għall- pazjenti b’ epatite B kronika, żiediet għoljin temporanji fil- livelli ta ’ ALT li xi drabi jaqbżu b’ 10 darbiet l- ogħla limitu tan- normal m’ humiex rari u jistgħu jirriflettu t- tneħħija mis- sistema immuni.
Treatment should normally not be initiated if ALT is > 10 times the upper limit of normal.
Il - kura normalment m’ għandiex tinbeda jekk l- ALT huwa > 10 darbiet l- ogħla limitu tan- normal.
Consideration should be given to continuing treatment with more frequent monitoring of liver function during ALT flares.
Għandha tingħata konsiderazzjoni għat- tkomplija tal- kura b’ sorveljanza aktar frekwenti tal- funzjoni tal- fwied waqt iż- żiediet ta ’ ALT.
If the Pegasys dose is reduced or withheld, therapy can be restored once the flare is subsiding (see section 4.4).
Jekk id- doża ta ’ Pegasys titnaqqas jew titwaqqaf, it- terapija tista ’ terġa ’ titkompla la darba iż- żieda fil- livelli ta ’ ALT tibda tbatti (see sezzjoni 4. 4).
Elderly Adjustments in the recommended dosage of 180 micrograms once weekly are not necessary when instituting Pegasys therapy in elderly patients (see section 5.2).
Anzjani M' hemmx bżonn ta ’ tibdil fid- doża rakkomandata ta ’ 180 mikrogrammi fil- ġimgħa meta tibda tingħata terapija b' Pegasys f’ pazjenti anzjani (ara sezzjoni 5. 2).
Patients under the age of 18 years The safety and efficacy of Pegasys have not been established in this population.
Pazjenti b’ età taħt it- 18- il sena Is- sigurtà u l- effikaċja ta 'Pegasys f’ din il- popolazzjoni ma ġietx stabilita.
Pegasys is contraindicated in neonates and young children up to 3 years old, because of the excipient benzyl alcohol (see sections 4.3 and 4.4).
Pegasys huwa kontra- indikat fi trabi tat- twelied u tfal żgħar sa età ta ’ 3 snin, minħabba s- sustanza mhux attiva benzyl alcohol (ara sezzjonijiet 4. 3 u 4. 4).
Patients with renal impairment In patients with end stage renal disease, a starting dose of 135 micrograms should be used (see section 5.2).
6 Pazjenti b’ indeboliment tal- kliewi F’ pazjenti b’ marda tal - kliewi ta ’ l- aħħar stadju, għandha tintuża doża inizjali ta ’ 135 mikrogrammi (ara sezzjoni 5. 2).
Regardless of the starting dose or degree of renal impairment, patients should be monitored and appropriate dose reductions of Pegasys during the course of therapy should be made in the event of adverse reactions.
Irrispettivament mid- doża inizjali jew mill- livell ta ’ indeboliment tal- kliewi, il- pazjenti għandhom jiġu monitorjati u għandu jkun hemm tnaqqis xieraq fid- doża ta ’ Pegasys matul it- terapija f’ każ ta ’ reazzjonijiet avversi.
6 Patients with hepatic impairment In patients with compensated cirrhosis (eg, Child-Pugh A), Pegasys has been shown to be effective and safe.
Pazjenti b’ indebboliment tal- fwied F’ pazjenti b’ ċirrożi kompensata (eż, Child- Pugh A), Pegasys deher li huwa effettiv u mingħajr periklu.
Pegasys has not been evaluated in patients with decompensated cirrhosis (eg, Child-Pugh B or C or bleeding oesophageal varices) (see section 4.3).
Pegasys ma ġiex evalwat f’ pazjenti b’ ċirrożi dekompensata (eż, Child- Pugh B jew Ċ jew variċi ta ’ l - esofagu li jinfasdu (ara sezzjoni 4. 3).
The Child-Pugh classification divides patients into groups A, B, and C, or "Mild", "Moderate" and "Severe" corresponding to scores of 5-6, 7-9 and 10-15, respectively.
Il- klassifikazzjoni Child- Pugh taqsam il- pazjenti fi gruppi A, B, u Ċ, jew “ Ħafif ”, “ Moderat ” u “ Sever ” li jikkorrispondu għall- punteġġ ta ’ 5- 6, 7- 9 u 10- 15, rispettivament.
Modified Assessment Assessment Encephalopathy
Stima Modifikata Stima Enċefalopatija
Degree of abnormality None Grade 1-2 Grade 3-4*
Grad ta ’ anormalità Ebda Grad 1- 2 Grad 3- 4 *
Score 1 2 3
Punti 1 2 3
S-Bilirubin (mg/ dl)
Axxite Bilirubina- S (mg/ dl)
< 2 2.0- 3> 3
Assenti Ftit Moderat < 2 2. 0- 3 > 3
SI unit = μ mol/ l)
Kejl SI = μmol/ l
S-Albumin (g/ dl)
< 34 2 34- 51 3 > 51 Albumina- S (g/ dl)
> 3.5 3.5-2.8 < 2.8
> 3. 5 3. 5- 2. 8 < 2. 8
< 1.7 1.7- 2.3> 2.3
< 1. 7 1. 7- 2. 3 > 2. 3
*Grading according to Trey, Burns and Saunders (1966)
* Klassifikazzjoni skond Trey, Burns u Saunders (1966)
• Hypersensitivity to the active substance, to alpha interferons, or to any of the excipients • Autoimmune hepatitis • Severe hepatic dysfunction or decompensated cirrhosis of the liver • Neonates and young children up to 3 years old, because of the excipient benzyl alcohol (see section 4.4 for benzyl alcohol) • A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months (see section 4.4) • Initiation of Pegasys is contraindicated in HIV-HCV patients with cirrhosis and a Child-Pugh score ≥ 6
• Sensittività eċċessiva għas- sustanza attiva, għall- alfa interferons, jew għal xi sustanzi mhux attivi. • Epatite awto- immunitarja • Disfunzjoni epatika severa jew ċirrożi dekompensata tal- fwied • Trabi u tfal żgħar taħt it- 3 snin, minħabba s- sustanża mhux attiva benzyl alcohol (ara sezzjoni 4. 4 għal benzyl alcohol) • Passat ta ’ mard sever tal- qalb eżistenti minn qabel, inkluż mard tal- qalb mhux stabbli jew mhux ikkontrollat fis- sitt xhur ta ’ qabel (ara sezzjoni 4. 4) • Bidu ta ’ Pegasys huwa kontra- indikat f’ pazjenti b’ HIV- HCV li għandhom ċirrożi u punteġġ Child- Pugh ta ’ ≥ 6.
For contraindications to ribavirin, please refer also to the ribavirin Summary of Product Characteristics (SPC) when Pegasys is to be used in combination with ribavirin.
Għall- kontra- indikazzjonijiet ta ’ ribavirin, jekk jogħġbok ara ukoll is- Sommarju tal- Karatteristiċi tal - Prodott (SPC) ta ’ ribavirin meta Pegasys jkun ser jintuża flimkien ma ’ ribavirin.
4.4 Special warnings and precautions for use
7 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
Psychiatric and Central Nervous System (CNS):
Sistema Nervuża Ċentrali (CNS) u Psikjatrika:
Severe CNS effects, particularly depression, suicidal ideation and attempted suicide have been observed in some patients during Pegasys therapy, and even after treatment discontinuation mainly during the 6-month follow-up period.
Effetti severi fuq is- CNS, speċjalment depressjoni, ħsibijiet ta ’ suwiċidju u attentat ta ’ suwiċidju kienu osservati f’ xi pazjenti waqt kura b’ Pegasys, u anki wara l- waqfien tal- kura prinċipalment waqt il- perijodu tas- 6 xhur ta ’ wara.
Other CNS effects including aggressive behaviour (sometimes directed against others), confusion and alterations of mental status have been observed with alpha interferons.
Effetti oħra tas- CNS inklużi mġieba aggressiva (xi kultant lejn oħrajn), konfużjoni u tibdil fl- istat mentali kienu osservati b ’ alpha interferons.
Patients should be closely monitored for any signs or symptoms of psychiatric disorders.
Il- pazjenti għandhom jiġu sorveljati mill- viċin għal xi sinjali u sintomi ta ’ disturbi psikjatriċi.
If psychiatric symptoms persist or worsen, or
Jekk sintomi bħal dawn jitfaċċaw, is- serjetà potenzjali ta ’ dawn l- effetti mhux mixtieqa trid tittieħed f’ konsiderazzjoni mit- tabib li qed jippreskrivi u għandu jiġi kkunsidrat l- bżonn ta ’ mmaniġġjar terapewtiku xieraq.
7 suicidal ideation is identified, it is recommended that treatment with Pegasys be discontinued, and the patient followed, with psychiatric intervention as appropriate.
Jekk is- sintomi psikjatriċi jippersistu jew imorru għal agħar, jew jiġi identifikat ħsieb ta ’ suwiċidju, huwa rakkomandat li l- kura b’ Pegasys titwaqqaf, u l- pazjent jiġi segwit b’ intervent psikjatriku kif jixraq.
Patients with existence of, or history of severe psychiatric conditions:
Pazjenti b’ kondizzjonijiet psikjatriċi severi eżistenti jew fil- passat:
If treatment with Pegasys is judged necessary in patients with existence or history of severe psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and therapeutic management of the psychiatric condition.
Jekk kura b’ Pegasys hija meqjusa neċessarja f’ pazjenti b’ kondizzjonijiet psikjatriċi severi eżistenti jew fil- passat, din għandha tinbeda biss wara li jiġi żgurat immaniġġjar dijanjostiku u terapewtiku individwalizzat xieraq għall - kondizzjoni psikjatrika.
Please refer also to the ribavirin Summary of Product Characteristics (SPC) when Pegasys is to be used in combination with ribavirin.
Jekk jogħġbok ara ukoll is- Sommarju tal- Karatteristiċi tal- Prodott (SPC) ta ’ ribavirin meta Pegasys jkun ser jintuża flimkien ma ’ ribavirin.
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (ie, patients with genotype 2 or 3), treatment may be possible without histological confirmation.
Il- pazjenti kollha fl- istudji ta ’ l- epatite Ċ kronika saritilhom bijopsija tal- fwied qabel ma bdew it - terapija, iżda f’ xi każi (jiġifieri, pazjenti bil- ġenotip 2 jew 3), il- kura hija possibli mingħajr konferma istoloġika.
Current treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing treatment.
Il- linji gwida kurrenti fuq jekk hemmx bżonn ta ’ bijopsija tal- fwied qabel ma tinbeda l- kura għandhom jiġu kkonsultati.
In patients with normal ALT, progression of fibrosis occurs on average at a slower rate than in patients with elevated ALT.
F’ pazjenti b’ ALT normali, progressjoni tal- fibrożi ġeneralment isseħħ b’ rata aktar baxxa milli f’ pazjenti b’ ALT għoli.
This should be considered in conjunction with other factors, such as HCV genotype, age, extrahepatic manifestations, risk of transmission, etc. which influence the decision to treat or not.
Dan għandu jiġi kkunsidrat flimkien ma ’ fatturi oħra, bħall- ġenotip HCV, età, manifestazzjonijiet ekstra- epatiċi, riskju ta ’ trasmissjoni, eċċ. li jinfluwenzaw id- deċiżjoni jekk tingħatax il- kura jew le.
Benzyl alcohol.
Benzyl alcohol.
Pegasys is contraindicated in infants or young children up to 3 years old because of the excipient benzyl alcohol.
Pegasys huwa kontra- indikat fi trabi u tfal żgħar ta ’ età sa 3 snin minħabba s- sustanza mhux attiva benzyl alcohol.
Laboratory tests prior to and during therapy Prior to beginning Pegasys therapy, standard haematological and biochemical laboratory tests are recommended for all patients.
Testijiet tal- laboratorju ta ’ qabel u ta ’ waqt it- terapija Qabel ma tinbeda terapija b' Pegasys, huwa rakkomandat li jsiru testijiet ematoloġiċi stàndard u testijiet bijokimiċi tal- laboratorju fil- pazjenti kollha.
The following may be considered as baseline values for initiation of treatment:
Li jmiss jistgħu jiġu meqjusa bħala valuri normali biex tinbeda t- terapija:
- Platelet count ≥ 90,000/ mm3
Numru ta ’ plejtlits ≥ 90, 000/ mm3
- Absolute neutrophil counts ≥ 1500/ mm3
Numru Assolut ta ’ Newtrofili ≥ 1500/ mm3
- Adequately controlled thyroid function (TSH and T4)
- Funzjoni tat- tirojde kontrollata kif jixraq (TSH u T4)
Haematological tests should be repeated after 2 and 4 weeks and biochemical tests should be performed at 4 weeks.
It- testijiet tad- demm għandhom jiġu ripetuti wara ġimagħtejn u 4 ġimgħat u testijiet bijokimiċi għandhom isiru wara 4 ġimgħat.
Additional testing should be performed periodically during therapy.
Testijiet oħra għandhom isiru perjodikament matul it- terapija.
In clinical trials, Pegasys treatment was associated with decreases in both total white blood cell (WBC) count and absolute neutrophil count (ANC), usually starting within the first 2 weeks of treatment (see section 4.8).
Fil- provi kliniċi, kura b 'Pegasys kienet assoċjata ma ’ tnaqqis fin- numru totali kemm ta ’ ċelloli bojod tad- demm (WBC) kif ukoll fin- Numru Assolut ta ’ Newtrofili (ANC), li ssoltu jidhru fl- ewwel ġimgħatejn (2) tal- kura (ara sezzjoni 4. 8).
Progressive decreases after 8 weeks of therapy were infrequent.
F' każi rari ħafna, dan it- tnaqqis kompla wara 8 ġimgħat ta ’ terapija.
The decrease in ANC was reversible upon dose reduction or cessation of therapy (see section 4.2), reached normal values by 8 weeks in the majority of patients and returned to baseline in all patients after about 16 weeks.
It- tnaqqis fl- ANC kien riversibbli wara li tnaqqset id- doża jew twaqqfet it- terapija (ara sezzjoni 4. 2), laħaq valuri normali wara 8 ġimgħat fil- maġġoranza tal- pazjenti u rritorna għall- linja bażi fil - pazjenti kollha wara madwar 16- il ġimgħa.
Pegasys treatment has been associated with decreases in platelet count, which returned to pre- treatment levels during the post-treatment observation period (see section 4.8).
B’ kura b' Pegasys deher tnaqqis fin- numru ta 'plejtlits, li rritornaw għall- livelli ta ’ qabel il- kura fil - perijodu ta ’ osservazzjoni ta ’ wara l- kura (ara sezzjoni 4. 8).
In some cases, dose modification may be necessary (see section 4.2).
F’ xi każi, tibdil tad- doża jista ’ jkun neċessarju (ara sezzjoni 4. 2).
The occurrence of anaemia (haemoglobin < 10 g/ dl) has been observed in up to 15% of chronic hepatitis C patients in clinical trials on the combined treatment of Pegasys with ribavirin.
8 Il- preżenza ta ’ anemija (emoglobina < 10 g/ dl) deheret f’ mhux aktar minn 15% tal- pazjenti b’ epatite Ċ kronika fi provi kliniċi fuq il- kura kombinata ta ’ Pegasys ma ’ ribavirin.
The frequency depends on the treatment duration and the dose of ribavirin (see section 4.8,).
Il- frekwenza tiddependi fuq it - tul ta ’ kemm iddum il- kura u fuq id- doża ta ’ ribavirin (ara sezzjoni 4. 8).
The risk of developing anaemia is higher in the female population.
Ir- riskju ta ’ żvilupp ta ’ anemija huwa akbar fil- popolazzjoni femminilli.
As with other interferons, caution should be exercised when administering Pegasys in combination with other potentially myelosuppressive agents.
Kif isir waqt l- użu ta ’ interferons oħra, għandu jkun hemm attenzjoni meta Pegasys jingħata ma ’ sustanzi potenzjalment majelosoppressivi oħrajn.
The use of Pegasys and ribavirin combination therapy in chronic hepatitis C patients who failed prior treatment has not been adequately studied in patients who discontinued prior therapy for
L- użu ta ’ terapija kombinata ta ’ Pegasys u ribavirin f’ pazjenti b’ epatite Ċ kronika li fallew kura minn qabel ma ġietx studjata b’ mod adegwat f’ pazjenti li waqqfu l- kura ta ’ qabel minħabba avvenimenti avversi ematoloġiċi.
Physicians considering treatment in these patients should carefully weigh the risks versus the benefits of re-treatment.
Tobba li qed jikkunsidraw kura mill- ġdid f’ dawn il- pazjenti għandhom jiżnu r - riskji u l- benefiċċji b’ attenzjoni.
Endocrine system Thyroid function abnormalities or worsening of pre-existing thyroid disorders have been reported with the use of alpha interferons, including Pegasys.
Sistema endokrinarja Dehru anormalitajiet fil- funzjoni tat- tirojde jew tħażżin ta ’ mard tat- tirojde eżistenti minn qabel waqt l - użu ta ’ alpha interferons, inkluż Pegasys.
Prior to initiation of Pegasys therapy, TSH and T4 levels should be evaluated.
Qabel ma tinbeda terapija b' Pegasys, il- livelli ta ’ TSH u T4 għandhom jitkejlu.
Pegasys treatment may be initiated or continued if TSH levels can be maintained in the normal range by medication.
Kura b' Pegasys tista ’ tinbeda jew titkompla jekk il- livelli ta ’ TSH jistgħu jinżammu fil- valuri normali bil- mediċini.
TSH levels should be determined during the course of therapy if a patient develops clinical symptoms consistent with possible thyroid dysfunction (see section 4.8).
Il- livelli ta ’ TSH għandhom jitkejlu matul it- terapija jekk pazjent jiżviluppa sintomi kliniċi konsistenti ma ’ possibilità ta ’ disfunzjoni tat- tirojde (ara sezzjoni 4. 8).
As with other interferons, hypoglycaemia, hyperglycaemia and diabetes mellitus have been observed with Pegasys (see section 4.8).
Bħal b’ interferons oħra, ipogliċemija, ipergliċemija u dijabete mellitus kienu osservati b’ Pegasys (ara sezzjoni 4. 8).
Patients with these conditions who cannot be effectively controlled by medication should not begin Pegasys monotherapy nor Pegasys/ ribavirin combination therapy.
Pazjenti b’ dawn il- kondizzjonijiet li ma jistgħux jiġu kkontrollati b’ mod effettiv permezz ta ’ medikazzjoni, m’ għandhomx jibdew, la monoterapija b’ Pegasys u lanqas terapija kombinata b’ Pegasys/ ribavirin.
Patients who develop these conditions during treatment and cannot be controlled with medication should discontinue Pegasys or Pegasys/ ribavirin therapy.
Pazjenti li jiżviluppaw dawn il- kondizzjonijiet waqt il- kura u ma jistgħux jiġu kkontrollati b’ medikazzjoni għandom iwaqqfu l- kura b’ Pegasys jew b’ Pegasys/ ribavirin.
Cardiovascular system Hypertension, supraventricular arrhythmias, congestive heart failure, chest pain and myocardial infarction have been associated with alpha interferon therapies, including Pegasys.
Sistema kardjovaskulari Pressjoni għolja, arritmija supraventrikolari, insuffiċjenza tal- qalb konġestiva, uġigħ fis- sider u infart mijokardijaku kienu assoċjati ma ’ terapiji b’ alfa interferons, inkluż Pegasys.
It is recommended that patients who have pre-existing cardiac abnormalities have an electrocardiogram prior to initiation of Pegasys therapy.
Huwa rakkomandat li pazjenti li għandhom anormalitajiet kardijaċi eżistenti minn qabel għandhom jagħmlu elettrokardjogramma qabel ma tinbeda terapija b' Pegasys.
If there is any deterioration of cardiovascular status, therapy should be suspended or discontinued.
Jekk l- istat kardjovaskulari jmur għall- agħar, it- terapija għandha tiġi sospiża jew imwaqqfa.
In patients with cardiovascular disease, anaemia may necessitate dose reduction or discontinuation of ribavirin (see section 4.2).
F’ pazjenti b’ mard kardjovaskulari, l- anemija jista ’ jkollha bżonn tnaqqis fid- doża jew li jitwaqqaf ribavirin (ara sezzjoni 4. 2).
Liver function In patients who develop evidence of hepatic decompensation during treatment, Pegasys should be discontinued.
Funzjoni tal- fwied Pegasys għandu jitwaqqaf f’ pazjenti li jiżviluppaw sinjali ta ’ dekompensazzjoni epatika waqt il- kura.
As with other alpha interferons, increases in ALT levels above baseline have been observed in patients treated with Pegasys, including patients with a viral response.
Bħal fl- użu ta ’ alpha interferons oħra, żidiet fil- livelli ta ’ ALT ’ l fuq mill- linja bażi dehru f’ pazjenti kurati b' Pegasys, inklużi pazjenti b’ rispons virali.
When the increase in ALT levels is progressive and clinically significant, despite dose reduction, or is accompanied by increased direct bilirubin, therapy should be discontinued (see sections 4.2 and 4.8).
Meta ż- żieda fil- livelli ta ’ ALT tkompli u tkun klinikament sinifikanti, minkejja li titnaqqas id- doża, jew ikun hemm ukoll żieda diretta ta ’ bilirubina, it- terapija għandha titwaqqaf (ara sezzjonijiet 4. 2 u 4. 8).
In chronic hepatitis B, unlike chronic hepatitis C, disease exacerbations during therapy are not uncommon and are characterised by transient and potentially significant increases in serum ALT.
B’ differenza minn epatite Ċ kronika, f’ epatite B kronika, rkadar tal- marda waqt it- terapija mhux rari u huwa kkaratterizzat minn żiediet temporanji u potenzjalment sinifikanti fl- ALT fis- serum.
In clinical trials with Pegasys in HBV, marked transaminase flares have been accompanied by mild changes in other measures of hepatic function and without evidence of hepatic decompensation.
Fi provi kliniċi b’ Pegasys f’ HBV, żiediet konsiderevoli fit- transaminase kienu akkompanjati minn bidliet żgħar fir- riżultati l- oħra tal- funzjoni tal- fwied u mingħajr evidenza ta ’ dekompensazzjoni epatika.
In approximately half the case of flares exceeding 10 times the upper limit of normal, Pegasys dosing was reduced or withheld until the transaminase elevations subsided, while in the rest therapy was continued unchanged.
F’ madwar nofs il- każijiet ta ’ żiediet li kienu ogħla minn 10 darbiet l- għola livell tan- normal, id- dożaġġ ta ’ Pegasys kien imnaqqas jew imwaqqaf sakemm iż- żiediet fit- transaminase tbaxxew, filwaqt li l- bqija tat- terapija tkompliet mingħajr bidla.
More frequent monitoring of hepatic function was recommended in all instances.
Sorveljanza aktar frekwenti tal- funzjoni epatika kienet rakkomandata f’ kull każ.
Hypersensitivity Serious, acute hypersensitivity reaction (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis) have been rarely observed during alpha interferon therapy.
Sensittività eċċessiva Reazzjoni gravi ta ’ sensittività eċċessiva akuta (eż, urtikarja, anġjoedema, bronkokonstrizzjoni, anafilassi) kienu rarament osservati matul terapija b’ alpha interferons.
If this occurs, therapy must be discontinued and appropriate medical therapy instituted immediately.
Jekk dan iseħħ, it- terapija għandha titwaqqaf u tingħata kura medika xierqa immedjatament.
Transient rashes do not necessitate interruption of treatment.
M' hemmx bżonn li titwaqqaf it - terapija f’ każ ta ’ raxx temporanju.
Autoimmune disease The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha interferons.
9 Mard awtoimmuni L- iżvilupp ta ’ awto- antikorpi u ta ’ mard awtoimmuni deher waqt kura b’ alpha interferons.
Patients predisposed to the development of autoimmune disorders may be at increased risk.
Pazjenti li huma predisposti għall- iżvilupp ta ’ mard awtoimmuni jistgħu ikunu f’ riskju ogħla.
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and the benefit-risk of continued interferon therapy should be reassessed (see also Endocrine System in sections 4.4 and 4.8).
Pazjenti b’ sinjali jew b’ sintomi kompatibbli ma ’ mard awtoimmuni għandhom jiġu evalwati bir- reqqa, u r- riskju- benefiċju li titkompla t- terapija b’ interferon għandu jerġa ’ jiġi evalwat (ara wkoll Sistema Endokrinarja f’ sezzjonijiet 4. 4 u 4. 8).
Fever/ infections While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, other causes of persistent fever, particularly serious infections (bacterial, viral, fungal) must be ruled out, especially in patients with neutropenia.
Deni/ infezzjonijiet Waqt li deni jista ’ jkun assoċjat ma ’ sindromu li jixbaħ l- influenza li jidher ta ’ spiss waqt terapija b’ interferon, kawżi oħrajn ta ’ deni persistenti, partikolarment infezzjonijiet serji (ikkawżati minn batterja, virus, jew moffa) għandhom jiġu esklużi, speċjalment f’ pazjenti b’ newtropenja.
Serious infections (bacterial, viral, fungal) have been reported during treatment with alpha interferons including Pegasys.
Infezzjonijiet serji (ikkawżati minn batterja, virus, jew moffa) kienu rrapportati waqt kura b’ alpha interferons inkluż Pegasys.
Appropriate anti-infective therapy should be started immediately and discontinuation of therapy should be considered.
Terapija anti- infettiva xierqa għandha tinbeda minnufiħ u t- twaqqif tat- terapija għandu jiġi kkunsidrat.
9 Ocular changes As with other interferons retinopathy including retinal haemorrhages, cotton wool spots, papilloedema, optic neuropathy and retinal artery or vein obstruction which may result in loss of vision have been reported in rare instances with Pegasys.
Tibdil okulari Bħall- interferons oħra, retinopatija inkluż emorraġija tar- retina, cotton wool spots, papilloedima, newropatija ottika u sadd tal- vina jew arterja tar- retina li jistgħu jwasslu għal telf tal- vista dehru f’ każijiet rari b' Pegasys.
All patients should have a baseline eye examination.
Il- pazjenti kollha għandhom jagħmlu eżami bażiku ta ’ l- għajnejn.
Any patient complaining of decrease or loss of vision must have a prompt and complete eye examination.
Kull pazjent li jilmenta bi tnaqqis jew telf tal- vista għandu jagħmel eżaminazzjoni ta ’ l- għajnejn kompleta u fil- pront.
Patients with preexisting ophthalmologic disorders (eg, diabetic or hypertensive retinopathy) should receive periodic ophthalmologic exams during Pegasys therapy.
Pazjenti b’ mard oftalmiku eżistenti minn qabel (eż, dijabete jew retinopatija ipertensiva) għandhom jirċievu perjodikament visti oftalmoloġiċi waqt terapija b' Pegasys.
Pegasys treatment should be discontinued in patients who develop new or worsening ophthalmologic disorders.
Il- kura b' Pegasys għandha tieqaf f’ pazjenti li jiżviluppaw mard oftalmoloġiku ġdid jew jekk il- mard oftalmoloġiku jmur għall- agħar.
Pulmonary changes As with other alpha interferons, pulmonary symptoms, including dyspnoea, pulmonary infiltrates, pneumonia, and pneumonitis have been reported during therapy with Pegasys.
Tibdil pulmonari Bħall- alpha interferons oħrajn, sintomi pulmonari, li jinkludu qtugħ ta ’ nifs, infiltrati pulmonari, pnewmonja, u pulmonite dehru waqt terapija b' Pegasys.
In case of persistent or unexplained pulmonary infiltrates or pulmonary function impairment, treatment should be discontinued.
F’ każ ta ’ infiltrati pulmonari jew problemi fil - funzjoni pulmonari persistenti jew inspjegabbli, il- kura għandha titwaqqaf.
Pegasys must be used with caution in patients with psoriasis, and in cases of onset or worsening of psoriatic lesions, discontinuation of therapy should be considered.
Disturbi fil- ġilda L- użu ta ’ alpha interferons kien assoċċjat ma ’ tifrix jew kien il- kawża ta ’ psorjasi u sarkojdosi, u f’ każijiet ta ’ fejn ikun hemm bidu jew aggravar ta ’ feriti psorjatiċi, it- twaqqif tat- terapija għandu jiġi kkunsidrat.
Transplantation The safety and efficacy of Pegasys treatment have not been established in patients with liver transplantation.
Trapjant Is- sigurtà u l- effikaċja ta ’ kura b’ pegasys ma ġewx stabiliti f’ pazjenti li rċevew trapjant tal- fwied.
HIV-HCV coinfection Please refer to the respective Summary of Product Characteristics of the antiretroviral medicinal products that are to be taken concurrently with HCV therapy for awareness and management of toxicities specific for each product and the potential for overlapping toxicities with Pegasys with or without ribavirin.
Infezzjoni fl- istess ħin b’ HIV- HCV Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tal- prodotti mediċinali antiretrovirali li jkunu ser jittieħdu fl- istess ħin mat- terapija ta ’ HCV għall- għarfien u l- immaniġġjar ta ’ tossiċitajiet speċifiċi għal kull prodott u l- potenzjal għall- tossiċitajiet li jikkoinċidu ma ’ Pegasys waħdu jew ma ’ ribavirin.
In study NR15961, patients concurrently treated with stavudine and interferon therapy with or without ribavirin, the incidence of pancreatitis and/ or lactic acidosis was 3% (12/ 398).
Fl- istudju NR15961, pazjenti kkurati fl- istess ħin b’ stavudine u b’ terapija b’ interferon flimkien ma ’ ribavirin jew mingħajru, l- inċidenza ta ’ pankrejatite u/ jew aċidożi lattika kienet ta ’ 3% (12/ 398).
Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy (HAART) may be at increased risk of developing lactic acidosis.
Pazjenti ko- infettati b’ HIV u li jkunu qed jirċievu Terapija Anti- Retrovirali Attiva Ħafna (HAART) jistgħu ikunu f’ riskju akbar li jiżviluppaw aċidożi lattika.
Caution should therefore be exercised when adding Pegasys and ribavirin to HAART therapy (see ribavirin SPC).
Għandha tingħata attenzjoni meta jiżdied Pegasys u ribavirin ma ’ terapija HAART (ara SPC ta ’ ribavirin).
Co-infected patients with advanced cirrhosis receiving HAART may also be at increased risk of hepatic decompensation and possibly death if treated with ribavirin in combination with interferons, including Pegasys.
Pazjenti ko- infettati b’ ċirrożi avvanzata li qed jirċievu HAART jistgħu jkunu ukoll f’ riskju ikbar ta ’ dekompensazzjoni epatika u possibilment mewt jekk jingħataw ribavirin flimkien ma ’ interferon, fosthom Pegasys.
Baseline variables in co-infected cirrhotic patients that may be associated with hepatic decompensation include: increased serum bilirubin, decreased haemoglobin, increased alkaline phosphatase or decreased platelet count, and treatment with didanosine (ddI).
Varjabbli tal- linja bażi f’ pazjenti infettatti ukoll b’ ċirrożi li jistgħu jkunu assoċjati ma ’ dekompensazzjoni epatika jinkludu: żieda tal- bilirubin fis- serum, tnaqqis fl- emoglobina, żieda fl - alkaline phosphatase jew tnaqqis fl- għadd ta ’ plejtlits, u kura b’ didanosine (ddI).
The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see section 4.5).
10 L- użu ta ’ ribavirin flimkien ma ’ zidovudine mhux rakkomandat minħabba żieda fir- riskju ta ’ anemija (ara sezzjoni 4. 5).
Co-infected patients should be closely monitored, assessing their Child-Pugh score during treatment, and should be immediately discontinued if they progress to a Child-Pugh score of 7 or greater.
Pazjenti ko- infettati għandhom jiġu sorveljati bir- reqqa, il- punteġġ Child- Pugh għandu jiġi stmat waqt il- kura, u l- kura għandha titwaqqaf immedjatament jekk ikollhom punteġġ Child- Pugh ta ’ 7 jew ogħla.
In patients co-infected with HIV-HCV, limited efficacy and safety data (N = 51) are available in subjects with CD4 counts less than 200 cells/ uL.
F’ pazjenti infettati ukoll b’ HIV- HCV, tagħrif limitat dwar l- effikaċja u s- sigurtà (N = 51) huwa disponibbli f’ individwi b’ għadd ta ’ CD4 inqas minn 200 ċelluli/ uL.
Caution is therefore warranted in the treatment of patients with low CD4 counts.
Għalhekk għandu jkun hemm kawtela fil- kura ta ’ pazjenti b’ għadd ta ’ CD4 baxx.
Dental and periodontal disorders Dental and periodontal disorders, which may lead to loss of teeth, have been reported in patients receiving Pegasys and ribavirin combination therapy.
Disturbi dentali u paradentali Disturbi dentali u paradentali, li jistgħu jwasslu għal telf ta ’ snien, kienu rrapportati f’ pazjenti li rċevew terapija kombinata ta ’ Pegasys u ribavirin.
In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the combination of Pegasys and ribavirin.
Barra minn hekk, waqt kura fit- tul bit- taħtila ta ’ Pegasys u ribavirin, ħalq xott jista ’ jagħmel ħsara lis- snien u lill- membrana mukuża tal- ħalq.
Patients should brush their teeth thoroughly twice daily and have regular
Il- pazjenti għandhom jaħslu snienhom sew darbtejn kuljum u jkollhom eżaminazzjonijiet dentali regolari.
In addition some patients may experience vomiting.
Barra minn hekk xi pazjenti jista ’ jkollhom esperjenza ta ’ remettar.
If this reaction occurs, they should be advised to rinse out their mouth thoroughly afterwards.
Jekk isseħħ din ir- reazzjoni, għandom jiġu rakkomandati biex ilaħalħu ħalqhom sew wara.
Use of peginterferon as long term maintenance monotherapy (unapproved use) In a randomised, controlled US study (HALT-C) of HCV non-responder patients with varied degrees of fibrosis where 3.5 years of treatment with 90 micrograms/ week of Pegasys monotherapy was studied, no significant reductions were observed in the rate of fibrosis progression or related clinical events.
L- użu ta ’ peginterferon bħala monoterapija ta ’ manteniment fit- tul (użu mhux approvat) Fi studju randomised, ikkontrollat fl- Istati Uniti (HALT- C) ta ’ pazjenti b’ HCV bi gradi differenti ta ’ fibrosi li ma rrispondewx, fejn kienu studjati 3. 5 snin ta ’ kura b’ 90 mikrogramma/ ġimgħa ta ’ monoterapija ta ’ Pegasys, ma kien osservat l- ebda tnaqqis sinifikanti fir- rata ta ’ progressjoni tal- fibrożi jew fl- avvenimenti kliniċi relatati.
Administration of Pegasys 180 micrograms once weekly for 4 weeks in healthy male subjects did not show any effect on mephenytoin, dapsone, debrisoquine and tolbutamide pharmacokinetics profiles, suggesting that Pegasys has no effect on in vivo metabolic activity of cytochrome P450 3A4, 2C9, 2C19 and 2D6 isozymes.
Meta Pegasys 180 mikrogrammi ingħata darba fil- ġimgħa għal 4 ġimgħat f’ irġiel b’ saħħithom ma kien hemm l- ebda effett fuq il- profili farmakokinetiċi ta ’ mephenytoin, dapsone, debrosquine u tolbutamide, li tissuġġerixxi li Pegasys m’ għandu l- ebda effett fuq l- attività metabolika in vivo ta ’ isożimi taċ - ċitokromju P450 3A4, 2C9, 2C19 u 2D6.
In the same study, a 25% increase in the AUC of theophylline (marker of cytochrome P450 1A2 activity) was observed, demonstrating that Pegasys is an inhibitor of cytochrome P450 1A2 activity.
Fl- istess studju, żieda ta ’ 25% fl- AUC ta ’ theophylline (markatur ta ’ l- attivita ’ taċ- ċitokromju P450 1A2) kienet osservata, li turi li Pegasys huwa impeditur ta ’ l- attivita ’ taċ- ċitokromju P450 1A2.
Serum concentrations of theophylline should be monitored and appropriate dose adjustments of theophylline made for patients taking theophylline and Pegasys concomitantly.
Il - konċentrazzjonijiet fis- serum ta ’ theophylline għandhom ikunu monitorati u tibdiliet xierqa fid- doża ta ’ theophylline għandhom isiru f’ pazjenti li qedgħin jieħdu theophylline u Pegasys flimkien.
The interaction between theophylline and Pegasys is likely to be maximal after more than 4 weeks of Pegasys therapy.
L - interazzjoni bejn theophylline u Pegasys huwa probabli li tkun l- ogħla wara aktar minn 4 ġimgħat ta ’ terapija b' Pegasys.
Results from pharmacokinetic substudies of pivotal phase III trials demonstrated no pharmacokinetic interaction of lamivudine on Pegasys in HBV patients or between Pegasys and ribavirin in HCV patients.
Ir- riżultati minn sub- studji farmakokinetiċi pivitali tat- III fażi ma wrew l- ebda interazzjoni farmakokinetika ta ’ lamivudine fuq Pegasys f’ pazjenti b’ HBV jew bejn Pegasys u ribavirin f’ pazjenti b’ HCV.
In a pharmacokinetic study of 24 HCV patients concomitantly receiving methadone maintenance therapy (median dose 95 mg; range 30 mg to 150 mg), treatment with Pegasys 180 micrograms sc once weekly for 4 weeks was associated with mean methadone levels that were 10% to 15% higher than at baseline.
Fi studju farmakokinetiku ta ’ 24 pazjent b’ HCV li kienu qed jirċievu terapija ta ’ manteniment ta ’ methadone fl- istess ħin (doża medjana ta ’ 95mg; firxa ta ’ 30mg sa 150mg), kura b’ Pegasys 180 mikrogramma sc darba fil- ġimgħa għal 4 ġimgħat kienet assoċjata ma ’ livelli medji ta ’ methadone li kienu 10% sa 15% ogħla mil- linja bażi.
The clinical significance of this finding is unknown; nonetheless, patients should be monitored for the signs and symptoms of methadone toxicity.
Is- sinifikat kliniku ta ’ din is- sejba mhux magħruf; madanakollu, l- pazjenti għandhom jiġu sorveljati għal sinjali u sintomi ta ’ tossiċita b’ methadone.
Especially in patients on a high dose of methadone, the risk for QTc prolongation should be considered.
Ir- riskju ta ’ titwil ta ’ QTc għandu jiġi kkunsidrat, speċjalment f’ pazjenti fuq doża għolja ta ’ methadone.
HIV-HCV co-infected patients No apparent evidence of drug interaction was observed in 47 HIV-HCV co-infected patients who completed a 12 week pharmacokinetic substudy to examine the effect of ribavirin on the intracellular phosphorylation of some nucleoside reverse transcriptase inhibitors (lamivudine and zidovudine or stavudine).
Pazjenti ko- infettati b’ HIV- HCV Ma kienet osservata l- ebda evidenza apparenti ta ’ interazzjoni ta ’ mediċini f’ 47 pazjent ko- infettati b’ HIV- HCV li temmew substudju farmakokinetiku ta ’ 12- il ġimgħa li eżamina l- effett ta ’ ribavirin fuq il- fosforilizazzjoni intraċellolari ta ’ uħud mill- inibituri ta ’ nucleoside reverse transcriptase (lamivudine
However, due to high variability, the confidence intervals were quite wide. Plasma exposure of ribavirin did not appear to be affected by concomitant administration of nucleoside reverse transcriptase inhibitors (NRTIs).
Ma deherx li l- espożizzjoni fil- plażma ta ’ ribavirin kienet affettwata mill- għotja fl- istess ħin ta ’ inibituri ta ’ nucleoside reverse transcriptase (NRTIs).
Co-administration of ribavirin and didanosine is not recommended.
L- għotja flimkien ta ’ ribavirin u didanosine mhux rakkomandata.
Exposure to didanosine or its active metabolite (dideoxyadenosine 5’ -triphosphate) is increased in vitro when didanosine is co- administered with ribavirin.
L- espożizzjoni għal didanosine jew għall- metabolit attiv tiegħu (dideoxyadenosine 5 ’ - triphosphate) tiżdied in vitro meta didanosine jingħata flimkien ma ’ ribavirin.
Reports of fatal hepatic failure as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactataemia/ lactic acidosis have been reported with use of ribavirin.
Rapporti ta ’ insuffiċjenza epatika fatali kif ukoll newropatija periferali, pankreatite, u iperlaktejtimja sintomatika/ aċidożi lattika kienu rrapportati bl- użu ta ’ ribavirin.
Exacerbation of anaemia due to ribavirin has been reported when zidovudine is part of the regimen used to treat HIV although the exact mechanism remains to be elucidated.
Kienet irrapportata anemija li marret għall- agħar minħabba ribavirin meta zidovudine huwa parti mill - kors użat għall- kura ta ’ HIV għalkemm il- mekkaniżmu eżatt għad irid jinstab.
The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see section 4.4).
L- użu ta ’ ribavirin flimkien ma ’ zidovudine mhux rakkomandat minħabba żieda fir- riskju ta ’ anemija (ara sezzjoni 4. 4).
Consideration should be given to replacing zidovudine in a combination ART regimen if this is already established.
Għandha tingħata konsiderazzjoni għas- sostituzzjoni ta ’ zidovudine f’ kors ART kombinat jekk dan huwa diġà stabbilit.
This would be particularly important in patients with a known history of zidovudine induced anaemia.
Dan ikun importanti b’ mod partikolari f’ pazjenti b’ passat magħruf ta ’ anemija ikkaġunata minn zidovudine.
11 4.6 Pregnancy and lactation
4. 6 Tqala u treddigħ
There are no adequate data on the use of peginterferon alfa-2a in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ peginterferon alfa- 2a waqt it- tqala.
Studies in animals with interferon alfa-2a have shown reproductive toxicity (see section 5.3) and the potential risk for humans is unknown.
Studji fuq bhejjem b’ interferon alfa- 2a urew ħsara fuq is- sistema riproduttiva (ara sezzjoni 5. 3) u mhux magħruf r- riskju potenzjali fuq in- nies.
Pegasys is to be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Pegasys għandu jintuża waqt it- tqala biss jekk il- benefiċċju potenzjali jiġġustifika r- riskju potenzjali għall- fetu.
It is not known whether the components of this medicinal product are excreted in human milk.
Mhux magħruf jekk il- komponenti ta ’ dan il- prodott mediċinali joħorġux mal- ħalib tas- sider fil - bniedem.
Because of the potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of treatment.
Minħabba l- potenzjal ta ’ reazzjonijiet avversi li jistgħu iseħħu b’ Pegasys fi trabi li jkunu qed jieħdu l- ħalib tas- sider, it- treddigħ għandu jitwaqqaf qabel ma tinbeda l- kura.