Procedure number NL/H/PSUR/0003/002
Gadoteric acid (intraarticular)
Active substance
Innovator name of product in the P-RMS
<for MRP products also procedure number>
Pharmaceutical form(s)/strength
Artirem
NL/H/0381/006
Solution for injection, 0,0025 mmol/ml
Agreed CSP
P-RMS comment:
Please note that the CSP includes the minimally required safety related information to be reflected in all local
SPCs. At national level the SPC may include additional information or more stringent requirements for use.
4.2.
Posology and method of administration
Paediatric population
The safety and efficacy of Artirem in children less than 18 years has not been established. Currently
available data are described in section 4.8 but no recommendation on a posology can be made.
Method of administration
The product must be administered under strict aseptic conditions by intraarticular injection, sometimes after
injecting a small quantity of iodinated contrast agent in order to visualise the intraarticular cavity.
4.3.
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Contraindications
Hypersensitivity to gadoteric acid, to meglumine or to any medicinal products containing gadolinium.
4.4.
Special warnings and precautions for use
Artirem is for strict intraarticular injection. Precautions must be taken to avoid accidental extraarticular
injection.
Artirem must not be administered by subarachnoid (or epidural) injection.
Intraarticular injection of Artirem in infected joints should be avoided.
The usual precaution measures for MRI examination should be taken, such as exclusion of patients with
pacemakers, ferromagnetic vascular clips, infusion pumps, nerve stimulators, cochlear implants, or
suspected intracorporal metallic foreign bodies, particularly in the eye.
There is always a risk of hypersensitivity regardless of the dose injected.
As with other gadolinium containing contrast media hypersensitivity reactions can occur, including lifethreatening hypersensitivity reactions (see section 4.8). Hypersensitivity reactions may be either allergic
(described as anaphylactic reactions when serious) or nonallergic. They can be either immediate (less than
60 minutes), or delayed (up to 7 days). Anaphylactic reactions occur immediately and can be fatal. They are
independent of the dose, can occur after even the first dose of the product, and are often unpredictable.
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To permit immediate emergency countermeasures, appropriate drugs (e.g. epinephrine and antihistamines),
an endotracheal tube and a respirator should be ready to hand.
Patients who have already experienced a reaction during previous administration of a gadolinium-containing
MRI contrast agent present an increased risk of experiencing another reaction on subsequent administration
of the same product, or possibly other products, and are therefore considered to be at high risk.
The injection of Artirem may aggravate symptoms of an existing asthma. In patients with asthma unbalanced
by the treatment, the decision to use Artirem must be made after careful evaluation of the risk/benefit ratio.
Before any contrast medium is injected, the patient should be questioned for a history of allergy (e.g.
seafood allergy, hay fever, hives), sensitivity to contrast media and bronchial asthma as the reported
incidence of adverse reactions to contrast media is higher in patients with these conditions and
premedication with antihistamines and/or glucocorticoids may be considered.
4.5.
Interaction with other medicinal products and other forms of interaction
No interactions with other medicinal products have been observed. Formal drug interaction studies have not
been carried out.
In the absence of specific studies, Artirem should not be mixed with other substances.
Iodinated contrast media must not be administered simultaneously with Artirem, since the efficacy of Artirem
may be reduced (see section 6.6).
Concomitant medications to be taken into account
Beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, angiotensin II receptor
antagonists: these medicinal products decrease the efficacy of the mechanisms of cardiovascular
compensation for blood pressure disorders: the radiologist must be informed before injection of gadolinium
complexes, and resuscitation equipment must be at hand.
4.6.
Fertility, pregnancy and lactation
Pregnancy
There are no data from the use of gadoteric acid in pregnant women. Animal studies showed no direct or
indirect harmful effects in animals receiving high intravenous doses of gadoteric acid with respect to
reproductive toxicity (see section 5.3).
Artirem should not be used during pregnancy unless the clinical condition of the woman requires use of
Artirem.
Lactation
Gadolinium-containing contrast agents are excreted into breast milk in very small amounts (see section 5.3).
At clinical doses, no effects on the infant are anticipated due to the small amount excreted in milk and poor
absorption from the gut.
As the dose of gadoteric acid injected in an arthrographic examination is very low and the administration is
local (intraarticular), it is not necessary to interrupt breastfeeding following an examination carried out with
Artirem.
4.7.
Effects on ability to drive and use machines
No studies of the effects on the ability to drive and use machines have been performed.
Effects on the ability to drive and use machines are not expected. However, joint effusions may impair the
ability to drive because of a reduced mobility of the joint.
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4.8.
Undesirable effects
Adverse reactions related to the use of Artirem are generally mild to moderate, and transient.
The adverse reactions most commonly reported during administration of Artirem since marketing are mild
pain or local discomfort in the examined joint and hypersensitivity reactions.
The effects most commonly observed during hypersensitivity reactions are skin rashes, which can be
localized, extensive or generalized. These reactions are usually immediate (during the injection or over the
hour following the start of the injection) or sometimes delayed (one hour to several days after the injection),
and then appear in the form of adverse skin reactions.
Immediate reactions comprise one or several, successive or concomitant effects, usually including skin
reactions, respiratory and/or cardiovascular disorders, which may be the first signs of shock, which can rarely
be fatal.
Adverse reactions are presented in the following table by system organ class and by frequency according to
the following categories: very common (≥1/10), common (≥1/100 to 1<1/10), uncommon (≥1/1 000 to
1<1/100), rare (≥1/10 000 to <1/1,000), very rare (<1/10,000), undetermined frequency (cannot be estimated
on the basis of available data). The frequencies presented are derived from the data of an observational
study on 463 patients.
System Organ Class
Frequency: adverse reaction
Immune system disorders
Uncommon: hypersensitivity
Musculoskeletal and connective tissue disorders
Uncommon: arthralgia
Adverse reactions in children
The expected nature of adverse reactions related to Artirem is identical to that reported in adults. The
frequency of these reactions can not be estimated on the basis of available data.
4.9.
Overdose
No signs of intoxication secondary to an overdose have so far been observed or reported in clinical practice
with Artirem.
On the basis of the results of the toxicity studies conducted with gadoteric acid solutions at higher
concentrations, a risk of acute intoxication is highly unlikely following the use of Artirem by intra-articular
injection.
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