Gadopiclenol

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.

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.

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.

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.

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

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. Gadopiclenol should not be used during pregnancy unless the clinical condition of the woman requires use of gadopiclenol.

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 gadopiclenol, should be at the discretion of the doctor and breast-feeding mother.

Fertility

Animals studies do not indicate impairment of fertility.

Gadopiclenol 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

The table below 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).

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.

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.