natgillin/translations-raw huggingface dataset:
Elimination: Ca. 90 % af rosuvastatin dosis udskilles uomdannet i fæces (bestående af absorberet og uabsorberet stof) og den resterende del i urinen.
Excretion: Approximately 90% of the rosuvastatin dose is excreted unchanged in the faeces (consisting of absorbed and non-absorbed active substance) and the remaining part is excreted in urine.
Det var fortrinsvis CYP2C9 som var involveret og 2C19, 3A4 og 2D6 i mindre grad.
CYP2C9 was the principal isoenzyme involved, with 2C19, 3A4 and 2D6 involved to a lesser extent.
Crestor bør seponeres eller dosis reduceres ved vedvarende serum transaminaser større end 3 gange den øvre normale grænseværdi.
Crestor should be discontinued or the dose reduced if the level of serum transaminases is greater than 3 times the upper limit of normal.
33 % af patienterne nåede EAS guideline målene for LDL-C niveauer (<3
33% of patients reached EAS guidelines for LDL-C levels (<3 mmol/l).
Race: Farmakokinetiske studier viser en ca. fordoblet stigning i gennemsnits AUC sammenlignet med vestlige kaukasiere hos både Japanske patienter bosiddende i Japan og Kinesiske patienter bosiddende i
Race: Pharmacokinetic studies show an approximate 2-fold elevation in median AUC compared with western Caucasians in both Japanese subjects residing in Japan, and Chinese subjects living in
I kontrollerede kliniske undersøgelser måtte færre end 4 % af de patienter som fik Crestor udgå af undersøgelserne på grund af bivirkninger.
In controlled clinical trials, less than 4% of Crestor-treated patients were withdrawn due to adverse events.
Hvis en patient bliver gravid under anvendelse af Crestor, skal behandlingen seponeres med det samme.
If a patient becomes pregnant during use of this product, treatment should be discontinued immediately.
Der foreligger ingen farmakokinetiske data fra personer som har taget Crestor og hormonsubstitutionsbehandling samtidig og derfor kan en lignende effekt ikke udelukkes.
There are no pharmacokinetic data available in subjects taking concomitant Crestor and HRT and therefore a similar effect cannot be excluded.
- samtidig anvendelse af fibrater
- concomitant use of fibrates.
Crestor reducerer forhøjet LDL-kolesterol, total kolesterol og triglycerider og øger HDL kolesterol.
Crestor reduces elevated LDL-cholesterol, total cholesterol and triglycerides and increases HDLcholesterol.
Crestor 5 mg filmovertrukne tabletter
Crestor 5 mg film-coated tablets.
Dosis bør individualiseres efter behandlingsmål og patientrespons, i henhold til gældende guidelines.
The dose should be individualised according to the goal of therapy and patient response, using current consensus guidelines.
Samtidig administration af itraconazol (en hæmmer af CYP3A4) og rosuvastatin medførte en stigning på 28 % i AUC for rosuvastatin.
Concomitant administration of itraconazole (an inhibitor of CYP3A4) and rosuvastatin resulted in a 28% increase in AUC of rosuvastatin.
Måling af creatinin kinase (CK) bør ikke foretages efter anstrengende motion eller ved tilstedeværelsen af en anden mulig grund til CK øgning, som kan påvirke resultatet.
Creatine Kinase (CK) should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase which may confound interpretation of the result.
- i patienter med aktiv leversygdom inklusiv uforklarlige, vedvarende stigninger i serum transaminaser og enhver transaminase stigning som overstiger 3 gange den øvre normale grænseværdi (ULN).
- in patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x the upper limit of normal
Rosuvastatin tegner sig for mere end 90 % af den cirkulerende HMG-CoA reduktase aktivitet.
Rosuvastatin accounts for greater than 90% of the circulating HMG-CoA reductase inhibitor activity.
Crestor sænker også forholdene LDL-C/HDL-C, total C/HDL-C og nonHDL-C/HDL-C samt ApoB/ApoA-I.
Crestor also lowers the LDL-C/HDL-C, total C/HDL-C and nonHDL-C/HDL-C and the ApoB/ApoA-I
Crestor‘s bivirkninger er generelt milde og forbigående.
The adverse events seen with Crestor are generally mild and transient.
Rosuvastatin er en selektiv og kompetitiv inhibitor af HMG-CoA reduktase, det hastighedsbegrænsende enzym som omdanner 3-hydroxy-3-methylglutaryl coenzym A til mevalonat, et forstadie til kolesterol.
Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor for cholesterol.
- under graviditet og amning samt hos kvinder i den fødedygtige alder som ikke benytter sikker antikonception.
- during pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.
Efter titrering til en daglig dosis på 40 mg (12 ugers behandling) var
Following titration to a daily dose of 40 mg (12 weeks of treatment), LDL-C
Hvis denne test bekræfter en baselinie CK >5xULN bør behandling ikke startes.
If the repeat test confirms a baseline CK >5xULN, treatment should not be started.
Disse faktorer kan være: - moderat nedsat nyrefunktion (kreatinin clearence <60 ml/min)
Such factors include: - moderate renal impairment (creatinine clearence < 60 ml/min)
Alder og køn: Alder og køn har ingen klinisk relevant effekt på rosuvastatin's farmakokinetik.
Age and sex: There was no clinically relevant effect of age or sex on the pharmacokinetics of rosuvastatin.
AstraZeneca A/SRoskildevej 22 DK-2620 Albertslund
AstraZeneca A/SRoskildevej 22 DK-2620 Albertslund Denmark
N-desmethyl metabolitten er ca. halvt så aktiv som rosuvastatin hvorimod laktonformen betragtes som klinisk inaktiv.
The Ndesmethyl metabolite is approximately 50% less active than rosuvastatin whereas the lactone form is considered clinically inactive.
De identificerede hovedmetabolitter er N-desmethyl og lakton metabolitterne.
The main metabolites identified are the N-desmethyl and lactone metabolites.
Glyceroltriacetat
Glycerol triacetate
Behandling bør seponeres, hvis CK værdierne er markant forhøjede (>5xULN) eller ved svære muskelsymptomer med dagligt ubehag (også hvis CK niveauer er ≤5xULN).
Therapy should be discontinued if CK levels are markedly elevated (>5xULN) or if muscular symptoms are severe and cause daily discomfort (even if CK levels are ≤ 5x ULN).
På baggrund af data fra specifikke interaktionsstudier forventes der ingen farmakokinetisk relevante interaktioner med fenofibrat, mens der kan indtræffe en farmakodynamisk interaktion.
Based on data from specific interaction studies no pharmacokinetic relevant interaction with fenofibrate is expected, however a pharmacodynamic interaction may occur.
Antal LDLC
Dose N LDLC
Ciclosporin: Ved samtidig behandling med Crestor og ciclosporin var rosuvastatin's AUC værdier i gennemsnit 7 gange højere end hos raske frivillige (se afsnit 4.3 Kontraindikationer).
Cyclosporin: During concomitant treatment with Crestor and cyclosporin, rosuvastatin AUC values were on average 7 times higher than those observed in healthy volunteers (see Section 4.3 Contraindications).
Crestor bør ikke anvendes hos patienter med en akut, alvorlig tilstand som tyder på myopati eller ved prædisponering for udvikling af nyresvigt sekundært til rhabdomyolyse (f.eks. sepsis, hypotension, større kirurgiske indgreb, traume, alvorlige metaboliske, endokrine eller elektrolyt forstyrrelser; eller ukontrollerede kramper).
Crestor should not be used in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures).
Valg af startdosis bør indeholde overvejelser omkring den enkelte patients individuelle kolesterolværdi og fremtidige risiko for hjertekarsygdom såvel som den mulige risiko for bivirkninger (se nedenfor).
The choice of start dose should take into account the individual patient's cholesterol level and future cardiovascular risk as well as the potential risk for adverse reactions (see below).
Hos individer med svær nyreinsufficiens (CrCl < 30 ml/min) sås en 3-foldig stigning i plasmakoncentration og en 9-foldig stigning i koncentrationen af N-desmethyl metabolitten sammenlignet med raske frivillige.
Subjects with severe impairment (CrCl <30 ml/min) had a 3-fold increase in plasma concentration and a 9-fold increase in the N-desmethyl metabolite concentration compared to healthy volunteers.
Dog viste to individer med Child-Pugh score på 8 og 9 en stigning i systemisk eksponering som var mindst fordoblet sammenlignet med individer med lavere Child-Pugh score.
However, two subjects with Child-Pugh scores of 8 and 9 showed an increase in systemic exposure of at least 2-fold compared to subjects with lower Child-Pugh scores.
Almindelig: Obstipation, kvalme, abdominale smerter.
Common: constipation, nausea, abdominal pain
Denne transporter er vigtig for rosuvastatins' leverelimination.
This transporter is important in the hepatic elimination of rosuvastatin.
I en stor undersøgelse af patienter med heterozygot familiær hyperkolesterolæmi fik 435 individer Crestor fra 20 mg til 80 mg i et force-titrerings design.
In a large study, 435 patients with heterozygous familial hypercholesterolaemia were given Crestor from 20 mg to 80 mg in a force-titration design.
Der er ikke observeret klinisk relevante interaktioner mellem rosuvastatin og enten fluconazol (en hæmmer af CYP2C9 og CYP3A4) eller ketoconazol (en hæmmer af
No clinically relevant interactions have been observed between rosuvastatin and either fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and
I et force-titrerings open label studie blev 42 patienter med homozygot familiær hyperkolesterolæmi evalueret for deres respons på 20-40 mg Crestor.
In a force-titration, open label trial, 42 patients with homozygous familial hypercholesterolaemia were evaluated for their response to Crestor 20 - 40 mg.
Proteinuri har ikke vist sig at være tegn på akut eller progressiv nyresygdom (se afsnit 4.8 Bivirkninger).
Proteinuria has not been shown to be predictive of acute or progressive renal disease (see Section 4.8 Undesirable effects).
- i patienter med samtidig administration af ciclosporin.
- in patients receiving concomitant cyclosporin.
Antacida: Samtidig dosering af Crestor med en syreneutraliserende suspension af aluminium og magnesiumhydroxid medførte et fald i rosuvastatin's plasmakoncentration med ca. 50 %.
Antacid: The simultaneous dosing of Crestor with an antacid suspension containing aluminium and magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%.
- hypothyreoidisme
- hypothyroidism
- i patienter med svær nyreinsufficiens (creatinin clearence <30 ml/min).
- in patients with severe renal impairment (creatinine clearance <30 ml/min).
Cytochrom P450 enzymer: Resultater fra in vitro og in vivo studier viser, at rosuvastatin hverken inhiberer eller inducerer cytochrom P450 isoenzymer.
Cytochrome P450 enzymes: Results from in vitro and in vivo studies show that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes.
Ved valg af startdosis bør der snarere tages hensyn til mulige sikkerhedsmæssige betænkeligheder vedrørende den enkelte patient, f.eks. baseret på følsomhed for bivirkninger og farmakokinetiske overvejelser.
Rather, the choice of start dose should take into account potential safety concerns in the individual patient based e.g. on sensitivity to adverse reactions and pharmacokinetic considerations.
Distribution: Rosuvastatin optages hovedsagelig af leveren, det primære organ for kolesterolsyntese og LDL-C clearence.
Distribution: Rosuvastatin is taken up extensively by the liver which is the primary site of cholesterol synthesis and LDL-C clearance.
Lactose monohydrat
Lactose monohydrate
At vurdere relevansen af en sådan trinvis reduktion er en kompliceret opgave, som må inddrage den foreliggende dokumentation for behandlingsresultater i kliniske undersøgelser med denne kategori af lægemidler.
The assessment of relevance of this incremental reduction is complex, and must take into account the body of evidence available from outcome trials for this class of agents.
Rosuvastatin's steady state plasmakoncentrationer hos patienter i hæmodialyse var ca. 50 % større sammenlignet med raske frivillige.
Steady-state plasma concentrations of rosuvastatin in subjects undergoing haemodialysis were approximately 50% greater compared to healthy volunteers.
Rosuvastatin øger antallet af lever-LDL receptorer på celleoverfladen og fremmer dermed optagelse og katabolisering af LDL og det hæmmer syntesen af VLDL i leveren, hvorved det totale antal af VLDL og LDL partikler reduceres.
Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.
Der forventes derfor ingen interaktioner stammende fra cytochrom P450 medieret metabolisme.
Therefore, drug interactions resulting from cytochrome P450-mediated metabolism are not expected.
(se afsnit 4.4 Særlige advarsler og forsigtighedsregler vedrørende brugen, 4.5 Interaktion med andre lægemidler og andre former for interaktion og 5.2 Farmakokinetiske egenskaber)
(See sections 4.4 Special warnings and special precautions for use, 4.5 Interaction with other medicinal products and other forms of interaction and 5.2 Pharmacokinetic properties).
De samlede erfaringer med rosuvastatin 5 mg er mere begrænsede end med 10 mg, men de foreliggende oplysninger fra kliniske undersøgelser og post-marketing oplysninger giver ikke holdepunkt for, at 5 mg doseringen på gruppeniveau skulle have nogen relevant sikkerhedsmæssig fordel frem for 10 mg doseringen.
The overall experience with rosuvastatin 5 mg is more limited than that with 10 mg but available clinical trials information and post-marketing data do not support relevant safety benefit at group level of the 5 mg dose, in comparison with the 10 mg dose.
(feks.
(ULN).
Dosisjustering er ikke nødvendig hos patienter med mild til moderat nyreinsufficiens.
No dose adjustment is necessary in patients with mild to moderate renal impairment.
Plasmaudskillelseshalveringstiden stiger ikke ved højere doser.
The elimination half-life does not increase at higher doses.
Der er ingen erfaring hos individer med Child-Pugh score over 9.
There is no experience in subjects with Child-Pugh scores above 9.
Crestor er kontraindikeret hos patienter med aktiv leversygdom (se afsnit 4.3 Kontraindikationer).
Crestor is contraindicated in patients with active liver disease (see Section 4.3 Contraindications).
I kliniske undersøgelser var der ikke tegn på øget påvirkning af skeletmuskulaturen hos det lille antal patienter, der fik Crestor og anden samtidig behandling.
In clinical trials there was no evidence of increased skeletal muscle effects in the small number of patients dosed with Crestor and concomitant therapy.
Om nødvendigt, kan dosisjustering til næste dosis niveau foretages efter 4 uger (se afsnit 5.1
A dose adjustment to the next dose level can be made after 4 weeks, if necessary (see Section 5.1 Pharmacodynamic properties).
Hos patienter behandlet med rosuvastatin er der set en dosisafhængig øgning i CK niveauer; de fleste tilfælde var milde, asymptomatiske og forbigående.
A dose-related increase in CK levels has been observed in patients taking rosuvastatin; the majority of cases were mild, asymptomatic and transient.
Plasmaudskillelseshalveringstiden er ca. 19 timer.
The plasma elimination half-life is approximately 19
5.2 Farmakokinetiske egenskaber Absorption: Maksimale plasmakoncentrationer af rosuvastatin opnås ca. 5 timer efter peroral administration.
Absorption: Maximum rosuvastatin plasma concentrations are achieved approximately 5 hours after oral administration.
Gemfibrozil øger risikoen for myopati når det gives sammen med nogle HMG-CoA reduktasehæmmere.
Gemfibrozil increases the risk of myopathy when given concomitantly with some HMG-CoA reductase inhibitors.
LDL-C reduceret med 53 %.
was reduced by 53%.
Rosuvastatins primære virkningsted er leveren, målorganet for kolesterolsænkning.
The primary site of action of rosuvastatin is the liver, the target organ for cholesterol lowering.
In vitro metabolisme undersøgelser med humane hepatocytter indikerer at rosuvastatin er et ringe substrat for cytochrom P450 baseret metabolisme.
In vitro metabolism studies using human hepatocytes indicate that rosuvastatin is a poor substrate for cytochrome P450
(se afsnit 4.3 Kontraindikationer og
(see Section 4.3 Contraindications).
Anbefalet startdosis er 5 mg hos patienter med prædisponeringsfaktorer for myopati (se afsnit 4.4
The recommended start dose is 5 mg in patients with predisposing factors to myopathy (see Section 4.4
Hvis CK niveauerne er markant forhøjede ved baselinie (>5xULN) bør behandling ikke startes.
If CK levels are significantly elevated at baseline (>5xULN) treatment should not be started.
Doser på 40 mg er kontraindiceret hos patienter med prædisponeringsfaktorer for myopati/rhabdomyolyse.
The 40 mg dose is contraindicated in patients with pre-disposing factors for myopathy/rhabdomyolysis.
Anbefalet startdosis er 5 eller 10 mg peroralt én gang daglig hos patenter som ikke tidligere har været i behandling med statin og patienter som skifter fra andre HMG-CoA reduktase inhibitorer.
The recommended start dose is 5 or 10 mg orally once daily in both statin naïve or patients switched from another HMG CoA reductase inhibitor.
Som med andre HMG-CoA reduktasehæmmere involverer rosuvastain's leveroptagelse membrantransporteren OATP-C.
As with other HMG-CoA reductase inhibitors, the hepatic uptake of rosuvastatin involves the membrane transporter OATP-C.
Indehavere af markedsføringstilladelse/ansøge re
Marketing Authorisation Holders/Applicants
Nyreinsufficiens: I en undersøgelse hos individer med varierende grad af nyresinsufficiens, havde mild til moderat nyresygdom ingen indflydelse på rosuvastatin's eller N-desmethyl metabolittens plasmakoncentration.
Renal insufficiency: In a study in subjects with varying degrees of renal impairment, mild to moderate renal disease had no influence on plasma concentration of rosuvastatin or the N-desmethyl metabolite.
Rosuvastatin er bundet ca. 90 % til plasmaproteiner, hovedsagelig til albumin.
The volume of distribution of rosuvastatin is approximately 134 L. Approximately 90% of rosuvastatin is bound to plasma proteins, mainly to albumin.
Doser hos patienter med prædisponeringsfaktorer for myopati
Dosage in patients with pre-disposing factors to myopathy
konkluderes det, at benefit/risk forholdet er gunstigt for Crestor 5 mg og Crestor 10 mg som alternative startdoser.
The conclusion is that the benefit/risk ratio is favourable for Crestor 5 mg or Crestor 10 mg as alternative start doses.
Det kan konkluderes, at benefit/risk-forholdet er gunstigt for Crestor 5 og Crestor 10 mg som alternative startdoser.
In conclusion, the benefit/risk ratio is favourable for Crestor 5 or Crestor 10 mg as alternative start doses.
Dog er der set en stigning i incidensen af myositis og myopati hos patienter behandlet med andre HMG-CoA reduktasehæmmere sammen med fibrinsyrederivater inklusiv gemfibrozil, ciclosporin, nikotinsyre, azol antifungalmidler,
However, an increase in the incidence of myositis and myopathy has been seen in patients receiving other HMG-CoA reductase inhibitors together with fibric acid derivatives including gemfibrozil, cyclosporin, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics.
Dyrestudier giver begrænset bevis på reproduktionstoksicitet (se afsnit 5.3 Prækliniske sikkerhedsdata).
Animal studies provide limited evidence of reproductive toxicity (see Section 5.3
Leverpåvirkning: Som med andre HMG-CoA reduktasehæmmere er der hos et lille antal patienter behandlet med rosuvastatin, set en dosis relateret stigning i transaminaser ; de fleste tilfælde var milde,
Liver Effects: As with other HMG-CoA reductase inhibitors, a dose-related increase in transaminases has been observed in a small number of patients taking rosuvastatin; the majority of cases were mild,
Gemfibrozil og andre lipidsænkende produkter: Samtidig behandling med Crestor og gemfibrozil medførte en 2-foldig stigning i rosuvastatin's Cmax og AUC (se afsnit 4.4 Særlige advarsler og forsigtighedsregler vedrørende brugen).
Gemfibrozil and other lipid-lowering products: Concomitant use of Crestor and gemfibrozil resulted in a 2-fold increase in rosuvastatin C max and AUC (see Section 4.4 Special warnings and special precautions for use).
Som med andre HMG-CoA reduktasehæmmere bør Crestor anvendes med forsigtighed hos patienter som indtager store mængder alkohol og/eller tidligere har haft leversygdom.
As with other HMG-CoA reductase inhibitors, Crestor should be used with caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease.
Der er observeret proteinuri (påvist ved sticktest og hovedsagelig tubulær af oprindelse) hos patienter behandlet med højere Crestor doser, specielt 40 mg hvor det i de fleste tilfælde var forbigående eller periodisk tilbagevendende.
Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with higher doses of Crestor, in particular 40 mg, where it was transient or intermittent in most cases.
Crestor bør, som andre HMG-CoA reduktasehæmmere, anvendes med forsigtighed hos patienter med prædisponeringsfaktorer for myopati/rhabdomyolyse.
Crestor, as with other HMG-CoA reductase inhibitors, should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis.
Da kolesterol og andre produkter fra kolesterolbiosyntesen er essentielle for fosterets udvikling er den potentielle risiko ved hæmning af
Since cholesterol and other products of cholesterol biosynthesis are essential for the development of the foetus, the potential risk from inhibition of HMG-CoA reductase outweighs the advantage of treatment during pregnancy.
I en præ-og postnatal undersøgelse hos rotter sås reproduktionstoksicitet i form af reduktion i kuldstørrelser, kuldvægt og ungernes overlevelse.
In a rat pre- and postnatal study, reproductive toxicity was evident from reduced litter sizes, litter weight and pup survival.
Patienter bør instrueres i straks at melde tilbage ved uforklarlige muskelsmerter, muskelsvaghed eller kramper specielt ved samtidig ubehag eller feber.
Patients should be asked to report inexplicable muscle pain, weakness or cramps immediately,
Doser på 40 mg er kontraindiceret hos patienter med moderat nedsat nyrefunktion.
The 40 mg dose is contraindicated in patients with moderate renal impairment.
Fordelen ved yderligere sænkning af lipidniveauerne ved kombineret brug af Crestor og fibrater eller niacin bør vægtes nøje mod den potentielle risiko ved disse kombinationer.
Crestor with fibrates or niacin should be carefully weighed against the potential risks of such combinations.
Roskildevej 22 DK-2620 Albertslund
DK-2620 Albertslund Denmark
Hvis CK niveauer er forhøjede (>5xULN) bør behandlingen afbrydes (se afsnit 4.4 Særlige advarsler og forsigtighedsregler vedrørende brugen).
If CK levels are elevated (>5xULN), treatment should be discontinued (see Section 4.4 Special warnings and special precautions for use).
Ingen oplysninger underbygger, at dosis-bivirkningskurven (myopati, hepatotoksicitet) skulle være stejlere for rosuvastatin end for andre statiner.
There are no data to support a steeper dose relationship for adverse reactions (myopathy, hepatotoxicity) for rosuvastatin, compared with other statins.
En startdosis på 5 mg anbefales til patienter > 70 år (se afsnit 4.4 Særlige advarsler og forsigtighedsregler vedrørende brugen).
A start dose of 5 mg is recommended in patients > 70 years (see section 4.4 Special warnings and precautions for use).
I den samlede population var middel LDL-C
In the overall population, the mean LDL-C reduction was 22%.
Doser på 40 mg er kontraindiceret i disse patienter (se afsnit 4.3 Kontraindikationer).
The 40 mg dose is contraindicated in some of these patients (see Section 4.3 Contraindications).