natgillin/translations-raw huggingface dataset:
Magnesium-/aluminiumholdige antacida skal tages tidsforskudt fra administrationen af Dovato (mindst 2 timer efter eller 6 timer før).
Magnesium/ aluminium-containing antacids should be taken well separated in time from the administration of Dovato (minimum 2 hours after or 6 hours before).
Da dolutegravir i høj grad er bundet til plasmaproteiner, er det usandsynligt, at det vil kunne elimineres signifikant ved dialyse.
As dolutegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis.
Renal clearance af uomdannet aktivt stof er en mindre vej til elimination af dolutegravir.
Renal clearance of unchanged active substance is a minor pathway of elimination for dolutegravir.
Det er ikke nødvendigt at justere dosis af orale kontraceptiva, når disse administreres sammen med Dovato.
No dose adjustment of oral contraceptives is necessary when co-administered with Dovato.
Virkningen af Dovato understøttes af data fra 2 identiske 148-ugers randomiserede, dobbeltblindede, non-inferiore, kontrollerede fase III-multicenterstudier med parallelle grupper, GEMINI-1 (204861) og GEMINI-2 (205543).
The efficacy of Dovato is supported by data from 2 identical 148-week, Phase III, randomised, double-blind, multicentre, parallel-group, non-inferiority controlled trials GEMINI-1 (204861) and GEMINI-2 (205543).
Hiv-1-isolater (CRF01_AE, n=12; CRF02_AG, n=12 og undertype C eller CRF_AC, n=13) fra 37 ubehandlede patienter i Afrika og Asien var følsomme over for lamivudin (IC50 gange ændring <3,0).
HIV-1 isolates (CRF01_AE, n=12; CRF02_AG, n=12; and Subtype C or CRF_AC, n=13) from 37 untreated patients in Africa and Asia were susceptible to lamivudine (IC50 fold changes < 3.0.
Nukleosid- og nukleotidanaloger kan påvirke mitokondriefunktionen i varierende grad, hvilket er mest udtalt for stavudin, didanosin og zidovudin.
Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.
Baseret på manglende effekt på in vivo-farmakokinetikken af OAT-substratet tenofovir, er in vivohæmning af OAT1 usandsynlig.
Based on the lack of effect on the in vivo pharmacokinetics of the OAT substrate tenofovir, in vivo inhibition of OAT1 is unlikely.
I alt 1.433 hiv-1-inficerede voksne personer, som ikke tidligere havde fået antiretroviral behandling, blev behandlet i studierne.
A total of 1433 HIV-1 infected antiretroviral treatment-naïve adult subjects received treatment in the trials.
In vivo havde dolutegravir ingen effekt på midazolam, en CYP3A4-probe.
In vivo, dolutegravir did not have an effect on midazolam, a CYP3A4 probe.
Dovato er indiceret til behandling af infektion med Human Immundefekt Virus type 1 (hiv-1) hos voksne og unge over 12 år, der vejer mindst 40 kg, uden kendt eller formodet resistens over for integrasehæmmerklassen eller lamivudin (se pkt.
Dovato is indicated for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults and adolescents above 12 years of age weighing at least 40 kg, with no known or suspected resistance to the integrase inhibitor class, or lamivudine (see section 5.1).
Effekt af dolutegravir og lamivudin på farmakokinetikken af andre lægemidler
Effect of dolutegravir and lamivudine on the pharmacokinetics of other medicinal products
Det karcinogene potentiale af en kombination af dolutegravir og lamivudin er ikke undersøgt.
The carcinogenic potential of a combination of dolutegravir and lamivudine has not been tested.
Selvom ætiologien anses for at være multifaktoriel (herunder kortikosteroidforbrug, bisphosphonater, alkoholforbrug, svær immunosuppression, højere BMI), er der rapporteret tilfælde af osteonekrose hos patienter med fremskreden hiv-sygdom og/eller langvarig eksponering for CART.
Although the aetiology is considered to be multifactorial (including corticosteroid use, biphosphonates, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported in patients with advanced HIV-disease and/or long-term exposure to CART.
32 % af den samlede orale dosis udskilles i urinen og består af et etherglukuronid af dolutegravir (18,9 % af den samlede dosis), en metabolit, der er dannet ved N-dealkylering (3,6 % af den samlede dosis), og en metabolit, der er dannet ved oxidation ved det benzyliske carbon (3,0 % af den samlede dosis).
Thirty-two percent of the total oral dose is excreted in the urine, represented by ether glucuronide of dolutegravir (18.9% of total dose), N-dealkylation metabolite (3.6% of total dose), and a metabolite formed by oxidation at the benzylic carbon (3.0% of total dose).
Hos diegivende rotter, som fik en enkelt oral dosis dolutegravir på 50 mg/kg 10 dage post partum, blev der påvist dolutegravir i mælken i koncentrationer, som typisk var højere end i blodet.
In lactating rats that received a single oral dose of 50 mg/kg at 10 days postpartum, dolutegravir was detected in milk at concentrations typically higher than blood.
Tag Dovato-pakningen med, hvis det er muligt.
If possible, show them the Dovato pack.
Resultaterne af to mikronukleusanalyser udført in vivo hos rotter med lamivudin var negative.
The results from two in vivo rat micronucleus tests with lamivudine were negative.
Metformin elimineres renalt, og det er derfor vigtigt at monitorere nyrefunktionen ved administration sammen med Dovato.
Metformin is eliminated renally and, therefore, it is of importance to monitor renal function when co-treated with Dovato.
Dolutegravir elimineres overvejende gennem metabolisering via uridindifosfatglukuronosyltransferase (UGT) 1A1.
Dolutegravir is eliminated mainly through metabolism by uridine diphosphate glucuronosyl transferase (UGT) 1A1.
Mitokondriel dysfunktion
Mitochondrial dysfunction
Lamivudintriphosphat viser signifikant mindre affinitet for værtscelle-dna-polymeraser.
Lamivudine triphosphate shows significantly less affinity for host cell DNA polymerases.
• Aktive stoffer: dolutegravir og lamivudin.
• The active substances are dolutegravir and lamivudine.
Dovato filmovertrukne tabletter er ovale, bikonvekse, hvide tabletter præget med "SV 137" på den ene side.
Dovato film-coated tablets are oval, biconvex, white tablets debossed with 'SV 137' on one face.
Patienter, der i forvejen har leverdysfunktion, herunder kronisk aktiv hepatitis, oplever en øget frekvens af problemer med leverfunktionen under antiretroviral kombinationsbehandling, og disse patienter skal monitoreres i henhold til standardpraksis.
Patients with pre-existing liver dysfunction, including chronic active hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy, and should be monitored according to standard practice.
Antiretrovirale lægemidler Non-nukleosid revers transkriptasehæmmere Etravirin uden boostede proteasehæmmere/dolutegravir
Antiretroviral medicinal products Non-nucleoside reverse transcriptase inhibitors Etravirine without boosted protease inhibitors /
• cladribin til behandling af leukæmi eller multipel sclerose
• cladribine, to treat leukaemia or multiple sclerosis
Hver pakning består af en flaske, der indeholder 30 filmovertrukne tabletter.
Each pack consists of one bottle containing 30 filmcoated tablets.
• phenytoin og phenobarbital til behandling af epilepsi
• phenytoin and phenobarbital, to treat epilepsy
Da hepatisk udskillelse spiller en mindre rolle i clearance af lamivudin, er det usandsynligt, at lægemiddelinteraktioner, der skyldes hæmning af OCT1, har nogen klinisk signifikans.
As hepatic elimination plays a minor role in the clearance of lamivudine, drug interactions due to inhibition of OCT1 are unlikely to be of clinical significance.
→ Tal med lægen for yderligere råd om, hvordan du skal tage syreneutraliserende lægemidler sammen med Dovato.
→ Talk to your doctor for further advice on taking acid-lowering medicines with Dovato.
Hvis Dovato seponeres hos patienter, der samtidig er inficeret med hepatitis B, anbefales regelmæssig monitorering af både leverfunktionstests og markører for HBV-replikation, da seponering af lamivudin kan medføre akut eksacerbation af hepatitis.
If Dovato is discontinued in patients co-infected with hepatitis B virus, periodic monitoring of both liver function tests and markers of HBV replication is recommended, as withdrawal of lamivudine may result in an acute exacerbation of hepatitis.
Ved baseline i den sammenlagte analyse var medianalderen på personerne 33 år, 15 % var kvinder, 68 % var hvide, 9 % var i CDC stadie 3 (aids), 20 % havde hiv-1-RNA >100.000 kopier/ml, og 8 % havde CD4+-celletal under 200 celler pr. mm3; disse karakteristika var de samme i studier og behandlingsarme.
At baseline, in the pooled analysis, the median age of subjects was 33 years, 15% were female, 68% were white, 9% were CDC Stage 3 (AIDS), 20% had HIV-1 RNA >100,000 copies/mL, and 8% had CD4+ cell count less than 200 cells per mm3; these characteristics were similar between studies and treatment arms.
udslæt, pruritus, alopeci
rash, pruritus, alopecia
• Øvrige indholdsstoffer: mikrokrystallinsk cellulose, natriumstivelsesglycolat, magnesiumstearat, mannitol (E421), povidon (K29/32), natriumstearylfumarat, hypromellose (E464), macrogol, titandioxid (E171).
• The other ingredients are microcrystalline cellulose, sodium starch glycolate, magnesium stearate, mannitol (E421), povidone (K29/32), sodium stearyl fumarate, hypromellose (E464), macrogol, titanium dioxide (E171).
• øget niveau af leverenzymer (aminotransferaser)
• increase in the level of liver enzymes (aminotransferases)
Disse fund bør overvejes hos alle børn, der har været eksponeret for nukleosid- og nukleotidanaloger in utero, som har svære kliniske symptomer af ukendt ætiologi, især neurologiske symptomer.
These findings should be considered for any child exposed in utero to nucleoside and nucleotide analogues, who presents with severe clinical findings of unknown aetiology, particularly neurologic findings.
I de sammenlagte GEMINI-studier blev der observeret en gennemsnitlig ændring i forhold til baseline på 10,3 µmol/l (interval -36,3 µmol/l til 55,7 µmol/l) efter 48 ugers behandling.
In the pooled GEMINI studies a mean change from baseline of 10.3 µmol/L (range: -36.3 µmol/L to 55.7 µmol/L) was observed after 48 weeks of treatment.
Dovato indeholder dolutegravir og lamivudin; derfor er eventuelle identificerede interaktioner for disse individuelle aktive stoffer relevante for Dovato.
Dovato contains dolutegravir and lamivudine, therefore any interactions identified for these individually are relevant to Dovato.
Ledipasvir/sofosbuvir/lamivudin (med abacavir)
Ledipasvir/Sofosbuvir/ Lamvudine (with abacavir)
For information omkring in vitro-resistens og krydsresistens over for andre stoffer i integrase- og NRTI-klassen henvises til produktresuméerne for dolutegravir og lamivudin.
For information around in vitro resistance, and cross resistance to other agents of the integrase- and NRTI class, please refer to the SmPCs of dolutegravir and lamivudine.
Dolutegravir er også et substrat for UGT1A3, UGT1A9, CYP3A4, P-glycoprotein (P-gp) og brystcancerresistensprotein (BCRP).
Dolutegravir is also a substrate of UGT1A3, UGT1A9, CYP3A4, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP).
Dolutegravir hæmmer hiv-integrase ved at binde til det aktive sted på integrase og blokere strand transfer-trinnet i integrationen af retroviral deoxyribonukleinsyre (dna), hvilket er essentielt for hiv's replikationscyklus.
Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral Deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle.
† Baseret på CMH-stratificeret analyse med justering for følgende stratificeringsfaktorer ved baseline: Plasma hiv-1-RNA (≤100.000 c/ml vs. >100.000 c/ml) og CD4+-celletal (≤200 celler/mm3 vs. >200 celler/mm3).
† Based on CMH-stratified analysis adjusting for the following baseline stratification factors: Plasma HIV-1 RNA (≤100,000 c/mL vs. >100,000 c/mL) and CD4+ cell count (≤200 cells/mm3 vs. >200 cells/mm3).
Meget sjældne bivirkninger, der muligvis kan ses i blodprøver, er: • manglende dannelse af nye røde blodceller i knoglemarven (ren erytrocytaplasi).
Very rare side effects that may show up in blood tests are: • a failure of the bone marrow to produce new red blood cells (pure red cell aplasia).
Hvis Dovato indtages i fastende tilstand, skal sådanne tilskud tages mindst 2 timer efter eller 6 timer før indtagelse af Dovato.
- If Dovato is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Dovato.
I uge 48 var dolutegravir plus lamivudin non-inferior til dolutegravir plus tenofovirdisoproxil/emtricitabin FDC i studierne GEMINI-1 og GEMINI-2.
At week 48, dolutegravir plus lamivudine was non-inferior to dolutegravir plus tenofovir disoproxil/emtricitabine FDC in GEMINI-1 and GEMINI-2 studies.
Absorptionen af dolutegravir reduceres af visse metalkationholdige syreneutraliserende stoffer og tilskud (se tabel 1).
The absorption of dolutegravir is reduced by certain metal cation-containing anti-acid substances and supplements (see Table 1).
Med sine aktive metabolitter 5'-triphosphater (TP) (en analog for cytidin) hæmmer lamivudin revers transkriptase af hiv-1 og hiv-2 ved at inkorporere monophosphatformen i den virale dna-kæde, hvilket resulterer i kædetermination.
Lamivudine, via its active metabolite 5'-triphosphates (TP) (an analogue for cytidine), inhibits reverse transcriptase of HIV-1 and HIV-2 through incorporation of the monophosphate form into the viral DNA chain, resulting in chain termination.
Synk tabletten med væske.
Swallow the tablet with some liquid.
Det er ikke nødvendigt at justere dosis hos patienter med let til moderat nedsat leverfunktion (Child-Pugh-klasse A eller B).
No dosage adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh grade A or B).
Virkningen af Dovato eller kombinationen af dolutegravir plus lamivudin (som enkeltstoffer) er ikke undersøgt hos børn og unge.
The efficacy of Dovato, or the dual combination of dolutegravir plus lamivudine (as single entities) has not been studied in children or adolescents.
I fase III-studierne for dolutegravir som enkeltstof var det tilladt for patienter med co-infektion med hepatitis B og/eller C at deltage, såfremt baseline leverparametertests ikke overskred 5 gange den øvre grænse for normal (ULN).
In the Phase III studies for the dolutegravir single agent, patients with hepatitis B and/or C co-infection were permitted to enrol provided that baseline liver chemistry tests did not exceed 5 times the upper limit of normal (ULN).
Der forventes ingen klinisk signifikante lægemiddelinteraktioner mellem dolutegravir og lamivudin.
No clinically significant drug interactions are expected between dolutegravir and lamivudine.
Patienter med kronisk hepatitis B eller C, som behandles med antiretroviral kombinationsbehandling, har øget risiko for svære og potentielt fatale leverbivirkninger.
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk of severe and potentially fatal hepatic adverse reactions.
Symptomer på infektion og betændelse
Symptoms of infection and inflammation
Dolutegravir er til stede i genitalorganerne hos kvinder og mænd.
Dolutegravir is present in the female and male genital tract.
Der sås ingen relevante effekter af dolutegravir på QTc-intervallet ved behandling med cirka 3 gange højere dosis end den kliniske dosis.
No relevant effects were seen with dolutegravir on the QTc interval, with doses exceeding the clinical dose by approximately three fold.
In vitro var dolutegravir ikke et substrat for humant OATP 1B1, OATP 1B3 eller OCT 1.
In vitro, dolutegravir was not a substrate of human OATP 1B1, OATP 1B3 or OCT 1.
Autoimmune lidelser (såsom Graves' sygdom og autoimmun hepatitis) er også rapporteret, men den rapporterede tid til udbrud er mere variabel, og disse hændelser kan ske mange måneder efter initiering af behandling (se pkt.
Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see section 4.4).
Oval, bikonveks, hvid filmovertrukket tablet på ca. 18,5 x 9,5 mm præget med "SV 137" på den ene side.
Oval, biconvex, white, film coated tablet, approximately 18.5 x 9.5 mm, debossed with “SV 137” on one face.
In vivo kan dolutegravir øge plasmakoncentrationerne af lægemidler, for hvilke udskillelsen afhænger af OCT2 eller MATE-1 (f.eks. metformin) (se tabel 1 og pkt.
In vivo, dolutegravir may increase plasma concentrations of medicinal products in which excretion is dependent upon OCT2 or MATE-1 (e.g. metformin) (see Table 1 and section 4.3).
Dolutegravir øgede koncentrationen af metformin.
Dolutegravir increased metformin concentrations.
Uigennemsigtige, hvide HDPE (højdensitetspolyethylen)-flasker lukket med børnesikret lukke af polypropylen med en polyethylenbelagt induktionsforsegling.
Opaque, white HDPE (high density polyethylene) bottles closed with child resistant polypropylene closures, with a polyethylene faced induction heat seal liner.
De tilgængelige toksikologiske data fra dyreforsøg viser, at dolutegravir udskilles i mælk.
Available toxicological data in animals has shown excretion of dolutegravir in milk.
Samtidig administration af Dovato og andre lægemidler, der hæmmer UGT1A1, UGT1A3, UGT1A9, CYP3A4 og/eller P-gp, kan derfor øge plasmakoncentrationen af dolutegravir.
Co-administration of Dovato and other medicinal products that inhibit UGT1A1, UGT1A3, UGT1A9, CYP3A4, and/or P-gp may, therefore, increase dolutegravir plasma concentration.
MÆRKNING, DER SKAL ANFØRES PÅ DEN YDRE EMBALLAGE INTERMEDIÆR KARTON (UDEN BLUE BOX - DEL AF MULTIPAKNING)
PARTICULARS TO APPEAR ON THE OUTER PACKAGING INTERMEDIATE CARTON (WITHOUT BLUE BOX - COMPONENT OF MULTIPACK)
opkastning, flatulens, abdominalsmerter/-ubehag
vomiting, flatulence, abdominal pain/ discomfort
Administration af en enkelt Dovato-tablet sammen med et måltid med højt fedtindhold øgede dolutegravirs AUC(0-∞) og Cmax med henholdsvis 33 % og 21 % og reducerede lamivudins Cmax med 30 % sammenlignet med fastetilstand.
Administration of a single Dovato tablet with a high fat meal increased dolutegravir AUC(0-∞) and Cmax by 33% and 21%, respectively, and decreased the lamivudine Cmax by 30% compared to fasted conditions.
Almindelige bivirkninger, der muligvis kan ses i blodprøver, er:
Common side effects that may show up in blood tests are:
Mens den totale koncentration af dolutegravir i plasma var ens for de to grupper, blev en 1,5- til 2-gange øgning i ubundet eksponering for dolutegravir observeret hos patienter med moderat nedsat leverfunktion sammenlignet med raske kontroller.
While the total dolutegravir concentration in plasma was similar, a 1.5 to 2 fold increase in unbound exposure to dolutegravir was observed in subjects with moderate hepatic impairment compared to healthy controls.
Dovato er indiceret i fravær af dokumenteret eller mistænkt resistens over for integrasehæmmerklassen og over for lamivudin (se pkt.
Dovato is indicated in the absence of documented or suspected resistance to the integrase inhibitor class and to lamivudine (see section 4.1).
* Resultaterne af den sammenlagte analyse er i overensstemmelse med de individuelle studier, hvori det primære endepunkt (proportionsforskel <50 kopier/ml plasma hiv-1-RNA i uge 48 baseret på snapshot-algoritmen for dolutegravir plus lamivudin versus dolutegravir plus tenofovirdisoproxil/emtricitabin FDC) blev opfyldt.
* The results of the pooled analysis are in line with those of the individual studies, for which the primary endpoint (difference in proportion <50 copies/mL plasma HIV-1 RNA at Week 48 based on the Snapshot algorithm for dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil /emtricitabine FDC) was met.
Den ubundne fraktion af dolutegravir i plasma øges ved lave niveauer af serumalbumin (<35 g/l), som der er set hos personer med moderat nedsat leverfunktion.
The unbound fraction of dolutegravir in plasma is increased at low levels of serum albumin (<35 g/L) as seen in subjects with moderate hepatic impairment.
Dovato og andre mistænkte lægemidler skal omgående seponeres, hvis der udvikles tegn eller symptomer på overfølsomhedsreaktioner (herunder, men ikke begrænset til, svært udslæt eller udslæt ledsaget af et øget niveau af leverenzymer, feber, generel utilpashed, træthed, muskel- eller ledsmerter, blærer, orale læsioner, konjunktivitis, ansigtsødem, eosinofili, angioødem).
Dovato and other suspect medicinal products should be discontinued immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by raised liver enzymes, fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial oedema, eosinophilia, angioedema).
Ingen specifikke symptomer eller tegn er blevet identificeret efter akut overdosering med dolutegravir eller lamivudin ud over de tegn og symptomer, der er anført som bivirkninger.
No specific symptoms or signs have been identified following acute overdose with dolutegravir or lamivudine, apart from those listed as adverse reactions.
• høj kropstemperatur (feber)
• a high temperature (fever)
• selvmordsforsøg (særligt hos patienter, som tidligere har haft depression eller psykiske problemer)
• suicidal attempt (particularly in patients who have had depression or mental health problems before)
Der er i sjældne tilfælde rapporteret nogle sent forekommende neurologiske forstyrrelser (hypertoni, kramper, abnorm adfærd).
Some late-onset neurological disorders have been reported rarely (hypertonia, convulsion, abnormal behaviour).
Der er begrænsede farmakokinetiske data om personer med co-infektion med hepatitis B (se pkt.
There are limited pharmacokinetic data on subjects with hepatitis B co-infection (see section 4.4).
NAVN OG ADRESSE PÅ INDEHAVEREN AF MARKEDSFØRINGSTILLADELSEN ViiV Healthcare BV
NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER ViiV Healthcare BV
Blod og lymfesystem: Ikke almindelig:
Blood and lymphatic systems disorders: Uncommon:
Der er begrænsede data hos unge, der fik en daglig dosis på 300 mg lamivudin.
Limited data are available in adolescents receiving a daily dose of 300 mg of lamivudine.
På baggrund af en begrænset mængde data på enkeltkomponenten dolutegravir eller enkeltkomponenten lamivudin anvendt i kombination med andre antiretrovirale lægemidler til behandling af unge (12 til 17 år) sås ingen yderligere typer bivirkninger ud over dem, der blev set hos den voksne population.
Based on limited available data with the dolutegravir single entity or lamivudine single entity used in combination with other antiretroviral agents to treat adolescents (12 to 17 years), there were no additional types of adverse reactions beyond those observed in the adult population.
Der er ikke udført interaktionsstudier med Dovato.
No drug interaction studies have been conducted using Dovato.
Ingen af de seks personer i dolutegravir plus lamivudin-gruppen eller de fire personer i dolutegravir plus tenofovirdisoproxil/emtricitabin FDC-gruppen, der opfyldte de virologiske seponeringskriterier til og med uge 48 i studierne GEMINI-1 (204861) og GEMINI-2 (205543), havde behandlingsrelateret resistens over for integrasehæmmer- eller NRTI-klassen.
None of the six subjects in the dolutegravir plus lamivudine group or the four subjects in the dolutegravir plus tenofovir disoproxil/emtricitabine FDC group that met virological withdrawal criteria through Week 48 across the GEMINI-1 (204861) and GEMINI-2 (205543) studies had treatment emergent integrase inhibitor or NRTI class resistance.
træthed
fatigue