Detection and incidence of muscular adverse drug reactions: a prospective analysis from laboratory signals.
OBJECTIVE
The awareness of muscular adverse drug reactions (ADRs) increased since the withdrawal of cerivastatin, a HMG-CoA reductase inhibitor, from the market in August 2001. Our objectives were to assess the detection and incidence of muscular ADRs in a University Hospital using biochemical laboratory data and to evaluate the underreporting rate of drug-induced muscular disorders.


METHODS
A prospective study was undertaken at Toulouse University Hospital, France, for 1 week per month from November 2001 to October 2002. Patients were selected by means of a computerized process using biochemical laboratory data based on serum creatine phosphokinase (CPK) values (over twofold normal). Medical records of all selected patients were then consulted.


RESULTS
During the period of the study, 2017 CPK tests were performed, among which 171 values were over twofold normal corresponding to 129 patients. Because of lack of data, 26 patients were excluded. Among these patients ( n=103), 28 cases of muscular ADRs were suspected, 22 of which were detected in outpatient departments. Four patients were totally asymptomatic and five had an increase of CPK over fivefold normal. Nine cases were classified as "serious". Withdrawal of suspected drugs were done in 16 cases with regression of ADRs in 13 cases. According to hospitalization data, the incidence of muscular ADRs was estimated as 7.2 (2.6-15.7) per 10,000 inpatients and 9.3 (5.8-14.1) per 10,000 outpatients over 12 weeks. The involved drugs were mainly: statins (46.4%), fibrates (14.3%), antiretrovirals (14.3%), angiotensin-II receptor antagonists (10.7%), immunosuppressants (7.1%) or hydroxychloroquine (7.1). Only two cases, judged as "serious", were spontaneously reported by physicians during the same period.


CONCLUSIONS
The results of this survey underline the importance to take into account drug hypothesis in muscular injuries diagnosis.
Dugué
A
A
Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'informations sur le Médicament, Centre Hospitalier Universitaire, Faculté de Médecine, 37 allées Jules Guesde, BP 7202, 31073 Toulouse Cedex 7, France.
Bagheri
H
H
Lapeyre-Mestre
M
M
Tournamille
J F
JF
Sailler
L
L
Dedieu
G
G
Salvayre
R
R
Thouvenot
J P
JP
Massip
P
P
Montastruc
J L
JL
D000328:Adult; D000368:Aged; D003402:Creatine Kinase / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D011446:Prospective Studies; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology
D003402:Creatine Kinase