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 and older. Deferasirox is also indicated for the treatment of chronic iron overload due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in the following patient groups: patients with other anemias; patients aged 2 to 5 years; patients with beta thalassemia major with iron overload due to infrequent blood transfusions (< 7 ml/kg/month of packed red blood 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

1. It is recommended that serum creatinine and/or creatinine clearance be assessed in duplicate before initiating therapy and monitored monthly thereafter together with tests for proteinuria.

2. Exjade® is contraindicated for patient with creatinine clearance <40 mL/min or serum creatinine >2 times the age-appropriate upper limit of normal.

3. 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 in patients with creatinine clearance between 40 and less than 60 mL/min or serum creatinine levels above the age-appropriate upper limit of the normal range, particularly in cases where there are additional risk factors that may impair renal function such as concomitant medications, dehydration, or severe infections.

4. If there is a progressive increase in serum creatinine beyond the upper limit of normal, Exjade® should be interrupted. Therapy with Exjade® may be reinitiated depending on the individual clinical circumstances.

5. For adult patients, the daily dose of Exjade® may be reduced by 10 mg/kg if a non-progressive rise in serum creatinine by >33% above the average of the pre-treatment measurements is seen at two consecutive visits, and cannot be attributed to other causes.

6. Patients with pre-existing renal conditions, or patients who are receiving medicinal products that may depress renal function may be more at risk of complications and weekly monitoring of serum creatinine and/or creatinine clearance is recommended in the first month after initiation or modification of therapy, and monthly thereafter.

7. Serum creatinine should be monitored monthly in all patients and if necessary daily doses can be reduced by 10 mg/kg.

8. For paediatric patients, the dose may be reduced by 10 mg/kg if serum creatinine levels rise above the age-appropriate upper limit of normal at two consecutive visits. If there is a progressive increase in serum creatinine beyond the upper limit of normal, Exjade® should be interrupted. Therapy with Exjade® may be reinitiated depending on the individual clinical circumstances.

9. Care should be taken to maintain adequate hydration in patients who develop diarrhoea or vomiting.

Risk minimization plan for increased liver transaminases

1. It is recommended that serum transaminases, bilirubin and alkaline phosphatase be monitored before the initiation of treatment, every 2 weeks during the first month and monthly thereafter.

2. If there is a persistent and progressive increase in serum transaminase levels that cannot be attributed to other causes, Exjade® should be interrupted.

3. Once the cause of the liver function test abnormalities has been clarified or after return to normal levels, cautious reinitiation of Exjade® treatment at a lower dose followed by gradual dose escalation may be considered.

    

Risk minimization plan for gastrointestinal haemorrhage and ulcer; oesophagitis

1. It is recommended that platelet counts should be assessed before initiation of therapy

2. Exjade is contraindicated for patient with platelet count <50 x 109/L

3. Caution should be exercised in patients who are taking Exjade® in combination with drugs that have known ulcerogenic potential, such as NSAIDs, corticosteroids, or oral bisphosphonates.

4. Caution should be exercised in patients receiving anticoagulants.

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:

National Pharmacovigilance Center (NPC)

Saudi Food and Drug Authority-Drug sector

3292 Northern Ring Road

Al Nafal District

Riyadh 13312 – 6288

Kingdom of Saudi Arabia

Tel: 012759222 ext. 2334, 2352, 2353, 2354, 2356

Fax: 012107398

Email :

Website: