natgillin/translations-raw huggingface dataset:
Medicinsk behandling kan initieres samtidigt med diæt og motion.
Drug therapy can be initiated simultaneously with diet and exercise.
< Zocord > er effektivt alene eller kombineret med galdesyrebindende lægemidler.
< Zocord > is effective alone or in combination with bile acid sequestrants.
Dosering bør foretages enten > 2 timer før eller > 4 timer efter indgivelse af et galdesyrebindende lægemiddel.
Dosing should occur either > 2 hours before or > 4 hours after administration of a bile acid sequestrant.
Hos patienter i samtidig behandling med ciclosporin, gemfibrozil, andre fibrater (undtagen fenofibrat) eller lipidsænkende doser (≥ 1 g/ dag) af niacin samtidigt med < Zocord >, bør dosis af < Zocord > ikke overstige 10 mg/ dag.
In patients taking cyclosporine, gemfibrozil, other fibrates (except fenofibrate) or lipid-lowering doses (≥ 1 g/ day) of niacin concomitantly with< Zocord >, the dose of < Zocord > should not exceed 10 mg/day.
Hos patienter, der tager amiodaron eller verapamil samtidigt med < Zocord >, bør dosis ikke overstige 20 mg/ dag.
In patients taking amiodarone or verapamil concomitantly with< Zocord >, the dose of < Zocord > should not exceed 20 mg/day.
4. 4 og 4. 5).
(See sections 4.4 and 4.5.)
Dosering ved nyreinsufficiens
Dosage in renal insufficiency
Ændringer i dosering er som regel ikke nødvendig hos patienter med moderat nyreinsufficiens.
No modification of dosage should be necessary in patients with moderate renal insufficiency.
Hos patienter med alvorlig nyreinsufficiens (creatinin clearance < 30 ml/ min) bør doser over 10 mg/ dag overvejes omhyggeligt, og om nødvendigt initieres forsigtigt.
In patients with severe renal insufficiency (creatinine clearance < 30 ml/ min), dosages above 10 mg/ day should be carefully considered and, if deemed necessary, implemented cautiously.
Anvendelse til børn og yngre personer
Use in children and adolescents
< Zocord > bør ikke anvendes til børn, da der ikke er dokumentation for sikkerhed og effekt hos børn.
Therefore< Zocord > is not recommended for paediatric use.
4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen CPMP/ 459/ 04 Myopati/ rhabdomyolyse
CPMP/ 459/ 04 4.3 Contraindications
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Som andre HMG- CoA reduktasehæmmere, forårsager Simvastatin ind imellem myopati, der manifesterer sig som muskelsmerter, ømhed eller muskelsvaghed med kreatininkinase (CK) over ti gange den øvre normalgrænse (ULN).
Myopathy/ Rhabdomyolysis Simvastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN).
Der er i meget sjældne tilfælde set dødsfald.
Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and very rare fatalities have occurred.
Risikoen for myopati øges af høje koncentrationer af HMG- CoA reduktasehæmmeraktivitet i plasma.
The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma.
Risikoen for myopati/ rhabdomyolyse er dosisrelateret.
The risk of myopathy/ rhabdomyolysis is dose related.
Incidensen i kliniske undersøgelser, hvor patienterne blev omhyggeligt monitoreret og visse interagerende lægemidler blev udelukket, har været cirka 0, 03% ved 20 mg, 0, 08% ved 40 mg og 0, 4% ved 80 mg.
The incidence in clinical trials, in which patients were carefully monitored and some interacting medicinal products were excluded, has been approximately 0.03% at 20 mg, 0.08% at 40 mg and 0.4% at 80 mg.
Kreatininkinase måling Kreatininkinase (CK) bør ikke måles efter anstrengende motion eller ved tilstedeværelsen af eventuelle andre tilsyneladende årsager til forøgelse af CK, da dette vil vanskeliggøre værdifortolkningen.
Creatine Kinase measurement Creatine Kinase (CK) should not be measured following strenuous exercise or in the presence of any plausible alternative cause of CK increase as this makes value interpretation difficult.
Hvis CK niveauerne er signifikant forhøjede ved baseline (> 5 x ULN), bør disse niveauer kontrolleres igen senest 5- 7 dage senere for at bekræfte resultaterne.
If CK levels are significantly elevated at baseline (> 5 x ULN), levels should be re-measured within 5 to 7 days later to confirm the results.
Før behandling Når behandling med simvastatin påbegyndes, eller dosis af simvastatin øges, skal alle patienter informeres om risikoen for myopati og instrueres i straks at rapportere alle uforklarlige muskelsmerter, ømhed eller svaghed.
Before the treatment All patients starting therapy with simvastatin, or whose dose of simvastatin is being increased, should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness.
For at etablere en referenceværdi for baseline bør CK niveauet måles før behandlingsstart i følgende situationer:
In order to establish a reference baseline value, a CK level should be measured before starting a treatment in the following situations:
• Ældre (> 70 år) • Nyresvækkelse • Ukontrolleret hypothyroidisme • Personlig eller familiær historie med arvelige muskulære lidelser • Tidligere historie med muskulær toksicitet med statin eller fibrat • Alkoholmisbrug
• Elderly (age > 70 years) • Renal impairment • Uncontrolled hypothyroidism • Personal or familial history of hereditary muscular disorders • Previous history of muscular toxicity with a statin or fibrate • Alcohol abuse.
I sådanne situationer skal risikoen ved behandlingen overvejes i relation til den mulige gavn for patienten, og klinisk monitorering anbefales.
In such situations, the risk of treatment should be considered in relation to possible benefit, and clinical monitoring is recommended.
Hvis en patient tidligere har oplevet en muskellidelse på en fibrat eller en statin, bør behandling med et andet medlem af samme klasse kun initieres med forsigtighed.
If a patient has previously experienced a muscle disorder on a fibrate or a statin, treatment with a different member of the class should only be initiated with caution.
Hvis CK niveauerne er signifikant forhøjede ved baseline (> 5 x ULN), bør behandling ikke initieres.
If CK levels are significantly elevated at baseline (> 5 x ULN), treatment should not be started.
Under behandlingen Hvis muskelsmerter, svaghed eller kramper opstår mens patienten er i behandling med et statin, skal CK niveauerne måles.
Whilst on treatment If muscle pain, weakness or cramps occur whilst a patient is receiving treatment with a statin, their CK levels should be measured.
Hvis disse niveauer viser sig at være signifikant forhøjede (> 5 x ULN), uden forudgående hård motion, bør behandlingen stoppes.
If these levels are found, in the absence of strenuous exercise, to be significantly elevated (> 5 x ULN), treatment should be stopped.
Hvis de muskulære symptomer er alvorlige og dagligt forårsager ubehag, selvom CK niveauerne er < 5 x ULN, bør ophør af behandlingen overvejes.
If muscular symptoms are severe and cause daily discomfort, even if CK levels are < 5 x ULN, treatment discontinuation may be considered.
Hvis der er mistanke om myopati af andre årsager, skal behandlingen afbrydes.
If myopathy is suspected for any other reason, treatment should be discontinued.
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4. 2).
The risk of myopathy and rhabdomyolysis is significantly increased by concomitant use of simvastatin with potent inhibitors of CYP3A4 (such as itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone), as well as gemfibrozil and cyclosporine (see section 4.2)
4. 2 og 4. 5).
The risk of myopathy and rhabdomyolysis is also increased by concomitant use of other fibrates, lipid-lowering doses (≥ 1 g/ day) of niacin or by concomitant use of amiodarone or verapamil with higher doses of simvastatin (see sections 4.2 and 4.5).
Der er også en let forøget risiko, når diltiazem anvendes sammen med simvastatin 80 mg.
There is also a slight increase in risk when diltiazem is used with simvastatin 80 mg.
4. 3 og 4. 5).
Consequently, regarding CYP3A4 inhibitors, the use of simvastatin concomitantly with itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone is contraindicated (see sections 4.3 and 4.5).
Hvis behandling med itraconazol, ketoconazol, erythromycin, clarithromycin eller telithromycin ikke kan undgås, skal simvastatin afbrydes under behandlingsforløbet.
If treatment with itraconazole, ketoconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.
4. 2 og 4. 5).
Moreover, caution should be exercised when combining simvastatin with certain other less potent CYP3A4 inhibitors: cyclosporine, verapamil, diltiazem (see sections 4.2 and 4.5).
Samtidig indtagelse af grapefrugtjuice og simvastatin bør undgås.
Concomitant intake of grapefruit juice and simvastatin should be avoided.
Simvastatindosis må ikke overstige 10 mg dagligt hos patienter, der samtidigt behandles med ciclosporin, gemfibrozil eller lipidsænkende doser (≥ 1 g/ dag) af niacin.
The dose of simvastatin should not exceed 10 mg daily in patients receiving concomitant medication with cyclosporine, gemfibrozil, or lipid-lowering doses (≥ 1 g/ day) of niacin.
Samtidig brug af simvastatin og gemfibrozil bør undgås, med mindre det er sandsynligt, at fordelene opvejer den forøgede risiko ved denne kombination af lægemidler.
The combined use of simvastatin with gemfibrozil should be avoided, unless the benefits are likely to outweigh the increased risks of this drug combination.
Fordelene ved den samtidige brug af simvastatin 10 mg daglig og andre fibrater (med undtagelse af fenofibrat), niacin eller ciclosporin bør nøje opvejes mod de potentielle risici ved disse kombinationer.
The benefits of the combined use of simvastatin 10 mg daily with other fibrates (except fenofibrate), niacin or cyclosporine should be carefully weighed against the potential risks of these combinations.
4. 2 og 4. 5).
(See sections 4.2 and 4.5.)
Der bør udvises forsigtighed ved ordination af fenofibrat med simvastatin, da begge stoffer kan forårsage myopati hver for sig.
Caution should be used when prescribing fenofibrate with simvastatin, as either agent can cause myopathy when given alone.
4. 2 og 4. 5).
The combined use of simvastatin at doses higher than 20 mg daily with amiodarone or verapamil should be avoided unless the clinical benefit is likely to outweigh the increased risk of myopathy (see sections 4.2 and 4.5).
I kliniske undersøgelser har man hos nogle få voksne patienter behandlet med simvastatin set vedvarende stigninger (op til > 3 x ULN) i serumtransaminaser.
In clinical studies, persistent increases (to > 3 x ULN) in serum transaminases have occurred in a few adult patients who received simvastatin.
Når simvastatinbehandlingen blev afbrudt eller seponeret hos disse patienter, faldt transaminaseniveauerne sædvanligvis langsomt til samme niveau som før behandlingen.
When simvastatin was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pre-treatment levels.
Det anbefales at udføre leverfunktionsprøver før behandlingen påbegyndes, and derefter når det er klinisk indikeret.
It is recommended that liver function tests be performed before treatment begins and thereafter when clinically indicated.
Hvis transaminaseniveauerne viser tegn på progression, specielt hvis de stiger til 3 x ULN og er vedvarende, bør behandlingen afbrydes.
Patients titrated to the 80-mg dose should receive an additional test prior to titration, 3 months after titration to the 80-mg dose, and periodically thereafter (e. g., semi-annually) for the first year of treatment.
Produktet bør anvendes med forsigtighed hos patienter, der indtager store mængder alkohol.
Special attention should be paid to patients who develop elevated serum transaminase levels, and in these patients, measurements should be repeated promptly and then performed more frequently.
Som ved andre lipidsænkende stoffer er der fundet moderate (< 3 x ULN) stigninger af serumtransaminase efter behandling med simvastatin.
If the transaminase levels show evidence of progression, particularly if they rise to 3 x ULN and are persistent, simvastatin should be discontinued.
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Interaktioner med lipidsænkende lægemidler, der kan forårsage myopati, når det gives alene Risikoen for myopati, herunder rhabdomyolyse, forøges ved samtidig indgivelse af fibrater og niacin (nikotinsyre) (≥ 1 g/ dag).
Interactions with lipid-lowering medicinal products that can cause myopathy when given alone The risk of myopathy, including rhabdomyolysis, is increased during concomitant administration with fibrates and niacin (nicotinic acid) (≥ 1 g/ day).
Desuden er der farmakokinetisk interaktion med gemfibrozil, hvilket resulterer i forhøjede simvastatin plasmaniveauer (se nedenfor under Farmakokinetiske interaktioner samt pkt.
Additionally, there is a pharmacokinetic interaction with gemfibrozil resulting in increased simvastatin plasma levels (see below Pharmacokinetic interactions and sections 4.2 and 4.4).
Når simvastatin og fenofibrat gives samtidig, er der ikke tegn på, at risikoen for myopati overstiger summen af risici for de enkelte stoffer.
When simvastatin and fenofibrate are given concomitantly, there is no evidence that the risk of myopathy exceeds the sum of the individual risks of each agent.
Hvad angår andre fibrater, er der ikke tilstrækkelige data tilgængelige med henblik på pharmacovigilance og farmakokinetiske data.
Adequate pharmacovigilance and pharmacokinetic data are not available for other fibrates.
Andre lægemidlers påvirkning af simvastatin
Effects of other medicinal products on simvastatin
Interaktioner med CYP3A4 Simvastatin er et substrat af cytokrom P450 3A4.
Interactions involving CYP3A4 Simvastatin is a substrate of cytochrome P450 3A4.
Potente hæmmere af cytokrom P450 3A4 forøger risikoen for myopati og rhabdomyolyse ved at øge koncentrationen af HMG- CoA reduktasehæmmeraktivitet i plasma i forbindelse med simvastatinbehandling.
Potent inhibitors of cytochrome P450 3A4 increase the risk of myopathy and rhabdomyolysis by increasing the concentration of HMG-CoA reductase inhibitory activity in plasma during simvastatin therapy.
Disse hæmmere omfatter itraconazol, ketoconazol, erythromycin, clarithromycin, telithromycin, HIV proteasehæmmere og nefazodon.
Such inhibitors include itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, and nefazodone.
Samtidig indgivelse af itraconazol resulterede i mere end en 10 gang forøgelse i optagelsen af simvastatinsyre (den aktive β- hydroxysyre metabolit).
Concomitant administration of itraconazole resulted in a more than 10-fold increase in exposure to simvastatin acid (the active beta-hydroxyacid metabolite).
Telithromycin forårsagede en 11 gang forøgelse i optagelsen af simvastatinsyre.
Telithromycin caused an 11-fold increase in exposure to simvastatin acid.
Derfor er kombination med itraconazol, ketoconazol, HIV proteasehæmmere, erythromycin, clarithromycin, telithromycin and nefazodon kontraindikeret.
Therefore, combination with itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone is contraindicated.
Hvis behandling med itraconazol, ketoconazol, erythromycin, clarithromycin eller telithromycin er uundgåelig, skal behandling med simvastatin indstilles under dette behandlingsforløb.
If treatment with itraconazole, ketoconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.
4. 2 og 4. 4).
Caution should be exercised when combining simvastatin with certain other less potent CYP3A4 inhibitors: cyclosporine, verapamil, diltiazem (see sections 4.2 and 4.4).
Ciclosporin Risikoen for myopati/ rhabdomyolyse forøges ved samtidig indgivelse af ciclosporin, især sammen med højere doser simvastatin (se pkt.
Cyclosporine The risk of myopathy/ rhabdomyolysis is increased by concomitant administration of cyclosporine particularly with higher doses of simvastatin (see sections 4.2 and 4.4).
Derfor bør simvastatin dosis ikke overstige 10 mg daglig for patienter, der samtidig får ciclosporin.
Therefore, the dose of simvastatin should not exceed 10 mg daily in patients receiving concomitant medication with cyclosporine.
Selvom mekanismen ikke er helt forstået, øger ciclosporin simvastatinsyrens AUC, delvist, formodentlig, på grund af CYP3A4 hæmningen.
Although the mechanism is not fully understood, cyclosporine increases the AUC of simvastatin acid presumably due, in part, to inhibition of CYP3A4.
4. 2 og 4. 4).
Gemfibrozil Gemfibrozil increases the AUC of simvastatin acid by 1.9-fold, possibly due to inhibition of the glucuronidation pathway (see sections 4.2 and 4.4).
4. 4).
Amiodarone and verapamil The risk of myopathy and rhabdomyolysis is increased by concomitant administration of amiodarone or verapamil with higher doses of simvastatin (see section 4.4).
I en igangværende klinisk undersøgelse er der blevet rapporteret myopati hos 6% af de patienter, der får simvastatin 80 mg og amiodaron.
In an ongoing clinical trial, myopathy has been reported in 6% of patients receiving simvastatin 80 mg and amiodarone.
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dosis ikke overstige 40 mg dagligt for patienter, der samtidig får diltiazem, med mindre den kliniske fordel kan opveje den forøgede risiko for myopati og rhabdomyolyse.
Therefore, the dose of simvastatin should not exceed 40 mg daily in patients receiving concomitant medication with diltiazem, unless the clinical benefit is likely to outweigh the increased risk of myopathy and rhabdomyolysis.
Grapefrugtjuice Grapefrugtjuice hæmmer cytochrom P450 3A4.
Grapefruit juice Grapefruit juice inhibits cytochrome P450 3A4.
Samtidig indtagelse af store mængder (over 1 liter dagligt) grapefrugtjuice og simvastatin resulterede i en 7 gange forøgelse i optagelsen af simvastatinsyre.
Concomitant intake of large quantities (over 1 litre daily) of grapefruit juice and simvastatin resulted in a 7-fold increase in exposure to simvastatin acid.
Indtagelse af 240 ml grapefrugtjuice om morgenen og simvastatin om aftenen medførte også en 1, 9 gang forøgelse.
Intake of 240 ml of grapefruit juice in the morning and simvastatin in the evening also resulted in a 1.9-fold increase.
Indtagelse af grapefrugtjuice under behandling med simvastatin bør derfor undgås.
Intake of grapefruit juice during treatment with simvastatin should therefore be avoided.
Orale antikoagulantia I to kliniske undersøgelser, den ene med normale frivillige og den anden med hyperkolesterolæmipatienter, gav simvastatin 20- 40 mg dagligt en beskeden øgning i effekt af coumarin antikoagulantia: protrombintiden, rapporteret som International Normalized Ratio (INR), forøgedes fra en baseline på henholdsvis 1, 7 til 1, 8 og fra 2, 6 til 3, 4 i undersøgelsen med frivillige og patientundersøgelsen.
Oral anticoagulants In two clinical studies, one in normal volunteers and the other in hypercholesterolaemic patients, simvastatin 20-40 mg/ day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies, respectively.
Meget sjældne tilfælde af forhøjet INR er rapporteret.
Very rare cases of elevated INR have been reported.
Hos patienter, der får coumarin antikoagulantia, bør protrombintiden måles, før behandling med simvastatin påbegyndes og følges regelmæssigt i den tidlige del af behandlingsforløbet for at sikre, at der ikke sker signifikant ændring i protrombintiden.
In patients taking coumarin anticoagulants, prothrombin time should be determined before starting simvastatin and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs.
Når der er påvist stabil protrombintid, kan protrombintiden monitoreres med intervaller, der sædvanligvis anbefales for patienter i behandling med coumarin antikoagulantia.
Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants.
Hvis simvastatindosis ændres eller afbrydes, bør proceduren gentages.
If the dose of simvastatin is changed or discontinued, the same procedure should be repeated.
Simvastatinbehandling har ikke været associeret med blødning eller med ændringer i protrombintid hos patienter, der ikke tager antikoagulantia.
Simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.
Simvastatins effekt på andre lægemidlers farmakokinetik Simvastatin har ikke en hæmmende effekt på cytochrom P450 3A4.
Effects of simvastatin on the pharmacokinetics of other medicinal products Simvastatin does not have an inhibitory effect on cytochrome P450 3A4.
Derfor forventes simvastatin ikke at påvirke plasmakoncentrationen i substanser metaboliseret via cytochrom P450 3A4.
Therefore, simvastatin is not expected to affect plasma concentrations of substances metabolised via cytochrome P450 3A4.
4. 3).
< Zocord > is contraindicated during pregnancy (see section 4.3).
Sikkerheden hos gravide kvinder er ikke undersøgt.
Safety in pregnant women has not been established.
Der er ikke udført kliniske undersøgelser med simvastatin hos gravide kvinder.
No controlled clinical trials with simvastatin have been conducted in pregnant women.
Der har været sjældne rapporteringer om kongenitte anomalier efter intrauterin påvirkning af HMG- CoA reduktasehæmmere.
Rare reports of congenital anomalies following intrauterine exposure to HMG-CoA reductase inhibitors have been received.
I en analyse af cirka 200 prospektivt fulgte graviditeter, hvor der i første trimester blev behandlet med < Zocord > eller anden nært beslægtet HMG- CoA reduktasehæmmer, var incidensen af kongenitte anomalier dog sammenlignelig med incidensen hos befolkningen i almindelighed.
However, in an analysis of approximately 200 prospectively followed pregnancies exposed during the first trimester to< Zocord > or another closely related HMG-CoA reductase inhibi tor, the incidence of congenital anomalies was comparable to that seen in the general population.
Af disse grunde bør < Zocord > ikke gives til gravide kvinder, kvinder der forsøger at blive gravide, eller kvinder der tror, de er gravide.
This number of pregnancies was statistically sufficient to exclude a 2.5-fold or greater increase in congenital anomalies over the background incidence.
4. 7 Virkninger på evnen til at føre motorkøretøj eller betjene maskiner CPMP/ 459/ 04
CPMP/ 459/ 04
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< Zocord > har ingen eller ubetydelig indflydelse på evnen til at føre bil eller betjene maskiner. > Der skal dog tages højde for, når man kører bil eller betjener maskiner, at der har været rapporteret sjældne tilfælde af svimmelhed efter markedsføringen.
(See section 4.3.)
5. 1).
The frequencies of the following adverse events, which have been reported during clinical studies and/ or post-marketing use, are categorized based on an assessment of their incidence rates in large, long-term, placebo-controlled, clinical trials including HPS and 4S with 20,536 and 4,444 patients, respectively (see section 5.1).
Med henblik på HPS blev kun alvorlige bivirkninger registreret så som myalgia, forhøjede transaminaser i serum og CK.
For HPS, only serious adverse events were recorded as well as myalgia, increases in serum transaminases and CK.
Med henblik på 4S blev alle nedenfor nævnte bivirkninger registreret.
For 4S, all the adverse events listed below were recorded.
Hvis incidenshyppigheden for simvastatin var mindre end eller sammenlignelig med placebo i disse undersøgelser, og der var spontane rapporter om rimeligt sammenlignelige årsagssammenhænge, kategoriseret disse bivirkninger som ” sjældne ”.
If the incidence rates on simvastatin were less than or similar to that of placebo in these trials, and there were similar reasonably causally related spontaneous report events, these adverse events are categorized as “ rare”.