Fexeric

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

 

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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Fexeric 1 g film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 1 g of ferric citrate coordination complex (equivalent to 210 mg of 
ferric iron).  
 
Excipients with known effect:  
Each film-coated tablet contains sunset yellow FCF (E110) (0.99 mg) and Allura Red AC (E129) 
(0.70 mg). 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
Peach-coloured, oval shaped, film-coated tablet, embossed with “KX52”. Tablets are 19 mm long, 
7.2 mm thick and 10 mm wide. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Fexeric is indicated for the control of hyperphosphataemia in adult patients with chronic kidney 
disease (CKD). 
 
4.2 Posology and method of administration 
 
Posology 
 
Starting dose 
 
The recommended starting dose of Fexeric is 3 to 6 g (3 to 6 tablets) per day based on serum 
phosphorus levels.   
 
CKD patients who are not on dialysis require the lower starting dose, 3 g (3 tablets) per day.  
 
Fexeric must be taken in divided doses with or immediately after meals of the day.  
 
Patients previously on other phosphate binders who are switched to Fexeric should start taking 3 to 6 g 
(3 to 6 tablets) per day. 
 
Patients receiving this medicine should adhere to their prescribed low phosphate diets. 
 
Dose titration 
 
Serum phosphorus concentrations should be monitored within 2 to 4 weeks of starting or changing the 
dose of Fexeric, and approximately every 2-3 months when stable. The dose can be increased or 

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decreased by 1 to 2 g (1 to 2 tablets) per day at 2- to 4-week intervals as needed to maintain serum 
phosphorus at recommended target levels up to a maximum of 12 g (12 tablets) per day. 
 
There are limited data available for doses higher than 9 g (9 tablets) per day in CKD patients not on 
dialysis; therefore in this population doses higher than 9 g/day should be used with caution. 
 
Temporarily discontinue Fexeric if the serum phosphorus is < 3 mg/dl and resume at a lower dose 
once the serum phosphorus has returned to the target range. 
 
Treatment with Fexeric may lead to elevations in iron stores, particularly in patients receiving 
concomitant intravenous iron therapy. Fexeric should be temporarily discontinued if serum ferritin 
exceeds 800 ng/ml (see section 4.4).  
 
Long term safety data are limited in non-dialysis and peritoneal dialysis (PD) patients (see section 
5.1). 
 
Paediatric population 
 
The safety and efficacy of Fexeric in children and adolescents aged 0 to 18 years have not yet been 
established. No data are available. 
 
Elderly population 
 
Fexeric has been administered to over 400 patients ≥ 65 years of age in studies where the dose was 
titrated to achieve target serum phosphorus levels. The elderly patients were treated according to the 
recommended dosing regimen without any safety concerns. Experience from clinical studies in 
patients above the age of 75 years is limited. 
 
Hepatic impairment 
 
Experience from clinical studies in patients with hepatic impairment is limited. No dosage reduction is 
considered necessary but patients with hepatic impairment should initiate treatment with the lower 
starting dose, 3 g (3 tablets) per day (see section 5.1).  
 
Method of administration  
 
For oral use. Tablets should be taken whole.  
Patients must take Fexeric with or immediately after meals. The total daily dose should be divided 
across the meals of the day. 
 
4.3 Contraindications 
 
 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 Hypophosphataemia  
 Active severe gastrointestinal disorders (e.g. gastrointestinal bleeding) 
 Haemochromatosis or laboratory tests indicating possible haemochromatosis  
 Other iron overload (primary or secondary) syndromes  

 
4.4 Special warnings and precautions for use 
 
Monitoring iron parameters 
 
Increases in ferritin and transferrin saturation (TSAT) are observed with Fexeric use. This medicine 
should be used only in the absence of iron overload syndromes and with caution if serum ferritin rises 
above 500 ng/ml. Fexeric should be temporarily discontinued if serum ferritin exceeds 800 ng/ml. 
Significantly elevated ferritin levels were observed particularly when concomitant intravenous iron 
was used.  

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All patients receiving this medicine require at least quarterly monitoring of serum iron storage 
parameters (serum ferritin and TSAT). 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 Fexeric should not receive concomitant treatment with other oral iron 
preparations.  
 
Reductions in intravenous iron and erythropoiesis-stimulating agent (ESA) use with this medicine 
have been observed. Therefore, patients may need reduction in, or discontinuation of, intravenous iron 
and/or ESAs.  
 
Inflammatory bowel disease 
 
Patients with active, symptomatic inflammatory bowel disease were excluded from clinical trials. 
Fexeric should only be used in these patients following careful assessment of benefit/risk. 
 
General 
 
Each 1 g film-coated tablet contains sunset yellow FCF (E110) (0.99 mg) and Allura Red AC (E129) 
(0.70 mg) which may cause allergic reaction.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effects of other medicinal products on Fexeric 
 
Results from subgroup analyses in the pivotal clinical study in dialysis patients show that the 
concomitant use of frequently co-prescribed medications in CKD patients (fluoroquinolones, 
tetracyclines, proton pump inhibitors, thyroid hormones, sertraline, Vitamin D, warfarin, 
acetylsalicylic acid) do not affect the efficacy of Fexeric with respect to its ability to lower serum 
phosphorus.  
 
Effects of Fexeric on other medicinal products 
 
Since citrate is known to increase aluminium absorption, aluminium-based compounds should be 
avoided while patients receive Fexeric. 
 
Treatment with Fexeric may lead to elevations in iron stores, particularly in patients receiving 
concomitant intravenous iron therapy. Patients with elevated ferritin levels receiving intravenous iron 
may require a reduction in dose or discontinuation of intravenous iron therapy.  
 
Reductions in ESA use with Fexeric have been observed. Therefore, patients may need a reduction in 
the dose of ESAs. 
 
In drug-drug interaction studies in healthy male and female subjects, Fexeric 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 Fexeric and ciprofloxacin 
were taken 2 hours apart. Consequently, ciprofloxacin should not be taken at the same time, but at 
least 2 hours before or after Fexeric. Fexeric did not alter the bioavailability of the following 
medicinal products when concomitantly administered: clopidogrel, digoxin, diltiazem, glimepiride, 
losartan. 
 
From in vitro studies, certain antibiotic (doxycycline, cefdinir), anticonvulsant (valproate sodium), 
antidepressant (sertraline HCl), bisphosphonate (alendronate sodium), anti-parkinsonian (levodopa) 

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and immunosuppressant (methotrexate) medications showed the potential to interact with Fexeric: any 
of these or other medicinal products that have the potential to interact with Fexeric, should be taken at 
least 2 hours before or after Fexeric. 
 
Since iron-based preparations are known to reduce the absorption of levothyroxine (thyroxine), 
physicians should consider monitoring suitable markers or clinical signs of efficacy if these medicinal 
products are concomitantly administered with Fexeric.  
 
Although the potential for interactions with medicinal products seems low, for concomitant treatment 
with products with a narrow therapeutic window, the clinical effect/adverse events should be 
monitored on initiation or dose adjustment of Fexeric or the concomitant product. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy and women of childbearing potential 
 
There are no data regarding the use of ferric citrate coordination complex in pregnant women. Animal 
studies are insufficient with respect to reproductive toxicity (see section 5.3). Fexeric is not 
recommended during pregnancy and in women of childbearing potential not using contraceptive 
methods. 
 
Breast-feeding 
 
It is not known 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 Fexeric 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 Fexeric on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Fexeric has no influence on the ability to drive and use machines.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most commonly reported adverse reactions in dialysis-dependent chronic kidney disease (CKD 
5D) patients during treatment were discoloured faeces and diarrhoea occurring in 18% and 13% of 
patients, respectively. These adverse reactions are characteristic of iron-containing medicinal products 
and abated with time with continued dosing. All serious adverse reactions were gastrointestinal in 
nature (abdominal pain, constipation, diarrhoea, gastritis, gastritis erosive, and haematemesis). These 
serious adverse reactions were uncommon (less than 1 case of each per 100 patients) and were each 
reported in 0.2% (1/557) of CKD 5D patients who received Fexeric.  
 
The most commonly reported adverse reactions in non-dialysis dependent CKD (CKD ND) patients 
during treatment were discoloured faeces, constipation and diarrhoea occurring in 27%, 13% and 11% 
of patients, respectively. None of the reported serious events in Study 204 were considered to be 
possibly related to Fexeric. In the remaining non-dialysis studies, a total of 3 serious adverse reactions 
reported in 2 patients were gastrointestinal in nature (gastrointestinal ulcer, gastric polyps and colonic 
polyps).  
 
Increases in ferritin and TSAT above safety thresholds are observed with Fexeric use. 

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Tabulated list of adverse reactions 
 
The safety of Fexeric for the treatment of hyperphosphataemia has been investigated in 18 clinical 
trials involving a total of 1388 CKD 5D patients with treatment duration of up to 2 years and 145 
CKD ND patients with treatment duration of 12 weeks to 1 year. 
 
In CKD 5D patients, the primary evaluation of safety is based on the integrated analysis of data from 4 
studies involving 557 CKD 5D patients treated with Fexeric for up to 1 year. In CKD ND patients, the 
primary evaluation of safety is based on data from the pivotal study (Study 204), where 75 patients 
were treated with Fexeric for 12 weeks. Adverse reactions reported in CKD 5D and CKD ND patients 
are presented in Tables 1 and 2, respectively. 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); and very rare (< 1/10,000). 
 
Table 1:  Adverse reactions observed during clinical studies in which Fexeric was administered 

in CKD 5D patients on haemodialysis or peritoneal dialysis. 

System organ class by MedDRA Adverse Reaction 
Infections and Infestations  
Uncommon: Bronchitis 
Metabolism and nutrition disorders  
Uncommon: Decreased appetite, hyperkalaemia, 

hypophosphataemia, increased appetite 
Nervous system disorders  
Uncommon: Dizziness, headache 
Cardiac disorders  
Uncommon: Palpitations, dyspnoea 
Vascular disorders  
Uncommon: Malignant hypertension 
Respiratory, Thoracic and Mediastinal 
disorders 

 

Uncommon: Pulmonary oedema, wheezing 
Gastrointestinal disorders  
Very common: Diarrhoea, discoloured faeces 
Common:  Abdominal pain/discomfort/distension, 

constipation, nausea, vomiting 
Uncommon:  Abnormal faeces, bowel movement irregularity, 

dry mouth, dysgeusia, dyspepsia, flatulence, 
frequent bowel movements, gastritis, gastritis 
erosive, gastrooesophageal reflux disease, 
haematemesis, peptic ulcer 

Skin and subcutaneous tissue disorders  
Uncommon: Pruritus, rash 
Renal and urinary disorders  
Uncommon: Incontinence 
General disorders and administration site 
conditions 

 

Uncommon: Pain, thirst 
Investigations  
Uncommon: Abnormal breath sounds, increased serum ferritin, 

increased transferrin saturation, increased weight 
Injury, Poisoning and Procedural 
Complications 

 

Uncommon: Muscle injury 
 

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Table 2:  Adverse reactions observed during clinical studies in which Fexeric was administered 
in CKD ND patients.  

System Organ Class by MedDRA Adverse Reaction 
Metabolism and nutrition disorders  
Common: Hypophosphataemia 
Gastrointestinal disorders  
Very common: Diarrhoea, constipation, discoloured faeces  
Common:  abdominal pain/discomfort, nausea, vomiting, 

haemorrhoids, haematochezia, mucous stools, 
dyspepsia, flatulence, dry mouth 

 
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. 
 
4.9 Overdose 
 
No data are available regarding overdose of Fexeric in humans. In patients with CKD, the maximum 
dose studied was 12 g (12 tablets) of Fexeric per day.  
 
Iron overdose is dangerous, particularly in children, and requires immediate attention. The symptoms 
of acute iron overdose include vomiting, diarrhoea, abdominal pain, irritability, and drowsiness. If 
someone is known or suspected to have accidentally or intentionally ingested an overdose of Fexeric, 
immediate medical attention should be sought. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs for treatment of hyperkalemia and hyperphosphatemia 
ATC code: V03AE08 
 
Mechanism of action 
 
This medicine contains ferric citrate coordination complex as the active substance. The iron 
component reacts with dietary phosphate in the gastrointestinal (GI) tract and precipitates phosphate as 
ferric phosphate. This compound is insoluble and is excreted in the stool, reducing the amount of 
phosphate that is absorbed from the GI tract. By binding phosphate in the GI tract and decreasing 
absorption, Fexeric lowers the levels of serum phosphorus.  Following absorption, citrate is converted 
into bicarbonate by the tissues.  
 
Clinical efficacy 
 
The ability of Fexeric to control serum phosphorus in CKD patients was principally evaluated in one 
long-term, pivotal Phase III trial (Study 304) in CKD 5D patients, and in one pivotal Phase II, 12 
week, placebo-controlled trial (Study 204) in CKD ND patients with anaemia. Both studies were 
performed in North American and/or Asian patients.  
As a secondary endpoint in dialysis patients, and a co-primary endpoint in non-dialysis patients, the 
ability of Fexeric to increase iron stores was also evaluated.  
 

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Effects on phosphorus homeostasis 
 
In the pivotal dialysis study 304, following a 2-week washout period, 441 CKD 5D patients with 
hyperphosphatemia were randomised to receive Fexeric (n=292) or active control (sevelamer 
carbonate and/or calcium acetate; n=149) open-label for 52 weeks. The starting dose of Fexeric was 
6 tablets/day (6 g/day), in divided doses with meals. The starting dose of active control was the 
patient's dose prior to the washout period. 
 
The dose of phosphate binder was titrated as needed to maintain serum phosphorus levels between 3.5 
and 5.5 mg/dl, to a maximum of 12 g/day. Non-inferiority to sevelamer carbonate was determined at 
Week 12. Following completion of the 52-week active-controlled period, patients were eligible to 
enter a 4-week placebo-controlled period in which they were re-randomized to receive Fexeric (n=96) 
or placebo (n=96).  
 
After 12 weeks of treatment, the mean (± SD) change in serum phosphorus from baseline was −2.02 ± 
2.0 mg/dl for Fexeric and −2.21 ± 2.18 mg/dl for sevelamer carbonate, demonstrating non-inferiority 
of Fexeric to sevelamer. During the overall 52-week active-controlled period, the decrease in serum 
phosphorus (approximately 2.0 mg/dl following up to a 2 week washout period) and the percentage of 
patients who achieved and maintained serum phosphorus ≤ 5.5 mg/dl (approximately 62%) were 
comparable in both the Fexeric and the active control groups (Table 3). During the subsequent 4-week 
placebo-controlled period, the serum phosphorus levels remained stable in patients receiving Fexeric 
(mean decrease of 0.24 mg/dl), whereas patients receiving placebo had a mean increase of 1.79 mg/dl 
(p < 0.0001 for treatment difference).  
 
In the pivotal non-dialysis study 204, a total of 148 CKD ND patients with hyperphosphatemia and 
iron deficiency anaemia received treatment with study drug; there were 141 patients in the intent-to-
treat population (Fexeric: 72 patients; Placebo: 69 patients). The starting dose of Fexeric was 3 tablets 
a day (3 g/day) in divided doses with meals and was adjusted as needed to a maximum of 12 g/day in 
order to maintain serum phosphorus levels between 3.0 and 3.5 mg/dl. 
 
During the 12-week treatment period, patients treated with Fexeric had a significant decrease in serum 
phosphorus, compared to the placebo group (p < 0.001 for treatment difference) (Table 3). Urinary 
phosphorus excretion and FGF-23 were also significantly decreased relative to baseline in the 
CKD ND patients treated with Fexeric compared to patients treated with placebo. 
 
Table 3:  Summary of efficacy parameters on phosphorus homeostasis at Week 12 and Week 52 

in Study 304 (CKD 5D) and at Week 12 in Study 204 (CKD ND) 

Parameter 

Study 304 (CKD 5D) Study 204 (CKD ND) 
Fexeric 
N=281 

Active Control 
N=146 

Fexeric 
N=72 

Placebo 
N=69 

Baseline serum phosphorus 
(mean ± SD, mg/dl) 

7.41 ± 1.6 7.56 ± 1.7 4.5 ± 0.61 4.7 ± 0.60 

Serum phosphorus change 
from baseline at Week 12§ 
(mean ± SD, mg/dl) 

−2.02 ± 2.0 

−2.22 ± 2.1 
(−2.21 ± 2.2  

for sevelamer 
only) 

−0.7 ± 0.61 −0.3 ± 0.74 

Serum phosphorus change 
from baseline at Week 52 
(mean ± SD, mg/dl) 

−2.03 ± 2.0 −2.18 ± 2.3 NAP Me
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Parameter 

Study 304 (CKD 5D) Study 204 (CKD ND) 
Fexeric 
N=281 

Active Control 
N=146 

Fexeric 
N=72 

Placebo 
N=69 

Proportion of serum 
phosphorus responders at 
Week 12 (%) 

60.9* 63.7* 69.4** 27.5** 

Proportion of serum 
phosphorus responders at 
Week 52 (%) 

62.3* 63.0* NAP 

§ Primary endpoint in Study 304; Co-primary endpoint in Study 204.  
*Proportion of patients achieving serum phosphorus ≤ 5.5 mg/dl in CKD 5D patients;  
**Proportion of patients achieving serum phosphorus ≤ 4.0 mg/dl in CKD ND patients 
NAP: not applicable; SD: standard deviation 
 
Effects on iron homeostasis 
 
In the pivotal dialysis study 304, CKD 5D patients treated with Fexeric, compared with patients 
treated with active control, had significantly higher increases in ferritin and TSAT levels after 
52 weeks of treatment (Table 4), and significantly lower cumulative intravenous iron (96 versus 
149 mg/month) and ESA use (7,713 versus 9,183 IU/week) during the same period. During the 
52-week treatment period, haemoglobin remained relatively stable in the Fexeric group compared to 
the active control group (Table 4).  
 
In the pivotal non-dialysis study 204 CKD ND patients treated with Fexeric had a significant increase 
in serum TSAT, ferritin and haemoglobin levels compared to the placebo group after 12 weeks of 
treatment (p< 0.001 for treatment difference for each parameter) (Table 4).  
 
Table 4:  Summary of results on iron homeostasis at Week 12 and Week 52 in Study 304 (CKD 

5D) and at Week 12 in Study 204 (CKD ND) 

Parameter 

Study 304 (CKD 5D) Study 204 (CKD ND) 
Fexeric 
N=281 

Active Control 
N=146 

Fexeric 
N=72 

Placebo 
N=69 

Baseline TSAT 
(mean ± SD, %) 

31.3 ± 11.2 30.8 ± 11.6 21.6 ± 7.4 21.0 ± 8.3 

TSAT change from 
baseline at Week 12§ 
(mean ± SD, %) 

8.8 ± 18.3 0.5 ±15.8 10.2 ± 12.5 −1.0 ± 7.0 

TSAT change from 
baseline at Week 52 
(mean ± SD, %) 

7.9 ± 18.3 −1.0 ± 14.9 NAP 

 
Baseline ferritin 
(mean ± SD, ng/ml) 

592.8 ± 292.9 609.5 ± 307.7 115.8 ± 83.1 110 ± 80.9 

Ferritin change from 
baseline at Week 12 
(mean ± SD, ng/ml) 

162.7 ± 284.3 44.0 ± 270.4 73.5 ± 76.2 −4.4 ± 47.5 

Ferritin change from 
baseline at Week 52 
(mean ± SD, ng/ml) 

302.1 ± 433.7 22.4 ± 374.0 NAP 

 

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Parameter 

Study 304 (CKD 5D) Study 204 (CKD ND) 
Fexeric 
N=281 

Active Control 
N=146 

Fexeric 
N=72 

Placebo 
N=69 

Proportion with ferritin 
> 500 ng/ml at baseline 166 (59.1%) 87 (59.6%) 0 0 

Proportion with ferritin 
> 500 ng/ml at Week 12 174 (61.9%) 86 (58.9%) 3 (4.2%) 0 

Proportion with ferritin 
> 500 ng/ml at Week 52 160 (56.9%) 63 (43.2%) NAP 

 
Baseline Hgb 
(mean ± SD, g/dl) 

11.61 ± 1.24 11.71 ± 1.26 10.5 ± 0.81 10.6 ± 1.1 

Hgb change from baseline 
at Week 12 
(mean ± SD, g/dl) 

0.19 ± 1.41 −0.19 ± 1.53 0.4 ± 0.75 −0.2 ± 0.91 

Hgb change from baseline 
at Week 52 
(mean ± SD, g/dl) 

−0.20 ± 1.34 −0.55 ± 1.59 NAP 

§ Co-primary endpoint in Study 204. 
All other parameters were secondary or exploratory endpoints in the two studies.  
Hgb: haemoglobin; NAP: not applicable; SD: standard deviation; TSAT: transferrin saturation 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Fexeric in in one or more subsets of the paediatric population in the treatment of hyperphosphataemia 
related to chronic kidney disease (see section 4.2 for information on paediatric use). 
 
Hepatic impairment 
 
Of the 557 patients receiving Fexeric in the pooled safety population, there were 67 (12%) patients 
with evidence of liver dysfunction at baseline. These patients were treated according to the 
recommended dosing regimen without any safety concerns. 
There was no evidence of hepatic impairment or significant alteration of hepatic enzymes across the 
clinical studies with Fexeric, including the long-term studies.  
 
5.2 Pharmacokinetic properties 
 
Formal pharmacokinetic studies have not been performed due to the medicine's predominantly 
localised primary mechanism of action in the GI tract.  
Examination of serum iron storage parameters has shown that there is low systemic absorption of iron 
of approximately 1% from Fexeric. 
 
5.3 Preclinical safety data 
 
The non clinical programme was based on 7 repeat dose toxicology studies in rats and dogs. The target 
organ for primary toxicity of ferric citrate is the GI tract, with evidence of mucosal erosion and acute 
to sub-acute inflammation of the GI tract in dogs at elevated doses. In iron replete dogs, microscopic 
and macroscopic findings in the liver were consistent with signs of iron accumulation. 
 
Data on primary and secondary pharmacodynamics, safety pharmacology and pharmacokinetics of 
Fexeric were derived from the repeat dose toxicology studies, and did not reveal safety concerns for 
humans. 

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Information on genotoxicity, carcinogenic potential, toxicity to reproduction and development of ferric 
citrate was bridged from scientific literature. Data from carcinogenicity 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. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
Starch, pregelatinised  
Calcium stearate 
  
Film-coating 
Hypromellose  
Titanium Dioxide  
Triacetin  
Sunset Yellow FCF (E110) 
Allura Red AC (E129) 
Indigo Carmine  
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years. 
Shelf-life after first opening of the bottle: 60 days  
 
6.4 Special precautions for storage 
 
Do not store above 25°C.  
Keep the bottle tightly closed in order to protect from moisture. 
 
6.5 Nature and contents of container 
 
HDPE bottles with child-resistant closure with desiccant.  
Pack size: 200 film-coated tablets. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Akebia Europe Limited 
c/o Matheson 
70 Sir John Rogerson’s Quay 
Dublin 2 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  

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EU/1/15/1039/001 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 23 September 2015 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

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13 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE  
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Propak Health Ltd 
3-4 Ballyboggan Industrial Estate 
Ballyboggan Road 
Finglas 
Dublin 11 
Ireland 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic safety update reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

 

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• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Description Due date 
Non-interventional post-authorisation safety study (PASS): prospective, 
observational, multicentre study in CKD patients treated with Fexeric in order to 
gain long-term (2 years) safety data (including iron overload events, infective and 
gastrointestinal events) particularly in EU patients, elderly and very elderly 
patients, dialysed (HD, PD) and non-dialysed patients, and in addition reflecting 
the specific risks in subgroups of serum ferritin levels > 500 ng/ml and in patients 
in the range 200 to < 500 ng/ml. 

54 months 
after first 
launch in EU 

 

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16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

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17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
OUTER CARTON AND BOTTLE LABEL  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Fexeric 1 g film-coated tablets 
ferric citrate coordination complex 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 1 g of ferric citrate coordination complex (equivalent to 210 mg of 
ferric iron).  
 
 
3. LIST OF EXCIPIENTS 
 
Also contains sunset yellow FCF (E110), Allura Red AC (E129), see the package leaflet for futher 
information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film coated tablet 
200 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
Shelf life after first opening of the bottle: 60 days 
Open date: (Bottle only) 
 

 
 

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9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C 
Keep the bottle tightly closed in order to protect from moisture. 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Akebia Europe Limited 
c/o Matheson 
70 Sir John Rogerson’s Quay 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1039/001 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Fexeric 1 g (carton only) 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
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20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 

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Package leaflet: Information for the patient 

 
Fexeric 1 g film-coated tablets 

ferric citrate coordination complex  
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects.  
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 
 even if their signs of illness are the same as yours.  
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What Fexeric is and what it is used for  
2. What you need to know before you take Fexeric 
3. How to take Fexeric   
4. Possible side effects  
5. How to store Fexeric   
6. Contents of the pack and other information 
 
 
1. What Fexeric is and what it is used for 
 
Fexeric contains ferric citrate coordination complex as the active ingredient. In adults with impaired 
kidney function it is used to lower high blood phosphorus levels. 
 
Phosphorus is contained in many foods. Patients with kidneys that do not work properly are not able to 
eliminate phosphorus from their body adequately. This can lead to high phosphorus levels in the 
blood. Keeping the phosphorus level normal is important to maintain healthy bones and blood vessels 
and to prevent itchy skin, red eyes, bone pain or bone fractures. 
 
Fexeric binds to the phosphorus from food in your digestive tract to prevent it from being absorbed 
into your blood. The Fexeric-bound phosphorus is then excreted from your body in faeces.  
 
You may have been advised to follow a special diet to prevent the phosphorus in your blood rising to 
high levels. If this is the case, you must continue to follow the special diet even if you are taking 
Fexeric. 
 
 
2. What you need to know before you take Fexeric 
 
Do not take Fexeric 
- if you are allergic to ferric citrate coordination complex or any of the other ingredients of this 

medicine (listed in section 6) 
- if you have low levels of phosphorus in your blood  
- if you have a severe stomach or bowel disease such as stomach or bowel bleeding 

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- if you have haemochromatosis, a condition causing the body to absorb too much iron from the 
diet 

- if you have any other disorder associated with too much iron 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Fexeric if you have: 
- too much iron in your body  
- bowel inflammation 
  
Monitoring tests 
Fexeric increases iron levels in your body. Because too much iron is unsafe, your blood will be tested 
at regular intervals to check iron levels. This blood test may be part of your routine tests for your 
kidney disease. 
 
Children and adolescents 
Do not give this medicine to children and adolescents below the age of 18 years. The safety and 
effectiveness of Fexeric have not been studied in this population. 
 
Other medicines and Fexeric 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
 The following medicines can affect or be affected by Fexeric: 
• other iron-containing medicines 

Fexeric contains iron and your doctor may need to adjust the dose of your other iron-containing 
medicines. 

• aluminium containing medicines 
Fexeric should not be taken at the same time as aluminium containing medicines. 

• Also tell your doctor or pharmacist if you are taking or might take the medicines below. Your 
doctor may want to change the dose of these medicines or advise you to take these medicines 2 
hours before or after Fexeric. Monitoring blood levels of these medicines may also be considered:  
- ciprofloxacin, doxycycline, cefdinir: medicines to treat bacterial infections 
- valproic acid: a medicine to treat epilepsy and mental disorders 
- sertraline: a medicine to treat depression 
- methotrexate: a medicine to treat rheumatoid arthritis, cancer and the skin disease, psoriasis 
- alendronate: a medicine to treat decreased bone mass and density 
- levodopa: a medicine to treat Parkinson’s disease 
- levothyroxine: a medicine to treat thyroid hormone deficiency 

 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine.  
 

• pregnancy 
If you are able to become pregnant, you must use birth control during treatment. If you become 
pregnant during treatment, you must ask your doctor for advice. It is unknown whether Fexeric 
has any effect on unborn babies. 
• breast-feeding 
Tell your doctor if you wish to breast-feed your baby. It is unknown whether Fexeric may pass 
through breast milk and affect your baby. 

 
Driving and using machines 
Fexeric has no influence on your ability to drive and use machines. 
 
Fexeric contains sunset yellow FCF (E110) and Allura Red AC (E129) 
These may cause allergic reactions. 
 

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3. How to take Fexeric 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.  
 
The recommended dose is: 

- starting dose for adults: 3 to 6 tablets daily, in separated doses, with or immediately after 
main meals of the day. Taking the tablets with meals will help the medicine to work. 

Patients not on dialysis require the lower starting dose: 3 tablets daily, in separated doses, with or 
immediately after meals of the day. 
Your doctor may decrease or increase the starting dose depending on the level of phosphorus in 
your blood. Your doctor will monitor the phosphorus levels regularly. This blood test may be part 
of your routine tests for your kidney disease. 
- maximum dose: 12 tablets daily, in separated doses, with or immediately after meals of the 

day. 
 
Method of use 
Take the tablets whole, with one glass of water, with or immediately after meals. 
 
If you take more Fexeric than you should 
If you take too much Fexeric, tell your doctor of pharmacist. 
Contact a doctor or poison control centre immediately if a child accidentally takes Fexeric. 
 
If you forget to take Fexeric 
Take the next dose at the usual time with a meal. Do not take a double dose to make up for a forgotten 
dose. 
 
If you stop taking Fexeric 
Treatment of high blood phosphorus levels is usually required for a long period of time. It is important 
that you continue taking Fexeric for as long as your doctor prescribes the medicine.  
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Contact your doctor immediately if you experience: 
- severe abdominal pain or constipation (uncommon) 
- vomiting of blood (uncommon) 
- blood in the stools (uncommon) 
 
The following side effects have been reported with Fexeric in dialysis patients: 
 
Very common side effects (may affect more than 1 in 10 people): 
- discoloured stools 
- diarrhoea 
 
Common side effects (may affect up to 1 in 10 people): 
- constipation  
- abdominal pain/discomfort 
- abdominal distension or bloating 
- nausea, vomiting 
 

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Uncommon side effects (may affect up to 1 in 100 people): 
- changes in iron blood test results  
- decreased or increased appetite 
- indigestion, flatulence 
- inflammation of stomach lining, ulcer of mucosal lining of the stomach or the first part of the 

bowel 
- reflux of stomach juices in the oesophagus 
- abnormal stools, irregularity in bowel movement 
- low serum phosphorus levels 
- dry mouth 
- taste disturbance 
- headache 
-  dizziness 
- low serum potassium levels 
- incontinence 
- skin rash, itching 
- palpitations 
- shortness of breath, wheezing, abnormal breath sounds 
- pain 
- thirst 
- bronchitis 
-  muscle injury 
- increased weight 
- fluid in the lungs  
- very high blood pressure 
 
The most common side effects (affecting more than 1 in 10 people) in patients not on dialysis also 
concern the stomach or bowel: 
• discoloured stools 
• diarrhoea 
• constipation 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Fexeric 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the bottle and carton after “EXP”.  
The expiry date refers to the last day of that month. 
 
Do not store above 25°C. 
Keep the bottle tightly closed in order to protect from moisture. 
After first opening of the bottle, use within 60 days. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

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6. Contents of the pack and other information 
 
What Fexeric contains 
The active substance is ferric citrate coordination complex. 
Each film-coated tablet contains 1 g of ferric citrate coordination complex (equivalent to 210 mg of 
ferric iron). 
The other ingredients are pregelatinised starch, calcium stearate, hypromellose, titanium dioxide, 
triacetin, sunset yellow FCF (E110), allura red AC (E129), indigo carmine. 
 
What Fexeric looks like and contents of the pack 
Fexeric film-coated tablets are peach-coloured, oval-shaped tablets embossed with “KX52” on one 
side. Tablets are 19 mm long, 7.2 mm thick and 10 mm wide. 
 
The tablets are packed in plastic bottles with child-resistant caps. They are supplied in one pack size of 
200 tablets per bottle. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder: 
Akebia Europe Limited 
c/o Matheson 
70 Sir John Rogerson’s Quay 
Dublin 2 
Ireland 
 
Manufacturer: 
Propak Health Ltd. 
3-4 Ballyboggan Industrial Estate 
Ballyboggan Road 
Finglas 
Dublin 11 
Ireland 
 
For any information about this medicine, please contact the Marketing Authorisation Holder. 
 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET