natgillin/translations-raw huggingface dataset:
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- kontrollerede 24- ugers- undersøgelse af sitagliptin 100 mg én gang dagligt i kombination med metformin var incidensen 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.
5 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.
5 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.
Anorexi (Metabolisme og ernæring; hyppighed: ikke almindelig) og nedsat kropsvægt (Undersøgelser; hyppighed: ikke almindelig).
In pooled studies of up to 1 year in duration comparing sitagliptin/ metformin to a sulphonylurea agent/ metformin, adverse reactions considered as drug-related reported in patients treated with sitagliptin 100 mg occurring in excess (> 0.2% and difference > 1 patient) of that in patients receiving the sulphonylurea agent are as follows: anorexia (Metabolism and nutritional disorders; frequency uncommon) and weight decreased (Investigations; frequency uncommon).
Til sammenligning var bivirkningsincidensen 6, 6% hos de patienter, der blev behandlet med placebo/ glimepirid.
2 In this 24-week study of sitagliptin 100 mg once daily in combination with glimepiride, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ glimepiride compared to treatment with placebo/ glimepiride was 11.3% and 6.6%, 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 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 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.
Hovedpine, hypoglykæmi, obstipation og svimmelhed.
In addition, in monotherapy studies of up to 24 weeks in duration of sitagliptin 100 mg once daily alone compared to placebo, adverse reactions considered as drug-related reported in patients treated with sitagliptin in excess (> 0.2% and difference > 1 patient) of that in patients receiving placebo are headache, hypoglycaemia, constipation, and dizziness.
Disse hændelser inkluderede infektion i øvre luftveje og nasopharyngitis.
In addition to the drug-related adverse experiences described above, adverse experiences reported regardless of causal relationship to medication and occurring in at least 5% and more commonly in patients treated with Januvia included upper respiratory tract infection and nasopharyngitis.
Yderligere hændelser, der er rapporteret uden kendt årsagssammenhæng med medicinen, og som forekom hyppigere hos de patienter, der blev behandlet med Januvia (uden at nå 5% niveauet, men med en incidens > 0, 5%, der er højere i Januvia - end i kontrolgruppen) omfatter osteoartrose og smerter i ekstremiteterne.
Additional adverse experiences reported regardless of causal relationship to medication that occurred more frequently in patients treated with Januvia (not reaching the 5% level, but occurring with an incidence of > 0.5% higher with Januvia than that in the control group) included osteoarthritis and pain in extremity.
I en 24- ugers undersøgelse af den initiale kombinationsbehandling med sitagliptin og metformin to gange dagligt (sitagliptin/ metformin 50 mg/ 500 mg eller 50 mg/ 1. 000 mg) var den totale bivirkningsincidens, som blev anset for at være lægemiddelrelateret, henholdsvis 14, 0% og 9, 7% hos de patienter, der blev behandlet med kombinationen af sitagliptin og metformin sammenlignet med de patienter, der fik placebo.
In a 24-week study of initial combination therapy with sitagliptin and metformin administered twice daily (sitagliptin/ metformin 50 mg/ 500 mg or 50 mg/ 1000 mg), the overall incidence of adverse reactions considered as drug-related in patients treated with the combination of sitagliptin and metformin compared to patients treated with placebo was 14.0% and 9.7%, respectively.
6. 600 blodlegemer/ µl hvide blodlegemer ved baseline, hvilket skyldes en øget mængde neutrofile leukocytter.
Across clinical studies, a small increase in white blood cell count (approximately 200 cells/ microl difference in WBC vs. placebo; mean baseline WBC approximately 6600 cells/ microl) was observed due to an increase in neutrophils.
Dette blev observeret i de fleste - men ikke i alle - undersøgelser.
This observation was seen in most but not all studies.
6 Der blev ikke observeret klinisk relevante ændringer i vitale tegn eller i EKG (inklusive i QTc - intervallet) ved behandling med Januvia.
6 No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed with Januvia treatment.
Efter markedsføring:
Post-marketing Experience:
4. 4).
During post-marketing experience the following additional side effects have been reported (frequency not known): hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, and exfoliative skin conditions including Stevens-Johnson syndrome (see section 4.4).
13, 5% af dosis fjernet i løbet af en hæmodialysesession på 3- 4 timer.
In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour hemodialysis session.
Forlænget dialyse kan overvejes, hvis det er klinisk hensigtsmæssigt.
Prolonged hemodialysis may be considered if clinically appropriate.
DPP- 4- hæmmer, ATC- kode:
DPP-4 Inhibitor, ATC code:
Januvia tilhører en klasse af orale anti- hyperglykæmiske lægemidler, der kaldes dipeptidylpeptidase- 4 - hæmmere.
Januvia is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors.
Den forbedring i den glykæmiske kontrol, som blev observeret med dette lægemiddel, medieres via en stigning i de aktive inkretinhormoners niveauer.
The improvement in glycaemic control observed with this agent may be mediated by enhancing the levels of active incretin hormones.
Inkretinhormoner, inklusive glucagonlignende peptid 1 (GLP- 1) og glucoseafhængigt insulinotropt polypeptid (GIP), frigives i tarmene i løbet af dagen, og niveauerne øges som reaktion på et måltid.
Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal.
Når blodglucosekoncentrationen er normal eller forhøjet, bevirker GLP- 1 og GIP en øget insulinsyntese og frigørelsen af insulin fra de pankreatiske betaceller via intracellulære signalleringsveje, som inddrager cyklisk AMP.
When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP.
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.
Desuden sænker GLP- 1 glucagonsekretionen fra pankreatiske alfaceller.
In addition, GLP-1 lowers glucagon secretion from pancreatic alpha cells.
Effekten af GLP- 1 og GIP er glucoseafhængig, således at når blodglucosekoncentrationen er lav, ses der ikke en stimulering af insulinfrigørelse og hæmning af glucagonsekretion af GLP- 1.
The effects of GLP-1 and GIP are glucose-dependent such that when blood glucose concentrations are low, stimulation of insulin release and suppression of glucagon secretion by GLP-1 are not observed.
GLP- 1 og GIP øges insulinstimulationen, når glucose stiger over de normale koncentrationer.
For both GLP-1 and GIP, stimulation of insulin release is enhanced as glucose rises above normal concentrations.
Desuden nedsætter GLP- 1 ikke det normale glucagonrespons på hypoglykæmi.
Further, GLP-1 does not impair the normal glucagon response to hypoglycaemia.
Aktiviteten af GLP- 1 og GIP begrænses af DPP- 4- enzymet, som hurtigt hydrolyserer inkretinhormonerne til inaktive produkter.
The activity of GLP-1 and GIP is limited by the DPP-4 enzyme, which rapidly hydrolyzes the incretin hormones to produce inactive products.
Sitagliptin forhindrer DPP- 4s hydrolyse af inkretinhormoner, og øger dermed plasmakoncentrationerne af de aktive former af GLP- 1 og GIP.
Sitagliptin prevents the hydrolysis of incretin hormones by DPP-4, thereby increasing plasma concentrations of the active forms of GLP-1 and GIP.
Ved at øge de aktive inkretinniveauer øger sitagliptin insulinfrigørelsen og reducerer glucagonniveauet afhængigt af glucosekoncentrationen.
By enhancing active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in a glucose- dependent manner.
Hos patienter med type 2- diabetes med hyperglykæmi fører disse ændringer i insulin - og glucagonniveauer til lavere hæmoglobin A1c (HbA1c) samt lavere koncentration af faste plasmaglucose (FPG) og postprandial glucose (PPG).
In patients with type 2 diabetes with hyperglycaemia, these changes in insulin and glucagon levels lead to lower hemoglobin A1c (HbA1c) and lower fasting and postprandial glucose concentrations.
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.
The glucose-dependent mechanism of sitagliptin is distinct from the mechanism of sulphonylureas, which increase insulin secretion even when glucose levels are low and can lead to hypoglycaemia in patients with type 2 diabetes and in normal subjects.
Sitagliptin er en potent og høj- selektiv
Sitagliptin is a potent and
7 hæmmer af enzymet DPP- 4 og hæmmer ikke de nært beslægtede enzymer DPP- 8 eller DPP- 9 ved terapeutiske koncentrationer.
7 highly selective inhibitor of the enzyme DPP-4 and does not inhibit the closely-related enzymes DPP-8 or DPP-9 at therapeutic concentrations.
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).
Der er udført to undersøgelser, der vurderede effekt og sikkerhed af Januvia- monoterapi.
Two studies were conducted to evaluate the efficacy and safety of Januvia monotherapy.
Sammenlignet med placebo gav behandling med sitagliptin 100 mg én gang dagligt som monoterapi signifikante forbedringer i HbA1c, i faste- plasma 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.
Forbedring af surrogatmarkører for betacellefunktionen, inklusive HOMA- β (Homøostatisk modelvurdering- β), proinsulin/ insulin ratio samt resultater fra en frequently sampled meal tolerance test blev observeret.
Improvement of surrogate markers of beta cell function, including HOMA-β (Homeostasis Model Assessment-β), proinsulin to insulin ratio, and measures of beta cell responsiveness from the frequently-sampled meal tolerance test were observed.
Den observerede incidens af hypoglykæmi hos de patienter, der blev behandlet med Januvia var den samme som for placebo.
The observed incidence of hypoglycaemia in patients treated with Januvia was similar to placebo.
I en undersøgelse af patienter med type 2- diabetes og kronisk nyreinsufficiens (kreatinin- clearance < 50 ml/ min) blev sikkerheden og tolerancen for reducerede doser af sitagliptin undersøgt og var generelt den samme som for placebo.
In a study in patients with type 2 diabetes and chronic renal insufficiency (creatinine clearance < 50 ml/ min), the safety and tolerability of reduced doses of sitagliptin were investigated and generally similar to placebo.
5. 2).
In addition, the reductions in HbA1c and FPG with sitagliptin compared to placebo were generally similar to those observed in other monotherapy studies in patients with normal renal function (see section 5.2).
Antallet af patienter med moderat til svær nyreinsufficiens var for lavt til at bekræfte, at det er sikkert at anvende sitagliptin til denne type patienter.
The number of patients with moderate to severe renal insufficiency was too low to confirm safe use of sitagliptin in this type of patients.
I to 24- ugers undersøgelser gav sitagliptin én gang dagligt som supplerende behandling, den ene i kombination med metformin og den anden med pioglitazon, en signifikant glykæmisk forbedring, sammenlignet med placebo.
Sitagliptin 100 mg once daily provided significant improvements in glycaemic parameters compared with placebo in two 24-week studies of sitagliptin as add-on therapy, one in combination with metformin and one in combination with pioglitazone.
En 24- ugers placebo- kontrolleret undersøgelse blev designet til at evaluere effekten samt sikkerheden af sitagliptin (100 mg en gang dagligt) som supplement til glimepirid alene eller glimepirid i kombination med metformin.
A 24-week placebo-controlled study was designed to evaluate the efficacy and safety of sitagliptin (100 mg once daily) added to glimepiride alone or glimepiride in combination with metformin.
I en 24- ugers placebokontrolleret faktoriel undersøgelse af initialbehandling 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.
The decrease in body weight with the combination of sitagliptin and metformin was similar to that observed with metformin alone or placebo; there was no change from baseline for patients on sitagliptin alone.
HbA1c resultater i placebo- kontrollerede monoterapi- og kombinationsterapi - undersøgelser *
HbA1c results in placebo-controlled monotherapy and combination therapy studies*
Undersøgelse
Placebo-corrected mean
Gennemsnitlig Gennemsnitlig
Mean change from
Placebokontrolleret
change in HbA1c (%) at
gennemsnitlig ændring
HbA1c (%)
Monoterapiundersøgelser
Sitagliptin 100 mg once daily§
i 24. uge †
Week 24†
(%) i 24. uge † (95% CI)
Sitagliptin 100 mg once daily added to
8, 0 8, 0
HbA1c (%)
- 0, 5 - 0, 6
at Week 24†
- 0, 6 ‡ (- 0, 8; - 0, 4) - 0, 8 ‡ (- 1, 0; - 0, 6) - 0, 7 ‡
(95% CI) -0.7‡
som supplement til metforminbehandling (N=453) Sitagliptin 100 mg én gang dagligt
ongoing metformin therapy (N=453) Sitagliptin 100 mg once daily added to
(- 0, 8; - 0, 5) - 0, 7 ‡
(-0.8, -0.5) -0.7‡
som supplement til pioglitazonbehandling (N=163) Sitagliptin 100 mg én gang dagligt
ongoing pioglitazone therapy (N=163) Sitagliptin 100 mg once daily added to
(- 0, 9; - 0, 5) - 0, 6 ‡
(-0.9, -0.5) -0.6‡
som supplement til glimepiridbehandling (N=102) Sitagliptin 100 mg én gang dagligt
ongoing glimepiride therapy (N=102) Sitagliptin 100 mg once daily added to
(- 0, 8; - 0, 3)
(-0.8, -0.3)
som supplement til glimepirid + metforminbehandling (N=115) Initialbehandling (to gange dagligt):
ongoing glimepiride + metformin therapy (N=115) Initial therapy (twice daily):
- 0, 9 ‡ (- 1, 1; - 0, 7) - 1, 6 ‡
-0.9‡ (-1.1, -0.7) -1.6‡
Sitagliptin 50 mg + metformin 500 mg (N=183) Initialbehandling (to gange dagligt):
Sitagliptin 50 mg + metformin 500 mg (N=183) Initial therapy (twice daily):
(- 1, 8; - 1, 3) - 2, 1 ‡
(-1.8, -1.3)
Sitagliptin 50 mg + metformin 1000 mg (N=178) *
Sitagliptin 50 mg + metformin 1000 mg (N=178)
(- 2, 3; - 1, 8)
-2.1‡ (-2.3, -1.8)
Population; alle behandlede patienter (analyse med henblik på behandling) † Mindste kvadratsmetode 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.
I en undersøgelse af effekt og sikkerhed af tillægsbehandling med Januvia 100 mg én gang dagligt eller glipizid (et sulfonylurinstof) til patienter med utilstrækkelig glykæmisk kontrol på metforminmonoterapi, var sitagliptin sammenlignelig med glipizid mht. reduktion af HbA1c.
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.
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).
Incidensen af hypoglykæmi i gruppen, som blev behandlet med sitagliptin (4, 9%), var signifikant lavere end i glipizidgruppen (32, 0%).
The incidence of hypoglycaemia in the sitagliptin group (4.9%) was significantly lower than that in the glipizide group (32.0%).
Absorption Efter oral administration af en 100 mg dosis til raske personer absorberedes sitagliptin hurtigt, med peak- plasmakoncentrationer (median Tmax) 1- 4 timer efter dosering, gennemsnitlig plasma- AUC for sitagliptin var 8, 52 µM• hr, Cmax var 950 nM.
Absorption Following oral administration of a 100-mg dose to healthy subjects, sitagliptin was rapidly absorbed, with peak plasma concentrations (median Tmax) occurring 1 to 4 hours post-dose, mean plasma AUC of sitagliptin was 8.52 μ M• hr, Cmax was 950 nM.
Eftersom samtidig administration af et fedtrigt måltid sammen med Januvia ikke havde nogen effekt på farmakokinetikken, kan Januvia administreres med eller uden mad.
Since coadministration of a high-fat meal with Januvia had no effect on the pharmacokinetics, Januvia may be administered with or without food.
Plasma- AUC for sitagliptin øgedes proportionalt med dosis.
Plasma AUC of sitagliptin increased in a dose-proportional manner.
198 l.
Distribution The mean volume of distribution at steady state following a single 100-mg intravenous dose of sitagliptin to healthy subjects is approximately 198 liters.
Ca.
9 Metabolism Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway.
Seks metabolitter blev påvist på sporstofniveau og forventes ikke at bidrage til sitagliptins plasma DPP- 4- hæmmende aktivitet i plasma.
Six metabolites were detected at trace levels and are not expected to contribute to the plasma DPP-4 inhibitory activity of sitagliptin.
In vitro- data viste, at sitagliptin ikke er en hæmmer af CYPisozymerne 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.
100% af den administrerede radioaktivitet i fæces (13%) eller urin (87%) inden for en uge efter dosering.
Elimination Following administration of an oral [14C]sitagliptin dose to healthy subjects, approximately 100% of the administered radioactivity was eliminated in faeces (13%) or urine (87%) within one week of dosing.
Den tilsyneladende terminale halveringstid (t½) efter indgift af en 100 mg oral dosis sitagliptin var ca.
The apparent terminal t1/ 2 following a 100-mg oral dose of sitagliptin was approximately 12.4 hours.
I en klinisk undersøgelse havde sitagliptin en lille effekt på digoxinkoncentrationerne i plasma, som tyder på, at sitagliptin kan være en mild hæmmer af p- glycoprotein.
In a clinical study sitagliptin had a small effect on plasma digoxin concentrations indicating that sitagliptin may be a mild inhibitor of p-glycoprotein.
Patientkarakteristika Sitagliptins farmakokinetik var generelt den samme hos raske personer og hos patienter med type 2 - diabetes.
Characteristics in patients The pharmacokinetics of sitagliptin were generally similar in healthy subjects and in patients with type 2 diabetes.
Nyreinsufficiens I en åben undersøgelse med enkeltdosis blev farmakokinetikken for en reduceret dosis sitagliptin (50 mg) vurderet hos patienter med varierende grader af kronisk nyreinsufficiens sammenlignet med normale raske kontrolpersoner.
Renal insufficiency A single-dose, open-label study was conducted to evaluate the pharmacokinetics of a reduced dose of sitagliptin (50-mg) in patients with varying degrees of chronic renal insufficiency compared to normal healthy control subjects.