Bracco UK Limited

Section 4.3
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A history of previous hypersensitivity to ProHance, its constituents or other gadolinium-based contrast

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ProHance is contra-indicated in patients with hypersensitivity to the active substance gadoteridol or any of its constituents or other gadolinium-based contrast.


Section 4.4
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    Anaphylactic reactions have been observed following the use of gadoteridol

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Patients with a history of allergy, drug reactions, or other hypersensitivity-like disorders should be closely observed during the procedure and the contrast medium administration, as well as for the time the physician deems useful given the patient condition.

As with other gadolinium chelates, there have been reports of anaphylactic/anaphylactoid/ hypersensitivity reactions with gadoteridol These reactions manifested with various degrees of severity, including anaphylactic shock or death. They involved one or more body systems, mostly respiratory, cardiovascular and/or mucocutaneous systems.

Anaphylactic shock has been very rarely been reported with the use of gadoteridol

Section 4.7
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    There are no known effects of ProHance on the ability to drive or operate machinery.

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  On the basis of the pharmacokinetic and pharmacodynamic profiles, no or negligible influence is expected with the use of ProHance on the ability to drive or use machines.


Section 4.8
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Side effects: Taste disturbance (primarily metallic taste) nausea, urticaria, pain at injection site, convulsions and hypotension have been reported. Headache and chest pain have been rarely reported. These occurrences were transient and resolved without residual effect. The occurrences were not related to age, gender, rate of injection or dose administered.

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The accepted safety considerations and procedures that are required for Magnetic Resonance Imaging are applicable when ProHance is used for contrast enhancement.

The following adverse reactions have been reported with ProHance. adverse reactions from clinical trials have been included with an indication of the frequency. Adverse reactions from spontaneous reporting are included with the frequency “not known”. There were no adverse reactions with an incidence greater than 2%.

Description of selected adverse reactions

*Vasovagal reactions

Vasovagal reactions, rarely leading to vasovagal syncope have been reported during or immediately after ProHance administration. The condition is often related to emotional distress or painful/unpleasant stimuli (e.g. needle puncture for IV placement). Symptoms commonly experienced include nausea, dizziness and diaphoresis.

In severe cases possibly leading to syncope, patients are usually pale and diaphoretic with altered state of consciousness and bradycardia. In addition patients could frequently experience apprehension, restlessness, faintness and salivary hypersecretion. Proper recognition of this reaction and differential diagnosis with hypersensitivity/anaphylactoid reaction is vital in order to apply the appropriate treatment measures to revert the vagal stimulation.

**Acute renal failure

Cases of acute renal failure have been reported in patients with pre-existing severe renal impairment.

***Anaphylactic/anaphylactoid reactions

As with other gadolinium chelates, there have been reports of anaphylactic/anaphylactoid/ hypersensitivity reactions with gadoteridol. These reactions manifested with various degrees of severity, including anaphylactic shock or death. They involved one or more body systems, mostly respiratory, cardiovascular and/or mucocutaneous systems. Commonly reported symptoms include throat tightness, throat irritation, dyspnoea, chest discomfort, feeling hot, dysphagia, burning sensation, oedema in pharynx or larynx, and hypotension.

Section 10
Date update to 23/03/2011

Special Populations

Impaired renal function

ProHance should only be used in patients with severe renal impairment (GFR < 30 ml/min/1.73m²) 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 (see section 4.4). If it is necessary to use ProHance, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, ProHance injections should not be repeated unless the interval between injections is at least 7 days.

Infants from 6 months to 1 year of age

Due to immature renal function in infants up to 1 year of age, ProHance should only be used in patients 6 to 12 months of age after careful consideration at a dose not exceeding 0.1 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, ProHance injections should not be repeated unless the interval between injections is at least 7 days.

Use of ProHance is not recommended in children less than 6 months of age.

Use for whole body MRI is not recommended in children less than 18 years of age

Elderly (aged 65 years and above)

No dosage adjustment is considered necessary


Section 4.3 new additional text:

Impaired renal function

Prior to administration of ProHance, it is recommended that all patients are screened for renal dysfunction by obtaining laboratory tests.

Pregnancy

There are no data from the use of gadoteridol in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). ProHance should not be used during pregnancy unless the clinical condition of the woman requires use of gadoteridol.

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. Continuing or discontinuing breast feeding for a period of 24 hours after administration of ProHance, should be at the discretion of the doctor and lactating mother.

Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with ProHance, most of which were in patients co-administered other gadolinium-containing contrast agents (see section 4.4).

ProHance can be removed by haemodialysis. However there is no evidence that haemodialysis is suitable for prevention of nephrogenic systemic fibrosis (NSF).

The peel-off tracking label on the vials should be stuck onto the patient record to enable accurate recording of the gadolinium contrast agent used. The dose used should also be recorded.

28/09/2010