qanastek/EMEA-V3 huggingface dataset:
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
It- terapija antiretrovirali kkombinata ġiet assoċjata ma ’ problemi metaboliċi mhux normali bħal ipertrigliċeridemija, iperkolosterolemija, reżistenza għall- insulina, ipergliċemija u iperlactataemija (ara sezzjoni 4. 4).
33 Undesirable effects in clinical studies in adult patients Infections and infestations
37 Effetti mhux mixtieqa fi studji kliniċi f’ pazjenti adulti
Otitis media, bronchitis, sinusitis, furunculosis, bacterial infections, viral infection
Otite medja, bronkite, sinusite, furunkulożi, infezzjoni batterika, infezzjoni virali
Skin benign neoplasm, cyst
Neoplażma beninja tal- ġilda, ċesta
Hypergonadism male, Cushing syndrome, hypothyroidism
Ipogonadiżmu maskili, Sindromu ta ’ Cushing, ipotajojdiżmu
Avitminosis, dehydration, oedema, increased appetite, lactic acidosis, obesity, anorexia, diabetes mellitus, hyperglycaemia, hypocholesteramia
Nuqqas ta ’ vitamini, deidratazzjoni, edema, żieda fl- aptit, acidożi laktika, obesita ’, anoressija, dijabete mellitus
Abnormal dreams, agitation, anxiety, confusion, depression, dyskinesia, emotional lability, decreased libido, nervousness, abnormal thinking
Ħolm mhux normali, aġitazzjoni, ansjeta ’, konfużjoni, depressjoni, diżkinesija, instabbilita emozzjonali, tnaqqis fil- libido, nervożiżmu, ħsieb mhux normali
Eye disorder Ear and labyrinth disorders Cardiac disorders Vascular disorders
Viżjoni mhux normali, problemi fl- għajn
Uncommon Uncommon Uncommon Uncommon
Disturbi fil- widnejn u fis - sistema labirintika
Abnormal vision, eye disorder Tinnitus Palpitation, lung oedema, myocardial infarc1 Hypertension, thrombophlebitis, vasculitis, varicose vein, deep thrombophlebitis, vascular disorder
Ipertensjoni, tromboflebite, vaskulite, vini varikożi, tromboflebite, problemi vaskulari
Abdomen enlarged, constipation, dry mouth, dysphagia, entercolitis, eructation, oesophagitis, faecal incontinence, gastritis, gastroenteritis, haemorrhagic colitis, mouth ulcerations, panreatitis2, sialadenitis, stomatitis, ulcerative stomatitis, peridontitis
Tinfiħ addominali, stitikezza, nixfa fil- ħalq, disfaġja, enterokolite erutazzjoni, esofaġite, inkontinenza ta ’ l- iskart tal- ġisem, gastrite, gastroenterite, kolite emorraġika, ulċerazzjoni tal- ħalq, pankreatite2, sialadenite, stomatite, stomatite ulċerativa, periodontite
Hepatobiliary disorders
38 Disturbi fil- fwied u fil- marrara
Alopecia, dry skin, eczema, exfoliative dermatitis, maculopapular rash, nail disorder, Pruritis, seborrhoea, skin discoloration, skin ulcer, face oedema, sweating, skin striae
Qrugħa, ġilda niexfa, ekżema, dermatite esfoljativa, raxx makulopapulari, problemi tad- difer, prurite, seborreja, telf ta ’ kulur al - ġilda, ulċera tal- ġilda, edema tal- wiċċ, perspirazzjoni, strije fil- ġilda
34 Musculoskeletal and connective tissue disorder
Disturbi muskolu- skeltrali u tal - connective tissue
Arthralgia, arthosis, myalgia, back pain, joint disorder
Artralġja, artrożi, mialġja, uġigħ tad- dahar, Disturbi fil- ġogi
Kidney calculus, urine abnormality, albuminuria, hypercalcinuria, hypericaemia
Ġebla fil- kliewi, urina mhux normali, albuminurja, iperkalċinurja, iperuriċemija
Asthemia, pain
Astenja, uġigħ
Chest pain, chest pain substernal, chills, fever, flu syndrome, malaise, peripheral oedema, drug interaction
Uġiegħ fis- sider, uġiegħ fis- sider substernali, dehx, deni, sindromu ta ’ l- influenza, tħossok mintix f’ siktek, edema periferali, interazzjoni ma mediċini oħra żieda fit- trigliċeridi, żieda fil- kolesterol totali,
Very common (Grade 3or 4)
Komuni ħafna (Grad 3 jew 4) Komuni
Increased triglycerides, increased total cholesterol, increased GGT
żieda GGT
This event had a fatal outcome.
SGOT/ AST, żieda SGPT/ ALT, testijiet tal -
Uncommon
funzjoni tal- fwied mhux normali
Decreased glucose tolerance, weight gain, weight loss, increased bilirubin, hormone level altered, lab test abnormal
Mhux komuni Tnaqqis fit- toleranza tal- glukożju, żieda fil - piż, tnaqqis fil- piż, żieda fil- bilirubin, livelli alterati ta ’ l- ormuni, testijiet tal- laboratorju mhux normali 1 Kellu effett fatali 2 ara sezzjoni 4. 4: pankreatite u lipidi
In children 2 years of age and older, the nature of the safety profile is similar to that seen in adults.
39 Pazjenti Pedjatriċi Fit- tfal ta ’ sentejn u ikbar, in- natura tal- profil ta ’ sigurta ’ huwa simili għal dak fl- adulti.
Undesirable effects in clinical studies in paediatric patients Infections and infestations
Effetti mhux mixtieqa fi studji kliniċi f’ pazjenti pedjatriċi Infezzjonijiet u infestazzjonijiet Komuni
Viral infection
Infezzjoni virali
Nervous system disorders
Disturbi fis- sistema nervuża Komuni
Taste perversion
Perverżjoni tat- togħma
Gastrointestinal disorders
Disturbi Gastro- Intestinali
Constipation, vomiting, pancreatitis*
Stitikezza, vomtar, pankreatite *
Hepatomegaly
Tkabbir fid- daqs tal- fwied
Rash, dry skin
Raxx, ġilda niexfa
35 Post marketing experience
Esperjenza wara li l- prodott tpoġġa fuq is- suq
The adverse clinical signs observed in dogs included salivation, emesis and diarrhoea/ abnormal stool.
Is- sinjali kliniċi avversi osservati fil- klieb kienu jinkludu salivazzjoni, emeżi u diareja / skart tal- ġisem mhux normali.
There is no specific antidote for overdose with Kaletra.
40 M’ hemm l- ebda antidotu speċifiku għal doża eċċessiva b’ Kaletra.
Administration of activated charcoal may also be used to aid in removal of unabsorbed active substance.
Amministrazzjoni ta ’ faħam attivat jista ’ jintweża biex jgħin fit- tneħħija tas- sustanza attiva mhux attivata.
5.1 Pharmacodynamic properties
5. 1 Tagħrif farmakodimaniku
The two regimens resulted in exposures on Day 3 which were approximately 1.5 and 3- fold higher than those observed with recommended once daily or twice daily LPV/ r doses at steady state.
Iż- żewġ reġimen irriżultaw f’ esponimenti f’ Ġurnata 3, li kienu ta ’ bejn wieħed u ieħor 1. 5 u 3 darbiet ogħla minn dawk osservati meta ngħataw id- dożi fissi rrakkomandati ta ’ LPV/ r darba kuljum jew darbtejn kuljum.
In the absence and presence of 50% human serum, the mean IC50 of
Fl- assenza ta ’ serum uman, il- medja IC50 ta ’ lopinavir kontra ħames razzi differenti ta ’ HIV- 1 tal- laboratorju kien 19 nM.
36 lopinavir against HIV-1IIIB in MT4 cells was 17 nM and 102 nM, respectively.
Fl- assenza u presenza ta ’ 50% serum uman, il- medja IC50 ta ’ lopinavir kontra HIV- 1IIIB f’ ċelluli MT4 kien 17 nM u 102 nM, rispettivament.
Genotypic and phenotypic analysis of viruses selected in these passages suggest that the presence of ritonavir, at these concentration ratios, does not measurably influence the selection of lopinavir-resistant viruses.
Kollox ma kollox, il- karatterizazzjoni in vitro ta ’ cross -
Overall, the in vitro characterisation of phenotypic cross-resistance between lopinavir and other protease inhibitors suggest that decreased susceptibility to lopinavir correlated closely with decreased susceptibility to ritonavir and indinavir, but did not correlate closely with decreased susceptibility to amprenavir, saquinavir, and nelfinavir.
41 resistance fenotipika bejn lopinavir u inibituri tal- protease oħrajn tissuġġerixxi li t- tnaqqis fis - suxxettibilità għal lopinavir tikkorrelata mill- qrib ma tnaqqis fis- suxxettibilità għal ritonavir u indinavir, iżda ma tikkorrelatax mill- qrib ma tnaqqis fis- suxxettibilità għal amprenavir, saquinavir, u nelfinavir.
Analysis of resistance in ARV-naïve patients:
Analiżi ta ’ reżistenza f’ pazjenti li qatt ma esponew ruħhom qabel għal ARV:
Of these, isolates from 96 nelfinavir-treated subject and 51 lopinavir/ ritonavir-treated subjects could be amplified for resistance testing.
Minn dawn, iżolati minn 96 suġġetti trattati b’ nelfinavir u 51minn suġġetti trattati b’ lopinavir/ ritonavir setgħu jiġu amplifikati għal- istudju fuq reżistenza.
37 Antiviral activity of Kaletra in patients failing protease inhibitor therapy: the clinical relevance of reduced in vitro susceptibility to lopinavir has been examined by assessing the virologic response to Kaletra therapy, with respect to baseline viral genotype and phenotype, in 56 patients previous failing therapy with multiple protease inhibitors.
L- attività antivirali ta ’ Kaletra f’ pazjenti li qed ifallu fit- terapija ta ’ inibituri tal- protease: ir- rilevanza klinika tas- suxxettibilità in vitro għal lopinavir ġiet eżaminata billi ġie analizzat ir- respons viroloġiku tat- terapija b’ Kaletra, fir- rigward tal- linja bażi tal- ġenotip u fenotip virali, fi 56 pazjent li qabel kienu qed ifallu t- terapija b’ inibituri multipli tal- protease.
Isolates retained susceptibility to tipranavir with a median increase of IC50 in baseline and rebound isolates of 1.9- and 1.8– fold, respectively, compared to wild type virus.
L- iżolati żammew is- suxxetibilita għal tipranavir b’ żieda medjana ta ’ IC50 fil- linja bażi u f’ dawk li marru lura ta ’ 1. 9- il darba u 1. 8- il darba rispettivament, mqabbla ma virus tat- tip mhux ikkultivat.
Please refer to the Aptivus Summary of Product Characteristics for additional information on the use of tipranavir, including genotypic predictors of response, in treatment of lopinavir-resistant HIV-1 infection.
Jekk jogħġbok irreferi għal Aptivus karatteristiċi tal- prodott fil- qosor għal iktar informazzjoni dwar l- użu ta ’ tipranavir, inklużi il- ġenotipiċi preditturi tar- rispons, fit- trattament ta ’ infezzjoni ta ’ l- HIV reżistenti għall - lopinavir.
2 to 949 cells/ mm3) and mean baseline plasma HIV-1 RNA was 4.9 log10 copies/ ml (range:
2. 6 għal 6. 8
2.6 to 6.8 log10 copies/ ml).
43 log10 kopji/ ml).
The mean increase from baseline in CD4 cell count was 207 cells/ mm3 in the Kaletra arm and 195 cells/ mm3 in the nelfinavir arm.
Iż- żieda medja mill- linja bażi fl- għadd ta ’ ċelluli CD4 kienet ta ’ 207 ċelluli/ mm3 fis- sezzjoni Kaletra u 195 ċelluli/ mm3 fis- sezzjoni nelfinavir.
Through 48 weeks of therapy, a statistically significantly higher proportion of patients in the Kaletra arm had HIV RNA < 50 copies/ ml compared to the nelfinavir arm.
Tul 48 ġimgħa ta ’ terapija, proporzjon ogħla statistikament sinifikattiv ta ’ pazjenti fis- sezzjoni Kaletra kellhom HIV RNA < 50 kopji/ ml mqabbla mas- sezzjoni nelfinavir.
All patients converted to open-label Kaletra at the 400/ 100 mg twice daily
Bejn ġimgħa 48 u ġimgħa 72, il- pazjenti kollha qalbu għal Kaletra open - label meta ngħataw id- doża ta ’ 400/ 100 mg darbtejn kuljum.
Thirty-nine patients (39%) discontinued the study, including 16 (16%) discontinuations due to adverse events, one of which was associated with a death.
Disgħa u tletin pazjent (39%) ma komplewx l- istudju, inklużi 16 (16%) waqfiet minħabba eventi avversi, li waqfa minnhom kienet assoċjata ma ’ mewt.
Median baseline CD4 cell count was 349 cells/ mm3 (range 72 to 807 cells/ mm3) and median baseline plasma HIV-1 RNA was 4.0 log10 copies/ ml (range 2.9 to 5.8 log10 copies/ ml).
Il- linja bażi medjana fl- għadd ta ’ ċelluli CD4 kien 349 ċelluli/ mm3 (limiti 72 għal 807 ċelluli / mm3) u l - linja bażi medjana tal- plażma HIV- 1 RNA kienet 4. 0 log10 kopji/ ml (limiti 2. 9 għal 5. 8 log10 kopji/ ml).
By intent-to-treat analysis where patients with missing values are considered virologic failures, the proportion of patients with HIV RNA < 400 (< 50) copies/ ml at 24 weeks was 75% (58%) and the mean increase from baseline in CD4 cell count was 174 cells/ mm3 for the 36 patients receiving the 400/ 100 mg dose of Kaletra.
Bl- intenzjoni li jittrattaw l- analiżi fejn pazjenti b’ valuri nieqsa huma kkunsidrati fallimenti viroloġiċi, il- proporzjon ta ’ pazjenti b’ HIV RNA < 400 (< 50) kopji/ ml fi 24 ġimgħat kien 75% (58%) u ż- żieda mill- linja bażi fl- għadd taċ- ċelluli CD4 kien 174 ċelloli/ ml għat- 36 pazjent li qed jingħataw 400/ 100 mg doża ta ’ Kaletra.
Median baseline CD4 cell count was 220 cells/ mm3 (range13 to 1030 cells/ mm3).
Il- medjan tal - linja bażi fl- għadd taċ- ċelluli CD4 kien 220 ċelluli/ ml (limiti 13 għal 1030 ċelluli/ ml).
By intent-to-treat analysis of both dose groups combined (n=57), where patients with missing values are considered virologic failures, the proportion of patients with HIV RNA < 400 copies/ ml at 48 weeks was 65% and the mean increase from baseline CD4 cell count was 94 cells/ mm3.
Bl- intenzjoni li jittrataw ż- żewġ gruppi b’ dożi kkumbinati (n=57), fejn pazjenti b’ valuri nieqsa huma kkunsidrati fallimenti viroloġiċi, il- proporzjon ta ’ pazjenti b’ HIV RNA < 400 kopji/ ml fil- ġimgħa 48 kien 65% u ż - żieda medja mill- linja bażi fl- għadd ta ’ ċelluli CD4 kien 94 ċelluli/ mm3.
Through 48 weeks of therapy, the proportion of patients with HIV RNA < 400 copies/ ml was 84% for antiretroviral naïve patients and 75% for antiretroviral experienced patients and the mean increase from baseline in CD4 cell count were 404 cells/ mm3 and 284 cells/ mm3 respectively.
44 Tul 48 ġimgħa ta ’ terapija, il- proporzjon ta ’ pazjenti b’ HIV RNA < 400 kopji/ ml kien 84% għal pazjenti novizzi għat- terapiji antiretrovirali u 75% għal pazjenti b’ esperjenza ta ’ terapiji antiretrovirali, u żidiet medji mill- linja bażi fl- għadd taċ- ċelluli CD4 kien 404 ċelluli/ mm3 u 284 ċelluli/ mm3, rispettivament.
39 Absorption: multiple dosing with 400/ 100 mg Kaletra twice daily for 3 to 4 weeks and without meal restriction produced a mean ± SD lopinavir peak plasma concentration (Cmax) of 9.6 ± 4.4 μ g/ ml, occurring approximately 4 hours after administration.
Dużaġġ multiplu b ’ 400/ 100 mg Kaletra darbtejn kuljum għal 3 sa 4 ġimgħat u mingħajr restrizzjoni fuq l- ikel ipproduċiet medja ± SD l- ogħla konċentrazzjoni ta ’ lopinavir fil- plażma lopinavir (Cmax) ta ’ 9. 6 ± 4. 4 μg/ ml, li ntlaħqet approssimattivament 4 sigħat wara s- somministrazzjoni.
Lopinavir is extensively metabolised by the hepatic cytochrome P450 system, almost exclusively by isozyme CYP3A.
Il- lopinavir huwa estensivament metabolizzat mis- sistema ċitokroma epatika P450, kważi esklussivament mill- iżożima CYP3A.
Ritonavir is a potent CYP3A inhibitor which inhibits the metabolism of lopinavir and therefore, increases plasma levels of lopinavir.
Ir- ritonavir huwa inibitur ta’ CYP3A potenti li jinibixxi il- metaboliżmu ta’ lopinavir u għalhekk iżid il- livelli tal- plażma ta’ lopinavir.
At least 13 lopinavir oxidative metabolites have been identified in man.
Mill- inqas 13 - il metabolita ossidattivi ta ’ lopinavir ġew identifikati fil- bniedem.
40 Gender, Race and Age:
Sess, Razza u Età:
Mild renal tubular degeneration was confined to mice exposed with at least twice the recommended human exposure; the kidney was unaffected in rats and dogs.
Deġenerazzjoni renali tubulari ħafifa kienet ristretta għall ġrieden esposti b’ almenu darbtejn l- esponiment rakkomandat għall bniedem; il- kilwa ma ’ kenitx effettwata fil- far u fil -
During in vitro studies, cloned human cardiac potassium channels (HERG) were inhibited by 30% at the highest concentrations of lopinavir/ ritonavir tested, corresponding to a lopinavir exposure 7-fold total and 15-fold free peak plasma levels achieved in humans at the maximum recommended therapeutic dose.
Waqt studju in vitro kanali kardijaċi tal- potassju umani klonati (HERG) kienu inibiti bi 30% fl- ogħla konċentrazzjonijiet ta ’ lopinavir/ ritonavir ippruvati, li kienu jikkorrispondu għal esponiment għal lopinavir ta ’ total ta ’ 7 darbiet u 15 il- darba livelli ta ’ plażma quċċata libera li ġew ottenuti fil- bniedem bid- doża terapewtika massima li ġiet irrikmandata.
These effects have been assumed to be caused by electrolyte disturbance.
Huwa preżunt li dawn l- effetti huma kawża ta ’ disturb minn elektrolite.
The clinical relevance of these preclinical data is unknown, however, the potential cardiac effects of this product in humans cannot be ruled out (see also sections 4.4 and 4.8).
Ir- rilevanza klinika ta ’ dan it- tagħrif ta ’ qabel l- użu kliniku, ma ’ huwiex magħruf, iżda l- effetti potenzjali kardijaċi ta ’ dan il- prodott fil- bniedem ma ’ jista jiġi eskluż (ara ukoll sezzjoni 4. 4. u 4. 8).
41 Long-term carcinogenicity studies of lopinavir/ ritonavir in mice revealed a nongenotoxic, mitogenic induction of liver tumours, generally considered to have little relevance to human risk.
Studji karċinoġeniċi fuq perijodu twil, tal- lopinavir/ ritonavir fil- ġrieden żvela induzzjoni mhux ġenotossika u mitoġenika ta ’ tumuri fil- fwied, li ġeneralment huma kkunsidrati li għandhom ftit rilevanza ta ’ riskju għall bniedem.
Oral solution contains: alcohol (42% v/ v), high fructose corn syrup, propylene glycol, purified water, glycerol, povidone, magnasweet-110 flavour (mixture of monoammonium glycyrrhizinate and glycerol), vanilla flavour (containing p-hydroxybenzoic acid, p-hydroxybenzaldehyde, vanillic acid, vanillin, heliotrope, ethyl vanillin), polyoxyl 40 hydrogenated castor oil, cotton candy flavour (containing ethyl maltol, ethyl vanillin, acetoin, dihydrocoumarin, propylene glycol), acesulfame potassium, saccharin sodium, sodium chloride, peppermint oil, sodium citrate, citric acid, menthol.
Alkoħol (42% v/ v), high fructose corn syrup, propylene glycol, ilma ppurifikat, glycerol, povidone, Magnasweet- 110 flavour (taħlita ta ’ monoammonium glycyrrhizinate and glycerol), vanilla flavour (containing p- hydroxybenzoic acid, p- hydroxybenzaldehyde, vanillic acid, vanillin, heliotrope, ethyl vanillin), polyoxyl 40 hydrogenated castor oil, cotton candy flavour (fih ethyl maltol, ethyl vanillin, acetoin, dihydrocoumarin, propylene glycol), acesulfame potassium, saccharin sodium, sodium chloride, peppermint oil, sodium citrate, citric acid, menthol.
Store in a refrigerator (2°C - 8°C).
6. 4 Prekawzjonijiet speċjali għall- ħażna Aħżen fi friġġ (2°C – 8°C).
Avoid exposure to excessive heat.
Evita l- esponiment għal sħana eċċessiva.
Amber coloured multiple-dose polyethylene terephthalate (PET) bottles in a 60 ml size.
Fliexken kulur ambra għal dożi multipli magħmulin minn polyethylene terephthalate (PET), ta ’ daqs ta ’ 60 ml.
Each pack contains 5 bottles of 60 ml (300 ml).
Kull pakkett fih 5 fliexken ta ’ 60 ml (300 ml).
The pack also contains 5 x 5 ml syringes with 0.1 ml graduations from 0 to 5 ml (400/ 100 mg).
Il- pakkett fih ukoll 5 x 5 ml siringi bi gradazzjonijiet ta ’ 0. 1 ml minn 0 sa 5 ml (400/ 100 mg).
42 7.
48 7.
Kaletra 200 mg/ 50 mg film-coated tablets
Kaletra 200 mg/ 50 mg pilloli miksija b' rita
Each film-coated tablet contains 200 mg of lopinavir co-formulated with 50 mg of ritonavir as a pharmacokinetic enhancer.
Kull pillola miksija b’ rita fiha 200 mg lopinavir ko- formulata ma ’ 50 mg ritonavir bħala qanqiel farmakokinetiku.
Yellow embossed with [Abbott logo] and “ KA”.
Safra intaljata bl- arma ta ’ Abbott u “ KA ”
Kaletra is indicated for the treatment of HIV-1 infected adults and children above the age of 2 years, in combination with other antiretroviral agents.
Kaletra huwa indikat għat- trattament ta ’ adulti u tfal il- fuq minn sentejn infettati bl- HIV- 1, ikkombinat ma aġenti antiretrovirali oħra.
Kaletra tablets should be swallowed whole and not chewed, broken or crushed
Il- pilloli Kaletra għandhom jinbelgħu sħaħ, u mhux jiġu mimgħudin, imkissra jew mgħaffġa.
Adult and adolescent use: the recommended dosage of Kaletra tablets is two 200/ 50 mg tablets twice daily taken with or without food..
Użu fl- adulti u fl- adoloxxenti: id- dużaġġ irrikmandat ta ’ Kaletra huwa ta ’ żewġ pilloli ta ’ 200/ 50 mg darbtejn kuljum waħedhom jew ma ’ l- ikel.
Oral solution is available to patients who have difficulty swallowing.
Is- soluzzjoni orali hija disponibbli għal min għandu diffikultà biex jibla ’.
Refer to the Summary of Product Characteristics for Kaletra oral solution for dosing instructions.
Irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tas- soluzzjoni orali Kaletra għall- istruzzjonijiet dwar id- dożaġġ.
Paediatric use (2 years of age and above): the adult dose of Kaletra tablets (400/ 100 mg twice daily) may be used in children 40 kg or greater or with a Body Surface Area (BSA)* greater than 1.4 m2.
Id- doża adulta tal- pilloli ta ’ Kaletra, 2 pilloli (400/ 100 mg darbtejn kuljum), tista tingħata fi tfal li jiżnu 40kg jew iktar, b’ arja tal- wiċċ tal- ġisem (BSA *) ikbar minn 1. 4m2.
For children weighing less than 40 kg or with a BSA between 0.5 and 1.4 m2 and able to swallow tablets, please refer to the Kaletra 100 mg/ 25 mg tablets Summary of Product Characteristics.
Għal tfal li jiżnu inqas minn 40kg jew li għandhom BSA ta ’ bejn 0. 5 u 1. 4 m2 u li jafu jibilgħu il- pilloli, jekk joġgħbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tal- pilloli Kaletra 100 mg/ 25 mg.
For children unable to swallow tablets, please refer to the Kaletra oral solution Summary of Product Characteristics.
Fil- każ ta ’ tfal li ma jafux jibilgħu, jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tas - soluzzjoni orali Kaletra.
BSA (m2) = √ (Height (cm) X Weight (kg) / 3600)
50 * L- arja tal- wiċċ tal- ġisem tista tiġi kkalkulata bill- fomula li jmiss BSA (m2) = √ (Tul (ċentimetri) X Piż (kilogrammi) / 3600)
Kaletra is not recommended for use in children below 2 years of age due to insufficient data on safety and efficacy (see section 5.1).
Kaletra mhux irrikmandat għal użu fi tfal li għandhom inqas minn 2 snin minħabba data limitata ta ’ sigurtà u effikaċja (ara sezzjoni 5. 1).
44 Concomitant Therapy:
Terapija konkomitanti:
Efavirenz or nevirapine
Efavirenz jew nevirapine
The following table contains dosing guidelines for Kaletra tablets based on BSA when used in combination with efavirenz or nevirapine in children.
It- tabella li jmiss fiha l- linji gwida dwar id- dożaġġ għall- pilloli Kaletra, ibbażati fuq BSA meta dawn jingħataw lit- tfal flimkien ma ’ efavirenz jew nevirapine.
Recommended lopinavir/ ritonavir dosing (mg) twice daily.
Linji Gwida dwar id- Dożaġġ għat- tfal flimkien ma ’ l- għoti ta ’ efavirenz jew nevirapine Id- doża rrakkomandata ta ’ L- erja tas- superfiċje tal - lopinavir/ ritonavir (mg) darbtejn kuljum. ġisem (m2) Id- doża adegwata tista ’ tintlaħaq biż- żewġ dożaġġi disponibbli tal- pilloli Kaletra:
100/ 25 mg and 200/ 50 mg. *
100/ 25 mg u 200/ 50 mg. *
≥ 0.5 to < 0.8 ≥ 0.8 to < 1.2
≥ 0. 5 to < 0. 8 ≥ 0. 8 to < 1. 2
≥ 1.2 to < 1.4 ≥ 1.4
≥ 1. 2 to < 1. 4 ≥ 1. 4
* Kaletra tablets must not be chewed, broken or crushed.
* Il- pilloli Kaletra m’ għandhomx jiġu mimgħuda, imkissra jew mgħaffġa.
In HIV-infected patients with mild to moderate hepatic impairment, an increase of approximately 30% in lopinavir exposure has been observed but is not expected to be of clinical relevance (see section 5.2).
F’ pazjenti infettati bl- HIV u b’ indeboliment tal- fwied ħafif għal moderat, ġiet osservata żieda approssimattiva ta ’ 30% ta ’ esposizzjoni għal lopinavi, imma mhix mistennija li tkun klinikament ta ’ importanza (ara sezzjoni 5. 2).
Renal impairment: no dose adjustment is necessary in patients with renal impairment.
L- ebda arranġament fid- doża m’ hu neċessarju f’ pazjenti b’ indeboliment tal - kliewi.
Hypersensitivity to the active substances or to any of the excipients.
Pazjenti sensittivi għal lopinavir, ritonavir jew għal xi sustanzi mhux attivi.
These medicinal products include astemizole, terfenadine, oral midazolam (for caution on parenterally administered midazolam, see section 4.5), triazolam, cisapride, pimozide, amiodarone, ergot alkaloids (e. g. ergotamine, dihydroergotamine, ergonovine and methylergonovine) and vardenafil.
Dawn il- prodotti mediċinali jinkludu astemizole, terfenadine, midazolam li jittieħed mill- ħalq (sabiex tiġi eżerċitata kawtela meta midazolam jiġi mgħoti parenteralment, ara sezzjoni 4. 5), triazolam, cisapride, pimozide, amiodarone, ergot alkaloids (eż. ergotamine, dihydroergotamine, ergonovine u methylergonovine) u vardenafil.
Herbal preparations containing St John’ s wort (Hypericum perforatum) must not be used while taking lopinavir and ritonavir due to the risk of decreased plasma concentrations and reduced clinical effects of lopinavir and ritonavir (see section 4.5).
51 Preparazzjonijiet mill- ħxejjex li fihom St John’ s wort (Hypericum perforatum) m’ għandhomx jintużaw waqt it- teħid ta ’ lopinavir u ritonavir minħabba r- riskju ta’ tnaqqis fil - konċentrazzjoni fil- plażma u tnaqqis fl- effetti kliniċi ta ’ lopinavir u ritonavir (ara sezzjoni 4. 5).
45 Patients with pre-existing liver dysfunction including chronic hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
Pazjenti b’ disfunzjoni tal- fwied ġa eżistenti, inkluża l- epatite kronika għandhom żieda fil- frekwenza funzjoni tal- fwied mhux normali waqt terapija kkombinata antiretrovirali, u għandhom ikunu monitorati kif titlob il- pratika standard.
Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of pancreatitis should occur.
Il- pankreatite għandha tkun ikkunsidrata jekk sintomi kliniċi (nawsja, rimettar, uġigħ addominali) jew valuri tal- laboratorju mhux normali (bħal żieda fis- serum lipase u valuri tal- amilase) suġġestivi ta ’ pankreatite iseħħu.
Hyperglycaemia
52 Ipergliċemija
Fat redistribution and metabolic disorders
Ridistribuzzjoni tax- xaħam u problemi metaboliċi
Clinical examination should include evaluation for physical signs of fat
Eżami kliniku għandu jinkludi evalwazzjoni għal sinjali fiżici ta ’ redistribuzzjoni tax- xaħam.
These increases of plasma concentrations of co-administered medicinal products could increase or prolong their therapeutic effect and adverse events (see sections 4.3 and 4.5).
Dawn iż- żidiet ta ’ konċentrazzjonjiet fil- plażma ta ’ prodotti mediċinali ko- somministrati jistgħu jżidu jew jipprolungaw l- effett terapewtiku u l- eventi avversi (ara sezzjoni 4. 3 u 4. 5).
The HMG-CoA reductase inhibitors simvastatin and lovastatin are highly dependent on CYP3A for metabolism, thus concomitant use of Kaletra with simvastatin or lovastatin is not recommended due to an increased risk of myopathy including rhabdomyolysis.
53 L- inibituri HMG- CoA reductase simvastatin u lovastatin jiddependu ħafna fuq CYP3A għal metaboliżmu, allura teħid flimkien ta ’ Kaletra ma ’ simavastatin jew lovastatin mhuwiex rakkomandat minħabba żieda fir- riskju ta ’ mijopatija li jinkludi rabdomilożi.
47 Other
Oħrajn
It does not reduce the risk of passing HIV to others through sexual contact or blood contamination.
Ma tnaqqasx ir- riskju li tgħaddi l- HIV lil ħaddieħor minn kuntatt sesswali jew kontaminazzjoni tad- demm.
4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l - effett farmaċewtiku tal- prodott
All interaction studies, when otherwise not stated, were performed using Kaletra capsules, which gives an approximately 20% lower exposure of lopinavir than the 200/ 50 mg tablets.
L- istudji kollha dwar l- effetti ta ’ mediċina fuq mediċina oħra, meta ma jingħadx il- kuntlarju, kienu magħmula bl- uzu tal- kapsuli Kaletra, li jagħtu esponiment ta ’ lopinavir li hu bejn wieħed u ieħor 20% inqas milli jagħtu l- pilloli ta ’ 200/ 50 mg.
Antiretroviral agents
54 Aġenti antiretrovirali
Didanosine: it is recommended that didanosine be administered on an empty stomach; therefore, didanosine may be co-administered with Kaletra tablets without food.
Didanosine: huwa rrikmandat illi didanosine jiġi amministrat fuq stonku vojt; allura, didanosine jista jingħata ma Kaletra mingħajr ikel.
Kaletra induces glucuronidation; therefore Kaletra has the potential to reduce zidovudine and abacavir plasma concentrations.
Kaletra jinduċi glukoronidazzjoni, allura Kaletra għandu l- potenzjal inaqqas il - konċentrazzjoni fil- plażma ta ’ zidovudine u abacavir.
In a study performed in healthy volunteers to explore the interaction between Kaletra tablets (400/ 100 mg twice daily) and efavirenz (600 mg once daily), efavirenz has been shown to decrease the lopinavir concentrations by 30 - 40%.
Fi studju magħmul f’ voluntiera f’ saħħithom sabiex jesploraw l- interazzjonijiet bejn il- pilloli ta ’ Kaletra (400/ 100 mg darbtejn kuljum) u efavirenz (600 mg darba kuljum), efavirenz ġie ppruvat li jnaqqas il - konċentrazzjoni ta ’ lopinvir bi 30- 40%.
When Kaletra tablet dosages were increased to 500/ 125 mg twice daily during co-administration of efavirenz 600 mg once daily in healthy volunteers, lopinavir pharmacokinetic parameters were similar to those obtained with Kaletra tablets 400/ 100 mg twice daily administered alone.
Meta, f’ voluntiera f’ saħħithom, id- dożaġġ tal- pilloli Kaletra ġie miżjud għal 500/ 125 mg darbtejn kuljum waqt li kienu qed jingħataw ukoll 600 mg efavirenz darba kuljum, il- parametri tal- farmakokinetika ta ’ lopinavir kienu simili għal dawk milħuqa bil- pilloli Kaletra ta ’ 400/ 100 mg darbtejn kuljum mgħotija waħedhom.
Therefore, the Kaletra tablets dosage should be increased to 500/ 125 mg twice daily when co-administered with efavirenz 600 mg once daily.
Għalhekk, id- dożaġġ tal- pilloli Kaletra għandu jiżdied għal 500/ 125 mg darbtejn kuljum meta jinghata flimkien ma ’ 600 mg efavirenz darba kuljum.
48 Similar pharmacokinetic interactions are expected for the co-administration of Kaletra tablets with the NNRTI nevirapine and with the protease inhibitors nelfinavir and amprenavir.
Interazzjonijiet farmakokinetiċi simili huma mistennija fil- ko- amministrazzjoni tal- pilloli ta ’ Kaletra ma NNRTI nevirapine u mal- inibituri tal- protease nelfinavir u amprenavir.
The same recommendations for monitoring apply in these cases of co-administration.
L- istess rakommandazzjonijiet ta ’ monitoraġġ jgħoddu għal dawn il- każijiet tal- ko- amministrazzjoni.
Co-administration with other HIV protease inhibitors (PIs):
Ko- amministrazzjoni ma inibituri oħra ta ’ HIV- protease (PIs):
Amprenavir: see recommendations described for Kaletra tablets co-administration with efavirenz.
Amprenavir: ara ir- rakommandazzjonijiet tal- ko- amministrazzjoni ma efavirenz
Therefore, concomitant administration of these medicinal products is not recommended.
55 ngħataw flimkien minghajr ebda żieda fl- effikaċja viroloġika.
Furthermore, concentrations of lopinavir do not appear to be affected when both medicinal products, Kaletra and indinivir, are combined, based on historical comparison with Kaletra alone.
Barra min hekk, il- konċentrazzjonijiet ta ’ lopinavirma jidhrux li huma affetwati meta ż- żewġ prodotti mediċinali, Kaletra u indinivir, huma kkombinati, ibbażat fuq paragun storiku ta ’ Kaletra mogħti waħdu.
Nelfinavir: see recommendations described for Kaletra tablets co-administration with efavirenz.
Nelfinavir: ara r- rakkomandazzjonijiet spjegati għal pilloli ta ’ Kaletra ko- amministrati ma efavirenz.
Kaletra co-administered with an additional 100 mg ritonavir twice daily resulted in an increase of lopinavir AUC and Cmin of 33% and 64%, respectively, as compared to Kaletra alone.
Kaletra ko- somministrat ma 100 mg addizjonali ta ’ ritonavir darbtejn kuljum irriżulta f’ żieda ta ’ AUC u Cmin ta ’ lopinavir ta ’ 33% u 64% rispettivament, meta mqabbel ma Kaletra waħdu.
49 Antiarrhythmics:
Antiarritmiċi:
(bepridil, systemic lidocaine and quinidine): concentrations may be increased when co-administered with Kaletra.
(bepridil, lidocaine sistemiku u quinidine): il- konċentrazzjonijiet jistgħu jiżdiedu meta dawn jiġu ko- somministrati ma Kaletra.
Anticoagulants: warfarin concentrations may be affected when co-administered with Kaletra.
Antikoagulanti: il - konċentrazzjonijiet ta ’ warfarin jistgħu jiġu affetwati meta ko- somministrati ma Kaletra.
Bupropion: in healthy volunteers, the AUC and Cmax of bupropion and of its active metabolite, hydroxybupropion, were decreased by about 50% when co-administered with lopinavir/ ritonavir capsules 400/ 100 mg twice daily at steady-state.
Dan l- effett jista ’ jkun ikkawżat mill- induzzjoni tal -
This effect may be due to induction of bupropion metabolism.
56 metaboliżmu ta ’ bupropion.
However, it is unknown whether the combination of lopinavir/ ritonavir causes a similar increase in trazodone exposure.
Minkejja dan, mhuwiex mgħaruf jekk it- taħlit ta ’ lopinavir ma ritonavir jikkawża żieda simili ta ’ esposizzjoni għal trazodone.
Digoxin: plasma concentrations of digoxin may be increased when co-administered with Kaletra.
Digoxin: konċentrazzjonijiet ta ’ digoxin fil- plażma jistgħu jogħlew meta ikun amministrat ma Kaletra.
The metabolism of pravastatin and fluvastatin is not
Riżultati minn studju t’ interazzjoni ma Kaletra u pravastatin żvelaw l- ebda interazzjoni klinikament sinifikanti.
50 dependent on CYP3A4, and interactions are not expected with Kaletra.
Il- metaboliżmu ta ’ pravastatin u fluvastatin ma jiddependix fuq CYP3A4, u interazzjonijiet mhumiex mistennija ma Kaletra.
Cyclosporin, sirolimus (rapamycin) and tacrolimus: concentrations may be increased when co-administered with Kaletra.
57 Cyclosporin, sirolimus (rapamycin) u tacrolimus: konċentrazzjonijiet jistgħu jiżdiedu meta ko - somministrati ma Kaletra. Monitoraġġ iżjed frekwenti tal- konċentrazzjoni terapewtika hija rakkomandata sakemm jistabbilixu ruħhom il- livelli fil- plażma ta ’ dawn il- prodotti.
More frequent therapeutic concentration monitoring is recommended until plasma levels of these products have been stabilised.
Dożi għolja ta ’ ketoconazole u itraconazole (> 200 mg/ ġurnata) mhumiex rakkomandati.
Ketoconazole and itraconazole: may have serum concentrations increased by Kaletra.
Clarithromycin: żidiet moderati fi clarithromycin AUC huma mistennija meta ko- somministrati ma Kaletra.
High doses of ketoconazole and itraconazole (> 200 mg/ day) are not recommended.
Għal pazjenti b’ indeboliment tal - kliewi jew tal- fwied tnaqqis fid- doża ta’ clarithromycin għandu jiġi kkunsidrat (ara sezzzjoni 4. 4).
Voriconazole: due to the potential for reduced voriconazole concentrations, co-administration of voriconazole and low dose ritonavir (100 mg twice daily) as contained in Kaletra should be avoided unless an assessment of the benefit/ risk to patient justifies the use of voriconazole.
Kaletra jista ’ jiġi ko- somministrat ma ’ buprenorphine mingħajr bżonn ta ’ aġġustament fid- doża.
Clarithromycin: moderate increases in clarithromycin AUC are expected when co-administered with Kaletra.
Ġie muri li Kaletra inaqqas il- konċentrazzjoni fil- plażma ta ’ methadone.
For patients with renal or hepatic impairment dose reduction of clarithromycin should be considered (see section 4.4).
Monitoraġġ tal - konċentrazzjoni fil- plażma ta ’ methadone huwa rakkomandat.
Buprenorphine: buprenorphine (dosed at 16 mg daily) co-administered with lopinavir/ ritonavir (dosed at 400/ 100 mg twice daily) showed no clinically significant interaction.
Kontraċettivi: livelli ta ’ ethinyl oestradiol naqsu meta kontraċċetivi orali ġew ko- amministrati ma Kaletra.
Kaletra can be co-administered with buprenorphine with no dose adjustment.
F’ każijiet meta Kaletra jiġi ko- amministrat ma kontraċettivi li fihom ethinyl estradiol (tkun xi tkun il- formulazzjoni eż.
Methadone:
Fuq il- bażi ta ’ din id- data, tnaqqis fid- doża ta ’ rifabutin ta ’ 75% (i. e.
Kaletra was demonstrated to lower plasma concentrations of methadone.
150 mg ġurnata iva u ġurnata 3 darbiet fil - ġimgħa) huwa irrikmandat meta somministrat ma ’ Kaletra.
Monitoring plasma concentrations of methadone is recommended.
Riduzzjoni ulterjuri għandha mnejn tkun neċċesarja.
Contraceptives: levels of ethinyl oestradiol were decreased when oestrogen-based oral contraceptives were co-administered with Kaletra.
Rifampicin: l- għoti ta ’ Kaletra flimkien ma ’ rifampicin m’ huwiex rakkommandat.
In case of co-administration of Kaletra with contraceptives containing ethinyl oestradiol (whatever the contraceptive formulation e. g. oral or patch), alternative methods of contraception are to be used.
Rifampicin mgħoti flimkien ma ’ Kaletra jikkawża tnaqqis kbir fil- konċentrazzjoni ta ’ lopinavir, u dan jista ’ min- naħa tiegħu inaqqas b’ mod sinifikanti l- effett terapewtiku ta ’ lopinavir.
Rifabutin: when rifabutin and Kaletra were co-administered for 10 days, rifabutin (parent substance and active 25-O-desacetyl metabolite) Cmax and AUC were increased by 3.5- and 5.7-fold, respectively.
Madanakollu, dan l- aġġustament tad- doża jista ’ jkun assoċjat ma ’ żiediet fl- ALT/ AST u ma ’ żieda fid- disturbi gastrointestinali.
On the basis of these data, a rifabutin dose reduction of 75% (i. e.
Għalhekk, dan l- għoti flimkien għandu jiġi evitat sakemm ma jkunx strettament neċessarju.
150 mg every other day or 3 times per week) is recommended when administered with Kaletra.
Jekk jiġi deċiż li dan l- għoti flimkien ma jistax jiġi evitat, doża miżjuda ta ’ Kaletra 400 mg/ 400 mg darbtejn kuljum tista ’ tingħata flimkien ma ’ rifampicin taħt monitoraġġ mill - qrib għas- sigurtà u mediċina terapewtika.
Further reduction may be necessary.
Id- doża ta ’ Kaletra għandha tiġi miżjuda ftit ftit biss wara li jkun inbeda jingħata rifampicin (ara sezzjoni 4. 4).
Rifampicin administered with Kaletra causes large decreases in lopinavir concentrations which may in turn significantly decrease the lopinavir therapeutic effect.
St John’ s wort: livelli fis- serum ta ’ lopinavir u ritonavir jistgħu jitnaqqsu bl- użu konkomitanti ta ’ preparazzjoni ta ’ ħxejjex St John’ s wort (Hypericum perforatum).
A dose adjustment of Kaletra 400 mg/ 400 mg twice daily has allowed compensating for the CYP 3A4 inducer effect of rifampicin.
Dan huwa minħabba li St. John’ s wort jinduċi enżimi li jimmetaboliżaw il- mediċini.
However, such a dose adjustment might be associated with ALT/ AST elevations and with increase in gastrointestinal disorders.
Preparazzjonjiet tal- ħxejjex li fihom St John’ s wort m’ għandhomx jiġu kkombinati ma lopinavir u ritonavir.
Therefore, this co-administration should be avoided unless judged strictly necessary.
Jekk pazjent ġja qed jieħu St John’ s wort, waqqaf St John’ s wort u jekk huwa possibli ikkonferma l- livelli virali.
If this co-administration is judged unavoidable, increased dose of Kaletra at 400 mg/ 400 mg twice daily may be administered with rifampicin under close safety and therapeutic drug monitoring.
Il- livelli ta ’ Lopinavir u ritonavir jistgħu jiżdiedu mat- twaqqif ta ’ St John’ s wort.
The Kaletra dose should be titrated upward only after rifampicin has been initiated (see section 4.4).
Id- doża ta ’ Kaletra għandha mnejn għandha
51 St John’ s wort: serum levels of lopinavir and ritonavir can be reduced by concomitant use of the herbal preparation St John’ s wort (Hypericum perforatum).
L- effett induċenti jista ’ jibqa jippersisti għall 2 ġimgħat wara ’ t- twaqqif mit- trattament bi St John’ s wort (ara sezzjoni 4. 3).
This is due to the induction of drug metabolising enzymes by St John’ s wort.
Midazolam: midazolam huwa fil- biċċa l- kbira tiegħu metabolizzat b’ CYP3A4.
Herbal preparations containing St John’ s wort should therefore not be combined with lopinavir and ritonavir.
L- għoti tiegħu flimkien ma ’ Kaletra jista ’ jikkaġuna żieda kbira fil- konċentrazzjoni ta ’ dan il- benzodiazepine.
If a patient is already taking St John’ s wort, stop St John’ s wort and if possible check viral levels.
Studju li sar fuq 14 - il voluntier b’ saħħithom b’ taħlita ta ’ fenotip wera żieda ta ’ madwar 13 - il darba aktar ta ’ AUC meta ingħata medazolam mill- ħalq u żieda ta ’ madwar 4 darbiet aktar meta ingħata midazolam parenterali.
The dose of Kaletra may need adjusting.
Għalhekk, Kaletra m’ għandux jingħata ma ’ midazolam mittieħed mill- ħalq (ara sezzjoni 4. 3), u wieħed irid joqgħod attent meta jkun hemm it- teħid flimkien ta ’ Kaletra u midazolam parenterali.
The inducing effect may persist for at least 2 weeks after cessation of treatment with St John’ s wort (see section 4.3).
Għandu jiġi kkunsirat aġġustament fid- doża ta ’ midazolam, speċjalment jekk tkun ingħatat aktar minn doża waħda ta ’ midazolam.
Midazolam: midazolam is extensively metabolised by CYP3A4.
Effetti ikbar jistgġu ikunu mistennija fluticasone propionate ikun inalat.
Co-administration with Kaletra may cause a large increase in the concentration of this benzodiazepine.
Budesonide.
A phenotyping cocktail study in 14 healthy volunteers showed an increase of AUC by about 13 fold with oral midazolam and an increase by about 4 fold with parenteral midazolam.
Konsekwentement, amministrazzjoni ta ’ Kaletra u dawn il- glikokortikojdi flimkiem m’ hijiex irrikmandata sakemm il- benefiċċju potenzjali tat - trattament jegħleb it- riskju ta ’ effetti sistemiċi ta’ kortikosterojdi (ara sezzjoni 4. 4).
Therefore, Kaletra should not be co-administered with orally administered midazolam (see section 4.3), whereas caution should be used with co-administration of Kaletra and parenteral midazolam.
Tnaqqis fid- doża tal - glukokortikojd għandha tiġi kkunsidrata ma monitoraġġ attent ta ’ effetti lokali jew sistemiċi, jew bdil għal glukokortikojd li m’ huwiex sustanza tal- CYP3A4 (eż.
If Kaletra is co-administered with parenteral midazolam, it should be done in an intensive care unit (ICU) or similar setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/ or prolonged sedation.
Barra minn hekk f’ każi ta ’ sintomi ta ’ rtirar mill- glukokortikosterojdi, tnaqqis progressiv tad- doża fuq żmien twil jista ’ jkun bżonnjuż.
Dosage adjustment for midazolam should be considered especially if more than a single dose of midazolam is administered.
L- effetti ta ’ esposizzjoni sistemika għolja għal fluticasone fuq livelli ta ’ ritonavir fil- plażma għadhom mhux magħrufa.
Fluticasone propionate (interaction with ritonavir): in a clinical study where ritonavir 100 mg capsules twice daily were co − administered with 50 μ g intranasal fluticasone propionate (4 times daily) for seven days in healthy subjects, the fluticasone propionate plasma levels increased significantly, whereas the intrinsic cortisol levels decreased by approximately 86% (90% confidence interval 82 − 89%).
Ibbażżat fuq profili metaboliċi magħrufa, mhumiex mistennija interazzjonijiet klinikament sinifikanti bejn Kaletra u fluvastatin, dapsone, trimethoprim/ sulfamethoxazole, azithromycin jew fluconazole.
Greater effects may be expected when fluticasone propionate is inhaled.
M’ hemm l- ebda data mill- użu ta ’ Kaletra f’ nisa tqal.
A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (eg beclomethasone).
Studji fl- animali urew tossiċita riproduttiva (ara sezzjoni 5. 3).
Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period.
Ir- riskju potenzjali għall- bnedmin mhuwiex magħruf.
The effects of high fluticasone systemic exposure on ritonavir plasma levels is yet unknown.
Kaletra m’ għandux jintuża waqt it - tqala sakemm m’ hemmx bżonn ċar ta ’ dan.
Based on known metabolic profiles, clinically significant interactions are not expected between Kaletra and fluvastatin, dapsone, trimethoprim/ sulfamethoxazole, azithromycin or fluconazole.
Mhuwiex magħruf jekk dan il- prodott mediċinali huwiex mneħħi fil- ħalib tas- sider uman.
4.6 Pregnancy and lactation
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
There are no data from the use of Kaletra in pregnant women.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
Studies in animals have shown reproductive toxicity (see section 5.3).
Il- pazjenti għandhom jiġu infurmati li ġew irrappurtati każi ta ’ nawseja waqt il- kura b’ Kaletra (ara sezzjoni 4. 8).
The potential risk for humans is unknown.
59 4. 8 Effetti mhux mixtieqa
Kaletra should not be used during pregnancy unless clearly necessary.
F’ xi ftit studji, Kaletra kien użat ikkombinat ma ’ efavirenz jew nevirapine.
It is not known whether this medicinal product is excreted in human milk.
L- iżjed event avers li huwa assoċjat mat- terapija b’ Kaletra kienet diareja li ġeneralment kienet ta ’ severita ħafifa għal moderata.
HIV infected women must not breast-feed their infants under any circumstances to avoid transmission of HIV.
Twaqqif minħabba eventi avversi kien 4. 5% (f’ pazjent li qatt ma ħadu dan it- trattament) u 9% (pazjenti b’ esperjenza) f’ perjodu ta ’ 48 ġimgħa.
4.7 Effects on ability to drive and use machines
(ara sezzjoni 4. 4: sezzjoni pancreatite u żieda fil- lipidi).
No studies on the effects on the ability to drive and use machines have been performed.
Żieda fi CPK, mialġja, mijożite, u rarament, rabdomilożi kienu rrapurtati b’ inibituri tal- protease, partikolarment ikkombinati ma ’ inibituri nucleoside reverse transcriptase.
Patients should be informed that nausea has been reported during treatment with Kaletra (see section 4.8).
It- terapija antiretrovirali kkombinata ġiet assoċjata ma ’ problemi metaboliċi mhux normali bħal ipertrigliċeridemija, iperkolosterolemija, reżistenza għall- insulina, ipergliċemija u iperlactataemija (ara sezzjoni 4. 4).
52 4.8 Undesirable effects
Reazzjonijiet avversi:
The safety of Kaletra has been investigated in 612 patients in Phase II/ III clinical trials, of which 442 have received a dose of 400/ 100 mg twice daily.
Ir- reazzjonjiet avversi li jmiss ta ’ intensita moderata għal severa b’ relazzjoni possibli jew probabbli għal Kaletra ġew irrappurtati.
In some studies, Kaletra was used in combination with efavirenz or nevirapine.
Ir- reazzjonjiet avversi huma murija bi klassi tas- sistema ta ’ l- organi.
The most common adverse reaction associated with Kaletra therapy was diarrhoea and was generally of mild to moderate severity.
60 Effetti mhux mixtieqa fi studji kliniċi f’ pazjenti adulti
Discontinuation due to adverse reactions was 4.5% (naïve patients) and 9% (experienced patients) over a 48 week period.
Infezzjonijiet u infestazzjonijiet
It is important to note that cases of pancreatitis have been reported in patients receiving Kaletra, including those who developed hypertriglyceridaemia.
Mhux komuni Mhux komuni
Increased CPK, myalgia, myositis, and rarely, rhabdomyolysis have been reported with protease inhibitors, particularly in combination with nucleoside reverse transcriptase inhibitors.
Otite medja, bronkite, sinusite, furunkulożi, infezzjoni batterika, infezzjoni virali
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
Neoplażmi beninni, malinni u dawk mhux speċifikati (inklużi ċesti u polipi)
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
Neoplażma beninja tal- ġilda, cyst
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
Disturbi tad- demm u tas- sistema limfatika
Adult patients
Mhux komuni
Adverse reactions:
Mhux komuni
The following adverse reactions of moderate to severe intensity with possible or probable relationship to Kaletra have been reported.
Ipogonadiżmu maskili, Sindromu ta ’ Cushing, ipotirojdiżmu
The adverse reactions are displayed by system organ class.
Disturbi fil- metaboliżmu u n - nutrizzjoni
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness: very common > 1/ 10, common > 1/ 100 ,< 1/10, uncommon > 1/ 1000, < 1/ 100.
Nuqqas ta ’ vitamini, deidratazzjoni, edema, żieda fl- aptit, acidożi laktika, obesita ’, anoressija, dijabete mellitus
53 Undesirable effects in clinical studies in adult patients Infections and infestations
Disturbi psikjatriċi
Otitis media, bronchitis, sinusitis, furunculosis, bacterial infection, viral infection
Ħolm mhux normali, aġitazzjoni, ansjeta ’, konfużjoni, depressjoni, diżkinesija, instabbilita emozzjonali, tnaqqis fil- libido, nervożiżmu, ħsieb mhux normali
Neoplasms benign, malignant and unspecified (including cysts and polyps)
Disturbi fis- sistema nervuża
Skin benign neoplasm, cyst
Uġigħ ta ’ ras, paresteżija
Blood and lymphatic system disorders
Disturbi fl- għajnejn
Anaemia, leucopenia and lymphadenopathy
Viżjoni mhux normali, problemi fl- għajn
Endocrine disorders
Tisfir tal- widnejn