In a healthy volunteer study, the concomitant administration of deferasirox as a moderate CYP2C8 inhibitor (30 mg/kg daily), with repaglinide, a CYP2C8 substrate, given as a single dose of 0.5 mg, increased repaglinide AUC and Cmax about 2.3-fold (90% CI [2.03-2.63]) and 1.6-fold (90% CI [1.42-1.84]), respectively. Since the interaction has not been established with dosages higher than 0.5 mg for repaglinide, the concomitant use of deferasirox with repaglinide should be avoided. If the combination appears necessary, careful clinical and blood glucose monitoring should be performed (see section 4.4). An interaction between deferasirox and other CYP2C8 substrates like paclitaxel cannot be excluded.

In a healthy volunteer study, the concomitant administration of EXJADE as a CYP1A2 inhibitor (repeated dose of 30 mg/kg/day) and the CYP1A2 substrate theophylline (single dose of 120 mg) resulted in an increase of theophylline AUC by 84% (90% CI: 73% to 95%). The single dose Cmax was not affected, but an increase of theophylline Cmax is expected to occur with chronic dosing. Therefore, the concomitant use of EXJADE with theophylline is not recommended. If EXJADE and theophylline are used concomitantly, monitoring of theophylline concentration and theophylline dose reduction should be considered. An interaction between EXJADE and other CYP1A2 substrates cannot be excluded. For substances that are predominantly metabolised by CYP1A2 and that have a narrow therapeutic index (e.g. clozapine, tizanidine), the same recommendations apply as for theophylline.

The concomitant administration of EXJADE and aluminium-containing antacid preparations has not been formally studied. Although deferasirox has a lower affinity for aluminium than for iron, it is not recommended to take EXJADE tablets with aluminium-containing antacid preparations.

The concomitant administration of EXJADE and vitamin C has not been formally studied. Doses of vitamin C up to 200 mg per day have not been associated with adverse consequences.

No interaction was observed between EXJADE and digoxin in healthy adult volunteers.

4.6 Pregnancy and lactation

 Pregnancy

No clinical data on exposed pregnancies are available for deferasirox. Studies in animals have shown some reproductive toxicity at maternally toxic doses (see section 5.3). The potential risk for humans is unknown.

As a precaution, it is recommended that EXJADE is not used during pregnancy unless clearly necessary.

Breast-feeding

In animal studies, deferasirox was found to be rapidly and extensively secreted into maternal milk. No effect on the offspring was noted. It is not known if deferasirox is secreted into human milk. Breast-feeding while taking EXJADE is not recommended.

Fertility

No fertility data is available for humans. In animals, no adverse effects on male or female fertility were found (see section 5.3).

4.7 Effects on ability to drive and use machines

 No studies on the effects of EXJADE on the ability to drive and use machines have been performed. Patients experiencing the uncommon adverse reaction of dizziness should exercise caution when driving or operating machinery (see section 4.8).

4.8 Undesirable effects

 Summary of the safety profile

The most frequent react