qanastek/EMEA-V3 huggingface dataset:
Administration of Kaletra with a high fat meal (872 kcal, 55.8% from fat) increased lopinavir AUC and Cmax by 96% and 43%, respectively, for soft capsules, and 130% and 56%, respectively, for oral solution.
Is - somministrazzjoni ta ’ Kaletra flimkien ma ’ ikla b’ kontenut għoli ta ’ xaħam (872 kcal, 55. 8% mix - xaħam) żiedet l- AUC u Cmax ta ’ lopinavir bi 96% u 43%, rispettivament, għal kapsuli rotob, u 130% u 56%, rispettivament, għat- taħlita likwida orali.
To enhance bioavailability and minimise variability Kaletra is to be taken with food.
Sabiex tkabbar il- bijodisponibilita ’ u timminimizza l - varjabilita ’ l- Kaletra għandha tittieħed mal- ikel.
Distribution: at steady state, lopinavir is approximately 98 − 99% bound to serum proteins.
Fi steady- state lopinavir huwa approssimattivament 98 - 99% marbut mal- proteini tas - serum.
Lopinavir binds to both alpha-1-acid glycoprotein (AAG) and albumin, however, it has a higher affinity for AAG.
Lopinavir jgħaqqad kemm mal- aċidu glikoproteina alpha- 1( AAG) u mal- albumina, imma għandha affinita ogħla mal- AAG.
At steady state, lopinavir protein binding remains constant over the range of observed concentrations after 400/ 100 mg Kaletra twice daily, and is similar between healthy volunteers and HIV-positive patients.
Fi steady- state t- tagħqid tal- proteina ta ’ lopinavir jibqa kostanti fuq l- medda ta ’ konċentrazzjonijiet osservati wara 400/ 100 mg Kaletra darbtejn kuljum, u hija simili bejn volontiera b’ saħħithom u pazjenti li huma HIV- posittivi.
Metabolism: in vitro experiments with human hepatic microsomes indicate that lopinavir primarily undergoes oxidative metabolism.
Esperimenti in vitro b’ mikrożomi epatiċi umani jindikaw illi primarjament lopinavir jgħaddi minn metaboliżmu ossidattiv.
Ritonavir is a potent CYP3A inhibitor which
Il- lopinavir huwa estensivament metabolizzat mis- sistema ċitokroma epatika P450, kważi esklussivament mill- iżożima CYP3A.
18 inhibits the metabolism of lopinavir and therefore, increases plasma levels of lopinavir.
Ir- ritonavir huwa inibitur ta’ CYP3A potenti li jinibixxi il- metaboliżmu ta’ lopinavir u għalhekk iżid il- livelli tal- plażma ta’ lopinavir.
A 14 C-lopinavir study in humans showed that 89% of the plasma radioactivity after a single 400/ 100 mg Kaletra dose was due to parent active substance.
Studji ta ’ 14C - lopinavir fil- bniedem urew illi 89% tar- radjoattivita ’ tal- plażma wara doża unika ta ’ 400/ 100 mg Kaletra kienet dovuta għas- sustanza attiva oriġinali.
At least 13 lopinavir oxidative metabolites have been identified in man.
Mill- inqas 13 - il metabolita ossidattivi ta’ lopinavir ġew identifikati fil- bniedem.
The 4-oxo and 4-hydroxymetabolite epimeric pair are the major metabolites with antiviral activity, but comprise only minute amounts of total plasma radioactivity.
Il- par (koppja) epimeriku/ a 4- oxo u 4 - idroximetabolita huma l- metaboliti maġġuri b’ attività antivirali, imma jikkomprendu biss ammonti żgħar ħafna mit- total kollu tar- radjoattivita tal- plażma.
Ritonavir has been shown to induce metabolic enzymes, resulting in the induction of its own metabolism, and likely the induction of lopinavir metabolism.
Ritonavir ġie muri li jinduċi l- enżimi metaboliċi, b’ hekk jirriżulta fl- induzzjoni tal- metaboliżmu tiegħu stess u aktarx l- induzzjoni tal - metaboliżmu ta’ lopinavir.
Pre-dose lopinavir concentrations decline with time during multiple dosing, stabilising after approximately 10 days to 2 weeks.
Konċentrazzjonijiet ta’ lopinavir ta ’ qabel id- doża maż- żmien jonqsu matul l - għoti ta ’ dużaġġ multiplu, u jistabiliżżaw ruħhom wara approssimattivament 10 tijiem sa 2 gimgħat.
Elimination: after a 400/ 100 mg 14C-lopinavir/ ritonavir dose, approximately 10.4 ± 2.3% and 82.6 ± 2.5% of an administered dose of 14C-lopinavir can be accounted for in urine and faeces, respectively.
Wara doża ta ’ 400/ 100 mg 14C- lopinavir/ ritonavir, approssimattivament 10. 4 ± 2. 3% u 82. 6 ± 2. 5% ta ’ doża somministrata ta ’ 14C- lopinavir tista tiġi stabbilita fl- urina u fl- iskart imneħħi mill - ġisem, rispettivament.
Unchanged lopinavir accounted for approximately 2.2% and 19.8% of the administered dose in urine and faeces, respectively.
Lopinavir mhux mibdul kien approssimattivament 2. 2% u 19. 8% tad- doża somministrata fl- urina u fl- iskart imneħħi mill- ġisem, rispettivament.
After multiple dosing, less than 3% of the lopinavir dose is excreted unchanged in the urine.
Wara dużaġġ multiplu inqas minn 3% tad- doża ta ’ lopinavir hija mneħħija mhux mibdula fl- urina.
The effective (peak to trough) half-life of lopinavir over a 12 hour dosing interval averaged 5 − 6 hours, and the apparent oral clearance (CL/ F) of lopinavir is 6 to 7 l/ h.
Il- half- life effettiva ta ’ lopinavir (massimu sa minimu) tul intervall ta ’ dużaġġ ta’ 12 il- siegħa kellu medja ta ’ 5 - 6 sigħat, u t- tneħħija orali (CL/ F) apparenti ta ’ lopinavir hi 6 sa 7 l/ siegħa.
Special Populations
Pazjenti Speċjali
Paediatrics:
Pedjatriċi:
There are limited pharmacokinetic data in children below 2 years of age.
Hemm tagħrif farmakokinetiku limitat fi tfal ta ’ taħt is- sentejn età.
The pharmacokinetics of Kaletra 300/ 75 mg/ m2 twice daily and 230/ 57.5 mg/ m2 twice daily have been studied in a total of 53 paediatric patients, ranging in age from 6 months to 12 years.
Il- farmakokinetika ta ’ Kaletra 300/ 75 mg/ m2 darbtejn kuljum u 230/ 57. 5 mg/ m2 darbtejn kuljum ġew studjati f’ total ta ’ 53 pazjent pedjatriku li jvarjaw fl- età minn 6 xhur sa 12 il- sena.
The lopinavir mean steady-state AUC, Cmax, and Cmin were 72.6 ± 31.1 μ g• h/ ml, 8.2 ± 2.9 μ g/ ml and 3.4 ± 2.1 μ g/ ml, respectively after Kaletra 230/ 57.5 mg/ m2 twice daily without nevirapine (n=12), and were 85.8 ± 36.9 μ g• h/ ml, 10.0 ± 3.3 μ g/ ml and 3.6 ± 3.5 μ g/ ml, respectively after 300/ 75 mg/ m2 twice daily with nevirapine (n=12).
Il- medja fi steady- state tal- AUC, Cmax, u Cmin ta ’ lopinavir kien72. 6± 31, 1μg• h/ ml, 8. 2± 2. 9μg• h/ ml and 3. 4± 2. 1μg• h/ ml rispettivament wara Kaletra 230/ 57. 5 mg/ m2 darbtejn kuljum mingħajr nevirapine (n=12), u kienu 85. 8 ± 36. 9 μg• h/ ml, 10. 0 ± 3. 3 μg/ ml u 3. 6 ± 3. 5 μg/ ml, rispettivament wara 300/ 75 mg/ m2 darbtejn kuljum b’ nevirapine (n=12).
The 230/ 57.5 mg/ m2 twice daily regimen without nevirapine and the 300/ 75 mg/ m2 twice daily regimen with nevirapine provided lopinavir plasma concentrations similar to those obtained in adult patients receiving the 400/ 100 mg twice daily regimen without nevirapine.
Il - 230/ 57. 5 mg/ m2 dożaġġ darbtejn kuljum mingħajr nevirapine u t - 300/ 75 mg/ m2 dożaġġ darbtejn kuljum b’ nevirapine pprovdew konċentrazzjonijiet tal- plażma ta ’ lopinavir simili għal dawk ottenuti f’ pazjenti adulti li kienu qed jirċievu 400/ 100 mg dożaġġ darbtejn kuljum mingħajr nevirapine.
Kaletra soft capsules and Kaletra oral solution are bioequivalent under nonfasting conditions.
Taħt kundizzjonijiet mhux ta ’ sawm il- kapsuli rotob Kaletra u t- taħlita likwida orali Kaletra huma bijoekwivalenti.
Gender, Race and Age:
Sess, Razza u Età:
Kaletra pharmacokinetics have not been studied in the elderly.
Il- farmakokinetika ta ’ Kaletra ma ’ ġietx studjata fl- anzjani.
No age or gender related pharmacokinetic differences have been observed in adult patients.
F’ pazjenti adulti ma ’ ġiet innutata l- ebda differenza farmakokinetika li huma relatati ma ’ l- età jew is- sess.
Pharmacokinetic differences due to race have not been identified.
Differenzi farmakokinetiċi minħabba razza ma ’ ġewx identifikati.
Renal Insufficiency:
Problemi fil- kliewi:
Kaletra pharmacokinetics have not been studied in patients with renal insufficiency; however, since the renal clearance of lopinavir is negligible, a decrease in total body clearance is not expected in patients with renal insufficiency.
Iżda peress li t- tneħħija ta ’ lopinavir mill- kliewi hija negliġibbli, f’ pazjenti bi problemi fil- kliewi tnaqqis fit- total tat- tneħħija mill- ġisem ma ’ hijiex mistennija.
Hepatic Insufficiency:
Problemi Epatiċi:
The steady state pharmacokinetic parameters of lopinavir in HIV-infected patients with mild to moderate hepatic impairment were compared with those of HIV-infected patients with normal hepatic function in a multiple dose study with lopinavir/ ritonavir 400/ 100 mg twice daily.
Il- parametri farmakokinetiċi steady- state ta ’ lopinavir f’ pazjenti infettati bl- HIV bi problemi epatiċi minn ħfief għal moderati ġew mqabbla ma dawk ta ’ pazjenti infettati bl- HIV b’ funzjoni epatika normali fi studju ta ’ dożi multipla b’ lopinavir/ ritonavir 400/ 100 mg darbtejn kuljum.
A limited increase in total lopinavir concentrations of approximately 30% has been observed which is not expected to be of clinical relevance (see section 4.2).
Żieda limitata ta ’ approssimament 30% fil- konċentrazzjonijiet ta ’ lopinavir ġiet osservata, imma mhix mistennija li tkun ta ’ ebda relevanza klinika (ara sezzjoni 4. 2).
Repeat-dose toxicity studies in rodents and dogs identified major target organs as the liver, kidney, thyroid, spleen and circulating red blood cells.
Studji tossiċi fuq bażi ta ’ dożi ripetuti fil- gerriema u fil- klieb identifikaw bħala bersalli prinċipali organi bħal fwied, il- kliewi, it- tarojd, il- marrara u ċelluli tad- demm ħomor ċirkulanti.
Hepatic changes indicated cellular swelling with focal degeneration.
Bidliet epatiċi urew nefħa ċellulari b’ deġenerazzjoni fokali.
While exposure eliciting these changes were comparable to or below human clinical exposure, dosages in animals were over 6-fold the recommended clinical dose.
Fil- waqt li l- esposizzjoni li minnu ħarġu dawn il- bidliet kien komparabbli mal jew inqas mill- esponiment kliniku uman, dożi fl- annimali kienu iktar minn 6 darbiet id- doża klinika rakkomandata.
Mild renal tubular
Deġenerazzjoni renali tubulari ħafifa kienet ristretta għall ġrieden esposti
19 degeneration was confined to mice exposed with at least twice the recommended human exposure; the kidney was unaffected in rats and dogs.
22 b’ almenu darbtejn l- esponiment rakkomandat għall bniedem; il- kilwa ma ’ kenitx effettwata fil- far u fil - klieb.
Reduced serum thyroxine led to an increased release of TSH with resultant follicular cell hypertrophy in the thyroid glands of rats.
Serum thyroxine imnaqqas wassal għall rilaxxament akbar ta ’ TSH li rriżulta f’ ipertrofija taċ - ċellula follikulari fil- glandola tajrod tal- far.
These changes were reversible with withdrawal of the active substance and were absent in mice and dogs.
Dawn il- bidliet kienu mreġġa lura wara l- irtirar tas- sustanza attiva u kienu assenti fil- ġrieden u fil- klieb.
Coombs-negative anisocytosis and poikilocytosis were observed in rats, but not in mice or dogs.
Anisoċitożi Coombs- negative u pojkiloċitożi kienu osservati fil- far, iżda mhux fil- ġrieden u l- klieb.
Enlarged spleens with histiocytosis were seen in rats but not other species.
Marrari minfuħa bl- istjoċitożi ġew innutati fil- far iżda mhux fi speċi oħra.
Serum cholesterol was elevated in rodents but not dogs, while triglycerides were elevated only in mice.
Is- serum kolosterol kien għoli fil- gerriema iżda mhux fil- klieb, waqt li t- trigliċeridi kienu għolja biss fil- ġrieden.
During in vitro studies, cloned human cardiac potassium channels (HERG) were inhibited by 30% at the highest concentrations of lopinavir/ ritonavir tested, corresponding to a lopinavir exposure 7-fold total and 15-fold free peak plasma levels achieved in humans at the maximum recommended therapeutic dose.
Waqt studju in vitro, kanali kardijaċi tal- potassju umani klonati (HERG) kienu inibiti bi 30% fl- ogħla konċentrazzjonijiet ta ’ lopinavir/ ritonavir ippruvati, li kienu jikkorrispondu għal esponiment għal lopinavir ta ’ total ta ’ 7 darbiet u 15 il- darba livelli ta ’ plażma quċċata libera li ġew ottenuti fil- bniedem bid- doża terapewtika massima li ġiet irrikmandata.
In contrast, similar concentrations of lopinavir/ ritonavir demonstrated no repolarisation delay in the canine cardiac Purkinje fibres.
B’ kuntrast, konċentrazzjonijiet simili ta ’ lopinavir/ ritonavir ma ’ urew l- ebda dewmien fir- ripolarizzazjoni fil- fibri kardijaċi Purkinje tal- klieb.
Lower concentrations of lopinavir/ ritonavir did not produce significant potassium (HERG) current blockade.
Konċentrazzjonijiet iktar baxxi ta ’ lopinavir/ ritonavir ma’ ipproduċewx imblokk kurrenti tal- potassju (HERG) sinifikanti.
Tissue distribution studies conducted in the rat did not suggest significant cardiac retention of the active substance; 72-hour AUC in heart was approximately 50% of measured plasma AUC.
Studji dwar id- distribuzzjoni tat- tessuti li saru fuq il- far ma ssuġġerewx żamma kardijaka sinifikanti tas- sustanza attiva; 72 siegħa AUC fil- qalb kienet approssimattivament 50% tal - plażma AUC imkejjla.
Therefore, it is reasonable to expect that cardiac lopinavir levels would not be significantly higher than plasma levels.
Għalhekk huwa raġjonevoli li wieħed jistenna li l- livelli kardijaċi ta ’ lopinavir ma ’ jkunux sinifikantement ogħla mill- livelli tal- plażma.
In dogs, prominent U waves on the electrocardiogram have been observed associated with prolonged PR interval and bradycardia.
Fil- klieb, mewġ U prominenti fuq l- elektrokardjogramma ġew osservati (bħala li kienu) assoċjati ma ’ intervall PR prolongat u mal- bradikardja.
These effects have been assumed to be caused by electrolyte disturbance The clinical relevance of these preclinical data is unknown, however, the potential cardiac effects of this product in humans cannot be ruled out (see also sections 4.4 and 4.8).
Ir- rilevanza klinika ta ’ dan it- tagħrif ta ’ qabel l- użu kliniku, ma ’ huwiex magħruf, iżda l- effetti potenzjali kardijaċi ta ’ dan il- prodott fil- bniedem ma ’ jista jiġi eskluż (ara ukoll sezzjoni 4. 4. u 4. 8).
In rats, embryofoetotoxicity (pregnancy loss, decreased foetal viability, decreased foetal body weights, increased frequency of skeletal variations) and postnatal developmental toxicity (decreased survival of pups) was observed at maternally toxic dosages.
Fil- far, embrijofetotossiċita (telf ta ’ tqala, vijabilita ’ fetali imnaqqsa, piżijiet tal- korp fetali imnaqqsa, frekwenza akbar ta ’ varjazzjonijiet skeletali) u tossiċita ’ ta ’ l- iżvilupp ta ’ wara t- twelid (għixien imnaqqsa taż- żgħar) ġiet osservata f’ dożaġġi tossiċi materni.
The systemic exposure to lopinavir/ ritonavir at the maternal and developmental toxic dosages was lower than the intended therapeutic exposure in humans.
L- esponiment sitematiku għall lopinavir/ ritonavir fid- dożaggi materni u żviluppatorji kien iktar baxx mill- esposizzjoni terapewtiku ppjanat fil- bniedem.
Long-term carcinogenicity studies of lopinavir/ ritonavir in mice revealed a nongenotoxic, mitogenic induction of liver tumours, generally considered to have little relevance to human risk.
Studji karċinoġeniċi fuq perijodu twil, tal- lopinavir/ ritonavir fil- ġrieden żvela induzzjoni mhux ġenotossika u mitoġenika ta ’ tumuri fil- fwied, li ġeneralment huma kkunsidrati li għandhom ftit rilevanza ta ’ riskju għall bniedem.
Carcinogenicity studies in rats revealed no tumourigenic findings.
Studji karċinoġeniċi fil- far ma ’ żvelaw l- ebda sejbiet tumoriġeniċi.
Lopinavir/ ritonavir was not found to be mutagenic or clastogenic in a battery of in vitro and in vivo assays including the Ames bacterial reverse mutation assay, the mouse lymphoma assay, the mouse micronucleus test and chromosomal aberration assays in human lymphocytes.
Lopinavir/ ritonavir ma ’ instabx li hu mutaġeniku jew klastoġeniku f’ serje sħiħa ta ’ provi in vitro u in vivo inklużi l- prova Ames bacterial reverse mutation, il- prova tal- limfoma fil- ġurdien, it- test mikronukleju fil- ġurdien u provi ta ’ aberrazzjoni kromosomatika fil- limfoċiti umani.
Capsule contents: oleic acid, propylene glycol, polyoxyl 35 castor oil, purified water
Kontenut tal- kapsula: oleic acid, propylene glycol, polyoxyl 35 castor oil, purified water
Capsule shell: gelatine, anhydrized liquid sorbitol (mixture of sorbitol, sorbitol anhydrides and mannitol), glycerol, titanium dioxide (E171), sunset yellow (E110) medium-chain triglycerides, lecithin
Qoxra tal- kapsula: ġelatina, anhydrized liquid sorbitol (taħlita ta ’ sorbitol, sorbitol anhydrides u mannitol), glycerol, titanium dioxide (E171), sunset yellow (E110) medium- chain triglycerides, lecithin
Black ink containing: propylene glycol, black iron oxide (E172), polyvinyl acetate phthalate, polyethylene glycol 400, ammonium hydroxide
Inka sewda li fiha: propylene glycol, black iron oxide (E172), polyvinyl acetate phthalate, polyethylene glycol 400, ammonium hydroxide
In use storage:
Ħażna waqt l- użu:
If kept outside of the refrigerator, do not store above 25°C and discard any unused contents after 42 days (6 weeks).
Jekk miżmum barra mill- friġġ, Taħżinx f’ temperatura 'l fuq minn 25°C u armi l - kontenut mhux użat wara 42 ġurnata (6 ġimgħat).
It is advised to write the date of removal from the refrigerator on the package.
Qed tiġi avżat li tikteb id- data tat- tneħħija mill- friġġ fuq il- pakkett ta ’ barra.
Avoid exposure to excessive heat.
Evita l- esponiment għall- sħana eċċessiva.
High density polyethylene (HDPE) bottles closed with polypropylene caps.
Polyethylene ta ’ densità għolja (HDPE) fliexken magħluqin b’ kappi ta ’ polypropylene.
Each bottle contains 90 capsules.
Kull flixkun fih 90 kapsula.
Each pack contains 2 bottles (180 capsules).
Kull pakkett fih 2 fliexken (180 kapsula).
Blisters consisting of PVC/ fluoropolymer foil.
Folji jikkonsistu minn PVC/ fojl tal- fluoropolymer.
Each carton contains 6 foil blisters each containing 6 capsules (36 capsules).
Kull kartuna fiha 6 folji tal- fojl li kull waħda fiha 6 kapsuli (36 kapsula).
Each pack contains 5 cartons (180 capsules).
Kull pakkett fih 5 kartuniet (180 kapsula).
Abbott Laboratories Limited Queenborough Kent ME11 5EL United Kingdom
Abbott Laboratories Limited Queenborough Kent ME11 5EL Renju Unit
20 March 2001 Date of last renewal:
20 ta ’ Marzu 2001 Data ta ’ Tiġdid ta ’ l- awtorizzazzjoni:
20 March 2006
20 ta ’ Marzu 2006
Kaletra (80 mg + 20 mg) / ml oral solution
Kaletra (80 mg + 20 mg) / ml soluzzjoni orali
Each 5 ml of Kaletra oral solution contains 400 mg of lopinavir co-formulated with 100 mg of ritonavir as a pharmacokinetic enhancer.
Kull 5 ml Kaletra taħlita likwida li tittieħed mill- ħalq fiha 400 mg ta ’ lopinavir ko- formulata ma 100 mg ritonavir bħala mġiegħel farmakokinetiku.
Quantity per ml
Kwantità għal kull ml
- excipient (s)
- sustanza( i) mhux attiva( i)
Alcohol (42% v/ v) High fructose corn syrup Propylene glycol Glycerol Polyoxyl 40 hydrogenated castor oil Acesulfame potassium
Alkoħol (42% v/ v) High fructose corn syrup Propylene glycol Glycerol Polyoxyl 40 hydrogenated castor oil Acesulfame potassium
For a full list of excipients, see section 6.1.
Għal sustanzi mhux attivi, ara sezzjoni 6. 1.
Oral solution
Soluzzjoni orali.
The solution is light yellow to golden.
Is- soluzzjoni hija safra ċara fid- dehbieni.
Kaletra is indicated for the treatment of HIV-1 infected adults and children above the age of 2 years, in combination with other antiretroviral agents.
Kaletra huwa indikat għat- trattament ta ’ adulti u tfal ’ il fuq minn sentejn infettati bl- HIV- 1, ikkombinat ma aġenti antiretrovirali oħra.
Most experience with Kaletra is derived from the use of the product in antiretroviral therapy naïve patients.
L- aktar esperjenza b’ Kaletra hija derivata mill- użu ta ’ dan il- prodott f’ terapija antiretrovirali fi pazjenti ġodda għal din it- terapija.
Data in heavily pretreated protease inhibitor experienced patients are limited.
Data f’ pazjenti prettratati bil- kbir bi inibituri tal- protease hija limitata.
The choice of Kaletra to treat protease inhibitor experienced HIV-1 infected patients should be based on individual viral resistance testing and treatment history of patients (see sections 4.4 and 5.1).
Ix- xelta li tuża Kaletra biex tittrata pazjenti infettati bl- HIV- 1 prettratati bil- kbir bi inibituri tal- protease għandha tkun ibbażżata fuq testijiet ta ’ reżistenza virali individwali u storja ta ’ trattament tal- pazjenti (ara sezzjonijiet 4. 4 u 5. 1).
4.2 Posology and method of administration
26 4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata
Adult and adolescent use: the recommended dosage of Kaletra is 5 ml of oral solution (400/ 100 mg) twice daily taken with food.
Użu fl- Adulti u fl- adoloxxenti: id- dużaġġ irrikmandat ta ’ Kaletra huwa ta ’ 5 ml ta ’ soluzzjoni orali (400/ 100 mg) darbtejn kuljum ma ’ l- ikel.
23 Paediatric use (2 years of age and above): the recommended dosage of Kaletra is 230/ 57.5 mg/ m2 twice daily taken with food, up to a maximum dose of 400/ 100 mg twice daily.
Użu Pediatriku (sentejn u fuqhom): id- doża rrikmandata ta ’ Kaletra hija ta 230/ 57. 5 mg/ m2 darbtejn kuljum ma l- ikel, sa doża massima ta ’ 400/ 100 mg darbtejn kuljum.
The 230/ 57.5 mg/ m2 dosage might be insufficient in some children when co-administered with nevirapine or efavirenz.
Id- doża ta ’ 230/ 57. 5 mg/ m2 tista ma tkunx biżżejjed f’ xi tfal meta tkun ko- amministrata ma nevirapine jew efavirenz.
An increase of the dose of Kaletra to 300/ 75 mg/ m2 should be considered in these patients.
Żieda fid- doża ta ’ Kaletra sa 300/ 75 mg/ m2 għandha tkun ikkunsidrata f’ dawn il- pazjenti.
Dose should be administered using a calibrated oral dosing syringe.
Id- doża għandha tkun mogħtija ġermess tas- siringa tal- ħalq kkalibrata.
The oral solution is the recommended option for the most accurate dosing in children based on body surface area.
Is - soluzzjoni orali hija l- għażla irrikandata għal dużaġġ akkurat fi tfal ibbażat fuq l- arja tal- wiċċ tal - ġisem * (jekk jogħġbok irreferi għall- Karatteristiċi tal- Prodott fil qosor tas- Soluzzjoni Orali ta ’ Kaletra).
However, if it is judged necessary to resort to soft capsules in children, they should be used with particular caution since they are associated with less precise dosing capabilities.
Minkejja dan, jekk jiġi meqjus neċessarju rikorriment għall- kapsuli rotob fi tfal, il- kapsuli għandhom jiġu użati b’ kawtiela partikulari għaliex huma assoċċjati ma preċiżjoni inqas fil- kapaċitajiet ta ’ dużaġġ.
Therefore, children receiving soft capsules might have higher exposure (with the risk of increased toxicity) or suboptinal exposure (with the risk of insufficient efficacy).
Għalekk, tfal li jirċievu kapsuli rotob jistgħu ikunu iktar esposti (bir- riskju ta’ aktar tossiċita) jew ikollhom esposizzjoni sub- ottimali (bir- riskju ta ’ mhux biżżejjed effikaċja).
Consequently when dosing children with soft capsules, therapeutic drug monitoring may be a useful tool to ensure appropriate lopinavir exposure in an individual patient.
Għal din ir- raġuni meta tfal jieħdu dużaġġ ta ’ kapsuli rotob, monitoraġġ terapewtiku tal- mediċina jista jkun ta ’ għajnuna biex jiġi assigurat esposizzjoni appropjata ta ’ lopinavir f’ pazjent individwali.
Paediatric Dosing Guidelines for the Dose 230/ 57.5 mg/ m2
Linji Gwida ta ’ Dożaġġ Pedjatriku għad- doża ta ’ 230/ 57. 5 mg/ m2
Body Surface Area* (m2)
Kapsuli rotob doża ta ’
Twice
(m2)
Daily Oral Solution Dose (dose in mg)
darbtjen kuljum (doża f’ mg)
Twice Daily Soft Capsule Dose (dose in mg)
darbtjen kuljum (doża f’ mg)
1.2 ml (96/ 24 mg)
1. 2 ml (96/ 24 mg)
1 soft capsule (133.3/ 33.3 mg)
1 kapsula ratba (133. 3/ 33. 3 mg)
0.75 0.80 1.00 1.25 1.3 1.4 1.5 1.7
0. 50 0. 75 0. 80 1. 00 1. 25 1. 3 1. 4 1. 5 1. 75
2.2 ml (172.5/ 43.1 mg) 2.3 ml (184/ 46 mg) 2.9 ml (230/ 57.5 mg) 3.6 ml (287.5/ 71.9 mg) 3.7 ml (299/ 74.8 mg) 4.0 ml (322/ 80.5 mg) 4.3 ml (345/ 86.3 mg) 5 ml (402.5/ 100.6 mg)
1. 4 ml (115/ 28. 8 mg) 2. 2 ml (172. 5/ 43. 1 mg) 2. 3 ml (184/ 46 mg) 2. 9 ml (230/ 57. 5 mg) 3. 6 ml (287. 5/ 71. 9 mg) 3. 7 ml (299/ 74. 8 mg) 4. 0 ml (322/ 80. 5 mg) 4. 3 ml (345/ 86. 3 mg) 5 ml (402. 5/ 100. 6 mg)
1 soft capsule (133.3/ 33.3 mg) 2 soft capsules (266.6/ 66/ 6 mg) 2 soft capsules (266.6/ 66/ 6 mg) 2 soft capsules (266.6/ 66/ 6 mg) 2 soft capsules (266.6/ 66/ 6 mg) 3 soft capsules (400/ 100 mg) 3 soft capsules (400/ 100 mg) 3 soft capsules (400/ 100 mg)
1 kapsula ratba (133. 3/ 33. 3 mg) 1 kapsula ratba (133. 3/ 33. 3 mg) 2 kapsuli rotob (266. 6/ 66. 6 mg) 2 kapsuli rotob (266. 6/ 66. 6 mg) 2 kapsuli rotob (266. 6/ 66. 6 mg) 2 kapsuli rotob (266. 6/ 66. 6 mg) 3 kapsuli rotob (400/ 100 mg) 3 kapsuli rotob (400/ 100 mg) 3 kapsuli rotob (400/ 100 mg)
Kaletra is not recommended for use in children below 2 years of age due to insufficient data on safety and efficacy (see section 5.1).
Kaletra m’ huwiex rakkommandat għall- użu minn tfal li għandhom inqas minn sentejn minħabba data limitata ta ’ sigurtà u effikacja.
Paediatric patients should switch from Kaletra oral solution to soft capsules as soon as they are able to swallow the capsule formulation (see section 4.4).
Pazjenti pedjatriċi għandhom jaqilbu għal kapsuli rotob ta ’ Kaletra malli jkunu kapaċi jibilgħu il- kapsula (ara sezzjoni 4. 4)
In HIV-infected patients with mild to moderate hepatic impairment, an increase of approximately 30% in lopinavir exposure has been observed but is not expected to be of clinical relevance.
F’ pazjenti infettati bl- HIV u b’ indeboliment tal- fwied ħafif għal moderat, ġiet osservata żieda approssimattiva ta ’ 30% ta ’ esposizzjoni għal lopinavi, imma mhix mistennija li tkun klinikament ta ’ importanza (ara sezzjoni 5. 2).
No data are available in patients with severe hepatic impairment.
Ma hawnx informazzjoni ta ’ użu f ’ pazjenti b’ indebboliment serju ħafna tal- fwied.
Renal impairment:
27 Indeboliment tal- kliewi:
No dose adjustment is necessary in patients with renal impairment.
L- ebda arranġament fid- doża m’ hu neċessarju f’ pazjenti b’ indeboliment tal - kliewi.
These medicinal products include astemizole, terfenadine, oral midazolam (for
Kaletra m’ għandux jiġi ko- amministrat ma prodotti mediċinali dipendenti fuq CYP3A għat- tneħħija mill- ġisem u prodotti mediċinali li konċentrazzjoni elevata fil- plażma tagħhom hija assoċjata ma avvenimenti serji li huma ta ’ periklu għall- ħajja.
24 caution on parenterally administered midazolam, see section 4.5), triazolam, cisapride, pimozide, amiodarone, ergot alkaloids (e. g. ergotamine, dihydroergotamine and ergonovine and methylergonovine) and vardenafil.
Dawn il- prodotti mediċinali jinkludu astemizole, terfenadine, midazolam li jittieħed mill- ħalq (sabiex tiġi eżerċitata kawtela meta midazolam jiġi mgħoti parenteralment, ara sezzjoni 4. 5), triazolam, cisapride, pimozide, amiodarone, ergot alkaloids (eż. ergotamine, dihydroergotamine, ergonovine u methylergonovine) u vardenafil.
Kaletra oral solution is contraindicated in children below the age of 2 years, pregnant women, patients with hepatic or renal failure and patients treated with disulfiram or metronidazole due to the potential risk of toxicity from the excipient propylene glycol (see section 4.4).
Is- soluzzjoni orali ta ’ Kaletra hija kontr- indikata fi tfal taħt is- sentejn, nisa tqal, pazjenti b’ disfunzjoni tal- fwied jew kliewi u pazjenti li huma trattati b’ disulfiram jew metronidazole, minħabba tossiċita potenzjali mill- eċċipjent propylene glycol (ara sezzjoni 4. 4).
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions.
Pazjenti b’ epatite B jew Ċ u ttratati b ’ taħlita ta ’ terapija antiretrovirali qiedgħin f’ riskju akbar ta ’ reazzjonijiet avversi serji ħafna u potenzjalment fatali għall- fwied.
In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued.
F’ iżjed min- nofs il- każi rappurtati, t- trattament b’ inibituri tal- protease tkompla jew ġie re- introdott jekk it- trattament kien twaqqaf.
Haemophiliac patients should therefore be made aware of the possibility of increased bleeding.
Pazjenti emofiliċi għandhom ikunu magħrrfa bill - possibilita ta ’ żieda fit- telf ta ’ demm.
Lipid elevations
28 Elevazzjonijiet fil- lipidi
Patients with advanced HIV disease may be at risk of elevated triglycerides and pancreatitis.
Pazjenti bill- marda ta ’ l- HIV avvanzata jista ’ jkollom riskju ta ’ trigliċeridi elevati u pankreatite.
25 Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of pancreatitis should occur.
Il- pankreatite għandha tkun ikkunsidrata jekk sintomi kliniċi (nawsja, rimettar, uġigħ addominali) jew valuri tal- laboratorju mhux normali (bħal żieda fis- serum lipase u valuri tal- amilase) suġġestivi ta ’ pankreatite iseħħu.
Fat redistribution & metabolic disorders
Ridistribuzzjoni tax- xaħam u problemi metaboliċi
A connection between visceral lipomatosis and protease inhibitors (PIs) and lipoatrophy and nucleoside reverse transcriptase inhibitors (NRTIs) has been hypothesised.
Konnessjoni bejn lipomatożi vixxerali u inibituri tal- protease( PIs) u lipoatrofija u inibituri ta ’ nucleoside reverse transcriptase (NRTIs) ġie ipotizzat.
Osteonecrosis
29 Ostjonekrożi
Interactions with medicinal products
Interazzjonijiet ma ’ prodotti mediċinali
Kaletra is likely to increase plasma concentrations of medicinal products that are primarily
Kaletra x’ aktarx li jżid il- konċentrazzjoni fil- plażma ta ’ prodotti mediċinali li primarjament huma metabolizzati minn CYP3A.
These increases of plasma concentrations of co-administered medicinal products could increase or prolong their therapeutic effect and adverse events (see sections 4.3 and 4.5).
Dawn iż- żidiet ta ’ konċentrazzjonjiet fil- plażma ta ’ prodotti mediċinali ko - somministrati jistgħu jżidu jew jipprolungaw l- effett terapewtiku u l- eventi avversi (ara sezzjoni 4. 3).
If treatment with an HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended (see section 4.5).
Jekk it- trattament b’ inibitur HMG- CoA reductase huwa indikat, pravastatin jew fluvastatin huma rakkomandati (ara sezzjoni 4. 5).
Indeed, Kaletra could increase concentrations of the co-administered medicinal products and this may result in an increase of their associated cardiac adverse events.
Tassew, Kaletra jista iżid il- konċentrazzjonjiiet ta ’ prodotti mediċinali ko- amministrati u dan jista ’ jirriżulta f’ żieda fl- avvenimenti avversi kardijaċi assoċjati.
Rifampicin in combination with Kaletra causes large decreases in lopinavir concentrations which may in turn significantly decrease the lopinavir therapeutic effect.
Rifampicin użat flimkien ma ’ Kaletra jista ’ jikkawża tnaqqis kbir fil- konċentrazzjoni ta ’ lopinavir li sussegwentement jista ’ inaqqas il - konċentrazzjoni l- effett terapewtiku ta ’ lopinavir b’ mod sinifikattiv.
Patients taking the oral solution, particularly those with renal impairment or with decreased ability to metabolise propylene glycol (e. g. those of Asian origin), should be monitored for adverse reactions potentially related to propylene glycol toxicity (i. e. seizures, stupor, tachycardia, hyperosmolarity, lactic acidosis, renal toxicity, haemolysis) (see section 4.3).
Dawk ta ’ oriġini Asjatika), għandhom ikunu mmonitorati għar- reazzjonijiet avversi potenzjalment relatati ma tossiċita ’ ta ’ propylene glycol (i. e. attakki ta ’ puplesija, sturdament, takikardija, iperosmolarita, aċidozi lattika, tossiċita tal- kliewi, emolisi tad- demm) (ara sezzjoni 4. 3).
Kaletra is not a cure for HIV infection or AIDS.
30 Kaletra mhijiex kura għall- infezzjoni ta ’ l- HIV jew AIDS.
Besides propylene glycol as described above, Kaletra oral solution contains alcohol (42% v/ v) which is potentially harmful for those suffering from liver disease, alcoholism, epilepsy, brain injury or disease as well as for pregnant women and children.
Minbarra il- propylene glycol kif ġie spjegat hawn fuq, is- soluzzjoni orali ta ’ Kaletra fiha alkoħol (42% v/ v) li huwa ta ’ ħsara potenzjali għal min ibati min mard tal- fwied, alkoħoliżmu, epilessjia, ħsara jew mard fil- moħħ u għal nisa tqal u tfal.
It may modify or increase the effects of other medicines.
Jista jimmodifika jew iżid l- effetti ta ’ mediċini oħra.
Kaletra oral solution contains up to 0.8 g of fructose per dose when taken according to the dosage recommendations.
Is - soluzzjoni orali ta ’ Kaletra fiha daqs 0. 8g ta ’ fructose għal kull doża meta tittieħed kif irrikmandata.
This may be unsuitable in hereditary fructose intolerance.
Din tista ma taqbilx ma min għandu intoleranza ta ’ fructose ereditarja.
Kaletra oral solution contains up to 0.3 g of glycerol per dose.
Is- soluzzjoni oralo ta ’ Kaletra fih daqs 0. 3g ta ’ glycerol għal kull doża.
Only at high inadvertent doses, it can cause headache and gastrointestinal upset.
Tista tikkawża uġigħ ta ’ ras u qlib gastrointestinali meta jingħataw dożi għolja involontarjament.
Furthermore, polyoxol 40 hydrogenated castor oil and potassium present in Kaletra oral solution may cause only at high inadvertent doses gastrointestinal upset.
Barra minn hekk, polyoxol 40 castor oil idroġenat u potassju preżenti fis - soluzzjoni orali ta ’ Kaletra jistgħu jikkawżaw taqlib gastrointestinali f’ dożi għolja meħudin involontarjament.
Patients on a low potassium diet should be cautioned.
Pazjenti fuq dieta baxxa f’ potassju għandhom jiġu mwissa.
27 4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l - effett farmaċewtiku tal- prodott
Zidovudine and Abacavir:
Zidovudine u Abacavir:
Tenofovir: when tenofovir disoproxil fumarate was co-administered with Kaletra, tenofovir concentrations were increased by approximately 30% with no changes noted in lopinavir or ritonavir concentrations.
31 Tenofovir: meta tenofovir disoproxil fumarate kien ko- amministrat ma Kaletra, il- konċentrazzjonijiet ta ’ tenofovir żdiedu approssimament bi 30%, u ebda bidla ma ġiet innutata fil- konċentrazzjonijiet ta ’ lopinavir jew ritonavir.
Higher tenofovir concentrations could potentiate tenofovir associated adverse events, including renal disorders.
Konċentrazjonijiet ogħla ta ’ tenofovir jistgħu jsaħħu eventi avversi assoċjati ma tenofovir, inklużi problemi fil- kliewi.
Results from a study in HIV-positive paediatric patients revealed a decrease in lopinavir concentrations during nevirapine co-administration.
Ir- riżultati mill- istudju f’ pazjenti pedjatriċi b’ HIV - positive żvela tnaqqis fill- konċentrazzjoni ta ’ lopinavir waqt il- ko- amministrazzjoni ta ’ nevirapine.
The effect of nevirapine in HIV-positive adults is expected to be similar to that in paediatric patients and lopinavir concentrations may be decreased.
L - effett ta ’ nevirapine f’ adulti b’ HIV- positive huwa mistenni li jkun simili għal dawk f’ pazjenti pedjatriċi u il- konċentrazzjonijiet ta ’ lopinavir jistgħu jitnaqqsu.
The clinical significance of the pharmacokinetic interaction is unknown.
Is- sinifikat kliniku ta ’ din l- interazzjoni farmakokinetika mhix magħrufa.
No formal recommendation could be drawn on dosage adjustment when Kaletra is used in combination with nevirapine.
L- ebda rakkomandazzjoni formali ma setgħet taffettwa l- aġġustament tad- dużaġġ meta Kaletra jintuża f’ kombinazjoni ma nevirapine.
However, based on clinical experience, Kaletra dose increase to 533/ 133 mg twice daily (~6.5 ml) may be considered when co-administered with nevirapine, particularly for patients in whom reduced lopinavir susceptibility is likely.
Iżda, ibbażat fuq esperjenza klinika, żieda fid- doża ta ’ Kaletra għal 533/ 133 mg (~6. 5 ml) darbtejn kuljum tista tiġi kkunsidrata meta ko - amministrati ma nevirapine, partikolarment għall- pazjenti li fihom hija mistennija suxettibilita mnaqqsa għal lopinavir.
Efavirenz: when used in combination with efavirenz and two nucleoside reverse transcriptase inhibitors in multiple protease inhibitor-experienced patients, increasing the dose of Kaletra 33.3% from 400/ 100 mg (3 capsules) twice daily to 533/ 133 mg (4 capsules) twice daily yielded similar lopinavir plasma concentrations as compared to historical data of Kaletra 400/ 100 mg (3 capsules) twice daily.
Efavirenz: meta wżat flimkien ma efavirenz u 2 inibituri ta ’ nucleoside reverse transcriptase f’ pazjenti b’ esperjenza ta ’ numru ta ’ inibituri tal- protease, żieda fid- doża ta ’ Kaletra bi 33. 3% minn 400/ 100 mg (3 kapsuli) darbtejn kuljum għal 533/ 133 mg (4kapsuli) darbtejn kuljum wassal għal konċentrazzjonijiet simili ta ’ lopinavir fil- plażma, meta mqabbla ma data storika ta ’ Kaletra 400/ 100 mg (3 kapsuli) darbtejn kuljum.
Dosage increase of Kaletra from 400/ 100 mg (5 ml) twice daily to 533/ 133 mg (~6.5 ml) twice daily should be considered when co-administered with efavirenz.
Żieda fid- doża ta ’ Kaletra minn 400/ 100 mg (5 ml) darbtejn kuljum għal 533/ 133 mg (~6. 5 ml) darbtejn kuljum trid tkun meqjusa meta jkun hemm ko- amministrazzjoni ma efavirenz.
28 Co-administration with other HIV protease inhibitors (PIs):
Ko- amministrazzjoni ma inibituri oħra ta ’ HIV- protease (PIs):
On the other hand, the AUC of lopinavir decreases by 38%.
Amprenavir: l- użu konkomittanti ta ’ Kaletra ma amprenavir 750 mg darbtejn kuljum, irriżulta f’ żieda f’ amprenavir AUC bi 70% u tas- Cmin b’ 4. 6- il darba, relativment ma amprenavir 1200 mg darbtejn kuljum mogħti waħdu. Mill- banda l- oħra, AUC ta ’ lopinavir jonqos bi 38%.
Combined with Kaletra, amprenavir concentrations were lower (approximately 30%) relative to boosted amprenavir (amprenavir 600 mg/ ritonavir 100 mg) twice daily alone.
Meta ikkombinat ma Kaletra, il- konċentrazzjonijiet ta’ amprenavir kienu inqas (xi 30%) relativament ma amprenavir li ġie imħeġġeġ (amprenavir 600 mg/ ritonavir 100 mg) darbtejn kuljum mogħti waħdu.
Co-administration of increased doses of fosamprenavir 1400 mg twice daily with lopinavir/ ritonavir 533/ 133 mg twice daily to protease inhibitor-experienced patients resulted in a higher incidence of gastrointestinal adverse events and elevations in triglycerides with the combination regimen without increases in virological efficacy, when compared with standard doses of fosamprenavir/ ritonavir.
Meta mqabbla ma ’ dożi standard ta ’ fosamprenavir/ ritonavir, l- għoti ta ’ dożi miżjuda ta ’ fosamprenavir ta ’ 1400 mg darbtejn kuljum flimkien ma ’ 533/ 133 mg lopinavir/ ritonavir darbtejn kuljum lil pazjenti li ġieli ngħataw inibituri protejaż, irriżulta f’ inċidenza ogħla ta ’ effetti avversi gastrointestinali u f’ żiediet fit- trigliċeridi meta
Furthermore, concentrations of lopinavir do not appear to be affected when both medicinal products, Kaletra and indinivir, are combined, based on historical comparison with Kaletra alone.
Barra min hekk, il- konċentrazzjonijiet ta ’ lopinavirma jidhrux li huma affetwati meta ż - żewġ prodotti mediċinali, Kaletra u indinivir, huma kkombinati, ibbażat fuq paragun storiku ta ’ Kaletra mogħti waħdu.
Saquinavir 800 mg twice daily co-administered with Kaletra resulted in an increase of saquinavir AUC by approximately 30% relative to saquinavir/ ritonavir 1000/ 100 mg twice daily, and produces similar exposure to those reported after saquinavir/ ritonavir 400/ 400 mg twice daily.
Saquinavir 800 mg darbtejn kuljum ko- amministrat ma Kaletra irriżulta f’ żieda ta ’ AUC ta ’ saquinavir b ’ xi 30% relativament ma saquinavir/ ritonavir 1000/ 100 mg darbtejn kuljum, u jipproduċi esposizzjoni simili għal dawk rappurtati wara saquinavir/ ritonavir 400/ 400 mg darbtejn kuljum.
29 Other medicinal products:
Prodotti mediċinali oħrajn:
Antiarrhythmics:
Antiarritmiċi:
(bepridil, systemic lidocaine and quinidine): concentrations may be increased when co-administered with Kaletra.
(bepridil, lidocaine sistemiku u quinidine): il- konċentrazzjonijiet jistgħu jiżdiedu meta dawn jiġu ko- amministrati ma Kaletra.
In addition, co-administration of phenytoin and lopinavir/ ritonavir resulted in moderate decreases in steady-state phenytoin concentrations.
33 Barra minn hekk, l- għoti flimkien ta ’ phenytoin u lopinavir/ ritonavir wassal għal tnaqqis moderat fil - konċentrazzjoni fissa ta ’ phenytoin.
Bupropion: in healthy volunteers, the AUC and Cmax of bupropion and of its active metabolite, hydroxybupropion, were decreased by about 50% when co-administered with lopinavir/ ritonavir capsules 400/ 100 mg twice daily at steady-state.
Bupropion: f’ voluntiera f’ saħħithom, l- AUC u C max ta ’ bupropion u tal- metabolit attiv tiegħu, hydroxybupropion, naqsu b’ madwar 50% meta ngħataw flimkien ma ’ kapsuli lopinavir/ ritonavir ta ’ 400/ 100 mg darbtejn kuljum fi stat fiss.
However, it is unknown whether the combination of lopinavir/ ritonavir causes a similar increase in trazodone exposure.
Minkejja dan, mhuwiex mgħaruf jekk it- taħlit ta ’ lopinavir ma ’ ritonavir jikkawża żieda simili ta ’ esposizzjoni għal trazodone.
Digoxin: plasma concentrations of digoxin may be increased when co-administered with Kaletra.
Digoxin: konċentrazzjonijiet ta ’ digoxin fil- plażma jistgħu jogħlew meta ikun amministrat ma ’ Kaletra.
Initiation of digoxin in patients already taking Kaletra is expected to result in lower increase of digoxin concentrations.
Introduzzjoni ta ’ digoxin f’ pazjenti li diġa qiegħdin jieħdu Kaletra huwa mistenni li jirriżulta f’ inqa żieda ta ’ konċentrazzjonijniet ta ’ digoxin.
Kaletra oral solution contains alcohol which can produce disulfiram-like reactions when co-administered with disulfiram or other medicinal products that produce this reaction.
Disulfiram, metronidazole: is- soluzzjoni orali ta ’ Kaletra fija alkoħol li jista jikkawża reazzjoni bħal ta ’ disulfiram meta ikun hemm ko- amministrazzjoni ma disulfiram jew mediċinali oħra li jagħmlu din ir - reazzjoni.
Since increased concentrations of HMG-CoA
Inibituri HMG- CoA reductase li jiddependu ħafna fuq metaboliżmu ta ’ CYP3A4, bħal lovastatin u simvastatin, huma mistennija li jkollom żieda fil- konċentrazzjonijiet fil - plażma markata meta ikunu ko- amministrati ma Kaletra.
30 reductase inhibitors may cause myopathy, including rhabdomyolysis, the combination of these medicinal products with Kaletra is not recommended.
Minħabba żieda fil- konċentrazzjonijiet ta ’ inibituri HMG- CoA reductase jistgħu jikkawżaw mijopatija, inkluż rabdomilożi, il- kombinazzjoni ta ’ dawn il- prodotti mediċinali ma Kaletra mhuwiex rakkomandat.
Phosphodiesterase inhibitors: phosphodiesterase inhibitors which are dependent on CYP3A4 metabolism, such as tadalafil and sildenafil, are expected to result in an approximately 2-fold and 11-fold increase in AUC respectively, when co-administered with ritonavir containing regimens including Kaletra and may result in an increase in PDE5 inhibitor associated adverse reactions including hypotension, synope, visual changes and prolonged erection.
Dan jista jirriżulta f’ żieda ta ’ inibitur PDE5 li huwa assoċjat ma eventi avversi bħal pressjoni baxxa, sinope, bdil viżwali, u erezzjoni prolongata.
Particular caution must be used when prescribing sildenafil or tadalafil in patients receiving Kaletra with increased monitoring for adverse events.
Kawietla partikulari għandha tingħata meta sildenafil jew tadalafil jiġu preskritti f’ pazjenti li qiegħdin jieħdu Kaletra biex ikun hemm monituraġġ għal eventi avversi.
The use of vardenafil with Kaletra is contraindicated (see section 4.3).
L- użu ta ’ vardenafil ma Kaletra huwa kontra- indikat (ara sezzjoni 4. 3).
Ketoconazole and itraconazole: may have serum concentrations increased by Kaletra.
Ketoconazole u itraconazole: jista jkollom il- konċentrazzjoni fis- serum miżjuda minn Kaletra.
Clarithromycin: moderate increases in clarithromycin AUC are expected when co-administered with Kaletra.
Clarithromycin: żidiet moderati fi clarithromycin AUC huma mistennija meta ko- somministrati ma Kaletra.
For patients with renal or hepatic impairment dose reduction of clarithromycin should be considered (see section 4.4).
Għal pazjenti b’ indeboliment tal - kliewi jew tal- fwied tnaqqis fid- doża ta’ clarithromycin għandu jiġi kkunsidrat (ara sezzzjoni 4. 4).
Contraceptives: levels of ethinyl oestradiol were decreased when oestrogen-based oral contraceptives were co-administered with Kaletra.
Kontraċettivi: livelli ta ’ ethinyl oestradiol naqsu meta kontraċettivi orali ġew ko- amministrati ma Kaletra.
31 Rifampicin: co-administration of Kaletra with rifampicin is not recommended.
Rifampicin: l- għoti ta ’ Kaletra flimkien ma ’ rifampicin m’ huwiex rakkommandat.
If this co-administration is judged unavoidable, increased dose of Kaletra at 400 mg/ 400 mg twice daily may be administered with rifampicin under close safety and therapeutic drug monitoring.
Jekk jiġi deċiż li dan l- għoti flimkien ma jistax jiġi evitat, doża miżjuda ta ’ Kaletra 400 mg/ 400 mg darbtejn kuljum tista ’ tingħata flimkien ma ’ rifampicin taħt monitoraġġ mill -
The Kaletra dose should be titrated upward only after rifampicin has been initiated (see section 4.4).
Id- doża ta ’ Kaletra għandha tiġi miżjuda ftit ftit, biss wara li jkun inbeda jingħata rifampicin (ara sezzjoni 4. 4).
If Kaletra is co-administered with parenteral midazolam, it should be done in an intensive care unit (ICU) or similar setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/ or prolonged sedation.
Jekk Kaletra jingħata flimkien ma ’ midazolam parenterali, dan għandu jseħħ f’ post għal kura intensiva (ICU) jew post simili fejn ikunu jsiru osservazzjoni klinikali mill- qrib u treġija medika adegwata f’ każ illi jkun hemm deppressjoni respiratorja u/ jew sedazzjoni twila aktar milli sippost.
Dosage adjustment for midazolam should be considered especially if more than a single dose of midazolam is administered.
Għandu jiġi kkunsirat aġġustament fid- doża ta ’ midazolam, speċjalment jekk tkun ingħatat aktar minn doża waħda ta ’ midazolam.
Fluticasone propionate (interaction with ritonavir): in a clinical study where ritonavir 100 mg capsules twice daily were co − administered with 50 μ g intranasal fluticasone propionate (4 times daily) for seven days in healthy subjects, the fluticasone propionate plasma levels increased significantly, whereas the intrinsic cortisol levels decreased by approximately 86% (90% confidence interval 82 − 89%).
Fluticasone propionate (interazzjoni ma ritonavir): fi studju kliniku 100 mg kapsuli darbtejn kuljum ta ’ ritonavir ġew ko- amministrati ma 50ug fluticasone propionate fl- imnieħer (4 darbiet kuljum) għal 7 - ijiem f’ suġġetti f’ saħħithom, il- livelli fil- plażma ta ’ fluticasone propionate għolew sinifikament, filwaqt li il- livelli intrinsiċi tal- korisol tbaxxew b’ approssimament 86% (90% intervall ta ’ fiducja ta ’ 82- 89%).
HIV-infected women must not breast-feed their infants under any circumstances to avoid transmission of HIV.
Nisa infettati bl- HIV m’ għandhomx irreddgħu t - trabi tagħhom taħt l- ebda ċirkustanza sabiex jevvitaw it- trażmissjoni ta ’ l- HIV.
32 4.7 Effects on ability to drive and use machines
36 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Kaletra oral solution contains approximately 42% v/ v alcohol.
Is- soluzzjoni orali ta ’ Kaletra fih approssimament 42% v/ v alkoħol.
The most common adverse event associated with Kaletra therapy was diarrhoea and was generally of mild to moderate severity.
L- iżjed avveniment avers li huwa assoċjat mat- terapija b’ Kaletra kienet diareja li ġeneralment kienet ta ’ severita ħafifa għal moderata.
Discontinuation due to adverse reactions was 4.5% (naïve patients) and 9% (experienced patients) over a 48 week period.
Twaqqif minħabba avvenimen avversi kien 4. 5% (f’ pazjent li qatt ma ħadu dan it- trattament) u 9% (pazjenti b’ esperjenza) f’ perjodu ta ’ 48 ġimgħa.
It is important to note that cases of pancreatitis have been reported in patients receiving Kaletra, including those who developed hypertriglyceridaemia.
Huwa importanti li ninnutaw li każi ta ’ pankreatite ġew rappurtati f’ pazjenti li qed jieħdu Kaletra, inklużi dawk li żvillupaw ipertrigliċeridemija.
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
It- terapija antiretrovirali kkombinata ġiet assoċjata ma redistribuzzjonji tax- xaħam (lipodistrofija) f’ pazjenti bl- HIV, li jinkludi t- telf ta ’ xaħam periferali u tal- wiċċ, żieda fix- xaħam intra- addominali u vixxerali, ipertrofija tal- mammarja u akkumulazzjoni dorsoċervikali ta ’ xaħam (buffalo hump).