Drug information of Deferasirox

Deferasirox

Drug group:

 Deferasirox is an oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. It is the first oral medication approved in the USA for this purpose.

Mechanism of effect

Two molecules of deferasirox are capable of binding to 1 atom of iron. Deferasirox works in treating iron toxicity by binding trivalent (ferric) iron (for which it has a strong affinity), forming a stable complex which is eliminated via the kidneys.

Pharmacodynamic

Deferasirox is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain.

Pharmacokinetics

Absorption

Bioavailability: 70%

Peak Plasma Time: 1.5-4 hr

Peak plasma concentration and AUC increase in a linear fashion (accumulation factor ~1.3-2.3 following multiple doses)

Distribution

Protein Bound: 99% (mostly to albumin)

Vd: 14.37 L (adults)

Metabolism

Glucuronidation, mainly by UGT1A1 and to a lesser extent by UGT1A3

Inhibits CYP1A2, CYP2C8

Induces CYP3A4

Elimination

Half-life: 8-16 hr

Excretion: 84% feces; 8% urine

Dosage

Iron Overload

Adults and 2 years and older

Exjade(R):
Initial dose: 20 mg/kg, orally, once a day - calculate dose to the nearest whole tablet
Monitor serum ferritin monthly: Adjust dose every 3 to 6 months, by 5 to 10 mg/kg, based on serum ferritin trends
Maximum dose: 40 mg/kg

Jadenu(R):
Initial dose: 14 mg/kg, orally, once a day - calculate dose to the nearest whole tablet
Monitor serum ferritin monthly: Adjust dose every 3 to 6 months, by 3.5 to 7 mg/kg, based on serum ferritin trends
Maximum dose: 28 mg/kg

 Thalassemia

Adults and 10 years and older:

Exjade(R):
Initial dose: 10 mg/kg, orally, once a day - calculate dose to the nearest whole tablet
-If baseline liver iron concentration (LIC) is over 15 Fe/g dw, consider increasing dose to 20 mg/kg/day after 4 weeks
Maximum dose: 20 mg/kg/day

After 6 months therapy:
-If LIC remains above 7 mg Fe/g dw: increase to 20 mg/kg/day
-If LIC is 3 to 7 mg Fe/g dw: Continue at no more than 10 mg/kg/day

Jadenu(R):
Initial dose: 10 mg/kg, orally, once a day - calculate dose to the nearest whole tablet
-If baseline liver iron concentration (LIC) is over 15 Fe/g dw, consider increasing dose to 14 mg/kg/day after 4 weeks
Maximum dose: 14 mg/kg

Drug contraindications

hypersensitivity to this drug

Alerts

Renal failure

  • Can cause acute renal failure and death, especially with comorbidities and advanced stages of hematologic disorders
  • Measure serum creatinine and determine creatinine clearance in duplicate prior to treatment initiation; monitor renal function at least monthly thereafter
  • If baseline renal impairment or increased risk of acute renal failure exist, monitor creatinine weekly for the first month, then at least monthly
  • Consider dose reduction, interruption, or discontinuation based on increases in serum creatinine

Hepatic failure

  • Can cause hepatic injury including hepatic failure and death
  • Obtain serum transaminases and bilirubin in all patients prior to initiating treatment, every 2 weeks during the first month, and at least monthly thereafter
  • Avoid with severe (Child-Pugh C) hepatic impairment and reduce the dose with moderate (Child Pugh B) hepatic impairment

Gastrointestinal hemorrhage

  • Can cause gastrointestinal (GI) hemorrhages, which may be fatal, especially in elderly patients who have advanced hematologic malignancies and/or low platelet counts
  • Monitor and discontinue for suspected GI ulceration or hemorrhage
  • If you are 65 or older, use this medicine (deferasirox tablets) with care. You could have more side effects.

Points of recommendation

  • Take on an empty stomach or with a light meal.
  • Take this medicine by mouth with water or other liquid.
  • If you cannot swallow tablets, the tablet may be crushed and added to a small amount of soft food. Take the mixture right away. Do not store for future use.
  • Take this medicine (deferasirox tablets) at the same time of day.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine (deferasirox tablets) affects you.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Have an eye exam as you have been told by your doctor.
  • Have a hearing test before starting this medicine and while you take this medicine (deferasirox tablets).
  • Do not take antacids that have aluminum in them with this medicine.

Pregnancy level

C

Related drugs

Deferiprone , Succimer , Deferoxamine


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