NEW YORK (Reuters Health) - Coadministration of certain statin drugs with cytochrome P450-3A4 (CYP3A4) inhibitors should be avoided, a researcher from Atlanta points out in the November 1st issue of the American Journal of Cardiology.
“Although exceedingly well tolerated, treatment with statins incurs a small risk of myopathy or potentially fatal rhabdomyolysis, particularly when co-administered with medications that increase their systemic exposure,” Dr. Terry A. Jacobson from Emory University School of Medicine notes.
He reports results from four small, short-term, parallel-group studies looking at the pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin, when coadministered with four CYP3A4 inhibitors (verapamil, mibefradil, itraconazole, and clarithromycin) in healthy adults.
Taken together, the studies demonstrate that these inhibitors “elicit profound increases in the systemic exposures of the lipophilic statins simvastatin and atorvastatin and their active metabolites.”
In contrast, he observes, pravastatin, which is a hydrophilic non-CYP substrate that has no active metabolites, “exhibits a neutral pharmacokinetic interaction profile with respect to CYP substrates.”
Dr. Jacobson notes that the findings are consistent with current U.S. Food and Drug Administration labeling for statins.
Earlier this month, Britain’s Medicines and Healthcare Products Regulatory Agency issued a bulletin reminding clinicians about potential statin drug interactions. (See Reuters Health report Nov 2, 2004).
Source: Am J Cardiol 2004;94:1140-1146. [ Google search on this article ]
MeSH Headings:Benzimidazoles: Cytochrome P-450: Cytochromes: Enzymes, Coenzymes, and Enzyme Inhibitors: Heterocyclic Compounds: Heterocyclic Compounds, 2-Ring: Hydroxylases: Naphthalenes: Polycyclic Hydrocarbons: Polycyclic Hydrocarbons, Aromatic: Tetrahydronaphthalenes: Mibefradil: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
