Normal pregnancy in a patient with β-thalassaemia major receiving iron chelation therapy with deferasirox (Exjade®)

To the Editor: Improvements in managing b-thalassaemia major have allowed many patients to survive beyond puberty. Fertility can, however, be impaired as a result of iron overload-related hypogonadism (1), although assisted reproductive techniques and advances in treating iron overload have increased the number of successful pregnancies in such patients (2–9). During pregnancy, patients may require additional blood transfusions to treat complications such as pre-eclampsia or severe anaemia, increasing the need for effective iron chelation therapy. Clinical data are limited regarding the use of chelation therapy during pregnancy, and it is unclear whether these agents pose any risk to the developing foetus. However, there are case reports of successful pregnancies following treatment with deferoxamine (Desferal ; Novartis Pharmaceuticals Corp, East Hanover, NJ, USA) (10, 11). This case study discusses a patient who became pregnant while receiving deferasirox (Exjade ; Novartis Pharmaceuticals Corp), the oncedaily, oral iron chelator. As deferasirox use is contraindicated during pregnancy, no recommendation can be made on the safety of iron chelation in pregnancy. The 35-yr-old female patient (born June 1972) was diagnosed with b-thalassaemia major at 8 months of age. She has received red blood cell (RBC) transfusions since diagnosis and was treated with continuous deferoxamine from the age of 6 yr. Due to poor compliance and subsequent lack of efficacy, she was switched to deferiprone monotherapy (Ferriprox ; Apotex Inc., Toronto, ON, Canada) aged 29 yr. She received deferiprone for 2 yr, before switching to deferoxamine and ⁄or deferiprone because of a lack of efficacy; she remained on this regimen until August 2006. The patient had her first menstruation at the age of 12 and had regular menstrual cycles until she was 30 yr old, when hormonal replacement therapy was required. She was splenectomised aged 27 yr. Obstetric history included two planned abortions and one successful pregnancy by in vitro fertilisation. She did not receive any chelation therapy during this pregnancy. The patient was switched to deferasirox in August 2006 following enrolment into a clinical trial; at this point, she was receiving two RBC units every 20 d. Prior to enrolment, her compliance with deferoxamine had been poor, which led to substantially elevated body iron levels; the patient’s clinical characteristics at this time are shown in Table 1. Deferasirox treatment was initiated at a dose of 18.9 mg ⁄kg ⁄d. Before starting deferasirox, a serum b-hCG pregnancy test was performed and proved negative. The dose was increased to 23.6 mg ⁄kg ⁄d after 3 months (November 2006) because of slow decrease in serum ferritin and increased weight. A mild skin rash was initially observed, although this resolved spontaneously without discontinuing deferasirox treatment. The patient also experienced persistent constipation for which she received lactulose (Duphalac ; Solvay S.A., Brussels, Belgium). During a random examination by her gynaecologist on 24 December 2006, the patient was confirmed to be 22 wk pregnant; her last menstruation occurred 4 August 2006. During this period, the patient was receiving hormone replacement therapy. This second pregnancy was spontaneous. Deferasirox treatment was stopped immediately, at which point serum ferritin levels had decreased by >1000 ng ⁄mL (Table 1). From the 17th week until the confirmation of pregnancy, the patient’s haemoglobin level decreased (average 7.5–8.0 g ⁄dL). Once deferasirox was withdrawn, the patient’s constipation resolved completely, suggesting it may have been treatment related. Cardiac function, as assessed by Triplex and Doppler (General Electric Logiq), was normal during follow-up.