Ferric citrate Other names: Iron(III) citrate

Patients with hepatic impairment should initiate treatment with the lower starting dose, 3 g per day.

The following medicinal products have the potential to interact with Xoanacyl and should not be taken at the same time, but at least 2 hours before or after Xoanacyl:

• Calcium supplements;
• Calcium based and magnesium based antacids (e.g. containing oxides, hydroxides or salts of magnesium and calcium).

Since citrate is known to increase aluminium absorption, aluminium-based compounds (e.g. antacids containing aluminium hydroxide) should be avoided while patients receive ferric citrate.

The following medicinal products have the potential to interact with ferric citrate and should not be taken at the same time, but at least 2 hours before or after ferric citrate:

• Levothyroxine (thyroxine). Since iron-based preparations are known to reduce the absorption of levothyroxine a reduction in levothyroxine availability could occur. Thyroid function should be monitored, in particular after initiation and dose adjustments of ferric citrate. Levothyroxine dose may need to be adjusted during treatment with ferric citrate.
• Certain antiparkinsonian treatments (levodopa, benserazide, entacapone);
• Captopril (angiotensin-converting enzyme inhibitor with sulfhydryl group);
• Iron chelating agents (e.g. penicillamine);
• Biphosphonates (e.g. alendronate sodium);
• Methyldopa (alpha-2-adrenergic receptor agonist);
• Certain antibiotics: tetracyclines (e.g. doxycycline), cefdinir, fluoroquinolones (e.g. ciprofloxacin, levofloxacin). In drug-drug interaction studies in healthy male and female subjects, ferric citrate decreased the bioavailability of concomitantly administered ciprofloxacin (as measured by the area under the curve [AUC]) by approximately 45%. However, there was no interaction when ferric citrate and ciprofloxacin were taken 2 hours apart.

Ferric citrate is contraindicated in patients with active severe gastrointestinal disorders. Patients with active, symptomatic inflammatory bowel disease and recent symptomatic gastrointestinal bleeding were excluded from clinical studies. Ferric citrate should only be used in these patients following careful assessment of benefit/risk and monitoring of gastrointestinal symptoms following initiation of treatment should occur with discontinuation in case of exacerbation.

There are no or limited amount of data from the use of ferric citrate coordination complex in pregnant women. Animal studies are insufficient with respect to reproductive toxicity. Ferric citrate is not recommended during pregnancy and in women of childbearing potential not using contraception.

It is unknown whether ferric citrate coordination complex/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from ferric citrate therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

No data are available on the potential influence of ferric citrate on fertility.

Ferric citrate has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most commonly reported adverse reactions in CKD patients treated with ferric citrate were diarrhoea and faeces discoloured which occurred in 20.2% and 19.5% of patients, respectively.

Tabulated list of adverse reactions

Adverse reactions reported based on clinical studies in CKD patients (N=858) are presented in the following table. The adverse reactions are listed by SOC (system organ class) and by frequency, most frequent adverse reaction first. Frequencies of adverse reactions are defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Adverse reactions observed during clinical studies in which ferric citrate was administered to CKD patients:

Description of selected adverse reactions

Gastrointestinal tract disturbances

The most common adverse events occurred in the System Organ Class Gastrointestinal disorders (42.1%), including severe cases (2.7%) and cases that led to drug discontinuation (5.9%). Severe gastrointestinal adverse reactions included diarrhoea (1.3%), abdominal pain (0.6%) and nausea (0.1%). Gastrointestinal adverse reactions resulting in discontinuation were most frequently reported due to diarrhoea (3.4%).

Iron overload

Increases in ferritin and TSAT above safety thresholds have been observed with ferric citrate use.