qanastek/EMEA-V3 huggingface dataset:
Careful monitoring of therapeutic and adverse effects is recommended when buspirone is concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta buspirone jingħata fl- istess ħin ma ’ indinavir/ ritonavir.
STEROIDS
L- interazzjoni indinavir/ ritonavir ma ġietx studjata, għoti kombinat huwa mistenni li jżid b’ mod sinjifikanti l - konċentrazzjonijiet ta ’ midazolam, b’ mod partikolari meta midazolam jingħata mill- ħalq (Inibizzjoni ta ’ CYP3A4).
CRIXIVAN with ritonavir and oral midazolam should not be coadministered (see section 4.3).
CRIXIVAN ma ’ ritonavir u midazolam li jittieħed mill - ħalq ma għandhomx jingħataw flimkien (ara sezzjoni 4. 3).
Caution should be used with coadministration of CRIXIVAN with ritonavir and parenteral midazolam.
Għandha tingħata kawtela meta CRIXIVAN b ’ ritonavir u midazolam parenterali jingħataw flimkien.
If CRIXIVAN with ritonavir is coadministered with parenteral midazolam, it should be done in an intensive care unit with close clinical monitoring in case of respiratory depression and/ or prolonged sedation.
Jekk CRIXIVAN ma ’ ritonavir jingħata fl- istess ħin ma ’ midazolam parenterali, dan għandu jsir f’ taqsima ta ’ kura intensiva b’ monitoraġġ kliniku mill- qrib fil- każ ta ’ depressjoni respiratorja u/ jew sedazzjoni mtawwla.
Dosage adjustment for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Għandu jkun ikkunsidrat aġġustament fid- doża għal midazolam, b’ mod speċjali jekk tingħata aktar minn doża waħda ta ’ midazolam.
Dexamethasone Interaction with indinavir/ ritonavir not studied ↑ dexamethasone exposure expected (CYP3A inhibition). ↓ indinavir plasma concentrations may be expected (CYP3A induction).
L- interazzjoni indinavir/ ritonavir ma ġietx studjata ↑ mistennija espożizzjoni ta ’ dexamethasone (inibizzjoni ta ’ CYP3A). ↓jistgħu jkunu mistennija konċentrazzjonijiet tal- plażma ta ’ indinavir (induzzjoni CYP3An).
Careful monitoring of therapeutic and adverse effects is recommended when dexamethasone is concomitantly administered with indinavir/ ritonavir.
Huwa rrakkomandat monitoraġġ attent ta ’ l- effetti terapewtiċi u avversi meta dexamethasone jingħata fl - istess ħin ma ’ indinavir/ ritonavir.
For information regarding diet or the effect of food on indinavir absorption (see
Għal informazzjoni dwar id- dieta jew l- effett ta ’ ikel fuq l- assorbiment ta ’ indinavir (ara sezzjoni 4. 2 u 5. 2).
section 4.2 and 5.2).
4. 6 Tqala u Treddigħ
Use during pregnancy There are no adequate and well-controlled studies in pregnant patients.
Użu waqt it- tqala M’ hemmx studji adegwati u kkontrollati sew f’ pazjenti tqal.
Indinavir should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Indinavir għandu jintuża fit- tqala biss meta l- potenzjal għall- benefiċċju jiġġustifika r- riskju potenzjali lill- fetu.
Given that substantially lower antepartum exposures have been observed in a small study of HIV-infected pregnant patients and the limited data in this patient population, indinavir use is not recommended in HIV-infected pregnant patients (see section 5.2).
Billi fi studju żgħir ta ’ pazjenti tqal infettati bl- HIV ġew osservati espożizzjonijiet/ qabel il- ħlas sostanzjalment iktar baxxi, u meta wieħed jikkonsidra wkoll it- tagħrif limitat f’ din il- popolazzjoni ta ’ pazjenti, l- użu ta ’ indinavir ta ’ indinavir mhux rakkomandat f’ pazjenti tqal infettati bl- HIV (ara sezzjoni 5. 2).
Hyperbilirubinaemia, reported predominantly as elevated indirect bilirubin, has occurred in 14% of patients during treatment with indinavir.
L- iperbilirubinemija, li kien irrapurtat l- iktar bħala livell elevat ta ’ bilirubina indiretta, seħħet f’ 14% tal- pazjenti waqt il- kura b’ indinavir.
Because it is unknown whether indinavir will exacerbate physiologic hyperbilirubinaemia in neonates, careful consideration must be given to the use of indinavir in pregnant women at the time of delivery (see section 4.8).
Billi mhux magħruf jekk indinavir iħarraxx l- iperbiliribinemija fiżjoloġika fi trabi li għadhom kemm twieldu, trid issir attenzjoni kbira meta indinavir jingħata lil nisa tqal waqt il- ħlas (ara sezzjoni 4. 8).
In Rhesus monkeys, administration of indinavir to neonates caused a mild exacerbation of the transient physiologic hyperbilirubinaemia seen in this species after birth.
F’ xadini Rhesus, meta indinavir ngħata lil trabi li għadhom kemm twieldu l- iperbilirubinemija fiżjoloġika li tgħaddi ħżienet fi ftit f’ din l- ispeċi wara t- twelid.
Administration of indinavir to pregnant Rhesus monkeys during the third trimester did not cause a similar exacerbation in neonates; however, only limited placental transfer of indinavir occurred.
L- amministrazzjoni ta ’ indinavir lix - xadini Rhesus ħobla waqt it- tielet semestru ma wasslitx għal tħarrix simili fit- trabi li għadhom kemm twieldu; madankollu ftit kien hemm trasferiment ta ’ indinavir mill- plaċenta.
Use during lactation It is recommended that HIV− infected women do not breast− feed their infants under any circumstances in order to avoid transmission of HIV.
Użu waqt li l- omm qed tredda ’ Huwa rakkomandat li nisa infettati bl- HIV ma jreddgħu bl- ebda mod lil uliedhom biex jevitaw li jittrażmettu l- HIV.
It is not known whether indinavir is excreted in human milk.
Mhux magħruf jekk indinavir joħroġx mal- ħalib tas- sider.
Mothers should be instructed to discontinue breast− feeding during treatment.
L- ommijiet għandhom jingħataw istruzzjonijiet li ma jkomplux ireddgħu waqt il- kura.
4.7 Effects on ability to drive and use machines
18 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- effett fuq il- ħila biex issuq u tħaddem il- magni.
There are no data to suggest that indinavir affects the ability to drive and use machines.
M’ hemmx tagħrif li jindika li indinavir jafettwa l- ħila li ssuq u li tħaddem il- magni.
However, patients should be informed that dizziness and blurred vision have been reported during treatment with indinavir.
Madankollu, il- pazjenti għandhom ikunu infurmati li ġew irrapurtati sturdamenti u viżta mċajpra waqt il- kura b’ indinavir.
In controlled clinical trials conducted world– wide, indinavir was administered alone or in combination with other antiretroviral agents (zidovudine, didanosine, stavudine, and/ or lamivudine) to approximately 2,000 patients, the majority of whom were adult Caucasian males (15% females).
Fi provi kliniċi kkontrollati li saru madwar id- dinja, indinavir ingħata waħdu jew flimkien ma ’ aġenti oħra antiretrovirali (zidovudine, didanosine, stavudine, u/ jew lamivudine) li bejn wieħed u ieħor 2000 pazjent, li l- maġġoranza tagħhom kienu rġiel adulti Kawkażiċi (15% nisa).
Indinavir did not alter the type, frequency, or severity of known major adverse effects associated with the use of zidovudine, didanosine, or lamivudine.
Indinavir ma biddilx it- tip, frekwenza jew is- severita` ta ’ l- effetti prinċipali negattivi li huma marbuta ma ’ l- użu ta ’ zidovudine, didanosine, jew lamivudine.
Clinical adverse reactions reported by the investigators as possibly, probably, or definitely related to CRIXIVAN in ≥ 5% of patients treated with CRIXIVAN alone or in combination (n = 309) for 24 weeks are listed below.
L- investigaturi rrapurtaw reazzjonijiet kliniċi negattivi li hemm possibilita`, probabbilita` jew ċertezza li huma marbuta ma ’ CRIXIVAN f’ ≥ 5% tal- pazjenti li ġew ikkurati bi CRIXIVAN biss jew flimkien ma ’ aġenti oħrajn (n = 309) għal 24 ġimgħa, u li jinġiebu hawn taħt.
Many of these adverse reactions were also identified as common pre– existing or frequently occurring medical conditions in this population.
Ħafna mir- reazzjonijiet negattivi kienu identifikati wkoll bħala li huma kondizzjonijiet mediċi komuni li jkunu hemm minn qabel jew li jseħħu sikwit f’ din il- popolazzjoni.
These adverse reactions were: nausea (35.3%), headache (25.2%), diarrhoea (24.6%), asthenia/ fatigue (24.3%), rash (19.1%), taste perversion (19.1%), dry skin (16.2%), abdominal pain (14.6%), vomiting (11.0%), dizziness (10.7%).
Dawn ir- reazzjonijiet negattivi kienu: tqallih (35. 3%), uġigħ ta ’ ras (25. 2%), dijarrea (24. 6%), astenja/ għeja (24. 3%), raxx (19. 1%), perverżjoni tat- togħma( 19. 1%), ġilda xotta (16. 2%), uġigħ fiż- żaqq (14. 6%), rimettar (11. 0%), sturdament (10. 7%).
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 tar- 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.
This overall safety profile remained similar for 107 patients treated with CRIXIVAN alone or in combination for up to 48 weeks.
Dawn il- karatteristiċi ta ’ sigurta` kienu simili wkoll għal 107 pazjenti kkurati bi CRIXIVAN waħdu jew flimkien ma ’ aġenti oħra għal perjodu sa 48 ġimgħa.
Adverse reactions, including nephrolithiasis, may lead to treatment interruption.
Reazzjonijiet negattivi, inkluż nefrolitjasis, jistgħu iwasslu għall- waqfien tal- kura.
Adverse reactions have also been reported during post-marketing experience* as they are derived from spontaneous reports, incidences cannot be determined.
Ġew irrapurtati wkoll reazzjonijiet avversi fl- esperjenza ta ’ wara t- tqegħid fis- suq * li ttieħdu minn rapporti spontanji, l- inċidenza mhix magħrufa.
17 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 (≥ 1/ 10); Common (≥ 1/ 100, < 1/ 10); Uncommon (≥ 1/ 1,000, < 1/ 100); Rare (≥ 1/ 10,000, < 1/ 1,000); Very rare (< 1/ 10,000); not known (cannot be estimated from the available data).
Komuni ħafna (≥ 1/ 10); Komuni (≥ 1/ 100, < 1/ 10); Mhux komuni (≥ 1/ 1, 000, < 1/ 100); Rari (≥1/ 10, 000, < 1/ 1, 000); Rari ħafna (< 1/ 10, 000); mhux magħruf (ma jistax jiġi mkejjel mit- tagħrif li għandna).
Blood and the lymphatic disorders:
Distrubi tad- demm u tas- sistema limfatika:
Not known*: increased spontaneous bleeding in patients with haemophilia; anemia including acute haemolytic anaemia; thrombocytopenia (see section 4.4).
Mhux magħruf *: żieda spontanja tal- fsad f’ pazjenti b’ emofilja; anemija inkluż anemija emolitika akuta; tromboċitopenja (ara sezzjoni 4. 4).
Immune system disorders:
Disturbi tas- sistema immunitarja:
Not known*: anaphylactoid reactions.
Mhux magħruf *: reazzjonijiet anafilaktojdi.
Metabolism and nutrition disorders:
Disturbi fil- metaboliżmu u fin- nutrizzjoni:
Not known*: new onset diabetes mellitus or hyperglycaemia, or exacerbation of pre-existing diabetes mellitus (see section 4.4).
Mhux magħruf *: episodju ġdid ta ’ dijabete mellitus jew ipergliċemija, jew tħarrix ta ’ dijabete mellitus diġà preżenti (ara sezzjoni 4. 4).
Very common: headache, dizziness Common: insomnia; hypoaesthesia; paraesthesia Not known*: oral paraesthesia.
Mhux magħruf *: parastesja orali.
Gastrointestinal disorders:
Disturbi gastro- intestinali
Very common: nausea; vomiting; diarrhoea; dyspepsia Common: flatulence; dry mouth; acid regurgitation Not known*: hepatitis, including reports of hepatic failure; pancreatitis.
19 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.
Very common: rash, dry skin Common: pruritus Not known*: rash including erythema multiforme and Stevens Johnson syndrome; hypersensitivity vasculitis; alopecia, hyperpigmentation; urticaria; ingrown toenails and/ or paronychia
Disturbi tal- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni ħafna: raxx; ġilda xotta Komuni: ħakk Mhux magħruf *: raxx inkluż eritema multiforme u Sindromu ta ’ Stevens Johnson; ipersensitività vaskulite, alopeċja, iperpigmentazzjoni; urtikarja; dwiefer tas- saqajn li jikbru ‘ l ġewwa u/ jew paronikja
Musculoskeletal, connective tissue and bone disorders:
Disturbi muskolu- skeletali, tat- tessut konnettiv ’ u ta ’ l- għadam:
Common: myalgia Not known*: myositis; rhabdomyolysis
Komuni: uġigħ fil- muskoli Mhux magħruf *: majożite, rabdomajlożi
Renal and urinary disorders:
Disturbi fil- kliewi u fis- sistema urinarja:
Very common: nephrolithiasis in paediatric patients 3 years of age and older.
Komuni ħafna: nefrolitijasi f’ pazjenti tfal ta ’ 3 snin jew ikbar.
Common: nephrolithiasis in adults; dysuria.
Komuni: nefrolitijasi f’ pazjenti adulti; disurja.
Nephrolithiasis, including flank pain with or without haematuria (including microscopic haematuria), has been reported in approximately 10% (252/ 2,577) of patients receiving CRIXIVAN in clinical trials at the recommended dose compared to 2.2% in the control arms.
Fi provi kliniċi ġie rrapurat nefrolitjasis, inkluż uġigħ fil- ġenb bid- demm fl- urina jew mingħajru (inkluż ammont mikroskopiku ta ’ demm fl- urina), bejn wieħed u ieħor f’ 10% (252/ 2, 577) tal- pazjenti li kienu qed jingħataw CRIXIVAN bid- doża rakkomandata meta mqabbel ma ’ 2. 2% fil- grupp ta ’ kontroll.
In general, these events were not associated with renal dysfunction and resolved with hydration and temporary interruption of therapy (e. g., 1– 3 days).
B’ mod ġenerali, dawn l- episodji ma kinux assoċjati ma ’ mard fil- kliewi u ġew ikkurati bl - idrazzjoni jew bl- interruzzjoni temporanja tat- terapija (ngħidu aħna bejn jum u 3 ijiem).
In clinical trials in paediatric patients 3 years of age and older, the adverse experience profile was similar to that for adult patients except for a higher frequency of nephrolithiasis of 29% (20/ 70) in paediatric patients who were treated with CRIXIVAN at the recommended dose of 500 mg/ m2 every 8 hours.
Fi studji kliniċi f’ pazjenti tfal ta ’ tliet snin jew ikbar, it- tip ta ’ esperjenzi negattivi kienu l- istess bħal tal- pazjenti adulti ħlief għal frekwenzi ogħla ta ’ nefrolitjatsis ta ’ 29% (20/ 70) f’ pazjenti tfal li kienu kkurati bi CRIXIVAN bid- doża rakkomandata ta ’ 500 mg/ m2 kull 8 sigħat.
Not known*: nephrolithiasis, in some cases with renal insufficiency or acute renal failure; pyelonephritis; interstitial nephritis, sometimes associated with indinavir crystal deposits.
Mhux magħruf *: nefrolitjasis, f’ xi każijiet b’ insuffiċjenza renali jew insuffiċjenza renali akuta; pajlonefrite; nefrite interstitjali, xi kultant marbut ma ’ depożiti ta ’ kristalli ta ’ indinavir.
In some patients, resolution of the interstitial nephritis did not occur following discontinuation of indinavir therapy; renal insufficiency; renal failure; leucocyturia (see section 4.4).
F’ xi pazjenti, ir- riżoluzzjoni ta ’ nefrite interstitjali ma seħħitx wara li twaqqfet it- terapija b’ indinavir; insuffiċjenza renali; kollass renali; lewkoċiturja (ara sezzjoni 4. 4).
18 General disorders and administration site conditions:
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata:
Very common: asthenia/ fatigue; taste perversion; abdominal pain.
Komuni ħafna: astenja/ għejja; perverżjoni tat- togħma, uġigħ addominali.
Not known*:
Mhux magħruf *:
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 fat and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
It- terapija kombinata antiretrovirali ġiet marbuta ma ’ ridistribuzzjoni tax- xaħam tal - ġisem (lipodistrofija) f’ pazjenti bl- HIV, inkluż it- telfien tax- xaħam periferali u tal- wiċċ ta ’ taħt il- ġilda, żieda fix- xaħam addominali u fil- vixxri, ipertrofija tas- sider u akkumulazzjoni ta ’ xaħam madwar ix - xewka tad- dahar (ħotba ta ’ buflu).
Combination antiretroviral therapy has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia (see section 4.4).
(ara sezzjoni 4. 4).
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).
Ġew irrapurtati każijiet ta ’ ostejonekrożi, speċjalment f’ pazjenti b’ fatturi ta ’ riskju ġeneralment rikonoxxuti, mard ta ’ l- HIV avvanzat jew espożizzjoni fit- tul ta ’ terapija antiretrovirali kombinata (CART).
The frequency of this is unknown (see section 4.4).
Il- frekwenza ta ’ dan mhux magħruf (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).
(ara sezzjoni 4. 4).
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:
Tagħrif mit- testijiet fil- laboratorju 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:
Very common (> 10%)
Komuni ħafna (> 10%)
Blood and lymphatic system disorders: increases in MCV, decreases in neutrophils.
Distrubi 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.
Disturbi 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.
Disturbi 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.
Most patients continued treatment with CRIXIVAN without dosage reduction and bilirubin values gradually declined toward baseline.
Ħafna mill- pazjenti komplew il- kura bi CRIXIVAN mingħajr ma naqqsu d- doża u l- valuri tal- bilirubina naqsu bil- mod lejn in- normal.
Hyperbilirubinaemia occurred more frequently at doses exceeding 2.4 g/ day compared to doses less than 2.4 g/ day.
L - iperbilirubinimja seħħet l- iktar b’ dożi ta ’ iktar minn 2. 4 g/ jum imqabbla ma ’ dożi ta ’ inqas minn 2. 4 g/ jum.
Increased ALT and AST.
Livelli ogħla ta ’ ALT u AST.
In clinical trials with CRIXIVAN in paediatric patients 3 years of age and older, asymptomatic pyuria of unknown etiology was noted in 10.9% (6/ 55) of patients who received CRIXIVAN at the recommended dose of 500 mg/ m2 every 8 hours.
Fi provi kliniċi bi CRIXIVAN f’ pazjenti tfal ta ’ tliet snin jew ikbar, kien innutat ħruq fl- urina asintomatiku li mhux magħruf mnejn ġej f’ 10. 9% (6/ 55) mill- pazjenti li ngħataw CRIXIVAN fid - doża rakkomandata ta ’ 500 mg/ m2. kull 8 sigħat.
Some of these events were associated with mild elevation of serum creatinine.
Xi wħud minn dawn il- pazjenti kienu assoċjati ma ’ livelli kemmxejn ogħla ta ’ kreatinina fis- serum.
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:
Apparti dan, 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 marbutin mal- metaboliżmu u nutrizzjoni: żieda fit- trigliċeridi tas- serum, żieda fil- kolesterol tas- serum.
Hepato-biliary disorders: liver function abnormalities.
Disturbi tal- fwied u tal- marrara: anormalitajiet fil- funzjoni tal- fwied.
Musculoskeletal and connective tissue and bone disorders: increased CPK.
Disturbi muskolu- skeletali, tat- tessut konettiv u ta ’ l- għadam: żieda fiċ- CPK.
There have been reports of human overdose with CRIXIVAN.
Kien hemm rapporti ta ’ doża eċċessiva bi CRIXIVAN fil- bnedmin.
The most commonly reported symptoms were gastro-intestinal (e. g., nausea, vomiting, diarrhoea) and renal (e. g., nephrolithiasis, flank pain, haematuria).
L- iktar sintomi komuni li ġew irrappurtati kienu gastro- intestinali (bħal tqallih, rimettar, dijarrea) u fil- kliewi (bħan- nefrolitjasis, uġigħ fil- ġenb, demm fl- urina).
It is not known whether indinavir is dialyzable by peritoneal or haemodialysis.
M’ hux magħruf jekk indinavir hux dijalizzabbli b’ mod peritonali jew b’ ħemodijaliżi.
Protease inhibitor, ATC code JO5AE02
Inibitur tal- protease, Kodiċi ATC JO5AE02
Mechanism of action Indinavir inhibits recombinant HIV– 1 and HIV– 2 protease with an approximate tenfold selectivity for HIV– 1 over HIV– 2 proteinase.
21 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.
Indinavir binds reversibly to the protease active site and inhibits competitively the enzyme, thereby preventing cleavage of the viral precursor polyproteins that occurs during maturation of the newly formed viral particle.
Indinavir jintrabat b’ mod reversibbli mas- sit attiv tal- protease u jinibixxi b’ mod kompetittiv l- enzima, u b’ hekk iwaqqaf milli l- poliproteini prekursuri virali jinqasmu li sseħħ waqt il- maturazzjoni tal- partiċella virali li għadha kemm ġiet iffurmata.
The resulting immature particles are non– infectious and are incapable of establishing new cycles of infection.
Il- partiċelli immaturi li jiffurmaw b’ dan il- mod m’ humiex infettivi u ma jistgħux jistabbilixxu ċikli ġodda ta ’ infezzjoni.
Indinavir did not significantly inhibit the eukaryotic proteases human renin, human cathepsin D, human elastase, and human factor Xa.
Indinavir ma ’ jinibixxix b’ mod sinifikanti eukaryotic proteases human renin, human cathepsin D, human elastase, u human factor Xa.
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.
Mikrobijoloġija 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.
Indinavir at concentrations of 25 to 100 nM mediated 95% inhibition of viral spread in cultures of mitogen– activated human peripheral blood mononuclear cells infected with diverse, primary clinical isolates of HIV− 1, including isolates resistant to zidovudine and non– nucleoside reverse transcriptase inhibitors (NNRTIs).
Indinavir f’ konċentrazzjonjiet minn 25 sa 100 nM immedja95% ta ’ l- inibizzjoni tal- firxa virali f’ kulturi ta ’ ċelluli mononukleari periferali tad- demm uman attivati bil- mitoġen infettati b’ iżolati kliniċi primarji diversi ta ’ l- HIV- 1, inkluż iżolati reżistenti għal zidovudine u inibituri mhux nukleosidi reverse transkriptase (NNRTIs).
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 NNRTIs.
Drug resistance Loss of suppression of viral RNA levels occurred in some patients; however, CD4 cell counts were often sustained above pre– treatment levels.
Reżistenza għall- mediċina F’ xi pazjenti ma tkomplitx is- soppressjoni tal- livelli virali RNA; madankollu, l- għadd taċ- ċelluli CD4 ħafna drabi baqa ’ fil- livelli ta ’ qabel il- kura.
When loss of viral RNA suppression occurred, it was typically associated with replacement of circulating susceptible virus with resistant viral variants.
Fejn seħħet it- tneħħija tas- soppressjoni tal- livelli virali RNA, tipikament dan kien marbut mal- bdil tal- virus suxxettibbli ċirkulanti b’ varjanti reżistenti tal - virus.
Resistance was correlated with the accumulation of mutations in the viral genome that resulted in the expression of amino acid substitutions in the viral protease.
Ir- reżistenza kienet korrelatata ma ’ l- akkumulu tal- mutazzjonijiet fil- ġenoma virali li permezz tagħha ħarġu s- sostituzzjonijiet ta ’ l- amino aċidi fil- protease virali.
At least eleven amino acid sites in the protease have been associated with indinavir resistance:
Hemm mill- inqas ħdax- il sit ta ’ l- amino aċidi fil- protease li ġew marbuta mar- reżistenza lil indinavir:
L10, K20, L24, M46, I54, L63, I64, A71, V82, I84, and L90.
L10, K20, L24, M46, I54, L63, I64, A71, V82, I84, u L90.
The basis for their contributions to resistance, however, is complex.
Madankollu, ir- raġuni għall - kontribuzzjonijiet tagħhom għar- reżistenza hija komplessa.
None of these substitutions was either necessary or sufficient for resistance.
L- ebda waħda minn dawn is - sostituzzjonijiet ma kienet neċessarja jew biżżejjed biex ikun hemm reżistenza.
For example, no single substitution or pair of substitutions was capable of engendering measurable (≥ four– fold) resistance to indinavir, and the level of resistance was dependent on the ways in which multiple substitutions were combined.
Ngħidu aħna, ma kienx hemm sostituzzjoni waħedha jew par ta ’ sostituzzjonijiet li setgħu iwasslu biex ikun hemm reżistenza għal indinavir li setgħet titkejjel (≥ erba ’ darbiet), u l- livell ta ’ reżistenza kien jiddependi mill- modi kif kienu kkombinati s- sostituzzjonijiet multipli.
In general, however, higher levels of resistance resulted from the co– expression of greater numbers of substitutions at the eleven identified positions.
B’ mod ġenerali, iżda, meta kien hemm livelli ogħla ta ’ reżistenza, dawn ġew minn ko- espressjoni ta ’ numri ikbar ta ’ sostituzzjonijiet fil- ħdax- il pożizzjoni identifikati.
V82 (to A or F), M46 (to I or L), and L10 (to I or R).
Fost il- pazjenti li reġa ’ kellhom qabża fl- RNA virali waqt li kienu qed jiġu kkurati b’ indinavir biss b’ doża ta ’ 800 mg q8h, fil- maġġoranza tal- pazjenti ġew osservati sostituzzjonijiet f’ żewġ jew tliet siti biss V82 (sa A jew F), M46 (sa I jew L), and L10 (sa I jew R).
Other substitutions were observed less frequently.
Sostituzzjonijiet oħra ġew osservati b’ mod inqas frekwenti.
The observed amino acid substitutions appeared to accumulate sequentially and in no consistent order, probably as a result of ongoing viral replication.
Is- sostituzzjonijiet ta ’ l- amino aċidi li ġew osservati dehru li qed jakkumulaw b’ sekwenza u mhux b’ xi ordni konsistenti, aktarx minħabba r- replikazzjoni virali li kienet għadha għaddejja.
It should be noted that the decrease in suppression of viral RNA levels was seen more frequently when therapy with indinavir was initiated at doses lower than the recommended oral dose of 2.4 g/ day.
Għandu jiġi nnutat li t- tnaqqis fis- soppressjoni tal- livelli virali ta ’ l- RNA iktar ġew osservati meta l - kura b’ indinavir inbdiet b’ dożi iżgħar mid- doża orali rakkomandata ta ’ 2. 4 g/ jum.
Therefore, therapy with indinavir should be initiated at the recommended dose to increase suppression of viral replication and therefore inhibit the emergence of resistant virus.
Għalhekk, il- kura bl- indinavir għandha tinbeda mid- doża rakkomandata biex tkabbar is- soppressjoni tar - replikazzjoni virali u għalhekk tinibixxi l- iżvilupp ta ’ virus reżistenti.
The concomitant use of indinavir with nucleoside analogues (to which the patient is naive) may lessen the risk of the development of resistance to both indinavir and the nucleoside analogues.
L- użu flimkien ta ’ indinavir ma ’ nukleosidi analogi (li l- pazjent qatt ma jkun uża qabel) jista ’ jnaqqas ir- riskju ta ’ l- iżvilupp tar- reżistenza kemm għal indinavir kif ukoll għan- nukleosidi analogi.
20 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).
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.
22 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.
Complete cross− resistance was noted between indinavir and ritonavir; however, cross− resistance to saquinavir varied among isolates.
Ġiet innutata reżistenza sħiħa li tintiret bejn indinavir u ritonavir; madankollu, ir- reżistenza li tintiret lil saquinavir kienet tvarja minn iżolat għal iżolat.
Many of the protease amino acid substitutions reported to be associated with resistance to ritonavir and saquinavir were also associated with resistance to indinavir.
Ħafna mis- sostituzzjonijiet ta ’ l- amino aċidi tal- protease li ġew irrapurtati li kienu marbuta ma ’ reżistenza għal ritonavir u saquinavir kienu marbuta wkoll ma ’ reżistenza għal indinavir.
Pharmacodynamic effects
Effetti farmakodinamiċi
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.
Adulti 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.
In one published study, 20 HIV-infected patients with undetectable plasma viral load (< 200 copies / ml) receiving indinavir 800 mg every 8 hours were switched in an open, cross-over design to indinavir/ ritonavir 400/ 100 mg every 12 hours.
Fi studju wieħed ippubblikat, 20 pazjent infettat bl- HIV b’ tagħbija virali tal- plażma li ma tistax tiġi ntraċċata (< 200 kopja/ ml) li kienu qegħdin jirċievu 800 mg kull 8 sigħat inqelbu għal disinn miftuħ, cross- over għal indinavir/ ritonavir 400/ 100 mg kull 12- il siegħa.
Eighteen patients completed the study to week 48.
Tmintax il- pazjent temmew l- istudju sa ġimgħa 48.
Viral load remained < 200 copies/ mL for 48 weeks in all patients.
It- tagħbija virali baqgħet < 200 kopja/ mL għal 48 ġimgħa fil- pazjenti kollha.
Another published study evaluated the efficacy and safety of indinavir/ ritonavir 400/ 100 mg every 12 hours in 40 antiretroviral-naïve patients.
Studju ieħor ippubblikat evalwa l- effikaċja u s- sigurtà ta ’ indinavir/ ritonavir 400/ 100 mg kull 12- il siegħa f’ 40 pazjent li qatt ma kienu ħadu antiretrovirali.
Thirty subjects completed 48 weeks of treatment.
Tletin suġġett temmew 48 ġimgħa ta ’ kura.
At week 4, the indinavir Cmin was 500 ng/ mL with substantial trough variability (range 5 to 8100 ng/ mL).
F’ ġimgħa 4, il- Cmin ta ’ indinavir kien 500 ng/ mL b’ varjabilità minima sostanzjali (medda ta ’ 5 sa 8100 ng/ mL).
By intent to treat analysis 65% of patients had HIV RNA < 400 copies/ mL and 50% had viral load < 50 copies/ mL; by on-treatment analysis 96% of patients had HIV RNA < 400 copies/ mL and 74% had viral load < 50 copies/ mL.
B’ intenzjoni li tiġi ttrattata analiżi, 65% tal- pazjenti kellhom HIV RNA < 400 kopja/ mL u 50% kellhom tagħbija virali < 50 kopja/ mL; b’ analiżi fuq it- trattament 96% tal- pazjenti kellhom HIV RNA < 400 kopja/ mL u 74% kellhom tagħbija virali < 50 kopja/ mL.
Eighty antiretroviral naïve patients were entered into a third published study.
Tmenin pazjent antiretrovirali ddaħħlu f’ tielet studju ppubblikat.
In this open label non- randomized single arm study, patients were treated with stavudine and lamivudine plus indinavir/ ritonavir 400/ 100 mg every 12 hours.
F’ dan l- istudju ta ’ fergħa waħda, mhux randomizzat b’ tikketta mikxufa, il- pazjenti ġew ittrattati b’ stavudine u lamivudine flimkien ma ’ indinavir/ ritonavir 400/ 100 mg kull 12- il siegħa.
Sixty-two patients completed the study to week 96.
Tnejn u sittin pazjent temmew l- istudju sa ġimgħa 96.
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 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.
Indinavir alone or in combination with nucleoside analogues (zidovudine/ stavudine and lamivudine) has been shown to delay clinical progression rate compared with nucleoside analogues and to provide a sustained effect on viral load and CD4 count.
Intwera li indinavir waħdu jew flimkien ma ’ analogi nukleosidi (zidovudine/ stavudine u lamivudine) idawwar il- progressjoni klinika meta mqabbel ma ’ analogi nukleosidi u jipprovdi effett sostnut fuq l - ammont ta ’ virus u l- għadd CD4.
In zidovudine experienced patients, indinavir, zidovudine and lamivudine in combination compared with lamivudine added to zidovudine reduced the probability of AIDS defining illness or death (ADID) at 48 weeks from 13% to 7%.
F’ pazjenti li diġa` kienu jieħdu ziduvudine, meta indinavir, zidovudine u lamivudine ittieħdu flimkien u dan tqabbel ma ’ lamivudine miżjud ma ’ zidovudine, kien hemm tnaqqis tal- probabbilta` ta ’ mwiet jew mard minħabba AIDS (ADID) fit- 48 ġimgħa minn 13% għal 7%.
Similarly, in antiretroviral naive patients, indinavir with and without zidovudine compared with zidovudine alone reduced the probability of ADID at 48 weeks from 15% with zidovudine alone to approximately 6% with indinavir alone or in combination with zidovudine.
Bl- istess mod, f’ pazjenti li qabel ma kinux qed jieħdu kura antiretrovirali, indinavir waħdu jew ma ’ zidovudine meta mqabbel ma ’ zidovudine waħdu naqqas il- probabbilta` ta ’ ADID fit- 48 ġimgħa minn 15% b’ zidovudine biss għal bejn wieħed u ieħor 6% b’ indinavir biss jew flimkien ma ’ zidovudine.
Effects on viral load were consistently more pronounced in patients treated with indinavir in combination with nucleoside analogues, but the proportion of patients with serum viral RNA below the limit of quantification (500 copies/ ml) varied between studies, at week 24 from 40% to more than 80%.
L- effetti fuq l- ammont ta ’ virus kienu iktar qawwija b’ mod konsistenti f’ pazjenti kkurati b’ indinavir flimkien ma ’ analogi nukleosidi, imma l- proporzjon ta ’ pazjenti bis- serum virali RNA taħt il- livell minimu ta ’ kwantifikazzjoni (500 kopji/ ml) kien ivarja minn studju għal ieħor, fl- 24 ġimgħa minn 40% sa iktar minn 80%.
This proportion tends to remain stable over prolonged periods of follow– up.
Dan il- proporzjon aktarx li jibqa ’ stabbli għal perjodi twal wara l- kura.
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.
Bl - istess mod, l- effetti fuq l- għadd ta ’ ċelluli CD4 aktarx li ma jkunux iktar qawwija f’ pazjenti kkurati b’ indinavir flimkien ma ’ analogi nukleosidi meta mqabbla ma ’ indinavir waħdu.
Within studies, this effect is sustained also after prolonged periods of follow– up.
Fl- istudji, dan l- effett jibqa ’ anke għal perjodi twal wara l- kura.
Paediatric patients Two clinical trials in 41 paediatric patients (4 to 15 years of age) were designed to characterise the safety, antiretroviral activity, and pharmacokinetics of indinavir in combination with stavudine and
Pazjenti tfal Żewġ provi kliniċi f’ 41 pazjent li huma tfal (minn 4 sa 15- il sena) nbnew biex joħorġu l- karatteristiċi ta ’ sigurta`, attivita` antiretrovirali u l- karatteristiċi farmakokinetiċi ta ’ indinavir flimkien ma ’ stavudine u lamivudine.
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 23 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%.
At week 60, the proportion of patients with plasma viral RNA below 400 copies/ ml was 59%.
Fis- 60 ġimgħa, il- proporzjon ta ’ pazjenti bil- plażma virali RNA taħt l- 400 kopja/ ml kien ta ’ 59%.
In another study, at week 16, the proportion of patients with plasma viral RNA below 400 copies/ ml was 59%; the mean increase in CD4 cell counts was 73 cells/ mm3; and the mean increase in percent CD4 cell counts was 1.2%.
Fi studju ieħor, fis- 16- il ġimgħa, il- proporzjon ta ’ pazjenti bil- plażma virali RNA taħt l- 400 kopja/ ml kien ta ’ 59%; iż- żieda medja fl- għadd taċ- ċelluli CD4 kien ta ’ 73 ċellula/ mm3; iż- żieda medja perċentwali ta ’ l- għadd ta ’ ċelluli CD4 kienet ta ’ 1. 2%.
At week 24, the proportion of patients with plasma viral RNA below 400 copies/ ml was 60%.
Ma ’ l- 24 ġimgħa, il- proporzjon ta ’ pazjenti bil- plażma virali RNA taħt l- 400 kopja/ ml kien ta ’ 60%.
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.).
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.).
A greater than dose– proportional increase in indinavir plasma concentrations was observed over the 200 – 800 mg dose range.
Ġiet osservata żieda fil - konċentrazzjonijiet fil- plażma li kienet ikbar miż- żieda fi proporzjon mad- doża, fil- medda ta ’ dożi ta ’ 200- 400 mg.
Between 800– mg and 1,000– mg dose levels, the deviation from dose– proportionality is less pronounced.
Bejn il- livelli ta ’ doża minn 800 mg u 1, 000 mg, id- devjazzjoni mill- proporzjonalita` mad- doża kienet inqas kbira.
As a result of the short half– life, 1.8 ± 0.4 hours, only a minimal increase in plasma concentrations occurred after multiple dosing.
Minħabba l- half life qasira, ta ’ 1. 8 ± 0. 4 sigħat, wara iktar minn doża waħda kien hemm biss żieda minima fil- konċentrazzjonijiet tal- plażma.
The bioavailability of a single 800– mg dose of indinavir was approximately 65% (90% CI, 58 – 72%).
Il- biodisponibbilita` ta ’ doża waħda ta ’ 800mg ta ’ indinavir kienet bejn wieħed u ieħor ta ’ 65% (90% CI, 58 – 72%).
Data from a steady state study in healthy volunteers indicate that there is a diurnal variation in the pharmacokinetics of indinavir.
Tagħrif minn studju fiss f’ voluntiera f’ saħħithom jindika li hemm varjazzjoni waqt il- ġurnata fil - karatterisitiċi farmakokinetiċi ta ’ indinavir.
Following a dosage regimen of 800 mg every 8 hours, measured peak plasma concentrations (Cmax) after morning, afternoon and evening doses were 15,550 nM, 8,720 nM and 8,880 nM, respectively.
Wara kura b’ doża ta ’ 800 mg kull 8 sigħat, l- ogħla konċentrazzjonijiet imkejla tal- plażma (Cmax) wara d- dożi ta ’ filgħodu, ta ’ wara nofsinhar u ta ’ filgħaxija kienu ta ’ 15, 550 nM, 8, 720 nM u 8, 880 nM, rispettivament.
Corresponding plasma concentrations at 8 hours post dose were 220 nM, 210 nM and 370 nM, respectively.
Il- konċentrazzjonijiet korrispondenti tal- plażma 8 sigħat wara d- dożi kienu 220 nM, 210 nM u 370 nM, rispettivament.
The relevance of these findings for ritonavir boosted indinavir is unknown.
Mhux magħruf ir- relevanza ta ’ dan it- tagħrif għal indinavir imsaħħaħ ma ’ ritonavir.
At steady state following a dosage regimen of 800 mg every 8 hours, HIV– seropositive adult patients in one study achieved geometric means of:
Fi stat fiss wara kura b’ dożaġġ ta ’ 800 mg kull 8 sigħat, pazjenti adulti HIV- seropożittivi fi studju wieħed kellhom medji ġeometriċi ta ’:
AUC0-8h of 27,813 nM*h (90% confidence interval = 22,185, 34,869), peak plasma concentrations 11,144 nM (90% confidence interval = 9,192, 13,512) and plasma concentrations at 8 hours post dose 211 nM (90% confidence interval = 163, 274).
AUC0- 8h ta ’ 27813 nM* h (intervall tad- 90% = 22185, 34869), l- ogħla konċentrazzjonijiet tal- plażma 11144 nM (intervall tad- 90% = 9192, 13512) u l- ogħla konċentrazzjonijiet tal- plażma 8 sigħat wara d- doża 211 nM (intervall tad- 90% = 163, 274).
Food effect At steady state following a dosage regimen of 800 mg/ 100 mg of indinavir/ ritonavir every 12 hours with a low-fat meal, healthy volunteers in one study achieved geometric means:
Effett ta ’ l- ikel Fi stat fiss wara kura b’ dożaġġ ta ’ 800 mg/ 100mg b’ indinavir/ ritonavir kull 12- il siegħa wara ikla bi ftit xaħam, f’ studju wieħed voluntiera f’ saħħithom kellhom medji ġeometriċi ta ’:
AUC0-12h 116,067 nM*h (90% confidence interval = 101,680, 132,490), peak plasma concentrations 19001 nM (90% confidence interval = 17,538, 20,588), and plasma concentrations at 12 hours post dose 2274 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).
No significant difference in exposure was seen when the regimen was given with a high-fat meal.
Ma ħarġet l- ebda differenza sinifikanti fl - espożizzjoni meta l- kura ngħatat ma ’ ikla b’ ħafna xaħam.
Indinavir boosted regimen.
Reġimen imsaħħaħ b’ Indinavir.
Limited data are available on the pharmacokinetics of indinavir in association with low dose ritonavir.
Hemm data limitata dwar il- farmakokinetika ta ’ indinavir f’ assoċjazzjoni ma ’ ritonavir ta ’ doża baxxa.
The pharmacokinetics of indinavir (400 mg) with ritonavir (100 mg) dosed twice daily was examined in two studies.
Il- farmakokinetika ta ’ indinavir (400 mg) ma ’ ritonavir (100 mg) iddożat darbtejn kuljum kienet eżaminata f’ żewġ studji.
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 27,412 nM*h, peak plasma concentrations of 12,182 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.
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 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.
During pregnancy, it has been demonstrated that the systemic exposure of indinavir is relevantly decreased (PACTG 358.
Waqt it- tqala, ġie dimostrat li espożizzjoni sistemika għal indinavir jitnaqqas b’ mod rilevanti (PACTG 358.
Crixivan, 800 mg every 8 hours + zidovudine 200 mg every 8 hours and lamivudine 150 mg twice a day).
Crixivan, 800 mg kull 8 sigħat + zidovudine 200 mg kull 8 sigħat u lamivudine 150 mg darbtejn kuljum).
The mean indinavir plasma AUC0-8hr at week 30-32 of gestation (n=11) was 9,231 nM∗ hr, which is 74% (95% CI:
IL- medja għall- plażma AUC0- 8hr ta ’ indinavir fit- 30- 32 ġimgħa tat- tqala (n=11) kienet 9, 231 nM∗hr, li hi 74% (95% CI:
50%, 86%) lower than that observed 6 weeks postpartum.
50%, 86%) inqas minn dik osservata 6 ġimgħat 24 wara l- ħlas.
The pharmacokinetics of
6 minn dawn il- 11 (55%) – il pazjent kellhom konċentrazzjonijiet medji tal- plażma ta ’ indinavir 8 sigħat wara d- doża (Cmin) taħt l- għatba ta ’ l- assay għal kwantifikazzjoni li tista ’ torbot fuqha.
22 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).
Administration of indinavir with a meal high in calories, fat, and protein resulted in a blunted and reduced absorption with an approximate 80% reduction in AUC and an 86% reduction in Cmax.
Meta indinavir ngħata ma ’ ikla b’ ħafna kaloriji, xaħam u proteini, l- assorbiment tiegħu tnaqqas bejn wieħed u ieħor bi 80% fl- AUC u tnaqqas bi 86% f ’ Cmax.
Administration with light meals (e. g., dry toast with jam or fruit conserve, apple juice, and coffee with skimmed or fat– free milk and sugar or corn flakes, skimmed or fat– free milk and sugar) resulted in plasma concentrations comparable to the corresponding fasted values.
Meta l- aġent ngħata ma ’ ikliet ħfief (ngħidu aħna ħobż mixwi niexef bil- ġamm jew frott ikkonservat, meraq tat- tuffieħ, kafe` b’ ħalib b’ xaħam imnaqqas jew bla xaħam u zokkor jew ‘ corn flakes ’, b’ ħalib b’ xaħam imnaqqas jew bla xaħam u zokkor), il- konċentrazzjonijiet tal- plażma jistgħu jitqabblu mal- valuri korrispondenti waqt sawm.
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.
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.
In HIV– infected paediatric patients, the pharmacokinetic parameters of indinavir in apple sauce were:
F’ pazjenti tfal infettati bl- HIV, il- parametri farmakokinetiċi ta ’ indinavir fiz- zalza tat- tuffieħ kienu: