natgillin/translations-raw huggingface dataset:
The implants should be positioned in a fan-shaped distribution at least 5 mm from the incision, and palpable after placement. 
Implantate treba rasporediti u obliku lepeze najmanje 5 mm od incizije i implantati moraju biti opipljivi nakon ugradnje.
Improper removal carries risk of implant-site infection and implant breakage. 
Nepravilno uklanjanje nosi rizik od infekcije na mjestu implantata i pucanja implantata.
The primary endpoint was proportion of responders, defined as patients with no more than 2 of 6 months with evidence of illicit opioid use based on a composite of both urine and self-report results. 
Primarna mjera ishoda bila je udio ispitanika s odgovorom definiranim kao uporaba nedopuštenih opioida tijekom najviše 2 od 6 mjeseci dokazana na temelju kompozitne mjere sastavljene od rezultata analize mokraće i upitnika za samoprocjenu.
Hepatitis and hepatic events 
Hepatitis i događaji povezani s jetrom
At steady state, a small decrease in buprenorphine concentrations was also recorded between week 4 and week 24. 
U stanju dinamičke ravnoteže bilo je zabilježeno i malo smanjenje koncentracija buprenorfina između 4. i 24. tjedna.
• If it is not possible to palpate the remaining implant, an ultrasound or MRI should be performed per techniques described in section 4.2 under “Instructions for removal of Sixmo”. 
• Ako nije moguće napipati preostali dio implantata, treba napraviti pregled ultrazvukom ili MRom prema tehnikama opisanima u dijelu 4.2 pod “ Upute za uklanjanje implantata Sixmo”.
Buprenorphine is an opioid partial agonist/antagonist which binds to the μ (mu) and κ (kappa) 
Buprenorfin je parcijalni opioidni agonist/antagonist koji se veže za μ (mu) i κ (kappa) receptore u mozgu.
Generally, concentrations were comparable to the trough buprenorphine concentration of 8 mg per day sublingual buprenorphine. 
koncentracije su bile usporedive s najnižim koncentracijama buprenorfina kod doze od 8 mg na dan sublingvalnog buprenorfina.
Please note: Buprenorphine can cause severe, possibly fatal, breathing depression (shortness of breath or stops breathing) in children who are accidentally exposed to it. 
Napomena: buprenorfin može uzrokovati tešku depresiju disanja s mogućim smrtnim ishodom (nedostatkom daha ili prestankom disanja) u djece koja mu nehotice budu izložena.
They are removed by the end of the sixth month. 
Uklanjanju se na kraju tog šestomjesečnog razdoblja.
• instrument stand covered with sterile drape 
• kolica za instrumente pokrivena sterilnom prekrivkom
Sixmo is formulated as a diversion and abuse deterrent formulation. 
Sixmo ima formulaciju koja sprječava nedopuštenu uporabu i zlouporabu.
Using the surgical marker, mark the location of the implants and the location of the incision. 
Kirurškim markerom označite mjesto na kojem se nalaze implantati i mjesto incizije.
• consistency in participation in recommended behavioural therapy/peer support programme 
• dosljedno sudjelovanje u preporučenoj bihevioralnoj terapiji / grupi za samopomoć i uzajamnu podršku
In clinical studies and from post-marketing data 7 cases of clinically relevant implant breakage (breakage associated with an adverse reaction) were observed. 
U kliničkim ispitivanjima i prema podacima nakon stavljanja lijeka u promet opaženo je 7 slučajeva klinički važnog lomljenja implantata (pucanje povezano s nuspojavom).
Step 8: While holding the obturator in place on the arm, retract the cannula along the obturator, leaving the implant in place (Figure 11). 
Korak 8: Dok držite opturator na istom mjestu na ruci, povucite kanilu unatrag duž opturatora, ostavljajući implantat na mjestu (slika 11).
In a subset of patients, Sixmo implants broke during implant removal. 
U podskupini bolesnika došlo je do lomljenja implantata Sixmo tijekom njihova uklanjanja.
Study PRO-806 
Ispitivanje PRO-806
CYP3A4 inhibitors may inhibit the metabolism of buprenorphine resulting in increased Cmax and AUC of buprenorphine and norbuprenorphine. 
Inhibitori CYP3A4 mogu inhibirati metabolizam buprenorfina, što dovodi do povišenja vrijednosti Cmax i AUC-a buprenorfina i norbuprenorfina.
The healthcare professional should review the patient's treatment history for concomitant use of CYP3A4 inhibitors prior to initiating Sixmo treatment to determine suitability (see section 4.5). 
Liječnik treba u povijesti liječenja bolesnika provjeriti je li bolesnik već istodobno primao inhibitore CYP3A4 prije početka liječenja implantatima Sixmo, kako bi odredio prikladnost tog liječenja (vidjeti dio 4.5).
Each dose consists of four implants, for subcutaneous insertion in the inner side of the upper arm. 
Jedna doza sastoji se od četiri implantata koji se ugrađuju supkutano s unutarnje strane nadlaktice.
The physician educational programme, provided in conjunction with the Summary of Product Characteristics (SmPC), should include lecture slides and a detailed, face to face, step-by step description and live demonstration of the surgical procedure for SIXMO insertion and removal. 
Edukacijski program za liječnike, koji se osigurava zajedno sa sažetkom opisa svojstava lijeka, mora uključiti prezentaciju s predavanja (slajdove), detaljni opis svakog koraka licem u lice i uživo demonstraciju kirurškog zahvata ugradnje i uklanjanja implantata SIXMO.
• period free from opioid drug abuse 
• razdoblje bez zlouporabe opioida
If pregnancy occurs during treatment with Sixmo the benefit to the patient should be weighed against the risk to the foetus. 
Sixmo nastupi trudnoća, potrebno je procijeniti korist za bolesnicu u odnosu na rizik za fetus.
General precautions relevant to the administration of opioids 
Opće mjere opreza važne kod primjene opioida
• reactions at the implant site infection, including wound infection rash, scaring reduced healing swollen area containing pus 
• reakcije na mjestu implantata infekcija, uključujući infekciju rane osip, ožiljak usporeno cijeljenje otečeno područje s gnojnim sadržajem
Sixmo is contraindicated in patients with a history of keloid or hypertrophic scar formation at the site where Sixmo would be implanted, as difficulties in retrieving the implant are possible (see section 
Sixmo je kontraindiciran u bolesnika s anamnezom stvaranja keloida ili hipertrofičnih ožiljaka na mjestu gdje bi se ugradio Sixmo jer su moguće poteškoće s uklanjanjem implantata (vidjeti dio 4.3).
If another set of implants is not inserted on the same day as the previous set is removed: A dose of between 2 and 8 mg buprenorphine daily, given under the tongue, is recommended until repeat treatment occurs. 
Ako se drugi komplet implantata ne ugradi istog dana kad se uklonio prethodni komplet: Preporučuje se primijeniti dozu između 2 i 8 mg buprenorfina dnevno, pod jezik, do ponovnog liječenja implantatima.
In many cases the presence of pre-existing hepatic impairment (genetic disease, liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, alcohol abuse, anorexia, concomitant use of other potentially hepatotoxic medicines) and ongoing injecting drug use may have a causative or contributory role. 
U mnogim su slučajevima to mogli uzrokovati ili tome pridonijeti već postojeće oštećenje jetre (genetska bolest, abnormalnosti jetrenih enzima, infekcija virusom hepatitisa B ili hepatitisa C, alkoholizam, anoreksija, istodobna primjena drugih potencijalno hepatotoksičnih lijekova) i aktualna intravenska uporaba droga.
It is recommended that the healthcare professional is in a seated position during the entire insertion procedure so that the insertion site and the movement of the needle just under the skin can be clearly seen from the side. 
Liječniku se preporučuje da sjedi tijekom cijelog postupka ugradnje, tako da sa strane može jasno vidjeti mjesto ugradnje i pomicanje igle neposredno ispod kože.
Do not use Sixmo if you: 
Nemojte primjenjivati Sixmo:
After one subcutaneous insertion in each arm (for a total of two treatments cycles), most patients should be transitioned back to their previous sublingual buprenorphine dose (i.e. the dose from which they were transferred to Sixmo treatment) for continued treatment. 
Nakon što su implantati bili supkutano ugrađeni u svaku ruku (za ukupno dva ciklusa liječenja), većinu bolesnika treba prebaciti na prethodnu dozu sublingvalnog buprenorfina (tj. dozu s koje su prebačeni na liječenje implantatima Sixmo) zbog nastavka liječenja.
Although some patients may require occasional supplemental dosing with buprenorphine, patients should not be provided with prescriptions for sublingual buprenorphine-containing products for asneeded use. 
Iako nekim bolesnicima može povremeno trebati dodatna doza buprenorfina, ne smije im se dati recept za lijek koji sadrži sublingvalni buprenorfin da ga uzmu po potrebi.
4.5 Interaction with other medicinal products and other forms of interaction Buprenorphine should not be administered together with: 
4.5 Interakcije s drugim lijekovima i drugi oblici interakcija
Properly placed implants are those placed just under the skin, using the implant applicator, about 80 to 100 mm (8 to 10 cm) above the medial epicondyle, in the sulcus between the biceps and triceps muscle of the inner side of the upper arm. 
Ispravno ugrađeni implantati su oni postavljeni pomoću aplikatora implantata neposredno ispod kože, oko 80 do 100 mg (8-10 cm) iznad medijalnog epikondila, u sulkusu između bicepsa i tricepsa na unutarnjoj strani nadlaktice.
• reduced sense of touch or sensation 
• smanjen osjet dodira ili osjetljivost na podražaj
Patients previously treated with sublingual buprenorphine or sublingual buprenorphine + naloxone, must be on stable doses between 2 to 8 mg/day for at least 30 days and deemed clinically stable by the treating healthcare professional. 
Bolesnici prethodno liječeni sublingvalnim buprenorfinom ili sublingvalnim buprenorfinom u kombinaciji s naloksonom moraju biti na stabilnoj dozi između 2 mg i 8 mg na dan tijekom najmanje 30 dana i, prema procjeni nadležnog liječnika, klinički stabilni.
Sixmo is a white/off-white to pale yellow rod-shaped implant, 26.5 mm long and 2.4 mm in diameter. 
Sixmo je bijeli/gotovo bijeli do blijedožuti implantat u obliku štapića, duljine 26,5 mm i promjera 2,4 mm.
Mark the insertion site with the surgical marker. 
Označite mjesto ugradnje kirurškim markerom.
• Implant insertion and six-month removal date(s) 
• datum(e) ugradnje i uklanjanja implantata nakon šest mjeseci
• sleep disorder, disinterest 
• poremećaj spavanja, ravnodušnost
Sixmo is indicated for substitution treatment for opioid dependence in clinically stable adult patients who require no more than 8 mg/day of sublingual buprenorphine, within a framework of medical, social and psychological treatment. 
Sixmo je indiciran kao nadomjesna terapija u liječenju ovisnosti o opioidima u klinički stabilnih odraslih bolesnika kojima, u sklopu medicinskog, socijalnog i psihološkog liječenja, nije potrebno više od 8 mg na dan sublingvalno primjenjenog buprenorfina.
Adverse reactions (implant and non-implant) reported are listed in the following table. 
Zabilježene nuspojave (implantata i djelatne tvari) navedene su u tablici u nastavku.
Two additional randomised, double-blind, placebo-controlled Phase 3 studies provide supportive data on efficacy and PK (Studies PRO-805 and PRO-806). 
Dva dodatna randomizirana, dvostruko slijepa, placebom kontrolirana ispitivanja faze 3 pružila su podatke koji potkrijepljuju djelotvornost i farmakokinetiku (ispitivanja PRO-805 i PRO-806).
Apply the sterile drape to the patient's arm. Anaesthetise the incision site and the subcutaneous space containing the implants (for example, by injecting 5 to 7 mL lidocaine 1% with adrenaline 1:100,000). 
Anestezirajte mjesto incizije i potkožno tkivo u kojem se nalaze implantati (na primjer, ubrizgavanjem 5-7 ml 1%-tnog lidokaina s adrenalinom 1:100 000).
Patients with mild to moderate hepatic impairment (Child-Pugh A and B) should be monitored for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine (miosis, lip cyanosis, sedation, bradycardia, hypotension, respiratory depression). 
Bolesnike s blagim do umjerenim oštećenjem jetrene funkcije (Child-Pugh A i B) treba pratiti zbog moguće pojave znakova i simptoma toksičnosti ili predoziranja uzrokovanih povišenim razinama buprenorfina (mioza, cijanoza usana, sedacija, bradikardija, hipotenzija, respiratorna depresija).
Patients with mild to moderate hepatic impairment should be monitored for signs and symptoms of toxicity, or overdose caused by increased levels of buprenorphine (see section 4.2). 
Bolesnike s blagim do umjerenim oštećenjem jetrene funkcije treba pratiti zbog mogućih znakova i simptoma toksičnosti ili predoziranja uzrokovanih povišenim razinama buprenorfina (vidjeti dio 4.2).
In study PRO-805, the primary endpoint was the CDF of the percentage of urine samples that were negative for illicit opioids over weeks 1 to 16, while the CDF over weeks 17 to 24 was evaluated as secondary endpoint. 
U ispitivanju PRO-805, primarna mjera ishoda bio je KFD postotka uzoraka mokraće koji su bili negativni na nedopuštene droge tijekom razdoblja od 1. do 16. tjedna, dok se KFD od 17. do 24. tjedna ocjenjivao kao sekundarna mjera ishoda.
Opioids should be used with caution in patients with myxoedema, hypothyroidism or adrenal cortical insufficiency (e.g. Addison's disease). 
Opioide treba primjenjivati s oprezom u bolesnika s miksedemom, hipotireozom ili insuficijencijom kore nadbubrežne žlijezde (npr. Addisonovom bolešću).
Injury, poisoning and procedural complications common procedural pain*, procedural site reaction* uncommon post procedural complication (*), contusion (*), wound dehiscence*, migration of implanted drug***, device breakage*** 
Ozljede, trovanja i proceduralne komplikacije često bol uzrokovana postupkom*, reakcija na mjestu postupka* manje često postproceduralna komplikacija (*), kontuzija (*), dehiscencija rane *, migracija implantiranog lijeka***, lomljenje implantata***
Preparations for handling or administering the medicinal product 
Pripreme za rukovanje ili primjenu lijeka
White/Off-white to pale yellow, rod-shaped implant, 26.5 mm long and 2.4 mm in diameter. 
Bijeli/gotovo bijeli do blijedožuti implantat u obliku štapića, duljine 26,5 mm i promjera 2,4 mm.
• naltrexone, nalmefene, used to treat addiction They can block the effects of buprenorphine. 
• naltrekson, nalmefen, koji se primjenjuju za liječenje ovisnosti Mogu blokirati učinke buprenorfina.
Only a healthcare professional who is trained in the insertion of Sixmo should perform the procedure, using only the implant applicator, with the recommended local anaesthetic available. 
Ovaj postupak smije provoditi samo liječnik obučen za ugradnju implantata Sixmo, koristeći samo aplikator implantata, uz dostupan preporučeni lokalni anestetik.
Grasp the centre of the implant with the X-plant clamp(s) (Figure 17) and apply gentle traction. 
Hvataljkom (hvataljkama) X-plant uhvatite implantat po sredini (slika 17) i nježno ga povucite.
Opioids should be used with caution in patients with hypotension, prostatic hypertrophy or urethral stenosis. 
Opioide treba primjenjivati s oprezom u bolesnika s hipotenzijom, hipertrofijom prostate ili stenozom uretre.
If Sixmo implants are not immediately replaced upon removal, patients should be maintained on sublingual buprenorphine (2 to 8 mg/day), as clinically indicated, until Sixmo treatment is resumed. 
Ako se implantati Sixmo ne zamijene odmah nakon uklanjanja, bolesnike treba održavati na sublingvalnom buprenorfinu (2-8 mg na dan), kako je klinički indicirano, sve do nastavka liječenja implantatima Sixmo.
Metabolism and nutrition disorders common decreased appetite uncommon abnormal weight gain, dehydration, increased appetite 
Poremećaji metabolizma i prehrane često smanjeni apetit manje često abnormalno povećanje tjelesne težine, dehidracija, pojačan apetit
The implants will then be inserted under the skin in the inner side of the upper arm. 
Zatim će ugraditi implantate pod kožu s unutarnje stranje nadlaktice.
Follow steps 6 through 9 for the insertion of the three remaining implants through the same incision. 
Za ugradnju preostala tri implantata kroz istu inciziju slijedite korake 6 do 9.
Sixmo was shown to be noninferior to sublingual buprenorphine, the proportion of responders being 87.6% in the sublingual buprenorphine and 96.4% in the Sixmo group. 
Da je Sixmo neinferioran sublingvalnom buprenorfinu pokazao je udio bolesnika s odgovorom od 87,6% u skupini koja je primala sublingvalni buprenorfin i 96,4% u skupini koja je imala Sixmo,.
Instruct the patient that the pressure bandage can be removed after 24 hours and the adhesive bandage removed in three to five days, and to apply an ice pack on the arm for 40 minutes every two hours for the first 24 hours, then as needed. 
Bolesniku dajte uputu da ukloni kompresijski zavoj nakon 24 sata, a flaster nakon tri do pet dana te da tijekom prva 24 sata stavlja hladni oblog na ruku svaka dva sata i drži ga 40 minuta, a poslije po potrebi.
If implant(s) or implant fragment(s) are not removed during a removal attempt, the patient should undergo imaging for localisation as soon as is feasible with the subsequent removal attempt performed on the same day as localisation. 
Ako se implantat(i) ili dio (dijelovi) implantata ne uklone tijekom postupka uklanjanja, u bolesnika treba čim prije slikovnim tehnikama utvrditi mjesto na kojem se nalazi, s time da sljedeći postupak uklanjanja treba provesti istog dana kada i utvrđivanje mjesta implantata.
Retention in treatment was high in the Sixmo groups, with 65.7% and 64.0% of patients completing studies PRO-805 and PRO-806, respectively. 
Ostanak u liječenju bio je visok u skupinama koje su dobile Sixmo i ispitivanje je dovršilo 65,7% bolesnika u ispitivanju PRO-805 i njih 64,0% u ispitivanju PRO-806.
The treating physician should consider implant removal if: 
Kriteriji za prekid liječenja Nadležni liječnik treba razmotriti uklanjanje implantata:
Patients in all groups were allowed to use supplemental sublingual buprenorphine to control potential withdrawal symptoms/cravings according to pre-specified criteria. 
Bolesnici u svim skupinama smjeli su uzimati dodatni sublingvalni buprenorfin prema prethodno utvrđenim kriterijima radi kontrole mogućih simptoma ustezanja/žudnje za drogom.
• sleeplessness, anxiety, hostility, nervousness 
• nesanica, tjeskoba, neprijateljsko ponašanje, nervoza
The Sixmo PK was assessed in opioid-dependent patients treated with Sixmo in studies TTP-400-0201, PRO-810, PRO-805, PRO-806, PRO-807 and PRO-811. 
Sixmo procijenjena je u bolesnika s ovisnošću o opioidima liječenih implantatima Sixmo u ispitivanjima TTP-400-02-01, PRO-810, PRO-805, PRO-806, PRO-807 i PRO-811.
• sutures, such as 4-0 Prolene™ with an FS-2 cutting needle (may be absorbable) 
• kirurški konac, kao što je 4-0 Prolene™ s kirurškom iglom FS-2 (može biti resorptivni)
A number of cases of death due to respiratory depression have been reported while on buprenorphine, particularly when buprenorphine was used in combination with benzodiazepines (see section 4.5) or when buprenorphine was not used according to prescribing information. 
Respiratorna depresija i depresija središnjeg živčanog sustava (SŽS) Zabilježen je određeni broj smrtnih slučajeva zbog respiratorne depresije u bolesnika dok su primali buprenorfin, osobito kad se buprenorfin primjenjivao u kombinaciji s benzodiazepinima (vidjeti dio 4.5) ili kada se buprenorfin nije primjenjivao u skladu s informacijama za propisivanje.
• pain, such as abdominal pain, bone pain, muscle pain, chest pain, headache 
• bol, kao što je bol u trbuhu, bol u kostima, bol u mišićima, bol u prsnom košu, glavobolja
• iris scissors 
• iris škarice
Buprenorphine is a partial agonist at the µ (mu)-opioid receptor and chronic administration produces dependence of the opioid type. 
Ovisnost Buprenorfin je parcijalni agonist µ-opioidnih receptora pa njegova kronična primjena stvara opioidni tip ovisnosti.
Patients treated with CYP inhibitors (e.g. ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, verapamil, diltiazem, amiodarone, amprenavir, fosamprenavir, aprepitant, fluconazole, erythromycin and grapefruit juice) should be monitored for signs and symptoms of toxicity or overdose (miosis, lip cyanosis, sedation, bradycardia, hypotension, respiratory depression). 
Bolesnike liječene inhibitorima CYP-a (kao što su ritonavir, ketokonazol, itrakonazol, troleandomicin, klaritromicin, nelfinavir, nefazodon, verapamil, diltiazem, amiodaron, amprenavir, fosamprenavir, aprepitant, flukonazol, eritromicin i sok od grejpfruta) treba pratiti zbog mogućih znakova i simptoma toksičnosti ili predoziranja (mioza, cijanoza usana, sedacija,
Caution is recommended when dosing patients with severe renal impairment (creatinine clearance < 30 mL/min) (see sections 4.2 and 5.2). 
Preporučuje se oprez kod primjene u bolesnika s teškim oštećenjem bubrežne funkcije (klirens kreatinina < 30 ml/min) (vidjeti dijelove 4.2 i 5.2).
In Studies PRO-805 and PRO-806, 62.0% and 39.5% of Sixmo-treated subjects required supplemental SL buprenorphine. 
U ispitivanjima PRO-805 i PRO-806, 62,0% odnosno 39,5% ispitanika liječenih implantatima
• have severe breathing problems 
• ako imate teške probleme s disanjem
Step 7: While holding the cannula in place, unlock the obturator and remove the obturator. 
Korak 7: Dok držite kanilu na mjestu postavljanja, oslobodite i izvucite opturator.
Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of buprenorphine. 
Inhibitori CYP3A Lijekovi koji inhibiraju enzim CYP3A4 mogu dovesti do povišenja koncentracija buprenorfina.
Skin and subcutaneous tissue disorders common hyperhidrosis uncommon cold sweat, dry skin, rash, skin lesion, ecchymosis* 
Poremećaji kože i potkožnog tkiva često hiperhidroza manje često hladan znoj, suha koža, osip, kožna lezija, ekhimoza*
Subcutaneous use 
sublingvalni buprenorfin
Instruct the patient that the pressure bandage can be removed after 24 hours and the adhesive bandage in three to five days. 
Bolesniku dajte uputu da ukloni kompresijski zavoj nakon 24 sata, a flaster nakon tri do pet dana.
While applying counter-traction to the skin, at a slight angle (no greater than 20 degrees), insert only the tip of the applicator into the subcutaneous space (depth of 3 to 4 mm below the skin), with the bevel-up stop marking on the cannula facing upwards and visible with the obturator locked fully into the cannula (Figure 5). 
Povlačeći kožu na suprotnu stranu, uvedite vršak aplikatora pod malim kutom (ne većim od 20 stupnjeva) u potkožni prostor (dubine 3-4 mm ispod kože), tako da urezana oznaka za zaustavljanje na držaču kanile gleda prema gore i da je vidljivo kako je opturator potpuno pričvršćen u kanili (slika 5).
• have severly reduced liver function 
• ako imate jako smanjenu funkciju jetre
Sixmo implants are intended to be in place for 6 months of treatment and provide a sustained delivery of buprenorphine. 
Implantati Sixmo predviđeni su da ostanu na mjestu ugradnje tijekom 6 mjeseci liječenja i osiguravaju kontinuirano otpuštanje buprenorfina.
A key secondary endpoint in Study PRO-806 was the difference in proportions of urine samples that were negative for opioids over 24 weeks for Sixmo versus sublingual buprenorphine. 
Ključna sekundarna mjera ishoda u ispitivanju PRO-806 bila je razlika u udjelu uzoraka mokraće koji su bili negativni na opioide tijekom 24 tjedna u skupini koja je imala ugrađen Sixmo naspram one koja je primala sublingvalni buprenorfin.
• enlarged prostate or narrowed urethra 
• povećanu prostatu ili suženu mokraćnu cijev
• mild or moderate liver problems 
• blage ili umjerene probleme s jetrom
Figure 1: Cumulative Distribution Function of the Percentage of Urine Samples Negative for Opioids in Weeks 1-16, Study PRO-805 (ITT) 
Slika 1: Kumulativna funkcija distribucije postotka uzoraka mokraće negativnih na opioide u razdoblju od 1. do 16. tjedna, ispitivanje PRO-805 (ITT)
Caution is recommended when dosing patients with severe renal impairment (creatinine clearance < 30 mL/min) (see sections 4.4 and 5.2). 
Preporučuje se oprez kod primjene u bolesnika s teškim oštećenjem bubrežne funkcije (klirens kreatinina < 30 ml/min) (vidjeti dijelove 4.4 i 5.2).