Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Bracco UK Ltd, Unit 15, Valley Business Centre, Gordon Road, High Wycombe, Buckinghamshire HP13 6EQ, United Kingdom
MultiHance is contra-indicated in:
The use of diagnostic contrast media, such as MultiHance, should be restricted to hospitals or clinics staffed for intensive care emergencies and where cardiopulmonary resuscitation equipment is readily available.
Patients should be kept under close supervision for 15 minutes following the injection as the majority of severe reactions occur at this time. The patient should remain in the hospital environment for one hour after the time of injection.
The accepted general safety procedures for Magnetic Resonance Imaging, in particular the exclusion of ferromagnetic objects, for example cardiac pace-makers or aneurysm clips, are also applicable when MultiHance is used.
Caution is advised in patients with cardiovascular disease.
In patients suffering from epilepsy or brain lesions the likelihood of convulsions during the examination may be increased. Precautions are necessary when examining these patients (e.g. monitoring of the patient) and the equipment and medicinal products needed for the rapid treatment of possible convulsions should be available.
After administration of gadobenic acid, gadolinium can be retained in the brain and in other tissues of the body (bones, liver, kidneys, skin) and can cause dose-dependent increases in T1-weighted signal intensity in the brain, particularly in the dentate nucleus, globus pallidus, and thalamus. Clinical consequences are unknown. The possible diagnostic advantages of using MultiHance in patients who will require repeated scans should be weighed against the potential for deposition of gadolinium in the brain and other tissues.
As with other gadolinium chelates, the possibility of a reaction, including serious, life-threatening, or fatal anaphylactic and anaphylactoid reactions involving one or more body systems, mostly respiratory, cardiovascular and/or mucocutaneous systems, should always be considered, especially in patients with a history of asthma or other allergic disorders.
Prior to MultiHance administration, ensure the availability of trained personnel and medications to treat hypersensitivity reactions.
Insignificant quantities of benzyl alcohol (<0.2%) may be released by gadobenate dimeglumine during storage. Nonetheless, MultiHance should not be used in patients with a history of sensitivity to benzyl alcohol.
As with other gadolinium-chelates, a contrast-enhanced MRI should not be performed within 7 hours of a MultiHance-enhanced MRI examination to allow for clearance of MultiHance from the body.
Exercise caution to avoid local extravasation during intravenous administration of MultiHance. If extravasation occurs, evaluate and treat as necessary if local reactions develop (see section 4.8 Undesirable Effects).
Prior to administration of MultiHance, 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<30ml/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 MultiHance, it should therefore be avoided in patients with severe renal impairment and in patients in the perioperative liver transplantation period unless the diagnostic information is essential and not available with non-contrast enhanced MRI.
Haemodialysis shortly after MultiHance administration may be useful at removing MultiHance 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 gadobenate dimeglumine may be impaired in the elderly, it is particularly important to screen patients aged 65 years and older for renal dysfunction.
Interaction studies with other medicinal products were not carried out during the clinical development of MultiHance. However no drug interactions were reported during the clinical development programme.
There are no data from the use of gadobenate dimeglumine in pregnant women. Animal studies have shown reproductive toxicity at repeated high doses (see section 5.3). MultiHance should not be used during pregnancy unless the clinical condition of the woman requires use of gadobenate dimeglumine.
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 into milk and poor absorption from the gut. Continuing or discontinuing breast feeding for a period of 24 hours after administration of MultiHance should be at the discretion of the doctor and lactating mother.
MultiHance has no or negligible influence on the ability to drive and use machines.
The following adverse events were seen during the clinical development of MultiHance.
Clinical trials:
Common (≥1/100, <1/10)
Uncommon (≥1/1,000, <1/100)
Rare (≥1/10,000, <1/1,000)
Post-marketing surveillance:
Frequency unknown**
Rare: Anaphylactic/anaphylactoid reaction, Hypersensitivity reaction
Frequency unknown**: Anaphylactic shock
Common: Headache
Uncommon: Paraesthesia, Hypoaesthesia, Dizziness, Taste perversion
Rare: Convulsion, Syncope, Tremor, Parosmia
Frequency unknown**: Loss of consciousness
Rare: Visual disturbance
Frequency unknown**: Conjunctivitis
Uncommon: First-degree atrioventricular block, Tachycardia
Rare: Myocardial ischaemia, Bradycardia
Frequency unknown**: Cardiac arrest, Cyanosis
Uncommon: Hypertension, Hypotension, Flushing
Rare: Dyspnoea, Laryngospasm, Wheezing, Rhinitis, Cough
Frequency unknown**: Respiratory failure, Laryngeal oedema, Hypoxia, Bronchospasm, Pulmonary oedema
Common: Nausea
Uncommon: Diarrhoea, Vomiting, Abdominal pain
Rare: Faecal incontinence, Salivary hypersecretion, Dry mouth
Frequency unknown**: Oedema mouth
Uncommon: Urticaria, Rash including erythematous rash, macular, maculopapular and papular rash, Pruritus, Sweating increased
Rare: Face oedema
Frequency unknown**: Angioedema
Rare: Myalgia
Uncommon: Proteinuria
Common: Injection Site Reaction including, injection site pain, inflammation, burning, warmth, coldness, discomfort, erythema, paraesthesia and pruritus
Uncommon: Chest pain, Pyrexia, Feeling hot
Rare: Asthenia, Malaise, Chills
Frequency unknown**: Injection site swelling
Uncommon: Electrocardiogram abnormalities*, Blood bilirubin increased, Blood iron increased, Increases in serum transaminases, gamma-glutamyl- transferase, lactic dehydrogenase and creatinine
Rare: Blood albumin decreased, Alkaline phosphatase increased
* Electrocardiogram abnormalities include electrocardiogram QT prolonged, electrocardiogram QT shortened, electrocardiogram T wave inversion, electrocardiogram PR prolongation, electrocardiogram QRS complex prolonged.
** Since the reactions were not observed during clinical trials with 4,956 subjects, best estimate is that their relative occurrence is rare (≥ 1/10,000 to <1/1000).
The most appropriate MedDRA (version 16.1) term is used to describe a certain reaction and its symptoms and related conditions.
Laboratory findings were mostly seen in patients with evidence of pre-existing impairment of hepatic function or pre-existing metabolic disease.
The majority of these events were non-serious, transient and spontaneously resolved without residual effects. There was no evidence of any correlation with age, gender or dose administered.
As with other gadolinium-chelates, there were reports of anaphylactic/anaphylactoid/hypersensitivity reactions. These reactions manifested with various degrees of severity up to anaphylactic shock and death, and involved one or more body system, mostly respiratory, cardiovascular, and/or mucocutaneous systems.
In patients with history of convulsion, brain tumours or metastasis, or other cerebral disorders, convulsions have been reported after MultiHance administration. (see section 4.4 Special warnings and precautions for use).
Injection site reactions due to extravasation of the contrast medium leading to local pain or burning sensations, swelling, blistering and, in rare cases when localised swelling is severe, necrosis have been reported.
Localised thrombophlebitis has also been rarely reported (see section 4.4 Special warnings and precautions for use).
Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with MultiHance in patients co-administered other gadolinium-containing contrast agents (see Section 4.4).
Clinical Trials:
Common (≥1/100 to <1/10)
Uncommon (≥1/1000 to <1/100)
Uncommon: Dizziness
Uncommon: Eye pain, Eyelid oedema
Uncommon: Flushing
Common: Vomiting
Uncommon: Abdominal pain
Uncommon: Rash, Sweating increased
Uncommon: Chest pain, Injection site pain, Pyrexia
The adverse reactions reported among paediatric patients treated with MultiHance during clinical trials and tabulated above were non-serious. The adverse reactions identified during post-marketing surveillance indicate that MultiHance safety profile is similar in children and adults.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme – Website: www.mhra.gov.uk/yellowcard.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
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