Rienso
ferumoxytol
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.
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 Rienso is and what it is used for
What you need to know before you receive Rienso
How Rienso is given
Possible side effects
How to store Rienso
Contents of the pack and other information
Medicinal product no longer authorised
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.
Before you were prescribed Rienso, the doctor will have carried out a blood test to make sure that you have iron deficiency anaemia.
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.
Talk to your doctor, pharmacist or nurse before receiving Rienso:
if you have a history of medicine allergy.
if you have systemic lupus erythematosus.
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.
Rienso should not be given to children and adolescents under 18 years old.
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.
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.
Medicinal product no longer authorised
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.
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.
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.
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”.
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.
If you are on haemodialysis, you may receive Rienso via infusion over 15 minutes during a dialysis session.
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.
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.
Medicinal product no longer authorised
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:
bleeding, swelling, bruising, pain, rash, irritation or warmth at infusion/injection site
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
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")
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)
Medicinal product no longer authorised
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
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.
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.
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.
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.
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.
Medicinal product no longer authorised
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:
Takeda Belgium
Tél/Tel: +32 2 464 06 11
Takeda, UAB
Tel: +370 521 09 070
Такеда България
Teл.: + 359 2 958 27 36; + 359 2 958 15 29
Takeda Belgium
Tél./Tel: +32 2 464 06 11
Takeda Pharmaceuticals Czech Republic s.r.o. Tel: +420 234 722 722
Takeda Pharma A/S Tlf: +45 46 77 11 11
Takeda Italia S.p.A. Tel: +39 06 502601
Takeda GmbH
Tel: 0800 825 3325
Takeda Nederland bv Tel: +31 23 56 68 777
Takeda Pharma AS Tel: +372 6177 669
Takeda Nycomed AS Tlf: + 47 6676 3030
TAKEDA ΕΛΛΑΣ Α.Ε Tηλ: +30 210 6729570
Takeda Pharma Ges.m.b.H.
Tel: +43 (0) 800-20 80 50
Takeda Farmacéutica España S.A. Tel: +34 917 14 99 00
Medicinal product no longer authorised
Takeda Polska Sp. z o.o. Tel.: +48 22 608 13 00
Takeda France S.A.S Tél: +33 1 46 25 16 16
Takeda - Farmacêuticos Portugal, Lda. Tel: +351 21 120 1457
Takeda Pharmaceuticals Croatia d.o.o. Tel: +385 1 377 88 96
Takeda Pharmaceuticals SRL Tel: +40 21 335 03 91
Takeda Products Ireland Limited Tel: +353 (0) 1 6420021
Takeda GmbH, Podružnica Slovenija Tel: +386 (0) 59 082 480
Vistor hf.
Sími: +354 535 7000
Takeda Pharmaceuticals Slovakia s.r.o. Tel.: +421 (2) 20 602 600
Takeda Italia S.p.A. Tel: +39 06 502601
Oy Leiras Takeda Pharmaceuticals Ab Puh/Tel: +358 20 746 5000
Takeda Pharma A/S Tηλ: +45 46 77 11 11
Takeda Pharma AB Tel: + 46 8 731 28 00
Takeda Latvia SIA Tel: +371 67840082
Takeda UK Ltd
Tel: +44 (0)1628 537 900
Medicinal product no longer authorised
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: Haemodialysispatients:
Dosing should begin when blood pressure is stable and the patient has completed at least one hour of haemodialysis.
Forallpatients:
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.
Medicinal product no longer authorised
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.
Medicinal product no longer authorised
Taking into account the PRAC Assessment Report on the PSUR for Rienso, the scientific conclusions of PRAC are as follows:
Hypersensitivityreactions
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.
Medicinal product no longer authorised
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.
InterferencewithMagneticResonanceImaging(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.
The CHMP agrees with the scientific conclusions made by the PRAC.
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.
Medicinal product no longer authorised
The CHMP recommends that the terms of the Marketing Authorisation should be varied.