Has rhabdomyolysis been reported in intoxications with orphenadrine (Disipal)?/nClinical background

Fråga: Has rhabdomyolysis been reported in intoxications with orphenadrine (Disipal)? Clinical background: A 41-year-old man has, after an overdose of orphenadrine (totally 2.5 gram), developed rhabdomyolysis with a CK-value in serum of about 1000 uKat (reference value < 3.3 uKat). The patient has also taken zopiclon (Imovane) 5-6 tablets.

Sammanfattning: Thorough literature search revealed only one case report with evidence of rhabdomyolysis associated with orphenadrine overdose.

Svar: Rhabdomyolysis may be defined as a clinical and laboratory syndrome resulting from skeletal muscle injury with release of muscle cell contents into the plasma (1). Rhabdomyolysis associated with drug overdose is a rare event. In clinically asymptomatic rhabdomyolysis, early diagnosis is made only if routine laboratory tests include determination of serum creatine kinase. Determination of myoglobin in serum and urine is more sensitive and allows earlier diagnosis of muscle necrosis. Several drugs have been associated with rhabdomyolysis in drug overdose, eg phencyclidine, antihistamines, theophylline and barbiturates (2).

Orphenadrine is an antagonist of muscarinic cholinergic receptors used mainly in the treatment of Parkinson´s disease (3). Coma with or without hypoventilation, seizures, shock and dose-related cardiac rhythm disturbances can develop rapidly within one hour after overdosage. Several cases of death have been reported (cardiotoxic) occurring 3-5 hours after ingestion of a lethal dose (2-3 gram in adults) (4).

Clarke and co-workers (5) describe a schizophrenic 40-year-old man who developed rhabdomyolysis after acute poisoning with orphenadrine (the dose unknown). A drug screen revealed orphenadrine at a concentration of about 80 times the upper limit of the therapeutic range. His total creatine phosphokinase (CK) rose 100 times the upper limit but with a CK-MB fraction that was normal, indicating that significant myocardial damage had not occurred. His serum creatinine reached a peak of more than seven times the normal value and normalised within 10 days.

We have found no case of rhabdomyolysis reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) (6) in relation to orphenadrine treatment. A thorough literature search, including Medline, Drugline and common pharmacological handbooks, as well as communication with the Poison Control Center, has not revealed any relevant new information. Tis case should be reported to SADRAC.