her with serum iron parameters after a single dose and at steady state (after 1 week) in 24 subjects with iron deficiency, randomised to receive 30 mg, 60 mg or 90 mg Feraccru twice daily. Blood and urine samples were assayed for maltol and maltol glucuronide. Serum samples were assayed for iron parameters.
Maltol was transiently measured in plasma with a AUC0-t between 0.022 and 0.205 h.µg/mL across all dosing regimens and both study days. Non-clinical studies have shown that maltol is metabolised through UGT1A6 and by sulphation. It is not known if medical products that inhibit UGT enzymes have the potential to increase maltol concentration (see section 4.5). The maltol appeared to be rapidly metabolised to maltol glucuronide (AUC0-t between 9.83 and 30.9 h.µg/mL across all dosage regimens). Maximum maltol and maltol glucuronide concentrations were reached 1 to 1.5 hours after oral administration of Feraccru. Exposure to maltol glucuronide increased dose proportionally over the Feraccru 30 to 90 mg twice daily dosing range and there was no significant accumulation of either after 7 days treatment with Feraccru. Of the total maltol ingested, a mean of between 39.8 % and 60.0 % was excreted as maltol glucuronide. Peak transferrin saturation (TSAT) and total serum iron values were reached 1.5 to 3 hours after oral administration of Feraccru. Total serum iron concentrations and TSAT values were generally higher with increasing Feraccru doses. TSAT and total serum iron profiles were comparable between Day 1 and Day 8.
The pharmacokinetic properties of Feraccru were also investigated at steady state in 15 subjects who were already participating in the AEGIS1/2 study described above and who had been in the open-label treatment phase for at least 7 days (Feraccru 30 mg twice daily). Maltol was again transiently measured in plasma with a half-life of 0.7 hours, with a Cmax of 67.3 ± 28.3 ng/mL. The maltol appeared to be rapidly metabolised to maltol glucuronide (Cmax = 4677 ± 1613 ng/mL). Maximum maltol and maltol glucuronide concentrations were reached approximately 1 hour after oral administration of Feraccru. Maximum total iron serum concentrations were measured 1-2 hours after administration. The pharmacokinetic profiles of maltol/maltol glucuronide and iron parameters were independent of one another.
5.3 Preclinical safety data
Ferric maltol
Non-clinical studies revealed no special hazard for humans based on repeated dose toxicity and local tolerance studies conducted with ferric maltol.
Deposition of iron in the reticulo-endothelial system, liver and spleen was recorded in dogs adminstered 250 mg/kg/day ferric maltol.
No reproductive and developmental toxicity or carcinogenicity studies have been conducted with ferric maltol.
Maltol
Haemosiderin was observed in Kupffer cells of dogs administered 250 mg/kg/day maltol. At doses of 500 mg/kg/day testicular degeneration and toxic signs indicative of iron chelation were recorded. These effects were not observable in a second study in dogs receiving up to 300 mg/kg/day.
A possible potential genotoxic potential for maltol could not be fully ruled out. However, no carcinogenic effects were recorded in studies conducted in mice and rats receiving up to 400 mg/kg/day maltol.
6. Pharmaceutical particulars
6.1 List of excipients
Capsule contents:
Lactose monohydrate
Sodium laurilsulfate
Magnesium stearate
Colloidal anhydrous silica
Crospovidone (Type A)
Capsul |
