Source: Medicines and Medical Devices Safety Authority (NZ) Revision Year: 2017 Publisher: Manufactured by: Guerbet, 16-24 rue Jean Chaptal, 93600 Aulnay-sous-Bois, FRANCE, www.guerbet.com Distributed in NZ by: Obex Medical Limited, P O Box 26511, Epsom, AUCKLAND, Telephone: (09) 630 3456, Toll ...
Hypersensitivity to gadoteric acid, to meglumine or to any medicinal products containing gadolinium.
Do not use by intrathecal route. Take care to maintain strictly intravenous injection: extravasation may result in local intolerance reactions, requiring the usual local care.
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.
As with other gadolinium containing contrast media hypersensitivity reactions can occur, including life-threatening (see “4.8 Undesirable effects”). Hypersensitivity reactions may be either allergic (described as anaphylactic reactions when serious) or non allergic. 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.
There is always a risk of hypersensitivity regardless of the dose injected.
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 gadoteric acid may aggravate symptoms of an existing asthma. In patients with asthma unbalanced by the treatment, the decision to use gadoteric acid must be made after careful evaluation of the risk/benefit ratio.
As known from the use of iodinated contrast media, hypersensitivity reactions can be aggravated in patients on beta-blockers, and particularly in the presence of bronchial asthma. These patients may be refractory to standard treatment of hypersensitivity reactions with beta-agonists.
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.
During the examination, supervision by a physician is necessary. If hypersensitivity reactions occur, administration of the contrast medium must be discontinued immediately and – if necessary – specific therapy instituted. A venous access should thus be kept during the entire examination. To permit immediate emergency countermeasures, appropriate medicines (e.g. epinephrine and antihistamines), an endotracheal tube and a respirator should be ready at hand.
The current evidence suggests that gadolinium may accumulate in the brain after multiple administration of GBCAs. Increased signal intensity on non-contrast T1-weighted images of the brain has been observed after multiple administrations of GBCAs in patients with normal renal function. Gadolinium has been detected in brain tissue after multiple exposures to GBCAs, particularly in the dentate nucleus and globus pallidus. The evidence suggests that the risk of gadolinium accumulation is higher after repeat administration of linear than after repeat administration of macrocyclic agents.
The clinical significance of gadolinium accumulation in the brain is presently unknown; however, gadolinium accumulation may potentially interfere with the interpretation of MRI scans of the brain. In order to minimise potential risks associated with gadolinium accumulation in the brain, it is recommended to use the lowest effective dose and perform a careful benefit risk assessment before administering repeated doses.
Prior to administration of gadoteric acid, it is recommended that all patients are screened for renal dysfunction by obtaining laboratory tests.
There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of some gadolinium- containing contrast agents in patients with acute or chronic severe renal impairment (GFR<30 ml/min/1.73m²). Patients undergoing liver transplantation are at particular risk since the incidence of acute renal failure is high in this group. As there is a possibility that NSF may occur with gadoteric acid, it should therefore only be used in patients with severe renal impairment and in patients in the perioperative liver transplantation period after careful risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast enhanced MRI.
Haemodialysis shortly after gadoteric acid administration may be useful at removing gadoteric acid from the body. There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients not already undergoing haemodialysis.
As the renal clearance of gadoteric acid may be impaired in the elderly, it is particularly important to screen patients aged 65 years and older for renal dysfunction.
Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, gadoteric acid should only be used in these patients after careful consideration.
Like with other gadolinium containing contrast agents special precaution is necessary in patients with a low threshold for seizures. Precautionary measures should be taken, e.g. close monitoring. All equipment and medicines necessary to counter any convulsion which may occur must be made ready for use beforehand.
No interactions with other medicinal products have been observed. Formal drug interaction studies have not been carried out.
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.
There are no data from the use of gadoteric acid in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Gadoteric acid should not be used during pregnancy unless the clinical condition of the woman requires use of gadoteric acid.
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. Continuing or discontinuing breast feeding for a period of 24 hours after administration of gadoteric acid, should be at the discretion of the doctor and lactating mother.
No data is available.
No studies on the effects on the ability to drive and use machines have been performed. Ambulant patients while driving vehicles or operating machinery should take into account that nausea may incidentally occur.
Side effects in association with the use of gadoteric acid are usually mild to moderate in intensity and transient in nature. Injection site reactions, nausea and headache are the most frequently observed reactions.
During clinical trials, nausea, headache, injection site reactions, feeling cold, hypotension, somnolence, dizziness, feeling hot, burning sensation, rash, asthenia, dysgeusia and hypertension were the most frequent, uncommonly observed (≥1/1000 to <1/100) related adverse events.
Since post-marketing, the most commonly reported adverse reactions following administration of gadoteric acid have been nausea, vomiting, pruritus and hypersensitivity reactions.
In hypersensitivity reactions, the reactions most frequently observed are skin reactions, which can be localized, extended or generalized.
These reactions occur most often immediately (during the injection or within one hour after the start of injection) or sometimes delayed (one hour to several days after injection), presenting as skin reactions in this case.
Immediate reactions include one or more effects, which appear simultaneously or sequentially, which are most often cutaneous, respiratory, gastrointestinal, articular and/or cardiovascular reactions.
Each sign may be a warning sign of a starting shock, however, it is very rarely fatal.
Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with gadoteric acid, most of which were in patients co-administered other gadolinium-containing contrast agents (see section 4.4).
The adverse reactions are listed in the table below by SOC (System Organ Class) and by frequency with the following guidelines: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data). The data presented are from clinical trials involving 2822 patients when available, or from a pool of observational studies involving 185,500 patients.
Uncommon: hypersensitivity
Very rare: anaphylactic reaction, anaphylactoid reaction
Rare: anxiety
Very rare: agitation
Uncommon: headache, dysgeusia, dizziness, somnolence, paraesthesia (including burning sensation)
Rare: presyncope
Very rare: coma, convulsion, syncope, tremor, parosmia
Rare: eyelid edema
Very rare: conjunctivitis, ocular hyperaemia, vision blurred, lacrimation increased
Rare: palpitations
Very rare: tachycardia, cardiac arrest, arrhythmia, bradycardia
Uncommon: hypotension, hypertension
Very rare: pallor, vasodilatation
Rare: sneezing
Very rare: cough, dyspnoea, nasal congestion, respiratory arrest, bronchospasm, laryngospasm, pharyngeal oedema, dry throat, pulmonary oedema
Uncommon: nausea, abdominal pain
Rare: vomiting, diarrhoea, salivary hypersecretion
Uncommon: rash
Rare: urticaria, pruritus, hyperhidrosis
Very rare: erythema, angioedema, eczema
Not known: nephrogenic systemic fibrosis
Very rare: muscle cramps, muscular weakness, back pain
Uncommon: feeling hot, feeling cold, asthenia, injection site reactions (extravasation, pain, discomfort, oedema, inflammation, coldness)
Rare: chest pain, chills
Very rare: malaise, chest discomfort, pyrexia, face oedema, injection site necrosis (in case of extravasation), phlebitis superficial
Very rare: decreased oxygen saturation
The following adverse reactions were reported with other intravenous contrast agents for MRI:
Blood and lymphatic system disorders: Haemolysis
Psychiatric disorders: Confusion
Eye disorders: Blindness transient, eye pain
Ear and labyrinth disorders: Tinnitus, ear pain
Respiratory, thoracic and mediastinal disorders: Asthma
Gastrointestinal disorders: Dry mouth
Skin and subcutaneous tissue disorders: Dermatitis bullous
Renal and urinary disorders: Urinary incontinence, renal tubular necrosis, renal failure acute
Investigations: Electrocardiogram PR prolongation, blood iron increased, blood bilirubin increased, serum ferritin increased, liver function test abnormal
Safety of paediatric patients was considered in clinical trials and postmarketing studies. As compared to adult, the safety profile of gadoteric acid did not show any specificity in children. Most of reactions are gastrointestinal symptoms or signs of hypersensitivity.
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
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