Although lercanidipine possesses a tertiary amin, a functional group that has been associated with MI-complex formation and mechanism-based inhibition of CYP enzymes in other substrates, lercanidipine has not been reported to be mechanism-based inhibitor of any CYP enzymes.

Dihydropyridine calcium antagonist

Lercanidipine is used in the treatment of mild to moderate essential hypertension. It is administered orally.

Lercanidipine is extensively metabolized by CYP3A4 (Klotz 2002, SPC). In vitro studies with human liver microsomes have found lercanidipine to inhibit CYP3A4 and CYP2D6 (SPC). However, inhibition was found at concentrations 150-fold higher than the maximal plasma concentration after administration of doses of 20 mg. In vivo coadministration of lercanidipin and the CYP3A4 substrate simvastatin showed a 56 % and 28 % increase in the AUC of simvastatin and its active metabolite, respectively (Zhou 2013). According to the FDAs classification of inhibitors, lercanidipine may thus be described as a weak inhibitor of CYP3A4 in vivo (FDA). On the other hand lercanidipine did not alter the metabolism of the CYP3A4 substrate midazolam or the CYP2D6 substrate metoprolol, when coadministrated in vivo (McClellan 2000). Lercanidipine possesses a tertiary amine. Tertiary amines may undergo N-dealkylation resulting in a metabolic intermediate which has been shown in other drugs to cause mechanism-based inhibition of CYP enzymes (Riley 2007, Zhou 2007). Lercanidipine has not been reported to be a mechanism-based inhibitor of any CYP enzymes. Lercanidinpine is not listed as a mechanism-based inhibitor or an inducer (Hisaka 2010, Isoherranen 2009, Pelkonen 2008).

Uneventful use reported in 1 patient with acute porphyria.