Gadopiclenol

No dose adjustment is necessary for patients with any level of renal impairment. Gadopiclenol should only be used in patients with severe renal impairment (GFR <30 mL/min/1.73 m²) 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. If it is necessary to use gadopiclenol, the dose should not exceed 0.05 mmol/kg BW. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, gadopiclenol injections should not be repeated unless the interval between injections is at least 7 days.

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.

Data on the use of gadolinium-based contrast agents including gadopiclenol 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. 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 presents adverse reactions based on clinical trials including 1083 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 and 36 paediatric patients aged less than 2 years received an injection of gadopiclenol at the dose of 0.1 mL/kg BW (0.05 mmol/kg BW) in two clinical trials.

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

Overall, 69 Treatment Emergent Adverse Events (TEAEs) occurred during and/or after gadopiclenol administration for 33 patients out of 116(28.4%).

Among these TEAEs, 2 events in 2 patients (1.7%), one under 2 years old and one 9 years old, were considered related to gadopiclenol (erythema and maculopapular rash).