Deferasirox (deferasirox)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Deferasirox is a heavy metal antagonist that chelates iron.
Deferasirox chelates iron by binding ferric ions and forming a stable, soluble complex. The drug is a tridentate ligand with high binding affinity for iron in a 2:1 ratio (2 ligand molecules binding 1 iron atom). At dosages of 10, 20, and 40 mg/kg daily, deferasirox is capable of sequestering 0.1, 0.3, and 0.4 mg of iron, respectively, per kg of body weight daily.
The drug demonstrates 2-5 times higher potency than deferoxamine in mobilizing and excreting tissue iron. Deferasirox reduces liver iron burden; preliminary data suggest that the drug also mobilizes cardiac iron stores.
Deferasirox chelates zinc and copper, but with very low binding affinity. Decreased concentrations of zinc and copper have been reported in humans during therapy; however, the clinical importance of this effect is unknown. Deferasirox has the potential to chelate with aluminum, but has lower binding affinity for aluminum than for iron.
Deferasirox is well absorbed following oral administration, with peak plasma concentrations usually attained within 1.5-4 hours. The absolute oral bioavailability of tablets for oral suspension (Exjade(R)) is 70%. Food variably increases bioavailability of Exjade(R).
The bioavailability of Jadenu(R) film-coated tablets and deferasirox granules for oral use (Jadenu(R) Sprinkle) granules is 36 and 52% greater than Exjade(R) tablets for oral suspension, respectively. Exposure to Jadenu(R) tablets and deferasirox granules for oral use (Jadenu(R) Sprinkle) when administered with a light meal is similar to that under fasting conditions. Exposure to deferasirox based on maximum serum concentrations and AUC increases in a linear fashion after single doses and under steady-state conditions.
Deferasirox is approximately 99% bound to plasma proteins, mainly albumin. Deferasirox is metabolized principally in the liver via glucuronidation by uridine diphosphate-glucuronosyltransferase (UGT) 1A1 and to a lesser extent by UGT1A3. Deconjugation of glucuronide metabolites and subsequent enterohepatic recirculation are likely to occur.
Deferasirox is minimally metabolized (8%) by oxidative cytochrome P-450 (CYP) enzymes. Deferasirox and its metabolites are eliminated principally in feces via bile (84%) and to a lesser extent in urine (8%). The mean elimination half-life of deferasirox is 8-16 hours.
Deferasirox is principally eliminated via glucuronidation in the liver. Pharmacokinetics not specifically studied in geriatric patients 65 years of age and older. Clearance of the drug in females is moderately lower (i.e., 17.5%) than that in males.
Following oral administration of single or multiple doses, systemic exposure of adolescents and children to deferasirox was less than in adult patients; systemic exposure to deferasirox is approximately 50% lower in children under 6 years of age compared to adults.
USES: This medication is used to treat ongoing high levels of iron in the body caused by multiple blood transfusions. It is also used to treat high levels of iron in people with a certain blood disorder who do not require blood transfusions (non-transfusion-dependent thalassemia). It works by binding to iron, allowing the body to pass extra iron out in the stool.
Deferasirox belongs to a class of drugs known as iron-chelating agents. Frequent blood transfusions are often needed in certain types of blood diseases (such as sickle cell disease, anemia). Blood transfusions have very helpful benefits, but they can cause the body to hold on to too much iron.
The extra iron can build up in the body and cause problems such as heart failure, liver disease, and diabetes. Getting rid of extra iron can decrease the risk of these diseases.
Generic name: deferasirox
Pronunciation: (dee-FER-a-sir-ox)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Deferasirox
Indications
The following indications are listed for Deferasirox:
- Chronic Iron Overload Due To Repeated Blood Transfusions
- Chronic Iron Overload In Patient With Non-Transfusion-Dependent Thalassemia (Ntdt)
Also known as: Secondary Iron Overload From Multiple Blood Transfusions, Transfusion Hemosiderosis, Transfusion-Induced Iron Overload, Transfusional Hemosiderosis, Transfusional Iron Overload.
Dosing
For patients currently receiving deferasirox tablets for oral suspension (e.g., Exjade(R)) for chelation therapy, when converting to film-coated tablets or granules (e.g., Jadenu(R)) the dosage should be reduced by about 30%, rounded to the nearest whole tablet or whole sachet dosage strength (Table 1).
Table 1. Conversion from Deferasirox Tablets for Oral Suspension to Deferasirox Film-Coated Tablets or Granules for Oral Use
Dosage of Deferasirox Dosage of Deferasirox Tablets for Oral Tablets or Granules for Suspension Oral Use Transfusion-Dependent Iron Overload Starting Dose 20 mg/kg per day 14 mg/kg per day Titration Increments 5-10 mg/kg 3.5-7 mg/kg Maximum Dose 40 mg/kg per day 28 mg/kg per day Non-Transfusion-Dependen t Thalassemia Syndrome Starting Dose 10 mg/kg per day 7 mg/kg per day Titration Increments 5-10 mg/kg 3.5-7 mg/kg Maximum Dose 20 mg/kg per day 14 mg/kg per day
Deferasirox is administered orally as tablets for oral suspension (e.g., Exjade(R)), as film-coated tablets for oral use (e.g., Jadenu(R)), and as granules for oral use (e.g., Jadenu(R) Sprinkle). Dosing conversion is required when switching between deferasirox formulations. In patients currently receiving chelation therapy with deferasirox tablets for oral suspension (e.g., Exjade(R)), conversion to film-coated tablets use (e.g., Jadenu(R)) or granules for oral use (e.g., Jadenu(R) Sprinkle) requires a decrease in dosage.
Administer deferasirox tablets for oral suspension (e.g., Exjade(R)) and film-coated tablets or granules (e.g., Jadenu(R)) once daily on an empty stomach (at least 30 minutes before eating), preferably at the same time each day. Film-coated tablet and granule preparations may also be administered with a light meal (containing less than 7% fat and approximately 250 calories).
Store all deferasirox preparations between 20-25degreesC (excursions permitted between 15-30degreesC). Protect from moisture.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Deferasirox is metabolized principally by uridine diphosphate-glucuronosyltransferase (UGT) 1A1 and to a lesser extent by UGT1A3; cytochrome P-450 (CYP) isoenzymes appear to play a minor role (approximately 8%). Deferasirox inhibits CYP isoenzymes 3A4, 2C8, 1A2, 2A6, 2D6, and 2C19 in vitro.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*eGFR less than 40 mL/minute per 1.73 m2
*Poor performance status
*High-risk myelodysplastic syndrome
*Advanced malignancy
*Platelet counts less than 50,000/mm3
*Known hypersensitivity to deferasirox or any ingredient in the formulation
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in more than 5% of patients receiving deferasirox with transfusional iron overload include diarrhea, vomiting, nausea, abdominal pain, rash, and increases in serum creatinine concentration.
Adverse effects reported in more than 5% of patients receiving deferasirox with NTDT syndromes include diarrhea, rash, and nausea.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy for transfusional iron overload have not been established in children younger than 2 years of age.
Use of deferasirox for transfusional iron overload is based on data from 292 pediatric patients ranging from 2 to less than 16 years of age with various congenital and acquired anemias.
Safety and efficacy for chronic iron overload in non-transfusion-dependent thalassemia (NTDT) syndromes have not been established in children younger than 10 years of age.
Use of deferasirox for chronic iron overload in NTDT is based on data from 16 pediatric patients with chronic iron overload and NTDT who were 10 to less than 16 years of age with a liver iron concentration (LIC) of at least 5 mg Fe/g dry weight and a serum ferritin concentration of more than 300 mcg/L. Additional data from well-designed pediatric and adult studies support this use.
Systemic exposure of deferasirox in children less than 6 years of age is lower than that in adults.
No data are available to inform the drug-associated risk of deferasirox use in pregnancy. Animal reproductive studies demonstrated decreases in offspring viability and increases in renal anomalies at doses less than or similar to the equivalent human dose. Use deferasirox during pregnancy only if benefits clearly outweigh the potential risks of treatment.
Deferasirox is distributed into milk in rats; it is not known whether the drug is distributed into human milk. The effects of deferasirox on milk production, and the effects on the breastfed infant are not known. Consider the benefits of breastfeeding along with the potential for adverse effects from deferasirox exposure to the breast-fed infant, along with the mother's clinical need for the drug. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
The manufacturer makes no specific dosage recommendations in geriatric patients; however, in clinical trials, geriatric patients experienced a higher frequency of adverse reactions compared to younger adult patients. Due to decreased hepatic, renal, and cardiac function, in addition to the presence of other coexisting conditions, careful selection of the dosage of deferasirox is necessary in geriatric patients, and dosing is usually initiated at the lower end of the dosing range.
Deferasirox should be used with caution in geriatric patients because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly. Geriatric patients receiving deferasirox should be monitored closely for early signs and/or symptoms of adverse reactions that may require dosage adjustment. Select the dose cautiously in geriatric patients.
In clinical studies of deferasirox, geriatric patients 65 years of age or older experienced a higher incidence of adverse reactions than younger adults. The majority of these geriatric patients had myelodysplastic syndrome (MDS).
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.