MAGNEVIST 2MMOL/ L SOLUTION FOR INJECTION

Active substance: GADOPENTETIC ACID DIMEGLUMINE SALT

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dimeglumine gadopentetate

Read all of this leaflet carefully before you are given this
medicine.
 Keep this leaflet. You may need to read it again.
 If you have any further questions, please ask the doctor
giving you Magnevist 2mmol/l (the radiologist) or the
hospital/MRI-centre staff.
 If any of the side effects gets serious, or if you notice any
side effects not listed in this leaflet, please tell your doctor,
radiologist or the hospital/MRI-centre staff.
In this leaflet:
1. What Magnevist 2mmol/l is and what it is used for
2. Before you are given Magnevist 2mmol/l
3. How you will be given Magnevist 2mmol/l
4. Possible side effects
5. How to store Magnevist 2mmol/l
6. Further information

1. What Magnevist 2mmol/l is and what it is
used for
Magnevist 2mmol/l is used together with a technique called
Magnetic Resonance Imaging (MRI) to create artificial contrast
or enhancement to help make an MRI scan of your joints
clearer.
MRI is a modern scanning technique which produces very high
quality pictures of various parts of your body without using
X-rays. The use of MRI can provide a quick, early and accurate
diagnosis.
The scanner uses a strong magnetic field and radiowaves to
measure the magnetic properties of body tissues. Using a
computer, this information is converted into a black and white
picture which can help your doctor see and investigate the
differences between normal and abnormal tissue.
Sometimes MRI is used in areas where it cannot produce a clear
black and white picture. This is when Magnevist 2mmol/l is
used. Magnevist 2mmol/l produces a clearer image and allows
the doctor to see the area of interest better. Sometimes several
scans will be taken before Magnevist 2mmol/l is injected and
then further scans taken after the injection.
This medicine is for diagnostic use only.

2. Before you are given Magnevist 2mmol/l
Do not use Magnevist 2mmol/l if:
 you are, or suspect you are, allergic (hypersensitive) to any
of the ingredients of Magnevist 2 mmol/l
(see Section 6: Further Information)
 you have a heart pacemaker or if there are any implants or
clips containing iron inside your body. (This is not because of
an interaction with Magnevist 2mmol/l but because if you
have any of these, you should not be placed in a strong
magnetic field).
Take special care with Magnevist 2mmol/l
Your doctor will need to take special care when giving you
Magnevist 2mmol/l if:
 you have a history of allergy (e.g. hay fever, hives), asthma,
or have had a reaction to another type of contrast media.
This is because you may be more likely to have an allergic
reaction. If you have had any of these in the past, tell the
radiologist or MRI-centre staff.
 you have an infected joint.
Before you receive Magnevist 2mmol/l, you must tell the
radiographer or MRI-centre staff if any of these apply to you.
Taking or using other medicines
Please tell the radiologist or MRI-centre staff if you are taking
or have recently taken any other medicines, including
medicines obtained without prescription.

Magnevist® 2 mmol/l solution for injection
Pregnancy and breast-feeding
Tell the MRI-centre staff if you are pregnant, think you may be
pregnant or are breast-feeding. A very small amount of
Magnevist enters the breast milk, but this isn’t likely to cause
any harm.
Driving and using machines
The volume of Magnevist 2mmol/l injected into your joint may
limit your movement. Do not drive if your movement is
affected.

1. NAME OF THE MEDICINAL PRODUCT
Magnevist® 2 mmol/l solution for injection

2. QUALITATIVE AND QUANTITATIVE
COMPOSITION
1ml aqueous solution contains 1.876 mg gadopentetic acid,
dimeglumine salt as active ingredient (equivalent to
0.002 mmol gadopentetic acid, dimeglumine, containing
0.32 mg gadolinium).
For excipients see section 6.1.

3. How you will be given Magnevist 2mmol/l

3. PHARMACEUTICAL FORM

You will be asked to sit or lie down and Magnevist 2mmol/l will
be injected into the joint which is being investigated. Scanning
may start immediately after the Magnevist 2mmol/l injection.
The MRI staff will observe you for at least 30 minutes after the
injection just in case you have any side effects.
Adults:
The dose of Magnevist 2mmol/l varies depending on which
joint is investigated. For most joints, 20 ml is used, but up to
50 ml may be used for the knee joint. The doctor will decide
how much Magnevist 2mmol/l is needed for your investigation.
Children:
Magnevist 2mmol/l is not recommended for use in children.
If you receive more Magnevist 2mmol/l than you should
Overdosing is unlikely. If this does occur no serious ill-effects
are expected.

Solution for injection.

4. CLINICAL PARTICULARS
4.1 Therapeutic indications
For contrast enhancement in direct magnetic resonance
arthrography.
4.2 Posology and method of administration
This medicinal product is for diagnostic use by intraarticular
administration only.
The usual precautions for MRI (e.g. exclusion of cardiac
pacemakers and other ferro-magnetic objects including
vascular clips etc) must be observed.
The dose required is administered via intraarticular injection
under strict aseptic technique and according to the instructions
provided in section 6.6. ‘Instructions for use and handling’.
Contrast-enhanced MRI can be commenced immediately
afterwards.
The recommendations for the use of Magnevist 2 mmol/l apply
to a field strength between 0.2 Tesla and 1.5 Tesla.
Intraarticular administrations of contrast agents are to be
given with the patient lying or sitting. After the end of the
injection, the patient should be kept under supervision for at
least half an hour.
Adults:
In general, for all joints the administration of up to 20 ml (knee
joint up to 50 ml) Magnevist 2 mmol/l is sufficient for good
opacification and to answer all the relevant clinical questions.
A volume leading to a slight distension of the joint capsule
should be injected. Only so much contrast medium should be
injected until discrete resistance is felt and/or the patient
experiences a mild feeling of pressure.
Guidelines on volumes to be administered:



Joint
Shoulder
Elbow
Wrist
Finger joint
Hip
Knee
Ankle

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Volume required
15-20 ml
~ 10 ml
4 ml
1-2 ml
10-20 ml
25-50 ml
12-20 ml

Children:
The product is not recommended in the paediatric age group
until further data become available.
4.3 Contraindications
Hypersensitivity to any of the ingredients.

4.4 Special warnings and precautions for use
Strict aseptic technique is required to prevent infection.
Fluoroscopic control should be used to ensure proper needle
placement and prevent extracapsular injection. Undue pressure
should not be exerted during injection.
Intraarticular injections of Magnevist 2 mmol/l should be
avoided in infected joints.
 Hypersensitivity
Severe systemic hypersensitivity reactions cannot be totally
excluded (see section 4.8).
Mild angioedema, conjunctivitis, coughing, pruritus, rhinitis,
sneezing and urticaria, which can occur irrespective of the
amount administered and the mode of administration, may be
the first signs of incipient state of shock.
As with other contrast agents, delayed reactions may occur
(hours later or up to several days).
As with other contrast enhanced diagnostic procedures, postprocedure observation of the patient is recommended.
Medication for the treatment of hypersensitivity reactions as
well as readiness for institution of emergency measures are
necessary. Appropriate drugs and instruments
(e.g. endotracheal tube and ventilator) must be readily
available.
The risk of hypersensitivity reactions is higher in case of;
 previous reaction to contrast media,
 history of bronchial asthma,
 history of allergic disorders
The decision to use Magnevist 2 mmol/l must be made after
particularly careful evaluation of the risk-benefit-ratio in
patients with an allergic disposition.
4.5 Interaction with other medicinal products and other
forms of interaction
As for all other gadolinium containing contrast media, no
interactions with other medicaments have been observed.
Formal drug interaction studies have not been carried out. See
also section 6.2 Incompatibilities.
Magnevist should be administered without the addition of
iodinated contrast media as iodinated contrast media reduce
the level of contrast achievable with Magnevist (see Section
6.6 Instructions for use and handling).
4.6 Pregnancy and lactation
 Pregnancy
For gadopentetic acid, dimeglumine no clinical study data on
exposed pregnancies are available. Animal studies do not
indicate direct or indirect harmful effects with respect to
embryonal / foetal development (see section 5.3).
Caution should be exercised using Magnevist 2mmol/l in
pregnant women.
 Lactation
No data exist concerning intra-articular administration in
lactating women. After intravascular use minimal amounts of
gadopentetic acid, dimeglumine salt (a maximum of 0.04%) of
the intravenously administered dose enters the breast milk.
From experience gained so far, harm to the breast-fed infant is
considered unlikely.
4.7 Effects on ability to drive and use machines
No effects of Magnevist 2 mmol/l on driving ability and use of
machinery can be expected. However, joint effusion may affect
the ability to drive due to a limited joint mobility.

System Organ
Class
Nervous system
disorders
Vascular
disorders
Gastrointestinal
disorders
General
disorders and
administration
site conditions

Common
(≥1/100 to
<1/10)

Uncommon Rare
(≥1/1,000 to (≥1/10,000
<1/100)
to <1/1,000)
Headache
Dizziness
Vasovagal
reaction
Nausea
Vomiting

Injection site
pain/
Injection site
(joint)
pressure
sensation

The most appropriate MedDRA term is used to describe a
reaction and its synonyms and related conditions.
 Immune system disorders/Hypersensitivity/Allergic reaction
Systemic hypersensitivity may occur rarely in the form of skin
reactions. The possibility of a severe hypersensitivity reaction
cannot be totally excluded (see section 4.4).
 General disorders and administration site conditions
Injection of Magnevist 2 mmol/l into the joint is commonly
associated with transient discomfort, e.g. pressure and pain due
to the injected volume. Severe pain may often result from
undue use of pressure or the injection of large volumes.
Other adverse reactions commonly known from intravenous
injection of gadolinium chelates were so far not observed with
Magnevist 2 mmol/l, due to the low dose and the topical
administration.
4.9 Overdose
No signs of intoxication secondary to an overdose have so far
been observed or reported on clinical use.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Magnevist 2 mmol/l is a paramagnetic contrast agent for
magnetic resonance imaging. The contrast-enhancing effect is
mediated by the di-N-methylglucamine salt of gadopentetic
acid, dimeglumine - the gadolinium complex of pentetic acid
(diethylene triamine pentaacetic acid = DTPA). When a suitable
scanning sequence (e.g. T1-weighted spin-echo technique) is
used in proton magnetic resonance imaging, the gadolinium
ion-induced shortening of the spin-lattice relaxation time of
excited atomic nuclei leads to an increase of the signal
intensity and, hence, to an increase of the image contrast of
certain tissues.
Gadopentetic acid, dimeglumine is a highly paramagnetic
compound which leads to distinct shortening of relaxation
times, even in low concentrations. The paramagnetic efficacy,
the relaxivity (determined from the influence on the spin-lattice
relaxation time of protons) is 3.67 in water and about
4.95 l/mmol/sec in plasma, and displays only slight
dependency on the strength of the magnetic field.

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Bayer Schering Pharma
Code-Nr.: 702
Aufmachung: GB BPH

dimeglumine gadopentetate

Magnevist® 2 mmol/l solution for injection

4.8 Undesirable effects
Frequency of adverse reactions from clinical trial data
Based on experience in more than 4,900 patients, the
undesirable effects listed below have been observed and
classified by investigators as drug-related.
Adverse reactions with the use of Magnevist 2 mmol are usually
of mild to moderate intensity.
The most frequently reported reactions were local injection site
reactions, i.e. injection site pain and joint pressure sensations
which are mainly related to the procedure itself.
The table below reports adverse reactions by MedDRA system
organ classes (MedDRA SOCs).

PZ: 2589C-3

Summary of Product Characteristics

Packaging Technology Berlin RH
Seite 1
Mandant: 001
Stoff-Nr.: 82799355
Bezeichnung: GI-OUTS-MAGNEVIST 2MMOL
Farben: Black
Version: 12.07.2012/13
Freigabe:

Package Leaflet: Information for the user

Magnevist 2 mmol/l
Contrast medium concentration
(mg/ml)
Osmolality (Osm/kg H2O)
At 37°C
Viscosity (mPa·s)
At 20°C
At 37°C
Density (g/ml)
At 20°C
At 37°C
pH-value

1.88
0.29

1.03
0.71
1.01
1.00
4.8-8.0

5.2 Pharmacokinetic properties
The pharmacokinetic properties of gadopentetic acid,
dimeglumine have been extensively studied after intravenous
and oral administration in doses exceeding the amount injected
intraarticularly.
After intraarticular injection the compound distributes in the
synovial fluid and diffuses into the interstitial space. Marginal
uptake into the cartilage is completely reversible.
After distribution in the extracellular space primarily through
diffusion controlled processes, the gadopentetic acid,
dimeglumine is eliminated unmetabolised via the kidneys by
glomerular filtration.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on
conventional studies of systemic toxicity, genotoxicity,
carcinogenic potential, toxicity to reproduction and contact
sensitising potential.
 Local tolerance
Experimental local tolerance studies with gadopentetic acid,
dimeglumine (at a concentration of 500 mmol/l) following
single subcutaneous and intramuscular administration in
animals indicated that slight local intolerance reactions could
occur at the injection site after inadvertent administration.

Like all medicines, Magnevist 2mmol/l can cause side effects,
although not everybody gets them.
Side effects you may get after being given a contrast medium
like Magnevist 2mmol/l are usually mild to moderate.
If you notice:
 itching of the skin, rash, wheals on the skin (urticaria)
 difficulty breathing, gagging, feeling of suffocation
 swelling of the face, neck or body
 itchy or watery eyes, tickling in the throat or nose,
hoarseness, coughing or sneezing
 headache, dizziness, feeling faint
 feeling particularly hot or cold, sweating
 paleness or reddening of the skin
 chest pain, cramp, tremor
 feeling sick
Tell the radiologist or MRI staff immediately as these may be
the first signs of allergic reaction or shock. Your investigation
will need to be stopped and you may need further treatment.
Apart from the symptoms listed above, these are the possible
side effects of Magnevist 2mmol/l, starting with the more
common ones:
Common
up to 10 in every 100 people are likely to get these
 sensations or reactions at the injection site (such as pain,
joint pressure and temporary discomfort)
Uncommon
up to 10 in every 1000 people are likely to get these
 feeling sick
 dizziness
 headache
Rare
up to 10 in every 10,000 people are likely to get these
 being sick
 slowed heartbeat; lowered blood pressure; fainting
 allergic-type skin reactions including itching, redness,
wheals on the skin

7. MARKETING AUTHORISATION HOLDER
Bayer plc
Bayer House
Strawberry Hill
Newbury
Berkshire
RG 14 1JA

8. MARKETING AUTHORISATION NUMBER

5. How to store Magnevist 2mmol/l
Keep out of the reach and sight of children.
Do not use Magnevist 2mmol/l after the expiry date which is
stated on the label. The expiry date refers to the last day of that
month.

6. Further Information

Bayer Schering Pharma
Code-Nr.: 702
Aufmachung: GB BPH

6.1 List of excipients
pentetic acid
meglumine
sodium chloride
water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product
must not be mixed with other medicinal products.
6.3 Shelf life
3 years
6.4 Special precautions for storage
None
6.5 Nature and contents of container
Prefilled syringe of 20ml
Glass barrel: glass type I, colourless
Plunger stopper: chlorinated butyl rubber
Tip cap: chlorinated butyl rubber
Luer Lock Adaptor: polysulphone
6.6 Instructions for use and handling, (and disposal)
The prefilled syringe must be taken from the pack and prepared
for the injection immediately before the examination and
injected under sterile conditions.
The tip cap should be removed from the prefilled syringe
immediately before use.
Any contrast medium solution not used in one examination
must be discarded.
Mixture of Magnevist 2 mmol/l with X-ray contrast media
before injection is not recommended as it may reduce efficacy.
The minimal amount of X-ray contrast medium required for
control of the needle position in the joint may be separately
injected prior to the administration of Magnevist 2 mmol/l
(0.5 ml to a maximum of 1.0 ml).

Delayed reactions can occur (after hours or days), if you are
concerned you should contact your doctor.
If any of the side effects gets serious, or if you notice any side
effects not listed in this leaflet, either while Magnevist 2mmol/l
is being given or for about a week afterwards, please tell your
doctor or the radiologist or the MRI-centre staff.

This leaflet was last revised in July 2012
To listen to or request a copy of this leaflet in Braille,
large print or audio please call, free of charge:

PZ: 2589C-3

4. Possible side effects

0800 198 5000 (UK only)
Please be ready to give the following information:
Product name

Packaging Technology Berlin RH
Seite 2
Mandant: 001
Stoff-Nr.: 82799355
Bezeichnung: GI-OUTS-MAGNEVIST 2MMOL
Farben: Black
Version: 12.07.2012/13
Freigabe:

6. PHARMACEUTICAL PARTICULARS

Reference number

00010/0544
Magnevist® 2mmol/l
solution for injection
This is a service provided by the Royal National
Institute of the Blind.

What Magnevist 2mmol/l contains
 The active substance is dimeglumine gadopentetate.
1 ml Magnevist 2mmol/l contains 1.876 mg of the
dimeglumine salt of gadopentetic acid.
 The other ingredients are meglumine, pentetic acid,
sodium chloride and water for injections.
What Magnevist 2mmol/l looks like and contents of
the pack
Magnevist 2mmol/l is available in 20ml pre-filled
syringes.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Bayer plc
Bayer House
Strawberry Hill
Newbury
Berkshire
RG14 1JA
Manufacturer:
Bayer Pharma AG
Berlin
Germany

Magnevist® 2 mmol/l
solution for injection

82799355

PL 00010/0544

9. DATE OF FIRST AUTHORISATION / RENEWAL
OF THE AUTHORISATION
01 May 2008

10. DATE OF REVISION OF THE TEXT
17 July 2012
Legal category: POM



The concentration of Magnevist 2 mmol/l corresponds to 1/250
of the concentration used for i.v. administration. This
concentration is sufficient to allow adequate imaging efficacy
even after further dilution with joint effusion. If the joint cavity
is filled with gadolinium-containing fluid, the signal in the
cavity increases on use of T1-weighted sequences, i.e. it
becomes bright and contrasts clearly with all structures with a
weak or intermediate signal (i.e. all intraarticular structures:
hyaline and fibrous cartilage, all ligaments, tendons and the
joint capsule). While normal, or even increased, joint fluid does
not differ in its signal behaviour in T1-weighted images from all
the other anatomical structures apart from fibrocartilage, the
intraarticular administration of Magnevist 2 mmol/l leads to
distinctly improved contrast situations.
DTPA forms a firm complex with the paramagnetic gadolinium
ion with extremely high in vivo and in vitro stability
(log K = 22 - 23). The dimeglumine salt of gadopentetic acid,
dimeglumine is a highly water-soluble, extremely hydrophilic
compound with a distribution coefficient between n-butanol
and buffer at pH 7.6 of about 0.0001. The substance does not
display any particular protein binding or inhibitory interaction
with enzymes (e.g. myocardial Na+ and K+ ATPase).
Magnevist 2 mmol/l does not activate the complement system
and, therefore, probably has a very low potential for inducing
anaphylactoid reactions.
Based on clinical experience, impairment of hepatic, renal or
cardiovascular function is not expected.
The physico-chemical properties of Magnevist 2 mmol/l listed
below are:

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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