Deferasirox


Concise Prescribing Info
Indications/Uses
Chronic iron overload.
Dosage/Direction for Use
Adult : PO For transfusion-related chronic Fe overload: Initial: 20 mg/kg/day. Max: 40 mg/kg/day. For Fe overload of non-transfusion dependent thalassaemia syndromes: Initial: 10 mg/kg/day. Max: 20 mg/kg/day. Adjust dose in increments or decrements of 5-10 mg/kg, 3-6 mthly.
Dosage Details
Oral
Chronic iron overload
Adult: For transfusion-related chronic Fe overload: Initially, 20 mg/kg once daily. Adjust dose in increments or decrements of 5-10 mg/kg, 3-6 mthly when needed. Max: 40 mg/kg daily. Discontinue treatment if serum-ferritin concentrations consistently fall below 500 mcg/L. For Fe overload of non-transfusion dependent thalassaemia syndromes: Initially, 10 mg/kg once daily, may increase to 20 mg/kg daily after 4 wk, if the baseline liver-Fe concentration is >15 mg Fe/g of liver dry wt. Adjust dose in increments or decrements of 5-10 mg/kg, 3-6 mthly when needed. Max: 20 mg/kg daily. Discontinue treatment if serum-ferritin concentrations consistently fall below 300 mcg/L.
Child: For transfusion-related chronic Fe overload: 2-5 yr Initially, 20 mg/kg once daily. May require higher titration doses. >5-17 yr Same as adult dose. For Fe overload of non-transfusion dependent thalassaemia syndromes: Max: 10 mg/kg daily.
Renal Impairment
CrCl (mL/min) Dosage
<60 Contraindicated.
Hepatic Impairment
Moderate: Considerably reduce dose followed by progressive increase up to a limit of 50%. Severe: Contraindicated.
Administration
Should be taken on an empty stomach. Take at least 30 min before meals preferably at the same time daily. Disperse tab completely by stirring in 100-200 mL of water/apple juice/orange juice until a fine susp is obtained; consume entire content. Rinse the glass w/ a little water/juice to resuspend any residue & drink remainder. Do not disperse tab in fizzy drinks/milk. Swallow whole, do not chew/break/crush tab. Do not take w/ Al-containing antacids.
Reconstitution
Completely disperse tab by stirring in water, orange or apple juice. Disperse <1 g in 105 mL and ≥1 g in 210 mL of liq. Following admin, any residue should be resuspended in a small vol of liq.
Contraindications
Patient w/ poor performance status, high-risk myelodysplastic syndromes, advanced malignancies. Platelet counts <50, 000 cells/mm3. CrCl <60 mL/min. Severe hepatic impairment.
Special Precautions
Moderate hepatic impairment. Childn. Pregnancy and lactation.
Adverse Reactions
Nausea, vomiting, diarrhoea and abdominal pain; rashes, erythema multiforme; headache, pyrexia, pruritus, anxiety, sleep disorders, fatigue, dizziness, skin pigmentation disorders, infections, pharyngolaryngeal pain, oedema; leucocytoclastic vasculitis, urticaria, alopecia; increase in serum creatinine and liver enzyme values, renal tubulopathy, proteinuria; hearing loss and visual disorders, including cataracts.
Potentially Fatal: Upper GI ulceration and haemorrhage, acute renal failure, hepatitis and hepatic failure, serious hypersensitivity reactions e.g. angioedema and anaphylaxis, agranulocytosis, neutropenia, thrombocytopenia.
MonitoringParameters
Monitor serum ferritin concentrations and tests for proteinuria mthly. Measure liver enzymes and bilirubin prior to, 2 wkly during the 1st mth and mthly thereafter. Perform auditory testing and ophthamologic examination before starting treatment and yrly thereafter. Monitor renal function and CBC before starting treatment and regularly during therapy.
Overdosage
Symptoms: Nausea, vomiting, headache, diarrhoea, hepatitis. Management: Symptomatic treatment. Induce emesis or perform gastric lavage.
Drug Interactions
May chelate Al when used w/ Al-containing antacids. Decreased exposure w/ colestyramine and potent inducers of UGT enzymes (e.g. carbamazepine, rifampicin, phenytoin). May increase serum concentration of CYP1A2 (e.g. duloxetine, theophylline) and CYP2C8 (e.g. repaglinide, paclitaxel) substrates, and decrease serum concentrations of CYP3A4 substrates (e.g. ciclosporin, hormonal contraceptives, simvastatin).
Food Interaction
Food variably increases bioavailability.
Action
Description: Deferasirox is an orally active chelator that is selective for Fe (III). It is a tridentate ligand that binds Fe w/ high affinity in a 2:1 ratio. It promotes excretion of Fe, primarily in the faeces and has low affinity for Zn and Cu.
Pharmacokinetics:
Absorption: Absorbed from the GI tract. Increased bioavailability in the presence of food. Absolute bioavailability: Approx 70%. Time to peak plasma concentration: Approx 1.5-4 hr.
Distribution: Distributed into erythrocytes (5%). Volume of distribution: Approx 14 L. Plasma protein binding: Approx 99% (mainly albumin).
Metabolism: Undergoes hepatic metabolism via glucuronidation by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and to a lesser extent by UGT1A3. Minimally metabolised (approx 8%) by oxidative cytochrome P-450 enzymes.
Excretion: Excreted mainly in the faeces, via bile as metabolites and unchanged drug; via urine (approx 8%). Mean elimination half-life: Approx 8-16 hr.
Chemical Structure

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Deferasirox, CID=214348, https://pubchem.ncbi.nlm.nih.gov/compound/Deferasirox (accessed on Jan. 20, 2020)

Storage
Store at 25°C. Protect from moisture.
ATC Classification
V03AC03 - deferasirox ; Belongs to the class of iron chelating agents. Used in the management of chronic iron overload associated with blood transfusion.
References
Anon. Deferasirox. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 26/11/2015.

Buckingham R (ed). Deferasirox. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/11/2015.

Jadenu Tablet, Film coated (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 26/11/2015.

Joint Formulary Committee. Deferasirox. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/11/2015.

McEvoy GK, Snow EK, Miller J et al (eds). Deferasirox. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 26/11/2015.

Disclaimer: This information is independently developed by MIMS based on Deferasirox from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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