VUEWAY Solution for injection Ref.[108266] Active ingredients: Gadopiclenol

The usual precautions for MRI examination should be applied, 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.

MRI images produced with this medicinal product should only be analysed and interpreted by the healthcare professionals trained in interpretation of gadolinium enhanced MRI.

There are no or limited clinical data investigating the performance of gadopiclenol for CNS imaging in patients with inflammatory, infectious, autoimmune or demyelinating disorders (such as multiple sclerosis), patients with acute or chronic infarct, or patients with intramedullary spine lesions. There are also no or limited clinical data investigating the performance of gadopiclenol for body imaging in patients with inflammatory, infectious and autoimmune conditions, including acute/chronic pancreatitis, inflammatory bowel disease, inflammatory diseases of head and neck region and endometriosis.

Potential for hypersensitivity or anaphylactic reactions

• As with other gadolinium-containing contrast agents, hypersensitivity reactions can occur, including life-threatening. Hypersensitivity reactions may be either allergic (described as anaphylactic reactions when serious) or non-allergic. They can occur either immediately (less than 60 minutes) after injection 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.
• During the examination, supervision by a physician is necessary. If hypersensitivity reactions occur, administration of the contrast agent must be discontinued immediately and – if necessary – a specific therapy must be instituted. A venous access should thus be kept during the entire examination. To permit immediate emergency countermeasures, appropriate drugs (e.g. epinephrine and antihistamines), an endotracheal tube and a respirator should be ready at hand.
• The risk of hypersensitivity reaction may be higher in patients with a history of previous reaction to gadolinium-containing contrast agents, bronchial asthma or allergy.

Renal impairment and nephrogenic systemic fibrosis (NSF)

Prior to administration of gadopiclenol, 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 gadoliniumcontaining contrast agents in patients with acute or chronic severe renal impairment (GFR <30 mL/min/1.73 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 gadopiclenol, it should only be used in patients with severe renal impairment and in patients in the perioperative liver transplantation period after careful benefit/risk assessment and if the diagnostic information is essential and not available with non-contrast enhanced MRI.

Haemodialysis shortly after gadopiclenol administration may be useful at removing it 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 gadopiclenol may be impaired in the elderly, it is particularly important to screen patients aged 65 years and older for renal dysfunction. Caution should be exercised in patients with renal impairment (see section 4.2).

Seizures

As with other gadolinium-containing contrast agents, special caution is necessary in patients with a lowered threshold for seizures. All equipment and drugs necessary to counter convulsions occurring during the MRI examination must be made ready for use beforehand.

Extravasation

Caution during administration is necessary to avoid any extravasation. In case of extravasation, the injection must be stopped immediately. In case of local reactions, evaluation and treatment should be carried out as necessary.

Cardiovascular disease

In patients with severe cardiovascular disease gadopiclenol should only be administrated after careful risk benefit assessment because no data are available so far.

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per 15 mL, that is to say essentially ‘sodium-free’.

No interaction studies have been performed.

Concomitant medicinal products to be taken into account

Beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists decrease the efficacy of the mechanisms of cardiovascular compensation for blood pressure disorders. The physician must obtain information before injection of gadopiclenol about the concomitant intake of those medicinal products.

Pregnancy

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

Breast-feeding

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 in milk and poor absorption from the gut. Continuing or discontinuing breast feeding for a period of 24 hours after administration of Vueway, should be at the discretion of the doctor and breast-feeding mother.

Fertility

Animals studies do not indicate impairment of fertility (see section 5.3).

Vueway has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most frequent adverse reactions were injection site pain, headache, nausea, injection site coldness, fatigue and diarrhoea.

Tabulated list of adverse reactions

Table 2 below presents adverse reactions based on clinical trials including 1047 subjects exposed to gadopiclenol ranging from 0.05 mL/kg BW (equivalent to 0.025 mmol/kg BW) to 0.6 mL/kg BW (equivalent to 0.3 mmol/kg BW).

The adverse reactions are listed below by SOC (System Organ Class) and by frequency with the following guidelines: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000).

Table 2. Adverse reactions reported following gadopiclenol administration:

^* Including immediate (dermatitis allergic, erythema, dyspnoea, dysphonia, throat tightness, throat irritation, paraesthesia oral and flushing) and delayed (periorbital oedema, swelling, rash and pruritus) reactions.
^** Injection site reaction includes the following terms: injection site pain, injection site oedema, injection site coldness, injection site warmth, injection site haematoma and injection site erythema.

Description of selected adverse reactions

Hypersensitivity

Immediate reactions include one or more effects, which appear simultaneously or sequentially, which are most often cutaneous, respiratory and/or vascular reactions. Each sign may be a warning sign of a starting shock and go very rarely to death.

Nephrogenic systemic fibrosis (NSF)

Isolated cases of NSF have been reported with other gadolinium-containing contrast agents (see section 4.4).

Paediatric population (2 years and older)

A total of 80 paediatric patients aged 2 years and older were included in the clinical trial.

As compared to adults, the safety profile of gadopiclenol in this population did not show any specific safety concern.

A total of 31 Treatment Emergent Adverse Events (TEAEs) occurred during and/or after gadopiclenol administration for 14 patients (17.5%). Twelve TEAEs were reported in the CNS cohort and 2 in the

Body cohort. Among these TEAEs, 1 event in 1 patient (1.25%) from the CNS cohort was considered related to gadopiclenol.

Reporting of suspected adverse reactions

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 national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.