7.4 Interaction with Theophylline and Other Agents Metabolized by CYP1A2
In a healthy volunteer study, the concomitant administration of Exjade (repeated dose of 30 mg/kg/day) and the CYP1A2 substrate theophylline (single dose of 120 mg) resulted in an approximate doubling of the theophylline AUC and elimination half-life. The single dose Cmax was not affected, but an increase in theophylline Cmax is expected to occur with chronic dosing. This increase in plasma concentrations could lead to clinically significant theophylline induced CNS or other adverse reactions. Avoid the concomitant use of theophylline or other CYP1A2 substrates with a narrow therapeutic index with Exjade. If you must co-administer theophylline with Exjade, monitor theophylline concentrations and consider theophylline dose modification.

Use caution when Exjade is administered with other drugs metabolized by CYP1A2 such as cyclobenzaprine, imipramine, haloperidol, fluvoxamine, mexiletine, olanzapine, tizanidine, zileuton, and zolmitriptan.

7.5 Interaction with Agents Inducing UDP-glucuronosyltransferase (UGT) Metabolism
In a healthy volunteer study, the concomitant administration of Exjade (single dose of 30mg/kg) and the potent UDP-glucuronosyltransferase (UGT) inducer rifampicin (600 mg/day for 9 days) resulted in a decrease of deferasirox systemic exposure (AUC) by 44%. Therefore, the concomitant use of Exjade with potent UGT inducers (e.g.,rifampicin, phenytoin, phenobarbital, ritonavir) may result in a decrease in Exjade efficacy.

Avoid the concomitant use of potent UGT inducers with Exjade. If you must co-administer these agents together, consider increasing the initial dose of Exjade to 30mg/kg and monitor serum ferritin levels and clinical responses for further dose modification [see Dosage and Administration (2.2)].

7.6 Interaction with Cholestyramine
The concomitant use of Exjade withcholestyramine may result in a decrease in Exjade efficacy. In healthy volunteers, the administration of cholesytramine after a single dose of deferasirox resulted in a 45% decrease in deferasirox exposure (AUC).Avoid the concomitant use of cholestyramine with Exjade. If you must co-administer these agents together, consider increasing the initial dose of Exjade to 30mg/kg and monitor serum ferritin levels and clinical responses for further dose modification [see Dosage and Administration (2.2)].

8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C

There are no adequate and well-controlled studies with Exjade in pregnant women. Administration of deferasirox to animals during pregnancy and lactation resulted in decreased offspring viability and an increase in renal anomalies in male offspring at exposures that were less than the recommended human exposure. Exjade should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In embryofetal developmental studies, pregnant rats and rabbits received oral deferasirox during the period of organogenesis at doses up to (100mg/kg/day in rats and 50mg/kg/day in rabbits) 0.8 times the MRHD (Maximum Recommended Huma