4.      Possible side effects

 Like all medicines, this medicine can cause side effects, although not everybody gets them.

 Serious side effects - tell your doctor or another healthcare professional immediately should you experience any of the following side effects:

-             reddening of the skin, sensation of warmth, nausea (feeling sick), chest tightness – these may be signs you are having an infusion‑related reaction (common – may affect up to 1 in 10 people).

 Other side effects

 Very common (may affect more than 1 in 10 people)

-             low blood potassium level (hypokalaemia)

-             diarrhoea

-             fever (pyrexia)

-             decreased red blood cells (anaemia)

 Common (may affect up to 1 in 10 people)

-             low blood magnesium level (hypomagnesaemia)

-             low blood phosphate level (hypophosphataemia)

-             low blood pressure (hypotension)

-             wheezing

-             vomiting

-             feeling sick (nausea)

-             stomach (abdominal) pain

-             constipation

-             redness of the skin (erythema)

-             rash

-             increased blood levels of alkaline phosphatase, an enzyme (protein) made in the liver, bones, kidney and gut

-             increased levels of liver enzymes (including alanine aminotransferase and aspartate aminotransferase)

-             increased blood levels of bilirubin, a breakdown product of red blood cells

 Uncommon (may affect up to 1 in 100 people)

-             high blood phosphate levels (hyperphosphataemia)

-             low blood sodium level (hyponatraemia)

-             skin or eyes become very sensitive to sunlight or other forms of light (phototoxicity)

-             shaking (tremor)

-             high blood levels of eosinophils (a type of white blood cell)

 Not known (frequency cannot be estimated from the available data)

Hives (urticaria)

6.      Contents of the pack and other information

 What REZZAYO contains

-             The active substance is rezafungin. Each vial contains 200 mg rezafungin (as acetate).

-             The other ingredients are mannitol, histidine, polysorbate 80, hydrochloric acid, sodium hydroxide (see section 2 “REZZAYO contains sodium”).

 What REZZAYO looks like and contents of the pack

 REZZAYO is a powder for concentrate for solution for infusion (powder for concentrate) in a glass vial with a rubber stopper and an aluminium seal with plastic flip‑off cap. It is a white to pale yellow cake or powder.

Each pack contains 1 vial

3.      PHARMACEUTICAL FORM

 Powder for concentrate for solution for infusion (powder for concentrate)

White to pale yellow cake or powder.

4.8    Undesirable effects

 Summary of the safety profile

Based on clinical trial experience, the most frequently reported adverse reactions for rezafungin were hypokalaemia, pyrexia, anaemia, 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 173 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.

5.1    Pharmacodynamic properties

Clinical efficacy

Candidaemia and invasive candidiasis in adult patients

The efficacy of rezafungin in the treatment of patients with candidaemia and/or invasive candidiasis (C/IC) was evaluated in a single Phase 3 study.

The Phase 3 study was multicentre, prospective, randomised and double‑blind. Patients with septic arthritis in a prosthetic joint, osteomyelitis, endocarditis or myocarditis, meningitis, endophthalmitis, chorioretinitis or any central nervous system infection, chronic disseminated candidiasis and urinary tract candidiasis secondary to obstruction or surgical instrumentation were excluded from the study. Subjects were randomised in a 1:1 ratio to receive rezafungin as a 400 mg loading dose on Day 1, followed by 200 mg on Day 8 and once weekly thereafter, for a total of 2 to 4 weeks or caspofungin as a single 70 mg intravenous loading dose on Day 1 followed by caspofungin 50 mg intravenous once daily for a total treatment of 14 days to 28 days.

For rezafungin and caspofungin treatment groups, 77.0% and 74.2 % patients, respectively, had a final diagnosis of candidaemia only. Most of them had a modified APACHE II score < 20, representing 84.4 % and 81.5 % of rezafungin and caspofungin subjects, respectively. For rezafungin and caspofungin treatment groups, 88.5 % and 91.1 % patients, respectively, had an ANC ≥ 500/mm3 at baseline.

The primary efficacy outcome was global response (confirmed by the Data Review Committee [DRC]) at Day 14. Global response was determined from clinical response, mycological response, and radiologic response (for qualifying subjects with IC). Non‑inferiority was to be concluded if the lower bound of the 95 % confidence interval (CI) for the difference in Day 14 cure rates (rezafungin - caspofungin) was > -20 %. Secondary efficacy outcomes included all‑cause mortality at Day 30 [30‑day ACM] and global response at Day 5. The results of these endpoints are shown in Table 2 for the mITT analysis set, defined as all subjects with a documented Candida infection based on Central Laboratory evaluation of a blood culture or a culture from a normally sterile site obtained ≤ 4 days (96 hours) before randomisation and who received ≥ 1 dose of investigational medicinal product.

Upload new SPC.

Uploading new PIL