natgillin/translations-raw huggingface dataset:
Patients are advised not to drive, operate complex machinery or engage in other potentially hazardous activities until it is known whether this medicinal product affects their ability to perform these activities.
Bolniki naj ne vozijo, ne upravljajo z zapletenimi stroji in ne opravljajo drugih potencialno nevarnih dejavnosti, dokler ni znano, ali to zdravilo vpliva na njihovo sposobnost za te dejavnosti.
No attempt has been made in either the design or the analysis of the CHAMPIX studies to distinguish between adverse events associated with study drug treatment or those possibly associated with nicotine withdrawal.
Nobenega poskusa ni bilo, da bi pri načrtovanju ali analizi študij zdravila CHAMPIX razlikovali med neželenimi učinki, povezanimi s proučevanim zdravilom, in neželenimi učinki, povezanimi z odtegnitvijo nikotina.
Clinical trials included approximately 4,000 patients treated with CHAMPIX for up to 1 year (average exposure 84 days).
84 dni).
In general, when adverse reactions occurred, onset was in the first week of therapy; severity was generally mild to moderate and there were no differences by age, race or gender with regard to the incidence of adverse reactions.
Če so se neželeni učinki pojavili, je bilo to praviloma v prvem tednu zdravljenja; na splošno so bili blagi do zmerni, pojavnost neželenih učinkov pa se ni razlikovala glede na starost, raso ali spol.
In patients treated with the recommended dose of 1mg BID following an initial titration period the adverse event most commonly reported was nausea (28.6%).
Pri bolnikih, ki so po uvodnem obdobju titriranja dobivali priporočeni odmerek 1 mg dvakrat na dan, je bila najpogosteje zabeleženi neželeni učinek navzea (28, 6%).
The treatment discontinuation rate due to adverse events was 11.4% for varenicline compared with 9.7% for placebo.
Delež prekinitev zdravljenja zaradi neželenih učinkov je bil 11, 4% pri bolnikih, ki so dobivali vareniklin, in 9, 7% pri tistih, ki so dobivali placebo.
0.2% for placebo).
V tej skupini so bili deleži prekinitev zdravljenja zaradi najpogostejših neželenih učinkov med bolniki, ki so dobivali vareniklin, kot sledi: navzea (2, 7% proti 0, 6% pri placebu), glavobol (0, 6% proti 1, 0% pri placebu), nespečnost (1, 3% proti 1, 2% pri placebu) in nenormalne sanje (0, 2% proti 0, 2% pri placebu).
In the table below all adverse reactions, which occurred at an incidence greater than placebo are listed by system organ class and frequency (very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100) and rare (≥ 1/ 10,000 to < 1/ 1,000)). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
V razvrstitvah pogostnosti so neželeni učinki navedeni po padajoči resnosti.
System Organ Class
Organski sistem Neželeni učinki zdravila Infekcijske in parazitske bolezni Občasne
Adverse Drug Reactions
bronhitis, nazofaringitis, sinuzitis, glivična okužba, virusna okužba
Infections and Infestations Uncommon
Presnovne in prehranske motnje Pogoste Občasne Psihiatrične motnje
Bronchitis, nasopharyngitis, sinusitis, fungal infection, viral infection,.
povečan apetit anoreksija, zmanjšan apetit, polidipsija
Metabolism and nutrition disorders Common Uncommon
Zelo pogoste
Increased appetite Anorexia, decreased appetite, polydipsia
nenormalne sanje, nespečnost
Psychiatric disorders Very common Uncommon
Organski sistem Občasne Bolezni živčevja
Abnormal dreams, insomnia Panic reaction, bradyphrenia, thinking abnormal, mood swings
Neželeni učinki zdravila panična reakcija, bradifrenija, nenormalno mišljenje, nihanje razpoloženja
Nervous system disorders Very common Common Uncommon Cardiac disorders
Zelo pogoste Pogoste Občasne Srčne bolezni
Headache Somnolence, dizziness, dysgeusia Tremor, coordination abnormal, dysarthria, hypertonia, restlessness, dysphoria, hypoaesthesia, hypogeusia, lethargy, libido increased, libido decreased
glavobol somnolenca, omotica, motnje okušanja tremor, nenormalna koordinacija, dizartrija, hipertonija, nemir, disforija, hipestezija, hipogevzija, letargija, zvečan libido, zmanjšan libido
Uncommon Eye disorders
Občasne Očesne bolezni
Atrial fibrillation, palpitations
atrijska fibrilacija, palpitacije
Scotoma, scleral discolouration, eye pain, mydriasis, photophobia, myopia, lacrimation increased
skotom, obarvanje beločnice, bolečine v očeh, midriaza, fotofobija, miopija, močnejše solzenje
Ear and labyrinth disorders Uncommon
Ušesne bolezni, vključno z motnjami labirinta Občasne
Respiratory, thoracic and mediastinal disorders Uncommon
Bolezni dihal, prsnega koša in mediastinalnega prostora Občasne Bolezni prebavil
Dyspnoea, cough, hoarseness, pharyngolaryngeal pain, throat irritation, respiratory tract congestion, sinus congestion, post nasal drip, rhinorrhoea, snoring
dispneja, kašelj, hripavost, faringolaringealne bolečine, draženje žrela, kongestija dihal, kongestija sinusov, pocejanje v žrelo, rinoreja, smrčanje
Gastrointestinal disorders Very common Common
Zelo pogoste Pogoste
Nausea Vomiting, constipation, diarrhoea, abdominal distension, stomach discomfort, dyspepsia, flatulence, dry mouth
navzea bruhanje, zaprtje, driska, napihnjenost trebuha, nelagodje v želodcu, dispepsija, flatulenca, suhost ust
Haematemesis, haematochezia, gastritis, gastrooesophageal reflux disease, abdominal pain, change of bowel habit, abnormal faeces, eructation, aphthous stomatitis, gingival pain, tongue coated
hematemeza, hematohezija, gastritis, gastroezofagealna refluksna bolezen, bolečine v trebuhu, spremembe navade v zvezi z odvajanjem blata, nenormalno blato, spahovanje, aftozni stomatitis, bolečine v dlesnih, obložen jezik
Skin and subcutaneous tissue disorders Uncommon
Bolezni kože in podkožja Občasne
Rash generalised, erythema, pruritus, acne, hyperhidrosis, night sweats
generaliziran izpuščaj, eritem, pruritus, akne, hiperhidroza, nočno znojenje
connective tissue disorders
Bolezni mišično- skeletnega sistema in vezivnega tkiva Občasne Bolezni sečil
Joint stiffness, muscle spasms, chest wall pain, costochondritis
togost sklepov, mišični krči, bolečine v steni prsnega koša, kostohondritis
Renal and urinary disorders Uncommon
Občasne Motnje reprodukcije Občasne
Reproductive system and breast disorders Uncommon
glikozurija, nokturija, poliurija in dojk menoragija, izcedek iz nožnice, spolna disfunkcija
General disorders and administration site conditions Common Uncommon Investigations
Splošne težave in spremembe na mestu aplikacije Pogoste Občasne Preiskave
Fatigue Chest discomfort, chest pain, pyrexia, feeling cold, asthenia, circadian rhythm sleep disorder, malaise, cyst
utrujenost nelagodje v prsih, bolečine v prsih, pireksija, občutek hladu, astenija, motnje cirkadianega ritma spanja, splošno slabo počutje, cista
Blood pressure increased, electrocardiogram ST segment depression, electrocardiogram T wave amplitude decreased, heart rate increased, liver function test abnormal, platelet count decreased, weight increased, semen abnormal, C-reactive protein increased, blood calcium decreased
zvišan krvni tlak, znižanje segmenta ST v elektrokardiogramu, zmanjšanje amplitude vala T v elektrokardiogramu, hitrejša srčna frekvenca, nenormalni izvidi testov za spremljanje jetrne funkcije, zmanjšano število trombocitov, povečanje telesne mase, nenormalnosti semena, zvišanje ravni C- reaktivnega proteina v krvi, znižanje ravni kalcija v krvi
Post-marketing cases of myocardial infarction, depression and suicidal ideation have been reported in patients taking varenicline (see section 4.4).
V obdobju trženja pri bolnikih, ki so jemali vareniklin, poročajo o primerih miokardnega infarkta, depresije in samomorilnih misli (glejte poglavje 4. 4).
There have also been reports of hypersensitivity reactions, such as angioedema and facial swelling.
Poročali so tudi o preobčutljivostnih reakcijah, kot je angioedem in otekanje obraza.
No cases of overdose were reported in pre-marketing clinical trials.
V okviru predmarketinških kliničnih preskušanj ni bilo opisanih primerov prevelikega odmerjanja.
6 In case of overdose, standard supportive measures should be instituted as required.
6 V primeru prevelikega odmerjanja je treba uvesti standardne podporne ukrepe, kot je potrebno.
Varenicline has been shown to be dialyzed in patients with end stage renal disease (see section 5.2), however, there is no experience in dialysis following overdose.
Dokazano je, da se vareniklin dializira pri bolnikih s končno odpovedjo ledvic (glejte poglavje 5. 2), ni pa izkušenj z dializiranjem po prevelikem odmerjanju.
Pharmacotherapeutic group:
Farmakoterapevtska skupina: zdravila za zdravljenje zasvojenosti z nikotinom.
Active substances used in nicotine dependence, ATC code:
Oznaka ATC:
Varenicline binds with high affinity and selectivity at the α 4β 2 neuronal nicotinic acetylcholine receptors, where it acts as a partial agonist - a compound that has both agonist activity, with lower intrinsic efficacy than nicotine, and antagonist activities in the presence of nicotine.
Vareniklin se z veliko afiniteto in selektivnostjo veže na α4β2 nevronske nikotinske holinergične receptorje in na njih deluje kot delni agonist – spojina, ki ima tako agonistično delovanje (z manjšo intrinzično učinkovitostjo kot nikotin) kot antagonistično delovanje v prisotnosti nikotina.
Electrophysiology studies in vitro and neurochemical studies in vivo have shown that varenicline binds to the α 4β 2 neuronal nicotinic acetylcholine receptors and stimulates receptor-mediated activity, but at a significantly lower level than nicotine.
Elektrofiziološke študije in vitro in nevrokemične študije in vivo so pokazale, da se vareniklin veže na α4β2 nevronske nikotinske holinergične receptorje (nAchR) in stimulira receptorsko posredovano delovanje, vendar bistveno manj kot nikotin.
Nicotine competes for the same human α 4β 2 nAChR binding site for which varenicline has higher affinity.
Nikotin pri človeku tekmuje za isto vezavno mesto α4β2 nAChR, za katero ima vareniklin veliko afiniteto.
Therefore, varenicline can effectively block nicotine's ability to fully activate α 4β 2 receptors and the mesolimbic dopamine system, the neuronal mechanism underlying reinforcement and reward experienced upon smoking.
Tako lahko vareniklin učinkovito onemogoči sposobnost nikotina za popolno aktiviranje receptorjev α4β2 in mezolimbičnega dopaminskega sistema, nevronskega mehanizma, ki je podlaga občutka okrepitve in ugodja pri kajenju.
Varenicline is highly selective and binds more potently to the α 4β 2 receptor subtype (Ki=0.15 nM) than to other common nicotinic receptors (α 3β 4 Ki=84 nM, α 7 Ki= 620 nM, α 1βγδ Ki= 3,400 nM), or to non-nicotinic receptors and transporters (Ki > 1µM, except to 5-HT3 receptors:
Vareniklin je močno selektiven in se na podvrsto receptorjev α4β2 veže močneje (Ki = 0. 15nM) kot na druge pogoste nikotinske receptorje (α3β4 Ki = 84 nM, α7 Ki = 620 nM, α1βγδ Ki = 3, 400 nM) ali na nenikotinske receptorje in transporterje (Ki > 1 µM, razen na receptorje 5- HT3:
The efficacy of CHAMPIX in smoking cessation is a result of varenicline's partial agonist activity at the α 4β 2 nicotinic receptor where its binding produces an effect sufficient to alleviate symptoms of craving and withdrawal (agonist activity), while simultaneously resulting in a reduction of the rewarding and reinforcing effects of smoking by preventing nicotine binding to α 4β 2 receptors (antagonist activity).
Učinkovitost zdravila CHAMPIX pri prenehanju kajenja je posledica delno agonističnega delovanja vareniklina na nikotinskih receptorjih α4β2, kjer njegova vezava zadostuje za ublažitev simptomov hlepenja in odtegnitve (agonistično delovanje), hkrati pa s preprečevanjem vezave nikotina na receptorje α4β2 zmanjšuje s kajenjem povezana občutka okrepitve in ugodja (antagonistično delovanje).
The efficacy of CHAMPIX in smoking cessation was demonstrated in 3 clinical trials involving chronic cigarette smokers (≥ 10 cigarettes per day).
Učinkovitost zdravila CHAMPIX pri opustitvi kajenja so dokazala 3 klinična preskušanja, ki so zajela kronične kadilce cigaret (≥ 10 cigaret na dan).
2619 patients received CHAMPIX 1mg BID (titrated during the first week), 669 patients received bupropion 150 mg BID (also titrated) and 684 patients received placebo.
2619 bolnikov je dobivalo zdravilo CHAMPIX v odmerku 1 mg dvakrat na dan (titriran med prvim tednom), 669 bolnikov je dobivalo bupropion v odmerku 150 mg dvakrat na dan (prav tako titriran), 684 bolnikov pa je dobivalo placebo.
Comparative Clinical Studies
Primerjalni klinični študiji
In these 52-week duration studies, patients received treatment for 12 weeks, followed by a 40-week non- treatment phase.
V teh 52- tedenskih študijah so bolniki 12 tednov dobivali zdravilo, sledila pa je 40- tedenska faza brez njega.
The primary endpoint of the two studies was the carbon monoxide (CO) confirmed, 4-week continuous quit rate (4W-CQR) from week 9 through week 12.
Glavni opazovani dogodek v obeh študijah je bil z ogljikovim monoksidom (CO) preverjeni 4- tedenski trajni delež opustitve (4W- CQR – “ 4- week continuous quit rate ”) od 9. do 12. tedna.
The primary endpoint for CHAMPIX demonstrated statistical superiority to bupropion and placebo.
Po 40- tedenski fazi brez zdravila je bil sekundarni opazovani dogodek v obeh študijah delež trajne abstinence (CA – “ continuous abstinence rate ”) v 52. tednu.
After the 40 week non-treatment phase, a key secondary endpoint for both studies was the Continuous Abstinence Rate (CA) at week 52.
Delež CA je bil opredeljen kot delež vseh zdravljenih oseb, ki od 9. do vključno 52. tedna niso kadile (niti vdiha cigarete) in jim v izdihanem
CA was defined as the proportion of all subjects treated who did not smoke (not even a puff of a cigarette) from Week 9 through Week 52 and did not have an exhaled CO measurement of > 10 ppm.
7 zraku niso izmerili > 10 ppm CO.
The 4W-CQR (weeks 9 through 12) and CA rate (weeks 9 through 52) from studies 1 and 2 are included in the following table:
4W- CQR (od 9. do vključno 12. tedna) in delež CA (od 9. do vključno 52. tedna) iz študij 1 in 2 zajema spodnja tabela:
Study 1 (n=1022)
študija 1 (n = 1. 022)
Study 2 (n=1023)
študija 2 (n = 1. 023)
4W CQR 44.4% 29.5% 17.7% 3.91
4W- CQR
Wk 9-52 4W CQR 22.1% 44.0% 16.4% 30.0% 8.4% 17.7% 3.13 3.85
tedni 4W- CQR 9- 52
CA
CA tedni 9- 52
Wk 9-52 23.0% 15.0% 10.3% 2.66
23, 0% 15, 0% 10, 3% 2, 66
CHAMPIX vs placebo Odds ratio CHAMPIX vs bupropion
CHAMPIX v primerjavi s placebom razmerje obetov
p < 0.0001 1.96 p < 0.0001
< 0, 0001 p
p < 0.0001 p < 0.0001 1.45 1.89 p=0.0640 p < 0.0001
< 0, 0001 p
p < 0.0001 1.72 p=0.0062
< 0, 0001
Patient reported craving, withdrawal and reinforcing effects of smoking Across both Studies 1 and 2 during active treatment, craving and withdrawal were significantly reduced in patients randomized to CHAMPIX in comparison with placebo.
p
Maintenance of Abstinence Study The third study assessed the benefit of an additional 12 weeks of CHAMPIX therapy on the maintenance of abstinence.
< 0, 0001
Patients in this study (n=1,927) received open-label CHAMPIX 1 mg twice daily for 12 weeks.
p < 0, 0001
Patients who stopped smoking by Week 12 were then randomized to receive either CHAMPIX (1 mg twice daily) or placebo for an additional 12 weeks for a total study duration of 52 weeks.
Bolniki, ki so do 12. tedna opustili kajenje, so bili nato randomizirani na prejemanje bodisi zdravila CHAMPIX (1 mg dvakrat na dan) ali placeba za dodatnih 12 tednov; celotna študija je trajala 52 tednov.
The primary study endpoint was the CO-confirmed continuous abstinence rate from week 13 through week 24 in the double-blind treatment phase.
Glavni opazovani dogodek študije je bil s CO preverjeni trajni delež abstinence od 13. do vključno 24. tedna v dvojno slepi fazi zdravljenja.
A key secondary endpoint was the continuous abstinence (CA) rate for week 13 through week 52.
Ključni sekundarni opazovani dogodek je bil delež trajne abstinence (CA) od 13. do vključno 52. tedna.
This study showed the benefit of an additional 12-week treatment with CHAMPIX 1 mg twice daily for the maintenance of smoking cessation compared to placebo.
Ta študija je pokazala, da dodatno 12- tedensko zdravljenje z zdravilom CHAMPIX v odmerku 1 mg dvakrat na dan za vzdrževanje prenehanja kajenja v primerjavi s placebom koristi.
The odds of maintaining abstinence at week 24, following an additional 12 weeks of treatment with CHAMPIX, were 2.47 times those for placebo (p < 0.0001).
Obeti za vzdrževanje abstinence do 24. tedna so bili 2, 47 v primerjavi s placebom (p < 0, 0001).
Superiority to placebo for CA was maintained through week 52 (Odds Ratio=1.35, p=0.0126).
Večja učinkovitost pri doseganju CA v primerjavi s placebom se je ohranila do vključno 52. tedna (razmerje obetov = 1, 35, p = 0, 0126).
The key results are summarised in the following table:
Ključne rezultate povzema naslednja tabela:
CHAMPIX n=602
razlika
Placebo n=604
razmerje
Difference (95% CI)
(95% interval
Odds ratio (95% CI)
(95% interval zaupanja)
CA wk 13-24
CA tedni 13- 24
(15.4%, 26.2%)
(15, 4
(1.95, 3.15)
%, 26, 2%)
CA wk 13-52
(1, 95, 3, 15)
44.0%
CA tedni 13- 52
6.9% (1.4%,12.5%)
(1, 4
There is currently limited clinical experience with the use of CHAMPIX among black people to determine clincial efficacy.
Trenutno je le malo kliničnih izkušenj z uporabo zdravila CHAMPIX z namenom določitve klinične učinkovitosti pri temnopoltih ljudeh.
Following administration of multiple oral doses to healthy volunteers, steady- state conditions were reached within 4 days.
Po uporabi več peroralnih odmerkov pri zdravih prostovoljcih je bilo stanje dinamičnega ravnovesja doseženo v 4 dneh.
Absorption is virtually complete after oral administration
Absorpcija po peroralni uporabi je skoraj popolna in sistemska razpoložljivost je velika.
Oral bioavailability of varenicline is unaffected by food or time-of- day dosing.
Hrana in dnevni čas uporabe ne vplivata na biološko uporabnost vareniklina.
Plasma protein binding of varenicline is low (< 20%) and independent of both age and renal function.
Vezava vareniklina na beljakovine v plazmi je nizka (≤ 20%) in ni odvisna od starosti in delovanja ledvic.
Varenicline undergoes minimal metabolism with 92% excreted unchanged in the urine and less than 10% excreted as metabolites.
Vareniklin se minimalno presnavlja; 92% se ga nespremenjenega izloči v urinu in manj kot 10% se ga izloči v obliki presnovkov.
Minor metabolites in urine include varenicline N- carbamoylglucuronide and hydroxyvarenicline.
Med manj pomembnimi presnovki v urinu sta vareniklinijev N- karbamoilglukuronid in hidroksivareniklin.
In circulation, varenicline comprises 91% of drug- related material.
V krvnem obtoku obsega vareniklin 91% z zdravilom povezanega materiala.
Minor circulating metabolites include varenicline N-carbamoylglucuronide and N- glucosylvarenicline.
Med manj pomembnimi presnovki v obtoku sta vareniklinov N- karbamoilglukuronid in N- glukozilvareniklin.
(see section 4.5).
Ledvično izločanje vareniklina poteka primarno z glomerulno filtracijo ob hkratni aktivni tubulni sekreciji prek organskega kationskega transporterja, OCT2 (glejte poglavje 4. 5).
Linearity/ Non linearity:
Linearnost/ nelinearnost:
Varenicline exhibits linear kinetics when given as single (0.1 to 3 mg) or repeated 1 to 3 mg/ day) doses.
Kinetika vareniklina, uporabljenega v posamičnem odmerku (od 0, 1 do 3 mg) ali ponavljajočih se odmerkih (od 1 do 3 mg/ dan), je linearna.
Pharmacokinetics in special patient populations:
Farmakokinetika v posebnih populacijah bolnikov:
There are no clinically meaningful differences in varenicline pharmacokinetics due to age, race, gender, smoking status, or use of concomitant medications, as demonstrated in specific pharmacokinetic studies and in population pharmacokinetic analyses.
Kot so pokazale specifične farmakokinetične študije in analize populacijske farmakokinetike, se farmakokinetika vareniklina ne razlikuje klinično pomembno glede na starost, raso, spol, kadilski status ali sočasno uporabo drugih zdravil.
(see section 4.2).
Ker se vareniklin v jetrih ne presnavlja pomembno, farmakokinetika vareniklina pri bolnikih z okvaro jeter ne bi smela biti spremenjena (glejte poglavje 4. 2).
Varenicline pharmacokinetics were unchanged in subjects with mild renal impairment (estimated creatinine clearance > 50 ml/ min and ≤ 80 ml/ min).
Farmakokinetika vareniklina pri osebah z blago okvaro ledvic (ocenjeni očistek kreatinina > 50 ml/ min in ≤ 80 ml/ min) ni bila spremenjena.
In patients with moderate renal impairment (estimated creatinine clearance ≥ 30 ml/ min and ≤ 50 ml/ min), varenicline exposure increased 1.5-fold compared with subjects with normal renal function (estimated creatinine clearance > 80 ml/ min).
Pri bolnikih z zmerno okvaro ledvic (ocenjeni očistek kreatinina ≥ 30 ml/ min in ≤ 50 ml/ min) je bila izpostavljenost vareniklinu 1, 5- krat večja kot pri preiskovancih z normalnim delovanjem ledvic (ocenjeni očistek kreatinina > 80 ml/ min).
In subjects with severe renal impairment (estimated creatinine clearance < 30 ml/ min), varenicline exposure was increased 2.1-fold.
Pri preiskovancih s hudo okvaro ledvic (ocenjeni očistek kreatinina < 30 ml/ min) je bila izpostavljenost vareniklinu 2, 1- krat večja.
In subjects with end-stage-renal disease (ESRD), varenicline was efficiently removed by haemodialysis (see section 4.2).
Pri preiskovancih s končno odpovedjo ledvic je hemodializa učinkovito odstranila vareniklin (glejte poglavje 4. 2).
The pharmacokinetics of varenicline in elderly patients with normal renal function (aged 65- 75 years) is similar to that of younger adult subjects (see section 4.2).
Farmakokinetika vareniklina je pri starejših bolnikih z normalnim delovanjem ledvic (starih od 65 do 75 let) podobna kot pri mlajših odraslih osebah (glejte poglavje 4. 2).
For elderly patients with reduced renal function please refer to section 4.2.
Za starejše bolnike z zmanjšanim delovanjem ledvic glejte poglavje 4. 2.
Adolescents:
Mladostniki:
When 22 adolescents aged 12 to 17 years (inclusive) received a single 0.5 mg and 1 mg dose of varenicline the pharmacokinetics of varenicline was approximately dose proportional between the 0.5 mg and 1 mg doses.
Ko je 22 mladostnikov, starih od 12 do (vključno) 17 let dobilo posamičen odmerek 0, 5 mg in 1 mg vareniklina, je bila farmakokinetika vareniklina med odmerkoma 0, 5 mg in 1 mg približno sorazmerna odmerku.
Systemic exposure, as assessed by AUC (0-inf), and renal clearance of varenicline were comparable to adults.
Sistemska izpostavljenost, ocenjena z AUC (0- ∞), in ledvični očistek vareniklina sta bila podobna kot pri odraslih.
An increase of 30% in Cmax and a shorter elimination half-life (10.9 hr) were observed in adolescents compared with adults (see section 4.2).
Pri mladostnikih so v primerjavi z odraslimi ugotovili 30% povečanje Cmax in krajši razpolovni čas izločanja (10, 9 ure) (glejte poglavje 4. 2).
In vitro studies demonstrate that varenicline does not inhibit cytochrome P450 enzymes (IC50 > 6,400 ng/ ml).
Študije in vitro kažejo, da vareniklin ne zavira encimov citokroma P450 (IK50 > 6. 400 ng/ ml).
The P450 enzymes tested for inhibition were:
Glede zavrtja so testirali naslednje encime P450:
1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4/ 5.
1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 in 3A4/ 5.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, fertility and embryo-foetal development.
Neklinični podatki na osnovi običajnih študij farmakološke varnosti, toksičnosti pri ponavljajočih se odmerkih, genotoksičnosti, plodnosti in embriofetalnega razvoja ne kažejo posebnega tveganja za človeka.
In the offspring of pregnant rats treated with varenicline there were decreases in fertility and increases in the auditory startle response (see section 4.6).
Pri mladičih podgan, ki so dobivale vareniklin, so ugotovili manjšo plodnost in močnejšo reakcijo na slušni dražljaj (glejte poglavje 4. 6).
Nonclinical data indicate varenicline has reinforcing properties albeit with lower potency than nicotine.
Neklinični podatki kažejo, da ima vareniklin okrepitvene učinke, čeprav so le- ti manj močni kot pri nikotinu.
Core Tablet
Jedro tablete