natgillin/translations-raw huggingface dataset:
Statinbehandling skal midlertidigt afbrydes, hvis CK værdierne er > 5 x øvre normalgrænse, eller hvis der forekommer svære kliniske symptomer.
Statin therapy should be temporarily interrupted when CK levels are > 5 x ULN or when there are severe clinical symptoms.
1 ud af 100. 000 patientårs) rhabdomyolyse med eller uden sekundær nyreinsufficiens.
Very rarely (in about 1 case over 100 000 patient-years), rhabdomyolysis occurs, with or without secondary renal insufficiency.
Rhabdomyolyse er en akut potentielt fatal tilstand for skeletmuskler, som kan CPMP/ 3257/ 03
Rhabdomyolysis is an acute potentially fatal condition of skeletal muscle which may develop at any time during treatment and is characterised by massive muscle destruction associated with major increase in CK (usually > 30 or 40 x ULN) leading to myoglobinuria.
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Risiko for myopati med statiner synes at være ekspositionsafhængig og kan variere med individuelle lægemidler (pga. lipofilicitet og farmakokinetiske forskelle), inklusive deres dosering og potentiale for lægemiddelinteraktioner.
The risk of myopathy with statins appears to be exposure-dependent and therefore may vary with individual drugs (due to lipophilicity and pharmacokinetic differences), including their dosage and potential for drug interactions.
Selvom der ikke er nogen muskulære kontraindikationer for ordination af et statin, kan visse disponerende faktorer øge risikoen for muskulær toksicitet og kan derfor berettige en omhyggelig evaluering af fordele/ risici samt særlig klinisk monitorering.
Although there is no muscular contraindication to the prescription of a statin, certain predisposing factors may increase the risk of muscular toxicity and therefore justify a careful evaluation of the benefit/risk and special clinical monitoring.
CK målinger er indiceret før start af statinbehandling hos disse patienter (se nedenfor).
CK measurement is indicated before starting statin therapy in these patients (see below).
Risiko og sværhedsgrad af muskelsygdomme under statinbehandling øges ved samtidig administration af interagerende lægemidler.
The risk and severity of muscular disorders during statin therapy is increased by the co-administration of interacting medicines.
Anvendelse af fibrater alene er lejlighedsvist forbundet med myopati.
The use of fibrates alone is occasionally associated with myopathy.
Kombineret anvendelse af statin og fibrater skal generelt undgås.
The combined use of a statin and fibrates should generally be avoided.
Samtidig administration af statiner og nikotinsyre skal foregå med forsigtighed.
The co-administration of statins and nicotinic acid should be used with caution.
Der er også beskrevet en øget forekomst af myopati hos patienter, der behandles med andre statiner i kombination med hæmmere af cytokrom P450 metabolismen.
An increase in the incidence of myopathy has also been described in patients receiving other statins in combination with inhibitors of cytochrome P450 metabolism.
I forbindelse med statinbehandling svinder muskelsymptomer sædvanligvis efter seponering af statinbehandlingen.
This may result from pharmacokinetic interactions that have not been documented for pravastatin (see section 4.5) When associated with statin therapy, muscle symptoms usually resolve following discontinuation of statin therapy.
Kreatin kinase målinger og fortolkning:
Creatine kinase measurement and interpretation:
Rutinemonitering af kreatin kinase (CK) eller andre muskelenzymværdier anbefales ikke hos asymptomatiske patienter i statinbehandling.
Routine monitoring of creatine kinase (CK) or other muscle enzyme levels is not recommended in asymptomatic patients on statin therapy.
Måling af CK anbefales dog før start af statinbehandling hos patienter med særlige disponerende faktorer samt hos patienter der udvikler muskulære symptomer under statinbehandling, som beskrevet nedenfor.
However, measurement of CK is recommended before starting statin therapy in patients with special predisposing factors, and in patients developing muscular symptoms during statin therapy, as described below.
5- 7 dage senere for at bekræfte resultaterne.
If CK levels are significantly elevated at baseline (> 5 x ULN), CK levels should be re measured about 5 to 7 days later to confirm the results.
Efter måling skal CK værdierne fortolkes i sammenhæng med andre potentielle faktorer, som kan forårsage forbigående muskelskade så som anstrengende træning og muskeltraumer.
When measured, CK levels should be interpreted in the context of other potential factors that can cause transient muscle damage, such as strenuous exercise or muscle trauma.
Før behandlingsstart:
Before treatment initiation:
Der skal udvises forsigtighed hos patienter med disponerende faktorer så som nyrefunktionsnedsættelse, hypothyreoidisme, forudgående anamnestisk muskeltoksicitet ved behandling med statin eller fibrat, personlig eller familiær anamnese med arvelige muskelsygdomme eller alkoholmisbrug.
Caution should be used in patients with predisposing factors such as renal impairment, hypothyroidism, previous history of muscular toxicity with a statin or fibrate, personal or familial history of hereditary muscular disorders, or alcohol abuse.
I disse tilfælde skal CK værdierne måle inden behandlingsstart.
In these cases, CK levels should be measured prior to initiation of therapy.
CK måling skal også overvejes inden behandlingsstart hos personer over 70 år, specielt ved tilstedeværelse af andre disponerende faktorer hos denne gruppe.
CK measurement should also be considered before starting treatment in persons over 70 years of age especially in the presence of other predisposing factors in this population.
Hvis CK værdierne er signifikant forhøjede (> 5 x øvre normalgrænse) ved baseline, skal behandling ikke iværksættes, og prøverne skal gentages efter 5- 7 dage.
If CK levels are significantly elevated (> 5 x ULN) at baseline, treatment should not be started and the results should be re-measured after 5-7 days.
Baseline CK værdier kan også anvendes som reference i tilfælde af senere øgning under statinbehandling.
The baseline CK levels may also be useful as a reference in the event of a later increase during statin therapy.
Patienterne skal tilrådes omgående at meddele uforklarlige muskelsmerter, ømhed, svækkelse eller kramper.
During treatment: patients should be advised to report promptly unexplained muscle pain, tenderness, weakness or cramps.
I disse tilfælde skal CK værdierne måles.
In these cases, CK levels should be measured.
Hvis der optræder en markant forhøjet (> 5 x øvre normalgrænse) CK værdi, skal statinbehandlingen seponeres.
If a markedly elevated (> 5 x ULN) CK level is detected, statin therapy must be interrupted.
Behandlingsophør skal også overvejes, hvis muskelsymptomerne er svære og forårsager dagligt ubehag, selv hvis CK øgning forbliver ≤ 5 x øvre normalgrænse.
Treatment discontinuation should also be considered if the muscular symptoms are severe and cause daily discomfort, even if the CK increase remains ≤ 5 x ULN.
Hvis symptomerne svinder og CK værdierne normaliseres, skal genoptagelse af statinbehandling overvejes med den laveste dosis og foregå under tæt monitorering.
If symptoms resolve and CK levels return to normal, then reintroduction of statin therapy may be considered at the lowest dose and with close monitoring.
Hvis der mistænkes en arvelig muskelsygdom hos en sådan patient, kan genoptagelse af statinbehandling ikke anbefales.
If a hereditary muscular disease is suspected in such patient, restarting statin therapy is not recommended.
Fibrater:
Fibrates:
Der er rapporteret en øget risiko for muskelrelaterede uønskede hændelser, inklusive rhabdomyolyse, hvis fibrater administreres sammen med andre statiner.
An increased risk of muscle related adverse events, including rhabdomyolysis, have been reported when fibrates are co- administered with other statins.
4. 4).
These adverse events with pravastatin cannot be excluded; therefore the combined use of pravastatin and fibrates (e.g. gemfibrozil, fenofibrate) should generally be avoided (see section 4.4).
Hvis denne kombination anses for nødvendig, er omhyggelig klinisk og CK monitorering af patienter i sådan behandling påkrævet.
If this combination is considered necessary, careful clinical and CK monitoring of patients on such regimen is required.
CPMP/ 3257/ 03
Cholestyramine/Colestipol:
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EMEA 2004
EMEA 2004 before
Colestyramin/ Colestipol:
Cyclosporin:
Samtidig administration af pravastatin og cyklosporin medfører ca.
Concomitant administration of pravastatin and cyclosporin leads to an approximately 4-fold increase in pravastatin systemic exposure.
4 gange øgning i systemisk eksposition for pravastatin Hos nogle patienter kan pravastatin ekspositionen dog være større.
In some patients, however, the increase in pravastatin exposure may be larger.
4. 2).
Clinical and biochemical monitoring of patients receiving this combination is recommended (see section 4.2).
Warfarin og andre orale antikoagulantia:
Warfarin and other oral anticoagulants:
Parametre for biotilgængelighed ved steady state for pravastatin blev ikke ændret efter administration af warfarin.
Bioavailability parameters at steady state for pravastatin were not altered following administration with warfarin.
Kronisk dosering af de to produkter medførte ingen ændring af warfarins antikoagulerende virkning.
Chronic dosing of the two products did not produce any changes in the anticoagulant action of warfarin.
Lægemidler der metaboliseres ved cytokrom P450:
Products metabolised by cytochrome P450:
Pravastatin metaboliseres ikke i klinisk signifikant udstrækning ved cytokrom P450 systemet.
Pravastatin is not metabolised to a clinically significant extent by the cytochrome P450 system.
Det er derfor at lægemidler, som metaboliseres ved eller hæmmes af cytokrom P450, kan tillægges til et stabilt pravastatin regime uden at forårsage signifikante ændringer i plasmaværdierne for pravastatin, hvilket er set med andre statiner.
This is why products that are metabolised by, or inhibitors of, the cytochrome P450 system can be added to a stable regimen of pravastatin without causing significant changes in the plasma levels of pravastatin, as have been seen with other statins.
Fravær af signifikant farmakokinetisk interaktion med pravastatin er specifikt blevet demonstreret for adskillige lægemidler, særligt de som er substrater/ inhibitorer af CYP3A4, f. eks. diltiazem, verapamil, itraconazol, ketoconazol, proteaseinhibitorer, grapefrugt juice og CYP2C9 inhibitorer (f. eks. fluconazol).
The absence of a significant pharmacokinetic interaction with pravastatin has been specifically demonstrated for several products, particularly those that are substrates/inhibitors of CYP3A4 e.g. diltiazem, verapamil, itraconazole, ketoconazole, protease inhibitors, grapefruit juice and CYP2C9 inhibitors (e.g. fluconazole).
I det ene af to interaktionsstudier med pravastatin og erytromycin sås en statistisk signifikant øgning i pravastatin AUC (70%) og Cmax (121%).
In one of two inter actions studies with pravastatin and erythromycin a statistically significant increase in pravastatin AUC (70%) and Cmax (121%) was observed.
I et lignende studie med claritromycin blev der observeret en statistisk signifikant øgning i AUC (110%) og Cmax (127%).
In a similar study with clarithromycin a statistically significant increase in AUC (110%) and Cmax (127%) was observed.
Selvom disse ændringer var af mindre grad, skal der udvises forsigtighed hvis pravastatin gives sammen med erytromycin eller claritromycin.
Although these changes were minor, caution should be exercised when associating pravastatin with erythromycin or clarithromycin.
Andre lægemidler:
Other products:
I interaktionsstudier sås der ingen statistisk signifikante forskelle i biotilgængelighed, når pravastatin blev administreret sammen med acetylsalicylsyre, antacider (ved administration en time før pravastatin), nikotinsyre eller probucol.
In interaction studies, no statistically significant differences in bioavailability were observed when pravastatin was administered with acetylsalicylic acid, antacids (when given one hour prior to pravastatin), nicotinic acid or probucol.
Pravastatin er kontraindiceret under graviditet og bør kun gives til fertile kvinder, hvis disse ikke har sandsynlighed for at blive gravide og har modtaget information om den potentielle risiko.
Pravastatin is contraindicated during pregnancy and should be administered to women of childbearing potential only when these patients are unlikely to conceive and have been informed of the potential risk.
Hvis en patient planlægger graviditet eller bliver gravid, skal lægen omgående informeres, og pravastatin skal seponeres pga. den potentielle risiko for fostret.
If a patient plans to become pregnant or becomes pregnant, the doctor has to be informed immediately and pravastatin should be discontinued because of the potential risk to the foetus.
4. 3).
A small amount of pravastatin is excreted in human breast milk, therefore pravastatin is contraindicated during breastfeeding (see section 4.3).
Pravastatin har ingen eller ubetydelig indflydelse på evnen til at føre bil eller betjene maskiner.
Pravastatin has no or negligible influence on the ability to drive and use machines.
Ved bilkørsel eller betjening af maskiner skal det dog tages i betragtning, at der kan forekomme svimmelhed under behandlingen.
However, when driving vehicles or operating machines, it should be taking into account that dizziness may occur during treatment.
Forekomsten af uønskede hændelser ordnes i henhold til følgende: meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100, < 1/ 10), usædvanlig (≥ 1/ 1. 000, < 1/ 100), sjælden (≥ 1/ 10. 000, < 1/ 1. 000), meget sjælden (< 1/ 10. 000).
The frequencies of adverse events are ranked according to the following: very common (≥1/10); common (≥1/100, < 1/10); uncommon (≥1/1000 < 1/100); rare (≥1/10000, < 1/1000); very rare (< 1/10000).
CPMP/ 3257/ 03 Kliniske studier: < (TRADENAME) > 40 mg er undersøgt i
CPMP/6214/03
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placebokontrollerede studier med > 21. 000 patienter behandlet med pravastatin (n= 10. 764) eller placebo (n = 10. 719), hvilket repræsenterer > 47. 000 patientårs eksponering for pravastatin. > 19. 000 patienter blev kontrolleret i median 4, 8- 5, 9 år.
Clinical trials: < (TRADENAME) > has been studied at 40mg in seven randomized double-blind placebo-controlled trials involving over 21000 patients treated with pravastatin (N=10764) or placebo (N=10719), representing over 47000 patients years of exposure to pravastatin.
Følgende uønskede lægemiddelreaktioner blev rapporteret; ingen af dem forekom med overvægtsrate på > 0, 3% i pravastatingruppen sammenlignet med placebogruppen.
Over 19000 patients were followed for a median of 4.8-5.9 years.
Usædvanlig: svimmelhed, hovedpine, søvnforstyrrelser, søvnløshed
The following adverse drug reactions were reported; none of them occurred at a rate in excess of 0.3% in pravastatin group compared to the placebo group.
Øjensygdomme:
Nervous system disorders:
Gastrointestinale sygdomme:
Uncommon: dizziness, headache, sleep disturbance, insomnia Eye disorders:
Usædvanlig: dyspepsi/ halsbrand, mavesmerter, kvalme/ opkastning, obstipation, diarré, flatulens
Uncommon: vision disturbance (including blurred vision and diplopia) Gastrointestinal disorders:
Usædvanlig: pruritus, udslæt, urticaria, ændringer af hovedbund/ hår (inklusive alopeci)
Uncommon: dyspepsia/heartburn, abdominal pain, nausea/vomiting, constipation, diarrhoea, flatulence Skin and subcutaneous tissue disorders:
Usædvanlig: abnorm urinudskillelse (inklusive dysuri, frekvens, nocturi)
Uncommon: pruritus, rash, urticaria, scalp/hair abnormality (including alopecia) Renal and urinary disorders:
Usædvanlig: seksuel dysfunktion
Uncommon: abnormal urination (including dysuria, frequency, nocturia) Reproductive system and breast disorders:
Usædvanlig: træthed
Uncommon: sexual dysfunction General disorders:
Hændelser af særlig klinisk interesse
Uncommon: fatigue
I kliniske studier er der rapporteret påvirkning af skeletmuskler, f. eks. muskuloskeletale smerter inklusive artralgi, muskelkramper, myalgi, muskelsvækkelse samt forhøjede CK værdier.
Events of special clinical interest Skeletal muscle: effects on the skeletal muscle, e.g. musculoskeletal pain including arthralgia, muscle cramps, myalgia, muscle weakness and elevated CK levels have been reported in clinical trials.
4. 4).
1.4% placebo) and muscle weakness (0.1% pravastatin vs. < 0.1% placebo) and the incidence of CK level > 3xULN and > 10xULN in CARE, WOSCOP and LIPID was similar to placebo (1.6% pravastatin vs.
Leverpåvirkning:
1.6% placebo and 1.0% pravastatin vs.
Der er rapporteret forhøjelse af serum transaminaser.
Liver effects: elevations of serum transaminases have been reported.
I de tre langtids -, placebokontrollerede studier CARE, WOSCOPS og LIPID forekom markante ændringer af ALAT og ASAT (> 3 x øvre normalgrænse) med samme frekvens (≥ 1, 2%) i begge behandlingsgrupper.
In the three long-term, placebo- controlled clinical trials CARE, WOSCOP and LIPID, marked abnormalities of ALT and AST (> 3 x ULN) occurred at similar frequency (≤ 1.2%) in both treatment groups.
Postmarketing
Very rare: pancreatitis,
Udover ovennævnte er følgende uønskede hændelser rapporteret meget sjældent ved postmarketing erfaring med pravastatin:
Very rare: jaundice, hepatitis, fulminant hepatic necrosis Musculoskeletal and connective tissue disorders Very rare: rhabdomyolysis, which can be associated with acute renal failure secondary to myoglobinuria, myopathy (see section 4.4) Isolated cases of tendon disorders, sometime complicated by rupture
Sygdomme i nervesystemet Meget sjælden: perifer polyneuropati, specielt ved lang tids anvendelse, paræstesier
There is no specific treatment in the event of overdose.
Forstyrrelser i immunsystemet Meget sjælden: hypersensitivitetsreaktioner, anafylaksi, angioødem, lupus erythematosus- lignende syndrom
In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required.
CPMP/ 3257/ 03 Meget sjælden: pancreatitis
PHARMACOLOGICAL PROPERTIES
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Sygdomme i lever og galde:
5.1 Pharmacodynamic properties
Sygdomme i bevægeapparatet og bindevæv:
Pharmacotherapeutic group:
4. 4) Isolerede tilfælde med senesygdomme, i nogle tilfælde kompliceret med ruptur.
Serum lipid reducing agents/cholesterol reducers/HMG- CoA reductase inhibitors, ATC-Code:
4. 9 Overdosering
C10AA03
5.
and
C10AA03
triglyceride
Pravastatin er en kompetitiv inhibitor af 3- hydroxy- 3- methylglutaryl- coenzyme A (HMG- CoA) reduktase, som er det enzym, der katalyserer det tidlige rate- begrænsende trin i kolesterol biosyntesen og som afstedkommer den lipidsænkende virkning på to måder.
Pravastatin is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase, the enzyme catalysing the early rate-limiting step in cholesterol biosynthesis, and produces its lipid- lowering effect in two ways.
For det første påvirker det den beskedne reduktion i syntesen af intracellulært kolesterol med sin reversible og specifikke kompetitive hæmning af HMG- CoA reduktase.
Firstly, with the reversible and specific competitive inhibition of HMG-CoA reductase, it effects modest reduction in the synthesis of intracellular cholesterol.
Dette medfører et øget antal af LDL- receptorer på celleoverfladerne og forstærket receptor- medieret katabolisme og clearance af cirkulerende LDL - kolesterol.
This results in an increase in the number of LDL-receptors on cell surfaces and enhanced receptor-mediated catabolism and clearance of circulating LDL-cholesterol.
Dernæst hæmmer pravastatin LDL produktionen ved at hæmme den hepatiske syntese af VLDL - kolesterol, LDL- kolesterol forløber.
Secondly, pravastatin inhibits LDL production by inhibiting the hepatic synthesis of VLDL cholesterol, the LDL-cholesterol precursor.
Hos både raske personer og patienter med hyperkolesterolæmi sænker pravastatin natrium følgende lipidværdier: total- kolesterol, LDL- kolesterol, apolipoprotein B, VLDL- kolesterol og triglycerider; mens HDL- kolesterol og apolipoprotein A øges.
In both healthy subjects and patients with hypercholesterolaemia, pravastatin sodium lowers the following lipid values: total cholesterol, LDL-cholesterol, apolipoprotein B, VLDL-cholesterol and triglycerides; while HDL-cholesterol and apolipoprotein A are elevated.
Primær prævention
Clinical efficacy:
"West of Scotland Coronary Prevention Study (WOSCOPS)" var et randomiseret, dobbeltblindt, placebo- kontrolleret studie med 6. 595 mandlige patienter i aldersgruppen 45- 64 år med moderat til svær hyperkolesterolæmi (LDL- C:
Primary prevention The "West of Scotland Coronary Prevention Study (WOSCOPS)" was a randomised, double-blind, placebo-controlled trial among 6,595 male patients aged from 45 to 64 years with moderate to severe hypercholesterolaemia (LDL-C:
155- 232 mg/ dl [4, 0- 6, 0 mmol/ l]) og uden anamnestisk myokardieinfarkt, gennemsnitligt behandlet i 4, 8 år med enten en 40 mg daglig dosis af pravastatin eller placebo som tillæg til diæt.
155-232 mg/dl [4.0-6.0 mmol/l]) and with no history of myocardial infarction, treated for an average duration of 4.8 years with either a 40 mg daily dose of pravastatin or placebo as an adjunct to diet.
Hos pravastatin- behandlede patienter viste resultaterne:
In pravastatin -tre ated patients, results showed:
- reduktion af risikoen for død pga. koronar sygdom og ikke- dødeligt myokardieinfarkt (relativ
- a decrease in the risk of mortality from coronary disease and of non-lethal myocardial infarction
risiko reduktion RRR var 31%; p= 0, 0001 med en absolut risiko på 7, 9% i placebogruppen og 5, 5% hos pravastatinbehandlede patienter); effekten på disse kumulative kardiovaskulære hændelsesrater var tydelige allerede efter 6 måneders behandling;
(relative risk reduction RRR was 31%; p = 0.0001 with an absolute risk of 7.9% in the placebo group, and 5.5% in pravastatin treated patients); the effects on these cumulative cardiovascular events rates being evident as early as 6 months of treatment;
- reduktion af det totale antal af dødsfald pga. kardiovaskulære hændelser (RRR 32%; p= 0, 03);
- a decrease in the total number of deaths from a cardiovascular event (RRR 32%; p = 0.03)
- når risikofaktorerne blev medregnet, blev der også observeret en RRR på 24% (p= 0, 039) i den
- when risk factors were taken into account, a RRR of 24% (p = 0.039) in total mortality was also
totale mortalitet hos patienter behandlet med pravastatin; CPMP/ 3257/ 03
- a decrease in the relative risk for undergoing myocardial revascularisation procedures (coronary
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- reduktion af den relative risikoen for at skulle gennemgå myokardiale
- a reduction in the relative risk of total mortality by 23% (p < 0.0001) and cardiovascular mortality by
revaskulariseringsprocedurer (koronar arterie bypass transplantat kirurgi eller koronar angioplastik) med 37% (p= 0, 009) og koronar angiografi med 31% (p= 0, 007).
25% (p < 0.0001);
Udbyttet af behandlingen efter de ovenfor nævnte kriterier er ikke kendt hos patienter > 65 år, som ikke kunne inkluderes i studiet.
- a reduction in the relative risk of undergoing myocardial revascularisation procedures (coronary
Pga. manglende data i dette studie er udbyttet af pravastatin behandling ikke fastslået hos patienter med hyperkolesterolæmi forbundet med triglyceridværdier > 6 mmol/ l (5, 3 g/ l) efter diæt i 8 uger.
artery bypass grafting or percutaneous transluminal coronary angioplasty) by 20% (p < 0.0001);
Sekundær prævention
- a reduction in the relative risk of stroke by 19% (p = 0.048).