Severe acute liver injury associated with lumiracoxib.

BACKGROUND AND AIM: Significant elevations in liver transaminases were noted in some patients during pre-marketing clinical trials with lumiracoxib, a selective COX-2 inhibitor. It was withdrawn from the Australian market in August 2007, because of an association with severe liver injury. We describe in detail three cases of severe liver injury in patients taking lumiracoxib METHODS: Three patients admitted to our hospital with severe liver injury and taking lumiracoxib are described in detail, together with information on a further six cases reported to the Australian Therapeutics Goods Administration (TGA), none of whom had pre-existing liver disease or obvious risk factors for liver disease. RESULTS: Liver histology showed severe hepatic necrosis. One patient required liver transplantation and another died. Autoantibodies were detected in all three patients. As with the other six cases reported to the TGA, all were females who had been taking lumiracoxib 200-400 mg daily, typically for a few months, for osteoarthritis. CONCLUSIONS: Lumiracoxib can be associated with severe liver injury. The presence of a variety of positive auto-antibodies suggests an altered immune response may be contributory.

Iatrogenic neuropsychiatric syndromes.

BACKGROUND: Although tramadol induced neuropsychiatric toxicity, dependence and withdrawal have been extensively reported in chronic pain sufferers, such cases continue to surface in clinical practice. OBJECTIVE: We describe two cases of atypical withdrawal after abrupt discontinuation of tramadol and a case of serotonin syndrome. The outcome was favourable in all three cases. DISCUSSION: Patients and prescribers are reminded of the risk of severe morbidity including seizures associated with tramadol withdrawal. Serotonin syndrome can be precipitated with tramadol use especially in combination with other serotonergic drugs.

Aminoglycoside-associated Fanconi syndrome.

The objective is to describe a case of probable aminoglycoside-induced Fanconi syndrome and make clinicians aware of the existence of this underrecognized and underdiagnosed complication in patients treated with a prolonged course of high-dose aminoglycosides. A 53-year-old man admitted for recurrent infective exacerbations of chronic bronchiectasis already colonized with Pseudomonas aeruginosa was treated intermittently with intravenous gentamicin (320 to 560 mg/d) for a total of 4 months to a total cumulative dose of 9.4 g. The patient developed profound hypophosphatemia, hypocalcemia, hyperphosphaturia, and aminoaciduria. Electrolyte disturbances persisted until gentamicin therapy was stopped, recurred with rechallenge, and did not correct with calcium and phosphate supplementation. This case shows that prolonged exposure to high-dose aminoglycoside therapy can be associated with Fanconi syndrome, which is a manifestation of proximal tubular dysfunction. There are only a few case reports to date of Fanconi syndrome as a probable complication of high-dose aminoglycoside therapy. The Naranjo Adverse Drug Reaction probability scale score indicated that this was a probable adverse reaction associated with administration of high-dose aminoglycosides. The differential diagnosis of electrolyte disturbances as a manifestation of proximal tubule dysfunction and type 2 renal tubular acidosis is vast; however, Fanconi syndrome needs to be considered in patients treated with high doses of aminoglycosides for longer than 6 days, after more common causes of hypophosphatemia are excluded.