REZZAYO Powder for solution for infusion Ref.[107889] Active ingredients: Rezafungin

The efficacy of rezafungin has only been evaluated in a limited number of neutropenic patients (see section 5.1).

Hepatic effects

In clinical trials, elevations in liver enzymes have been seen in some patients treated with rezafungin. In some patients with serious underlying medical conditions who were receiving multiple concomitant medications along with rezafungin, clinically significant hepatic dysfunction has occurred; a causal relationship to rezafungin has not been established. Patients who develop elevations in liver enzymes during rezafungin therapy should be monitored and the risk/benefit of continuing rezafungin therapy should be re-evaluated.

Infusion-related reactions

Transient infusion-related reactions have occurred with rezafungin, characterised by flushing, sensation of warmth, nausea, and chest tightness.

In clinical trials, infusion reactions resolved within minutes, some without interruption or discontinuation of the infusion. Patients should be monitored during the infusion. If the infusion is stopped due to a reaction, consideration may be given to restarting the infusion at a slower rate after the symptoms have resolved.

Phototoxicity

Rezafungin may cause increased risk of phototoxicity. Patients should be advised to avoid sun exposure and other sources of UV radiation without adequate protection during treatment and for 7 days after the last administration of rezafungin.

Sodium content

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

The drug-drug interaction potential of rezafungin with a number of probe substrates of cytochrome P450 enzymes and/or transporter proteins has been assessed clinically. The need for dose adjustments is considered unlikely for medicinal products that are substrates for the CYP2C8, CYP3A4, CYP1A2, and CYP2B6 enzymes and P-gp, BCRP, OATP, OCT1, OCT2, MATE1, and MATE2 transporter proteins, when administered with rezafungin.

The drug-drug interaction potential of rezafungin with a number of co-administered medicinal products has also been assessed clinically. The need for dose adjustments is considered unlikely for tacrolimus, cyclosporine, ibrutinib, mycophenolate mofetil, and venetoclax when administered with rezafungin.

In vitro rezafungin is metabolically stable and was found not to be a substrate for BCRP, P-gp, MRP2, OATP1B1, OATP1B3, OCT1, OCTN1, and OCTN2 transporter proteins. Therefore, the need for dose adjustments of rezafungin is considered unlikely when rezafungin is co-administered with other medicinal products.

Pregnancy

There are no data from the use of rezafungin in pregnant women. Studies in animals did not show reproductive or developmental toxicity (see section 5.3). Rezafungin has been shown to cross the placental barrier in animal studies. The potential risk for humans is unknown.

Rezafungin is not recommended to be used during pregnancy and in women of childbearing potential not using contraception unless the benefit outweighs the potential risk to the foetus.

Breast-feeding

There are no data from the use of rezafungin in lactating women. It is unknown whether rezafungin or its metabolites are excreted in human milk. Rezafungin excretion into milk was observed in rats (see section 5.3).

A risk to the breastfed child cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from rezafungin therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

No data on the effect of rezafungin on human fertility are available. Rezafungin did not affect fertility in female rats or reproductive performance in male rats, despite reversible testicular effects in male rats (see section 5.3).

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

Summary of the safety profile

Based on clinical trial experience, the most frequently reported adverse reactions for rezafungin were hypokalaemia, pyrexia, and diarrhoea (very common adverse reactions).

Transient infusion-related reactions have occurred with rezafungin, characterised by flushing, sensation of warmth, nausea, and chest tightness (see section 4.4).

Tabulated list of adverse reactions

The following table includes adverse reactions from 151 subjects that received rezafungin 400/200 mg listed by system organ class (SOC) and MedDRA preferred terms with frequency corresponding to 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) and from spontaneous reports with frequency not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. Table of adverse reactions:

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 except those mentioned in section 6.6.