Chemical formula: C₆H₇FeO₈ Molecular mass: 967.803 g/mol
There are no available data on ferric citratexia use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Animal reproduction studies have not been conducted using ferric citratexia. Skeletal and encephalic malformation was observed in neonatal mice when ferric gluconate was administered intraperitoneally to gravid dams on gestation days 7-9. However, oral administration of other ferric or ferrous compounds to gravid CD1-mice and Wistar-rats caused no fetal malformation.
An overdose of iron in pregnant women may carry a risk for spontaneous abortion, gestational diabetes and fetal malformation.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively.
The effect of ferric citratexia on the absorption of vitamins and other nutrients has not been studied in pregnant women. Requirements for vitamins and other nutrients are increased in pregnancy.
There are no human data regarding the effect of ferric citrate in human milk, the effects on the breastfed child, or the effects on milk production. Data from rat studies have shown the transfer of iron into milk by divalent metal transporter-1 (DMT-1) and ferroportin-1 (FPN-1). Hence, there is a possibility of infant exposure when ferric citrate is administered to a nursing woman. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for ferric citrate and any potential adverse effects on the breastfed child from ferric citrate or from the underlying maternal condition.
Data from carcinogenesis studies have shown that ferric citrate is not carcinogenic in mice and rats when administered intramuscularly or subcutaneously. Ferric citrate was neither mutagenic in the bacterial reverse mutation assay (Ames test) nor clastogenic in the chromosomal aberration test in Chinese hamster fibroblasts.
The potential for ferric citrate to impair reproductive performance or to cause fetal malformation has not been evaluated.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to adverse reaction rates in the clinical trials of another drug and may not reflect the rates observed in practice.
A total of 289 patients were treated with ferric citrate and 149 patients were treated with active control (sevelamer carbonate and/or calcium acetate) during the 52-week, randomized, open-label, active control phase of a trial in patients on dialysis. A total of 322 patients were treated with ferric citrate for up to 28 days in three short-term trials. Across these trials, 557 unique patients were treated with ferric citrate; dosage regimens in these trials ranged from 210 mg to 2,520 mg of ferric iron per day, equivalent to 1 to 12 tablets of ferric citrate.
Adverse reactions reported in more than 5% of patients treated with ferric citrate in these trials included diarrhea (21%), discolored feces (19%), nausea (11%), constipation (8%), vomiting (7%), and cough (6%).
During the 52-week, active-control period, 61 patients (21%) on ferric citrate discontinued study drug because of an adverse reaction, as compared to 21 patients (14%) in the active control arm. Patients who were previously intolerant to any of the active control treatments (calcium acetate and sevelamer carbonate) were not eligible to enroll in the study. Gastrointestinal adverse reactions were the most common reason for discontinuing ferric citrate (14%).
Across two trials, 190 patients with CKD-NDD were treated with ferric citrate. This included a study of 117 patients treated with ferric citrate and 116 patients treated with placebo in a 16-week, randomized, double-blind period and a study of 75 patients treated with ferric citrate and 73 treated with placebo in a 12-week randomized double-blind period. Dosage regimens in these trials ranged from 210 mg to 2,520 mg of ferric iron per day, equivalent to 1 to 12 tablets of ferric citrate.
Adverse reactions reported in at least 5% of patients treated with ferric citrate in these trials are listed in the following table.
Adverse Events Reported in Two Clinical Trials in at least 5% of patients receiving Ferric citrate:
| Body System Adverse Reaction | Ferric citrate % (N=190) | Placebo % (N=188) |
|---|---|---|
| Any Adverse Reaction | 75 | 62 |
| Metabolism and Nutrition Disorders | ||
| Hyperkalemia | 5 | 3 |
| Gastrointestinal Disorders | ||
| Discolored feces | 22 | 0 |
| Diarrhea | 21 | 12 |
| Constipation | 18 | 10 |
| Nausea | 10 | 4 |
| Abdominal Pain | 5 | 2 |
During the 16-week, placebo-control trial, 12 patients (10%) on ferric citrate discontinued study drug because of an adverse reaction, as compared to 10 patients (9%) in the placebo control arm. Diarrhea was the most common adverse reaction leading to discontinuation of ferric citrate (2.6%).
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
