natgillin/translations-raw huggingface dataset:
Laktacidose Laktacidose er en meget sjælden, men alvorlig metabolisk komplikation (høj mortalitet uden hurtig behandling), som kan opstå på grund af metforminophobning.
Lactic acidosis Lactic acidosis is a very rare, but serious (high mortality in the absence of prompt treatment), metabolic complication that can occur due to metformin accumulation.
De rapporterede tilfælde af laktacidose
Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure.
Forekomst af laktacidose kan og bør reduceres ved også at vurdere andre associerede risikofaktorer såsom dårligt kontrolleret diabetes, ketose, langvarig faste, meget stort indtag af alkohol, leverinsufficiens samt tilstande associeret med hypoxi.
3 risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any conditions associated with hypoxia.
Diagnose Laktacidose er karakteriseret ved acidotisk dyspnø, mavesmerter og hypotermi efterfulgt af koma.
Diagnosis Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain and hypothermia followed by coma.
Diagnostiske laboratoriefund viser nedsat pH i blodet, koncentration af plasmalaktat over 5 mmol/ l og øget anion- gap samt laktat/ pyruvatratio.
Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/ l, and an increased anion gap and lactate/ pyruvate ratio.
4. 9).
If metabolic acidosis is suspected, treatment with the medicinal product should be discontinued and the patient hospitalised immediately (see section 4.9).
Nyrefunktionen Metformin og sitagliptin udskilles hovedsageligt via nyrerne.
Renal function Metformin and sitagliptin are known to be substantially excreted by the kidney.
Derfor bør koncentrationen af serumkreatinin bestemmes regelmæssigt:
Metformin-related lactic acidosis increases with the degree of impairment of renal function, therefore, serum creatinine concentrations should be determined regularly:
- Mindst én gang årligt hos patienter med normal nyrefunktion.
- at least once a year in patients with normal renal function
- Mindst 2- 4 gange årligt hos patienter med koncentration af serumkreatinin ≥ øvre
- at least two to four times a year in patients with serum creatinine levels at or above the upper
normalgrænse og hos ældre patienter.
limit of normal and in elderly patients.
Der bør udvises særlig forsigtighed i situationer, hvor nyrefunktionen kan svækkes, f. eks. ved initiering af antihypertensiv eller diuretikabehandling, eller når behandling med et nonsteroid antiinflammatorisk stof (NSAID) påbegyndes.
Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive or diuretic therapy or when starting treatment with a nonsteroidal anti-inflammatory drug (NSAID).
Hypoglykæmi Patienter, der får Efficib sammen med et sulfonylurinstof, har øget risiko for at få hypoglykæmi.
Hypoglycaemia Patients receiving Efficib in combination with a sulphonylurea may be at risk for hypoglycaemia.
Derfor kan det være nødvendigt at reducere dosis af sulfonylurinstoffet.
Therefore, a reduction in the dose of the sulphonylurea may be necessary.
Anvendelse af Efficib sammen med insulin er ikke blevet tilstrækkeligt undersøgt.
The use of Efficib in combination with insulin has not been adequately studied.
Hypersensitivitetsreaktioner Efter markedsføring er der blevet rapporteret om alvorlige hypersensitivitetsreaktioner hos patienter, der er blevet behandlet med sitagliptin.
Hypersensitivity reactions Postmarketing reports of serious hypersensitivity reactions in patients treated with sitagliptin have been reported.
Disse reaktioner omfatter anafylaksi, angioødem og eksfoliative hudsygdomme, herunder Stevens- Johnsons syndrom.
These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome.
4. 8).
If a hypersensitivity reaction is suspected, discontinue Efficib, assess for other potential causes of the event, and institute alternative treatment for diabetes (see section 4.8).
Operation Da Efficib indeholder metforminhydrochlorid, bør behandlingen seponeres 48 timer før elektiv operation med generel, spinal eller epidural anæstesi.
Surgery As Efficib contains metformin hydrochloride, the treatment should be discontinued 48 hours before elective surgery with general, spinal or epidural anaesthesia.
Behandling med Efficib bør sædvanligvis ikke genoptages tidligere end 48 timer herefter og kun efter, at nyrefunktionen er blevet revurderet og fundet normal.
Efficib should not usually be resumed earlier than 48 hours afterwards and only after renal function has been re-evaluated and found to be normal.
Administration af jodholdigt kontraststof Intravaskulær administration af jodholdige kontraststoffer i forbindelse med radiologiske undersøgelser kan føre til nyresvigt, som er blevet associeret med laktacidose hos patienter, der får metformin.
Administration of iodinated contrast agent The intravascular administration of iodinated contrast agents in radiological studies can lead to renal failure which has been associated with lactic acidosis in patients receiving metformin.
4. 5).
Therefore, Efficib should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal (see section 4.5).
Ændring i klinisk status hos patienter med tidligere velbehandlet type 2- diabetes En patient med type 2- diabetes, der tidligere var velbehandlet på Efficib, og som udvikler unormale laboratorieværdier eller klinisk sygdom (især vagt eller uklart defineret sygdom) bør vurderes hurtigt med henblik på tegn på ketoacidose eller laktacidose.
4 Change in clinical status of patients with previously controlled type 2 diabetes A patient with type 2 diabetes previously well controlled on Efficib who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness) should be evaluated promptly for evidence of ketoacidosis or lactic acidosis.
Vurderingen bør inkludere måling af serumelektrolytter og ketoner, blodglucose og, hvis indiceret, blod- pH, laktat, pyruvat og
Evaluation should include serum electrolytes and ketones, blood glucose and, if indicated, blood pH, lactate, pyruvate, and metformin levels.
Hvis acidose i en eller anden form forekommer, skal Efficib stoppes omgående, og andre hensigtsmæssige og korrigerende handlinger initieres.
If acidosis of either form occurs, Efficib must be stopped immediately and other appropriate corrective measures initiated.
Samtidig administration af multiple doser af sitagliptin (50 mg to gange dagligt) og metformin (1. 000 mg to gange dagligt) ændrede ikke hverken sitagliptins eller metformins farmakokinetik betydeligt hos patienter med type 2- diabetes.
Co-administration of multiple doses of sitagliptin (50 mg twice daily) and metformin (1,000 mg twice daily) did not meaningfully alter the pharmacokinetics of either sitagliptin or metformin in patients with type 2 diabetes.
Der er ikke udført farmakokinetiske interaktionsundersøgelser med Efficib, men sådanne undersøgelser er udført med de enkelte aktive stoffer i Efficib, sitagliptin og metformin.
Pharmacokinetic drug interaction studies with Efficib have not been performed; however, such studies have been conducted with the individual active substances of Efficib, sitagliptin and metformin.
Der er øget risiko for laktacidose ved akut alkoholforgiftning (især i tilfælde af faste, dårlig ernæringstilstand eller leverinsufficiens) på grund af den aktive metforminsubstans i Efficib (se pkt.
There is increased risk of lactic acidosis in acute alcohol intoxication (particularly in the case of fasting, malnutrition or hepatic insufficiency) due to the metformin active substance of Efficib (see section 4.4).
Kationstoffer, som elimineres ved renal tubulær udskillelse (f. eks. cimetidin), kan interagere med metformin ved at konkurrere om det fælles renale tubulære transportsystem.
Cationic agents that are eliminated by renal tubular secretion (e. g., cimetidine) may interact with metformin by competing for common renal tubular transport systems.
En undersøgelse, der blev udført med 7 normale raske forsøgspersoner, viste at cimetidin, når det blev administreret som 400 mg to gange dagligt, øgede metformins systemiske eksponering (AUC) med 50% og Cmax med 81%.
A study conducted in seven normal healthy volunteers showed that cimetidine, administered as 400 mg twice daily, increased metformin systemic exposure (AUC) by 50% and Cmax by 81%.
Derfor bør tæt monitorering af den glykæmiske kontrol, dosisjustering inden for det anbefalede doseringsområde samt ændringer i diabetesbehandlingen overvejes, når kationstoffer, som elimineres via renal tubulær udskillelse, administreres samtidigt.
Therefore, close monitoring of glycaemic control, dose adjustment within the recommended posology and changes in diabetic treatment should be considered when cationic agents that are eliminated by renal tubular secretion are co-administered.
4. 4).
Therefore, Efficib should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal (see section 4.4).
Kombinationsbehandling, der kræver forholdsregler før anvendelse Glucokortikoider (givet systemisk og lokalt), beta- 2- agonister og diuretika har en selvstændig hyperglykæmisk virkning.
Combination requiring precautions for use Glucocorticoids (given by systemic and local routes) beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity.
ACE- hæmmere sænker blodglucoseniveauet.
ACE-inhibitors may decrease the blood glucose levels.
Andre lægemidlers indvirkning på sitagliptin De kliniske data, som er beskrevet nedenfor, tyder på, at risikoen for interaktioner af klinisk betydning mellem lægemidler, der administreres samtidigt, er lav.
Effects of other medicinal products on sitagliptin Clinical data described below suggest that the risk for clinically meaningful interactions following co- administration of other medicinal products is low.
Ciclosporin:
Cyclosporine:
Der er udført en undersøgelse til vurdering af ciclosporins (en potent hæmmer af p - glykoprotein) effekt på sitagliptins farmakokinetik.
A study was conducted to assess the effect of cyclosporine, a potent inhibitor of p-glycoprotein, on the pharmacokinetics of sitagliptin.
29% og 68%.
Co-administration of a single 100 mg oral dose of sitagliptin and a single 600 mg oral dose of cyclosporine increased the AUC and Cmax of sitagliptin by approximately 29% and 68%, respectively.
Der forventes derfor ingen betydende interaktioner med andre p- glykoproteinhæmmere.
Therefore, meaningful interactions would not be expected with other p-glycoprotein inhibitors.
In vitro- undersøgelser tyder på, at CYP3A4 primært er ansvarlig for sitagliptins begrænsede metabolisme, og at CYP2C8 medvirker hertil.
5 In vitro studies indicated that the primary enzyme responsible for the limited metabolism of sitagliptin is CYP3A4, with contribution from CYP2C8.
Hos patienter med normal nyrefunktion spiller metabolisme, inklusive metabolismen via CYP3A4, kun en lille rolle i sitagliptin- clearance.
In patients with normal renal function, metabolism, including via CYP3A4, plays only a small role in the clearance of sitagliptin.
Metabolisme kan derimod spille en mere betydningsfuld rolle ved eliminationen af sitagliptin ved svær nyreinsufficiens eller ESRD.
Metabolism may play a more significant role in the elimination of sitagliptin in the setting of severe renal insufficiency or ESRD.
5 itraconazol, ritonavir, clarithromycin) muligvis ændre sitagliptins farmakokinetik hos patienter med svær nyreinsufficiens eller ESRD.
For this reason, it is possible that potent CYP3A4 inhibitors (i. e., ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the phamacokinetics of sitagliptin in patients with severe renal insufficiency or ESRD.
Virkningen af potente CYP3A4- hæmmere ved nyreinsufficiens er ikke vurderet i en klinisk undersøgelse.
The effects of potent CYP3A4 inhibitors in the setting of renal insufficiency has not been assessed in a clinical study.
In vitro- transportundersøgelser har vist, at sitagliptin er et substrat for p- glycoprotein og OAT3.
In vitro transport studies showed that sitagliptin is a substrate for p-glycoprotein and OAT3.
OAT3- medieret transport af sitagliptin hæmmes in vitro af probenecid, selvom risikoen for klinisk relevante interaktioner anses for at være lav.
OAT3 mediated transport of sitagliptin was inhibited in vitro by probenecid, although the risk of clinically meaningful interactions is considered to be low.
Samtidig administration af OAT3- hæmmere er ikke vurderet in vivo.
Concomitant administration of OAT3 inhibitors has not been evaluated in vivo.
Sitagliptins indvirkning på andre lægemidler In vitro- data tyder på, at sitagliptin hverken hæmmer eller inducerer CYP450- isoenzymer.
Effects of sitagliptin on other medicinal products In vitro data suggest that sitagliptin does not inhibit nor induce CYP450 isoenzymes.
Dette giver in vivo evidens for lav tilbøjelighed til at forårsage interaktion med substrater for CYP3A4, CYP2C8, CYP2C9 og organisk kationtransportør (OCT).
In clinical studies, sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptives, providing in vivo evidence of a low propensity for causing interactions with substrates of CYP3A4, CYP2C8, CYP2C9, and organic cationic transporter (OCT).
Sitagliptin havde en lille effekt på digoxinkoncentrationen i plasma og kan være en mild hæmmer af p- glykoprotein in vivo.
Sitagliptin had a small effect on plasma digoxin concentrations, and may be a mild inhibitor of p-glycoprotein in vivo.
Sitagliptin havde en lille effekt på digoxinkoncentrationen i plasma.
Sitagliptin had a small effect on plasma digoxin concentrations.
Efter administration af 0, 25 mg digoxin samtidig med 100 mg sitagliptin dagligt i 10 dage øgedes plasma AUC for digoxin gennemsnitligt med 11% og plasma Cmax med gennemsnitligt 18%.
Following administration of 0.25 mg digoxin concomitantly with 100 mg of sitagliptin daily for 10 days, the plasma AUC of digoxin was increased on average by 11%, and the plasma Cmax on average by 18%.
Der er ikke tilstrækkelig dokumentation for anvendelse af sitagliptin til gravide.
There are no adequate data from the use of sitagliptin in pregnant women.
5. 3).
Studies in animals have shown reproductive toxicity at high doses of sitagliptin (see section 5.3).
5. 3).
Animal studies with metformin do not indicate harmful effects with respect to pregnancy, embryonic or foetal development, parturition or postnatal development (see also section 5.3).
Hvis en patient ønsker at blive gravid eller bliver gravid, bør behandling med Efficib seponeres, og der bør skiftes til insulinbehandling så snart som muligt.
If a patient wishes to become pregnant or if a pregnancy occurs, treatment with Efficib should be discontinued and switched to insulin treatment as soon as possible.
Der er ikke udført undersøgelser på diegivende dyr med de kombinerede aktive stoffer i Efficib.
No studies in lactating animals have been conducted with the combined active substances of Efficib.
Metformin udskilles i små mængder i modermælk hos mennesker.
Metformin is excreted in human milk in small amounts.
4. 3).
Efficib must therefore not be used in women who are breast-feeding (see section 4.3).
Der er ikke foretaget undersøgelser af virkningen af Efficib på evnen til at føre motorkøretøj eller betjene maskiner.
No studies on the effects on the ability to drive and use machines have been performed with Efficib.
Ved bilkørsel og betjening af maskiner bør der dog tages hensyn til, at svimmelhed og søvnighed er rapporteret med sitagliptin.
However, when driving or operating machines, it should be taken into account that dizziness and somnolence have been reported with sitagliptin.
Desuden bør patienter advares om risikoen for hypoglykæmi, når Efficib anvendes sammen med andre sulfonylurinstoffer.
In addition, patients should be alerted to the risk of hypoglycaemia when Efficib is used in combination with other sulfonylurea agents.
4. 8 Bivirkninger
6 4.8 Undesirable effects
5. 2).
There have been no therapeutic clinical trials conducted with Efficib tablets however bioequivalence of Efficib with co-administered sitagliptin and metformin has been demonstrated (see section 5.2).
Frekvenserne defineres som:
Sitagliptin and metformin Adverse reactions considered as drug related reported in excess (> 0.2% and difference > 1 patient) of placebo and in patients receiving sitagliptin in combination with metformin in double-blind studies are listed below as MedDRA preferred term by system organ class and absolute frequency (Table 1).
Meget almindelig (≥1/ 10); almindelig (≥1/ 100, < 1/ 10); ikke almindelig (≥1/ 1. 000, < 1/ 100); sjælden (≥1/ 10. 000, < 1/ 1. 000); meget sjælden (< 1/ 10. 000).
Frequencies are defined as: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000).
Bivirkningsfrekvens identificeret i placebokontrollerede kliniske undersøgelser
The frequency of adverse reactions identified from placebo-controlled clinical studies
Bivirkningsfrekvens i henhold til behandlingsregime
Frequency of adverse reaction by treatment regimen
Sitagliptin sammen med metformin1
Sitagliptin with Metformin1
Sitagliptin sammen med metformin og et sulfonylurinstof2
Sitagliptin with Metformin and a Sulphonylurea2
Nedsat blodglucose
blood glucose decreased
Nervesystemet
Nervous system disorders somnolence
Somnolens
Uncommon
Ikke almindelig
Gastrointestinal disorders
Mave- tarmkanalen
diarrhoea nausea constipation upper abdominal pain
Ikke almindelig Almindelig Ikke almindelig
Uncommon Common Uncommon
Metabolisme og ernæring
Metabolism and nutrition disorders hypoglycaemia* *
kombinationsbehandling med metformin var frekvensen af hypoglykæmi, der blev rapporteret for sitagliptin, den samme som for de patienter, der fik placebo.
In clinical trials of sitagliptin as monotherapy and sitagliptin as part of combination therapy with metformin, 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.
1 In this placebo-controlled 24-week study of sitagliptin 100 mg once daily added to ongoing metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin added to ongoing metformin compared to treatment with placebo added to ongoing metformin was 9.3% and 10.1%, respectively.
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 added to ongoing metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin added to ongoing metformin compared to sulphonylurea added to ongoing 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 added to ongoing metformin to a sulphonylurea agent added to ongoing 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).
2 I denne 24- ugers placebokontrollerede undersøgelse af sitagliptin 100 mg én gang dagligt sammen med kombinationsbehandling med glimepirid og metformin var den bivirkningsincidens, som blev anset for at være lægemiddelrelateret, 18, 1% hos de patienter, der blev behandlet med glimepirid og metformin.
2 In this 24-week placebo-controlled study of sitagliptin 100 mg once daily added to ongoing combination treatment with glimepiride and metformin, the overall incidence of adverse reactions considered as drug-related in patients treated with the addition of sitagliptin to the ongoing treatment
Til sammenligning var bivirkningsincidensen 7, 1% hos de patienter, der blev behandlet med placebo og glimepirid/ metformin.
7 with glimepiride and metformin was 18.1% compared to treatment with the addition of placebo to the ongoing treatment with glimepiride and metformin which was 7.1%.
I en 24- ugers undersøgelse af initial kombinationsbehandling med sitagliptin og metformin to gange dagligt (sitagliptin/ metformin 50 mg/ 500 mg eller 50 mg/ 1. 000 mg) var den totale
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/ 1,000 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.
De forskelle, der relaterede til sitagliptin alene, skyldtes primært gastrointestinale bivirkninger.
The overall incidence of adverse reactions considered as drug-related in patients treated with the combination of sitagliptin and metformin was comparable to metformin alone (14.0% each) and greater than sitagliptin alone (6.7%), with the differences relative to sitagliptin alone primarily due to gastrointestinal adverse reactions.
Hovedpine, hypoglykæmi, obstipation og svimmelhed.
Additional information on the individual active substances of the fixed dose combination Sitagliptin 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 reactions described above, adverse events (reported regardless of causal relationship to medicinal product) occurring in at least 5% and more commonly in patients treated with sitagliptin included upper respiratory tract infection and nasopharyngitis.
Yderligere hændelser, som forekom hyppigere hos de patienter, der blev behandlet med sitagliptin (uden at nå 5% niveauet, men med en incidens > 0, 5%, der er højere i sitagliptin - end i kontrolgruppen) omfatter osteoartritis og smerter i ekstremiteterne.
Additional adverse events that occurred more frequently in patients treated with sitagliptin (not reaching the 5% level, but occurring with an incidence of > 0.5% higher with sitagliptin than that in the control group) included osteoarthritis and pain in extremity.
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 (WBC) count (approximately 200 cells/ microl difference in WBC vs placebo; mean baseline WBC approximately 6,600 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.
Ændringen i disse laboratorieparametre anses ikke for at være klinisk relevant.
This change in laboratory parameters is not considered to be clinically relevant.