qanastek/EMEA-V3 huggingface dataset:
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 (3 capsules) twice daily.
Is- sigurta ta ’ Kaletra ġiet investigata fi 612 pazjent fi studji kliniċi fażi II/ III, fejn 442 ingħataw doża ta ’ 400/ 100 mg (3 kapsuli) darbtejn kuljum.
In some studies, Kaletra was used in combination with efavirenz or nevirapine.
F’ xi ftit studji, Kaletra kien użat ikkombinat ma ’ efavirenz jew nevirapine.
The most common adverse event associated with Kaletra therapy was diarrhoea and was generally of mild to moderate severity.
L- iżjed event avers li huwa assoċjat mat- terapija b’ Kaletra kienet diareja li ġeneralment kienet ta ’ severita ħafifa għal moderata.
Discontinuation due to adverse reactions was 4.5% (naïve patients) and 9% (experienced patients) over a 48 week period.
Twaqqif minħabba avvenimenti avversi kien 4. 5% (f’ pazjent li qatt ma ħadu dan it- trattament) u 9% (pazjenti b’ esperjenza) f’ perjodu ta ’ 48 ġimgħa.
It is important to note that cases of pancreatitis have been reported in patients receiving Kaletra, including those who developed hypertriglyceridaemia.
Huwa importanti li ninutaw li każi ta ’ pankreatite ġew rappurtati f’ pazjenti li qed jieħdu Kaletra, inklużi dawk li żvillupaw ipertrigliċeridemija.
Furthermore, rare increases in PR interval have been reported during Kaletra therapy (see section 4.4: sections pancreatitis and lipid elevations).
(ara sezzjoni 4. 4: sezzjoni pancreatite u żieda fil- lipidi).
Increased CPK, myalgia, myositis, and rarely, rhabdomyolysis have been reported with protease inhibitors, particularly in combination with nucleoside reverse transcriptase inhibitors.
Żieda fi CPK, mialġja, mijożite, u rarament, rabdomilożi kienu rrapurtati b’ inibituri tal- protease, partikolarment ikkombinati ma ’ inibituri nucleoside reverse transcriptase.
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).
12 It- terapija antiretrovirali kkombinata ġiet assoċjata ma redistribuzzjonji tax- xaħam (lipodistrofija) f’ pazjenti bl- HIV, li jinkludi t- telf ta ’ xaħam periferali u tal- wiċċ, żieda fix- xaħam intra- addominali u vixxerali, ipertrofija tal- mammarja u akkumulazzjoni dorsoċervikali ta ’ xaħam (buffalo hump).
11 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).
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).
F’ pazjenti infettati bl- HIV u b’ defeċjenza immunitarja serja ħafna fiż- żmien ta ’ l- introduzzjoni tat - terapija antiretrovirali kombinata (CART), reazzjoni infjammatorja għal infezzjonijiet mhux sintomatiċi jew residqali opportuniastiċi tista tiżviluppa (Ara sezzjoni 4. 4).
Adult patients
Pazjenti Adulti
Adverse reactions:
Reazzjonijiet avversi:
The following adverse reactions of moderate to severe intensity with possible or probable relationship to Kaletra have been reported.
Ir- reazzjonjiet avversi li jmiss ta ’ intensita moderata għal severa b’ relazzjoni possibli jew probabbli għal Kaletra ġew irrappurtati.
The adverse reactions are displayed by system organ class.
Ir- reazzjonjiet avversi huma murija bi klassi tas- sistema ta ’ l- organi.
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.
Fil- klassi tas- sistema ta ’ l- organi ir- reazzjonjiet avversi huma mniżżla f’ ordni ta ’ frekwenza, u inġabbru fit- titli li jmiss: komuni ħafna > 1/ 10, komuni > 1/ 100, < 1/ 10, mhux komuni > 1/ 1000, < 1/ 100.
Undesirable effects in clinical studies in adult patients Infections and infestations
13 Effetti mhux mixtieqa fi studji kliniċi f’ pazjenti adulti
Otitis media, bronchitis, sinusitis, furunculosis, bacterial infection, viral infections
Otite medja, bronkite, sinusite, furunkulożi, infezzjoni batterika, infezzjoni virali
Skin benign neoplasm, cyst
Neoplażma beninja tal- ġilda, cyst
Anaemia, leucopenia and lymphadenopathy
Anemija, lewkopenija u limfadenopatija
Hypogonadism male, Cushing syndrome, hypothyroidism
Ipogonadiżmu maskili, Sindromu ta ’ Cushing, ipotirojdiżmu
Metabolic and nutritional disorders
Disturbi fil- metaboliżmu u n - nutrizzjoni
Uncommon
Mhux komuni Komuni
Avitaminosis, dehydration, oedema, increased appetite, lactic acidosis, obesity, anorexia, diabetes, mellitus, hyperglycaemia, hypocholesteremia
Nuqqas ta ’ vitamini, deidratazzjoni, edema, żieda fl- aptit, acidożi laktika, obesita ’, anoressija, dijabete mellitus
Psychiatric disorder
Disturbi psikjatriċi
Insomnia
Nuqqas ta ’ irqad
Abnormal dreams, agitation, anxiety, confusion, depression, dyskenesia, emotional liability, decreased libido, nervousness, abnormal thinking
Ħolm mhux normali, aġitazzjoni, ansjeta ’, konfużjoni, depressjoni, diżkinesija, instabbilita emozzjonali, tnaqqis fil- libido, nervożiżmu, ħsieb mhux normali
Headache, parathesia
Uġigħ ta ’ ras, paresteżija
Dizziness, amnesia, ataxia, encephalopathy, facial paralysis, hypertonia, neuropathy, peripheral neuritis, somnolence, tremor, taste perversion, migraine, extrapyramidal syndrome
Sturdament, amneżija, ataksja, enkefalopatija, paraliżi tal- wiċċ, hypertonja, neuropatija, nevrite periferali, somnolenza (irqad żejjed), rogħda, perverżjoni tat- togħma, emikranja, simdrome estrapiramidali
Eye disorders Ear and labyrinth disorders Cardiac disorders Vascular disorders
Disturbi fil- widnejn u fis - sistema labirintika
Uncommon Uncommon Uncommon Uncommon
Palpitazzjoni, ilma fil- pulmun, Infart mijokardijaku1
Abnormal vision, eye disorder Tinnitus Palpitation, lung oedema, myocardial infarct1 Hypertension, thrombophebitis, vasculitis, varicose vein, deep thrombophlebitis, vascular disorder
Ipertensjoni, tromboflebite, vaskulite, vini varikożi, tromboflebite, problemi vaskulari
Dyspnoea, rhinitis, cough increased
Qtugħ ta ’ nifs, riħ; żieda fis- sogħla
12 Gastrointestinal disorders
Disturbi Gastro- intestinali
Nausea, vomiting, abdominal pain, abnormal stools, dyspepsia, flatulence, gastrointestinal disorder
Nawsja, vomtar, uġiegħ addominali, skart tal - ġisem mhux normali, ulċera fl- istonku, gass, problemi gastrointestinali
Abdomen enlarged, constipation, dry mouth, dysphagia, enterocolitis, eructation, oesophagitis, faecal incontinence, gastritis, gastroenteritis, haemorrhagic colitis, mouth ulcerations, pancreatitis2, sialadenitis, stomatitis, ulcerative stomatitis, periodontitis
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
Cholecystitis, hepatitis, hepatomegaly, liver fatty deposit, liver tenderness
Koleċistite, epatite, epatomegalite, depositu tax- xaħam fil- fwied, sensittivita tal- fwied
Rash, lipodystrophy, acne
Raxx, lipodistrofija, akne
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
Musculoskeletal and connective tissue disorder
Disturbi muskolu- skeltrali u tal - connective tissue
Arthralgia, arthrosis, myalgia, back pain, joint disorder
Artralġja, artrożi, mialġja, uġigħ tad- dahar, Disturbi fil- ġogi
Kidney calculus, urine abnormality, albuminuria, hypercalcinuria, hyperuricemia
Ġebla fil- kliewi, urina mhux normali, albuminurja, iperkalċinurja, iperuriċemija
Abnormal ejaculation, breast enlargement, gynecomastia, impotence, menorrhagia
Ejakulazzjoni mhux normali, żieda fid- daqs tal- sider, ġinekomastja
General disorders and administration site conditions
Disturbi ġenerali u kondizzjonijiet ta 'mnejn
Common
Momuni
Asthenia, pain
Astenja, uġigħ
Uncommon
jingħata
Chest pain, chest pain substernal, chills, fever, flu syndrome, malaise, peripheral oedema, drug interactions
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,
Investigations
Komuni ħafna
Very common (Grade 3 or 4)
(Grad 3 jew 4) żieda GGT Komuni
Common (Grade 3 or 4)
(Grad 3 jew 4)
Increased glucose, increased amylase, increased SGOT/ AST, increased SGPT/ ALT, liver function tests abnormal
żieda fil- glukożju, żieda fl- amilase, żieda
1 2
SGOT/ AST, żieda SGPT/ ALT, testijiet tal -
This event had a fatal outcome
funzjoni tal- fwied mhux normali
Uncommon
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
Decreased glucose tolerance, weigh gain, weight loss, increased bilirubin, hormone level altered, lab test abnormal
15 Pazjenti Pedjatriċi Fit- tfal ta ’ sentejn u ikbar, in- natura tal- profil ta ’ sigurta ’ huwa simili għal dak fl- adulti.
See Section 4.4 pancreatitis and lipids
Effetti mhux mixtieqa fi studji kliniċi f’ pazjenti pedjatriċi Infezzjonijiet u infestazzjonijiet Komuni
13 Paediatric patients
Infezzjoni virali
In children 2 years of age and older, the nature of the safety profile is similar to that seen in adults.
Disturbi fis- sistema nervuża Komuni Disturbi Gastro- Intestinali Komuni
Undesirable effects in clinical studies in paediatric patients Infections and infestations
Perverżjoni tat- togħma Stitikezza, vomtar, pankreatite *
Nervous system disorders
Disturbi fil- fwied u fil- marrara
Taste perversion
Tkabbir fid- daqs tal- fwied
Gastrointestinal disorders Hepatobiliary disorders Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Common Common Common
Komuni
Constipation, vomiting, pancreatitis Hepatomegaly Rash, Dry skin
Raxx, ġilda niexfa
Common (Grade 3 or 4)
Komuni (Grad 3 jew 4)
Increased activated partial thromboplastin time, decreased haemoglobin, decreased platelets, increased sodium, increased potassium, increased calcium, increased bilirubin, increased SGPT/ ALT, increased SGOT/ AST, increased total cholesterol, increased amylase, increased uric acid, decreased sodium, decreased potassium, decreased calcium, decreased neutrophils
Żieda fil- ħin parzjali attivat tat - tromboplastina, tnaqqis fl- emoglobina, tnaqqis fil- pjastrini, żieda fis- sodju, żieda fil - potassju, żieda fil- kalċju, żieda fil- bilirubin, żieda fi SGPT/ ALT, żieda fi SGOT/ AST, żieda fil- kolosterol total, żieda fl- amilase, żieda fl- aċidu uriku, tnaqqis fis- sodju, tnaqqis fil- potassju, tnaqqis fil- kalċju, tnaqqis fin - newtrofili
*see section 4.4: pancreatitis and lipids
* ara sezzjoni 4. 4
Post marketing experience
Esperjenza wara li l- prodott tpoġġa fuq is- suq
Hepatitis, and rarely jaundice, have been reported in patients on Kaletra therapy in the presence or absence of identifiable risk factors for hepatitis.
Epatite, u rarament suffejra, kienu rrapurtati f’ pazjenti fuq terapija ta ’ Kaletra fil- preżenza jew assenza ta ’ fatturi ta ’ riskju identifikabli għall- epatite.
Stevens-Johnson syndrome and erythema multiforme have been reported.
Is- sindromi ta ’ Stevens- Johnsons u eritema multiforme ġew ukoll irrapurtati.
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART).
Każijiet ta ’ ostjonekrożi ġew irrappurtati, partikolarment f’ pazjenti b’ fatturi ta ’ riskju li huma ġeneralment magħrufa, HIV avvanzat jew esposizzjoni fuq tul ta ’ żmien għal terapija antiretrovirali kombinata (CART).
The frequency of this is unknown (see section 4.4).
Il- frekwenza ta ’ dan m’ hijiex magħrufa (ara sezzjoni 4. 4).
To date, there is limited human experience of acute overdose with Kaletra.
Preżentement, hemm esperjenza limitata fil- bnedmin b’ doża qawwija u eċċessiva ta ’ Kaletra.
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.
The signs of toxicity observed in mice, rats or dogs included decreased activity, ataxia, emaciation, dehydration and tremors.
Is- sinjali ta ’ tossiċita osservati fil- ġrieden, firien jew klieb jinkludu tnaqqis fl- attività, ataksja, għelubija esaġerata, diżidratazzjoni u rogħda.
There is no specific antidote for overdose with Kaletra.
M’ hemm l- ebda antidotu speċifiku għal doża eċċessiva b’ Kaletra.
Treatment of overdose with Kaletra is to consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
It- trattament ta’ doża eċċessiva b ’ Kaletra għandu jikonsisti minn miżuri ġenerali ta ’ support li jinkludi monitoraġġ tas- sinjali vitali u osservazzjoni ta ’ l- istat kliniku tal- pazjent.
If indicated, elimination of unabsorbed active substance is to be achieved by emesis or gastric lavage.
Jekk indikat, eliminazzjoni ta ’ sustanza attiva mhux assorbita għandu jiġi milħuq b’ emeżi jew taħsila gastrika.
Administration of activated charcoal may also be used to aid in removal of unabsorbed active substance.
16 jintweża biex jgħin fit- tneħħija tas- sustanza attiva mhux attivata.
Since Kaletra is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.
Minħabba li Kaletra jingħaqad ħafna mal- proteini, d- dijaliżi tista ma tkunx ta ’ benefiċċju fit- tneħħija tas- sustanza attiva.
Pharmaco-therapeutic group: protease inhibitor, ATC code:
Kategorija farmakoterapewtika: inibitur protejaż, Kodiċi ATC:
Lopinavir provides the antiviral activity of Kaletra.
Lopinavir jipprovdi l- attività antivirali ta ’ Kaletra.
Lopinavir is an inhibitor of the HIV-1 and HIV-2 proteases.
Lopinavir huwa inibitur tal- proteases ta ’ HIV- 1 u HIV- 2.
Inhibition of HIV protease prevents cleavage of the gag-pol polyprotein resulting in the production of immature, non-infectious virus.
Inibizjoni ta ’ HIV protease jipprevjeni il- qtugħ tal- poliproteina gag - pol, u b’ hekk jirriżulta fil- produzzjoni ta ’ virus immatur, mhux infettiv.
Effects on the electrocardiogram:
Effetti fuq l- elettrokardjogramm:
QTcF interval was evaluated in a randomised, placebo and active (moxifloxacin 400 mg once daily) controlled crossover study in 39 healthy adults, with 10 measurements over 12 hours on Day 3.
L- intervall QTcF ġie evalwat fi studju tat- tip crossover li sar b’ ordni addoċċ li kien ikkontrollat mill- plaċebo u attiv (moxifloxacin 400mg darba kuljum) li sar fuq 39 pazjent f’ saħħtu, fejn f’ Ġurnata 3, ġie mkejjel 10 darbiet fi 12- il siegħa.
The maximum mean (95% upper confidence bound) differences in QTcF from placebo were 3.6 (6.3) and 13.1(15.8) for 400/ 100 mg twice daily and supratherapeutic 800/ 200 mg twice daily LPV/ r, respectively.
Id- differenzi medji massimi (95% upper confidence bound) fil- QTcF mill- plaċebo kienu ta ’ 3. 6 (6. 3) u 13. 1 (15. 8) fil- każ fejn ingħatat doża ta ’ 400/ 100 mg LPV/ r darbtejn kuljum u 800/ 200 mg LPV/ r aktar milli jingħata fit- terapija darbtejn kuljum, rispettivament.
The induced QRS interval prolongation from 6 ms to 9.5 ms with high dose lopinavir/ ritonavir (800/ 200 mg twice daily) contributes to QT prolongation.
It- titwil ikkawżat ta ’ l- intervall QRS minn 6 ms għal 9. 5 ms b’ doża għolja ta ’ lopinavir/ ritonavir (800/ 200 mg darbtejn kuljum) jikkontribwixxi għat- titwil fil QT.
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.
No subject experienced an increase in QTcF of ≥ 60 msec from baseline or a QTcF interval exceeding the potentially clinically relevant threshold of 500 msec.
L- ebda suġġett ma ġarrab żieda fil- QTcF li hi ≥ 60 msec mil- linja bażi jew intervall QTcF li jeċċedi l- limitu li hu potenzjalment klinikament rilevanti ta ’ 500 msec.
Modest prolongation of the PR interval was also noted in subjects receiving lopinavir/ ritonavir in the same study on Day 3.
Titwil mhux kbir ta ’ l- intervall PR ġie nnutat ukoll fl- istess studju f’ Ġurnata 3, f’ suġġetti li kienu qegħdin jirċievu lopinavir/ ritonavir.
The mean changes from baseline in PR interval ranged from 11.6 ms to 24.4 ms in the 12 hour interval post dose.
Fl- intervall ta ’ 12- il siegħa ta ’ wara li ngħatat id- doża, it- tibdil medju mil- linja bażi fl- intervall PR varja minn 11. 6 ms sa 24. 4 ms.
Maximum PR interval was 286 msec and no second or third degree heart block was observed (see section 4.4).
L- intervall PR massimu kien ta ’ 286 msec u ma ġie osservat l- ebda imblukkar tal- qalb tat- tieni jew tat- tielet grad (ara sezzjoni 4. 4).
Antiviral activity in vitro: the in vitro antiviral activity of lopinavir against laboratory and clinical HIV strains was evaluated in acutely infected lymphoblastic cell lines and peripheral blood lymphocytes, respectively.
Attività antivirali in vitro: l- attività antivirali in vitro ta ’ lopinavir kontra razzi ta ’ l- HIV tal- laboratorju u kliniċi kienet evalwata f’ linji ta ’ ċelluli limfoblastiċi infettati b’ mod akut, u limfoċiti tad- demm periferali, rispettivament.
In the absence of human serum, the mean IC50 of lopinavir against five different HIV-1 laboratory strains was 19 nM.
Fl- assenza ta ’ serum uman, il- medja IC50 ta ’ lopinavir kontra ħames razzi differenti ta ’ HIV- 1 tal- laboratorju kien 19 nM.
In the absence and presence of 50% human serum, the mean IC50 of 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.
In the absence of human serum, the mean IC50 of lopinavir was 6.5 nM against several HIV-1 clinical isolates.
Fl- assenza ta ’ serum uman, il- medja IC50 ta ’ lopinavir kien 6. 5 nM kontra bosta iżolati kliniċi HIV- 1.
In vitro selection of resistance:
Selezzjoni ta ’ reżistenza in vitro:
HIV-1 isolates with reduced susceptibility to lopinavir have been selected in vitro.
Iżolati HIV- 1 b’ suxxettibilità mnaqqsa għal lopinavir ġew mgħażula in vitro.
HIV-1 has been passaged in vitro with lopinavir alone and with lopinavir plus ritonavir at concentration ratios representing the range of plasma concentration ratios observed during Kaletra therapy.
HIV- 1 ġie mogħddi in vitro ma ’ lopinavir waħdu u ma ’ lopinavir flimkien ma ritonavir f’ konċentrazzjonijiet proporzjonati,; i jirrapreżentaw medda ta ’ konċentrazzjonijiet proporzjonati tal- plażma osservati waqt it- terapija b’ Kaletra.
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.
Analiżi ġenotipiku u fenotipiku ta ’ virus selezzjonati b’ dan il- passaġġ jisuġġerixxu li l - preżenza ta ’ ritonavir, f’ dawn il- konċentrazzjonijiet proporzjonati, ma jinfluenzax b ’ modd miżurabli is - selezzjoni ta ’ virus reżistenti għal lopinavir.
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.
Kollox ma kollox, il- karatterizazzjoni in vitro ta ’ cross - 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:
17 Analiżi ta ’ reżistenza f’ pazjenti li qatt ma esponew ruħhom qabel għal ARV:
In a Phase II study (M97-720) through 204 weeks of treatment, genotypic analysis of viral isolates was successfully conducted in 11 of 16 patients with confirmed HIV RNA above 400 copies/ ml revealed no primary or active site mutations in protease (amino acids at positions 8, 30, 32, 46, 47, 48, 50, 82, 84 and 90) or protease inhibitor phenotypic resistance.
Fi studju tat- tieni fażi (M98- 720) matul 204 ġimgħat ta ’ trattament, analiżi ġenotipika ta ’ virus iżolati kien mwettaq b’ suċċess fi 11 minn 16- il pazjent ikkonfermati b’ HIV RNA ogħla minn 400 kopji/ ml, ma irrivelaw l- ebda mutazzjonjiet primarji jew tas- sit attiv fi protease (amino aċidi fil- posizzjonijiet 8, 30, 32, 46, 47, 48, 50, 82, 84 u 90) jew resistenza fenotipika inibitorja tal- protease.
In a Phase III study (M98-863) of 653 patients randomised to receive stavudine plus lamivudine with either lopinavir/ ritonavir or nelfinavir, 113 nelfinavir-treated subjects and 74 lopinavir/ ritonavir- treated subjects had an HIV RNA above 400 copies/ ml while on treatment from Week 24 through Week 96.
Fi studju tat- tielet fażi (M98- 863) minn 653- il pazjenti randomi biex jirċievu stavudine u lamivudine ma lopnivar/ ritonavir jew nelfinavir, 113 suġġetti trattati b’ nelfinavir u 74 suġġetti trattati b’ lopinavir/ ritonavir kellhom HIV RNA ogħla minn 400 kopji/ ml waqt it- trattament mill- 24 ġimgħa għas- 96 ġimgħa.
Of these, isolates from 96 nelfinavir-treated subject and 51 lopinavir/ ritonavir-treated
Minn dawn, iżolati minn 96 suġġetti trattati b’ nelfinavir u 51minn suġġetti trattati b’ lopinavir/ ritonavir setgħu jiġu amplifikati għal- istudju fuq reżistenza.
Resistance to nelfinavir, defined as the presence of the D30N or L90M mutation in protease, was observed in 41/ 96 (43%) subjects.
Reżistenza għal nelfinavir, definita bħala il- preżenza ta ’ mutazzjoni D30N jew L90M kienet osservata f ’ 41/ 96 (43%) tas- suġġetti.
Resistance to lopinavir, defined as the presence of any primary or active site mutations in protease (see above), was observed in 0/ 51 (0%) subjects.
Reżistenza għal lopinavir, definita bħala l- preżenza ta ’ mutazzjonijiet tal- protease primarji jew tas- sit attiv (ara hawn fuq), kienet osservata f’ 0/ 51 (0%) tas- suġġetti.
Lack of resistance to lopinavir was confirmed by phenotypic analysis.
Nuqqas ta ’ reżistenza għal lopinavir kienet ikkonfermata minn analiżi fenotipika.
Analysis of resistance in PI-experienced patients:
Analiżi tar- reżistenza f’ pazjenti b’ esperjenza ta ’ PI:
The selection of resistance to lopinavir in patients having failed prior protease inhibitor therapy was characterised by analysing the longitudinal isolates from 19 protease inhibitor-experienced subjects in 2 Phase II and one Phase III studies who either experienced incomplete virologic suppression or viral rebound subsequent to initial response to Kaletra and who demonstrated incremental in vitro resistance between baseline and rebound (defined as emergence of new mutations or 2-fold change in phenotypic susceptibility to lopinavir).
Dawn kienu esperjenzaw suppressjoni viroloġika mhux kompluta jew kellhom virus li ma baqax suppressat wara reazzjoni tal- bidu għal Kaletra jew ukoll li wrew reżistenza inkrementali in vitro bejn il- linja bażi u definit bħala t- tfaċċar ta ’ mutazzjonijiet ġodda jew bidla għal suxxettibilità fenotipika dopjja għal lopinavir).
Incremental resistance was most common in subjects whose baseline isolates had several protease inhibitor-associated mutations, but < 40-fold reduced susceptibility to lopinavir at baseline.
Reżistenza inkrementali kienet l- iktar komuni f’ suġġetti li l- iżolati tal- linja bażi tagħhom kellhom ħafna mutazzjonijiet assoċjati ma ’ inibituri tal- proteases, imma b ’ < 40 inqas suxxettibilità għal lopinavir fil- linja bażi.
Mutations V82A, I54V and M46I emerged most frequently.
Mutazzjonijiet V82A, I54V u M461 kienu l- iktar li ħarġu.
Mutations L33F, I50V and V32I combined with I47V/ A were also observed.
Mutazjonijiet L33F, I50V u V321 ikkombinati ma 147V/ A kienu wkoll osservati.
The 19 isolates demonstrated a 4.3-fold increase in IC50 compared to baseline isolates (from 6.2- to 43-fold, compared to wild-type virus).
Id- 19- il iżolati wrew żieda ta ’ 4. 3- il darba f’ IC50 meta mqabbla ma iżolati tal- linja bażi (minn 6. 2- il darba għal 43- il darba, mqabbla ma virus tat - tip mhux kkultivat).
Genotypic correlates of reduced phenotypic susceptibility to lopinavir in viruses selected by other protease inhibitors.
Korrelati ġenotipiċi ta ’ suxxettibilità fenotipika mnaqqsa għal lopinavir fil- virus selezzjonati minn inibituri oħra tal- protease.
The in vitro antiviral activity of lopinavir against 112 clinical isolates taken from patients failing therapy with one or more protease inhibitors was assessed.
L- attività antivirali in vitro ta ’ lopinavir kontra 112 iżolati klinici meħuda minn pazjenti li kienu qed ifallu t- terapija b’ wieħed jew iżjed mill- inibituri tal- protease kienu analizzati.
Within this panel, the following mutations in HIV protease were associated with reduced in vitro susceptibility to lopinavir:
F’ dan il- kwadru, il- mutazzjonijiet f’ HIV protease kienu assoċjati bi tnaqqis ta ’ suxxettibilità in vitro għal lopinavir:
L10F/ I/ R/ V, K20M/ R, L24I, M46I/ L, F53L, I54L/ T/ V, L63P, A71I/ L/ T/ V, V82A/ F/ T, I84V and L90M.
L10F/ I/ R/ V, K20M/ R, L24I, M46I/ L, F53L, I54L/ T/ V, L63P, A71I/ L/ T/ V, V82A/ F/ T, I84V u L90M.
The median EC50 of lopinavir against isolates with 0 − 3, 4 − 5, 6 − 7 and 8 − 10 mutations at the above amino acid positions was 0.8, 2.7 13.5 and 44.0-fold higher than the EC50 against wild type HIV, respectively.
Il- medjan EC50 ta ’ lopinavir kontra l- iżolati bi 0 - 3, 4 - 5, 6 - 7 u 8 - 10 mutazzjonijiet fil- pożizzjonijiet tal- amino aċidi kif indikat hawn fuq kienu 0. 8, 2. 7 13. 5 u 44. 0 - il darba ogħla mill - EC50 kontra HIV tat- tip mhux ikkultivat, rispettivament.
The 16 viruses that displayed > 20-fold change in susceptibility all contained mutations at positions 10, 54, 63 plus 82 and/ or 84.
Is - 16 il- virus li urew > 20 - il darba bidla fis- suxxettibilità kollha kien fihom mutazzjonijiet fil- posizzjonijiet 10, 54, 63 u 82 u / jew 84.
In addition, they contained a median of 3 mutations at amino acid positions 20, 24, 46, 53, 71 and 90.
Madanakollu, kien fihom medjan ta ’ 3 mutazzjonijiet fil- pożizzjonijiet tal- amino aċidi 20, 24, 46, 53, 71 u 90.
In addition to the mutations described above, mutations V32I and I47A have been observed in rebound isolates with reduced lopinavir susceptibility from protease inhibitor experienced patients receiving Kaletra therapy.
Mal- mutazzjonijiet spjegati hawn fuq, kienu wkoll osservati il- mutazzjonijiet V321 u I47A f’ iżolati li marru lura b’ suxxettibilità mnaqqsa għal lopinavir fil- pazjenti b’ esperjenza ta ’ inibituri tal - protease li kienu jirċievu terapija ta ’ Kaletra.
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.
18 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.
The EC50 of lopinavir against the 56 baseline viral isolates ranged from 0.6 to 96-fold higher than the EC50 against wild type HIV.
Il - EC50 ta ’ lopinavir kontra il - 56 iżolati virali tal - linja bażi varjaw bejn 0. 6 u 96- il darba ogħla mill - EC50 kontra HIV ta ’ tip mhux ikkultivat.
After 48 weeks of treatment with Kaletra, efavirenz and nucleoside reverse transcriptase inhibitors, plasma HIV RNA ≤ 400 copies/ ml was observed in 93% (25/ 27), 73% (11/ 15), and 25% (2/ 8) of patients with< 10-fold, 10 to 40-fold, and > 40-fold reduced susceptibility to lopinavir at baseline, respectively.
Wara 48 ġimgħa ta ’ trattament b’ Kaletra, efavirenz u inibituri tan- nucleoside reverse transcriptase, plażma HIV RNA < 400 kopji/ ml kienu osservati fi 93% (25/ 27), 73% (11/ 15), u 25% (2/ 8) ta ’ pazjenti bi < 10 il darba, 10 għal 40- darba, u > 40 darba tnaqqis fis- suxxettibilità għal lopinavir fil- linja bażi, rispettivament.
In addition, virologic response was observed in 91% (21/ 23), 71% (15/ 21) and 33% (2/ 6) patients with 0 − 5, 6 − 7, and 8 − 10 mutations of the above mutations in HIV protease associated with reduced in vitro susceptibility to lopinavir.
Addizjonalment, rispons viroloġiku kien osservat fi 91% (21/ 23), 71% (15/ 21) u 33% (2/ 6) pazjenti bi 0 - 5, 6 - 7, u 8 - 10 mutazzjonijiet ta ’ dawk hawn fuq msemmija f’ HIV protease assoċjat ma ’ tnaqqis fis- suxxettibilità in vitro għal lopinavir.
Since these patients had not previously been exposed to either Kaletra or efavirenz, part of the response may be attributed to the antiviral activity of efavirenz, particularly in patients harbouring highly lopinavir resistant virus.
Minħabba li dawn il- pazjenti ma kienux esposti qabel għal Kaletra jew efavirenz, parti mir- respons jista ’ jiġi attribwit għal efavirenz, partikolarment f’ pazjenti li qed iħażnu virus b’ reżistenza għolja għal lopinavir.
The study did not contain a control arm of patients not receiving Kaletra.
L- istudju ma kienx fih kontrol fejn pazjenti ma kienux qed jingħataw Kaletra.
Activity of other protease inhibitors against isolates that developed incremental resistance to lopinavir after Kaletra therapy in protease inhibitor experienced patients:
Cross- resistance: Attività ta ’ inibituri oħra tal- protease kontra l- iżolati li żviluppaw reżistenza inkrementali għal lopinavir wara terapjia ta ’ Kaletra f’ pazjenti b’ esperjenza ta ’ inibituri tal- protease.
The presence of cross resistance to other protease inhibitors was analysed in 18 rebound isolates that had demonstrated evolution of resistance to lopinavir during 3 Phase II and one Phase III studies of Kaletra in protease inhibitor-experienced patients.
Il - preżenza ta ’ cross- resistance għal inibituri oħra tal- protease ġiet analizzata fi 18- il iżolat li marru lura, li kienu wrew żvilupp reżistenza għal lopinavir matul 3 mill- istudju tat- tieni fażi u minn 1 mill- istudju tat- tielet fażi ta ’ Kaletra f’ pazjenti b’ esperjenza ta ’ inibituri tal- protease.
The median fold IC50 of lopinavir for these 18 isolates at baseline and rebound was 6.9- and 63-fold, respectively, compared to wild type virus.
It- tinja tal- medjan IC50 ta ’ lopinavir ta ’ dawn it- 18- il iżolat fil- linja bażi u li marru lura kienet 6. 9- il darba u 63- il darba rispettivament, mqabbel ma virus tat- tip mhux ikkultivat.
In general, rebound isolates either retained (if cross-resistant at baseline) or developed significant cross-resistance to indinavir, saquinavir and atazanavir.
Ġeneralment iżolati li marru lura jew żammew (jekk reżistenti- inkroċjati fil- linja bażi) jew żviluppaw cross- resistance għal indinavir, saquinavir u atazanavir.
Modest decreases in amprenavir activity were noted with a median increase of IC50 from 3.7- to 8-fold in the baseline and rebound isolates, respectively.
Tnaqqis modest f’ attività ta ’ amprenavir ġew innutati b’ żieda medjana ta ’ IC50 minn 3. 7- il darba għal 8- il darba f’ iżolati tal- linja bażi jew li marru lura rispettivament.
Please refer to the Aptivus Summary of Product
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.
16 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.
Clinical pharmacodynamic data
Data Klinika farmakodinamika
The effects of Kaletra (in combination with other antiretroviral agents) on biological markers (plasma HIV RNA levels and CD4 counts) have been investigated in a controlled study of Kaletra of 48 weeks duration, and in additional studies of Kaletra of 360 weeks duration.
L- effetti ta ’ Kaletra (kkombinata ma aġenti antiretrovirali oħra) fuq markaturi bijoloġiċi (livelli ta ’ plażma HIV RNA u konti ta ’ CD4) ġew investigati fi studju kkontrollat ta ’ Kaletra twil 48- il ġimgħa, u studji oħra ta ’ Kaletra li damu 360 ġimgħa.
Adult Use
Użu fl- adulti
Patients without prior antiretroviral therapy
Pazjenti li qatt ma ħadu terapija antiretrovirali
Study M98-863 is a randomised, double-blind trial of 653 antiretroviral treatment naïve patients investigating Kaletra (400/ 100 mg twice daily) compared to nelfinavir (750 mg three times daily) plus nucleoside reverse transcriptase inhibitors.
Studju M98- 863 huwa fortuwitu u proċess double- blind bi 653 pazjenti ġodda għal trattament antiretrovirali fejn ġie investigat Kaletra (400/ 100 mg darbtejn kuljum) mqabbel ma ’ nelfinavir (750 mg tlett darbiet kuljum) u inibituri ta ’ reverse nucleoside transcriptase.
By intent to treat analysis where patients with missing values are considered virologic failures, the proportion of patients at 48 weeks with HIV RNA < 400 copies/ ml in the Kaletra arm was 75% and 63% in the nelfinavir arm.
Bl- intenzjoni li tkun trattata l - analiżi fejn pazjenti b’ valuri nieqsa huma kkunsidrati fallimenti viroloġiċi, il- proporzjon ta ’ pazjenti li wara 48 ġimgħa b’ HIV RNA < 400 kopji/ ml kienu, fis- sezzjoni Kaletra, 75% u 63% fis- sezzjoni nelfinavir.
Mean baseline CD4 cell count was 259 cells/ mm3 (range:
Il- linja bażi medja għadd ta ’ ċelluli CD4 kienet ta ’ 259 ċellula/ mm3( limiti:
2 to 949 cells/ mm3) and mean baseline plasma HIV-1 RNA was 4.9 log10 copies/ ml (range:
2 għal 949 ċelluli/ mm3) u medja tal- plażma linja bażi HIV- 1 RNA kienet 4. 9 log10 kopji/ ml (saff:
2.6 to 6.8 log10 copies/ ml).
2. 6 għal 6. 8 log10 kopji/ ml).
Through 48 weeks of therapy, the proportion of patients in the Kaletra arm with plasma RNA < 50 copies/ ml was 67% and 52% in the nelfinavir arm.
Tul 48 ġimgħa terapija, il- proporzjon ta ’ pazjenti fis- sezzjoni Kaletra bi plażma RNA < 50 kopji/ ml kien 67% u 52% fis- sezzjoni nelfinavir.
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.
Tul 48
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.
19 ġimgħa ta ’ terapija, proporzjon ogħla statistikament sinifikattiv ta ’ pazjenti fis- sezzjoni Kaletra kellhom HIV RNA < 50 kopji/ ml mqabbla mas- sezzjoni nelfinavir.
Sustained virological response to Kaletra (in combination with nucleoside/ nucleotide reverse transcriptase inhibitors) has been also observed in a small Phase II study (M97-720) through 360 weeks of treatment.
Respons viroloġiku sostenut għal Kaletra (ikkombinat ma ’ inibituri nukleòside/ nukleòtide reverse transcriptase) ġie osservat anke fi studju Fażi II żgħir (M97- 720) tul 360 ġimgħa ta ’ trattament.
One hundred patients were originally treated with Kaletra in the study (including 51 patients receiving 400/ 100 mg twice daily and 49 patients at either 200/ 100 mg twice daily or 400/ 200 mg twice daily).
Fl - istudju, mitt pazjent oriġinarjament ġew ikkurati b’ Kaletra (inkluż 51 pazjent li kienu qegħdin jirċievu 400/ 100 mg darbtejn kuljum u 49 pazjent li kienu qegħdin jirċievu jew 200/ 100 mg darbtejn kuljum jew 400/ 200 mg darbtejn kuljum).
All patients converted to open-label Kaletra at the 400/ 100 mg twice daily dose between week 48 and week 72.
Bejn ġimgħa 48 u ġimgħa 72, il- pazjenti kollha qalbu għal Kaletra open - label meta ngħataw id- doża ta ’ 400/ 100 mg darbtejn kuljum.
Sixty-one patients completed the study (35 patients received the recommended 400/ 100 mg twice daily dose throughout the study).
Wieħed u sittin pazjent spiċċaw l- istudju kollu (35 pazjent irċevew id- doża rakkomandata ta ’ 400/ 100 mg darbtejn kuljum matul l- istudju kollu.
Through 360 weeks of treatment, the proportion of patients with HIV RNA < 400 (< 50) copies/ ml was 61% (59%), and the corresponding mean increase in CD4 cell count was 501 cells/ mm3.
Matul 360 ġimgħa tat- trattament il- proporzjon ta ’ pazjenti b’ HIV RNA < 400 (< 50) kopji/ ml kien ta ’ 61% (59%) u ż- żieda medja ta ’ għadd ta ’ ċelluli CD4 kienet ta ’ 501 ċelluli/ mm3.
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 avvenimenti avversi, li waqfa minnhom kienet assoċjata ma ’ mewt.
Patients with prior antiretroviral therapy
Pazjenti li kellhom trattament antiretrovirali qabel
Study M97-765 is a randomised, double-blind trial evaluating Kaletra at two dose levels (400/ 100 mg and 400/ 200 mg, both twice daily) plus nevirapine (200 mg twice daily) and two nucleoside reverse transcriptase inhibitors in 70 single protease inhibitor experienced, non-nucleoside reverse transcriptase inhibitor naïve patients.
L- istudju M97- 765 hu prova fortuwita, double- blind li qed jevalwa Kaletra f’ żewġ livelli ta ’ dożi (400/ 100 mg u 400/ 200 mg, it- tnejn li huma darbtejn kuljum) u nevirapine (200 mg darbtejn kuljum) u żewġ inbituri ta ’ reverse transcriptase f ’ 70 pazjenti b’ esperjenza ta ’ inibituri tal- protease, imma novizzi għal inibituri ta ’ non - nucleoside reverse transcriptase.
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.
M98-957 is a randomised, open-label study evaluating Kaletra treatment at two dose levels (400/ 100 mg and 533/ 133 mg, both twice daily) plus efavirenz (600 mg once daily) and nucleoside reverse transcriptase inhibitors in 57 multiple protease inhibitor experienced, non-nucleoside reverse transcriptase inhibitor naïve patients.
M98- 957 huwa studju fortuwitu open- label fejn it- terapija Kaletra ġiet evalwata f’ żewġ livelli ta ’ dożi (400/ 100 mg u 533/ 133 mg, it- tnejn li huma darbtejn kuljum) u efavirenz (600 mg darba kuljum) u inibituri reverse nucleoside transcriptase f ’ 57 pazjenti b’ esperjenza ta ’ inibituri tal- protease, imma novizzi għal inibituri ta ’ non - nucleoside reverse transcriptase.
Between week 24 and 48, patients randomised to a dose of 400/ 100 mg were converted to a dose of 533/ 133 mg.
Bejn il- ġimgħa 24 u 48, pazjenti fortuwitament mogħtija doża ta ’ 400/ 100 mg kienu konvertiti għal doża ta ’ 533/ 133 mg.
Median baseline CD4 cell count was 220 cells/ mm3 (range 13 to 1030 cells/ mm3).
Il- medjan tal - linja bażi fl- għadd taċ- ċelluli CD4 kien 220 ċelluli/ ml (limiti 13 għal 1030 ċelluli/ ml).
17 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.
Paediatric Use
Użu pedjatriku
M98-940 is an open-label study of a liquid formulation of Kaletra in 100 antiretroviral naïve (44%) and experienced (56%) paediatric patients.
M98- 940 huwa studju open- label ta ’ taħlita likwida orali ta ’ Kaletra f ’ 100 novizzi għat- terapji antiretrovirali (44%) u (56%) pazjenti pedjatriċi bl- esperjenza ta ’ dawn it- trattamenti.
All patients were non-nucleoside reverse transcriptase inhibitor naïve.
Il- pazjenti kollha kienu novizzi għal inibituri non- nucleoside reverse transriptase.
Patients were randomised to either 230 mg lopinavir/ 57.5 mg ritonavir per m2 or 300 mg lopinavir/ 75 mg ritonavir per m2.
Pazjenti randomi kienu mogħtija 230 mg lopinavir/ 57. 5 mg ritonavir kull m2 jew 300 mg lopinavir/ 75 mg ritonavir kull m2.
Naïve patients also received nucleoside reverse transcriptase inhibitors.
Pazjenti novizzi ingħataw inibituri nucleoside reverse transcriptase.
Experienced patients received nevirapine plus up to two nucleoside reverse transcriptase inhibitors.
Pazjenti b’ esperjenza ingħataw nevirapine u sa żewġ inibituri nucleoside reverse transcriptase.
Safety, efficacy and pharmacokinetic profiles of the two dose regimens were assessed after 3 weeks of therapy in each patient.
Sigurta ’, effikaċja u l- profili farmakokinetiċi taż - żewġ duzaġġi kienu analiżati wara 3 ġimgħat terapija f’ kull pazjent.
Subsequently, all patients were continued on the 300/ 75 mg per m2 dose.
Sussegwentement il- pazjenti kollha komplew fuq id- doża 300/ 75 mg kull m2.
Patients had a mean age of 5 years (range 6 months to 12 years) with 14 patients less than 2 years old and 6 patients one year or less.
Pazjenti kellhom età medja ta ’ 5 snin (minn 6 xhur sa 12- il sena) b’ 14 li kellhom anqas minn sentejn u 6 pazjenti sena jew anqas.
Mean baseline CD4 cell count was 838 cells/ mm3 and mean baseline plasma HIV-1 RNA was 4.7 log10 copies/ ml.
Il- medja linja bażi fl- għadd ta ’ ċelluli CD4 kien 838 ċelluli/ mm3 u l- medja linja bażi plazma HIV- 1 RNA kien 4. 7 log10 kopji/ ml.
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 increases from baseline in CD4 cell count were 404 cells/ mm3 and 284 cells/ mm3 respectively.
20 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.
The pharmacokinetic properties of lopinavir co-administered with ritonavir have been evaluated in healthy adult volunteers and in HIV-infected patients; no substantial differences were observed between the two groups.
Il- karatteristiċi farmakokinetiċi ta ’ lopinavir ko- amministrat ma ritonavir ġew evalwati f’ voluntiera adulti f’ saħħithom u f’ pazjenti infettati bl- HIV; ma ’ ġiet innutata l- ebda differenza sostanzjali bejn iż - żewg gruppi.
Lopinavir is essentially completely metabolised by CYP3A.
Essenzjalment il- lopinavir huwa kompletament metaboliżżat minn CYP3A.
Ritonavir inhibits the metabolism of lopinavir, thereby increasing the plasma levels of lopinavir.
Ir- ritonavir jinibixxi l- metaboliżmu ta ’ lopinavir, b’ konsegwenza li jżid il- livelli fil- plażma ta’ lopinavir.
Across studies, administration of Kaletra 400/ 100 mg twice daily yields mean steady-state lopinavir plasma concentrations 15 to 20-fold higher than those of ritonavir in HIV-infected patients.
Tul studji, s- somministrazzjoni tal- Kaletra 400/ 100 mg darbtejn kuljum tagħti medja tal- konċentrazzjonijiet tal - plażma ta ’ lopinavir steady- state 15 sa 20- darba ogħla minn dawk ta ’ ritonavir f’ pazjenti infettati bl - HIV.
The plasma levels of ritonavir are less than 7% of those obtained after the ritonavir dose of 600 mg twice daily.
Il- livelli tal- plażma ta ’ ritonavir huma anqas minn 7% ta ’ dawk miksuba wara doża ta’ ritonavir ta ’ 600 mg darbtejn kuljum.
The in vitro antiviral EC50 of lopinavir is approximately 10-fold lower than that of ritonavir.
L - EC50 antivirali in vitro ta ’ lopinavir huwa approssimattivament 10 - darbiet inqas minn dak ta ’ ritonavir.
Therefore, the antiviral activity of Kaletra is due to lopinavir.
Għalhekk l- attività antivirali tal- Kaletra hija dovuta għal- lopinavir.
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.
The mean steady-state trough concentration prior to the morning dose was 5.5 ± 4.0 μ g/ ml.
Il- medja steady state tal- konċentrazzjoni minima qabel id- doża ta ’ filgħodu kienet 5. 5 ± 4. 0 μg/ ml.
Lopinavir AUC over a 12 hour dosing interval averaged 82.8 ± 44.5 μ g• h/ ml.
Lopinavir AUC fuq intervall ta ’ dożaġġ ta ’ 12 il- siegħa kellu medja ta ’ 82. 8 ± 44. 5 μg/ ml.
The absolute bioavailability of lopinavir co-formulated with ritonavir in humans has not been established.
Il- bijodisponibilita ’ assoluta ta ’ lopinavir ko- formulata ma’ ritonavir fil- bniedem, ma ’ ġietx stabbilita.
Effects of food on oral absorption:
Effetti tal- Ikel fuq l- assorbiment mill- ħalq:
Kaletra soft capsules and liquid have been shown to be bioequivalent under nonfasting conditions (moderate fat meal).
Kapsuli rotob u likwidu Kaletra ġew murija li huma bijoekwivalenti taħt kundizzjonijiet mhux ta ’ sawm, (ikla b’ kontenut ta ’ xaħam moderat).
Administration of a single 400/ 100 mg dose of Kaletra soft capsules with a moderate fat meal (500 – 682 kcal, 22.7 – 25.1% from fat) was associated with a mean increase of 48% and 23% in lopinavir AUC and Cmax, respectively, relative to fasting.
Is - somministrazzjoni ta ’ doża unika 400/ 100 mg ta ’ kapsuli rotob Kaletra flimkien ma ’ ikla b’ kontenut ta ’ xaħam moderat (500 – 682 kcal, 22. 7 – 25. 1% mix- xaħam) ġiet assoċjata ma ’ żieda medja ta ’ 48% u 23% fil- lopinavir AUC u Cmax, rispettivament, relattivament għas- sawm.
For Kaletra oral solution, the corresponding increases in lopinavir AUC and Cmax were 80% and 54%, respectively.
Għat- taħlita likwida orali ta ’ Kaletra, iż- żidiet korrispondenti f’ lopinavir AUC u Cmax kienu 80% u 54%, rispettivament.