mg on a body surface area basis). There were no adverse effects on survival of offspring, their behavior, sexual maturation or reproductive parameters.
8.2 Lactation
Risk Summary
The available published data on the use of ferric carboxymaltose in lactating women demonstrate that iron is present in breast milk. However, the data do not inform the full potential exposure of iron for the breastfed infant. Among the breastfed infants, there were no adverse events reported that were considered related to ferric carboxymaltose exposure through breastmilk. There is no information on the effects of ferric carboxymaltose on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Injectafer in addition to any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.
Clinical Considerations
Monitor breastfed infants for gastrointestinal toxicity (constipation, diarrhea).
8.4 Pediatric Use
Safety and effectiveness have not been established in pediatric patients.
8.5 Geriatric Use
Of the 1775 subjects in clinical studies of Injectafer, 50% were 65 years and over, while 25% were 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
10 OVERDOSAGE
Excessive dosages of Injectafer may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. A patient who received Injectafer 18,000 mg over 6 months developed hemosiderosis with multiple joint disorder, walking disability and asthenia. Hypophosphatemic osteomalacia was reported in a patient who received Injectafer 4000 mg over 4 months. Partial recovery followed discontinuation of Injectafer [see Adverse Reactions (6.2)].
11 DESCRIPTION
Ferric carboxymaltose, an iron replacement product, is an iron carbohydrate complex with the chemical name of polynuclear iron (III) hydroxide 4(R)-(poly-(1→4)-O-α-D-glucopyranosyl)-oxy-2(R),3(S),5(R),6-tetrahydroxy-hexanoate. It has a relative molecular weight of approximately 150,000 Da corresponding to the following empirical formula:
[FeOx(OH)y(H2O)z]n [{(C6H10O5)m (C6H12O7)}l]k,
where n ≈ 103, m ≈ 8, l ≈ 11, and k ≈ 4
(l represents the mean branching degree of the ligand).
The chemical structure is presented below:
Chemical Structure
Injectafer (ferric carboxymaltose injection) is a dark brown, sterile, aqueous, isotonic colloidal solution for intravenous injection. Each mL contains 50 mg iron as ferric carboxymaltose in water for injection. Injectafer is available in 15 mL single-dose vials. Sodium hydroxide and/or hydrochloric acid may have been added to adjust the pH to 5.0-7.0.
Vial closure is not made with natural rubber latex.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Ferric carboxymaltose is a colloidal iron (III) hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron.
12.2 Pharmacodynamics
Using positron emission tomography (PET) it was demonstrated that red cell uptake of 59Fe and 52Fe from Injectafer ranged from 61% to 99%. In patients with iron def |
