A cautionary tale: delayed onset rhabdomyolysis due to erythromycin/simvastatin interaction

A cautionary tale: delayed onset rhabdomyolysis due to erythromycin/simvastatin interaction An 80-year-old gentleman was admitted with a one-week history of myalgia and inability to walk. Investigations revealed an elevated AST (2069U/l), myoglobinuria (see Appendix Figure 1 on the website) and high creatine kinase (87564U/l). He subsequently developed renal failure requiring haemofiltration. His drug history showed a 4-week course of erythromycin whilst concurrently taking simvastatin. This interaction caused delayed onset of rhabdomyolysis from which he made a full recovery. There are a number of potential interactions with sim-vastatin, including erythromycin, clarithromycin, itracona-zole, ketoconazole, ciclosporin, HIV-protease inhibitors and grapefruit juice. Statins are metabolised by the cytochrome p450 3A4 enzyme, and interactions are thought to be due to the inhibition of this enzyme [1]. The British National Formulary advises avoidance of concomitant use of simvastatin and erythromycin [2]. The simvastatin product advice also states that simvastatin should be discontinued for the duration of treatment with interacting drugs [3]. Although statin-induced rhabdomyolysis is rare, it is important to be aware of this interaction as it is potentially fatal if not recognised and treated early. Informed Consent The patient has signed a written consent form for publication of this case report. An 80-year-old woman was referred by her GP with worsening disequilibrium over the previous 18 months. Medications included a megadose vitamin B6 preparation (reportedly approximately 200 mg per week). Examination revealed signs of a dorsal column sensory neuropathy. Appropriate investigation revealed no other cause for dorsal column sensory loss. Symptoms and signs improved completely on cessation of the supplement after a period of weeks. Dorsal column toxicity due to pyridoxine has been described since the 1980s [1–3]. In the series (n = 24, age range 20–53 years), the daily dose of B6 varied from 200 mg to 6 g. Only one serum level was reported as 'in excess of 30 ng/ml' (120 nmol/l) [1] which accords with the level (171 nmol/l) demonstrated in this case. A recent case report from the Netherlands suggested a toxic effect of B6 at a daily dose of 24–40 mg in two men in their seventh decade [4]. A similar dose to that is described here. A safe dose of 150–200 mg daily is suggested by the experience of one US centre [5] albeit in a younger cohort of 70 individuals. The US no-observed-adverse-effect level is set at 200 mg, safe upper limit at 100 mg and recommended daily …