Monograph
V03AC03 - Deferasirox |
Propably not porphyrinogenic |
PNP |
Rationale
Only insignificant Cyp metabolism. Interaction studies suggest that deferasirox has an inductive effect on CYP3A4, but this effect is probably too weak to be porphyrinogenic.
Chemical description
Deferasirox is a compound consisting of two hydroxyphenyls and one benzoic acid ring joined by a triazole ring.
Therapeutic characteristics
Deferasirox is an orally active iron chelator used in the treatment of chronic iron overload due to blood transfusions. It is administered orally.
Common adverse reactions of deferasirox that can be confused with an acute porphyric attack are constipation, vomiting, nausea and abdominal pain. Side effects as nausea, vomiting and diarrhoea may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmacokinetics
Deferasirox is metabolised mainly by glucuronidation at the carboxylate group to acyl glucuronide, and at the phenolic hydroxy groups to 2-O-glucuronides. Oxidative metabolism, probably by Cyp1A and Cyp2D6, are minor, representing only 6% and 2% of the dose, respectively (Waldmeier, 2010). Interaction studies suggest that deferasirox is a weak inhibitor of CYP2C8 and a weak inducer of CYP3A4 (Skerjanec, 2010). Defarasirox has a high degree of plasma albumin binding, and the unbound fraction is less than 2 % (Weiss, 2006).
References
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Citation details |
PMID |
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| * | Scientific articles |
| 1. |
Skerjanec, A, Wang, J. et al. Investigation of the Pharmacokinetic Interactions of Deferasirox, a Once-Daily Oral Iron Chelator, With Midazolam, Rifampin, and Repaglinide in Healthy Volunteers.
J Clin Pharmacol. 2010;50(2):205-13. |
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| 2. |
waldmeier, F, et al. Pharmacokinetics, metabolism, and disposition of deferasirox in beta-thalassemic patients with transfusion-dependent iron overload who are at pharmacokinetic steady state.
Drug Metab Dispos. 2010;38(5):808-16. |
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| 3. |
Weiss, H.M., Fresneau, M. et al. In vitro blood distribution and plasma protein binding of the iron chelator deferasirox (ICL670) and its iron complex Fe-[ICL670]2 for rat, marmoset, rabbit, mouse, dog, and human.
Drug Metab Dispos. 2006;34(6):971-5. |
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| * | Drug reference publications |
| 4. |
Sweetman SC, editor. Martindale: The complete drug reference. Deferasirox. Pharmaceutical Press 2009.
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| * | Government bodies |
| 5. |
European Public Assessment Report, Exjade (Scientific discussion).European Medicines Agency (EMEA). Accessible from: emea.europa.eu
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| * | Summary of Product Characteristics |
| 6. |
Norwegian medicines agency. Summary of Product Characteristics (SPC). Exjade.
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