Rienso

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 
 
Rienso 30 mg/ml solution for infusion. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
1 ml of solution contains 30 mg of iron as ferumoxytol.  
Each vial of 17 ml solution contains 510 mg of iron as ferumoxytol. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for infusion.  
Black to reddish brown solution 
Osmolality: 270-330 mosm/kg 
pH: 6.5 to 8.0 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Rienso is indicated for the intravenous treatment of iron deficiency anaemia in adult patients with 
chronic kidney disease (CKD). 
 
The diagnosis of iron deficiency must be based on appropriate laboratory tests (see section 4.2). 
 
4.2 Posology and method of administration 
 
Rienso should only be administered when staff trained to evaluate and manage anaphylactic reactions 
is immediately available, in an environment where full resuscitation facilities can be assured. 
Patients should be carefully monitored for signs and symptoms of hypersensitivity reactions including 
monitoring of blood pressure and pulse during and for at least 30 minutes following each infusion of 
Rienso. In addition, patients should be placed in a reclining or semi-reclining position during infusion 
and for at least 30 minutes thereafter (see section 4.4). 
 
Posology 
 
Treatment Course 
 
The recommended course of Rienso is based on the patient’s pre-treatment haemoglobin and body 
weight as provided in Table 1.  
 
Each 510 mg dose is administered as an intravenous infusion for at least 15 minutes. For patients 
receiving two doses, the second 510 mg infusion is to be administered 2 to 8 days later as per Table1.   
 

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Table 1: Recommended Dosing Table for Rienso Administration 
 
 Total Amount of Rienso to Administer 

mg of Iron (Number of vials) 
Haemoglobin ≤ 50 kg Body Weight > 50 kg Body Weight 
> 10-12 g/dl 510 mg iron (1 vial) 2 × 510 mg iron (2 vials) 
≤ 10 g/dl 2 × 510 mg iron (2 vials) 2 × 510 mg iron (2 vials) 
 
The maximum dose is 1020 mg (2 vials) and the two doses of Rienso must not be administered at the 
same time. 
 
Rienso should not be given to patients if their haemoglobin is greater than 12 g/dl, serum Transferrin 
Saturation (TSAT) is greater than 50% or Ferritin is greater than 800 ng/ml (see section 4.4). 
 
Patients should be re-assessed at least one month after the completion of a course of Rienso and this 
should include laboratory testing of haematologic and blood iron parameters.   
 
Re-treatment 
 
To maintain the target haemoglobin value, re-treatment with Rienso may be given after the patient has 
been re-assessed and confirmed to be iron deficient. For maintenance therapy and patient monitoring, 
the recommendations of current guidelines (e.g. Revised European Best Practice Guidelines) should 
be followed. 
 
Paediatric population 
 
The safety and efficacy of Rienso in children and adolescents below the age of 18 years has not been 
established. No data are available. Therefore Rienso should not be administered to children and 
adolescents below the age of 18 years (see section 5.1). 
 
Special population – patients receiving haemodialysis  
 
For patients receiving haemodialysis, Rienso should be administered once the blood pressure is stable 
and the patient has completed at least one hour of haemodialysis.  
 
Hepatic Impairment 
 
Rienso has not been specifically studied in patients with hepatic impairment; clinical experience is 
limited to 8 patients. In patients with liver dysfunction, parenteral iron should only be administered 
after careful risk/benefit assessment. No change in dosage is recommended from Table 1. 
 
Method of administration  
 
Intravenous use by infusion. 
 
Rienso should be administered as an infusion in 50-250 ml of sterile 0.9% sodium chloride or sterile 
5% glucose for at least 15 minutes (see sections 6.3 and 6.6). 
 
4.3 Contraindications 
 
The use of Rienso is contraindicated in cases of: 
• Hypersensitivity to the active substance, to Rienso or any of its excipients listed in section 6.1 
• Patients with any known history of drug allergy including hypersensitivity to other parenteral 

iron products  
• Evidence of iron overload 

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• Anaemia not caused by iron deficiency 
 
4.4 Special warnings and precautions for use 
 
Hypersensitivity Reactions 
Parenterally administered iron preparations can cause hypersensitivity reactions including serious and 
potentially fatal anaphylactic/anaphylactoid reactions. Hypersensitivity reactions have also been 
reported after previously uneventful doses of parenteral iron complexes.  
 
The risk is enhanced for patients with known allergies including drug allergies, including patients 
with a history of severe asthma, eczema or other atopic allergy (see section 4.3). 
There is also an increased risk of hypersensitivity reactions to parenteral iron complexes in patients 
with immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis). 
 
Rienso should only be administered when staff trained to evaluate and manage anaphylactic reactions 
is immediately available, in an environment where full resuscitation facilities can be assured. Patients 
should be carefully monitored for signs and symptoms of hypersensitivity reactions including 
monitoring of blood pressure and pulse during and for at least 30 minutes following each infusion of 
Rienso. In addition, patients should be placed in a reclining or semi-reclining position during infusion 
and for at least 30 minutes thereafter.  
 
If hypersensitivity reactions or signs of intolerance occur during administration, the treatment must be 
stopped immediately. Facilities for cardio respiratory resuscitation and equipment for handling acute 
anaphylactic/anaphylactoid reactions should be available, including an injectable 1:1000 adrenaline 
solution. Additional treatment with antihistamines and/or corticosteroids should be given as 
appropriate. 
 
Fatal and life-threatening hypersensitivity reactions have been observed with Rienso in the post 
marketing setting. Clinical presentation has included anaphylactic type reactions presenting with 
cardiac arrest/cardiorespiratory arrest, clinically significant hypotension, syncope, and 
unresponsiveness (see section 4.8).  
 
Elderly patients (> 65 years of age) or patients with multiple co-morbidities who experience a serious 
hypersensitivity reaction may have more severe outcomes.  
 
Hypotension 
Severe adverse reactions of clinically significant hypotension have been reported. Hypotension may 
follow Rienso administration with or without accompanying signs of hypersensitivity (see section 
4.8).  
 
Patients should be monitored for signs and symptoms of hypotension following each Rienso 
administration. 
 
Iron Overload 
Rienso should not be administered to patients with iron overload. Rienso must not be given to patients 
if their haemoglobin is greater than 12 g/dl, serum Transferrin Saturation (TSAT) is greater than 50% 
or ferritin is greater than 800 ng/ml (see section 4.2). 
 
Immunologic Disease or Infection 
Parenteral iron should be used with caution in cases of immunologic disease or acute or chronic 
infection. It is not recommended to administer Rienso to patients with ongoing bacteraemia. 
 
Re-treatment / Long term use 
Limited clinical study data is available regarding re-treatment with Rienso and no clinical study data 
is available for repeated long term use. For information on post-marketing experience see section 5.1. 

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Ethanol and sodium content 
This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg per 17 ml vial. 
This medicinal product contains less than 23 mg sodium per 17 ml vial, i.e., is essentially “sodium 
free”. 
 
Magnetic Resonance (MR) Imaging 
Administration of Rienso may transiently affect the diagnostic ability of MR imaging.  
Anticipated MR imaging studies should be conducted prior to the administration of Rienso.  
The effect on vascular MR imaging lasts approximately 1-2 days while tissue diagnostic imaging may 
be affected for up to 6 months.  
MR images are interpretable earlier by readers aware of the recent administration of Rienso or by the 
use of T1- or proton density-weighted MR pulse sequences. 
Rienso will not interfere with X-ray, computed tomography (CT), positron emission tomography 
(PET), single photon emission computed tomography (SPECT), ultrasound or nuclear medicine 
imaging. 
 
Interference with Serological Testing 
In the 24 hours following administration of Rienso, laboratory assays may overestimate serum iron 
and transferrin bound iron by also measuring the iron in the Rienso complex. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No drug-drug interaction studies have been performed. As with all parenteral iron preparations the 
absorption of oral iron is reduced when administered concomitantly. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential and pregnancy 
 
There are no adequate and well-controlled trials of Rienso in pregnant women. Studies in animals 
have shown reproductive toxicity (see section 5.3). A careful risk/benefit evaluation is therefore 
required before use during pregnancy and Rienso should not be used during pregnancy unless clearly 
necessary (see section 4.4). 
 
Iron deficiency anaemia occurring in the first trimester of pregnancy can in many cases be treated 
with oral iron. Treatment with Rienso should be confined to second and third trimester if the benefit is 
judged to outweigh the potential risk for both the mother and the foetus. 
 
Rienso is not recommended in women of childbearing potential not using adequate contraception. 
 
Breastfeeding 
 
It is unknown whether Rienso is excreted in human milk. Available pharmacokinetic data in animals 
have shown excretion of Rienso in milk (see section 5.3).  
 
A risk to breastfeeding newborns/infants cannot be excluded.  
 
A decision must be made whether to discontinue breast-feeding or to discontinue Rienso therapy, 
taking into account the benefit of breast-feeding for the child and the benefit of the therapy for the 
mother. 
 

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Fertility 
 
No adverse effects on fertility or general reproductive performance were noted in adult rats (see 
Section 5.3). In a prenatal and postnatal developmental study in rats adverse effects on sexual 
maturation and on the ability to produce a litter were noted in the F1-generation (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Rienso may have a minor influence on the ability to drive and use machines. In the case of symptoms 
of dizziness, confusion or light headedness following the administration of Rienso, patients should not 
drive or use machinery until the symptoms have ceased.  
 
No studies regarding effects on the ability to drive or operate machines have been performed. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
In clinical trials involving 1562 subjects with CKD, adverse reactions were seen in 7.9% of patients 
who received Rienso, of which 0.2% were considered serious. 
 
The most frequently reported adverse reactions were gastrointestinal symptoms (diarrhoea, 
constipation, nausea and vomiting), headache, dizziness and hypotension, all occurring in less than 
2.5% of patients. Serious hypersensitivity or hypotensive reactions are uncommon (less than 1 case 
per 100 patients) and were reported in 0.2% (3/1562) of subjects with CKD who received Rienso 
during the clinical studies. One of these three cases was also characterized as an anaphylactoid 
reaction.   
 
Tabulated list of adverse reactions 
 
Table 2 presents all adverse experiences observed during the clinical studies in which 1562 subjects 
with CKD received two injections of 510 mg of Rienso separated by an interval of 2 to 8 days and 
post-marketing experience. 
 
Table 2: Adverse reactions observed during clinical studies and post-marketing 

experience 
 
SYSTEM 
ORGAN 
CLASS 

COMMON  
(≥ 1/100 to 

< 1/10) 

UNCOMMON  
(≥ 1/1,000 to 

< 1/100) 

RARE 
(≥ 1/10,000 to 

< 1/1,000) 

FREQUENCY NOT 
KNOWN (CANNOT BE 
ESTIMATED FROM 
AVAILABLE DATA) 

Blood and 
lymphatic 
system disorders 

  Eosinophilia  

Immune system 
disorders  

 Hypersensitivity 
including 
anaphylaxis* 

 Life-threatening 
Anaphylactic/Anaphylactoid 
reactions* 

Metabolism and 
nutrition 
disorders 

 Decreased 
appetite 
Increased appetite 

Dehydration 
Gout 
Hyperkalaemia 

 

Nervous system 
disorders 

 Dizziness 
Dysgeusia  
Headache 
Somnolence  
Burning sensation 

Paraesthesia Syncope 
Unresponsiveness  
Loss of consciousness  

 

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SYSTEM 
ORGAN 
CLASS 

COMMON  
(≥ 1/100 to 

< 1/10) 

UNCOMMON  
(≥ 1/1,000 to 

< 1/100) 

RARE 
(≥ 1/10,000 to 

< 1/1,000) 

FREQUENCY NOT 
KNOWN (CANNOT BE 
ESTIMATED FROM 
AVAILABLE DATA) 

Eye disorders   Lacrimation 
increased 
Vision blurred 

 

Cardiac 
disorders 

   Tachycardia/Arrhythmia, 
Cardiac arrest 
Cardio-respiratory arrest 
Myocardial infarction 
Cyanosis 
Congestive heart failure 

Vascular 
disorders 

 Hypotension 
(hypotension, 
blood pressure 
decreased) 
Flushing (flushing, 
hot flush) 
Hypertension 
(hypertension, 
accelerated 
hypertension) 

 Vasodilation 

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Dyspnoea Epistaxis Bronchospasm 
Cough 
Hyperventilation  
Hypoxia 
Laryngeal oedema  
Pharyngeal oedema 
Respiratory arrest 
Respiratory failure 
Throat irritation 
Throat tightness 
Wheezing 

Gastrointestinal 
disorders 

 Diarrhoea 
Constipation 
Nausea 
Abdominal pain 
(Abdominal 
distension, 
abdominal pain 
upper, abdominal 
discomfort) 
Vomiting 
Faeces 
discoloured 

Dry mouth 
Dyspepsia 
Glossodynia 

Lip swelling  
Swollen tongue 

Hepatobiliary 
disorders 

  Hepatic function 
abnormal 

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SYSTEM 
ORGAN 
CLASS 

COMMON  
(≥ 1/100 to 

< 1/10) 

UNCOMMON  
(≥ 1/1,000 to 

< 1/100) 

RARE 
(≥ 1/10,000 to 

< 1/1,000) 

FREQUENCY NOT 
KNOWN (CANNOT BE 
ESTIMATED FROM 
AVAILABLE DATA) 

Skin & 
subcutaneous 
tissue disorders 

 Rash (rash, rash 
generalised, rash 
pruritic, urticaria) 
Pruritus (pruritus 
generalised) 
Ecchymosis 
Sweating 
(hyperhidrosis, 
night sweats) 
Skin 
hyperpigmentation 
Skin reaction 

 Angioedema 

Musculoskeletal 
and connective 
tissue disorders 

 Muscle/joint pain 
or stiffness 
(arthralgia, 
myalgia, muscular 
weakness, 
musculoskeletal 
stiffness) 
Back pain 
Muscle spasms 

  

General 
disorders and 
administration 
site conditions 

Injection site 
reactions 
(infusion/injection 
site bruising, pain, 
reaction, swelling, 
warmth, 
haemorrhage, 
irritation, rash) 

Fatigue (asthenia, 
fatigue) 
Chest pain (chest 
discomfort, chest 
pain) 
Chills 
Fever (feeling hot, 
pyrexia) 

 Injection site discolouration 
Injection site pruritus 

Investigations  Serum ferritin 
increased  

Blood glucose 
decreased 

Pulse absent 
Oxygen saturation decreased 

Injury, 
poisoning and 
procedural 
complications 

 Contusion   

 
Description of selected adverse reactions 
 
In clinical trials, adverse reactions leading to treatment discontinuation and occurring in ≥ 2 
Rienso-treated patients included hypotension, infusion site swelling, increased serum ferritin levels, 
chest pain, diarrhoea, dizziness, ecchymosis, pruritis, chronic renal failure and urticaria. 
 
*Fatal and life-threatening hypersensitivity reactions have been observed with Rienso in the post 
marketing setting (see sections 4.3 and 4.4). 
 
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions is an important way to gather more information to continuously 
monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be 
reported via the national reporting system listed in Appendix V. 
 

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http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 9 

4.9 Overdose 
 
No data from clinical trials are available regarding overdose of Rienso in humans. During the 
post-marketing phase, several patients received an overdose of Rienso ranging from 1 g in 1 day to 
2.5 g over 21 days. Only one case of minor rash was observed. Excessive administration of Rienso 
may lead to accumulation of iron in storage sites potentially leading to haemosiderosis.  
 
Periodic monitoring of laboratory parameters of iron storage, such as serum ferritin and transferrin 
saturation, enables recognition of iron accumulation. However, caution should be exercised in 
interpreting serum iron levels in the 24 hours following administration of Rienso as laboratory assays 
may overestimate serum iron and transferrin bound iron by also measuring the iron in Rienso. Please 
see the iron overload section 4.4 and for dosing guidance, see section 4.2. 
 
Overdose should be treated, if required, with an iron chelating agent. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Not yet assigned, ATC code: Not yet assigned 
 
Mechanism of Action 
 
Rienso is a colloidal iron-carbohydrate complex. It includes iron oxide particles with an iron oxide 
core surrounded by a polyglucose sorbitol-carboxymethylether shell. The shell isolates the bioactive 
iron from plasma components until the iron-carbohydrate complex enter reticuloendothelial system 
macrophages of the liver, spleen and bone marrow. The iron is then released intracellularly from the 
iron-carbohydrate complex within vesicles in macrophages. Iron then either enters the intracellular 
storage iron pool (e.g., ferritin) or is transferred to plasma transferrin for transport to erythroid 
precursor cells for incorporation into haemoglobin. 
 
Clinical Efficacy and Safety 
 
The safety and efficacy of Rienso (cumulative dose of 1.02 grams) for the treatment of iron deficiency 
in CKD patients with IDA were assessed in three randomized, open-label, controlled clinical studies 
(Studies 1, 2 and 3). The principal efficacy results at Day 35 from the controlled phase of each study 
are shown in Table 3. This includes the Baseline and mean change to Day 35 in haemoglobin 
(Hgb, g/dl), transferrin saturation (TSAT, %) and ferritin (ng/ml) as well as the proportion of subjects 
who were Hgb Responders at Day 35 (defined as proportion of subjects with an increase in Hgb of at 
least 1.0 g/dl) in each treatment group for Studies 1, 2, and 3. 

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Table 3: Summary of Efficacy Endpoints at Day 35 (Intent to Treat Population) 
 

Endpoint 

Study 1 
Non-dialysis CKD 

Study 2 
Non-dialysis CKD 

Study 3 
CKD on Haemodialysis 

Rienso 
n = 226 

Oral Iron 
n = 77 

Rienso 
n = 228 

Oral Iron 
n = 76 

Rienso 
n = 114 

Oral Iron 
n = 116 

Baseline Hgb 
(mean ± SD, g/dl) 

9.9  
± 0.8 

9.9  
± 0.7 

10.0  
± 0.7 

10.0  
± 0.8 

10.6  
± 0.7 

10.7  
± 0.6 

Hgb change from 
Baseline at Day 35 
(mean ± SD, g/dl) 

1.2*  
± 1.3 

0.5  
± 1.0 

0.8*  
± 1.2 

0.2  
± 1.0 

1.0*  
± 1.1 

0.5  
± 1.1 

Proportion of Hgb 
Responders (%) 51.8 19.5 39.0 18.4 49.1 25.0 

Baseline TSAT 
(mean ± SD, %) 

9.8  
± 5.4 

10.4  
± 5.2 

11.3 
± 6.1 

10.1  
± 5.5 

15.7  
± 7.2 

15.9  
± 6.3 

TSAT change from 
Baseline at Day 35 
(mean ± SD, %) 

9.2  
± 9.4 

0.3  
± 4.7 

9.8  
± 9.2 

1.3  
± 6.4 

6.4  
± 12.6 

0.6  
± 8.3 

Baseline ferritin 
(mean ± SD, ng/ml) 

123.7  
± 125.4 

146.2  
± 136.3 

146.1  
± 173.6 

143.5  
± 144.9 

340.5  
± 159.1 

357.6  
± 171.7 

Ferritin change from 
Baseline at Day 35 
(mean ± SD, ng/ml) 

300.7  
± 214.9 

0.3  
± 82.0 

381.7  
± 278.6 

6.9  
± 60.1 

233.9  
± 207.0 

-59.2  
± 106.2 

* p≤0.001 for main efficacy endpoint 
Hgb = haemoglobin; TSAT = transferrin saturation; SD = standard deviation 
 
In all three studies, patients with CKD and iron deficiency anaemia were randomized to treatment 
with Rienso or oral iron. Rienso was administered as two 510 mg intravenous injections (separated by 
2 to 8 days) and oral iron (ferrous fumarate) was administered at a total daily dose of 200 mg 
elemental iron for 21 days. The major study outcomes assessed the change in haemoglobin from 
Baseline to Day 35. Studies 1 and 2 enrolled patients with non-dialysis dependent CKD and Study 
3 enrolled patients who were undergoing haemodialysis. 
 
In Study 1, the mean age of patients was 66 years (range, 23 to 95); 60% were female; 65% were 
Caucasian, 32% were Black, and 2% were other races. In the Rienso and oral iron groups, 42% and 
44% of patients, respectively, were receiving erythropoiesis stimulating agents (ESAs) at Baseline. 
 
In Study 2, the mean age of patients was 65 years (range, 31 to 96); 61% were female; 58% were 
Caucasian, 35% were Black, and 7% were other races. In the Rienso and oral iron groups, 36% and 
43% of patients, respectively, were receiving ESAs at Baseline. 
 
In Study 3, the mean age of patients was 60 years (range, 24 to 87); 43% were female; 34% were 
Caucasian, 59% were Black, and 7% were other races. All patients were receiving ESAs at Baseline. 
 
Following completion of the controlled phase of each of the Phase 3 trials, patients who were iron 
deficient and anaemic could be optionally retreated and receive two additional 510 mg intravenous 
injections of Rienso for a total cumulative dose of 2.04 g. Overall, 69 patients received a total 
cumulative dose of 2.04 g. Adverse reactions following this repeat Rienso dosing were similar in 
character and frequency to those observed following the first two intravenous injections.   
 
In a placebo-controlled, cross-over trial, 713 patients with CKD received a single 510 mg dose of 
Rienso and placebo. Adverse reactions reported in these patients were similar in character and 
frequency to those observed in the other clinical trials. 
 

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Post-Marketing Data from Dialysis Clinics in the United States 
 
Retrospective observational data from three large haemodialysis clinics in the US over a 1 year period 
included the treatment of over 8,600 patients with more than 33,300 administered doses of Rienso; 
nearly 50% of patients received repeat dosing with 4 or more doses. Mean haemoglobin increased 
(0.5-0.9 g/dl) post-treatment and stabilised in the range of 11-11.7 g/dl over the 10 month post-dose 
period; no new safety signals were identified with repeat dosing. 
 
Paediatric Population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Rienso in one or more subsets of the paediatric population in the treatment of iron deficiency anaemia 
(see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic Properties 
 
The pharmacokinetic (PK) behaviour of Rienso has been examined in healthy subjects and in patients 
with CKD stage 5D on haemodialysis. Rienso exhibited dose-dependent, capacity-limited elimination 
from plasma with a half life of approximately 16 hours in humans. The clearance (CL) was decreased 
with increased doses of Rienso. Volume of distribution (Vd) was consistent with plasma volume, and 
the mean maximum observed plasma concentration (Cmax) and terminal half-life (t1/2) values increased 
with dose. The estimated values of CL and Vd following two 510 mg doses of Rienso administered 
intravenously within 24 hours were 69.1 ml/hr and 3.3 l, respectively. The Cmax and time of maximum 
concentration (tmax) were 206 mcg/ml and 0.32 hr, respectively. Rate of infusion had no influence on 
Rienso PK parameters. No gender differences in Rienso PK parameters were observed. Rienso is not 
removed by haemodialysis. 
 
5.3 Preclinical Safety Data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity, local tolerance and immunotoxicity. In a 4 week 
repeated dose toxicity study in rats after a recovery of 26 weeks hepatic changes (focal or multifocal 
haemorrhage, hemorrhagic necrosis, chronic inflammation, and/or bile duct hyperplasia) were seen in 
the female animals (the cumulative HED of the dose groups compares to a safety multiple of 5.1 and 
10.5 to the cumulative human therapeutic dose (2 x 510 mg Fe) in a 60 kg human). Such effects were 
not seen in the male animals of that study or in the 13 weeks repeated dose toxicity study in rats 
(without recovery). As seen from clinical data there is no evidence that these effects seen in female 
rats are relevant for humans. 
 
No carcinogenicity studies were performed with Rienso. 
 
No adverse effects on fertility or general reproductive performance were noted in rats given IV Rienso 
at doses up to 18 mg Fe/kg/day (Human Equivalent Dose of 2.9 mg Fe/kg/day).  
 
Administration of Rienso during organogenesis in rats at maternally toxic doses of 100 mg Fe/kg/day 
caused a decrease in foetal weights.  
 
In rabbits administration of Rienso during organogenesis induced decreased foetal weights and 
external and/or soft tissue malformations (malrotated or flexed fore- and malrotated hindlimbs, 
internal hydrocephaly, absent brains, cleft palate and microglossia) at the high dose of 
45.3 mg Fe/kg/day (HED of 14.6 mg Fe/kg/day), a dose which induced only minimal maternal 
toxicity.  
 
In a pre-natal and post-natal development study in rats sexual maturation was delayed in male pups in 
the high dose of 60 mg Fe/kg/day (HED of 9.7 mg Fe/kg/day). In female pups of the mid and high 
dose groups of 30 mg Fe/kg/day and 60 mg Fe/kg/day respectively (HED of 4.8 mg Fe/kg/day and 

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9.7 mg Fe/kg/day, respectively) sexual maturation was delayed and a disruption of the oestrus cycle 
was noted in some females. The ability to produce a litter (reproductive competence) was reduced in 
high dose males and in mid and high dose females, irrespective of whether F1 males were mated with 
F1 females or F1 males were mated with naive females and vice versa.  
 
In a lactation study in rats, there was minimal excretion of Rienso or Rienso-derived radioactivity into 
milk following single IV administration of approximately 100 mg Fe/kg (HED of 16.1 mg Fe/kg, 
approximately 2 times the recommended 510 mg human dose on a mg/m2 basis) of either the 
unlabelled, 59Fe or 14C-labelled product to lactating rats 10-11 days post-parturition, which peaked at 8 
to 24 hours post-administration. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Polyglucose-sorbitol carboxymethylether (PSC) 
Mannitol 
Water for Injections 
Sodium hydroxide (for pH adjustment) 
Hydrocholric acid (for pH adjustment) 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other 
medicinal products, except those mentioned in section 6.6. 
 
6.3 Shelf life 
 
48 months 
 
Shelf-life after first opening and after dilution for infusion:  
Chemical and physical in-use stability has been demonstrated for 96 hours at 25 °C. 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user and 
would not be longer than 4 hours at 25 °C. 
 
6.4 Special precautions for storage 
 
Rienso must only be mixed with sterile sodium chloride 9 mg/ml (0.9%) or sterile 5% glucose up to a 
final concentration of 2-8 mg iron per ml. 
 
No other intravenous dilution solutions and therapeutic agents should be used. For dilution 
instructions, please see section 4.2. 
 
Store in the original package in order to protect from light. 
Do not freeze. 
 
6.5 Nature and contents of container 
 
17 ml of solution in a vial (type I glass) with a stopper (chlorobutyl rubber) and an aluminium 
crimp-on seal. 
 
Available in packs sizes of 1, 2, 6 or 10 vials. 
 
Not all pack sizes may be marketed. 

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6.6 Special precautions for disposal and other handling 
 
Rienso Administration 
The vials are for single use only. 
The vials should be inspected visually to ensure the absence of particulate matter and damage prior to 
administration. 
 
Rienso should be administered as an intravenous infusion into a new or existing venous access site.  
 
Administration should be performed as follows:  
 
Haemodialysis patients: 
Dosing should begin when blood pressure is stable and the patient has completed at least one hour of 
haemodialysis. 
 
 For all patients: 
• Administer Rienso as an infusion as follows: 

o 510 mg (one vial) diluted in 50-250 ml of sterile 0.9% sodium chloride or sterile 5% 
glucose, administered for at least 15 minutes (concentration of 2-8 mg iron per ml). 

• Patients should be carefully monitored for signs and symptoms of hypersensitivity reactions 
including monitoring of blood pressure and pulse during and for at least 30 minutes following 
each infusion of Rienso. In addition, patients should be placed in a reclining or semi-reclining 
position during infusion and for at least 30 minutes thereafter. 

• Administer a single vial as an infusion. A second vial of the medicine should be administered as 
an infusion two to eight days later if indicated. 

• Any unused product or waste material should be disposed of in accordance with local 
requirements. 
 

 
7. MARKETING AUTHORISATION HOLDER 
 
Takeda Pharma A/S 
Dybendal Alle 10 
2630 Taastrup 
Denmark 
P: +45 4677 1111 
F: +45 4675 6640 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/774/001 
EU/1/12/774/002 
EU/1/12/774/003 
EU/1/12/774/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 15 June 2012 
 
 

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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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http://www.ema.europa.eu/


 15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 responsible for batch release 
Takeda Italia S.p.A. 
Via Crosa 86 
28065 Cerano (NO) 
Italy 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic Safety Update Reports 
 
The marketing authorisation holder shall submit periodic safety update reports for this product in 
accordance with the requirements set out in the list of Union reference dates (EURD list) provided for 
under Article 107c(7) of Directive 2001/83/EC and published on the European medicines web-portal. 
 
 
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.  

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 
• Additional risk minimisation measures 
 
Prior to the use of Rienso in each Member State the Marketing Authorisation Holder (MAH) must 
agree about the content and format of the educational programme, including communication media, 
distribution modalities, and any other aspects of the programme, with the National Competent 
Authority.  
 
The educational programme is aimed at highlighting the risks and warnings on hypersensitivity 
reactions and the monitoring of patients during and after administration. 
 

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The MAH shall ensure that in each Member State where Rienso is marketed, all healthcare 
professionals and patients/carers who are expected to use Rienso have access to/are provided with the 
following educational package: 
 
• Healthcare professional checklist 
• Patient alert card  
 
The healthcare professional checklist shall contain the following messages: 
 
• The checklist should include tick-boxes to check and document: 

o Confirmation on appropriate settings (emergency resuscitation equipment available ) prior to 
administration of ferumoxytol 

o Patient’s eligibility 
o Contraindications and warnings 
o Duration of administration 
o Semi-reclined position during administration 
o Duration of monitoring of patients after administration. 

 
The patient alert card shall contain the following key messages: 
 
• Information regarding the increased risk of serious including fatal hypersensitivity reactions: 

contraindications, special patient populations (e.g. pregnant women, elderly), warnings, 
symptoms of hypersensitivity reactions, monitoring by health care professionals during 
30 minutes after administration, warning on late onset of allergic reactions. 

 
• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Condition  Date  
The MAH shall conduct a PASS to further characterise 
the safety concerns on the hypersensitivity reactions. The 
study will also have to be reflected in the updated RMP 
submission. Final study report by:  

31 July 2016  

The MAH shall conduct a study to investigate the 
mechanism of hypersensitivity associated with the 
exposure to ferumoxytol, according to a protocol agreed 
by the CHMP. Final study report by:  

31 October 2016 

 

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 18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

 

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A. LABELLING 
 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton Label (1, 2, 6 or 10 vial pack) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rienso 30 mg/ml solution for infusion 
Iron as ferumoxytol 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains 30 mg of iron.  
510 mg iron/17 ml  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
Polyglucose-sorbitol carboxymethylether (PSC) 
Mannitol 
Water for injections 
Sodium hydroxide (for pH adjustment)  
Hydrochloric acid (for pH adjustment) 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for infusion 
1 vial 
2 vials 
6 vials 
10 vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use only. 
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 
 
 

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8. EXPIRY DATE 
 
EXP:  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light. 
Do not freeze. 
 
 
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 
 
Takeda Pharma A/S 
Dybendal Alle 10 
2630 Taastrup 
Denmark 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/774/001 
EU/1/12/774/002 
EU/1/12/774/003 
EU/1/12/774/004  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille is accepted 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial Label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Rienso 30 mg/ml infusion 
Iron as ferumoxytol 
For intravenous use only 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
510 mg/17 ml 
 
 
6. OTHER 
 
 

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B. PACKAGE LEAFLET 
 
 

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Package leaflet: Information for the patient 
 

Rienso 30 mg/ml solution for infusion 
Iron as ferumoxytol 

 
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 are given 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, pharmacist or nurse. 
- If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Rienso is and what it is used for 
2. What you need to know before you receive Rienso 
3. How Rienso is given 
4. Possible side effects 
5. How to store Rienso 
6. Contents of the pack and other information 
 
 
1. What Rienso is and what it is used for 
 
Rienso is an iron preparation, containing the active substance ferumoxytol, which is given by infusion 
into a vein. It is used to treat iron deficiency anaemia resulting from a lack of stored iron, in adult 
patients with reduced kidney function.  
 
Iron is an essential element required to make haemoglobin, a molecule in red blood cells that enables 
oxygen to be carried around the body. When there is insufficient iron in the body, haemoglobin 
cannot be formed, resulting in anaemia (low levels of haemoglobin). 
 
The aim of Rienso therapy is to replenish the body’s iron stores. 
 
 
2. What you need to know before you receive Rienso 
 
Before you were prescribed Rienso, the doctor will have carried out a blood test to make sure that you 
have iron deficiency anaemia.  
 
You must not receive Rienso: 
- if you are allergic (hypersensitive) to the product or any of the other ingredients of this 

medicine (listed in section 6). 
- if you have a history of medicine allergy or have experienced serious allergic (hypersensitive) 

reactions to other injectable iron preparations.  
- if you have iron overload (too much iron in your body). 
- if your anaemia is not caused by iron deficiency. 
 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse before receiving Rienso: 
- if you have a history of medicine allergy.  
- if you have systemic lupus erythematosus. 

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 25 

- if you have rheumatoid arthritis. 
- if you have severe asthma, eczema or other allergies. 
- if you have a problem with your liver. 
- if you have problems with your immune system.  
- if you have any infections, including infections which have spread to your blood stream. 
- if you are scheduled for magnetic resonance imaging (an MRI scan), as this medicine may 

interfere with the interpretation of the scan. For the same reason also talk to your doctor or 
radiographer if you have been given Rienso within the past 6 months and an MRI is 
subsequently arranged. 

Rienso can affect the interpretation of your blood iron test results. 
 
Children and adolescents 
Rienso should not be given to children and adolescents under 18 years old. 
 
Other medicines and Rienso 
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 
medicines. 
 
Pregnancy 
Rienso has not been tested in pregnant women. Studies in animals have shown reproductive toxicity. 
If you are pregnant, you should not receive Rienso. 
It is important to tell your doctor if you are pregnant, think you may be pregnant, or are planning to 
have a baby. 
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. 
Your doctor will decide whether or not you should be given this medicine. 
 
Breast-feeding 
It is not known whether the active substance in this medicine can pass into breast milk. If you are 
breast-feeding, ask your doctor for advice before you are given Rienso. 
 
Driving and using machines 
Some people may feel dizzy, confused or lightheaded after receiving treatment. If this happens to you, 
do not drive or use any tools or machinery. 
 
Rienso contains ethanol and sodium 
This medicine contains small amounts of ethanol (alcohol), less than 100 mg per 17 ml vial. 
This medicine contains less than 23 mg sodium per 17 ml vial, i.e., it is essentially “sodium free”. 
 
 
3. How Rienso is given 
 
Your doctor will decide how much Rienso to give you based on your weight and blood test results. 
The treatment you will receive can be 1 or 2 vials of Rienso (510 mg each) by infusion and each dose 
will be infused into a vein. For patients receiving two vials, the second one will be infused two to 
eight days after the first infusion. Your doctor will decide if additional doses of Rienso are needed 
and for how long. He or she will also monitor your blood test results to avoid iron accumulation. 
 
Your doctor or nurse will administer Rienso by infusion into a vein. You will be lying down and your 
blood pressure and pulse will be monitored. Rienso will be administered in an environment where any 
allergic event can receive appropriate and prompt treatment. 
 
You will be carefully observed during the infusion and for at least 30 minutes after each infusion by 
your doctor or nurse. Please immediately tell the doctor or nurse if you start to feel unwell. They may 
decide to stop the infusion. 
 

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If you are on haemodialysis, you may receive Rienso via infusion over 15 minutes during a dialysis 
session. 
 
If you receive more Rienso than you should 
 
Overdose can cause accumulation of iron in your body. Your doctor will monitor iron levels to avoid 
iron accumulation. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects: 
Tell your doctor or nurse immediately if you experience any of the following signs and symptoms 
indicating serious side effects during or shortly after treatment: 
rash, itching, (sudden) dizziness, light-headedness, (increasing) swelling, difficulty breathing, 
wheezing or any other problems you may have.   
 
In some patients these allergic reactions can become severe or life-threatening (known as anaphylactic 
reactions). These reactions can be associated with heart and circulation complications, loss of 
consciousness and may result in death. If you are older than 65 years or have an underlying condition, 
such as liver or heart disease, the risk of having severe consequences including death may be higher 
after a serious allergic reaction. 
 
Doctors are aware of these possible side effects and will monitor you during the infusion and for at 
least 30 minutes after the infusion, and also have emergency treatment available if required. 
 
Other side effects that you should tell your doctor, pharmacist or nurse about if they become 
serious:  
 
Common side effects (may affect up to 1 in 10 people): 
- bleeding, swelling, bruising, pain, rash, irritation or warmth at infusion/injection site 
 
Uncommon side effects (may affect up to 1 in 100 people): 
- dizziness 
- low blood pressure  
- feeling weak or tired 
- feeling drowsy or sleepy 
- flushing, hot flush 
- feeling hot, fever 
- sweating (including night sweats) 
- chills 
- high blood pressure (sudden increase in blood pressure) 
- skin rash, itching, darkening of an area of skin or nails, bruising, hives  
- burning sensation of skin 
- shortness of breath 
- diarrhoea  
- constipation 
- stomach pain/discomfort 
- stomach distension or bloating 
- nausea, vomiting 

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- discoloured stools 
- changes in taste 
- increased or decreased appetite 
- muscle/joint pain, weakness or stiffness, muscle spasms 
- headache 
- chest pain/discomfort 
- back pain 
- changes in blood test results (e.g. iron parameters) 
- allergic reaction including severe allergic reaction (see paragraph "serious side effects") 

 
Rare side effects (may affect up to 1 in 1,000 people): 
- burning, prickling, numbness or tingling sensation of skin 
- dehydration 
- upset stomach/indigestion 
- nose bleed 
- dry mouth 
- burning or tingling sensation of tongue/mouth 
- increased tearing 
- blurred vision 
- gout 
- abnormal blood tests (decreased glucose, elevated potassium, abnormal liver function, elevated 

type of white blood cell i.e. eosinophilia) 
 
Side effects of unknown frequency (frequency cannot be estimated from the available data) 
The following serious side effects have been reported shortly after receiving Rienso: 
- life-threatening and fatal allergic reactions (anaphylactic/anaphylactoid hypersensitivity) 
- cardiovascular complications (affecting the heart and blood vessels) including heart attack, 

congestive heart failure, palpitations, blood vessel dilation, changes in your pulse rate including 
weak/absent pulse, heart stops beating, heart and breathing stop, blue discolouration of skin 
and/or mucous membranes due to lack of oxygen in the blood (cyanosis) 

- fainting/loss of consciousness/unresponsiveness  
- sudden swelling up of skin or mucous membranes (angioedema), skin rash 
- wheezing (bronchospasm), cough, upper airway swelling, difficulty breathing (change to 

breathing rate), inability to breathe 
- throat irritation, throat tightness, lip swelling, tongue swelling 
- injection site discolouration, injection site itching and discolouration 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report any side effects directly to the national reporting 
system 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 Rienso 
 
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 label after EXP. The expiry date 
refers to the last day of that month. 
 
Store in the original package in order to protect from light.  
 
Do not freeze. 

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 28 

 
Before administration, the vials will be inspected by the person administering the medicine for signs 
of damage or deterioration. 
 
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 to protect the environment. 
 
 
6. Content of the pack and other information 
 
What Rienso contains  
 
- The active substance is iron as ferumoxytol 30 mg/ml. 
- 1 ml solution for infusion contains 30 mg of iron as ferumoxytol. 
- 17 ml solution for infusion contains 510 mg of iron as ferumoxytol.  
- The other ingredients are mannitol, Polyglucose-sorbitol carboxymethylether (PSC), Sodium 

hydroxide (for pH adjustment, Hydrochloric acid (for pH adjustment) and water for injections. 
 
What Rienso looks like and contents of the pack 
 
Rienso is a black to reddish-brown solution for infusion. 
Rienso is supplied in glass vials containing 17 ml. 
Rienso is available in packs sizes of 1, 2, 6 or 10 vials. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing authorisation holder: 
Takeda Pharma A/S 
Dybendal Alle 10 
2630 Taastrup 
Denmark 
P: +45 4677 1111 
F: +45 4675 6640 
 
Manufacturer: 
Takeda Italia S.p.A. 
Via Crosa, 86 
28065 Cerano (NO) 
Italy 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Takeda Belgium  
Tél/Tel: +32 2 464 06 11 
takeda-belgium@takeda.com 
 

Lietuva 
Takeda, UAB 
Tel: +370 521 09 070 
lt-info@takeda.com 
 

България 
Такеда България 
Teл.: + 359 2 958 27 36; + 359 2 958 15 29 
 

Luxembourg/Luxemburg 
Takeda Belgium  
Tél./Tel: +32 2 464 06 11 
takeda-belgium@takeda.com 
 

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mailto:takeda-belgium@takeda.com
mailto:lt-info@takeda.com
mailto:takeda-belgium@takeda.com


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Česká republika 
Takeda Pharmaceuticals Czech Republic s.r.o. 
Tel: +420 234 722 722 
 

Magyarország 
Takeda Pharma Kft. 
Tel.: +361 2707030 

Danmark 
Takeda Pharma A/S 
Tlf: +45 46 77 11 11 

Malta 
Takeda Italia S.p.A. 
Tel: +39 06 502601 
 

Deutschland 
Takeda GmbH 
Tel: 0800 825 3325 
medinfo@takeda.de 
 

Nederland 
Takeda Nederland bv 
Tel: +31 23 56 68 777 
nl.medical.info@takeda.com 
 

Eesti 
Takeda Pharma AS  
Tel: +372 6177 669 
 

Norge 
Takeda Nycomed AS 
Tlf: + 47 6676 3030 
infonorge@takeda.com 
 

Ελλάδα 
TAKEDA ΕΛΛΑΣ Α.Ε 
Tηλ: +30 210 6729570 
gr.info@takeda.com 
 

Österreich 
Takeda Pharma Ges.m.b.H. 
Tel: +43 (0) 800-20 80 50 
 

España 
Takeda Farmacéutica España S.A. 
Tel: +34 917 14 99 00 
spain@takeda.com 
 

Polska 
Takeda Polska Sp. z o.o. 
Tel.: +48 22 608 13 00  

France 
Takeda France S.A.S 
Tél: +33 1 46 25 16 16 
 

Portugal 
Takeda - Farmacêuticos Portugal, Lda. 
Tel: +351 21 120 1457 
 

Hrvatska 
Takeda Pharmaceuticals Croatia d.o.o. 
Tel: +385 1 377 88 96 

România 
Takeda Pharmaceuticals SRL 
Tel: +40 21 335 03 91 
 

Ireland 
Takeda Products Ireland Limited 
Tel: +353 (0) 1 6420021 
 

Slovenija 
Takeda GmbH, Podružnica Slovenija 
Tel: +386 (0) 59 082 480 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
vistor@vistor.is 
 

Slovenská republika 
Takeda Pharmaceuticals Slovakia s.r.o. 
Tel.: +421 (2) 20 602 600 
 

Italia 
Takeda Italia S.p.A. 
Tel: +39 06 502601 
 

Suomi/Finland 
Oy Leiras Takeda Pharmaceuticals Ab 
Puh/Tel: +358 20 746 5000 
 

Kύπρος 
Takeda Pharma A/S 
Tηλ: +45 46 77 11 11 
 

Sverige 
Takeda Pharma AB 
Tel: + 46 8 731 28 00 
infosweden@takeda.com 
 

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mailto:nl.medical.info@takeda.com
mailto:infonorge@takeda.com
mailto:gr.info@takeda.com
mailto:spain@takeda.com
mailto:vistor@vistor.is
mailto:infosweden@takeda.com


 30 

Latvija 
Takeda Latvia SIA 
Tel: +371 67840082 
 

United Kingdom 
Takeda UK Ltd 
Tel: +44 (0)1628 537 900 

 
This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 

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 31 

 
The following information is intended for healthcare professionals only (see Section 3): 
 
Rienso Administration 
 
Rienso should only be administered when staff trained to evaluate and manage anaphylactic reactions 
are immediately available. Rienso should be administered as an intravenous infusion into a new or 
existing venous access site.  
Administration should be performed as follows:  
 
Haemodialysis patients: 
 
Dosing should begin when blood pressure is stable and the patient has completed at least one hour of 
haemodialysis. 
 
For all patients: 
• Administer Rienso as an infusion as follows: 

o 510 mg (one vial) diluted in 50-250 ml of sterile 0.9% sodium chloride or sterile 5% 
glucose, administered for at least 15 minutes (concentration of 2-8 mg iron per ml). 

• Patients should be carefully monitored for signs and symptoms of hypersensitivity reactions 
including monitoring of blood pressure and pulse during and for at least 30 minutes following 
each infusion of Rienso. In addition, patients should be placed in a reclining or semi-reclining 
position during infusion and for at least 30 minutes thereafter. 

• Administer a single vial as an infusion. A second vial of the medicine should be administered as 
an infusion two to eight days later if indicated according to the SmPC. 

• Any unused product or waste material should be disposed of in accordance with local 
requirements. 

 
Incompatibilities 
• Rienso must not be mixed with other medicinal products, with the exception of the infusion 

fluids mentioned below. 
• Rienso must only be mixed with sterile sodium chloride 9 mg/ml (0.9%) or sterile 5% glucose 

up to a final concentration of 2-8 mg iron per ml. 
• No other intravenous dilution solutions and therapeutic agents should be used. 
 
Overdose 
• Overdose should be treated, if required with an iron chelating agent. See SmPC Section 4.9 for 

further information. 
 
Stability and Storage 
• Shelf-Life – 48 months 
• Shelf life after first opening and after dilution for infusion:  

Chemical and physical in-use stability has been demonstrated for 96 hours at 25 °C 
• From a microbiological point of view, the product should be used immediately after first 

opening or immediately after dilution. If not used immediately, in-use storage times and 
conditions prior to use are the responsibility of the user and would not be longer than 4 hours at 
25°C. 

• Store in the original package in order to protect from light. Do not freeze. 

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 32 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

SCIENTIFIC CONCLUSIONS AND GROUNDS RECOMMENDING THE VARIATION TO 
THE TERMS OF THE MARKETING AUTHORISATIONS 

 

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 33 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR for Rienso, the scientific conclusions 
of PRAC are as follows: 
 
Hypersensitivity reactions 
Cumulatively 21 cases of hypersensitivity (8 serious, 13 non-serious) have been reported during 
clinical trials. Cumulatively, since the granting of the marketing authorisation up to the data lock-
point (DLP) of the current PSUR, a total of 527 reported post-marketing cases of hypersensitivity 
reactions of which more than 50 % were serious including life threatening allergic reactions 
(264 serious, 263 non-serious). In total 42 fatal cases have been reported cumulatively. 29 of them 
were associated with hypersensitivity reactions. Within the limitations inherent to post-marketing 
reporting, the following reporting rate can be calculated: As of 30 June 2014, the cumulative overall 
post-marketing reporting rate of hypersensitivity based on 2 g per person per year is: 
527/266,914 × 100 = 0.20 %. During this PSUR covering period, 45 new cases of hypersensitivity 
reactions have been reported: 24 serious including one fatal case already reported as part of the 
previous PSUR as late-breaking information and 21 non-serious cases. 
 
After the DLP of the present PSUR, 6 additional fatal cases of hypersensitivity reactions with 
ferumoxytol have been reported. Two of these reports were included by the MAH as late breaking 
information into this PSUR. The additional four cases were reported after this PSUR was submitted 
for assessment. All six fatal hypersensitivity cases were reported in the US and involved elderly 
patients (> 65 years of age) with co-morbidities. One patient had a prior history of drug allergy. In 5 
out of these 6 cases, ferumoxytol was administered via IV injection (either quick or slow IV push), for 
the remaining case the method of administration is unknown. 
 
It should be noted that 28 out of the 35 fatal cases of hypersensitivity reactions occurred in elderly 
patients (> 65 years of age). There is no evidence that the risk of hypersensitivity reactions as such is 
increased in elderly patients however these patients have an increased risk of complications. 
 
Considering the cumulative number of reported cases of hypersensitivity reactions (serious, non-
serious) including 35 fatal cases, the PRAC considered new additional risk minimisation measures in 
addition to the ones already implemented as part of the previous PSUR, and recommended that a 
warning on the severity of the outcome of hypersensitivity reactions in patients over 65 or with co-
morbidities should be added in section 4.4 of the SmPC. 
 
Interference with Magnetic Resonance Imaging (MRI) 
No spontaneous post-marketing reports of MRI interference have been received to date. Within this 
PSUR, a further literature review has been provided by the MAH identifying 9 relevant publications 
addressing ferumoxytol and MRI. Four case reports have been published describing the 
supraparamagnetic effects of ferumoxytol on MR imaging and emphasized the importance for the 
radiologists to be aware if a patient received ferumoxytol recently. Based on a limited number of case 
reports, the influence of ferumoxytol on the interpretation of MRIs, due to its unique crystalline 
structure appears to be primarily noted in the first few weeks after administration and, based on 
animal data, dissipated within 3 months. The MAH is of the opinion that the current EU SmPC 
accurately reflects the current literature and provides appropriate guidance to EU practitioners. 
However, the MAH acknowledges that Rostoker and Cohen recommend a minimum of 6 months 
between ferumoxytol’s administration, which they base on the study with 6 healthy volunteers 
published by Storey et al. Therefore the MAH proposed as part of this PSUR to amend the current 
warning in section 4.4 of the SmPC to reflect that interference with MRI can occur up to 6 months 
after administration of ferumoxytoll which was agreed by the PRAC.  
 
Therefore, in view of available data regarding hypersensitivity reactions and interference with 
Magnetic Resonance Imaging (MRI), the PRAC considered that changes to the product information 
were warranted.  
 

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The CHMP agrees with the scientific conclusions made by the PRAC. 
 
Grounds recommending the variation to the terms of the Marketing Authorisation  
 
On the basis of the scientific conclusions for Rienso, the CHMP is of the opinion that the benefit-risk 
balance of the medicinal product containing the active substance ferumoxytol is favourable subject to 
the proposed changes to the product information. 
 
The CHMP recommends that the terms of the Marketing Authorisation should be varied. 
 

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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
	SCIENTIFIC CONCLUSIONS AND GROUNDS RECOMMENDING THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATIONS