FrancophonIA/ELRC3.0 huggingface dataset:
English: A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from mexiletine therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Slovenian: Odločiti se je treba med prenehanjem dojenja in prenehanjem/prekinitvijo zdravljenja z meksiletinom, pri čemer je treba pretehtati prednosti dojenja za otroka in prednosti zdravljenja za mater.
English: Check of heart function
Slovenian: Preverjanje delovanja srca
English: Based on the pharmacokinetic properties of mexiletine, no dosage adjustment is required in patients aged 65 years and over.
Slovenian: Na podlagi farmakokinetičnih lastnosti meksiletina prilagoditev odmerka pri bolnikih nad 65 let ni potrebna.
English: Caffeine
Slovenian: Kofein
English: • Guidance to identify (and exclude) patients at a greater risk of developing arrhythmias due to Namuscla treatment;
Slovenian: • Smernice za identifikacijo (in izključevanje) bolnikov z večjim tveganjem za pojav aritmij zaradi zdravljenja z zdravilom Namuscla;
English: The capsules should be swallowed with water, avoiding the supine position.
Slovenian: Kapsule je treba pogoltniti z vodo, česar po možnosti ne storimo v ležečem položaju.
English: Mexiletine blocks sodium channels with a stronger potency in situations of excessive burst of action potentials (use-dependent block) and/or prolonged depolarization (voltage-dependent block), as occurring in diseased tissues, rather than on physiological excitability (resting or tonic block).
Slovenian: Meksiletin blokira natrijeve kanale z močnejšo jakostjo v primerih prekomernega pojava akcijskega potenciala (uporaba odvisna od bloka) in/ali podaljšano depolarizacijo (blok odvisen od napetosti), ki se pojavljajo v obolelem tkivu, namesto fiziološke razdražljivosti (mirovanje ali tonični blok).
English: Stiffness score (VAS) (mm) Number of subjects
Slovenian: Rezultat okorelosti (VAS) (mm) Število udeležencev
English: Pharmacotherapeutic group: Cardiac therapy, antiarrhythmics, class Ib, ATC code: C01BB02.
Slovenian: Farmakoterapevtska skupina: zdravila za bolezni srca, antiaritmiki skupine IB, oznaka ATC: C01BB02.
English: It is recommended to reduce your caffeine intake by half while on treatment with mexiletine because the medicine can increase caffeine levels in your blood.
Slovenian: Priporoča se, da med zdravljenjem z meksiletinom za polovico zmanjšate vnos kofeina, saj lahko zdravilo zviša koncentracijo kofeina v krvi.
English: During Namuscla maintenance treatment, a detailed cardiac evaluation should be carried out every 24-48 hour.
Slovenian: Med vzdrževalnim zdravljenjem z zdravilom Namuscla je treba vsakih 24-48 ur opraviti podroben pregled srca.
English: Very common: insomnia
Slovenian: Zelo pogosti: insomnija
English: What you need to know before you take Namuscla 3.
Slovenian: Kaj morate vedeti, preden boste vzeli zdravilo Namuscla 3.
English: The efficacy and safety of mexiletine in non-dystrophic myotonia was evaluated in MYOMEX, a multi-centre, double-blind, placebo-controlled, cross-over (2 treatment periods of 18 days) study with a 4-day wash-out period in 13 patients with myotonia congenita (MC) and 12 patients with paramyotonia congenita (PC).
Slovenian: Varnost in učinkovitost meksiletina pri nedistrofični miotoniji so ocenjevali v študiji MYOMEX, multicentrični, dvojno slepi, s placebom nadzorovani, navzkrižni (2 obdobji zdravljenja po 18 dni) študiji s 4-dnevnim obdobjem izpiranja pri 13 bolnikih s prirojeno miotonijo (MC - myotonia congenita) in pri 12 bolnikih s prirojeno paramiotonijo (PC - paramyotonia congenita).
English: Taking Namuscla together with any of these medicines increases the risk of a serious heart rhythm disturbance called torsades de pointes.
Slovenian: Jemanje zdravila Namuscla sočasno z navedenimi zdravili poveča tveganje za resne motnje srčnega ritma, imenovane torsades de pointes.
English: The patient alert card (wallet size), to be handed by prescribing specialist and to be read in conjunction with the patient leaflet, should contain the following key messages:
Slovenian: Opozorilna kartica za bolnika (velikosti denarnice), ki jo mora zdravnik, ki predpisuje zdravilo, dati bolniku, in ki jo je treba prebrati skupaj z navodilom za uporabo, mora vsebovati naslednja ključna sporočila:
English: • Myocardial infarction (acute or past), or abnormal Q-waves
Slovenian: • Miokardni infarkt (akutni ali pretekli), ali nenormalni valovi Q
English: For cardiac disorders not listed in section 4.3, the benefit of the antimyotonic effects of mexiletine needs to be balanced against the risk of cardiac complications on a case by case basis.
Slovenian: Pri srčnih boleznih, ki niso na seznamu v poglavju 4.3, je treba pri vsakem posameznem primeru pretehtati koristi antimiotoničnih učinkov meksiletina v odnosu do tveganja za srčne zaplete.
English: You or your companion should contact the doctor immediately if you have tingling in the arms and legs, if you feel unable to think clearly or concentrate, if you have hallucinations, convulsions, if you feel that your heart beats slower, if you feel dizzy and faint, if you collapse or if your heart stops beating.
Slovenian: Vi ali vaš spremljevalec se takoj obrnite na zdravnika, če čutite mravljinčenje v rokah in nogah, če ne morete jasno razmišljati ali se osredotočiti, če imate halucinacije, krče, če čutite, da vaše srce bije počasneje, če ste omotični in čutite omedlevico, če doživite kolaps ali če vaše srce preneha biti.
English: Therefore, clinical and ECG monitoring, as well as adaptation of mexiletine dosage may be indicated throughout and after treatment with a CYP1A2 or CYP2D6 inhibitor.
Slovenian: Zato je lahko klinično in EKG spremljanje kot tudi prilagoditev odmerka meksiletina indicirano skozi celotno zdravljenje z zaviralcem CYP1A2 ali CYP2D6 in po njem.
English: The organic cation transporter 2 (OCT2) provides an important pathway for the uptake of cationic compounds in the kidney.
Slovenian: Organski kationski prenašalec 2 (OCT2 - organic cation transporter 2) zagotavlja pomembno pot za absorpcijo kationskih spojin v ledvicah.
English: Iron (III) oxide (E 172) Titanium dioxide (E 171) Gelatin
Slovenian: Ovojnica kapsule železov (III) oksid (E 172) titanov dioksid (E 171) želatina
English: The metabolic degradation proceeds via various pathways, including aromatic and aliphatic hydroxylation, dealkylation, deamination and N-oxidation.
Slovenian: Presnovna razgradnja poteka preko različnih poti, vključno z aromatsko in alifatsko hidroksilacijo, dealkilacijo, deaminacijo in N-oksidacijo.
English: Increased concentrations of caffeine occurring with the co-administration of mexiletine may be of concern in patients with cardiac arrhythmia.
Slovenian: Povišane koncentracije kofeina ob sočasnem jemanju meksiletina so lahko skrb vzbujajoče pri bolnikih s srčno aritmijo.
English: Mexiletine excretion may increase when the urinary pH is acidic, compared to normal or alkaline pH.
Slovenian: Izločanje meksiletina se lahko poveča pri kislem pH urina v primerjavi z normalnim ali alkalnim pH.
English: Electrolyte imbalance needs to be corrected before administering mexiletine and to be monitored throughout treatment (with a periodicity to be adapted patient by patient).
Slovenian: Elektrolitsko neravnovesje je treba odpraviti pred dajanjem meksiletina in ga spremljati skozi celotno zdravljenje (pogostnost spremljanja je treba prilagoditi posameznemu bolniku).
English: Effect of other medicinal products on mexiletine
Slovenian: Vpliv drugih zdravil na meksiletin
English: DRESS refers to a syndrome which includes in its complete form severe cutaneous eruptions, fever, lymphadenopathy, hepatitis, haematological abnormalities with eosinophilia and atypical lymphocytes, and can involve other organs.
Slovenian: DRESS se nanaša na sindrom, ki v svoji polni obliki vključuje hude kožne erupcije, vročino, limfadenopatijo, hepatitis, hematološke motnje z eozinofilijo in atipičnimi limfociti ter lahko prizadene druge organe.
English: The main observed effects in rats and/or dogs were vomiting, diarrhoea, tremor, ataxia, convulsions and tachycardia.
Slovenian: Glavni opaženi učinki pri podganah in/ali psih so bili bruhanje, driska, tremor, ataksija, krči in tahikardija.
English: If you or your doctor detects any heart rhythm disturbances or any of the conditions stated in section “Do not take Namuscla”, your doctor will stop your treatment with Namuscla.
Slovenian: Če vi sami ali vaš zdravnik odkrije morebitne motnje srčnega ritma ali katero koli od stanj, navedenih v poglavju »Ne jemljite zdravila Namuscla«, bo zdravnik prekinil vaše zdravljenje z zdravilom Namuscla.
English: After the oral administration of single (167 mg) and multiple (83 mg twice a day during 8 days) doses of mexiletine, total clearance of mexiletine is significantly increased in smokers (1.3 to 1.7-fold) due to induction of CYP1A2, resulting in a correspondingly decreased elimination half-life and drug exposure.
Slovenian: Po peroralni aplikaciji enojnih (167 mg) in večkratnih (83 mg dvakrat dnevno 8 dni) odmerkov meksiletina se skupni očistek meksiletina znatno poveča pri kadilcih (1,3- do 1,7-krat) zaradi indukcije CYP1A2, kar povzroči ustrezno manjšo razpolovno dobo izločanja in izpostavljenost zdravilu.
English: The CYP1A2 substrate blood levels should be monitored, particularly when the mexiletine dose is changed.
Slovenian: Treba je spremljati ravni substrata CYP1A2 v krvi, zlasti ob spremembi odmerka meksiletina.
English: Not known: diplopia, dysgeusia
Slovenian: Neznana: diplopia, disgevzija
English: Up to 10%
Slovenian: Do 10 %
English: There is an Alert Card distributed with Namuscla, to remind you and medical staff of the risk of cardiac arrythmias.
Slovenian: Zdravilu Namuscla je priložena opozorilna kartica, ki vas in zdravstveno osebje opomni na tveganje za pojav srčnih aritmij.
English: Throughout treatment with mexiletine, and in relation with dose changes, cardiac monitoring of patients needs to be adapted as a function of the heart condition of the patient:
Slovenian: Med zdravljenjem z meksiletinom in v povezavi s spremembami odmerka je treba pri bolnikih prilagoditi spremljanje srca glede na bolezensko stanje bolnikovega srca:
English: An appropriate adjustment in the dose of the OCT2 substrate should be considered.
Slovenian: Razmisliti je treba o ustrezni prilagoditvi odmerka substrata OCT2.
English: Holter-monitoring and echocardiography are recommended at least annually, or more frequently, if considered necessary, as part of routine cardiac assessment.
Slovenian: Holterjevo spremljanje in ehokardiografija sta priporočena najmanj enkrat letno ali pogosteje, če je to potrebno v sklopu rutinskega pregleda srca.
English: Several medicinal products including anticonvulsants, antibiotics and also mexiletine have been identified as possible causes.
Slovenian: Kot možni vzrok je bilo opredeljenih več zdravil, vključno z antiepileptiki, antibiotiki in tudi meksiletinom.
English: The most commonly reported adverse reactions in patients treated with mexiletine are abdominal pain (12%), vertigo (8%) and insomnia (12%).
Slovenian: Neželeni učinki, o katerih so najpogosteje poročali pri bolnikih, ki so se zdravili z meksiletinom, so bolečine v trebuhu (12 %), vrtoglavica (8 %) in nespečnost (12 %).
English: There is insufficient information on the effects of mexiletine in newborns/infants.
Slovenian: Podatki o učinku meksiletina na novorojenčke/dojenčke so nezadostni.
English: • Patients should inform the HCP about any ongoing medications or before starting any new medication, while on treatment with Namuscla;
Slovenian: • Bolniki morajo obvestiti zdravstvenega delavca o vseh zdravilih, ki jih jemljejo, oziroma pred začetkom jemanja katerega koli novega zdravila, medtem ko jemljejo zdravilo Namuscla;
English: Other antiarrhythmics (class Ib, II, IV antiarrhythmics):
Slovenian: Drugi antiaritmiki (antiaritmiki razredov Ib, II in IV):
English: Mexiletine dose may need to be increased if a patient starts to smoke and decreased if a patient stops to smoke.
Slovenian: Odmerek meksiletina bo morda treba zvišati, če bolnik začne kaditi oziroma znižati, če preneha kaditi.
English: Very rare: drug reaction with eosinophilia and systemic symptoms Not known: lupus-like syndrome, dermatitis exfoliative, Stevens-Johnson syndrome Psychiatric disorders
Slovenian: Zelo redki: reakcija na zdravilo z eozinofilijo in sistemskimi simptomi Neznana: lupusu podoben sindrom, eksfoliativni dermatitis, Stevens-Johnsonov sindrom Psihiatrične motnje
English: In a clinical study, co-administration of mexiletine with phenytoin resulted in a significant decrease in exposure to mexiletine (p < 0.003) due to enhanced clearance as reflected in significantly decreased elimination half-life (17.2 to 8.4 hours, p < 0.02).
Slovenian: V klinični študiji je sočasna uporaba meksiletina s fenitoinom povzročila znatno manjšo izpostavljenost meksiletinu (p < 0,003) zaradi boljšega očistka, kar se odraža v precej krajši razpolovni dobi izločanja (17,2 do 8,4 ure, p < 0,02).
English: Uncommon: bradycardia
Slovenian: Občasni: bradikardija
English: An appropriate adjustment in the dose of the CYP1A2 substrate should be considered.
Slovenian: Razmisliti je treba o ustrezni prilagoditvi odmerka substrata CYP1A2.
English: • Sinus node dysfunction (including sinus rate < 50 bpm)
Slovenian: • Disfunkcija sinusnega vozla (vključno s sinusnim ritmom < 50 utr./min)
English: The potential of mexiletine as a drug-drug-interaction perpetrator is unknown.
Slovenian: Potencial meksiletina kot učinkovine, ki povzroča interakcije med zdravili, ni znan.
English: If you notice that the rhythm of your heart changes (the heart beats faster or slower), if you feel fluttering or pain in your chest, if you have difficulty breathing, if you feel dizzy, if you sweat or if you faint, you have to contact an emergency centre immediately.
Slovenian: Če opazite spremembo srčnega ritma (hitrejše ali počasnejše bitje srca), če občutite drhtenje ali bolečino v prsnem košu, če težko dihate, občutite omotičnost, se potite ali omedlite, morate takoj poklicati center za nujno medicinsko pomoč.
English: You should talk to your doctor about this, together you will make a decision whether to abstain breast-feeding or to discontinue/abstain from mexiletine therapy.
Slovenian: Pogovoriti se morate z zdravnikom, s katerim se bosta skupaj odločila, ali se boste odpovedali dojenju ali pa boste prekinili zdravljenje/se prenehali zdraviti z meksiletinom.
English: The negative genotoxicity potential does not indicate an increased carcinogenic risk of treatment with mexiletine.
Slovenian: Negativni genotoksični potencial ne pomeni povečanega tveganja za nastanek rakastih bolezni pri zdravljenju z meksiletinom.
English: The influence of CYP2D6 phenotype on mexiletine metabolism has been extensively investigated.
Slovenian: Vpliv fenotipa CYP2D6 na presnovo meksiletina je bil temeljito raziskan.
English: • Ventricular tachyarrhythmia
Slovenian: • Ventrikularna tahiaritmija
English: What Namuscla is and what it is used for 2.
Slovenian: Kaj je zdravilo Namuscla in za kaj ga uporabljamo 2.
English: Several of the resulting metabolites are submitted to further conjugation with glucuronic acid (phase II metabolism); among these are the major metabolites p-hydroxymexiletine, hydroxy-methylmexiletine and N-hydroxymexiletine.
Slovenian: Več nastalih metabolitov je podvrženo nadaljnji konjugaciji z glukuronsko kislino (faza II presnove); med njimi so glavni metaboliti p-hidroksimeksiletin, hidroksi-metilmeksiletin in N-hidroksimeksiletin.
English: Namuscla may in rare cases cause tiredness, confusion, blurred vision: If you have these effects do not drive, cycle and use machines.
Slovenian: Zdravilo Namuscla v redkih primerih lahko povzroča utrujenost, zmedenost in zamegljen vid: če opazite take učinke, ne upravljajte vozil in strojev in ne kolesarite.
English: If mexiletine and other OCT2 substrates are to be used concurrently, the OCT2 substrate blood levels should be monitored, particularly when the mexiletine dose is changed.
Slovenian: Pri sočasni uporabi meksiletina z drugimi substrati OCT2 je treba spremljati ravni substrata OCT2 v krvi, zlasti ob spremembi odmerka meksiletina.
English: Namuscla is used to treat the symptoms of myotonia (when muscles relax slowly and with difficulty after they are used) in adults with non-dystrophic myotonic disorders, which are caused by genetic defects that affect muscle function.
Slovenian: Zdravilo Namuscla se uporablja za zdravljenje simptomov miotonije (počasno in težavno sproščanje mišic po njihovi uporabi) pri odraslih z nedistrofičnimi miotoničnimi motnjami, ki so posledica genetskih napak, ki vplivajo na delovanje mišic.
English: The most serious reported adverse reactions in patients treated with mexiletine are drug reaction with eosinophilia and systemic symptoms and arrhythmia (atrioventricular block, arrhythmia, ventricular fibrillation).
Slovenian: Najresnejši neželeni učinki pri bolnikih, ki so se zdravili z meksiletinom, so reakcija na zdravilo z eozinofilijo ter sistemskimi simptomi in aritmija (atrioventrikularni blok, aritmija, ventrikularna fibrilacija).
English: Musculoskeletal and connective tissue disorders Common: pain in the extremities
Slovenian: Bolezni mišičnoskeletnega sistema in vezivnega tkiva Pogosti: bolečine v okončinah
English: • Patient alert card
Slovenian: • opozorilna kartica za bolnika.
English: Up to 5%
Slovenian: Do 5 %
English: Common: flushing, hypotension
Slovenian: Pogosti: zardevanje, hipotenzija
English: Weight In population pharmacokinetic analyses, weight was found to influence mexiletine pharmacokinetics.
Slovenian: V populacijski farmakokinetični analizi je bilo ugotovljeno, da telesnamasa vpliva na farmakokinetiko meksiletina.
English: In order to prevent and / or minimise the important identified risks of Cardiac Arrhythmia in patients with Dystrophic Myotonia (off-label use) and Decreased Namuscla clearance, thus the risk of adverse reactions in patients with hepatic impairment, the MAH shall ensure that in each MS where Namuscla is marketed, all healthcare professionals (HCPs) and patients are provided, respectively, with:
Slovenian: Da se prepreči in/ali zmanjša pomembna identificirana tveganja za srčno aritmijo pri bolnikih z distrofično miotonijo (nenamenska uporaba) in zmanjšanje očistka zdravila Namuscla, torej tveganja za neželene učinke pri bolnikih z jetrno okvaro, mora imetnik dovoljenja za promet z zdravilom v vseh državah članicah, v katerih se trži zdravilo Namuscla zagotoviti, da bo vsem zdravstvenim delavcem in bolnikom na voljo:
English: Peak plasma concentrations following oral administration occur within 2 to 3 hours.
Slovenian: Največje plazemske koncentracije po peroralnem odmerjanju se pojavijo v 2 do 3 urah.
English: Therefore, electrolytic evaluation should be done prior to initiating therapy with mexiletine in every patient.
Slovenian: Zato je treba pri vsakem bolniku pred začetkom zdravljenja z meksiletinom opraviti elektrolitsko vrednotenje.
English: Drug reaction with eosinophilia and systemic symptoms (DRESS)
Slovenian: Reakcija na zdravilo z eozinofilijo in sistemskimi simptomi (Drug reaction with eosinophilia and systemic symptoms - DRESS)
English: In case of modification of the mexiletine dose, or if medicinal products susceptible to affect cardiac conduction are co-administered with mexiletine, patients should be closely monitored by ECG (especially patients with conduction anomalies) (see sections 4.3 and 4.4).
Slovenian: Pri spremembi odmerka meksiletina ali če bolniki sočasno z meksiletinom jemljejo zdravila, dovzetna za vpliv na srčno prevodnost, je treba take bolnike skrbno spremljati s snemanjem EKG (zlasti bolnike z anomalijami prevodnosti) (glejte poglavji 4.3 in 4.4).
English: Other medicines and Namuscla
Slovenian: Druga zdravila in zdravilo Namuscla
English: These tests will also be performed regularly during treatment with Namuscla, and before and after your dose of Namuscla is modified.
Slovenian: Take preglede boste redno opravljali tudi med zdravljenjem z zdravilom Namuscla ter pred spremembo odmerka zdravila Namuscla in po njem.
English: Do not take Namuscla - if you are allergic to mexiletine or to any of the other ingredients of this medicine (listed in section 6) - if you are allergic to any local anaesthetic - if you have had heart attack - if your heart does not work well enough - if you have certain disorders of the heart rhythm - if your heart beats too fast - if the blood vessels of your heart are damaged - if you also take certain medicines to treat disorders of the heart rhythm (see Other medicines and Namuscla) - if you also take certain medicines which have a narrow therapeutic window (see Other medicines and Namuscla).
Slovenian: Ne jemljite zdravila Namuscla: - če ste alergični na meksiletin ali katero koli sestavino tega zdravila (navedeno v poglavju 6), - če ste alergični na kateri koli lokalni anestetik, - če ste doživeli srčni infarkt, - če vaše srce ne deluje dovolj dobro, - če imate motnje srčnega ritma, - če imate pospešen srčni utrip, - če so žile v vašem srcu poškodovane, - če jemljete tudi določena zdravila za zdravljenje srčnega ritma (glejte poglavje Druga zdravila in zdravilo Namuscla).
English: • In patients without cardiac abnormalities, periodic ECG monitoring is recommended (every 2 years or more frequently if considered necessary).
Slovenian: • Pri bolnikih brez srčnih nepravilnosti je priporočljivo redno spremljanje EKG (vsaki dve leti ali pogosteje, če je to potrebno).
English: In case of seizure, benzodiazepines should be used.
Slovenian: Pri epileptičnih napadih je treba uporabiti benzodiazepine.
English: Namuscla capsules are Swedish orange hard shell gelatin capsules (20 mm) filled with white powder.
Slovenian: Kapsule Namuscla so kapsule iz trde želatine švedsko rdeče barve (20 mm), napolnjene z belim praškom.
English: • Information about symptoms of cardiac arrhythmias, which can be life-threatening, and when patients should seek HCP attention;
Slovenian: • Informacije o simptomih srčnih aritmij, ki so lahko smrtno nevarne, in o tem, kdaj morajo bolniki poiskati zdravniško pomoč;
English: Namuscla is indicated for the symptomatic treatment of myotonia in adult patients with nondystrophic myotonic disorders.
Slovenian: Zdravilo Namuscla je indicirano za simptomatsko zdravljenje miotonije pri odraslih bolnikih z nedistrofičnimi miotoničnimi motnjami.
English: A period of at least 7 days before dose increase must be respected to ensure that steady-state levels are reached, irrespective of the patient's CYP450 polymorphism.
Slovenian: Pred zvišanjem odmerka je treba počakati vsaj 7 dni, da se zagotovi, da so ravni v stanju dinamičnega ravnovesja, ne glede na polimorfizem CYP450 pri bolniku.
English: • Atrial tachyarrhythmia, fibrillation or flutter
Slovenian: • Atrijska tahiaritmija, fibrilacija ali undulacija
English: After at least 1 week of treatment, based on the clinical response, the daily dose can be increased to 333 mg daily (2 capsules per day).
Slovenian: Po najmanj enem tednu zdravljenja je mogoče glede na klinični odziv dnevni odmerek zvišati na 333 mg dnevno (2 kapsuli na dan).
English: Mexiletine may have minor influence on the ability to drive and use machines.
Slovenian: 4.7 Vpliv na sposobnost vožnje in upravljanja strojev Meksiletin ima lahko blag vpliv na sposobnost vožnje in upravljanja strojev.
English: Age There is no clinically relevant effect of age on the exposure of mexiletine in adults.
Slovenian: Starost Pri odraslih starost nima klinično pomembnega vpliva na izpostavljenost meksiletinu.
English: Mexiletine pharmacokinetics are characterised by significantly lower total and renal clearance resulting in prolonged elimination half-life, higher exposure, and lower volume of distribution in poor metabolisers compared to extensive metabolisers.
Slovenian: Za farmakokinetiko meksiletina je značilen bistveno nižji skupni in ledvični očistek, kar povzroči daljši razpolovni čas izločanja, večjo izpostavljenost in nižji volumen porazdelitve pri osebah, ki ga slabo presnavljajo, v primerjavi z osebami z močno presnovo.