Research into individual predisposition to develop acute rhabdomyolysis attributed to fenoverine.
A xenobiotic, well tolerated by the majority of treated patients, can cause serious complications in patients with individual susceptibility. Based on the hypothesis that such a phenomenon may occur in rare cases of rhabdomyolysis attributed to fenoverine (DCI), we designed a protocol to look for a genetic predisposition. Six patients were included who had previously had an episode of rhabdomyolysis after taking fenoverine. A seventh patient was added, who had only experienced myalgia without cytolysis. All patients were investigated by the following tests: 31-phosphorus nuclear magnetic resonance spectroscopy, histopathological examination of the muscle, muscle contraction tests and biochemical analysis of the muscle. All patients examined proved to have muscle abnormalities. The pathology found varied greatly from patient to patient: mitochondrial myopathy, lipid storage myopathy, sensitivity to malignant hyperthermia or disorders of oxidative metabolism. The probability of finding by chance such rare muscle disorders associated with the equally rare rhabdomyolysis attributed to fenoverine is practically zero. We conclude that there is a cause and effect link between underlying abnormalities and the muscular cytolysis attributed to fenoverine.
Centre anti-poisons- Pharmacovigilance, hôpital Salvator, Marseille, France.
J
J
Jouglard
G
G
Kozak-Ribbens
L
L
de Haro
P J
PJ
Cozzone
D001706:Biopsy; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010276:Parasympatholytics / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D010640:Phenothiazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D010759:Phosphorus Isotopes; D012206:Rhabdomyolysis / Q000139:chemically induced* / Q000235:genetics; D010879:Piperazines
D002334:Carnitine O-Palmitoyltransferase; D010276:Parasympatholytics; D010640:Phenothiazines; D010759:Phosphorus Isotopes; C048314:fenoverine; D010879:Piperazines