C08CA03 - Isradipine

Probably not porphyrinogenic

PNP

Mono.SideEffects

Abdominal discomfort is a common side effect of isradipine.

Mono.Rationale

Isradipine is a substrate CYP3A4. It is also a weak inhibitor of CYP3A4, but it is not a mechanism-based inhibitor.

Mono.ChemicalDescription

Dihydropyridine calcium antagonist.

Mono.TherapeuticCharacteristics

Isradipine is used in the treatment of essential hypertension.

Mono.MetabolismAndPharmacokinetics

Isradipine is a substrate of CYP3A4. At least 6 biologically inactive metabolites have been identified and mainly consist of mono acids of the pyridine derivative and a cyclic lactone product (Micromedex). In an in vitro study isradipine was found to be a week competitive inhibitor (Wang 1999). The results of an in -vivo study indicate that isradipine is not a clinically significant inhibitor of CYP3A4 in humans (Beckman 1999) and the SPC also states that isradipine does not seem to inhibit the cytochrome P450 enzymes, in particular CYP3A4, to a clinically significant extent.

Mono.PersonalCommunication

Uneventful use reported in one patient (C. Andersson).

Mono.IpnetDrugReports

Uneventful use reported in 1 patient with acute porphyria.

Mono.SimilarDrugs

Mono.ExploreAlternatives C08C / C08CA or Mono.GoBack.

Mono.References

#	Citation details	PubMed ID
1.	Mibefradil but not isradipine substantially elevates the plasma concentrations of the CYP3A4 substrate triazolam. Backman JT, Wang JS, et al. Clin Pharmacol Ther. 1999 Oct; 66(4):401-7.	10546924
2.	Midazolam alpha-hydroxylation by human liver microsomes in vitro: inhibition by calcium channel blockers, itraconazole and ketoconazole. Wang JS, Wen X, et al. Pharmacol Toxicol. 1999 Oct; 85(4):157-61.	10563513
Drug reference publications
3.	Micromedex® 2.0 (online). Labetalol. Comparative efficacy. (Drugdex System). (Sist oppdatert:2. november 2015).
Summary of Product Characteristics
4.	The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Prescal.