Simvastatin therapy may be associated with rare cases of interstitial lung disease. This is suggested by a retrospective study conducted on 34 patients with suspected pulmonary toxicity from simvastatin, which investigated the role of pharmacogenetic factors and concomitant therapies in the development of this syndrome.
In 70.5% of cases, pulmonary toxicity was due to the use of simvastatin concomitantly with CYP3A4 inhibitors or substrates capable of increasing its bioavailability, or with three or more drugs with the potential to induce acidosis by favoring the conversion of simvastatin in the lactone form, pharmacologically inactive, but toxic.
The presence of genetic polymorphisms associated with reduced activity of enzymes or transporters known to play a key role in simvastatin metabolism explained lung toxicity in only 20% of cases.
The study also evaluated the effect of stopping or replacing simvastatin with another statin on the course of pulmonary interstitial disease. Significant clinical improvement or stabilization was observed in all cases where simvastatin was discontinued or replaced with a hydrophilic statin, such as rosuvastatin. On the other hand, the replacement of simvastatin with another lipophilic statin such as atorvastatin was associated with a worsening of the clinical picture.
In practice, in patients with simvastatin-induced pulmonary toxicity who must continue to take a lipid-lowering drug, it is essential to consider on the one hand the metabolic properties of any drugs taken concomitantly, and on the other hand the change in therapy using a hydrophilic statin.
Reference:
Jessurun N, Drent M, et al. Role of drug-gene interactions and pharmacogenetics in simvastatin-associated pulmonary toxicity.
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