Category: pharmacological
Aliases: Baycol, Lipobay
HMG-CoA reductase inhibitor (statin) — withdrawn worldwide 2001-08-08 after 52 confirmed fatal rhabdomyolysis cases, predominantly attributable to coadministration with gemfibrozil. Mechanism of the fatal DDI: CYP2C8 inhibition by gemfibrozil glucuronide raises cerivastatin AUC ~6× (Backman 2002 PMID:12496749 — verbatim AUC 559% of control). Bayer paid $1.15 billion to settle lawsuits over the withdrawal. Retained in the registry for historical reference and as the canonical CYP2C8 DDI cautionary tale. PK (Baycol label + Mück 2000 PMID:10976657 review): Absolute F 60% (range 39–101%) due to presystemic first-pass, Tmax 2–3 h, terminal t½ 2–4 h, plasma protein binding >99%, apparent Vd ~0.3 L/kg (~21 L). Dual CYP2C8/CYP3A4 metabolism — the latter pathway only ~50% effective when both routes are inhibited, which is why gemfibrozil (CYP2C8 inhibitor, AUC ↑5.59× Wave 2a v1.1) and itraconazole (CYP3A4) produced lethal rhabdomyolysis combinations and led to the August 2001 worldwide withdrawal after 52 fatal cases.
PO: 3h