Deferasirox is indicated for the treatment of chronic iron overload due to frequent blood transfusions(≥ 7 ml/kg/month of packed red blood cells) in patients with beta thalassemia major aged 6 years andolder.Deferasirox is also indicated for the treatment of chronic iron overload due to blood transfusionswhendeferoxamine therapy is contraindicated orinadequate in the following patient groups: patientswith otheranemias; patients aged 2 to 5years; patients with beta thalassemia major with iron overloaddue to infrequent bloodtransfusions (< 7 ml/kg/month of packed redblood cells).
Identified risks due to the use of Deferasirox (Exjade®) are acute renal failure, increased serum creatinine, renal tubulopathy, elevations of liver transaminases and gastrointestinal haemorrhage.
Below details risk minimization plans to minimize these risks that should be followed by healthcare professionals.
Risk minimization plan for increased serum creatinine
It is recommended that serum creatinineand/or creatinine clearance be assessed induplicate before initiating therapy andmonitored monthly thereafter together with tests for proteinuria.
Exjade® is contraindicated for patient with creatinine clearance <40 mL/min or serumcreatinine >2 times the age-appropriate upperlimit of normal.
Exjade® treatment must be used with caution in patients with serum creatinine levels above the age-appropriate upper limit of the normal range. Caution should especially be used inpatients with creatinine clearance between 40and less than 60 mL/min or serum creatinine levels abovethe age-appropriate upper limit of the normalrange, particularly in caseswhere there are additional risk factors thatmay impair renal function such asconcomitant medications, dehydration, orsevere infections.
If there is a progressive increase in serumcreatinine beyond the upper limit of normal,Exjade® should be interrupted. Therapy withExjade® may be reinitiated depending on theindividual clinical circumstances.
For adult patients, the daily dose of Exjade®may be reduced by 10 mg/kg if a non-progressiverise in serum creatinine by >33%above the average of the pre-treatmentmeasurements is seen at two consecutivevisits, and cannot be attributed to othercauses.
Patients with pre-existing renal conditions, orpatients who are receiving medicinal productsthat may depress renal function may be moreat risk of complications and weekly monitoringof serum creatinine and/or creatinineclearance is recommended in the first monthafterinitiation or modification of therapy, andmonthly thereafter.
Serum creatinine should be monitoredmonthly in all patients and if necessary dailydoses can be reduced by 10 mg/kg.
For paediatric patients, the dose maybe reduced by 10 mg/kg if serum creatininelevels riseabove the age-appropriate upperlimit of normal at two consecutive visits. If there is a progressive increase in serumcreatinine beyond the upper limit of normal,Exjade® should be interrupted. Therapy withExjade® may be reinitiated depending on theindividual clinical circumstances.
Care should be taken to maintain adequate hydration in patients who develop diarrhoea or vomiting.
Risk minimization plan for increased liver transaminases
It is recommended thatserum transaminases, bilirubin and alkalinephosphatase bemonitored before theinitiation of treatment, every 2 weeks duringthe first month andmonthly thereafter.
If thereis a persistent and progressive increase inserum transaminase levels that cannot beattributed to other causes, Exjade® should beinterrupted.
Once thecause of the liverfunction test abnormalities has been clarifiedor after return to normallevels, cautious reinitiationof Exjade® treatment at a lower dosefollowed by gradual doseescalation may beconsidered.
Risk minimization plan for gastrointestinalhaemorrhage andulcer; oesophagitis
It is recommended that platelet counts should be assessed before initiation of therapy
Exjade is contraindicated for patient with platelet count <50 x 109/L
Caution should be exercised in patients whoare taking Exjade® in combination with drugsthat have known ulcerogenic potential, suchas NSAIDs, corticosteroids, or oralbisphosphonates.
Caution should be exercised in patients receivinganticoagulants.
Report Adverse Drug Reactions to the Saudi FDA
The SFDA urges both healthcare professionals and patients to report side effects from the use of Deferasirox (Exjade®) to the SFDA either online, by regular mail or by fax, using the following contact information: