An unusually impressive atorvastatin-induced elevation of serum alkaline phosphatase

Abstract

A 90-year-old woman is referred six months after a transient ischaemic attack (TIA) with asymptomatic cholestatic liver function test (LFT) derangement. Following the TIA, atorvastatin and clopidogrel therapy are initiated. This is added to pre-existent once daily nifedipine for hypertension. Nifedipine (a weak inhibitor of CYP3A4 and competing substrate) and clopidogrel (a competitive inhibitor of CYP3A4) may have affected the metabolism of atorvastatin, resulting in the elevation of serum alkaline phosphatase levels to over six times the upper limit of normal. More often, statin therapy elevates serum alanine aminotransferase levels. Drug-induced liver injury (DILI) was deemed 'probable' as judged by the Roussel Uclaf Causality Assessment Method score. Statin therapy remains overwhelmingly safe, with benefits outweighing risks in the vast majority. The UK recommended LFT monitoring regime facilitates early recognition of DILI. Case reports are examined where similar drug combinations resulted in severe morbidity and mortality.

Keywords: contraindications and precautions; drug interactions; drugs: gastrointestinal system; liver disease; unwanted effects / adverse reactions.

Figure 1

Graphical representation of serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) levels. Temporal association with pharmacological treatments is shown. Tabulated haematological and biochemical data also presented on the same timescale. CRP, C-reactive protein; Hb, haemoglobin; Plt, platelet count; TIA, transient ischaemic attack; WCC, white cell count.