qanastek/EMEA-V3 huggingface dataset:
AUC0– 8hr of 26,980 nM*h; peak plasma concentration of 13,711 nM; and plasma concentration at 8 hours post dose of 146 nM.
AUC0– 8hr ta ’ 26980 nM* h; l - ogħla konċentrazzjonijiet fil- plażma ta ’ 13711 nM; u konċentrazzjonijiet tal- plażma 8 sigħat wara d - doża ta ’ 146 nM.
Distribution Indinavir was not highly bound to human plasma proteins (39% unbound).
Distribuzzjoni Indinavir mhux marbut b’ mod qawwi mal- proteini tal- bniedem fil- plażma (39% mhux marbuta).
There are no data concerning the penetration of indinavir into the central nervous system in humans.
M’ hemmx tagħrif dwar il- penetrazzjoni ta ’ indinavir fis- sistema nervuża ċentrali fil- bnedmin.
Biotransformation Seven major metabolites were identified and the metabolic pathways were identified as glucuronidation at the pyridine nitrogen, pyridine– N– oxidation with and without 3’– hydroxylation on the indane ring, 3’– hydroxylation of indane, p– hydroxylation of phenylmethyl moiety, and N– depyridomethylation with and without the 3’– hydroxylation.
Bijotrasformazzjoni Ġew identifikati seba ’ metaboliti prinċipali u l- mogħdijiet metaboliċi ġew identifikati bħala glukuronidazzjoni ta ’ pyridine nitrogen, pyridine– N– oxidation bl- 3 ’ – idrossilazzjoni fuq l - indane ring jew mingħajru, 3 ’ – idrossilazzjoni ta ’ indane, p- idrossilazzjoni ta ’ phenylmethyl moiety, u N – depyridomethylation bl- 3 ’ – idrossilazzjoni jew mingħajru.
In vitro studies with human liver microsomes indicated that CYP3A4 is the only P450 isozyme that plays a major role in the oxidative metabolism of indinavir.
Studji in vitro b’ mikrożomi tal- fwied tal - bniedem indikaw li CYP3A4 huwa l- unika iżozima P450 li għandha sehem maġġuri fil- metaboliżmu ossidativ ta ’ indinavir.
Analysis of plasma and urine samples from subjects who received indinavir indicated that indinavir metabolites had little proteinase inhibitory activity.
L- analiżi ta ’ kampjuni tal- plażma u l- urina minn suġġetti li ngħataw indinavir indikat li l- metaboliti ta ’ indinavir ftit kellhom attivita` inibitorja fuq proteinase.
Elimination Over the 200– 1,000– mg dose range administered in both volunteers and HIV infected patients, there was a slightly greater than dose– proportional increase in urinary recovery of indinavir.
Tneħħija Matul il- medda ta ’ dożi ta ’ 200- 1, 000- mg li ngħatat kemm lil voluntiera kif ukoll lil pazjenti infettati bl- HIV, kienet hemm żieda kemmxejn ogħla minn dak proporzjonali għad- doża fit- tneħħija ta ’ indinavir bl- urina.
Renal clearance (116 ml/ min) of indinavir is concentration– independent over the clinical dose range.
It- tneħħija permezz tal- kliewi (116 ml/ min) ta ’ indinavir tiddependi mill - konċentrazzjoni fuq il- medda tad- doża.
Less than 20% of indinavir is excreted renally.
Inqas minn 20% ta ’ indinavir jitneħħa permezz tal- kliewi.
Mean urinary excretion of unchanged drug following single dose administration in the fasted state was 10.4% following a 700– mg dose, and 12.0% following a 1,000– mg dose.
Il - medja ta ’ tneħħija fl- urina ta ’ aġent mhux mibdul wara l- amministrazzjoni ta ’ doża waħda waqt sawm kienet ta ’ 10. 4% wara doża ta ’ 700- mg, u ta ’ 12% wara doża ta ’ 1, 000- mg.
Indinavir was rapidly eliminated with a half– life of 1.8 hours.
Indinavir tneħħa malajr b’ half life ta ’ 1. 8 sigħat.
Characteristics in patients Pharmacokinetics of indinavir do not appear to be affected by race.
Karatteristiċi fil- pazjenti Il- karatteristiċi farmakokinetiċi ta ’ indinavir ma jidhrux li huma affettwati minn razza.
There are no clinically significant differences in the pharmacokinetics of indinavir in HIV seropositive women compared to HIV seropositive men.
M’ hemmx differenzi b’ sinifikanza klinika fil- karatteristiċi farmakokinetiċi ta ’ indinavir f’ nisa bl- HIV seropożittivi meta mqabbla ma ’ rġiel bl- HIV seropożittivi.
Patients with mild– to– moderate hepatic insufficiency and clinical evidence of cirrhosis had evidence of decreased metabolism of indinavir resulting in approximately 60% higher mean AUC following a 400– mg dose.
Pazjenti li għandhom insuffiċenza tal- fwied minn- ħafif- sa- moderat u evidenza klinika ta ’ ċirrożi kellhom evidenza ta ’ tnaqqis tal- metaboliżmu ta ’ indinavir li wassal għal bejn wieħed u ieħor medja ogħla ta ’ 60% AUC wara doża ta ’ 400- mg.
The mean half– life of indinavir increased to approximately 2.8 hours.
Il- half life ta ’ indinavir jitwal bejn wieħed u ieħor għal 2. 8 sigħat.
Crystals have been seen in the urine of rats, one monkey, and one dog.
Ġew osservati kristalli fl- urina tal- firien, xadina waħda u kelb wieħed.
The crystals have not been associated with drug– induced renal injury.
Il- kristalli ma ġewx marbuta ma ’ ħsara fil- kliewi minħabba l- aġent.
An increase in thyroidal weight and thyroidal follicular cell hyperplasia, due to an increase in thyroxine clearance, was seen in rats treated with indinavir at doses ≥ 160 mg/ kg/ day.
Ġiet osservata żieda ta ’ piż tat- tirojde u iperplażja tirojdali taċ - 25 ċelluli follikulari, minħabba żieda fit- tneħħija ta ’ thyroxine, fil- firien ikkurati b’ indinavir b’ dożi ≥ 160 mg/ kg/ jum.
An increase in hepatic weight occurred in rats treated with indinavir at doses ≥ 40 mg/ kg/ day and was accompanied by hepatocellular hypertrophy at doses ≥ 320 mg/ kg/ day.
Żieda fil- piż tal- fwied seħħet fil- firien ikkurati b’ indinavir b’ dożi ≥ 40 mg/ kg/ jum u ġiet ma ’ ipertrofija fil- ċelluli tal- fwied b’ dożi ≥ 320 mg/ kg/ jum.
The maximum non– lethal oral dose of indinavir was at least 5,000 mg/ kg in rats and mice, the highest dose tested in acute toxicity studies.
Id- doża orali massima mhux letali ta ’ indinavir kienet mill- inqas 5, 000 mg/ kg fil- firien u l- ġrieden, l - ogħla doża ttestjata fi studji dwar it- tossiċita` akuta.
23 Studies in rats indicated that uptake into brain tissue was limited, distribution into and out of the lymphatic system was rapid, and excretion into the milk of lactating rats was extensive.
Studji fil- firien indikaw li l- assorbiment mit- tessuti tal- moħħ kien limitat, id- distribuzzjoni għal ġo u ‘ l barra mis- sistema limfatika kienet mgħaġġla, u l- eskrezzjoni fil- ħalib tal- firien ireddgħu kienet estensiva.
Distribution of indinavir across the placental barrier was significant in rats, but limited in rabbits.
Id- distribuzzjoni ta ’ indinavir mill- barriera tal- plaċenta kien sinifikanti, imma kien limitat fil- fniek.
Mutagenicity Indinavir did not have any mutagenic or genotoxic activity in studies with or without metabolic activation.
Mutaġeniċita` Fi studji b’ attivazzjoni metabolika u mingħajrha indinavir ma kellux attivita` mutaġenika jew ġenotossika.
Carcinogenicity No carcinogenicity was noted in mice at the maximum tolerated dose, which corresponded to a systemic exposure approximately 2 to 3 times higher than the clinical exposure.
Karċinoġeniċita` Ma ġietx innutata karċinoġeniċita` fil- ġrieden bid- doża massima tollerata, li kien jikkorrispondi għal espożizzjoni sistemika bejn wieħed u ieħor 2 jew 3 ogħla mill- espożizzjoni klinika.
In rats, at similar exposure levels, an increased incidence of thyroid adenomas was seen, probably related to an increase in release of thyroid stimulating hormone secondary to an increase in thyroxine clearance.
Fil- firien, b’ livelli simili ta ’ espożizzjoni, ġiet osservata inċidenza ogħla ta ’ adenomi tat- tirojde, aktarx marbuta ma ’ żieda fil- ħruġ ta ’ l- ormon li jistimula t- tirojde, li jiġi wara żieda fit- tneħħija bit- tajroksin.
The relevance of the findings to humans is likely limited.
Ir- relevanza ta ’ dan it- tagħrif għall- bnedmin x’ aktarx li jkun limitat.
Developmental Toxicity Developmental toxicity studies were performed in rats, rabbits and dogs (at doses which produced systemic exposures comparable to or slightly greater than human exposure) and revealed no evidence of teratogenicity.
Tossiċita` fl- Iżvilupp L- istudji tat- tossiċita` fl- iżvilupp li saru fil- firien, il- fniek u l- klieb (b’ dożi li pproduċew espożizzjonijiet sistemiċi li jistgħu jitqabblu jew huma kemmxejn ikbar mill- espożizzjoni tal- bniedem) ma wrewx evidenza ta ’ teratoġeniċita`.
No external or visceral changes were observed in rats, however, increases in the incidence of supernumerary ribs and of cervical ribs were seen.
Ma ġewx osservati bidliet esterni jew fil- vixxri fil- firien, madankollu, ġew osservati inċidenzi ogħla ta ’ kustilji żejda u kustilji ċervikali.
No external, visceral, or skeletal changes were observed in rabbits or dogs.
Ma ġewx osservati bidliet esterni, vixxerali jew fl- iskeltri tal- fniek u l- klieb.
In rats and rabbits, no effects on embryonic/ foetal survival or foetal weights were observed.
Fil- firien u l- fniek ma ġewx osservati effetti fuq il- ħajja ta ’ embrijuni u feti jew fil- piż tal- feti.
In dogs, a slight increase in resorptions was seen; however, all foetuses in medication– treated animals were viable, and the incidence of live foetuses in medication– treated animals was comparable to that in controls.
Fil- klieb, ġiet osservata żieda żgħira fir - riassorbiment, madankollu, il- feti kollha f’ annimali kkurati kienu vijabbli, u l- inċidenza ta ’ feti ħajjin setgħet titqabbel ma ’ dawk li kienu fil- grupp ta ’ kontroll.
Capsule content
Kontenut tal- kapsula
Capsule shell:
qoxra tal- kapsula:
- gelatin
- ġelatina
- titanium dioxide (E 171)
- titanium dioxide (E 171)
- sodium lauryl sulphate
- sodium lauryl sulphate
- printing ink: titanium dioxide (E 171), indigo carmine (E 132), and iron oxide (E 172).
- inka għall- istampar: titanium dioxide (E 171), indigo carmine (E 132), u iron oxide (E 172).
3 years
26 3 snin
Store in the original bottle.
Aħżen fil- flixkun oriġinali.
Keep the bottle tightly closed in order to protect from moisture.
Żomm il- flixkun magħluq sew biex il- prodott tipproteġih mill- umdita`..
HDPE bottles with a polypropylene cap and a foil induction cap containing 180 capsules.
Fliexken HDPE li jkun fihom 180 kapsula u li jkunu b’ tapp tal- polipropilin u tapp ta ’ l- induzzjoni tal - fojl.
The bottles contain desiccant canisters that should remain in the container.
Il- fliexken fihom bottijiet żgħar tad- dessikant u li għandhom jitħallew fil- kontenitur.
04/ 10/ 1996 Date of latest renewal:
04/ 10/ 1996 Data ta ’ l- aħħar tiġdid:
CRIXIVAN 200 mg hard capsules
CRIXIVAN 200 mg kapsuli ibsin
Each hard capsule contains indinavir sulphate corresponding to 200 mg of indinavir.
Kull kapsula iebsa fiha indinavir sulphate li jikkorrispondi għal 200 mg ta ’ indinavir.
Each 200 mg capsule contains 74.8 mg lactose.
Sustanza mhux attiva: kull kapsula ta ’ 200 mg fiha 74. 8 mg ta ’ lactose.
For a full list of excipients, see section 6.1
Għall- lista sħiħa ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1
The capsules are semi– translucent white and coded CRIXIVAN™ 200 mg in blue.
Il- kapsuli huma bojod semi– trasluċidi u kkodifikati CRIXIVAN™ 200 mg fil- blu.
26 Paediatric dose (500 mg/ m2) to be administered every 8 hours
28 Id- doża għat- tfal (50 mg / m2) li għandha tingħata kull 8 sigħat
Body Surface Area (m2) 0.50 0.75 1.00 1.25 1.50
Erja tal- wiċċ tal- ġisem (m2) 0. 50 0. 75 1. 00 1. 25 1. 50
CRIXIVAN dose Every 8 hours (mg) 300 400 500 600 800
Doża ta ’ CRIXIVAN Kull 8 sigħat (mg) 300 400 500 600 800
A dosage reduction of CRIXIVAN to 600 mg every 8 hours should be considered when administering itraconazole or ketoconazole concurrently (see section 4.5).
Konsiderazzjonijiet speċjali għall- adulti dwar id- doża Għandu jitqies tnaqqis fid- doża ta ’ CRIXIVAN għal 600 mg kull 8 sigħat meta jingħata ma itraconazole jew ketoconazole fl- istess ħin (ara sezzjoni 4. 5).
Combination of rifampicin with CRIXIVAN with or without concomitant low-dose ritonavir is contraindicated (see section 4.5).
Il- kombinazzjoni ta ’ rifampicin ma ’ CRIXIVAN bi jew mingħajr doża baxxa ta ’ ritonavir li tingħata fl- istess ħin hi kontrandikata (ara sezzjoni 4. 5).
Concurrent use of indinavir with herbal preparations containing St John’ s wort (hypericum perforatum) is contraindicated (see section 4.5).
L- użu fl- istess ħin ta ’ indinavir ma ’ preparazzjonijiet erbali li fihom St John’ s wort (hypericum perforatum) huwa kontrandikat (ara sezzjoni 4. 5).
27 In addition, indinavir with ritonavir should not be administered with alfuzosin, meperidine, piroxicam, propoxyphene, bepridil, encainide, flecanide, propafenone, quinidine, fusidic acid, clozapine, clorazepate, diazepam, estazolam and flurazepam.
29 Barra minn hekk, indinavir ma ’ ritonavir ma għandux jingħata ma ’ alfuzosin, meperidine, piroxicam, propoxyphene, bepridil, encainide, flecanide, propafenone, quinidine, fusidic acid, clozapine, clorazepate, diazepam, estazolam u flurazepam.
Medicinal products nteractions Indinavir should be used cautiously with other medicinal products that are potent inducers of CYP3A4.
Interazzjonjiet ta ’ prodotti mediċinali Indinavir għandu jintuża b’ kawtela ma ’ prodotti mediċinali oħra li jinduċu b’ mod qawwi CYP3A4.
Acute haemolytic anaemia Acute haemolytic anaemia has been reported which in some cases was severe and progressed rapidly.
30 Anemija emolitika akuta Ġiet irrapuratata anemija emolitika akuta li f’ xi każijiet kienet severa u żviluppat għall- agħar b’ mod mgħaġġel.
28 Hyperglycaemia New onset diabetes mellitus, hyperglycaemia or exacerbation of existing diabetes mellitus has been reported in patients receiving protease inhibitors (PIs).
Ipergliċemija F’ pazjenti li kienu qed jingħataw inibituri tal- protease (PIs) ġew irrappurati l- bidu tad- dijabete mellitus, l- ipergliċemija u t- tiħrix tad- dijabete mellitus eżistenti.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterial infectiosn, and Pneumocystis carinii pneumonia.
Eżempji relevanti huma: retinite citomegalovirus, infezzjonijiet mikobatterjali ġeneralizzati u/ jew fokali, u pulmonite Pneumocystis carinii.
Patients with mild– to– moderate hepatic insufficiency due to cirrhosis will require a dosage reduction of indinavir due to decreased metabolism of indinavir (see section 4.2).
31 Pazjenti li għandhom mard minn moderat sa qawwi fil- fwied minħabba ċirrożi jkollhom bżonn ta ’ tnaqqis fid- doża ta ’ indinavir minħabba l- metaboliżmu mnaqqas ta ’ indinavir (ara sezzjoni 4. 2).
Patients with severe hepatic impairment have not been studied.
Ma ġewx studjati pazjenti li għandhom mard qawwi fil- fwied.
29 Safety in patients with impaired renal function has not been studied; however, less than 20% of indinavir is excreted in the urine as unchanged drug or metabolites (see section 4.2).
Ma ġietx studjata s- sigurta` f’ pazjenti b’ mard fil- kliewi, madankollu, inqas minn 20% ta ’ indinavir jitneħħa ma ’ l- urina bħala mediċina mhux mibdula jew bħala metaboliti (ara sezzjoni 4. 2).
Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/ or long-term exposure to combination antiretroviral therapy (CART).
Għalkemm l- etjoloġija titqies li hi multifattorjali (inkluż l- użu ta ’ kortikosterojdi, il- konsum ta ’ l - alkolħol, immunosoppressjoni severa, indiċi ogħla tal- massa tal- ġisem), ġew irrapurtati każijiet ta ’ ostejonekrożi speċjalment f’ pazjenti b’ mard avvanzat ta ’ l- HIV u/ jew espożizzjoni fit- tul għat- terapija antiretrovirali kombinata (CART).
Table 1.
32 Tabella 1.
30 Medicinal products by therapeutic areas ANTI-INFECTIVES Antiretrovirals NRTIs
Prodotti medinċinali skond l- oqsma terapewtiċi ANTI- INFETTIVI Antiretrovirali NRTIs
Saquinavir 600 mg SD (hard gel capsule formulation) (Indinavir 800 mg TID)
35 Prodotti medinċinali skond l- oqsma terapewtiċi Saquinavir 600 mg SD
There are no interaction data available on the coadministration of indinavir/ ritonavir and amprenavir.
40
Rifampicin is a strong CYP3A4 inducer and has been shown to cause a 92% decrease in indinavir AUC which can result in virological failure and resistance development.
Rifampicin huwa induttur b’ saħħtu ta ’ CYP3A4 u ntwera li jikkawża tnaqqis ta ’ 92% fl - AUC ta ’ indinavir li tista ’ tirriżulta fi ħsara viroloġika u f’ reżistenza għall- iżvilupp.
Interaction with indinavir/ ritonavir not studied Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of fentanyl.
41
38 Medicinal products by therapeutic areas ANTIARRTHYMICS
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta l - morfina tingħata fl- istess ħin ma ’ indinavir/ ritonavir.
39 Medicinal products by Interaction therapeutic areas HMG-CoA REDUCTASE INHIBITORS IMMUNOSUPPRESSIVES
L- istess rakkomandazzjonijiet bħal ta ’ indinavir mingħajr tisħiħ ta ’ ritonavir (ara Tabella 1).
4.7 Effects on ability to drive and use machines
44 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
With the exception of dry skin, rash, and taste perversion, the incidence of clinical adverse reactions was similar or higher among patients treated with antiretroviral nucleoside analogue controls than among patients treated with CRIXIVAN alone or in combination.
Bl- eċċezzjoni tal- ġilda xotta, raxx u perverżjoni fit- togħma, l- inċidenza ta ’ reazzjonijiet kliniċi negattivi kien simili jew ogħla fost pazjenti li kienu kkurati b’ kontrolli analogi nukleosidi antiretrovirali bi CRIXIVAN waħdu jew flimkien ma ’ aġenti oħra.
41 The following adverse reactions have been reported during clinical studies and/ or post-marketing use for CRIXIVAN.
Ir- reazzjonijiet avversi li ġejjin ġew irrapurtati waqt studji kliniċi u/ jew l- użu wara t- tqegħid fis- suq ta ’ CRIXIVAN.
Very common: nausea; vomiting; diarrhoea; dyspepsia Common: flatulence; dry mouth; acid regurgitation Not known*: hepatitis, including reports of hepatic failure; pancreatitis.
Disturbi gastro- intestinali 45 Komuni ħafna: tqallih, rimettar, dijarrea, dispepsja Komuni: uġigħ ta ’ gass fl- istonku; ħalq niexef; rigurġitazzjoni ta ’ aċidu Mhux magħruf *: epatite, inkluż rapporti ta ’ insuffiċjenza epatika, pankreatite.
42 General disorders and administration site conditions:
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata:
The following additional laboratory abnormalities have been reported during post-marketing experience; they are derived from spontaneous reports for which precise incidences cannot be determined:
L- anormalitajiet fil- laboratorju li ġejjin ġew irrapurtati wara li l- prodott tpoġġa fis- suq; ġejjin minn rapporti spontanji li l- inċidenza tagħhom ma tistax tiġi determinata:
Metabolic and nutritional disorders: increased serum triglycerides, increased serum cholesterol.
Disturbi marbut mal- metaboliżmu u nutrizzjoni: żieda fit- trigliċeridi tas- serum, żieda fil- kolesterol tas - serum.
43 5.
47 5.
Mechanism of action Indinavir inhibits recombinant HIV– 1 and HIV– 2 protease with an approximate tenfold selectivity for HIV– 1 over HIV– 2 proteinase.
Kif jaħdem Indinavir jinibixxi l- protease rikombinanti ta ’ l- HIV- 1 u l- HIV- 2 b’ selettivita` bejn wieħed u ieħor ta ’ għaxar darbiet għall- HIV- 1 milli għall- HIV- 2 protease.
Synergistic antiretroviral activity was observed when human T– lymphoid cells infected with the LAI variant of HIV– 1 were incubated with indinavir and either zidovudine, didanosine, or NNRTIs.
Kienet osservata attivita` antiretrovirali sinerġistika meta ċelluli umani T- limfojdi infettati bil- varjant LAI ta ’ l- HIV- 1 kienu inkubati b’ indinavir u jew zidovudine, didanosine, jew l- NNRTIs.
In one comparative trial, combination therapy with nucleoside analogues (triple therapy with zidovudine plus didanosine) conferred protection against the selection of virus expressing at least one resistance–
Fi prova
44 associated amino acid substitution to both indinavir (from 13/ 24 to 2/ 20 at therapy week 24) and to the nucleoside analogues (from 10/ 16 to 0/ 20 at therapy week 24).
48 komparattiva, it- terapija kombinata b’ nukleosidi analogi (kura tripla b ’ zidovudine u didanosine) tat protezzjoni kontra l- għażla ta ’ virus li kellhom mill- inqas reżistenza waħda marbuta ma ’ sostituzzjoni amino aċida kemm lil indinavir (minn 13/ 24 sa 2/ 20 fl- 24 ġimgħa ta ’ kura) kif ukoll lin- nukleosidi analogi (minn 10/ 16 sa 0/ 20 fl- 24 ġimgħa ta ’ kura).
Cross resistance HIV− 1 patient isolates with reduced susceptibility to indinavir expressed varying patterns and degrees of cross– resistance to a series of diverse HIV PIs, including ritonavir and saquinavir.
Resistenza msallba L- iżolati tal- pazjenti bl- HIV- 1 b’ suxxettibilita` mnaqqsa għal indinavir kellhom varjeta` ta ’ forom u livelli ta ’ reżistenza li tintiret lil serje ta ’ HIV PIs differenti, inkluż ritonavir u saquinavir.
In the intent to treat and on treatment analyses the proportion of patients with HIV RNA of < 50 copies/ mL was 68.8% and 88.7%, respectively, at week 96.
Fl- intenzjoni li tiġi ttrattata l- analiżi Fl- intenzjoni li tiġi ttrattata l- analiżi u waqt it- trattament tagħha, il- proporzjon ta ’ pazjenti b’ HIV RNA ta ’ < 50 kopja/ mL kien ta ’ 68. 8% u 88. 7%, rispettivament, fil - ġimgħa 96.
Similarly, effects on CD4 cell count tend to be more pronounced in patients treated with indinavir in combination with nucleoside analogues compared with indinavir alone.
49 b’ indinavir flimkien ma ’ analogi nukleosidi meta mqabbla ma ’ indinavir waħdu.
In one study, at week 24, the proportion of patients with plasma viral RNA below 400 copies/ ml was 60%; the mean increase in CD4 cell counts was 242 cells/ mm3; and the mean increase in percent CD4 cell counts was 4.2%.
Fi studju wieħed, fl- 24 ġimgħa, il- proporzjon ta ’ pazjenti bi plażma virali RNA taħt l- 400 kopja/ ml kienet ta ’ 60%; iż- żieda medja ta ’ l- għadd fiċ- ċelluli CD4 kienet ta ’ 242 ċelluli/ mm3; iż- żieda prinċipali fil- persentaġġ ta ’ l- għadd ta ’ ċelluli CD4 kienet ta ’ 4. 2%.
AUC0-12h 116,067 nM*h (90% confidence interval = 101,680, 132,490), peak plasma concentrations 19,001 nM (90% confidence interval = 17,538, 20,588), and plasma concentrations at 12 hours post dose 2,274 nM (90% confidence interval = 1,701, 3,042).
AUC0- 12h 116067 nM* h (intervall tad- 90% = 101680, 132490), l- ogħla konċentrazzjonijiet tal- plażma ta ’ 19001 nM (intervall tad- 90% = 17538, 20588), u konċentrazzjonijiet tal- plażma 12- il siegħa wara d - doża ta ’ 2274 nM (intervall tad- 90% = 1701, 3042).
The AUC and peak plasma concentrations were generally similar to those previously observed in HIV– infected adults receiving the recommended dose of 800 mg every 8 hours; it should be observed that the plasma concentrations 8 hours post dose were lower.
B’ mod ġenerali l- AUC u l- ogħla konċentrazzjonijiet tal- plażma kienu simili għal dawk osservati qabel f’ adulti infettati bl- HIV li kienu 50 qed jingħataw id- doża rakkomandata ta ’ 800 mg kull 8 sigħat; għandu jiġi osservat li l - konċentrazzjonijiet tal- plażma 8 sigħat wara d- doża kienu iktar baxxi.
50%, 86%) lower than that observed 6 weeks postpartum.
50%, 86%) inqas minn dik osservata 6 ġimgħat wara l- ħlas.
46 indinavir in these 11 patients at 6 weeks postpartum were generally similar to those observed in non-pregnant patients in another study (see section 4.6).
Il- farmakokinetika ta ’ indinavir f’ dawn il- 11- il pazjenti fis- 6 ġimgħa wara l- ħlas kienu ġeneralment simili għal dawk osservati f’ pazjenti mhux tqal f ’ studju ieħor( ara sezzjoni 4. 6).
Patients with mild– to– moderate hepatic insufficiency and clinical evidence of cirrhosis had evidence of decreased metabolism of indinavir resulting in approximately 60% higher mean AUC following a 400– mg dose.
Pazjenti li għandhom insuffiċenza tal- fwied minn- ħafif- sa- moderat u evidenza klinika ta ’ ċirrożi kellhom evidenza ta ’ tnaqqis tal- metaboliżmu ta ’ indinavir li wassal għal bejn wieħed u ieħor medja 51 ogħla ta ’ 60% AUC wara doża ta ’ 400- mg.
An increase in thyroidal weight and thyroidal follicular cell hyperplasia, due to an increase in thyroxine clearance, was seen in rats treated with indinavir at doses ≥ 160 mg/ kg/ day.
Ġiet osservata żieda ta ’ piż tat- tirojde u iperplażja tirojdali taċ - ċelluli follikulari, minħabba żieda fit- tneħħija ta ’ thyroxine, fil- firien ikkurati b’ indinavir b’ dożi ≥ 160 mg/ kg/ jum.
47 Studies in rats indicated that uptake into brain tissue was limited, distribution into and out of the lymphatic system was rapid, and excretion into the milk of lactating rats was extensive.
Studji fil- firien indikaw li l- assorbiment mit- tessuti tal- moħħ kien limitat, id- distribuzzjoni għal ġo u ‘ l barra mis- sistema limfatika kienet mgħaġġla, u l- eskrezzjoni fil- ħalib tal- firien ireddgħu kienet estensiva.
- printing ink: indigo carmine (E 132).
- inka għall- istampar: indigo carmine (E 132).
6.2 Incompatibilities
52 6. 2 Inkompatibilitajiet
Keep the bottle tightly closed in order to protect from moisture.
Żomm il- flixkun magħluq sew biex il- prodott tipproteġih mill- umdita`.
HDPE bottles with a polypropylene cap and a foil induction cap containing 180, 270 or 360 capsules.
Fliexken HDPE li jkun fihom 180, 270 jew 360 kapsula u li jkunu b’ tapp tal- polipropilin u tapp ta ’ l - induzzjoni tal- fojl.
48 Not all pack sizes may be marketed.
Mhux il- qisien kollha jitpoġġew fis- suq.
CRIXIVAN 400 mg hard capsules
CRIXIVAN 400 mg kapsuli ibsin
Each hard capsule contains indinavir sulphate corresponding to 400 mg of indinavir.
Kull kapsula iebsa fiha indinavir sulphate li jikkorrispondi għal 400 mg ta ’ indinavir.
Each 400 mg capsule contains 149.6 mg of lactose.
Sustanza mhux attiva: kull kapsula ta ’ 400 mg fiha 149. 6 ta ’ lactose.
The capsules are semi– translucent white and coded CRIXIVAN™ 400 mg in green.
Il- kapsuli huma bojod semi– trasluċidi u kkodifikati CRIXIVAN™ 400 mg fl- aħdar.
50 Paediatric dose (500 mg/ m2) to be administered every 8 hours
54 Id- doża għat- tfal (50 mg / m2) li għandha tingħata kull 8 sigħat
51 In addition, indinavir with ritonavir should not be administered with alfuzosin, meperidine, piroxicam, propoxyphene, bepridil, encainide, flecanide, propafenone, quinidine, fusidic acid, clozapine, clorazepate, diazepam, estazolam and flurazepam.
55 Barra minn hekk, indinavir ma ’ ritonavir ma għandux jingħata ma ’ alfuzosin, meperidine, piroxicam, propoxyphene, bepridil, encainide, flecanide, propafenone, quinidine, fusidic acid, clozapine, clorazepate, diazepam, estazolam u flurazepam.
Acute haemolytic anaemia Acute haemolytic anaemia has been reported which in some cases was severe and progressed rapidly.
56 Anemija emolitika akuta Ġiet irrapuratata anemija emolitika akuta li f’ xi każijiet kienet severa u żviluppat għall- agħar b’ mod mgħaġġel.
52 Hyperglycaemia New onset diabetes mellitus, hyperglycaemia or exacerbation of existing diabetes mellitus has been reported in patients receiving protease inhibitors (PIs).
Ipergliċemija F’ pazjenti li kienu qed jingħataw inibituri tal- protease (PIs) ġew irrappurati l- bidu tad- dijabete mellitus, l- ipergliċemija u t- tiħrix tad- dijabete mellitus eżistenti.
Patients with mild– to– moderate hepatic insufficiency due to cirrhosis will require a dosage reduction of indinavir due to decreased metabolism of indinavir (see section 4.2).
57 Pazjenti li għandhom mard minn moderat sa qawwi fil- fwied minħabba ċirrożi jkollhom bżonn ta ’ tnaqqis fid- doża ta ’ indinavir minħabba l- metaboliżmu mnaqqas ta ’ indinavir (ara sezzjoni 4. 2).
53 Safety in patients with impaired renal function has not been studied; however, less than 20% of indinavir is excreted in the urine as unchanged drug or metabolites (see section 4.2).
Ma ġietx studjata s- sigurta` f’ pazjenti b’ mard fil- kliewi, madankollu, inqas minn 20% ta ’ indinavir jitneħħa ma ’ l- urina bħala mediċina mhux mibdula jew bħala metaboliti (ara sezzjoni 4. 2).
Lactose This medicinal product contains 299.2 mg of lactose in each 800 mg dose (maximum single dose).
Lactose Il- prodott mediċinali fih 299. 2 mg ta ’ lactose f’ kull doża ta ’ 800 mg (doża singola massima).
Table 1.
58 Tabella 1.
54 Medicinal products by therapeutic areas ANTI-INFECTIVES Antiretrovirals NRTIs
Prodotti medinċinali skond l- oqsma terapewtiċi ANTI- INFETTIVI Antiretrovirali NRTIs
Saquinavir 600 mg SD (hard gel capsule formulation) (Indinavir 800 mg TID)
61 Prodotti medinċinali skond l- oqsma terapewtiċi Saquinavir 600 mg SD
There are no interaction data available on the coadministration of indinavir/ ritonavir and amprenavir.
66
Rifampicin is a strong CYP3A4 inducer and has been shown to cause a 92% decrease in indinavir AUC which can result in virological failure and resistance development.
Rifampicin huwa induttur b’ saħħtu ta ’ CYP3A4 u ntwera li jikkawża tnaqqis ta ’ 92% fl - AUC ta ’ indinavir li jista ’ jirriżulta fi ħsara viroloġika u f’ reżistenza għall- iżvilupp.
The combination of rifampicin and CRIXIVAN with concomitant low-dose ritonavir is contraindicated (see section 4.3).
Il- kombinazzjoni ta ’ rifampicin u CRIXIVAN ma ’ ritonavir ta ’ doża baxxa konkomittanti hija kontraindikata (ara sezzjoni 4. 3).
Interaction with indinavir/ ritonavir not studied Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of fentanyl.
67
62 Medicinal products by therapeutic areas ANTIARRTHYMICS
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta l - morfina tingħata fl- istess ħin ma ’ indinavir/ ritonavir.
63 Medicinal products by Interaction therapeutic areas HMG-CoA REDUCTASE INHIBITORS IMMUNOSUPPRESSIVES
L- istess rakkomandazzjonijiet bħal ta ’ indinavir mingħajr tisħiħ ta ’ ritonavir (ara Tabella 1).
4.7 Effects on ability to drive and use machines
70 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
No studies on the effects on the ability to drive and use machines have been performed.
Ma sarux studji dwar l- effetti fuq i l- ħila biex issuq u tħaddem magni.
With the exception of dry skin, rash, and taste perversion, the incidence of clinical adverse reactions was similar or higher among patients treated with antiretroviral nucleoside analogue controls than among patients treated with CRIXIVAN alone or in combination.
Bl- eċċezzjoni tal- ġilda xotta, raxx u perverżjoni fit- togħma, l- inċidenza ta ’ r- reazzjonijiet kliniċi negattivi kien simili jew ogħla fost pazjenti li kienu kkurati b’ kontrolli analogi nukleosidi antiretrovirali bi CRIXIVAN waħdu jew flimkien ma ’ aġenti oħra.
Adverse recations, including nephrolithiasis, may lead to treatment interruption.
Reazzjonijiet negattivi, inkluż nefrolitjasis, jistgħu iwasslu għall- waqfien tal- kura.
65 The following adverse reactions have been reported during clinical studies and/ or post-marketing use for CRIXIVAN.
Ir- reazzjonijiet avversi li ġejjin ġew irrapurtati waqt studji kliniċi u/ jew l- użu wara t- tqegħid fis- suq ta ’ CRIXIVAN.
Very common: nausea; vomiting; diarrhoea; dyspepsia Common: flatulence; dry mouth; acid regurgitation Not known*: hepatitis, including reports of hepatic failure; pancreatitis.
Disturbi gastro- intestinali 71 Komuni ħafna: tqallih, rimettar, dijarrea, dispepsja Komuni: uġigħ ta ’ gass fl- istonku; ħalq niexef; rigurġitazzjoni ta ’ aċidu Mhux magħruf *: epatite, inkluż rapporti ta ’ insuffiċjenza epatika, pankreatite.
66 General disorders and administration site conditions:
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata:
Laboratory test findings The laboratory abnormalities reported by the investigators as possibly, probably, or definitely related to CRIXIVAN in ≥ 10% of patients treated with CRIXIVAN alone or in combination were:
72 L- anormalitajiet fil- laboratorju li ġew irrapurati mill- investigaturi bħala li hemm possibilita`, probabbilita` jew ċertezza li huma marbuta ma ’ CRIXIVAN f’ ≥ 10% mill- pazjenti li kienu kkurati bi CRIXIVAN biss jew flimkien ma ’ aġenti oħra kienu:
Blood and lymphatic system disorders: increases in MCV, decreases in neutrophils.
Mard tad- demm u tas- sistema limfatika: żidiet fl- MCV, tnaqqis fin- newtrofili.
Renal and urinary disorders: haematuria, proteinuria, crystalluria; pyuria in paediatric patients 3 years of age and older.
Mard tal- kliewi u tas- sistema urinarja: demm fl- urina, proteina fl- urina, kristalli fl- urina, urina taħraq f’ pazjenti tfal ta ’ tliet snin jew ikbar.
Hepato-biliary disorders: isolated asymptomatic hyperbilirubinaemia (total bilirubin ≥ 2.5 mg/ dl, 43 mcmol/ l), reported predominantly as elevated indirect bilirubin and rarely associated with elevations in ALT, AST, or alkaline phosphatase, has occurred in approximately 14% of patients treated with CRIXIVAN alone or in combination with other antiretroviral agents.
Mard tal- fwied u l- marrara: iperbilirubinimja asintomatika iżolata (bilirubina totali ≥ 2. 5 mg/ dl, 43 mcmol/ l), irrapurtata l- iktar bħala bilirubina indiretta elevata u rari marbuta ma ’ livelli ogħla fl - ALT, AST, jew alkaline phosphatase, seħħet f’ bejn wieħed u ieħor 14% tal- pazjenti kkurati bi CRIXIVAN biss jew flimkien ma ’ aġenti antiretrovirali oħra.
Metabolic and nutritional disorders: increased serum triglycerides, increased serum cholesterol.
Mard marbut mal- metaboliżmu u nutrizzjoni: żieda fit- trigliċeridi tas- serum, żieda fil- kolesterol tas - serum.
Hepato-biliary disorders: liver function abnormalities.
Mard tal- fwied u tal- marrara: anormalitajiet fil- funzjoni tal- fwied.
Musculoskeletal and connective tissue and bone disorders: increased CPK.
Mard muskolu- skeletali, tat- tessut konettiv u ta ’ l- għadam: żieda fiċ- CPK.
Microbiology Indinavir at concentrations of 50 to 100 nM mediated 95% inhibition (IC95) of viral spread (relative to an untreated virus– infected control) in human T– lymphoid cell cultures and primary human monocytes/ macrophages infected with HIV− 1 variants LAI, MN, RF, and a macrophage– tropic variant SF– 162, respectively.
73 Indinavir f’ konċentrazzjonjiet ta ’ minn 50 sa 100 nM immedja 95% ta ’ l- inibizzjoni (IC95) tal- firxa virali (meta mqabbel mal- kontroll mhux ikkurat infettat bil- virus) f’ kulturi ċellulari tat- T- limfojd umani u monoċiti u makrofaġi umani infettati bil- varjanti ta ’ l- HIV- 1 LAI, MN, RF, u varjant makrofagu- tropiku SF- 162, rispettivament.
68 associated amino acid substitution to both indinavir (from 13/ 24 to 2/ 20 at therapy week 24) and to the nucleoside analogues (from 10/ 16 to 0/ 20 at therapy week 24).
Fi prova komparattiva, it- terapija kombinata b’ nukleosidi analogi (kura tripla b ’ zidovudine u didanosine) tat protezzjoni kontra l- għażla ta ’ virus li kellhom mill- inqas reżistenza waħda marbuta ma ’ sostituzzjoni amino aċida kemm lil indinavir (minn 13/ 24 sa 2/ 20 fl- 24 ġimgħa ta ’ kura) kif ukoll lin- nukleosidi analogi (minn 10/ 16 sa 0/ 20 fl- 24 ġimgħa ta ’ kura).
Adults Treatment with indinavir alone or in combination with other antiretroviral agents (i. e., nucleoside analogues) has so far been documented to reduce viral load and increase CD4 lymphocytes in patients with CD4 cell counts below 500 cells/ mm3.
74 Il- kura b’ indinavir biss jew flimkien ma ’ aġenti antiretrovirali oħra (bħall- analogi nukleosidi) s’ issa ġew dokumentati li jnaqqsu l- ammont ta ’ virus u jkattru l- limfoċiti CD4 f’ pazjenti li kellhom l- għadd ta ’ ċelluli CD4 taħt il- 500 ċellula / mm3.
Absorption Indinavir is rapidly absorbed in the fasted state with a time to peak plasma concentration of 0.8 hours ± 0.3 hours (mean ± S. D.).
75 Assorbiment Indinavir jiġi assorbit malajr meta l- pazjent ikun sajjem bi żmien sakemm tintlaħaq l- ogħla konċentrazzjoni tal- plażma ta ’ 0. 8 sigħat ± 0. 3 sigħat (medja ± S. D.).
Indinavir boosted regimen.
Indinavir saħħaħ ir- reġimen.
Pharmacokinetic analysis in one study was performed on nineteen of the patients, with a median (range) indinavir AUC 0-12hr, Cmax, and Cmin of 25421 nM*h (21489-36236 nM*h), 5758 nM (5056-6742 nM) and 239 (169-421 nM), respectively.
Analiżi farmakokinetika fi studju wieħed twettqet fuq dsatax- il pazjent, b’ AUC 0- 12hr, Cmax, u Cmin medja (medda) ta ’ indinavir ta ’ 25421 nM* h (21489 - 36236 nM* h), 5758 nM (5056- 6742 nM) u 239 (169- 421 nM), rispettivament.
The pharmacokinetic parameters in the second study were comparable.
Il- parametri farmakokinetiċi fit- tieni studju kienu komparabbli.
In HIV− infected paediatric patients, a dosage regimen of indinavir hard capsules, 500 mg/ m2 every 8 hours, produced AUC0– 8hr values of 27412 nM*h, peak plasma concentrations of 12182 nM, and plasma concentrations at 8 hours post dose of 122 nM.
F’ pazjenti tfal infettati bl- HIV, kura b’ doża ta ’ kapsuli ibsin ta ’ indinavir ta ’ 500 mg/ m2 kull 8 sigħat, ipproduċiet valuri AUC0– 8hr ta ’ 27412 nM* h, l- ogħla konċentrazzjonijiet tal- plażma ta ’ 12182 nM, u konċentrazzjonijiet tal- plażma 8 sigħat wara d- doża ta ’ 122nM.
70 indinavir in these 11 patients at 6 weeks postpartum were generally similar to those observed in non-pregnant patients in another study (see section 4.6).
Il- farmakokinetika ta ’ indinavir f’ dawn il- 11- il pazjenti fis- 6 ġimgħa wara l- ħlas kienu ġeneralment simili għal dawk osservati f’ pazjenti mhux tqal f ’ studju ieħor( ara sezzjoni 4. 6).
The pharmacokinetics of indinavir taken as indinavir sulphate salt (from opened hard capsules) mixed in apple sauce were generally comparable to the pharmacokinetics of indinavir taken as hard capsules, under fasting conditions.
76 B’ mod ġenerali l- karatterisitiċi farmakokinetiċi ta ’ indinavir li jittieħed bħala indinavir sulphate salt (minn kapsuli ibsin miftuħa) mħallat maz- zalza tat- tuffieħ jistgħu jitqabblu mal- karatteristiċi farmakokinetiċi ta ’ indinavir li jittieħed bħala kapsuli ibsin, waqt sawm.
71 Studies in rats indicated that uptake into brain tissue was limited, distribution into and out of the lymphatic system was rapid, and excretion into the milk of lactating rats was extensive.
Studji fil- firien indikaw li l- assorbiment mit- tessuti tal- moħħ kien limitat, id- distribuzzjoni għal ġo u ‘ l barra mis- sistema limfatika kienet mgħaġġla, u l- eskrezzjoni fil- ħalib tal- firien ireddgħu kienet
- printing ink: titanium dioxide (E 171), indigo carmine (E 132) and iron oxide (E 172).
- inka għall- istampar: titanium dioxide (E 171), indigo carmine (E 132) u iron oxide (E 172).
2 years for HDPE bottles containing 18 hard capsules.
Sentejn għal fliexken HDPE li fihom 18- il kapsula iebsa.
3 years for HDPE bottles containing 90 and 180 hard capsules.
3 snin għal fliexken HDPE li fihom bejn 90 u 180 kapsula iebsa.
72 6.5 Nature and contents of container
78 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
HDPE bottles with a polypropylene cap and a foil induction cap containing 18, 90 or 180 capsules.
Fliexken HDPE li jkun fihom 18, 90 jew 180 kapsula u li jkunu b’ tapp tal- polipropilin u tapp ta ’ l - induzzjoni tal- fojl.
Not all pack sizes may be marketed.
Mhux il- qisien kollha jitpoġġew fis- suq.
73 ANNEX II
79 ANNESS II
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
DETENTUR TAL- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL- LOTT
CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE MARKETING AUTHORISATION HOLDER
• KUNDIZZJONIJIET JEW RESTRIZZJONIJIET FUQ IL- FORNIMENT U L- UŻU IMPOSTI FUQ ID- DETENTUR TA ’ L AWTORIZZAZZJONI GĦAT- TQEGĦID FIS - SUQ
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EEFECTIVE USE OF THE MEDICINAL PRODUCT
• KUNDIZZJONIJIET JEW RESTRIZZJONIJIET FIR- RIGWARD TA ’ L- UŻU MINGĦAJR PERIKLU U EFFETTIV TAL- PRODOTT MEDIĊINALI
OTHER CONDITIONS
• KUNDIZZJONIJIET OĦRA
The Marketing Authorisation Holder will continue to submit annual Periodic Safety Update Reports.
Id- Detentur ta ’ l- Awtorizzazzjoni tat- tqegħid fis- Suq se jkompli jissottometti Rapporti Perijodiċi Mġedda dwar is- Sigurtà.
75 ANNEX III
81 ANNESS III
77 PARTICULARS TO APPEAR ON THE OUTER PACKAGING CRIXIVAN 100 mg – pack of 180 capsules – Outer carton
CIRXIVAN 100 mg – pakkett ta ’ 180 kapsula – Kaxxa ta ’ barra
CRIXIVAN 100 mg hard capsules Indinavir
CRIXIVAN 100 mg kapsuli ibsin Indinavir
Anhydrous lactose.
Anhydrous lactose.
See leaflet for further information.
Għal iktar informazzjoni ara l- fuljett.
180 hard capsules
180 kapsula iebsa
METHOD AND ROUTES OF ADMINISTRATION
MOD TA ’ KIF U MNEJN JINGĦATA
Hard capsules should be swallowed whole.
Il- kapsuli ibsin għandhom jinbelgħu sħaħ.
Read the package leaflet before use.
Aqra l- fuljett tal- pakkett qabel tuża.
Desiccant should not be removed from the container.
Is- sustanza li tnixxef m’ għandhiex titneħħa mill- kontenitur.
Desiccant should not be swallowed.
Is- sustanza li tnixxef m’ għandhiex tinbela ’.
EXP
JIS [XX/ SSSS]
SPECIAL STORAGE CONDITIONS:
KUNDIZZJONIJIET SPEĊJALI TA 'KIF JINĦAŻEN
Keep the bottle tightly closed in order to protect from moisture.
Żomm il- flixkun magħluq sew biex tipproteġi mill- umdità.
79 PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
85 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT LI JMISS MAL- PRODOTT
CRIXIVAN 100 mg – pack of 180 capsules – Bottle label
CIRXIVAN 100 mg – pakkett ta ’ 180 kapsula – Tikketta tal- flixkun
CRIXIVAN 100 mg hard capsules Indinavir
CRIXIVAN 100 mg kapsuli iebsin Indinavir
Hard capsules should be swallowed whole.
Il- kapsuli iebsin għandhom jinbelgħu sħaħ.
Keep the bottle tightly closed in order to protect from moisture.
Żomm il- flixkun magħluq sew biex tilqa ’ mill- umdità.
Merck Sharp & Dohme Limited Hertford Road, Hoddesdon Hertfordshire EN11 9BU United Kingdom
Merck Sharp & Dohme Limited Hertford Road, Hoddesdon Hertfordshire EN11 9BU iR- Renju Unit
81 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
87 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
CRIXIVAN 200 mg – packs of 180, 270 and 360 capsules – Outer carton
CRIXIVAN 200 mg – pakketti ta ’ 180, 270 u 360 kapsula – Kartuna ta ’ barra
CRIXIVAN 200 mg hard capsules Indinavir
CRIXIVAN 200 mg kapsuli iebsin Indinavir
See leaflet for further information.
Ara l- fuljett għal iktar informazzjoni.
180 hard capsules 270 hard capsules 360 hard capsules
180 kapsula iebsa 270 kapsula iebsa 360 kapsula iebsa
Merck Sharp & Dohme Limited Hertford Road, Hoddesdon Hertfordshire EN11 9BU United Kingdom
Merck Sharp & Dohme Limited Hertford Road, Hoddesdon Hertfordshire EN11 9BU Ir- Renju Unit
EU/ 1/ 96/ 024/ 001 180 hard capsules EU/ 1/ 96/ 024/ 002 270 hard capsules EU/ 1/ 96/ 024/ 003 360 hard capsules
EU/ 1/ 96/ 024/ 001 180 kapsuli iebsin EU/ 1/ 96/ 024/ 002 270 kapsuli iebsin EU/ 1/ 96/ 024/ 003 360 kapsuli iebsin
83 PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
89 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT LI JMISS MAL- PRODOTT
CRIXIVAN 200 mg – packs of 180, 270 and 360 capsules – Bottle label
CRIXIVAN 200 mg – pakketti ta ’ 180, 270 u 360 kapsula – tikketta tal- flixkun
CRIXIVAN 200 mg hard capsules Indinavir
CRIXIVAN 200 mg kapsuli ibsin Indinavir
EU/ 1/ 96/ 024/ 001 180 hard capsules EU/ 1/ 96/ 024/ 002 270 hard capsules EU/ 1/ 96/ 024/ 003 360 hard capsules
EU/ 1/ 96/ 024/ 001 180 kapsuli ibsin EU/ 1/ 96/ 024/ 002 270 kapsuli ibsin EU/ 1/ 96/ 024/ 003 360 kapsuli ibsin
85 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
91 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
CRIXIVAN 400 mg – packs of 90, 180 and 18 capsules – Outer carton
CRIXIVAN 400 mg – pakketti ta ’ 90, 180 u 18- il kapsula – Kartuna ta ’ barra
CRIXIVAN 400 mg hard capsules Indinavir
CRIXIVAN 400 mg kapsuli ibsin Indinavir
See leaflet for further information.
Għal aktar informazzjoni ara l- fuljett.
90 hard capsules 180 hard capsules 18 hard capsules
90 kapsula iebsa 180 kapsula iebsa 18- il kapsula iebsa
EU/ 1/ 96/ 024/ 004 90 hard capsules EU/ 1/ 96/ 024/ 005 180 hard capsules EU/ 1/ 96/ 024/ 008 18 hard capsules
EU/ 1/ 96/ 024/ 004 90 kapsula iebsa EU/ 1/ 96/ 024/ 005 180 kapsula iebsa EU/ 1/ 96/ 024/ 008 18 il- kapsula iebsa
87 PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
93 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT LI JMISS MAL- PRODOTT
CRIXIVAN 400 mg – packs of 90, 180 and 18 capsules – Bottle label
CRIXIVAN 400 mg – pakketti ta ’ 90, 180 u 18- il kapsula – Tikketta tal- flixkun
CRIXIVAN 400 mg hard capsules Indinavir
CRIXIVAN 400 mg kapsuli iebsin Indinavir
Keep the bottle tightly closed in order to protect from moisture.
Żomm il- flixkun magħluq sew sabiex tilqa ’ mill- umdità.
90 PACKAGE LEAFLET:
96 FULJETT TA ’ TAGĦRIF:
CRIXIVAN 100 mg hard capsules indinavir
CRIXIVAN 100 mg kapsuli ibsin Indinavir
What CRIXIVAN is and what it is used for 2.
X’ inhu CRIXIVAN u għalxiex jintuża 2.
Before you take CRIXIVAN 3.
Qabel ma tieħu CRIXIVAN 3.
How to take CRIXIVAN 4.
Kif għandek tieħu CRIXIVAN 4.
Possible side effects 5.
Effetti sekondarji li jista ’ jkollu Kif taħżen CRIXIVAN 5.
WHAT CRIXIVAN IS AND WHAT IT IS USED FOR
X’ INHU CRIXIVAN U GĦALXIEX JINTUŻA
Pharmacotherapeutic Group CRIXIVAN is a member of a class of medicinal products called protease inhibitors.
Grupp farmakoterapewtiku CRIXIVAN huwa membru tal- klassi tal- prodotti mediċinali li jissejħu inibituri tal- protease.
It is active against the Human Immunodeficiency Virus (HIV) helping to reduce the number of HIV particles in blood.
Huwa attiv kontra l- Virus ta ’ l- Immunodefiċjenza Umana (HIV) u jgħin biex jitnaqqas l- għadd ta ’ partiċelli ta ’ l- HIV fid- demm.
Therapeutic Indications CRIXIVAN should be used in combination with other antiretroviral agents for the treatment of HIV– 1 infected adult and paediatric patients.
Indikazzjonijiet terapewtiċi CRIXIVAN għandu jintuża flimkien ma ’ aġenti retrovirali oħra għall- kura ta ’ pazjenti adulti u tfal infettati bl- HIV- 1.
CRIXIVAN has been shown to help reduce the risk of developing illnesses associated with HIV disease.
CIRXIVAN intwera li jgħin biex jonqos ir- riskju li jiżviluppa mard marbut mal- marda ta ’ l- HIV.
CRIXIVAN has also been shown to help lower the amount of HIV in your body (called “ viral load”) and raise your CD4 (T) cell count.
CRIXIVAN intwera wkoll li jgħin biex jitnaqqas l- ammont ta ’ HIV f’ ġismek (dak li jissejjaħ ‘ in - numru ta ’ virus ’) u biex jogħla l- għadd ta ’ ċelluli CD4 (T).
CD4 cells play a role in maintaining a healthy immune system to help fight infection.
Iċ- ċelluli CD4 għandhom rwol biex iżommu f’ saħħitha s- sistema immunitarja biex tgħin tikkumbatti l- infezzjoni.
CRIXIVAN may not have these effects in all patients.
CRIXIVAN jista ’ ma jkollux dawn l- effetti fuq il- pazjenti kollha.
BEFORE YOU TAKE CRIXIVAN
QABEL MA TIEĦU CRIXIVAN
Do not take CRIXIVAN
Tiħux CRIXIVAN
- if you are allergic (hypersensitive) to indinavir or any of the other ingredients of CRIXIVAN.
- jekk taf li tbati minn allerġiji (sensittività eċċessiva) għal indinavir attiva jew xi sustanzi oħra ta ’
Signs and symptoms of an allergic reaction may include: itchy skin, redness of the skin, wheals or hives, swelling of the face, lips, tongue and/ or throat, or difficulty breathing.
Is- sinjali u s- sintomi ta ’ reazzjoni allerġika jistgħu jkunu: ħakk fil- ġilda, ħmura fil- ġilda, tbenġil jew urtkarja, nefħa fil- wiċċ, xofftejn, ilsien u/ jew gerżuma, u diffikulta` biex tieħu n- nifs.
Do not take CRIXIVAN with or without ritonavir
Tiħux CRIXIVAN bi jew mingħajr ritonavir
- if you take products containing rifampicin, amiodarone, terfenadine, astemizole, cisapride,
- jekk qed tieħu prodotti li fihom rifampicin, amiodarone, terfenadine, astemizole, cisapride,
alprazolam, triazolam, oral (taken by mouth) midazolam (used to help you sleep and/ or to relieve anxiety), pimozide ergot derivatives such as ergot tartramine and ergot tartramine with caffeine, St.
alprazolam, triazolam, midazolam orali (meħud mill- ħalq), midazolam (li jintuża biex jgħinek torqod u/ jew biex tonqoslok l- ansjetà) pimozide jew derivattivi ta’ ergot bħal ergot tartramine u ergot tartramine bil- kafeina, St.
John's wort (Hypericum perforatum), simvastatin or lovastatin.
John’ s wort (Hypericum perforatum), simvastatin jew lovastatin.
In addition, do not take CRIXIVAN with ritonavir
Barra minn hekk, tiħux CRIXIVAN ma ’ ritonavir
- if you take products containing alfuzosin, meperidine, piroxicam, propoxyphene, bepridil,
- jekk qed tieħu prodotti li fihom alfuzosin, meperidine, piroxicam, propoxyphene, bepridil,
encainide, lecanide, propafenone, quinidine, fusidic acid, clozapine, clorazepate, diazepam, stazolam, and flurazepam.
encainide, lecanide, propafenone, quinidine, fusidic acid, clozapine, clorazepate, diazepam, stazolam, u flurazepam.
- if you have decompensated liver disease.
- jekk għandek mard tal- fwied dekompensat.
91 When CRIXIVAN is used with ritonavir, please tell your doctor and refer to the package leaflet for ritonavir for more information.
Meta jintuża CRIXIVAN ma ’ ritonavir, jekk jogħġbok għid lit- tabib tiegħek u rreferi għall- fuljett ta ’ tagħrif għal ritonavir għal aktar informazzjoni.