natgillin/translations-raw huggingface dataset:
Arthralgia, arthrosis, myalgia, back pain, joint disorder
V odsotnosti človeškega seruma je bila povprečna IC50 lopinavirja proti več kliničnim izolatom HIV- 1 6, 5 nM.
Renal and urinary disorders
80 Odpornost
Uncommon
In vitro selekcija odpornosti:
Kidney calculus, urine abnormality, albuminuria, hypercalcinuria, nephritis, hyperuricemia
Genotipska in fenotipska analiza virusov, selekcioniranih med temi prehodi, nakazuje, da prisotnost ritonavirja v teh koncentracijskih razmerjih nima merljivega vpliva na selekcijo virusov, odpornih proti lopinavirju.
Reproductive system and breast disorders
Analiza odpornosti pri bolnikih, naivnih za protiretrovirusna zdravila:
Uncommon
V študiji II. faze (M97- 720) so med 204 tedni zdravljenja uspešno opravili genotipsko analizo virusnih izolatov pri 11 od 16 bolnikov s potrjeno HIV RNA nad 400 kopij/ ml.
Abnormal ejaculation, amenorrhoea, breast enlargement, gynecomastia, impotence, menorrhagia
Analiza ni pokazala primarnih mutacij oz. mutacij aktivnega mesta na proteazi (aminokisline na položajih 8, 30, 32, 46, 47, 48, 50, 82, 84 in 90) ali fenotipske odpornosti proti zaviralcu proteaze.
General disorders and administration site conditions
Odsotnost odpornosti proti lopinavirju je potrdila fenotipska analiza.
Asthenia, pain
Analiza odpornosti pri bolnikih, izkušenih z zaviralci proteaz:
Uncommon
Pri teh bolnikih se je po uvodnem odzivu na zdravilo Kaletra pojavila bodisi nepopolna virološka supresija ali virusni preobrat, poleg tega se je pri njih kazala naraščajoča odpornost in vitro med izhodiščem in preobratom (opredeljenim kot pojav novih mutacij ali 2- kratna sprememba fenotipske občutljivosti za lopinavir).
Chest pain, chest pain substernal, chills, fever, flu syndrome, malaise, peripheral oedema, drug interaction
Naraščajoča odpornost je bila najpogostejša pri preiskovancih, ki so imeli v izhodiščnih izolatih več mutacij, povezanih z zaviralci proteaz, toda z izhodiščno < 40- kratno zmanjšano občutljivost za lopinavir.
Very common (Grade 3 or 4)
Najpogosteje so se pojavile mutacije V82A, I54V in M46I.
Increased triglycerides, increased total cholesterol, increased GGT
Opažali so tudi mutacije L33F, I50V in V32I v kombinaciji z I47V/ A.
Increased glucose, increased amylase, increased
L10F/ I/ R/ V, K20M/ R, L24I, M46I/ L, F53L, I54L/ T/ V, L63P, A71I/ L/ T/ V, V82A/ F/ T, I84V in L90M.
SGOT/ AST, increased SGPT/ ALT, liver function tests abnormal
Mediana EC50 lopinavirja proti izolatom z 0– 3, 4– 5, 6– 7 oz.
Decreased glucose tolerance, weight gain, 1 2
8– 10 mutacijami na omenjenih aminokislinskih položajih je bila 0, 8 -, 2, 7 -, 13, 5 - oz.
This event had a fatal outcome.
44, 0- krat večja kot EC50 proti divjemu tipu HIV.
Uncommon
81 Pri izolatih s preobratom, to je z manjšo občutljivostjo za lopinavir pri bolnikih, ki so dobivali zdravilo Kaletra, so opažali tudi mutaciji I47A in L76V.
weight loss, increased bilirubin, hormone level altered, lab test abnormal
Zaključki o pomembnosti določenih mutacij ali mutacijskih vzorcev se lahko spreminjajo z dodatnimi podatki, zato je priporočljivo, da se vedno upošteva trenutne sisteme interpretacije za analiziranje rezultatov preizkusa odpornosti.
See section 4.4: pancreatitis and lipids
Poleg tega so virološki odziv opažali pri 91% (21/ 23), 71% (15/ 21) oz.
Paediatric patients
33% (2/ 6) bolnikov z 0– 5, 6– 7 oz.
In children 2 years of age and older, the nature of the safety profile is similar to that seen in adults.
8– 10 zgoraj omenjenimi mutacijami proteaze HIV, povezan z manjšo občutljivostjo za lopinavir in vitro.
Undesirable effects in clinical studies in paediatric patients Infections and infestations
Študija ni obsegala kontrolnega kraka bolnikov brez zdravila Kaletra.
Viral infection
Navzkrižna odpornost:
Nervous system disorders
Klinični farmakodinamični podatki
Common
Učinke zdravila Kaletra (v kombinaciji z drugimi protiretrovirusnimi zdravili) na biološke označevalce (koncentracijo HIV RNA in število celic CD4 v plazmi) so raziskali v kontrolirani 48- tedenski študiji zdravila Kaletra ter v dodatnih 360- tedenskih raziskavah zdravila Kaletra.
Taste perversion
Uporaba pri odraslih
Gastrointestinal disorders
Bolniki brez predhodnega protiretrovirusnega zdravljenja
Common
Med 48 tedni zdravljenja je bil delež bolnikov z RNA v plazmi < 50 izvodov/ ml v kraku z zdravilom Kaletra 67% in v kraku z nelfinavirjem 52%.
Constipation, vomiting, pancreatitis*
Povprečno zvečanje števila celic CD4 od izhodišča je bilo 207 celic/ mm3 v kraku z
Hepatobiliary disorders
82 zdravilom Kaletra in 195 celic/ mm3 v kraku z nelfinavirjem.
Common
Devetintrideset bolnikov (39%) je prenehalo s študijo, vključno s 16 (16%) prenehanji zaradi neželenih dogodkov, eden izmed teh je bil povezan s smrtjo.
Skin and subcutaneous tissue disorders
Bolniki s predhodnim protiretrovirusnim zdravljenjem
Common
Po analizi z namenom zdravljenja, pri kateri so bili bolniki z manjkajočimi podatki obravnavani kot virološki neuspeh, sta bila delež bolnikov s HIV RNA < 400 izvodov/ ml po 24 tednih 75% (58%) in povprečno zvečanje števila celic CD4 od izhodišča 174 celic/ mm3 za 36 bolnikov, ki so dobivali zdravilo Kaletra v odmerku 400/ 100 mg.
Rash, dry skin
Med 24. in 48. tednom so bolniki, randomizirani na odmerek 400/ 100 mg, prešli na odmerek 533/ 133 mg.
General disorders and administration site conditions
Mediano izhodiščno število celic CD4 je bilo 220 celic/ mm3 (razpon od 13 do 1030 celic/ mm3).
Common (Grade 3 or 4)
Pediatrična uporaba
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
Bolnike so randomizirali bodisi na 230 mg lopinavirja/ 57, 5 mg ritonavirja na m2 ali 300 mg lopinavirja/ 75 mg ritonavirja na m2.
*see section 4.4: pancreatitis and lipids
Naivni bolniki so dobili tudi nukleozidne zaviralce reverzne transkriptaze.
75 Post marketing experience
Potem so vsi bolniki nadaljevali z odmerkom 300/ 75 mg na m2.
Hepatitis, and rarely jaundice, have been reported in patients on Kaletra therapy in the presence or absence of identifiable risk factors for hepatitis.
Povprečna starost bolnikov je bila 5 let (razpon: od 6 mesecev do 12 let); 14 bolnikov je bilo mlajših od 2 let in 6 jih je bilo starih eno leto ali manj.
Stevens-Johnson syndrome and erythema multiforme have been reported.
83 5. 2 Farmakokinetične lastnosti
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).
Farmakokinetične lastnosti lopinavirja, uporabljenega hkrati z ritonavirjem, so ocenili pri zdravih odraslih prostovoljcih in pri bolnikih, okuženih s HIV; med skupinama niso opazili bistvenih razlik.
The frequency of this is unknown (see section 4.4).
Lopinavir se v bistvu popolnoma presnovi s CYP3A.
4.9 Overdose
Absorpcija:
To date, there is limited human experience of acute overdose with Kaletra.
Tablete Kaletra lahko torej bolnik vzame s hrano ali brez nje.
The adverse clinical signs observed in dogs included salivation, emesis and diarrhoea/ abnormal stool.
Lopinavir se veže na alfa- 1- kisli glikoprotein (AKG) in na albumin, vendar ima večjo afiniteto za AKG.
The signs of toxicity observed in mice, rats or dogs included decreased activity, ataxia, emaciation, dehydration and tremors.
V stanju dinamičnega ravnovesja ostaja vezava lopinavirja na beljakovine v območju opazovanih koncentracij po 400/ 100 mg zdravila Kaletra dvakrat na dan stalna ter je pri zdravih prostovoljcih in pri HIV- pozitivnih bolnikih podobna.
There is no specific antidote for overdose with Kaletra.
Pri ljudeh je identificiranih vsaj 13 oksidativnih presnovkov lopinavirja.
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.
Glavna presnovka s protivirusnim delovanjem sta epimerni par 4- okso - in 4- hidroksimetabolita, vendar pomenita le neznaten delež skupne radioaktivnosti v plazmi.
If indicated, elimination of unabsorbed active substance is to be achieved by emesis or gastric lavage.
Ritonavir dokazano inducira presnovne encime; posledica je indukcija njegove lastne presnove, verjetno pa tudi indukcija presnove lopinavirja.
Administration of activated charcoal may also be used to aid in removal of unabsorbed active substance.
Predodmerna koncentracija lopinavirja med večkratnim odmerjanjem s časom upada in se stabilizira po približno 10 dneh do 2 tednih.
Since Kaletra is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.
Nespremenjeni lopinavir predstavlja v urinu približno 2, 2%, v blatu pa približno 19, 8% uporabljenega odmerka.
PHARMACOLOGICAL PROPERTIES
84 Posebne skupine bolnikov
5.1 Pharmacodynamic properties
Pediatrični bolniki:
Pharmaco-therapeutic group: protease inhibitor, ATC code:
Farmakokinetični podatki pri otrocih do 2. leta starosti so omejeni.
J05AE06
Spol, rasa in starost:
Mechanism of action: lopinavir provides the antiviral activity of Kaletra.
Farmakokinetika zdravila Kaletra pri starejših ni raziskana.
Lopinavir is an inhibitor of the HIV-1 and HIV-2 proteases.
Pri odraslih bolnikih niso opazili s starostjo ali spolom povezanih farmakokinetičnih razlik.
Inhibition of HIV protease prevents cleavage of the gag-pol polyprotein resulting in the production of immature, non-infectious virus.
Prav tako niso ugotovili farmakokinetičnih razlik zaradi rase.
Effects on the electrocardiogram:
Ledvična insuficienca:
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.
A ker je ledvični očistek lopinavirja zanemarljiv, pri bolnikih z ledvično insuficienco ni pričakovati zmanjšanja celotnega telesnega očistka.
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.
Farmakokinetične parametre lopinavirja v stanju dinamičnega ravnovesja pri s HIV okuženih bolnikih z blago do zmerno jetrno okvaro so primerjali s tistimi pri s HIV okuženih bolnikih z normalno jetrno funkcijo v študiji z multiplimi odmerki lopinavirja/ ritonavirja 400/ 100 mg dvakrat dnevno.
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.
Opazili so omejeno povečanje koncentracij lopinavirja za približno 30%, kar ni pričakovati, da bi bilo klinično pomembno (glejte poglavje 4. 2).
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.
5. 3 Predklinični podatki o varnosti
Modest prolongation of the PR interval was also noted in subjects receiving lopinavir/ ritonavir in the same study on Day 3.
Študije toksičnosti pri ponavljajočih odmerkih pri glodalcih in psih so pokazale, da so glavni ciljni organi jetra, ledvice, ščitnica, vranica in krožeče rdeče krvne celice.
The mean changes from baseline in PR interval ranged from 11.6 ms to 24.4 ms in the 12 hour interval post dose.
Pri podganah so opažali Coombs- negativno anizocitozo in poikilocitozo, pri miših in psih pa ne.
Maximum PR interval was 286 msec and no second or third degree heart block was observed (see section 4.4).
Zvečanje vranice in histiocitozo so zabeležili pri podganah, pri drugih vrstah pa ne.
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.
Med študijami in vitro so največje preizkušene koncentracije lopinavirja/ ritonavirja zavrle klonirane človeške srčne kanale za kalij (HERG) za 30%; izpostavljenost ustreza izpostavljenosti lopinavirju ob 7- kratni celotni ravni in 15- kratni prosti plazemski ravni, doseženi pri ljudeh z največjim priporočenim terapevtskim odmerkom.
In the absence of human serum, the mean IC50 of lopinavir against five different HIV-1 laboratory strains was 19 nM.
Nasprotno pa podobne koncentracije lopinavirja/ ritonavirja niso upočasnile repolarizacije v Purkinjejevih vlaknih srca kuncev.
In the absence and presence of 50% human serum, the mean IC50 of
Manjše koncentracije lopinavirja/ ritonavirja niso pomembno zavrle kalijevega toka (HERG).
76 lopinavir against HIV-1IIIB in MT4 cells was 17 nM and 102 nM, respectively.
85 približno 50% AUC, izmerjene v plazmi.
In the absence of human serum, the mean IC50 of lopinavir was 6.5 nM against several HIV-1 clinical isolates.
Zato je smiselno pričakovati, da koncentracija lopinavirja v srcu ni pomembno večja od koncentracije v plazmi.
Resistance
Domnevno so vzrok tega elektrolitske motnje.
In vitro selection of resistance:
Klinični pomen teh predkliničnih podatkov ni znan, vendar kardialnih učinkov tega zdravila pri človeku ni mogoče izključiti (glejte tudi poglavji 4. 4 in 4. 8).
HIV-1 isolates with reduced susceptibility to lopinavir have been selected in vitro.
Med uporabo odmerkov, toksičnih za mater, so pri podganah opažali embriofetotoksičnost (izgubo brejosti, manjšo viabilnost plodov, manjšo telesno maso plodov, pogostejše skeletne spremembe) in postnatalno razvojno toksičnost (manjše preživetje mladičev).
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.
Sistemska izpostavljenost lopinavirju/ ritonavirju je bila ob maternalnih in razvojno toksičnih odmerkih manjša, kot je predvidena terapevtska izpostavljenost pri človeku.
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.
Raziskave kancerogenosti pri podganah niso pokazale tumorigenosti.
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.
Mutagenost lopinavirja/ ritonavirja so preizkusili s skupino preskusov in vitro in in vivo, med drugim z Amesovim preskusom bakterijske reverzne mutacije, mišjim limfomskim preskusom, mikronukleusnim testom pri miših in preskusi kromosomskih aberacij v človeških limfocitih; nobeden ni pokazal, da bi bila kombinacija mutagena ali klastogena.
Analysis of resistance in ARV-naïve patients:
FARMACEVTSKI PODATKI
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.
6. 1 Seznam pomožnih snovi
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.
Vsebina tablete: kopovidon sorbitan lavrat koloidni brezvodni silicijev dioksid natrijev stearilfumarat
Of these, isolates from 96 nelfinavir-treated subject and 51 lopinavir/ ritonavir-treated subjects could be amplified for resistance testing.
Filmska obloga: polivinilalkohol titanov dioksid smukec makrogol 3350 rumeni železov oksid E172
Resistance to nelfinavir, defined as the presence of the D30N or L90M mutation in protease, was observed in 41/ 96 (43%) subjects.
Za shranjevanje zdravila niso potrebna posebna navodila.
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.
Plastenke iz polietilena velike gostote (HDPE), zaprte s propilensko zaporko.
Lack of resistance to lopinavir was confirmed by phenotypic analysis.
Eno pakiranje vsebuje 1 plastenko (60 tablet).
Analysis of resistance in PI-experienced patients:
86 6. 6 Navodila za pripravo in ravnanje z zdravilom
Mutations V82A, I54V and M46I emerged most frequently.
Ni posebnih zahtev.
Mutations L33F, I50V and V32I combined with I47V/ A were also observed.
Abbott Laboratories Limited Queenborough Kent ME11 5EL Velika Britanija
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).
ŠTEVILKA (ŠTEVILKE) DOVOLJENJA (DOVOLJENJ) ZA PROMET
Genotypic correlates of reduced phenotypic susceptibility to lopinavir in viruses selected by other protease inhibitors.
DATUM PRIDOBITVE/ PODALJŠANJA DOVOLJENJA ZA PROMET
Within this panel, the following mutations in HIV protease were associated with reduced in vitro susceptibility to lopinavir:
Datum pridobitve dovoljenja za promet:
L10F/ I/ R/ V, K20M/ R, L24I, M46I/ L, F53L, I54L/ T/ V, L63P, A71I/ L/ T/ V, V82A/ F/ T, I84V and L90M.
20. marec 2006
The 16 viruses that displayed > 20-fold change in susceptibility all contained mutations at positions 10, 54, 63 plus 82 and/ or 84.
DATUM ZADNJE REVIZIJE BESEDILA
In addition, they contained a median of 3 mutations at amino acid positions 20, 24, 46, 53, 71 and 90.
IMETNIK DOVOLJENJA ZA IZDELAVO ZDRAVILA, ODGOVOREN ZA SPROŠČANJE SERIJE
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.
IMETNIK DOVOLJENJA ZA IZDELAVO ZDRAVILA, ODGOVOREN ZA SPROŠČANJE SERIJE
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.
Ime in naslov izdelovalca, odgovornega za sproščanje serije
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.
Aesica Queenborough Limited, Queenborough, Kent ME11 5EL, Velika Britanija
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.
KG, Knollstrasse, 67061 Ludwigshafen, Nemčija
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.
V natisnjenem navodilu za uporabo zdravila mora biti navedeno ime in naslov izdelovalca, odgovornega za sproščanje zadevne serije.
The study did not contain a control arm of patients not receiving Kaletra.
• POGOJI ALI OMEJITVE GLEDE OSKRBE IN UPORABE, PREDPISANI IMETNIKU DOVOLJENJA ZA PROMET Z ZDRAVILOM
Cross-resistance:
Izdaja zdravila je le pod omejenimi pogoji in na recept (Glej Dodatek I:
Activity of other protease inhibitors against isolates that developed incremental resistance to lopinavir after Kaletra therapy in protease inhibitor experienced patients:
Pred začetkom prometa farmacevtske oblike tableta na trgu EU se CHMP odboru predloži v odobritev Pismo zdravniku.
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.
Imetnik dovoljenja za promet bo tesno sodeloval z vsakim nacionalnim pristojnim organom in zagotovil, da bodo pred začetkom prometa z zdravilom v posamezni državi članici zdravstveni delavci prejeli Pismo zdravniku, v katerem bodo obveščeni o možnostih zamenjave in napačnega odmerjanja zaradi hkratnega pojava obeh farmacevtskih oblik (mehke kapsule in filmsko obložene tablete) na trgu.
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.
Imetnik dovoljenja za promet mora zagotoviti, da je sistem farmakovigilance, kot je opisan v različici 2, ki je predložen v modulu 1. 8. 1. vloge za pridobitev dovoljenja za promet, vzpostavljen in funkcionalen pred in med prisotnostjo zdravila na trgu.
In general, rebound isolates either retained (if cross-resistant at baseline) or developed significant cross-resistance to indinavir, saquinavir and atazanavir.
Načrt upravljanja tveganja (» Risk Management Plan «)
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.
Imetnik dovoljenja za promet se zavezuje, da bo izvedel študije in dodatne farmakovigilančne aktivnosti, ki so opredeljene v farmakovigilančnem načrtu, kar se sklada z različico 2. 3 načrta upravljanja tveganja (» RMP – Risk Management Plan «), ki je predložen v modulu 1. 8. 2. vloge za pridobitev dovoljenja za promet, in z vsakimi sledečimi posodobitvami načrta upravljanja tveganja, ki bo odobren pri odboru CHMP.
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.
V skladu z navodili odbora CHMP “ Guideline on the risk management systems for medicinal products for human use "bo posodobljen načrt upravljanja tveganja predložen istočasno z naslednjim poročilom o varnosti zdravila (PSUR).
Clinical pharmacodynamic data
Poleg tega bo posodobljen načrt upravljanja tveganja predložen
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.
ob prejemu novih informacij, ki bi lahko vplivale na trenutne varnostne specifikacije, farmakovigilančni načrt ali aktivnosti zmanjševanja tveganja,
Adult Use
na zahtevo EMEA.
Patients without prior antiretroviral therapy
Periodična poročila o varnosti zdravila
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.
Imetnik dovoljenja za promet bo oddajal periodično poročilo o varnosti zdravila v enoletnih ciklih.
Mean baseline CD4 cell count was 259 cells/ mm3 (range:
Kaletra 133, 3/ 33, 3 mg mehke kapsule lopinavir/ ritonavir
2 to 949 cells/ mm3) and mean baseline plasma HIV-1 RNA was 4.9 log10 copies/ ml (range:
2.
2.6 to 6.8 log10 copies/ ml).
NAVEDBA ENE ALI VEČ ZDRAVILNIH UČINKOVIN
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.
Ena mehka kapsula vsebuje:
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).
133, 3 mg lopinavirja in 33, 3 mg ritonavirja (farmakokinetični stopnjevalec).
78 dose between week 48 and week 72.
SEZNAM POMOŽNIH SNOVI