What is the risk of cross reactivity with regard to angioedema as a side-effect of statins?

Fråga: What is the risk of cross reactivity with regard to angioedema as a side-effect of statins?

Sammanfattning: Angioedema is a known, but rare side-effect to all statins. Little is known regarding the risk for cross reactivity between different statins. Based on similarities of the chemical structure, and a few case reports, there might be an increased risk for cross reactivity between simvastatin, pravastatin and lovastatin.

Svar: Angioedema and other, similar hypersensitivity reactions, have been reported as rare side-effect of simvastatin, as well as of other statins (HMG-CoA reductase inhibitors). In the Swedish register of adverse drug reactions, there are 38 reports concerning statins and angioedema, most of which involve simvastatin (1). In one case, a 70-year-old woman reacted with rash and breathing problems after one week of atorvastatin treatment, even though she had previously tolerated fluvastatin.

A literature search in Pubmed, Drugline and pharmacological handbooks has revealed surprisingly few publications. The possibility of cross reactivity between different statins has been discussed in one earlier Drugline document (2). A case report from 1995 is cited; an older man developed asthma, angioedema and elevated IgE while on lovastatin, and reacted in a similar way after six months of pravastatin treatment (3). One further case report was retrieved in Pubmed, describing a nearly 80-year-old man with severe urticaria. Treatment with ramipril, atenolol, aspirin and simvastatin was stopped and the symptoms resolved. One month later, oral rechallenge was performed, one drug at a time, under supervision. A slight urticaria was noted after simvastatin at a low dose (0.2 mg). A prick test with different statins was positive for lovastatin only. Subsequently, the patient was treated with atorvastatin without side-effects (4).

In the publications above, the chemical structure of different statins is discussed. Simvastatin, pravastatin and lovastatin are derived from fungal metabolites and do all share a similar chemical structure; a hexahydronaphtalene ring with two side chains. On the other hand, atorvastatin, fluvastatin and rosuvastatin are synthetic compounds with different chemical structures. From a theoretical point of view, and as supported by the few cases above, there might be a risk for cross reactivity within the group of naphthalene ring-based statins.

In the present case, a careful challenge with a synthetic statin, e.g atorvastatin, could be tried. An adverse drug reaction report should be sent the Medical Product Agency. Swedis Drugline 17871 (year 2001) Fosso CK, Miller MJ, Solomon WR, Baker JR. Adverse effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors associated with elevated serum IgE and eosinophilia. J Allergy Clin Immunol 1995;95(5 PT 1):1053-5 Bellini V, Assalve D, Lisi P. Urticarial vasculitis from simvastatin: what is the alternative drug. Dermatitis 2010;21(4):223-4