Multihance

/ Dexcel

The lowest dose that provides sufficient enhancement for diagnostic purposes should be used.
MRI of the liver: the recommended dose of drug injection in adult patients is 0.05 mmol/kg body weight. This corresponds to 0.1 mL/kg of the 0.5 M solution.
MRI of the brain and spine: the recommended dose of drug injection in adult and in paediatric patients greater than 2 years of age is 0.1 mmol/kg body weight. This corresponds to 0.2 mL/kg of the 0.5 M solution.
MRA: the recommended dose of drug injection in adult patients is 0.1 mmol/kg body weight. This corresponds to 0.2 mL/kg of the 0.5 M solution.
MRI of the breast: the recommended dose of the agent in adult patients is 0.1 mmol/kg body weight. This corresponds to 0.2 mL/kg of the 0.5 M solution.

This medicinal product is for diagnostic use only.
This medicinal product is a paramagnetic contrast agent for use in diagnostic magnetic resonance imaging (MRI) indicated for:
MRI of the liver for the detection of focal liver lesions in patients with known or suspected primary liver cancer (eg. hepatocellular carcinoma) or metastatic disease.
MRI of the brain and spine where it improves the detection of lesions and provides diagnostic information additional to that obtained with unenhanced MRI.
Contrast-enhanced MR- angiography where it improves the diagnostic accuracy for detecting clinically significant steno-occlusive vascular disease in patients with suspected or known vascular disease of the abdominal or peripheral arteries.
MRI of the breast, for the detection of malignant lesions in patients where breast cancer is known or suspected on the basis of previous mammography or ultrasound results.

The medicine is contraindicated in: patients with hypersensitivity to the active substance or to any of the excipients. Patients with a history of allergic or adverse reactions to other gadolinium chelates.

The use of diagnostic contrast media, such as this agent, 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 this product 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.
Gadobenic acid must not be used intrathecally. Serious, life-threatening and fatal cases, primarily with neurological reactions (e.g. coma, encephalopathy, seizures), have been reported with intrathecal use.
Hypersensitivity reactions: 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 this agent 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 the medicine 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 an agent-enhanced MRI examination to allow for clearance of the medicine from the body.
Exercise caution to avoid local extravasation during intravenous administration of the agent. If extravasation occurs, evaluate and treat as necessary if local reactions develop.
Impaired renal function: Prior to administration of the medicine, 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 the agent, 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 the agent administration may be useful at removing medicine 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.
Elderly: 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.
Gadolinium retention: Gadolinium is retained for months or years in several organs. The highest concentrations (nanomoles per gram of tissue) have been identified in the bone, followed by other organs (e.g. brain, skin, kidney, liver, and spleen. The duration of retention also varies by tissue and is longest in bone. Linear GBCAs cause more retention than macrocyclic GBCAs.
The current evidence suggests that gadolinium may accumulate in the brain after multiple administrations 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 in the brain. In order to minimize 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.
While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions. Consider the retention characteristics of the agent when choosing a GBCA for these patients. Minimize repetitive GBCA imaging studies, particularly closely spaced studies when possible.

Common (≥1/100, <1/10); Uncommon (≥1/1,000, <1/100); Rare (≥1/10,000, <1/1,000); Frequency unknown – 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).
Immune system disorder: Rare: Anaphylactic /anaphylactoid reaction, Hypersensitivity reaction; Frequency unknown: Anaphylactic shock.
Nervous system disorders: Common: Headache; Uncommon: Paraesthesia, Hypoaesthesia, Dizziness, Taste perversion; Rare: Convulsion, Syncope, Tremor, Parosmia; Frequency unknown: Loss of consciousness.
Eye disorders: Rare: Visual disturbance; Frequency unknown: Conjunctivitis.
Cardiac disorders: Uncommon: Tachycardia, First-degree atrioventricular block; Rare: Myocardial ischaemia, Bradycardia; Frequency unknown: Cardiac arrest, Cyanosis.
Vascular disorders: Uncommon: Hypertension, Hypotension, Flushing.
Respiratory, thoracic and mediastinal disorders: Rare: Dyspnoea, Laryngospasm, Wheezing, Rhinitis, Cough; Frequency unknown: Respiratory failure, Laryngeal oedema, Hypoxia, Bronchospasm, Pulmonary oedema.
Gastrointestinal disorders: Common: Nausea; Uncommon: Diarrhoea, Vomiting, Abdominal pain; Rare: Faecal incontinence, Salivary hypersecretion, Dry mouth; Frequency unknown: Oedema mouth.
Skin & subcutaneous tissue disorders: Uncommon: Pruritus, Rash including erythematous rash, macular, maculo-papular and papular rash, Urticaria, Sweating increased; Rare: Face oedema;  Frequency unknown: Angioedema.
Musculoskeletal, connective tissue and bone disorders: Rare: Myalgia.
Renal and urinary disorders: Uncommon: Proteinuria.
General disorders and administration site conditions: 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.
Investigations: 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.
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 this medicine administration.
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. Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with this agent in patients co-administered other gadolinium-containing contrast agents.
Paediatric population
Nervous system disorders: Uncommon: Dizziness.
Eye disorders: Uncommon: Eye pain, Eyelid oedema.
Vascular disorders: Uncommon: Flushing.
Gastrointestinal disorders: Common: Vomiting; Uncommon: Abdominal pain.
Skin and subcutaneous tissue disorders: Uncommon: Rash, Sweating increased.
General disorders and administration site conditions: Chest pain, Injection site pain, Pyrexia.
The adverse reactions reported among paediatric patients treated with this agent during clinical trials and tabulated above were non-serious. The adverse reactions identified during post-marketing surveillance indicate that the medicine safety profile is similar in children and adults.

Interaction studies with other medicinal products were not carried out during the clinical development of this product. However no drug interactions were reported during the clinical development programme.

Pregnancy: Data on the use of gadolinium-based contrast agents including gadobenic acid in pregnant women is limited. Gadolinium can cross the placenta. It is unknown whether exposure to gadolinium is associated with adverse effects in the foetus. This medical product should not be used during pregnancy unless the clinical condition of the woman requires use of gadobenate dimeglumine.
Lactation: Gadolinium containing contrast agents are excreted into breast milk in very small amounts. 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 The product should be at the discretion of the doctor and lactating mother.

There have been no cases of overdose reported. Therefore, the signs and symptoms of overdosage have not been characterised. Doses up to 0.4 mmol/kg were administered to healthy volunteers, without any serious adverse events. However, doses exceeding the specific approved dosage are not recommended.  In the event of overdosage, the patient should be carefully monitored and treated symptomatically.
This agent can be removed by haemodialysis. However there is no evidence that haemodialysis is suitable for prevention of nephrogenic systemic fibrosis (NSF).

Effects on ability to drive and use machines: The agent has no or negligible influence on the ability to drive or use machines.