natgillin/translations-raw huggingface dataset:
Spontane indberetninger Indtil 8. august 2001 har Bayer Global Drug Safety modtaget i alt 5. 667 indberetninger med 11. 637 mistænkte bivirkninger i forbindelse med brug af cerivastatin.
Spontaneous reports Up to 8 August 2001 a total of 5,667 reports containing 11,637 suspected adverse drug reactions associated with the use of cerivastatin have been received by Bayer global drug safety.
Hovedparten af de indberettede bivirkninger (78%) omfatter følgende COSTART- kropssystemer: muskel- skelet- systemet (3. 417, 29%), kroppen som helhed (1. 814, 16%), fordøjelsessystemet (1. 663, 14%), stofskifte - og ernæringssystemet (1. 354, 12%), nervesystemet (914, 8%) og urogenitalsystemet (768, 7%).
The majority of the reported reactions (78%) belong to the following COSTART body systems- Musculoskeletal (3,417; 29%), Body as a whole (1,814; 16%), Digestive (1,663; 14%), Metabolic and Nutritional (1,354; 12%), Nervous (914; 8%) and Urogenital (768; 7%).
Af de alvorlige bivirkninger vedrørte 55% muskel- skelet -, urogenital - samt stofskifte - og ernæringssystemet og afspejler indberetningerne om rabdomyolyse.
For serious ADRs, 55% belonged to the Musculoskeletal, Urogenital and Metabolic and Nutritional body systems and reflect the reports of rhabdomyolysis.
"Mistænkt" rabdomyolyse omfatter derfor 51% af alle spontane indberetninger.
Rhabdomyolysis There were 1302 (23%) cases of confirmed and 1603 (28%) cases of unconfirmed rhabdomyolysis. “ Suspected” rhabdomyolysis therefore comprises 51% of all spontaneous reports.
Ved 0, 4 mg cerivastatin monoterapi er indberetningsfrekvensen for rabdomyolyse større end efter lavere doser af cerivastatin.
With 0.4 mg cerivastatin monotherapy, the reporting rate of rhabdomyolysis is greater than that seen with lower doses of cerivastatin.
Indberetningsfrekvensen for rhabdomyolyse for 0, 8 mg er væsentlig større end frekvensen for 0, 4 mg og lavere doser.
Reporting rates of rhabdomyolysis with the 0.8mg dose were greatly in excess of those seen with both the 0.4mg and lower doses.
I forbindelse med brug af cerivastatin kombineret med fibrater (primært gemfibrozil) steg indberetningsfrekvensen betydeligt ved stigende doser alt efter indberetningsregionen.
When cerivastatin was used concomitantly with fibrates (primarily gemfibrozil), there was a substantially higher reporting rate with increasing dose, depending on the reporting region.
Som for monoterapi er indberetningsfrekvensen for 0, 4 mg større end for lavere doser af cerivastatin.
As for monotherapy, the reporting rate for 0.4mg cerivastatin was higher than seen with the lower doses of cerivastatin.
Indberetningsfrekvensen for 0, 8 mg er væsentlig højere end for nogen af de lavere doser.
The reporting rate for 0.8mg cerivastatin was substantially higher than that with any of the lower doses.
En søgning i FDA- databasen Adverse Event Reporting System (AERS) til indberetning af bivirkninger gav 6. 489 indberetninger verden over af rabdomyolyse i forbindelse med brug af statin indtil slutningen af 2000.
A search of the FDA Adverse Event Reporting System (AERS) database found 6,489 reports worldwide of rhabdomyolysis associated with the use of any statin up to the end of 2000.
Indberetningsfrekvenserne for bekræftede og mistænkte tilfælde af rabdomyolyse i forbindelse med cerivastatinmonoterapi er større end for de øvrige statiner.
The reporting rates of confirmed and suspected cases of rhabdomyolysis in association with cerivastatin monotherapy is greater than that seen with any of the other statins.
WHO- databasen indeholder 546 indberetninger af rabdomyolyse i forbindelse med brug af cerivastatin.
The WHO database contains 546 reports of rhabdomyolysis associated with the use of cerivastatin.
Indberetningsfrekvensen for rabdomyolyse i forbindelse med cerivastatin er højere end for andre statiner, og imod forventning er den steget med tiden.
The reporting rate for rhabdomyolysis with cerivastatin is higher than with other statins and contrary to expectations has increased over time.
Af de 546 indberetninger af rabdomyolyse i forbindelse med cerivastatin var der i 302 (55%) tilfælde samtidig ordineret gemfibrozil.
Of the 546 reports of rhabdomyolysis with cerivastatin, 302 (55%) were with concomitant gemfibrozil.
Misforholdet mellem indberetningsfrekvensen for kombinationsbehandlingen sammenlignet med antallet af recepter indikerer en kraftig interaktion mellem de to lægemidler, som medfører øget risiko for rabdomyolyse.
The disproportion between the reporting rate on combination treatment compared with the proportion of prescriptions suggests a strong interaction between the two drugs leading to an increased risk of rhabdomyolysis.
Interaktionen mellem cerivastatin og gemfibrozil ser også ud til at skabe øget risiko for nyresvigt, muskelbetændelse, myopati og død.
The interaction between cerivastatin and gemfibrozil also appears to produce an increased risk of renal failure, myositis, myopathy and death.
Dataene vedrørende brug af gemfibrozil sammen med de øvrige statiner indikerer også en øget risiko, men misforholdet mellem indberetningsfrekvensen ved kombinationsbehandling og antallet af recepter er betydeligt mindre end ved cerivastatin.
The data for use of gemfibrozil with the other statins also suggest an increased risk however the disproportion between the reporting rate on combination treatment and the proportion of prescriptions is considerably less than that seen with cerivastatin.
Der ses en lignende uforholdsmæssig risiko ved samtidig ordinering af clopidogrel.
A similar disproportionate risk is also seen when clopidogrel is prescribed concomitantly.
Ud af 45 indberetninger om bivirkninger, hvor de to lægemidler blev ordineret samtidig, drejede 20 (44%) sig om rabdomyolyse.
Of 45 adverse reaction reports where the two drugs were administered concomitantly, 20 (44%) were of rhabdomyolysis.
CPMP/ 811/ 02 Dødstilfælde
CPMP/ 811/ 02 Fatal cases
Bekræftede tilfælde af rabdomyolyse havde en dødelighed på 7, 6%.
Confirmed rhabdomyolysis cases had a 7.6% fatality rate.
Fra lanceringen til slutningen af september 2001 blev der indberettet 99 dødstilfælde til Bayer.
From the beginning of marketing to the end of September 2001 ninety-nine fatal cases were reported to Bayer.
Hovedparten blev indberettet i USA (62, 63%), 21 tilfælde (21, 2%) i EU og andre i Japan og resten af verden.
The majority occurred in the USA (62.63%), 21 cases (21.2%) in the EU with others in Japan and the rest of the world.
Hovedparten af dødstilfældene blev indberettet i 2001 (70, 51%).
The majority of reported fatal cases occurred in 2001 (70.51%).
På trods af at der blev indført kontraindikationer i USA i 1999, fortsatte lægerne med at ordinere gemfibrozil sammen med cerivastatin.
Despite contraindications being introduced in the US in 1999, physicians there still continued to prescribe gemfibrozil with cerivastatin.
Dødsårsagen var sandsynligvis forbundet med rabdomyolyse i 52% af tilfældene og muligvis forbundet hermed i 33, 7% af tilfældene, mens den ikke var forbundet med rabdomyolyse i 14, 3% af tilfældene (ingen tidsmæssig sammenhæng, andre årsager).
Death was probably related to the rhabdomyolysis in 52% of cases, possibly related in 33.7% and not related in 14.3% (no temporal relationship, other aetiologies.) There were no sex differences and the mean age was 70.9 years.
Af dødstilfældene blev 36, 4% samtidig behandlet med gemfibrozil og 17, 7% med clopidogrel.
Of the fatal cases, 36.4% were treated concomitantly with gemfibrozil and 17.7% with clopidogrel.
Det skal bemærkes, at den vigtigste indberettede dødsårsag i forbindelse med cerivastatin var rabdomyolyse, mens den for andre statiner var leversvigt.
Of note is the fact that for cerivastatin the leading reported cause of death was rhabdomyolysis, while for other statins it was hepatic failure.
Indberetningsfrekvensen af leversvigt med dødelig udgang i forbindelse med cerivastatin var 2- 6 gange lavere end for de øvrige statiner.
The reporting rate of fatal hepatic failure with cerivastatin was 2-6 times lower than that of the other statins.
Cerivastatin forbindes med en højere indberetningsfrekvens af rabdomyolyse med dødelig udgang end atorvastatin, og brug af cerivastatin kombineret med gemfibrozil øger indberetningsfrekvensen af rabdomyolyse med dødelig udgang ved lavere doser cerivastatin.
Cerivastatin is associated with a higher reporting rate of fatal rhabdomyolysis than atorvastatin and the use of cerivastatin in combination with gemfibrozil increases the reporting rate of fatal rhabdomyolysis at lower doses of cerivastatin.
Undersøgelser i perioden efter markedsføring Mellem 1998 og 1999 blev der gennemført flere undersøgelser med overvågning efter markedsføring (PMO) i Tyskland.
Post marketing studies Between 1998 and 1999 several Post-marketing observational (PMO) studies were performed in Germany.
I alt blev 43. 366 patienter med hyperkolesterolæmi og en gennemsnitsalder på 59 år behandlet med cerivastatin.
In total 43,366 hypercholesterolaemic patients, average age 59 years, were treated with cerivastatin.
Den gennemsnitlige overvågningsperiode var på 10 uger.
The median observation period was 10 weeks.
Begyndelsesdoserne var på 0, 1 mg/ dag (15%), 0, 2 mg/ dag (56, 7%) og 0, 3 mg/ dag (26, 3%) med op - og nedtitrering mellem disse doser.
The starting doses were 0.1mg/ day (15%), 0.2mg/ day (56.7%) and 0.3 mg/ day (26.3%), with up- and down-titration between these doses.
32% af patienterne var tidligere blevet behandlet med lipidsænkende medicin, og for 15% var der tale om et statin.
Thirty-two percent of patients had previously been treated with lipid lowering medication, for 15% this was a statin.
172 af disse patienter (0, 4%) oplevede mindst én bivirkning, som indikerede myopati (forhøjet CPK, myopati, muskelbetændelse, muskelsmerter, muskelsvækkelse, ledsmerter).
One hundred and seventy two of these patients (0.4%) experienced at least one adverse event indicative of myopathy (CPK increased, myopathy, myositis, myalgia, myasthenia, arthralgia).
Der blev ikke observeret nogen tilfælde af rabdomyolyse.
No cases of rhabdomyolysis were observed.
Frekvensen af disse bivirkninger ser ikke ud til at være dosisafhængig.
The frequency of these adverse events does not appear to be dose-dependent.
For patienter, der tidligere var blevet behandlet med et statin, var forekomsten af disse bivirkninger dobbelt så høj som i andre grupper (0, 76% sammenlignet med 0, 35%).
For patients pre-treated with a statin the incidence of these AEs was twice that in other groups (0.76% vs 0.35%).
Forekomsten af disse bivirkninger var også højere hos patienter, der samtidig tog lipidsænkende medicin, sammenlignet med patienter, der ikke gjorde det (0, 58% sammenlignet med 0, 39%).
The incidence of these AEs was also higher in patients taking concomitant lipid lowering medications compared with those who did not (0.58% vs 0.39%).
Resultaterne af disse undersøgelser er ikke blevet publiceret.
Two further post-marketing studies have been conducted in Germany, the results of which have not been published.
Farmakoepidemiologiske undersøgelser
Pharmacoepidemiological studies
Pacificare Der blev foretaget flere farmakoepidemiologiske undersøgelser ved hjælp af reklamationsdatabasen Pacificare.
Pacificare Several pharmacoepidemiological studies were performed using the Pacificare claims database.
Den første undersøgelse fulgte patienter i 180 dage efter indeksordineringen af statin for at identificere eventuelle forekomster af myopati, som opfyldte myopatidefinitionen.
The first study followed up patients for 180 days after the index prescription of a statin to identify any occurrence of myopathy that fulfilled the case definition.
Myopatien skulle være indtruffet senest 30 dage efter ordineringen af statin, og patienten skulle have standset eller skiftet statinbehandling efter diagnosen.
Cases were also required to have occurred within 30 days of a statin prescription and to have stopped or switched statin treatments following diagnosis.
Der var 394 tilfælde af myopati, som opfyldte definitionen, ud af en kohorte på 133. 454 undersøgte personer i undersøgelse 1.
There were 394 myopathy cases fulfilling the study definition amongst a cohort of 133,454 study subjects in study 1.
Tabel 7 viser ukorrigerede absolutte risici efter sidste statin inden diagnosen og justerede OR (Odds Ratios) for myopati med sidste statin (med eller uden gemfibrozil) sammenlignet med ikke- samtidig cerivastatin.
Table 7 provides crude absolute risks by last statin prior to diagnosis and the adjusted Odds Ratios for myopathy with the last statin (with or without gemfibrozil) compared to non- concurrent cerivastatin.
Den ukorrigerede absolutte frekvens var den samme i hele klassen.
Crude absolute rates were similar across the class.
Justerede OR for myopati med sidste statin (med eller uden gemfibrozil) sammenlignet med ikke- samtidig cerivastatin var ikke væsentlige.
Adjusted Odds Ratios for myopathy with the last statin (with or without gemfibrozil) compared to non-concurrent cerivastatin were not significant.
De fleste tilfælde af myopati var ikke alvorlige.
Most cases of myopathy were non-serious.
CPMP/ 811/ 02
CPMP/ 811/ 02 Table 7:
Der meldtes ikke om, at andre statiner kombineret med gemfibrozil øgede risikoen for myopati sammenlignet med monoterapi.
Last Statin prior to case Absolute Risks Adjusted* Odds Ratios for myopathy with
diagnose
diagnosis
for myopati% statin (med eller uden gemfibrozil) (antal sammenlignet med ikke- samtidig eksponerede) cerivastatin
of Myopathy% the last statin (with or without (No. exposed) gemfibrozil) compared to non-concurrent cerivastatin
Simvastatin Cerivastatin Fluvastatin Atorvastatin Lovastatin Pravastatin * Korrigeret for alder, køn,
Simvastatin Cerivastatin Fluvastatin Atorvastatin Lovastatin Pravastatin
0, 2% (5. 279) 0, 8 (0, 4- 1, 7) 0, 3% (12. 340) Reference 0, 3% (31. 941) 1, 3 (0, 8- 2, 0) 0, 4% (29. 916) 1, 6 (1, 0- 2, 5) 0, 3% (809) 1, 0 (0, 2- 4, 3) 0, 2% (53. 169) 1, 1 (0, 7- 1, 8) diabetes, skift og dosis
0.2% (5,279) 0.8 (0.4-1.7) 0.3% (12,340) Reference 0.3% (31,941) 1.3 (0.8-2.0) 0.4% (29,916 1.6 (1.0-2.5) 0.3% (809) 1.0 (0.2-4.3) 0.2% (53,169) 1.1 (0.7-1.8)
Undersøgelse 2 var en forlængelse af den første undersøgelse og dækkede samme perioder plus yderligere 18 måneder.
Study 2 was an extension of the first study and covered the same time periods plus an additional 18 months.
Resultaterne indikerede, at cerivastatin havde den laveste risiko for myopati, mens fluvastatin havde den højeste.
The results suggested that cerivastatin was associated with the lowest risk of myopathy whilst fluvastatin had the highest.
En mulig forklaring på den øgede risiko for myopati i forbindelse med fluvastatin er større brug af erythromycin og azol antifungale midler i denne gruppe.
A possible explanation of the increased risk of myopathy with fluvastatin was there was a higher use of erythromycin and azole antifungals in this group.
Undersøgelse 3 drejede sig om problemer med dødsfald, myopatirelaterede hospitalsindlæggelser samt muligheden for manglende diagnose af rabdomyolyse.
Study 3 addressed the problems of death, myopathy related hospitalisations and the concern of missed rhabdomyolysis diagnosis.
De foreløbige resultater viste, at den generelle risiko for myopati var 0, 4%, og at indlæggelsesforekomsten for myopati i forbindelse med brug af cerivastatin i monoterapi ikke steg i forhold til de øvrige statiner.
The preliminary results suggested that the overall risk for myopathy was 0.4% and that the hospitalisation rate for myopathy associated with the use of cerivastatin monotherapy was not increased relative to the other statins.
Der var otte gange så stor risiko for myopati ved kombination af cerivastatin og gemfibrozil som ved monoterapi.
There was an 8-fold increased risk of myopathy when cerivastatin and gemfibrozil were taken concomitantly compared with monotherapy.
Alle disse undersøgelser benyttede den samme patientpopulation i varierende omfang og kan som sådan ikke betragtes som uafhængige.
All of these studies used the same population of patients to varying degrees and as such cannot be considered as independent.
GPRD- databasen Undersøgelsen benyttede en populationsbaseret kohorte af patienter, som for nylig havde fået diagnosticeret hyperlipidæmi, og/ eller som fik ordineret et hypolipidæmisk middel.
GPRD database The study used a population based cohort of subjects who were newly diagnosed with hyperlipidaemia and/ or who received a prescription for a hypolipidaemic agent.
Alle tilfælde af nyresvigt, muskeltoksicitet, fulminant leversvigt eller dødsfald i patientgruppen blev identificeret.
All cases of community acquired renal failure, myotoxicity, fulminant hepatic failure or death were identified.
Kohorten omfattede 68. 374 patienter, som for første gang fik registreret hyperlipidæmi.
The cohort comprised 68 374 patients with first-time recorded hyperlipidaemia.
Ud af disse patienter blev 23. 707 ikke behandlet i nogen tid under opfølgningen, 23. 343 fik ordineret statin, 2. 283 fik ordineret fibrat, og 900 fik ordineret statin og fibrat.
Of these subjects, 23707 were untreated for some time during follow-up, 23343 were given statin prescriptions, 2283 were given fibrate prescriptions and 900 were given statin and fibrate prescriptions.
2. 053 patienter meldte om muskelrelaterede symptomer, og ingen patienter havde et kreatinkinaseniveau på over 1. 000 U/ l.
Two thousand and fifty three patients reported muscle-related symptoms, no patients had a creatine kinase level of more than 1000 U/ l.
Der blev identificeret 16 tilfælde af mulig eller sandsynlig erhvervet nyresvigt.
Sixteen cases were identified as possible or probable cases of acquired renal failure.
10. 000 patientår i cerivastatingruppen.
The incidence in the statin group overall was 1.6 per 10,000 patient years with an incidence of 0 per 10,000 patient years in the cerivastatin group.
10. 000 patientår.
For the concurrent statin and fibrate group the rate was 27.2 per 10,000 patient years.
Der forekom ingen tilfælde af fulminant leversvigt under opfølgningen.
No cases of fulminant hepatic failure occurred during follow-up.
Der var i alt 992 dødsfald som følge af alle årsager.
A total of 992 deaths from all causes occurred.
1. 000 personår for cerivastatin, 7, 9 for atorvastatin, 10 for simvastatin, 10. 8 for pravastatin og 11. 9 for fluvastatin sammenlignet med 6, 3 for fibrater og 4. 2 i den ikke- behandlede gruppe.
The crude mortality rates were 8.3 per 1000 person- years for cerivastatin, 7.9 for atorvastatin, 10 for simvastatin, 10.8 for pravastatin and 11.9 for fluvastatin, as compared with 6.3 for fibrates, 4.2 in the untreated group.
Mediplus Denne britiske database blev undersøgt for førstegangstilfælde af myopati, muskelbetændelse eller nyresvigt efter ordinering af et statin.
Mediplus This UK database was examined for first time cases of myopathy, myositis or renal failure subsequent to any statin prescription.
Analysen blev gentaget for de patienter, som ikke havde skiftet
The analysis was repeated for those patients who had not switched statin.
CPMP/ 811/ 02
811/ 02 8
Yderligere data Gennemgangen af de originale data leveret af indehaveren af markedsføringstilladelsen frembragte flere punkter, som CPMP krævede yderligere belyst.
Additional data The review of the original data provided by the MAH elicited several issues for which the CPMP required further information.
CPMP vedtog derfor en liste over udestående problemer i december 2001.
As a consequence a List of Outstanding Issues was adopted by the CPMP in December 2001.
Interaktion mellem cerivastatin og clopidogrel
Interaction between cerivastatin and clopidogrel
In vitro- undersøgelser Der blev foretaget en undersøgelse af den potentielle farmakokinetiske interaktion mellem clopidogrel og cerivastatin i mikrosomer fra human lever.
In vitro studies An investigation of the potential pharmacokinetic clopidogrel/ cerivastatin interaction was conducted in human liver microsomes.
Resultaterne indikerer, at eventuel farmakokinetisk interaktion ikke skyldes hæmning af CYP450- medieret metabolisme af cerivastatin.
The results suggest that any pharmacokinetic interaction is not due to the inhibition of CYP450 mediated metabolism of cerivastatin
Kliniske undersøgelser Princess- undersøgelsen havde til formål at bestemme, om tidlig akutbehandling med cerivastatin efter en hjerteinfarkt ville reducere forekomsten af hjerte- kar- morbiditet og - mortalitet.
Clinical Trial data The Princess study was designed to determine whether early acute treatment with cerivastatin after a myocardial infarction would reduce the incidence of cardiovascular morbidity and mortality.
Patienterne blev randomiseret til enten 0, 4 mg eller placebo med mulighed for titrering til 0, 8 mg.
Patients were randomised to either 0.4mg or placebo with optional titration to 0.8mg.
Denne undersøgelse blev stoppet, efter at markedsføring og distribution af cerivastatin blev suspenderet.
This study was stopped following the suspension of marketing and distribution of cerivastatin.
Spontane data Ved en re- analyse af spontane data indberettet til indehaveren af markedsføringstilladelsen i perioden indtil 30. september 2001 fandt man 1. 579 bekræftede tilfælde af rabdomyolyse ud af 7. 620 indberetninger.
Spontaneous data A reanalysis of spontaneous data reported to the MAH up to 30 September 2001 found 1579 confirmed cases of rhabdomyolysis amongst 7,620 reports.
Der var samtidig ordineret gemfibrozil eller andre fibrater i 576 (36, 5%) af tilfældene og clopidogrel i 246 (15, 6%) af tilfældene.
Gemfibrozil or other fibrates had been co- prescribed in 576 (36.5%) of cases and clopidogrel in 246 (15.6%).
I seks tilfælde var der samtidig ordineret gemfibrozil og clopidogrel.
Six cases had been co-prescribed gemfibrozil and clopidogrel.
Hovedparten (85%) af de tilfælde af rabdomyolyse, som var indberettet i forbindelse med samtidig brug af clopidogrel, fandtes hos patienter, der fik enten 0, 4 eller 0, 8 mg cerivastatin.
The majority (85%) of rhabdomyolysis cases reported in association with concomitant clopidogrel use were in patients receiving either 0.4 or 0.8mg of cerivastatin.
17 af tilfældene havde dødelig udgang (17, 2% af alle dødstilfælde).
Seventeen cases had a fatal outcome (17.2% of all fatal cases).
Indberetningsfrekvensen for rabdomyolyse stiger, når cerivastatin ordineres i doser på 0, 4 mg eller derover sammen med clopidogrel, sammenlignet med monoterapi.
There was an increase in the reporting rate of rhabdomyolysis when cerivastatin was prescribed at doses of 0.4mg or more with clopidogrel compared with monotherapy.
Ved en cerivastatindosis på 0, 8 mg var indberetningsfrekvensen den samme som for denne dosis kombineret med gemfibrozil.
At a cerivastatin dose of 0.8mg, reporting rates were similar to those seen at that dose with concomitant gemfibrozil.
Der er omfattende klinisk dokumentation for, at interaktion mellem clopidogrel og cerivastatin medfører øgede plasmaniveauer af cerivastatin og en deraf følgende øget risiko for rabdomyolyse.
There is a large amount of clinical evidence for an interaction between clopidogrel and cerivastatin leading to increased plasma levels of cerivastatin and hence an increased risk of rhabdomyolysis.
Ud fra in vitro- dataene ser interaktionsmekanismen ikke ud til at skyldes hæmning af CYP450- medieret metabolisme, men den nøjagtige mekanisme kendes ikke.
Based on the in vitro data the mechanism of the interaction does not appear to be due to inhibition of CYP450 mediated metabolism but the exact mechanism remains unknown.
Hverken interaktionen med gemfibrozil eller clopidogrel kunne forudsiges på grundlag af cerivastatinets metabolisme.
Neither of the interactions with gemfibrozil or clopidogrel were predictable based on the metabolism of cerivastatin.
Mangelen på en bestemt mekanisme betyder, at det er vanskeligt at forudsige, hvor mange andre mulige tilfælde af interaktion der kan medføre øget risiko for rabdomyolyse.
The lack of a definite mechanism means that it is difficult to predict how many other possible interactions there may be which could lead to an increased risk of rhabdomyolysis.