natgillin/translations-raw huggingface dataset:
10 på basis af kreatinin- clearance som mild (50 til < 80 ml/ min), moderat (30 til < 50 ml/ min) og svær (< 30 ml/ min) samt patienter med ESRD i hæmodialyse.
The study included patients with renal insufficiency classified on the basis of creatinine clearance as mild (50 to < 80 ml/ min), moderate (30 to < 50 ml/ min), and severe (< 30 ml/ min), as well as patients with end-stage renal disease (ESRD) on hemodialysis.
Der blev observeret en stigning til ca. det dobbelte i sitagliptins plasma AUC hos patienter med moderat nyreinsufficiens, og en stigning til ca. det firdobbelte blev observeret hos patienter med svær nyreinsufficiens og hos patienter med ESRD i hæmodialyse sammenlignet med normale raske kontrolpersoner.
An approximately 2-fold increase in the plasma AUC of sitagliptin was observed in patients with moderate renal insufficiency, and an approximately 4-fold increase was observed in patients with severe renal insufficiency and in patients with ESRD on hemodialysis, as compared to normal healthy control subjects.
Sitagliptin elimineredes moderat ved hæmodialyse (13, 5% over en 3- 4 timers hæmodialysesession med start 4 timer efter dosering).
Sitagliptin was modestly removed by hemodialysis (13.5% over a 3- to 4-hour hemodialysis session starting 4 hours postdose).
Januvia anbefales ikke til patienter med moderat eller svær nyreinsufficiens, inklusive patienter med ESRD, da erfaringen med disse patientgrupper er for begrænset (se pkt.
Januvia is not recommended for use in patients with moderate or severe renal insufficiency including those with ESRD since experience in these patients is too limited.
4. 2.).
(See section 4.2.)
Leverinsufficiens Dosisjustering af Januvia er ikke nødvendig hos patienter med mild eller moderat leverinsufficiens (Child- Pugh score ≤9).
Hepatic insufficiency No dosage adjustment for Januvia is necessary for patients with mild or moderate hepatic insufficiency (Child-Pugh score ≤ 9).
Der er ingen klinisk erfaring for patienter med svær leverinsufficiens (Child - Pugh score > 9), men da sitagliptin primært elimineres renalt, forventes leverinsufficiens ikke at påvirke sitagliptins farmakokinetik.
However, because sitagliptin is primarily renally eliminated, severe hepatic insufficiency is not expected to affect the pharmacokinetics of sitagliptin.
Ældre Dosisjustering er ikke nødvendig på basis af alder.
10 Elderly No dosage adjustment is required based on age.
Andre patientkarakteristika Dosisjustering er ikke nødvendig på basis af køn, race eller body mass index (BMI).
Other patient characteristics No dosage adjustment is necessary based on gender, race, or body mass index (BMI).
Disse karakteristika havde ingen klinisk relevant virkning på sitagliptins farmakokinetik på basis af en sammensat analyse af fase I farmakokinetiske data og en farmakokinetisk populationsanalyse af fase I - og fase II- data.
These characteristics had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of Phase I pharmacokinetic data and on a population pharmacokinetic analysis of Phase I and Phase II data.
Der blev observeret nyre - og levertoksicitet hos gnavere ved systemiske eksponeringsniveauer, der var 58 gange højere end eksponeringsniveauet for mennesker, mens no- effect- niveauet fandtes ved niveauet 19 gange højere end eksponeringsniveauet for mennesker.
Renal and liver toxicity were observed in rodents at systemic exposure values 58 times the human exposure level, while the no-effect level was found at 19 times the human exposure level.
23 gange højere end i mennesker.
In addition, very slight to slight skeletal muscle degeneration was also observed histologically at doses resulting in systemic exposure levels of approximately 23 times the human exposure level.
Tilsvarende forandringer var ikke til stede ved en eksponering, der var 6 gange højere end i klinikken.
A no-effect level for these findings was found at an exposure 6-fold the clinical exposure level.
På grund af den høje sikkerhedsmargin (19 gange på dette no- effect niveau), anses disse neoplastiske ændringer ikke relevante for situationen hos mennesker.
Because of the high safety margin (19-fold at this no-effect level), these neoplastic changes are not considered relevant for the situation in humans.
11 Der blev ikke observeret bivirkninger i fertiliteten hos han - og hunrotter, der blev behandlet med sitagliptin før og under parringsperioden.
No adverse effects upon fertility were observed in male and female rats given sitagliptin prior to and throughout mating.
Reproduktive toksicitetsundersøgelser viste en let behandlingsrelateret øget forekomst af føtale ribbensdefekter (manglende, hypoplastiske og takkede ribben) hos rotteafkom ved en systemisk eksponering på mere end 29 gange eksponeringen for mennesker.
Reproductive toxicity studies showed a slight treatment-related increased incidence of fetal rib malformations (absent, hypoplastic and wavy ribs) in the offspring of rats at systemic exposure levels more than 29 times the human exposure levels.
Tabletkerne Mikrokrystallinsk cellulose (E460) Calciumhydrogenphosphat, vandfrit (E341) Croscarmellosenatrium (E468) Magnesiumstearat (E470b) Natriumstearylfumarat
Tablet core: microcrystalline cellulose (E460) calcium hydrogen phosphate, anhydrous (E341)
Filmovertræk Polyvinylalkohol Macrogol 3350 Talcum (E553b) Titandioxid (E171) Rød jernoxid (E172) Gul jernoxid (E172)
Film coating: polyvinyl alcohol macrogol 3350 talc (E553b) titanium dioxide (E171) red iron oxide (E172) yellow iron oxide (E172)
Pakninger med 14, 28, 56, 84 eller 98 filmovertrukne tabletter og 50 x 1 filmovertrukne tabletter i perforerede enkeltdosisblistre.
Packs of 14, 28, 56, 84 or 98 film-coated tablets and 50 x 1 film-coated tablets in perforated unit dose blisters.
12 6. 6 regler for destruktion og anden håndtering
6.6 Special precautions for disposal
Yderligere information om dette lægemiddel er tilgængelig på Det europæiske Lægemiddelagenturs (EMEAs) hjemmeside http: // www. emea. europa. eu /
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) web site: http: / /www. emea. europa. eu/.
Hver tablet indeholder sitagliptin phosphatmonohydrat, svarende til 50 mg sitagliptin.
Each tablet contains sitagliptin phosphate monohydrate, equivalent to 50 mg sitagliptin.
Rund, lys beige, filmovertrukken tablet mærket med ” 112 ” på den ene side.
Round, light beige film-coated tablet with “ 112” on one side.
• til at forbedre den glykæmiske kontrol i kombination med et sulfonylurinstof når diæt og motion plus meksimal veltolereret dosis af et sulfonylurinstof alene ikke giver tilstrækkelig glykæmisk kontrol og når metformin er uhensigtsmæssigt p. g. a. af kontraindikation eller intolerance.
• to improve glycaemic control in combination with a sulphonylurea when diet and exercise plus maximal tolerated dose of a sulphonylurea alone do not provide adequate glycaemic control and when metformin is inappropriate due to contraindications or intolerance.
14 Patienter med nyreinsufficiens Til patienter med mild nyreinsufficiens (kreatinin- clearance [CrCl] ≥50 ml/ min,), er dosisjustering for Januvia ikke nødvendig.
14 Patients with renal insufficiency For patients with mild renal insufficiency (creatinine clearance [CrCl] ≥ 50 ml/ min), no dosage adjustment for Januvia is required.
Her var hyppigheden for hypoglykæmi, der er rapporteret for de patienter, der fik sitagliptin, det samme som hos de patienter, der fik placebo.
Hypoglycaemia when used in combination with other anti-hyperglycaemic agents In clinical trials of Januvia as monotherapy and as part of combination therapy with agents not known to cause hypoglycaemia (i. e. metformin or pioglitazone), rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo.
15 Metformin:
15 Metformin:
Sitagliptin havde en lille effekt på digoxinkoncentrationen i plasma og kan være en mild hæmmer af p- glycoprotein in vivo.
Sitagliptin had a small effect on plasma digoxin concentrations, and may be a mild inhibitor of p- glycoprotein in vivo.
16
16 4.7 Effects on ability to drive and use machines
4. 8
However, when driving or operating machines, it should be taken into account that dizziness and somnolence have been reported.
I kliniske undersøgelser af Januvia som monoterapi og sitagliptin som del af en kombinationsbehandling med metformin eller pioglitazon var frekvensen af hypoglykæmi, der blev rapporteret for sitagliptin, den samme som for de patienter, der fik placebo.
In clinical trials of Januvia as monotherapy and sitagliptin as part of combination therapy with metformin or pioglitazone, rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo.
1 I denne placebo- komtrollerede 24- ugers- undersøgelse af sitagliptin 100 mg én gang dagligt i kombinationmed metformin var incidencen af formodede bivirkninger 9, 3% hos de patienter, der blev behandlet med sitagliptin/ metformin sammenlignet med 10, 1% hos de patienter, der fik placebo/ metformin.
17 1 In this placebo-controlled 24-week study of sitagliptin 100 mg once daily in combination with metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ metformin compared to treatment with placebo/ metformin was 9.3% and 10.1%, respectively.
17 I en supplerende 1- års undersøgelse af sitagliptin 100 mg én gang dagligt i kombination med metformin var incidensen af formodede bivirkninger hos de patienter, der blev behandlet med sitagliptin/ metformin sammenlignet med de patienter, der fik et sulfonylurinstof/ metformin henholdsvis 14, 5% og 30, 3%.
In an additional 1-year study of sitagliptin 100 mg once daily in combination with metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ metformin compared to sulphonylurea/ metformin was 14.5% and 30.3%, respectively.
3 I denne 24- ugers undersøgelse af sitagliptin 100 mg én gang dagligt i kombination med glimepirid og metformin, var bivirkningsincidensen, som blev anset for at være lægemiddel- relateret, henholdsvis 18, 1% og 7, 1% hos de patienter, der blev behandlet med sitagliptin i kombination med glimepirid/ metformin sammenlignet med patienterne, der blev behandlet med placebo i kombination med glimepirid/ metformin.
3 In this 24-week study of sitagliptin 100 mg once daily in combination with glimepiride and metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin in combination with glimepiride/ metformin compared to treatment with placebo in combination with glimepiride/ metformin was 18.1% and 7.1%, respectively.
4 I denne 24- ugers undersøgelse af sitagliptin 100 mg én gang dagligt i kombination med pioglitazon var incidensen af formodede bivirkninger hos de patienter, der blev behandlet med sitagliptin/ pioglitazon sammenlignet med de patienter, der blev behandlet med placebo/ pioglitazon henholdsvis 9, 1% og 9, 0%.
4 In this 24-week study of the combination of sitagliptin 100 mg once daily and pioglitazone, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ pioglitazone compared to patients treated with placebo/ pioglitazone was 9.1% and 9.0%, respectively.
18 Der blev ikke observeret klinisk relevante ændringer i vitale tegn eller i EKG (inklusive i QTc - intervallet) ved behandling med Januvia.
18 No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed with Januvia treatment.
Behandling med GLP- 1 eller DPP- 4 hæmmere i dyremodeller af type 2- diabetes har vist sig at forbedre betacellernes reaktion på glucose og at stimulere syntesen samt frigivelsen af insulin.
Treatment with GLP-1 or with DPP-4 inhibitors in animal models of type 2 diabetes has been demonstrated to improve beta cell responsiveness to glucose and stimulate insulin biosynthesis and release.
Ved at øge de aktive inkretinniveauer øger sitagliptin insulinfrigørelsen og reducerer glucagonniveauer afhængigt af glucosekoncentrationen.
By enhancing active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in a glucose- dependent manner.
19 hæmmer af enzymet DPP- 4 og hæmmer ikke de nært beslægtede enzymer DPP- 8 eller DPP- 9 ved terapeutiske koncentrationer.
19 highly selective inhibitor of the enzyme DPP-4 and does not inhibit the closely-related enzymes DPP-8 or DPP-9 at therapeutic concentrations.
Sammenlignet med placebo gav behandling med sitagliptin 100 mg én gang dagligt som monoterapi gav signifikante forbedringer i HbA1c, i fasteplasma glucose (FPG) og i 2- timers postprandial glucose (2- timers PPG), når det blev sammenlignet med placebo i to undersøgelser, hvor den ene var af 18 - ugers varighed og den anden af 24- ugers varighed.
Treatment with sitagliptin at 100 mg once daily as monotherapy provided significant improvements in HbA1c, fasting plasma glucose (FPG), and 2-hour post-prandial glucose (2-hour PPG), compared to placebo in two studies, one of 18- and one of 24-weeks duration.
I en 24- ugers placebokontrolleret faktoriel undersøgelse af initial behandling gav sitagliptin 50 mg to gange dagligt i kombination med metformin (500 mg eller 1. 000 mg to gange dagligt) en signifikant glykæmisk forbedring sammenlignet med monoterapi med enten det ene eller det andet.
In a 24-week placebo-controlled factorial study of initial therapy, sitagliptin 50 mg twice daily in combination with metformin (500 mg or 1000 mg twice daily) provided significant improvements in glycaemic parameters compared with either monotherapy.
Der var ingen ændring i forhold til baseline for patienter på sitagliptin alene.
HbA1c results in placebo-controlled monotherapy and combination therapy studies*
Incidensen af hypoglykæmi var den samme på tværs af behandlingsgrupperne.
(-0.8, -0.4) -0.8‡ (-1.0, -0.6)
20 Tabel 2.
20
Placebokontrolleret
Placebo-corrected mean
baseline
Mean
gennemsnit ændring
change in HbA1c (%) at
Monoterapiundersøgelser
Study
HbA1c (%)
baseline
i HbA1c (%) i 24. uge † (95% CI)
Sitagliptin 100 mg once daily added to
Population; alle behandlede patienter (analyse med henblik på behandling) † Mindste kvadratsmetode betyder justeret mht tidligere antihyperglykæmisk behandlingsstatus og baseline - værdi. ‡ p < 0, 001 sammenlignet med placebo eller placebo + kombinationsbehandling. § HbA1c (%) i 18. uge
* All Patients Treated Population (an intention-to-treat analysis). † Least squares means adjusted for prior antihyperglycaemic therapy status and baseline value. ‡ p < 0.001 compared to placebo or placebo + combination treatment. § HbA1c (%) at week 18.
40% af patienterne havde behov for en glipiziddosis på ≤5 mg/ dag i hele undersøgelsesperioden.
In a study comparing the efficacy and safety of the addition of Januvia 100 mg once daily or glipizide (a sulphonylurea agent) in patients with inadequate glycaemic control on metformin monotherapy, sitagliptin was similar to glipizide in reducing HbA1c The mean glipizide dose used in the comparator group was 10 mg per day with approximately 40% of patients requiring a glipizide dose of ≤ 5 mg/ day throughout the study.
De patienter, der blev behandlet med sitagliptin udviste et signifikant gennemsnitligt fald i kropsvægt i forhold til baseline sammenlignet med en signifikant vægtøgning hos patientgruppen, der fik glipizid (- 1, 5 versus +1, 1 kg).
Patients treated with sitagliptin exhibited a significant mean decrease from baseline in body weight compared to a significant weight gain in patients administered glipizide (-1.5 vs. +1.1 kg).
Ca.
21 Metabolism Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway.
In vitro- data viste, at sitagliptin ikke er en hæmmer af CYP- isozymerne CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19 eller 2B6, og det inducerer ikke CYP3A4 og CYP1A2.
In vitro data showed that sitagliptin is not an inhibitor of CYP isozymes CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19 or 2B6, and is not an inducer of CYP3A4 and CYP1A2.
22 på basis af kreatinin- clearance som mild (50 til < 80 ml/ min), moderat (30 til < 50 ml/ min) og svær (< 30 ml/ min) samt patienter med ESRD i hæmodialyse.
The study included patients with renal insufficiency classified on the basis of creatinine clearance as mild (50 to < 80 ml/ min), moderate (30 to < 50 ml/ min), and severe (< 30 ml/ min), as well as patients with end-stage renal disease (ESRD) on hemodialysis.
Ældre Dosisjustering er ikke nødvendig på basis af alder.
22 Elderly No dosage adjustment is required based on age.
Nogle af disse tyder på neural toksicitet:
Transient treatment-related physical signs, some of which suggest neural toxicity, such as open-mouth breathing, salivation, white foamy emesis, ataxia, trembling, decreased activity, and/ or hunched posture were observed in dogs at exposure levels approximately 23 times the clinical exposure level.
23 Der blev ikke observeret bivirkninger i fertiliteten hos han - og hunrotter, der blev behandlet med sitagliptin før og under parringsperioden.
No adverse effects upon fertility were observed in male and female rats given sitagliptin prior to and throughout mating.
6. 5 Emballagetype og pakningsstørrelse (art og indhold)
6.5 Nature and contents of container
24 6. 6 Regler for destruktion og anden håndtering
6.6 Special precautions for disposal
Hver tablet indeholder sitagliptin phosphatmonohydrat, svarende til 100 mg sitagliptin.
Each tablet contains sitagliptin phosphate monohydrate, equivalent to 100 mg sitagliptin.
Rund, beige, filmovertrukken tablet mærket med ” 277 ” på den ene side.
Round, beige film-coated tablet with “ 277” on one side.
• til at forbedre den glykæmiske kontrol i kombination med et sulfonylurinstof, når diæt og motion plus maksimal veltoleret dosis af sulfonylurinstof alene ikke giver tilstrækkelig glykæmisk kontrol og når metformin er uhensigtsmæssig p. g. a. af kontraindikationer eller intolerance.
• to improve glycaemic control in combination with a sulphonylurea when diet and exercise plus maximal tolerated dose of a sulphonylurea alone do not provide adequate glycaemic control and when metformin is inappropriate due to contraindications or intolerance.
26 Patienter med nyreinsufficiens Til patienter med mild nyreinsufficiens (kreatinin- clearance [CrCl] ≥50 ml/ min, er dosisjustering for Januvia ikke nødvendig.
26 Patients with renal insufficiency For patients with mild renal insufficiency (creatinine clearance [CrCl] ≥ 50 ml/ min), no dosage adjustment for Januvia is required.
Der er begrænsede sikkerhedsdata for patienter ≥75 år, og der bær udvises forsigtighed i denne aldersklasse.
Limited safety data is available in patients ≥ 75 years of age and care should be exercised.
Her var hyppigheden for hypoglykæmi, der er rapporteret for de patienter, der fik sitagliptindet samme som hos de patienter, der fik placebo.
Hypoglycaemia when used in combination with other anti-hyperglycaemic agents In clinical trials of Januvia as monotherapy and as part of combination therapy with agents not known to cause hypoglycaemia (i. e. metformin or pioglitazone), rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo.
27 Metformin:
27 Metformin:
28
28 4.7 Effects on ability to drive and use machines
1 I denne placebo- komtrollerede 24- ugers undersøgelse af sitagliptin 100 mg én gang dagligt i kombinationmed metformin var incidencen af formodede bivirkninger 9, 3% hos de patienter, der blev behandlet med sitagliptin/ metformin sammenlignet med 10, 1% hos de patienter, der fik placebo/ metformin.
29 1 In this placebo-controlled 24-week study of sitagliptin 100 mg once daily in combination with metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ metformin compared to treatment with placebo/ metformin was 9.3% and 10.1%, respectively.
29 I en supplerende 1- års undersøgelse af sitagliptin 100 mg én gang dagligt i kombination med metformin var incidensen af formodede bivirkninger hos de patienter, der blev behandlet med sitagliptin/ metformin sammenlignet med de patienter, der fik et sulfonylurinstof/ metformin henholdsvis 14, 5% og 30, 3%.
In an additional 1-year study of sitagliptin 100 mg once daily in combination with metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ metformin compared to sulphonylurea/ metformin was 14.5% and 30.3%, respectively.
3 I denne 24- ugers undersøgelse af sitagliptin 100 mg én gang dagligt i kombination med glimepirid og metformin, var bivirkningsincidensen, som blev anset for lægemiddelrelateret, henholdsvis 18, 1% og 7, 1% hos de patienter, der blev behandlet med sitagliptin i kombination med glimepirid/ metformin sammenlignet med patienterne, der blev behandlet med placebo i kombination med glimepirid/ metformin.
3 In this 24-week study of sitagliptin 100 mg once daily in combination with glimepiride and metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin in combination with glimepiride/ metformin compared to treatment with placebo in combination with glimepiride/ metformin was 18.1% and 7.1%, respectively.
4 I en 24- ugers undersøgelse af sitagliptin 100 mg i kombination med pioglitazon var incidensen af formodede bivirkninger hos de patienter, der blev behandlet med sitagliptin/ pioglitazon sammenlignet med patienterne, der blev behandlet med placebo/ pioglitazon henholdsvis 9, 1% og 9, 0%.
4 In this 24-week study of the combination of sitagliptin 100 mg once daily and pioglitazone, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ pioglitazone compared to patients treated with placebo/ pioglitazone was 9.1% and 9.0%, respectively.
Der blev ikke observeret klinisk relevante ændringer i vitale tegn eller i EKG (inklusive i QTc - intervallet) ved behandling med Januvia.
30 No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed with Januvia treatment.
30 Efter markedsføring:
Post-marketing Experience:
Januvia tilhører en klasse af orale anti- hyperglykæmiske lægemidler, der kaldes dipeptidylpeptidase - hæmmere.
Januvia is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors.
Ved at øge de aktive inkretinniveauer øger sitagliptin insulinfrigørelsen og reducerer glucagonniveauer afhængigt af glucosekoncentrationerne.
By enhancing active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in a glucose- dependent manner.
Sitagliptins glucoseafhængige mekanisme er forskellig fra sulfonylurinstoffers mekanisme, som øger insulinsekretionen, selv når glucosekoncentrationerne er lave og kan føre til hypoglykæmi hos patienter med type 2- diabetes og hos normale forsøgspersoner.
Sitagliptin is a potent and
Sitagliptin er en potent og høj- selektiv hæmmer af enzymet DPP- 4 og hæmmer ikke de nært beslægtede enzymer DPP- 8 eller DPP- 9 ved terapeutiske koncentrationer.
31 highly selective inhibitor of the enzyme DPP-4 and does not inhibit the closely-related enzymes DPP-8 or DPP-9 at therapeutic concentrations.
31 Målt som klinisk relevante reduktioner i HbA1c i forhold til baseline ved study endpoint (se Tabel 2) forbedrer sitagliptin totalt set den glykæmiske kontrol, når det gives som monoterapi, i kombination med metformin (initialt eller som tillægsterapi), i kombination med sulfonylurinstof (med eller uden metformin) og i kombination med et glitazon.
Overall, sitagliptin improved glycaemic control when given as monotherapy, when used in combination with metformin (initial or add-on therapy), in combination with a sulphonylurea (with or without metformin), and in combination with a thiazolidinedione, as measured by clinically relevant reductions in HbA1c from baseline at study endpoint (see Table 2).