To the Editor: A 71-year-old man was admitted to hospital in 2002 with nausea, abdominal discomfort and myalgia. He was dehydrated and had mild right upper quadrant tenderness. No muscle tenderness was noted.

Five weeks previously, an infected right femoropopliteal gortex graft had been surgically removed. Methicillin-resistant Staphylococcus aureus was present on culture. Therapy with fusidic acid (250 mg three times daily) and rifampicin (600 mg daily) had been commenced, and the patient’s condition improved. Fusidic acid therapy was continued because of unsatisfactory wound healing. On presentation he had been taking fusidic acid for 4 weeks. He had been taking simvastatin (40 mg nightly) for 8 years.

The patient had a history of generalised vascular disease and multiple bypass procedures. He had a background of paroxysmal atrial fibrillation, myocardial infarction, left ventricular failure, hypertension, hypercholesterolaemia and chronic airways limitation. His other medications were metoprolol, irbesartan, frusemide, warfarin, paracetamol and narcotic analgesics.

Test results showed the following biochemical concentrations: aspartate transaminase, 1618 U/L (normal range, < 40 U/L); alanine transaminase 657 U/L (normal range [NR], < 35 U/L); alkaline phosphatase 133 U/L (NR, 25–100 U/L); total bilirubin, 29 μmol/L (NR, < 20 μmol/L); γ-glutamyltransferase, 37 U/L (NR, < 50 U/L); urea, 24.7 mmol/L (NR, 3.0–8.0 mmol/L); creatinine, 0.35 mmol/L (compared with previous creatinine concentration of 0.11 mmol/L [NR, 0.06–0.12 mmol/L]).

Drug hepatitis, secondary to fusidic acid was suspected, and therapy with this drug was ceased.

The following day, the patient’s clinical status declined, with generalised muscle pains and weakness, significantly impairing his mobility. The serum creatine kinase concentration was elevated at 66 710 U/L (normal range, 60–220 U/L), with a normal troponin I concentration. Myoglobinuria (567 200 ng/mL) was detected.

Simvastatin therapy was ceased, and there was prompt clinical improvement, with recovery of renal function and a gradual fall in the concentration of serum creatine kinase. On discharge 14 days after admission, his serum creatine kinase concentration was 1153 U/L and creatinine concentration was 0.12 mmol/L. Transaminase concentration readings fell rapidly in line with the creatine kinase concentration, suggesting they were of muscular rather than hepatic origin.

Three other cases of rhabdomyolysis have been reported as a result of interaction between an HMG CoA-reductase inhibitor and fusidic acid,1-3 but there have been no previous reports from Australia.

Fusidic acid, like simvastatin, undergoes extensive first-pass metabolism in the liver (over 98%). Simvastatin is metabolised via the cytochrome P3A4 enzyme system. It is known that, if given concomitantly with inhibitors of this system (eg, macrolides and azole derivatives), statin concentrations can become elevated and lead to an increased likelihood of adverse effects.4 Fusidic acid is not known to be an inhibitor of this system (Peter Hobbs, Manager of Medical Affairs, CSL Limited [manufacturers of fucidin], personal communication), although our case is suggestive of such an interaction.

This case demonstrates the interaction of fusidic acid with simvastatin resulting in rhabdomyolysis. The extensive use of statin therapy in patients with vascular disease makes it important for doctors to be aware of this interaction when prescribing fusidic acid.