Ferasiro Drug Interactions

The safety of deferasirox in combination with other iron chelators has not been established. Therefore, it must not be combined with other iron chelator therapies (see Contraindications).
Interaction with food: The C_max of deferasirox film-coated tablets was increased (by 29%) when taken with a high-fat meal. FERASIRO film-coated tablets may be taken either on an empty stomach or with a light meal, preferably at the same time each day (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Agents that may decrease FERASIRO systemic exposure: Deferasirox metabolism depends on UGT enzymes. The concomitant administration of deferasirox (single dose of 30 mg/kg, dispersible tablet formulation) and the potent UGT inducer, rifampicin, (repeated dose of 600 mg/day) resulted in a decrease of deferasirox exposure. Therefore, the concomitant use of FERASIRO with potent UGT inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital, ritonavir) may result in a decrease in FERASIRO efficacy. The patient's serum ferritin should be monitored during and after the combination, and the dose of FERASIRO adjusted if necessary.
Cholestyramine significantly reduced the deferasirox exposure (see Pharmacology: Pharmacokinetics under Actions).
Interaction with midazolam and other agents metabolised by CYP3A4: The concomitant administration of deferasirox dispersible tablets and midazolam (a CYP3A4 probe substrate) resulted in a decrease of midazolam exposure. In the clinical setting, this effect may be more pronounced. Therefore, due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4 (e.g. ciclosporin, simvastatin, hormonal contraceptive agents, bepridil, ergotamine).
Interaction with repaglinide and other agents metabolised by CYP2C8: The concomitant administration of deferasirox as a moderate CYP2C8 inhibitor (30 mg/kg daily, dispersible tablet formulation), with repaglinide, a CYP2C8 substrate, given as a single dose of 0.5 mg, increased repaglinide AUC and C_max. 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 Precautions). An interaction between deferasirox and other CYP2C8 substrates like paclitaxel cannot be excluded.
Interaction with theophylline and other agents metabolised by CYP1A2: The concomitant administration of deferasirox as a CYP1A2 inhibitor (repeated dose of 30 mg/kg/day, dispersible tablet formulation) and the CYP1A2 substrate theophylline (single dose of 120 mg) resulted in an increase of theophylline AUC. The single dose C_max was not affected, but an increase of theophylline C_max is expected to occur with chronic dosing.
Therefore, the concomitant use of deferasirox with theophylline is not recommended. If deferasirox and theophylline are used concomitantly, monitoring of theophylline concentration and theophylline dose reduction should be considered. An interaction between deferasirox 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.
Other information: There is no data on concomitant administration of deferasirox and aluminium-containing antacid preparations. Although deferasirox has a lower affinity for aluminium than for iron, it is not recommended to take deferasirox tablets with aluminium-containing antacid preparations.
The concomitant administration of deferasirox with substances that have known ulcerogenic potential, such as NSAIDs (including acetylsalicylic acid at high dosage), corticosteroids or oral bisphosphonates may increase the risk of gastrointestinal toxicity (see Precautions). The concomitant administration of deferasirox with anticoagulants may also increase the risk of gastrointestinal haemorrhage. Close clinical monitoring is required when deferasirox is combined with these substances.
Concomitant administration of deferasirox and busulfan resulted in an increase of busulfan exposure (AUC), but the mechanism of the interaction remains unclear. If possible, evaluation of the pharmacokinetics (AUC, clearance) of a busulfan test dose should be performed to allow dose adjustment.