qanastek/EMEA-V3 huggingface dataset:
These reactions are listed in Table 1 by system organ class and frequency (very common (> 1/ 10), common (> 1/ 100 ,< 1/10), uncommon (> 1/ 1,000 to ≤ 1/ 100)).
Dawn ir- reazzjonijiet huma elenkati f’ Tabella 1 skond il- klassi tas- sistema ta ’ l- organi tas- sistema u l- frekwenza (komuni ħafna (> 1/ 10), komuni (> 1/ 100, < 1/ 10), mhux komuni (> 1/ 1, 000 sa ≤ 1/ 100)).
Treatment-related undesirable effects reported in the pivotal clinical study of Suboxone (≥ 0.1% of Suboxone-treated patients)
Effetti mhux mixtieqa relatati mat- trattament irrappurtati fi studju pivitali kliniku b’ Suboxone (≥ 0. 1% tal- pazjenti ttrattati b’ Suboxone)
Infections and infestations
Infezzjonijiet u infestazzjonijiet Komuni:
Common:
Infezzjoni Mhux komuni:
Infection Uncommon:
Vaġinite Disturbi tad- demm u tas- sistema limfatika Mhux komuni:
Vaginitis Blood and lymphatic system disorders
Anemija, tromboċitopenja, lewkopinja, limfadenopatija, lewkoċitożi Disturbi fis- sistema immuni Mhux komuni:
Anaemia, thrombocytopenia, leucopenia, lymphadenopathy, leukocytosis Immune system disorders
Reazzjoni allerġika Disturbi fil- metaboliżmu u n - nutrizzjoni Komuni:
Allergic reaction Metabolism and nutrition disorders
Edima periferali, tnaqqis fil- piż.
Peripheral oedema, weight decreased Uncommon:
Ipergliċemija, iperlipemija, ipogliċemija
Anxiety, nervousness, depression, libido decreased, thinking abnormal Uncommon:
Ansjetà, nervi, depressjoni, tnaqis fil- libido, ħsibijiet mhux Disturbi psikjatriċi Komuni: normali Mhux komuni:
Drug dependence, amnesia, hostility, speech disorder, depersonalization, abnormal dream, apathy, euphoria Nervous system disorders
Dipendenza fuq id- droga, amneżija, mġieba ostili, tixkil fil- kliem, tibdil fil- personalità, ħolm mhux normali, apatija u ewforja Disturbi fis- sistema nervuża Komuni ħafna:
Very Common:
Nuqqas ta ’ rqad Komuni:
Somnolence, dizziness, paresthesia, hypertonia Uncommon:
Ngħas, sturdament, parasteżija, ipertonija Mhux komuni:
Lacrimation disorder, amblyopia Uncommon:
Konvulżjonijiet, aġitazzjoni, rogħda, iperkineżja Disturbi fl- għajnejn Komuni:
Miosis, conjunctivitis Cardiac disorders
Disturbi tad- dmugħ, amblijopja Mhux komuni:
Uncommon:
Mijożi, konġunktivite Disturbi fil- qalb Mhux komuni:
Myocardial infarction, angina pectoris, palpitation, tachycardia, bradycardia
Infart mijokardijaku, anġina pektoris, palpitazzjonijiet, takikardja, bradikardja
7 Vascular disorders
7 Disturbi vaskulari
Vasodilation, hypertension, migraine Uncommon:
Pressjoni baxxa, stroke tas- sħana
Hypotension, heat stroke Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji, toraċiċi u medjastinali
Rhinitis, pharyngitis, cough increased Uncommon:
Mhux komuni:
Dyspnoea, asthma, yawn Gastrointestinal disorders
Disturbi gastro- intestinali
Very Common:
Komuni:
Constipation, nausea Common:
Mhux komuni:
Vomiting, dyspepsia, diarrhoea, anorexia, flatulence Uncommon:
Stomatite b’ ulċeri, ilsien jitlef il- kulur
Ulcerative stomatitis, tongue discolouration Hepatobiliary disorders
Disturbi fil- fwied u fil- marrara
Liver function abnormal Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Very Common:
ħafna:
Sweating Common:
Komuni:
Rash, pruritus, urticaria Uncommon:
Għaraq Raxx, ħakk, urtikarja
Arthralgia, myalgia, leg cramps Uncommon:
Dermatite bil- qxur, akne, noduli fil- ġilda, alopeċja, ġilda xotta
Arthritis Renal and urinary disorders
Disturbi muskolu- skeltrali, tal - connective tissue u tal- għadam
Albuminuria, urine abnormality Uncommon:
Artralġja, majalġja, bugħawwieġ
Impotence, amenorrhoea, abnormal ejaculation, menorrhagia, metrorrhagia General disorders
Disturbi fil- kliewi u fis- sistema urinarja
Withdrawal syndrome, headache Common:
Mhux komuni:
Asthenia, fever, flu syndrome, malaise, accidental injury, chills, chest pain, abdominal pain, back pain, pain Injury, poisoning and procedural complications
Ematurja, kalklu fil- kliewi, żieda fil- krejatinina, infezzjoni tal - passaġġ tal- awrina, diżurja, ritenzjoni tal- awrina
Uncommon:
Disturbi fis- sistema riproduttiva u fis- sider Mhux komuni:
Hypothermia
Ipotermja
Buprenorphine used alone for treatment of opioid dependency has been associated with the following symptoms (> 1%): constipation, headache, insomnia, asthenia, drowsiness, nausea and vomiting, fainting and dizziness, orthostatic hypotension, and sweating.
Buprenorphine użat waħdu għat- trattament ta ’ dipendenza ta ’ l- opjojd kien assoċjat ma ’ dawn is - sintomi (> 1%): stitikezza, uġigħ ta ’ ras, nuqqas ta ’ rqad, astenja, ngħas, dardir u rimettar, ħass ħażin u sturdament, pressjoni titbaxxa mal- pożizzjoni, u għaraq.
Other undesirable effects (< 0.1%) have been reported in association with buprenorphine alone.
Effetti oħra mhux mixtieqa (< 0. 1%) kienu rrappurtati meta ngħata buprenorphine waħdu.
These are: • respiratory depression (see sections 4.4 and 4.5), • hepatic necrosis and hepatitis (see section 4.4), • hallucinations,
Dawn huma: • depressjoni respiratorja (ara sezzjonijiet 4. 4 u 4. 5), • nekrożi epatika u epatite (ara sezzjoni 4. 4), • alluċinazzjonijiet, • każijiet ta ’ bronkospażmi, edima anġjonewrotika u xokk anafilattiku.
In cases of intravenous misuse, local reactions, sometimes septic, and potentially serious acute hepatitis have been reported (see section 4.4).
F’ każijiet ta ’ użu ħażin minn ġol- vini, reazzjonijiet lokali, kultant settiċi, u epatite akuta li tista ’ tkun serja kienu rrappurtati (ara sezzjoni 4. 4).
In patients presenting with marked drug dependence, initial administration of buprenorphine can produce a withdrawal effect similar to that associated with naloxone.
F’ pazjenti li jkunu dipendenti ħafna fuq id- drogi, l- għotja fil- bidu ta ’ buprenorphine tista ’ tikkawża effett ta ’ twaqqif simili għal dak assoċjat ma ’ naloxone.
Spontaneous abortion has been reported with both buprenorphine and buprenorphine-naloxone.
8 Abort spontanju kien rappurtat kemm b’ buprenorphine kif ukoll b’ buprenorphine- naloxone.
It is not possible to establish a causal relationship, since cases typically involve other drug use or risk factors for spontaneous abortion (see section 4.6).
Mhux possibli li tiġi stabbilita l- kawża, peress li f’ dawn il- każijiet normalment ikunu jinvolvu drogi oħrajn jew ikun hemm fatturi oħra li jżidu r- riskju għall- abort spontanju (ara sezzjoni 4. 6).
A neonatal abstinence syndrome has been reported among newborns of women who have received buprenorphine during pregnancy.
Sindrome ta ’ astinenza tat- tarbija tat- twelid kien irrappurtat fost trabi tat- twelid ta ’ nisa li kienu rċevew buprenorphine waqt it- tqala.
The syndrome may be milder and more protracted than that from short acting full µ-opioid agonists.
Is- sindrome jista ’ jkun eħfef u jdum aktar minn dak ikkawżat mill- agonisti tal - µ- opjojd sħaħ li jaħdmu fil- qosor.
The nature of the syndrome may vary depending upon the mother’ s drug use history (see section 4.6).
In- natura tas- sindrome tista ’ tvarja skond il- passat ta ’ l- użu tad- droga mill- omm (ara sezzjoni 4. 6).
In the event of overdose, general supportive measures should be instituted, including close monitoring of respiratory and cardiac status of the patient.
F’ każ ta ’ doża eċċessiva, miżuri ġenerali ta ’ support għandhom jingħataw, inklużi monitoraġġ mill - qrib ta ’ l- istat respiratorju u kardijaku tal- pazjent.
The major symptom requiring intervention is respiratory depression, which could lead to respiratory arrest and death.
L- aktar sintomu li jkollu bżonn intervent huwa d - depressjoni respiratorja, li jista ’ jwassal għall- arrest respiratorju u mewt.
If the patient vomits, care must be taken to prevent aspiration of the vomitus.
Jekk il- pazjent jirremetti, wieħed għandu joqgħod attent sabiex jiġi evitat li r- rimettar ikun aspirat.
Treatment:
Trattament:
Symptomatic treatment of respiratory depression, and standard intensive care measures, should be implemented.
Trattament tas- sintomi ta ’ depressjoni respiratorja, u miżuri ta ’ kura intensiva standard, għandhom ikunu implimentati.
A patent airway and assisted or controlled ventilation must be assured.
Huwa importanti li jkun żgurat il- passaġġ respiratorju u ventilazzjoni assistita jew kontrollata.
The patient should be transferred to an environment within which full resuscitation facilities are available.
Il- pazjent għandu jiġi trasferit f’ ambjent fejn il- faċilitajiet kollha għar - resuxxitazzoni jkunu disponibbli.
Use of an opioid antagonist (i. e., naloxone) is recommended, despite the modest effect it may have in reversing the respiratory symptoms of buprenorphine compared with its effects on full agonist opioid agents.
Huwa rrikkmandat l- użu ta ’ antagonist ta ’ l- opjojd (i. e. naloxone), minkejja l- effett modest li jista ’ jkollu biex ireġġa ’ lura s- sintomi ta ’ buprenorphine meta mqabbel ma ’ l- effetti tiegħu fuq sustanzi opjojd agonisti kompleti.
The long duration of action of Suboxone should be taken into consideration when determining the length of treatment and medical surveillance needed to reverse the effects of an overdose.
L- azzjoni fit- tul ta ’ Suboxone għandha titqies meta jkun qed jiġi determinat it- tul tat- trattament u s - sorveljanza medika meħtieġa sabiex l- effetti ta ’ doża eċċessiva jitreġgħu lura.
Drugs used in opioid dependence, ATC code:
Mediċini li jintużaw għad- dipendenza mill- opjojds, Kodiċi ATC:
Mechanism of action:
Mod kif jaħdem:
Buprenorphine is an opioid partial agonist/ antagonist which binds to the μ (mu) and κ (kappa) receptors of the brain.
Buprenorphine huwa agonist/ antagonist parzjali opjojd li jeħel mar- riċetturi µ (mu) u κ (kappa) fil - moħħ.
Its activity in opioid maintenance treatment is attributed to its slowly reversible properties with the μ receptors, which over a prolonged period, might minimise the need of addicted patients for drugs.
L- attività tiegħu fit- trattament tal- manteniment tal- opjojd huwa attribwit mill- karatteristika li jeħel bil- mod u b’ mod riversibbli mar- riċetturi µ, li fuq perijodu twil, jista ’ jnaqqas il- bżonn għad - drogi li jkollhom pazjenti bil- vizzju tad- drogi.
Opioid agonist ceiling effects were observed during clinical pharmacology studies in opioid-dependent persons.
Effetti li jilħqu l- quċċata ta ’ agonisti ta ’ l- opjojd dehru waqt studji farmakoloġiċi kliniċi f’ persuni dipendenti fuq opjojds.
Naloxone is an antagonist at μ (mu)-opioid receptors.
Naloxone huwa antagonist tar- riċetturi µ (mu) tal- opjojd.
When administered orally or sublingually in usual doses to patients experiencing opioid withdrawal, naloxone exhibits little or no pharmacological effect because of its almost complete first pass metabolism.
Meta jingħata b’ mod orali jew taħt l- ilsien fid- dożi tas- soltu lill- pazjenti li jkollhom sintomi tat- twaqqif ta ’ opjojd, naloxone juri ftit jew l- ebda effett farmakoloġiku minħabba l- metaboliżmu first pass kważi komplet.
However, when administered intravenously to opioid dependent persons, the presence of naloxone in Suboxone produces marked opioid antagonist effects and opioid withdrawal, thereby deterring intravenous abuse.
Madankollu, meta jingħata minn ġol- vina lill- persuni dipendenti fuq opjojds, il- preżenza ta ’ naloxone f’ Suboxone jikkawża effetti qawwija ta ’ antagonisti ta ’ l- opjojd u twaqqif ta ’ l- opjojds, b’ hekk jiskuraġġixxi l- abbuż minn ġol - vina.
9 Clinical efficacy:
Effikaċja klinika:
Efficacy and safety data for Suboxone are primarily derived from a one-year clinical trial, comprising a 4-week randomised double blind comparison of Suboxone, buprenorphine and placebo tablets followed by a 48 week safety study of Suboxone.
F’ din il- prova, 326 individwu
In this trial, 326 heroin-addicted subjects were randomly assigned to either Suboxone 16 mg per day, 16 mg buprenorphine per day or placebo tablets.
9 bil- vizzju ta ’ l- eroina, kienu magħżula b’ mod arbitrarju biex jingħataw Suboxone 16 mg kuljum, 16 mg buprenorphine kuljum jew pilloli plaċebo.
For subjects randomized to either active treatment, dosing began with one 8 mg tablet of buprenorphine on Day 1, followed by 16 mg (two 8 mg tablets) of buprenorphine on Day 2.
Għall- pazjenti li ntgħażlu b’ mod arbitrarju għal wieħed mit- trattamenti attivi, id- dużaġġ beda b’ pillola ta ’ 8 mg buprenorphine f’ Jum 1, segwit b’ 16 mg (żewġ pilloli ta ’ 8 mg) ta ’ buprenorphine f’ Jum 2.
On Day 3, those randomized to receive Suboxone were switched to the combination tablet.
F’ Jum 3, dawk li ntgħażlu b’ mod arbitrarju biex jirċievu Suboxone inqalbu għall- pillola kombinata.
Subjects were seen daily in the clinic (Monday through Friday) for dosing and efficacy assessments.
L- individwi kienu nviżtati kuljum fil- klinika (mit- Tnejn sal- Ġimgħa) għall- evalwar tad- dużaġġi u l- effikaċja.
Take-home doses were provided for weekends.
Għal tmiem il- ġimgħa, ingħataw dożi li setgħu jittieħdu d- dar.
The primary study comparison was to assess the efficacy of buprenorphine and Suboxone individually against placebo.
It- tqabbil ta ’ l- istudju ewlieni kien sabiex tiġi evalwata l- effikaċja ta ’ buprenorphine u Suboxone b’ mod individwali kontra l- plaċebo.
The percentage of thrice-weekly urine samples that were negative for non-study opioids was statistically higher for both Suboxone versus placebo (p < 0.0001) and buprenorphine versus placebo (p < 0.0001).
Il- perċentwal tal- kampjuni li ttieħdu tlett darbiet fil- ġimgħa li kienu negattivi għall- opjojds mhux ta ’ l- istudju kien statistikament ogħla kemm għal Suboxone kontra l- plaċebo (p < 0. 0001) u buprenorphine kontra l- plaċebo (p < 0. 0001).
In a double-blind, double-dummy, parallel-group study comparing buprenorphine ethanolic solution to a full agonist active control, 162 subjects were randomized to receive the ethanolic sublingual solution of buprenorphine at 8 mg/ day (a dose which is roughly comparable to a dose of 12 mg/ day of Suboxone), or two relatively low doses of active control, one of which was low enough to serve as an alternative to placebo, during a 3 to10 day induction phase, a 16-week maintenance phase and a 7- week detoxification phase.
Fi studju double- blind, double dummy, bi grupp parallel li qabbel is- soluzzjoni etanolika ta ’ buprenorphine ma ’ kontroll agonist attiv sħiħ, 162 individwu ntgħażlu b’ mod arbitrarju biex jirċievu soluzzjoni etanolika ta ’ taħt l- ilsien ta ’ buprenorphine 8 mg/ jum (doża li hija komparabbli bejn wieħed u ieħor ma ’ doża ta ’ 12 mg/ jum ta ’ Suboxone), jew żewġ dożi relattivament baxxi tal- kontroll attiv, li wieħed minnhom kien baxx biżżejjed li seta ’ jservi bħala alternattiv għall- plaċebo, waqt fażi ta ’ induzzjoni ta ’ 3 sa 10 ijiem, fażi ta ’ manteniment ta ’ 16- il ġimgħa u fażi ta ’ diżintossikazzjoni ta ’ 7 - ġimgħat.
Buprenorphine was titrated to maintenance dose by Day 3; active control doses were titrated more gradually.
Buprenorphine kien miżjud bil- mod għad- doża ta ’ manteniment ma ’ Jum 3; dożi tal- kontroll attiv kienu miżjuda aktar bil- mod.
Based on retention in treatment and the percentage of thrice- weekly urine samples negative for non-study opioids, buprenorphine was more effective than the low dose of the control, in keeping heroin addicts in treatment and in reducing their use of opioids while in treatment.
Skond ir- retenzjoni fit- trattament u l- perċentwali ta ’ kampjuni ta ’ l - awrina li ttieħdu tlett darbiet fil- ġimgħa li ġew negattivi għall- opjojdi mhux ta ’ l- istudju, buprenorphine kien aktar effettiv mid- doża baxxa tal- kontroll, sabiex iżomm persuni bil- vizzju ta ’ l - eroina fit- trattament u biex inaqqsilhom l- użu ta ’ opjojdi waqt it- trattament.
The effectiveness of buprenorphine, 8 mg per day was similar to that of the moderate active control dose, but equivalence was not demonstrated.
L- effikaċja ta ’ buprenorphine, 8 mg kuljum kienet simili għal dik tad- doża tal- kontroll attiv moderat, iżda l - ekwivalenza ma ġietx murija.
Buprenorphine
Buprenorphine
Buprenorphine, when taken orally, undergoes first-pass metabolism with N-dealkylation and glucuroconjugation in the small intestine and the liver.
Buprenorphine, meta jittieħed b’ mod orali, jgħaddi minn metaboliżmu first pass b ’ N- dealkalizazzjoni u glukurkonjugazzjoni fil- musrana ż- żgħira u l- fwied.
The use of this medicinal product by the oral route is therefore inappropriate.
Għalhekk l- użu ta ’ dan il- prodott mediċinali b’ mod orali mhux xieraq.
Peak plasma concentrations are achieved 90 minutes after sublingual administration.
Il- konċentrazzjonijiet l- aktar għoljin fil- plażma jintlaħqu 90 minuta wara li jittieħdu minn taħt l- ilsien.
Plasma levels of buprenorphine increased with the sublingual dose of Suboxone.
Il- livelli fil- plażma ta ’ buprenorphine żdiedu bid- doża minn taħt l- ilsien ta ’ Suboxone.
Both Cmax and AUC of buprenorphine increased with the increase in dose (in the range of 4-16 mg), although the increase was less than dose proportional.
Kemm Cmax kif ukoll AUC ta ’ buprenorphine żdiedu b’ żieda fid- doża (fil- medda ta ’ 4 – 16 mg), għalkemm iż- żieda kienet anqas mill- poporzjon tad- doża.
Pharmacokinetic Parameter
Parametru Farmakokinetiku
1.84 (39)
1. 84 (39)
3.0 (51)
3. 0 (51)
5.95 (38)
5. 95 (38)
AUC0-48 hour · ng/ ml
AUC0- 48 siegħa · ng/ ml
12.52 (35)
12. 52 (35)
20.22 (43)
20. 22 (43)
34.89 (33)
34. 89 (33)
The absorption of buprenorphine is followed by a rapid distribution phase (distribution half-life of 2 to 5 hours).
L- assorbiment ta ’ buprenorphine jiġi segwit b’ fażi ta ’ distribuzzjoni mgħaġġla (half- life tad - distribuzzjoni 2 sa 5 sigħat).
Metabolism and elimination:
Metaboliżmu u eliminazzjoni:
Buprenorphine is metabolised by 14-N-dealkylation and glucuroconjugation of the parent molecule and the dealkylated metabolite.
Buprenorphine huwa metabolizzat permezz ta ’ 14- N- dealkalizazzjoni u glukurkonjugazzjoni tal - molekula oriġinali u l- metabolu li jkun ġie dealkalizzat.
Clinical data confirm that CYP3A4 is responsible for the N-
Tagħrif kliniku jikkonferma li CYP3A4 huwa responsabbli għall- N- dealkalizazzjoni ta ’ buprenorphine.
N-dealkylbuprenorphine is a μ (mu)-opioid agonist with weak intrinsic activity.
N- dealkylbuorenorphine huwa agonist ta ’ opjojd µ (mu) b’ attività intrinsika dgħajfa.
Elimination of buprenorphine is bi- or tri-exponential, and has a mean half-life from plasma of 32 hours.
10 L- eliminazzjoni ta ’ buprenorphine hija bi - jew tri- esponenzjali, u għandha half- life medja mill- plażma ta ’ 32 siegħa.
Buprenorphine is eliminated in the faeces by biliary excretion of the glucuroconjugated metabolites (70%), the rest being eliminated in the urine.
Buprenorphine jitneħħa ma ’ l- ippurgar b’ eskrezzjoni mill- marrara tal- metaboli glukurokonjugati (70%), l- bqijja jitneħħa ma ’ l- awrina.
Following intravenous administration, naloxone is rapidly distributed (distribution half-life ~ 4 minutes).
Wara l- għotja minn ġol- vina, naloxone jinfirex malajr (half- life tad- distribuzzjoni ~ 4 minuti).
Following oral administration, naloxone is barely detectable in plasma; following sublingual administration of Suboxone, plasma naloxone concentrations are low and decline rapidly.
Wara l - għotja b’ mod orali, naloxone bil- kemm jiġi mkejjel fil- plażma; wara l- għotja ta ’ Suboxone minn taħt l- ilsien, il- konċentrazzjonijiet ta ’ naloxone fil- plażma jkunu baxxi u jaqaw malajr.
The medicinal product is metabolized in the liver, primarily by glucuronide conjugation, and excreted in the urine.
Il- prodott mediċinali jiġi metabolizzat fil- fwied, l- aktar b’ konjugazzjoni ta ’ glukuronajd, u eskretat fl - awrina.
Naloxone has a mean half-life from plasma of 1.2 hours.
Naloxone għandu half- life medja mill- plażma ta ’ 1. 2 sigħat.
No pharmacokinetic data in elderly patients are available.
M’ hemmx tagħrif farmakokinetiku f\ pazjenti anzjani.
Renal elimination plays a relatively small role (~30%) in the overall clearance of Suboxone.
L- eliminazzjoni renali għandha rwol relattivament żgħir (~30%) fit- tneħħija globali ta ’ Suboxone.
No dose modification based on renal function is required but caution is recommended when dosing subjects with severe renal impairment.
Mhux meħtieġ li jkun hemm tibdil fid- doża skond il- funzjoni renali iżda hija rrikkmandata l- attenzjoni meta jkunu qed jiġu mogħtija dożi lill- individwi li jkollhom indeboliment renali sever.
Hepatic elimination plays a relatively large role (~70%) in the overall clearance of Suboxone and the action of buprenorphine may be prolonged in subjects with impaired hepatic clearance.
L- eliminazzjoni epatika għandha rwol relattivament kbir (~70%) fit- tneħħija globali ta ’ Suboxone u l- azzjoni ta ’ buprenorphine tista ’ tittawwal f’ individwi li jkollhom tneħħija epatika indebolita.
Lower initial Suboxone doses and cautious titration of dosage may be required in patients with mild to moderate hepatic dysfunction.
Tnaqqis tad- dożi tal- bidu ta ’ Suboxone u żieda tad- dożi bil- mod bil- kawtela jistgħu jkunu meħtieġa f’ pazjenti b’ funzjoni epatika ħażina minn ħafifa għal moderata.
Suboxone is contraindicated in patients with severe hepatic dysfunction (see section 4.3).
Suboxone huwa kontra- indikat f’ pazjenti b’ funzjoni epatika ħażina severa (ara sezzjoni 4. 3).
The combination of buprenorphine and naloxone has been investigated in acute and repeated dose (up to 90 days in rats) toxicity studies in animals.
It- taħlita ta ’ buprenorphine ma ’ naloxone kienet investigata fi studji dwar it- tossiċità f’ annimali b’ dożi akuti u ripetuti (sa 90 jum fil- firien).
No synergistic enhancement of toxicity has been observed.
Ma deherx li kien hemm żieda sinerġistika tat- tossiċità.
Undesirable effects were based on the known pharmacological activity of opioid agonistic and/ or antagonistic substances.
Effetti mhux mixtieqa kienu bbażati fuq l- attività farmakoloġika magħrufa ta ’ agonisti tal- opjojd u/ jew sustanzi antagonisti.
The combination (4:1) of buprenorphine hydrochloride and naloxone hydrochloride was not mutagenic in a bacterial mutation assay (Ames test), and was not clastogenic in an in vitro cytogenetic assay in human lymphocytes or in an intravenous micronucleus test in the rat.
It- taħlita (4: 1) ta ’ buprenorphine hydrochloride u naloxone hydrochloride ma kienetx mutaġenika f’ essej ta ’ mutazzjoni batterika (Ames test), u ma kienetx klastoġenika f’ essej in vitro ċitoġeniku f’ limfoċiti umani jew f’ test mikronuklejus minn ġol- vina fil- far.
Reproduction studies by oral administration of buprenorphine: naloxone (ratio 1:1) indicated that embryolethality occurred in rats in the presence of maternal toxicity at all doses.
Studji dwar ir- riproduzzjoni b’ doża ta ’ buprenorphine mogħtija b’ mod orali: naloxone (proporzjon 1: 1) wera li d- doża kienet letali għall- embriju f’ firien meta seħħet tossiċità fl- omm bid- dożi kollha.
The lowest dose studied represented exposure multiples of 1x for buprenorphine and 5x for naloxone at the maximum human therapeutic dose calculated on a mg/ m² basis.
L - aktar doża baxxa li ġiet studjata kienet tirrapreżenta esponimenti f’ multipli ta ’ 1x għal buprenorphine u 5x għal naloxone bl- ogħla doża umana terapewtika kkalkulata fuq bażi ta ’ mg/ m2.
No developmental toxicity was observed in rabbits at maternally toxic doses.
Ma dehrietx tossiċità ta ’ l- iżvilupp fi fniek b’ dożi li kienu tossiċi għall- omm.
Further, no teratogenicity has been observed in either rats or rabbits.
Minbarra hekk, ma dehrietx teratoġeniċità la fil- firien u l- anqas fil- fniek.
A peri-postnatal study has not been conducted with Suboxone; however, maternal oral administration of buprenorphine at high doses during gestation and lactation resulted in difficult parturition (possible as a result of the sedative effect of buprenorphine), high neonatal mortality and a slight delay in the development of some neurological functions (surface righting reflex and startle response) in neonatal rats.
Ma sarx studju ta ’ waqt u wara t- tqala b’ Suboxone; madankollu, meta l- omm ingħatat buprenorphine b’ mod orali b’ dożi għoljin waqt it- tqala u treddigħ wassal għal tbatija fil- ħlas (jista ’ jkun minħabba l- effett sedattiv ta ’ buprenorphine), numru għoli ta ’ mwiet ta ’ frieħ tat- twelid u dewmien żgħir fl- iżvilupp ta ’ xi funzjonijiet newroloġiċi (rifless surface righting u respons għal ħasda) fil- firien tat- twelid.
11 Dietary administration of Suboxone in the rat at dose levels of 500 ppm or greater produced a reduction in fertility demonstrated by reduced female conception rates.
L- għotja ta ’ Suboxone mad- dieta fil- far b’ livelli tad- doża ta ’ 500 ppm jew aktar ikkawżaw tnaqqis fil - fertilità li dehret bi tnaqqis fin- numru ta ’ konċepiment.
A dietary dose of 100 ppm (estimated exposure approximately 2.4x for buprenorphine at a human dose of 24 mg Suboxone based on AUC, plasma levels of naloxone were below the limit of detection in rats) had no adverse effect on fertility in females.
Doża mad- dieta ta ’ 100 ppm (espożizzjoni 11 stmata madwar 2. 4x għal buprenorphine b’ doża fil- bniedem ta ’ 24 mg Suboxone bbażata fuq l- AUC, il- livelli ta ’ naloxone fil- plażma kienu taħt il- limitu li seta ’ jitkejjel fil- firien) ma kellux effetti avversi fuq il- fertilità fuq il- firien ta ’ sess femminili.
A carcinogenicity study with Suboxone was conducted in rats at doses of 7, 30 and 120 mg/ kg/ day, with estimated exposure multiples of 3 to 75 times, based on a human daily sublingual dose of 16 mg calculated on a mg/ m² basis.
Studju ta ’ kanċeroġeniċità b’ Suboxone sar fil- firien b’ dożi ta ’ 7, 30 u 120 mg/ kg/ jum, b’ esponimenti stmati b’ multipli ta ’ 3 sa 75 darba, ibbażati fuq doża ta ’ kuljum minn taħt l- ilsien fil- bniedem ta ’ 16 mg kkalkulata fuq bażi ta ’ mg/ m2.
Statistically significant increases in the incidence of benign testicular interstitial (Leydig's) cell adenomas were observed in all dosage groups.
Żiediet statistikament sinifikanti fl- inċidenza ta ’ adenomi beninni taċ- ċelluli fl- interstizju (ta ’ Leydig) tat- testikoli dehru fil- gruppi tad- dożi kollha.
Lactose monohydrate, Mannitol, Maize starch, Povidone K 30, Citric acid anhydrous, Sodium citrate, Magnesium stearate, Acesulfame potassium, Natural lemon and lime flavour.
Lactose monohydrate, Mannitol, Maize starch, Povidone K 30, Citric acid anhydrous, Sodium citrate, Magnesium stearate, Acesulfame potassium, Togħma tal- lumi naturali jew lumi qares.
7 tablets in blister packs Nylon/ Aluminum/ PVC.
7 pilloli f’ pakketti bil- folji tan- Nylon/ Aluminium/ PVC
28 tablets in blister packs Nylon/ Aluminum/ PVC.
28 pillola f’ pakketti bil- folji tan- Nylon/ Aluminium/ PVC
Medicines no longer required should not be disposed of via wastewater or the municipal sewage system.
Dawk il- mediċini li ma jkunux għadhom meħtieġa m’ għandhomx jintremew ma ’ l- ilma tad- dranaġġ tad- dar jew mas- sistema tad- dranaġġ muniċipali.
Patients should be instructed to return them to a pharmacy or to ask their pharmacist how to dispose of them in accordance with the national regulations.
Il- pazjenti għandhom jingħataw parir sabiex iġibuhom lura l- ispiżerija jew biex isaqsu lill- ispiżjar tagħhom kif għandhom jeħilsu minnhom skond ir- regolamenti nazzjonali.
These measures will help to protect the environment.
Dawn il- miżuri sejrin jgħinu biex jiġi mħares l- ambjent.
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION 26 September 2006
26 ta ’ Settembru 2006
Detailed information on this product is available on the web-site of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /.
Suboxone 8 mg/ 2 mg sublingual tablets
Suboxone 8 mg/ 2 mg pilloli għal taħt l- ilsien
Each tablet contains 8 mg buprenorphine (as buprenorphine hydrochloride) and 2 mg naloxone (as naloxone hydrochloride dihydrate).
Kull pillola fiha 8 mg buprenorphine (bħala buprenorphine hydrochloride) u 2 mg naloxone (bħala naloxone hydrochloride dihydrate).
Excipients: lactose 168 mg
Sustanza mhux attiva: lactose 168 mg
White hexagonal biconvex tablets, embossed with a sword logo on one side and “ N8” on the reverse side.
Pilloli konvessi miż- żewġ naħat, eżagonali bojod, imnaqqxin b’ logo ta ’ xabla fuq naħa u “ N8 ” fuq in - naħa l- oħra.
Treatment is intended for use in adults and adolescents over 15 years of age who have agreed to be treated for addiction.
It- trattament huwa għall- adulti u adolexxenti a’ eta ’ ’ l fuq minn 15- il sena li jkunu qablu li għandhom jingħataw kura għall- vizzju.
Suboxone containing 8 mg buprenorphine and 2 mg naloxone is referred to as the "8 mg" tablets.
Suboxone li jkun fih 8 mg buprenorphine u 2 mg naloxone jissejħu pilloli tat - “ 8 mg ”.
Prior to treatment induction, consideration should be given to the type of opioid dependence (i. e. long- or short-acting opioid), the time since last opioid use and the degree of opioid dependence.
14 Biex ikun evitat li jiġu preċipitati l- effetti tal waqfien tal- opjojd, induzzjoni b’ pilloli ta ’ Suboxone jew buprenorphine waħidhom għandha ssir meta l- għan u s- sinjali ċari tal- waqfien ikunu evidenti.
After a satisfactory stabilisation has been achieved the frequency of Suboxone dosing may be decreased to dosing every other day at twice the individually titrated daily dose.
Wara li l- pazjent ikun ġie stabbiliżżat b’ mod sodisfaċenti, il- frekwenza tad- dużaġġi ta ’ Suboxone tista ’ titnaqqas għal dużaġġi li jingħataw darba kull jumejn b ’ - doża li tkun darbtejn daqs d- doża ta ’ kuljum li tkun ġiet ikkalkulata bil- mod il- mod għall- individwu.
Paediatrics:
Tfal:
Suboxone is not recommended for use in children below age 15 years due to lack of data on safety and efficacy.
Suboxone mhux irrakkomandat għall- użu fit- tfal ta ’ taħt il- 15- il sena peress li m’ hemmx informazzjoni dwar is- sigurtà u l- effikaċja.
15 Patients with impaired hepatic function:
Pazjenti b’ indeboliment tal- funzjoni epatika:
The effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone is unknown.
15 L- effett ta ’ indeboliment epatiku fuq il- farmakokinetika ta ’ buprenorphine u nalxone mhux magħruf.
Caution is recommended when dosing patients with severe renal impairment (CLcr < 30 ml/ min) (see section 5.2).
Huwa rakkomandata li dożi lill- pazjenti b’ indeboliment renali sever (CLcr < 30 ml/ min) jingħataw b’ kawtela (ara sezzjoni 5. 2).
When initiating treatment with buprenorphine, the physician must be aware of the partial agonist profile of buprenorphine and that it can precipitate withdrawal in opioid-dependent patients particularly if administered less than 6 hours after the last use of heroin or other short acting opioid, or if administered less than 24 hours after the last dose of methadone (see section 4.2).
Meta jinbeda t- trattament b ’ buprenorphine, it- tabib għandu jkun jaf il- profil ta ’ l- agonist parzjali ta ’ buprenophine u li jista ’ jikkawża sintomi ta ’ twaqqif f’ pazjenti li jkunu dipendenti fuq opjojd l- aktar jekk jingħata f’ anqas minn 6 sigħat wara l- aħħar użu ta ’ eroina jew opjojd ieħor li jaħdem fil- qosor, jew jekk jingħata f’ anqas minn 24 siegħa wara l- aħħar doża ta ’ methadone (ara sezzjoni 4. 2).
The risk of serious undesirable effects such as overdose or treatment dropout is greater if a patient is under dosed with Suboxone and continues to self medicate withdrawal symptoms with opioids, alcohol or other sedative-hypnotics in particular benzodiazepines.
Ir- riskju ta ’ effetti mhux mixtieqa serji bħal doża eċċessiva, jew twaqqif tat- trattament huwa akbar jekk pazjent ikun mogħti doża aktar baxxa ta ’ Suboxone u jibqa jieħu l- mediċina waħdu sabiex jikkura s- sintomi tat- twaqqif b’ opjojds, alkoħol jew ipnotiċi- sedattivi oħrajn b’ mod partikolari b’ benżodijażepini partikolari.
16 Suboxone may cause drowsiness, particularly when taken together with alcohol or central nervous system depressants (such as tranquilisers, sedatives or hypnotics) (see section 4.5).
16 Suboxone jista ’ jikkawża n- ngħas, l- aktar jekk jittieħed flimkien ma ’ l- alkoħol jew sustanzi li jikkawżaw depressjoni tas- sistema nervuża ċentrali (bħall- kalmanti, sedattivi jew ipnotiċi) (ara sezzjoni 4. 5).
A number of cases of death due to respiratory depression have been reported, particularly when buprenorphine was used in combination with benzodiazepines (see section 4.5), or when buprenorphine was not used according to prescribing information.
Numru ta ’ każijiet ta ’ mwiet minħabba depressjoni respiratorja kienu rrappurtati, l- aktar meta buprenorphine kien tuża flimkien ma ’ benżodijażepini (ara sezzjoni 4. 5), jew meta buprenorphine ma ntużax skond l- informazzjoni preskritta.
In many cases the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant use of other potentially hepatotoxic medicines, and ongoing injecting drug use may have a causative or contributory role.
F’ ħafna każijiet, il- preżenza ta ’ anormalitajiet fl- enzimi tal- fwied, infezzjonijiet b’ virus ta ’ l- epatite B jew l- epatite Ċ, l- użu fl- istess ħin ta ’ mediċini oħra li jistgħu jikkawżaw ħsara epatika, u - injettar tad- drogi tista ’ tkun fattur li jkun qed jikkawża jew jikkontribwixxi.
Depending upon the findings, the medicinal product may be discontinued cautiously so as to prevent withdrawal symptoms and to prevent a return to illicit drug use.
Skond dawn is- sejbiet, il- prodott mediċinali jista ’ jitwaqqaf b’ attenzjoni sabiex jiġu evitati sintomi tat- twaqqif u jiġi evitat li jerġa ’ jibda jsir - użu illeċitu tad - droga.
This product should be used with care in patients with: asthma or respiratory insufficiency (cases of respiratory depression have been reported with buprenorphine); renal insufficiency (30% of the administered dose is eliminated by the renal route; thus, renal elimination may be prolonged); hepatic insufficiency (hepatic metabolism of buprenorphine may be altered) (see section 4.3).
Dan il- prodott għandu jintuża b’ kawtela f’ pazjenti b ’: ażżma jew insuffiċjenza respiratorja (każijiet ta depressjoni respiratorja kienu rrappurtati b ’ buprenorphine); insuffiċjenza renali (30% tad- doża mogħtija titneħħa permezz tal- kliewi, għalhekk, l- eliminazzjoni renali tista ’ tittawwal); insuffiċjenza epatika (metaboliżmu epatiku ta ’ buprenorphine jista ’ jinbidel) (ara sezzjoni 4. 3).
17 • benzodiazepines:
• benżodijażepini:
• CYP3A4 inhibitors: an interaction study of buprenorphine with ketoconazole (a potent inhibitor of CYP3A4) resulted in increased Cmax and AUC (area under the curve) of buprenorphine (approximately 70% and 50% respectively) and, to a lesser extent, of norbuprenorphine.
• inibituri CYP3A4: studju ta ’ interazzjoni bejn buprenorphine u ketoconazole (inibitur qawwi ta ’ CYP3A4) wassal għal żieda tas- Cmax u AUC (erja taħt il- kurva) ta ’ buprenorphine (madwar 70% u 50% rispettivament) u, b’ mod anqas, ta ’ norbuprenorphine.
Patients receiving Suboxone should be closely monitored, and may require dose-reduction if combined with potent CYP3A4 inhibitors (e. g. protease inhibitors like ritonavir, nelfinavir or indinavir or azole antifungals such as ketoconazole or itraconazole).
Pazjenti li jkunu qed jirċievu Suboxone għandhom ikunu monitorati mill- qrib, u jistgħu jeħtieġu tnaqqis tad- doża jekk jingħataw flimkien ma ’ inibituri qawwija ta ’ CYP3A4 (eż inibituri protease bħal ritonavir, nelfinavir jew indinavir jew mediċini kontra l- moffa azole bħal ketoconazole jew itraconazole).
There is very limited experience with buprenorphine/ naloxone in pregnant women.
Hemm esperjenza limitata ħafna b ’ buprenorphine/ naloxone f’ nisa waqt it- tqala.
Towards the end of pregnancy high doses of buprenorphine may induce respiratory depression in the neonate even after a short period of administration.
Lejn tmiem it- tqala, dożi għoljin ta ’ buprenorphine jistgħu ’ jikkawża depressjoni respiratorja fit- trabi tat- twelid anki jekk ikun ngħata għal perijodu qasir.
In general Suboxone has minor to moderate influence on the ability to move safely in traffic, use machines, or perform other hazardous activities.
Suboxone b’ mod ġenerali jinfluwenza b’ mod minuri għal moderat il- ħila sabiex tiċċaqlaq b’ mod sigur fit- traffiku, tħaddem magni, jew tagħmel attivitajiet perikolużi oħra.
18 The most common-treatment related undesirable effects reported during clinical trials with Suboxone were those related to withdrawal symptoms (e. g. abdominal pain, diarrhoea, muscle aches, anxiety, sweating).
L- aktar effetti mhux mixtieqa komuni, relatati mat- trattament, li kienu rrappurtati waqt il- provi kliniċi b’ Suboxone kienu dawk relatati ma’ s- sintomi tat- twaqqif (eż uġigħ fl- addome, dijarrea, weġgħat fil - muskoli, ansjetà, għaraq).
In the pivotal clinical study of Suboxone, 342 of 472 patients (72.5%) reported treatment related adverse reactions.
Fl- istudju pivitali fuq Suboxone, 342 minn 472 pazjent (72. 5%) irrappurtaw reazzjonijiet avversi relatati mat - trattament.
These reactions are listed in Table 1 by system organ class and frequency (very common (> 1/ 10), common (> 1/ 100 ,< 1/10), uncommon (> 1/ 1,000 to ≤ 1/ 100).
Dawn ir- reazzjonijiet huma elenkati f’ Tabella 1 skond il- klassi tas sistema ta ’ l- organi tas- sistema u l- frekwenza (komuni ħafna (> 1/ 10), komuni (> 1/ 100, < 1/ 10), mhux komuni (> 1/ 1, 000 sa ≤ 1/ 100)).
Vaginitis Blood and lymphatic system disorders
Reazzjoni allerġika
Uncommon:
Disturbi fil- metaboliżmu u n - nutrizzjoni Komuni:
Anaemia, thrombocytopenia, leucopenia, lymphadenopathy, leukocytosis Immune system disorders
Edima periferali, tnaqqis fil- piż.
Allergic reaction Metabolism and nutrition disorders
Ipergliċemija, iperlipemija, ipogliċemija
Hyperglycaemia, hyperlipemia, hypoglycemia Psychiatric disorders
Disturbi psikjatriċi
Anxiety, nervousness, depression, libido decreased, thinking abnormal Uncommon:
Ansjetà, nervi, depressjoni, tnaqis fil- libido, ħsibijiet mhux
Insomnia Common:
Komuni: normali Mhux komuni:
Convulsion, agitation, tremor, hyperkinesia
Dipendenza fuq id- droga, amneżija, mġieba ostili, tixkil fil- kliem, tibdil fil- personalità, ħolm mhux normali, apatija u ewforija Disturbi fis- sistema nervuża Komuni ħafna:
Common:
Nuqqas ta ’ rqad Komuni:
Lacrimation disorder, amblyopia Uncommon:
Ngħas, sturdament, parasteżija, ipertonija Mhux komuni:
Miosis, conjunctivitis Cardiac disorders
Konvulżjonijiet, aġitazzjoni, rogħda, iperkineżja Disturbi fl- għajnejn Komuni:
Uncommon:
Disturbi tad- dmugħ, amblijopja Mhux komuni:
Myocardial infarction, angina pectoris, palpitation, tachycardia, bradycardia
Mijożi, konġunktivite
19 Vascular disorders
19 Disturbi fil- qalb Mhux komuni:
In patients presenting with marked drug dependence, initial administration of buprenorphine can produce a withdrawal effect similar to that associated with naloxone.
20 F’ pazjenti li jkunu dipendenti ħafna fuq id- drogi, l- għotja fil- bidu ta ’ buprenorphine tista ’ tikkawża effett ta ’ twaqqif simili għal dak assoċjat ma ’ naloxone.
Spontaneous abortion has been reported with both buprenorphine and buprenorphine-naloxone.
Abort spontanju kien rappurtat kemm b ’ buprenorphine kif ukoll b ’ buprenorphine- naloxone.
The syndrome may be milder and more protracted than that from short acting full µ-opioid agonists.
Is- sindrome tista ’ tkun eħfef u jdum aktar minn dak ikkawżat mill- agonisti tal - µ- opjojd sħaħ li jaħdmu fil- qosor.
Use of an opioid antagonist (i. e., naloxone) is recommended, despite the modest effect it may have in reversing the respiratory symptoms of buprenorphine compared with its effects on full agonist opioid agents.
Huwa rrikkmandat l- użu ta ’ antagonist ta ’ l- opjojd (i. e. naloxone), minkejja l- effett modest li jista ’ jkollu biex ireġġa ’ lura s- sintomi ta ’ buprenorphine meta mqabbel ma l- effetti tiegħu fuq sustanzi opjojd agonisti kompleti.
However, when administered intravenously to opioid dependent persons, the presence of naloxone in Suboxone produces marked opioid antagonist effects and opioid withdrawal, thereby deterring intravenous abuse.
Madankollu meta jingħata minn ġol- vina lill- persuni dipendenti fuq opjojds, il- preżenza ta ’ naloxone f’ Suboxone jikkawża effetti qawwija ta ’ antagonisti ta ’ l- opjojd u twaqqif ta ’ l- opjojds, b’ hekk jiskuraġġixxi l- abbuż minn ġol - vina.
21 Clinical efficacy:
21 Effikaċja klinika:
Efficacy and safety data for Suboxone are primarily derived from a one-year clinical trial, comprising a 4-week randomised double blind comparison of Suboxone, buprenorphine and placebo tablets followed by a 48 week safety study of Suboxone.
Tagħrif dwar l- effikaċja u s- sigurtà ta ’ Suboxone jiġu fil- parti l- kbira minn prova klinika ta ’ sena, li tinkludi studju randomised double blind ta ’ 4 ġimgħat ta ’ tqabbil ta ’ Suboxone, buprenorphine u pilloli plaċebo segwiti bi studju ta ’ 48 ġimgħa dwar is- sigurtà ta ’ Suboxone.
In this trial, 326 heroin-addicted subjects were randomly assigned to either Suboxone 16 mg per day, 16 mg buprenorphine per day or placebo tablets.
F’ din il- prova, 326 individwu bil- vizzju tal- eroina, kienu magħżula b’ mod arbitrarju biex jingħataw Suboxone 16 mg kuljum, 16 mg buprenorphine kuljum jew pilloli plaċebo.
For subjects randomized to either active treatment, dosing began with one 8 mg tablet of buprenorphine on Day 1, followed by 16 mg (two 8 mg tablets) of buprenorphine on Day 2.
Għall- pazjenti li ntgħażlu b’ mod arbitrarju għal wieħed mit - trattamenti attivi, id- dużaġġ beda bi pillola ta ’ 8 mg buprenorphine f’ Jum 1, segwit b’ 16 mg (żewġ pilloli ta ’ 8 mg) ta ’ buprenorphine f’ Jum 2.
Subjects were seen daily in the clinic (Monday through Friday) for dosing and efficacy assessments.
L- individwi kienu nviżtati kuljum fil- klinika (mit Tnejn sal- Ġimgħa) għall- evalwar tad- dużaġġi u l- effikaċja.
The percentage of thrice-weekly urine samples that were negative for non-study opioids was statistically higher for both Suboxone versus placebo (p < 0.0001) and buprenorphine versus placebo (p < 0.0001).
Il- perċentwal tal- kampjuni li ttieħdu tlett darbiet fil - ġimgħa li kienu negattivi għall- opjojds mhux ta ’ l- istudju kien statistikament ogħla kemm għal Suboxone kontra l- plaċebo (p < 0. 0001) u buprenorphine kontra l- plaċebo (p < 0. 0001).
In a double-blind, double-dummy, parallel-group study comparing buprenorphine ethanolic solution to a full agonist active control, 162 subjects were randomized to receive the ethanolic sublingual solution of buprenorphine at 8 mg/ day (a dose which is roughly comparable to a dose of 12 mg/ day of Suboxone), or two relatively low doses of active control, one of which was low enough to serve as an alternative to placebo, during a 3 to10 day induction phase, a 16-week maintenance phase and a 7- week detoxification phase.
Fi studju double- blind, double dummy, bi grupp parallel li qabbel is- soluzzjoni etanolika ta ’ buprenorphine ma ’ kontroll agonist attiv sħieħ, 162 individwu kienu ntgħażlu b’ mod arbitrarju biex jirċievu soluzzjoni etanolika taħt l- ilsien ta ’ buprenorphine 8 mg/ jum (doża li hija komparabbli bejn wieħed u ieħor ma ’ doża ta ’ 12 mg/ jum ta ’ Suboxone), jew żewġ dożi relattivament baxxi tal- kontroll attiv, li wieħed minnhom kien baxx biżżejjed li seta ’ jservi bħala alternattiv għall- plaċebo, waqt fażi ta ’ induzzjoni ta ’ 3 sa 10 ijiem, fażi ta ’ manteniment ta ’ 16- il ġimgħa u fażi ta ’ diżintossikazzjoni ta ’ 7- ġimgħat.
Buprenorphine was titrated to maintenance dose by Day 3; active control doses were titrated more gradually.
Buprenorphine kien misżjud bil- mod għad- doża ta ’ manteniment ma ’ Jum 3; dożi tal - kontroll attiv kienu miżjuda aktar bil- mod.
Based on retention in treatment and the percentage of thrice- weekly urine samples negative for non-study opioids, buprenorphine was more effective than the low dose of the control, in keeping heroin addicts in treatment and in reducing their use of opioids while in treatment.
Skond ir- retenzjoni fit- trattament u l- perċentwali ta ’ kampjuni ta ’ l- awrina li ttieħdu tlett darbiet fil- ġimgħa li ġew negattivi għall - opjojdi mhux ta ’ l - istudju, buprenorphine kien aktar effettiv mid- doża baxxa tal- kontroll, sabiex iżomm persuni bil- vizzju ta ’ l- eroina fit- trattament u biex inaqqsilhom l- użu ta ’ opjojdi waqt it- trattament.
Buprenorphine, when taken orally, undergoes first-pass metabolism with N-dealkylation and glucuroconjugation in the small intestine and the liver.
Buprenorphine, meta jittieħed b’ mod orali, jgħaddi minn metaboliżmu first pass b ’ N - dealkalizazzjoni u glukurkonjugazzjoni fil- musrana ż- żgħira u l- fwied.
22 dealkylation of buprenorphine.
22 Metaboliżmu u eliminazzjoni:
Elimination of buprenorphine is bi- or tri-exponential, and has a mean half-life from plasma of 32 hours.
L- eliminazzjoni ta ’ buprenorphine hija bi - jew tri- esponenzjali, u għandha ta ’ half- life medja mill - plażma ta ’ 32 siegħa.
Following oral administration, naloxone is barely detectable in plasma; following sublingual administration of Suboxone, plasma naloxone concentrations are low and decline rapidly.
Wara l - għotja b’ mod orali, naloxone bil- kemm jiġi mkejjel fil- plażma: wara l- għotja ta ’ Suboxone minn taħt l- ilsien, il- konċentrazzjonijiet ta ’ naloxone fil- plażma jkunu baxxi u jaqaw malajr.
The medicinal product is metabolized in the liver, primarily by glucuronide conjugation, and excreted in the urine.
Il- prodott mediċinali jiġi metabolizzat fil- fwied, l- aktar b’ konjugazzjoni glukuronajd, u eskretat fl - awrina.
The combination of buprenorphine and naloxone has been investigated in acute and repeated dose (up to 90 days in rats) toxicity studies in animals.
It- taħlita ta ’ buprenorphine ma ’ naloxone kienet investigata fi studji dwar it- tossiċità f’ annimali b’ dożi akuti u ripetuti (sa 90 jum fi firien).
The combination (4:1) of buprenorphine hydrochloride and naloxone hydrochloride was not mutagenic in a bacterial mutation assay (Ames test), and was not clastogenic in an in vitro cytogenetic assay in human lymphocytes or in an intravenous micronucleus test in the rat.
It- taħlita (4: 1) ta ’ buprenorphine hydrochloride u naloxone hydrochloride ma kienetx mutaġenika f’ essej ta ’ mutazzjoni batterika (Ames test), u ma kienetx klastoġenika f’ essej in vitro ċitoġeniku f’ limfoċiti umani jew f’ test mikronuklejus minn ġol- vina f ’ - il- far.
The lowest dose studied represented exposure multiples of 1x for buprenorphine and 5x for naloxone at the maximum human therapeutic dose calculated on a mg/ m² basis.
L - aktar doża baxxa li ġiet studjata kienet tirrapreżenta esponimenti f’ multipli ta ’ 1x għal buprenorphine u 5x għal naloxone bl- ogħla doża umana terapewtika kkalkulata fuq bażi ta’ mg/ m2.
A peri-postnatal study has not been conducted with Suboxone; however, maternal oral administration of buprenorphine at high doses during gestation and lactation resulted in difficult parturition (possible as a result of the sedative effect of buprenorphine), high neonatal mortality and a slight delay in the development of some neurological functions (surface righting reflex and startle response) in neonatal rats.
Ma sarx studju ta ’ waqt u wara t- tqala b’ Suboxone; madankollu, meta l- omm ingħatat buprenorphine b’ mod orali b’ dożi għoljin waqt it- tqala u treddigħ wassal għal tbatija fil- ħlas (jista ’ jkun minħabba l- effett sedattiv ta ’ buprenorphine), numru għoli ta ’ 23 mwiet ta ’ frieħ tat- twelid u dewmien żgħir fl- iżvilupp ta ’ xi funzjonijiet newroloġiċi (rifless surface righting u respons għal- ħasda) fil- firien tat- twelid.
23 Dietary administration of Suboxone in the rat at dose levels of 500 ppm or greater produced a reduction in fertility demonstrated by reduced female conception rates.
L- għotja ta ’ Suboxone mad- dieta fil- far b’ livelli tad- doża ta ’ 500 ppm jew aktar ikkawżaw tnaqqis fil - fertilità li dehret bi tnaqqis fin- numru ta ’ konċepiment.
A dietary dose of 100 ppm (estimated exposure approximately 2.4x for buprenorphine at a human dose of 24 mg Suboxone based on AUC, plasma levels of naloxone were below the limit of detection in rats) had no adverse effect on fertility in females.
Doża mad- dieta ta ’ 100 ppm (espożizzjonistmata madwar 2. 4x għal buprenorphine b’ doża fil- bniedem ta ’ 24 mg Suboxone bbażata fuq l- AUC, il- livelli ta ’ naloxone fil- plażma kienu taħt il- limitu li seta ’ jitkejjel fil- firien) ma kellux effetti avversi fuq il- fertilità fuq il- firien ta ’ sess femminili.