Dose adjustment noncompliance in a thalassaemia patient
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Dose Adjustment/ Noncompliance in a Thalassaemia Patient. Background. Adequate dose titration and compliance with chelation therapy are crucial factors in achieving prolonged patient survival

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Dose adjustment noncompliance in a thalassaemia patient

Dose Adjustment/Noncompliance in a Thalassaemia Patient


  • Adequate dose titration and compliance with chelation therapy are crucial factors in achieving prolonged patient survival

    • The probability of surviving to at least 25 years of age in poorly chelated patient is only one third that of adequately chelated patients1

1. Brittenham GM et al. N Engl J Med. 1994;331:567-573.

Patient presentation
Patient Presentation

  • 30-year-old male with thalassaemia major

  • Patient presented with baseline liver iron concentration of 11.0 mg Fe/g dry weight and baseline serum ferritin of 2500 ng/mL

Thresholds for parameters used to evaluate iron overload
Thresholds for Parameters Used to Evaluate Iron Overload



Iron Overloaded State




LIC (mg Fe/g dw)





Serum ferritin (ng/mL)


>1000 to <2500


Transferrin saturation (%)



T2* (ms)





Alanine aminotransferase (U/L)



Labile plasma iron (μM)



Increased risk of complications

Increased risk of cardiac disease

Courtesy of A. Taher, MD.

Treatment history
Treatment History

  • Patient receives regular transfusions of 2 units of packed red blood cells per month

  • Since age 3, patient has been treated with desferrioxamine at 30 mg/kg/d, 5 days per week

  • Patient expressed dissatisfaction with the burdensome subcutaneous regimen and was often noncompliant with treatment


What should the next step be?

A. Counsel patient about the importance of compliance and continue him on desferrioxamine

B. Increase desferrioxamine dosage

C. Switch to oral deferasirox

Switch to deferasirox
Switch to Deferasirox

  • 3 iron chelators are approved for use in patients with thalassaemia: 2 oral agents, deferiprone (3 times daily) and deferasirox (once daily); and the subcutaneous drug, desferrioxamine

  • Given patient’s dissatisfaction with infusion treatment, an oral chelator seemed a more promising alternative than continuing on desferrioxamine

  • Deferiprone is associated with potentially serious neutropaenia and is administered 3 times daily

  • Because of the favourable toxicity profile and once-daily administration of deferasirox, patient was started on deferasirox 20 mg/kg/da

aAlthough 20 mg/kg/d is the usual starting dose of deferasirox, 10 mg/kg/d or 30 mg/kg/d can also be used, depending on transfusion frequency1.

1 European Agency for Evaluation of Medicinal Products guidelines, 2007.

Deferasirox dosing by transfusion requirements and therapeutic goals
Deferasirox Dosing by Transfusion Requirements and Therapeutic Goals

Recommended initial deferasirox dose

pRBCs >14 mL/kg/mo(~4 adult units)

pRBCs <7 mL/kg/mo(~2 adult units)

Maintenance of body iron

Desferrioxamine 40 mg/kg/d for 5 days per week

Deferasirox 20 mg/kg/d

30 mg/kg/d

20 mg/kg/d

Reduction of body iron

10 mg/kg/d

Starting doses may also be modified as follows:

Deferasirox dose

Transfusion requirement

Therapeutic goal

For patients well managed on desferrioxamine, suggested starting dose may be numerically half desferrioxamine dose, eg:

EXJADE® (deferasirox) Basic Prescribing Information. Novartis Pharma AG. National Prescribing Information should be followed.

Question Therapeutic Goals

Approximately 2 weeks after starting deferasirox, the patient developed skin rash of moderate severity. How should the rash be managed?

A. Continue treatment

B. Stop treatment; reintroduce drug at a low dose after rash has resolved

C. Stop treatment; reintroduce drug at low dose in combination with steroid after rash has resolved

Skin rash deferasirox dose modification algorithm
Skin Rash—Deferasirox Dose-Modification Algorithm Therapeutic Goals

Continue treatment without interruption

Mild to moderate rash

More severe rash

  • Interrupt treatment

  • Reintroduce deferasirox at lower dose after resolution of rash

  • Gradually escalate dose

  • Interrupt treatment

  • Reintroduce deferasirox at lower dose maybe in combination with oral steroid after resolution of rash

  • Gradually escalate dose

Severe rash

Deferasirox Basic Prescribing Information. Novartis Pharma AG. National Prescribing Information should be followed.

Managing deferasirox related skin rash
Managing Deferasirox-Related Therapeutic GoalsSkin Rash

  • Patient was continued on treatment without interruption

  • Rash resolved within 2 weeks

Response to treatment serum ferritin
Response to Treatment Therapeutic GoalsSerum Ferritin

  • Serum ferritin levels increased from 2500 to 3209 ng/mL between months 3 and 6; therefore, deferasirox dose was increased to 30 mg/kg/day

  • Serum ferritin showed steady decreases during months 7–9

  • During the next 3 months, serum ferritin levels began to increase again

Deferasirox increased to

30 mg/kg/d

Courtesy of A. Taher, MD

Question Therapeutic Goals

What might account for the increase in serum ferritin noted after month 9?

A. Inflammation/infection

B. Increased transfusion requirement

C. Noncompliance with treatment

Patient compliance
Patient Compliance Therapeutic Goals

  • There had been no change in patient’s transfusion requirement and there was no clinical indication of inflammation or infection

  • However, in talking with the patient, the clinician discovered that he had not been fully compliant with treatment, missing some pills and occasionally not taking the full deferasirox suspension

  • Therefore, lack of compliance seemed the most likely cause of the increase in serum ferritin levels noted after month 9

  • The patient was counseled about the importance of compliance and taking the medication as directed

Postcounseling outcome
Postcounseling Outcome Therapeutic Goals

  • Patient continued on deferasirox 30 mg/kg/d and was able to comply with the treatment regimen

    • Steady decreases in serum ferritin were observed

  • At month 24, serum ferritin levels had decreased to 812 ng/mL and liver iron concentration was 3.4 mg Fe/g dry weight

  • Deferasirox dose was decreased to a maintenance level of 10 mg/kg/d

    • Patient’s serum ferritin levels remain constant at around 800 ng/mL

  • He has had no further adverse events or abnormal laboratory values

Overall response to treatment
Overall Response to Treatment Therapeutic Goals

Serum Ferritin

Liver Iron Concentration

Courtesy of A. Taher, MD.

Conclusions Therapeutic Goals

  • Deferasirox dose should be reviewed regularly at 3- to 6-month intervals and adjusted according to changes in serum ferritin levels

  • Physicians need to stress to their patients the importance of full compliance with therapy if iron burden is to be reduced