GADOBUTROL

Gadobutrol should only be administered by healthcare professionals experienced in the field of clinical MRI practice. Method of administration This medicinal product is for intravenous administration only. The dose required is administered intravenously as a bolus injection.

Contrast- enhanced MRI can commence immediately afterwards (shortly after the injection depending on the pulse sequences used and the protocol for the examination). Optimal signal enhancement is observed during arterial first pass for CE-MRA and within a period of about 15 minutes after injection of gadobutrol for CNS indications (time depending on type of lesion/tissue).

T1 -weighted scanning sequences are particularly suitable for contrast-enhanced examinations. Intravascular administration of contrast media should, if possible, be done with the patient lying down. 4). 5 ml and 15 ml vials. Presentations for single or multi-dose use: 30 ml vials and 65 ml bottles.

For multi- dose use, gadobutrol must be administered in conjunction with an automatic injector which has been approved for multi-patient use. 6. Posology The lowest dose that provides sufficient enhancement for diagnostic purposes should be used.

The dose should be calculated based on the patient’s body weight, and should not exceed the recommended dose per kilogram of body weight detailed in this section. 1 mmol per kilogram body weight (mmol/kg BW). 0 M solution. 2 ml/kg BW within 30 minutes of the first injection may be performed.

1). 1 ml gadobutrol per kg body weight is sufficient to answer the clinical question. 15 mmol/kg BW). 3 mmol/kg BW). 4). 1 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, gadobutrol injections should not be repeated unless the interval between injections is at least 7 days.

1). 1 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, gadobutrol injections should not be repeated unless the interval between injections is at least 7 days.

Elderly (aged 65 years and above) No dosage adjustment is considered necessary. 4).

The overall safety profile of gadobutrol is based on data from more than 6,300 patients in clinical trials and from post-marketing surveillance. 5 %) in patients receiving gadobutrol are headache, nausea and dizziness. The most serious adverse drug reactions in patients receiving gadobutrol are cardiac arrest, acute respiratory distress syndrome / pulmonary oedema and severe anaphylactoid reactions (including respiratory arrest and anaphylactic shock).

4). Most of the undesirable effects were of mild to moderate intensity. The adverse drug reactions observed with gadobutrol are represented in the table below. They are classified according to System Organ Class (MedDRA). The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.

Adverse drug reactions from clinical trials are classified according to their frequencies. Frequency groupings are defined according to the following convention: common: ≥ 1/100 to < 1/10; uncommon: ≥ 1/1,000 to < 1/100; rare: ≥ 1/10,000 to < 1/1,000.

The adverse drug reactions identified only during post-marketing surveillance, and for which a frequency could not be estimated, are listed under ‘not known’. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

g. anaphylactoid shock§*, circulatory collapse§*, respiratory arrest§*, bronchospasm§, cyanosis§, oropharyngeal swelling§*, laryngeal oedema§, hypotension*, blood pressure increased§, chest pain§, urticaria, face oedema, angioedema§, conjunctivitis§, eyelid oedema, flushing, hyperhidrosis§, cough§, sneezing§, burning sensation§, pallor§) Nervous system disorders Headache Dizziness, Dysgeusia, Paraesthesia Loss of consciousness*, Convulsion, Parosmia Cardiac disorders Tachycardia, Palpitations Cardiac arrest* Respiratory, thoracic and mediastinal disorders Dyspnoea* Acute Respiratory Distress Syndrome (ARDS)*1 Pulmonary oedema*1 Gastrointestinal disorders Nausea Vomiting Dry mouth Skin and subcutaneous tissue disorders Erythema, Pruritus (including generalised pruritus), Rash (including generalised, macular, papular, pruritic rash) Nephrogenic Systemic Fibrosis (NSF) General disorders and administration site conditions Injection site reaction0, Feeling hot Malaise, Feeling cold ¹ These ADRs have been reported with and without the context of hypersensitivity reactions * There have been reports of life-threatening and/or fatal outcomes from this ADR # None of the individual symptoms ADRs listed under hypersensitivity/anaphylactoid reactions identified in clinical trials reached a frequency greater than rare (except for urticaria) § Hypersensitivity/anaphylactoid reactions identified only during post-marketing surveillance (frequency not known) 0 Injection site reactions (various kinds) comprise the following terms: Injection site extravasation, injection site burning, injection site coldness, injection site warmth, injection site erythema or rash, injection site pain, injection site haematoma Patients with an allergic disposition suffer more frequently than others from hypersensitivity reactions.

Gadobutrol must not be used intrathecally. g. coma, encephalopathy, seizures), have been reported with intrathecal use. While injecting gadobutrol into veins with a small lumen there is the possibility of adverse effects such as reddening and swelling.

The usual safety requirements for magnetic resonance imaging, especially the exclusion of ferromagnetic materials, also apply when using gadobutrol. , acute respiratory distress syndrome / pulmonary oedema with and without the context of hypersensitivity reactions), characterised by cardiovascular, respiratory or cutaneous manifestations, and ranging to severe reactions including shock.

In general, patients with cardiovascular disease are more susceptible to serious or even fatal outcomes of severe hypersensitivity reactions. The risk of hypersensitivity reactions may be higher in case of: - previous reaction to contrast media - history of bronchial asthma - history of allergic disorders In patients with an allergic disposition the decision to use gadobutrol must be made after the particularly careful evaluation of the risk-benefit ratio.

Most of these reactions occur within half an hour of administration. Therefore, post-procedure observation of the patient is recommended. 2). 8). Impaired renal function Prior to administration of gadobutrol, it is recommended that all patients are screened for renal dysfunction by obtaining laboratory tests.

73 m2 ). 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 gadobutrol, 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 magnetic resonance imaging (MRI).

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