XOANACYL Film-coated tablet Ref.[115986] Active ingredients: Ferric citrate

Monitoring iron parameters

All patients receiving this medicinal product require at least quarterly monitoring of serum iron storage parameters (serum ferritin and TSAT) to ensure sufficient effect and to avoid iron overload which may have negative health consequences, such as decreased bone mineral density.

Xoanacyl should be temporarily discontinued if serum ferritin is above 700 ng/mL and/or TSAT is above 40%. In this situation, the strategy for iron supplementation (including, if applicable, concomitant intravenous iron) should be revised.

Concomitant treatment with intravenous iron and ESA may be needed, especially in dialysis dependent patients. Doses should be carefully selected to achieve appropriate levels of haemoglobin taking into account the targets recommended for such products. The need for intravenous iron and ESA may vary over time.

Serum ferritin and TSAT levels increase after intravenous iron administration; hence, blood samples for measurement of iron storage parameters should be obtained at a time appropriate to reflect the patient's iron status after intravenous iron dosing taking into account the product used, the amount of iron given and the frequency of dosing, but a minimum of 7 days after intravenous iron dosing.

Patients treated with Xoanacyl should not receive concomitant treatment with other oral iron preparations.

Monitoring serum phosphorous levels

All patients receiving this medicinal product require at least quarterly monitoring of serum phosphorous. Xoanacyl should be temporary discontinued if hypophosphataemia develops (see section 4.8).

Patients treated with Xoanacyl should not receive concomitant treatment with other phosphate binders.

Inflammatory bowel disease and gastrointestinal bleeding

Xoanacyl is contraindicated in patients with active severe gastrointestinal disorders (see section 4.3). Patients with active, symptomatic inflammatory bowel disease and recent symptomatic gastrointestinal bleeding were excluded from clinical studies. Xoanacyl 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.

Gastrointestinal disturbances

Gastrointestinal adverse reactions have been reported including severe cases of diarrhoea, abdominal pain and nausea and their occurrence should be monitored (see section 4.8). Xoanacyl must be discontinued in patients with active severe gastrointestinal disorders (see section 4.3).

Excipients with known effect

Each film-coated tablet contains 0.99 mg sunset yellow FCF (E110) and 0.70 mg Allura Red AC (E129) which may cause allergic reaction.

Concomitant use not recommended

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

Medicinal products with special recommendations for concomitant use with Xoanacyl

Medicinal products that may act on iron absorption in the gastrointestinal (GI) tract

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).

Medicinal products that may interact with Xoanacyl

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:

• 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 Xoanacyl. Levothyroxine dose may need to be adjusted during treatment with Xoanacyl.
• 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, Xoanacyl 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 Xoanacyl and ciprofloxacin were taken 2 hours apart.

Pregnancy

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. Xoanacyl is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

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 Xoanacyl 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 Xoanacyl on fertility.

Xoanacyl 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 Xoanacyl 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 Table 1. 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.

Table 1. Adverse reactions observed during clinical studies in which Xoanacyl 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 Xoanacyl use (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.