ECALTA Powder for concentrate for solution for infusion Ref.[6192] Active ingredients: Anidulafungin

ECALTA has not been studied in patients with Candida endocarditis, osteomyelitis or meningitis.

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

Paediatric population

Treatment with ECALTA in neonates (<1 month old) is not recommended. Treating neonates requires consideration for coverage of disseminated candidiasis including central nervous system (CNS); nonclinical infection models indicate that higher doses of anidulafungin are needed to achieve adequate CNS penetration (see section 5.3), resulting in higher doses of polysorbate 80, a formulation excipient. High doses of polysorbates have been associated with potentially life-threatening toxicities in neonates as reported in the literature.

There is no clinical data to support the efficacy and safety of higher doses of anidulafungin than recommended in 4.2.

Hepatic effects

Increased levels of hepatic enzymes have been seen in healthy subjects and patients treated with anidulafungin. In some patients with serious underlying medical conditions who were receiving multiple concomitant medicines along with anidulafungin, clinically significant hepatic abnormalities have occurred. Cases of significant hepatic dysfunction, hepatitis, and hepatic failure were uncommon in clinical trials. Patients with increased hepatic enzymes during anidulafungin therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing anidulafungin therapy.

Anaphylactic reactions

Anaphylactic reactions, including shock, were reported with the use of anidulafungin. If these reactions occur, anidulafungin should be discontinued and appropriate treatment administered.

Infusion-related reactions

Infusion-related adverse events have been reported with anidulafungin, including rash, urticaria, flushing, pruritus, dyspnoea, bronchospasm and hypotension. Infusion-related adverse events are infrequent when the rate of anidulafungin infusion does not exceed 1.1 mg/min (see section 4.8).

Exacerbation of infusion-related reactions by co-administration of anaesthetics has been seen in a non-clinical (rat) study (see section 5.3). The clinical relevance of this is unknown. Nevertheless, care should be taken when co-administering anidulafungin and anaesthetic agents.

Excipients with known effect

Fructose

ECALTA contains fructose.

Patients with hereditary fructose intolerance (HFI) should not be given this medicine unless strictly necessary.

Babies and young children (below 2 years of age) may not yet be diagnosed with HFI. Medicines (containing fructose) given intravenously may be life-threatening and should not be administered in this population unless there is an overwhelming clinical need and no alternatives are available.

A detailed history with regard to HFI symptoms has to be taken of each patient prior to being given this medicinal product.

Sodium

ECALTA contains less than 1 mmol sodium (23 mg) per vial. Patients on low sodium diets can be informed that this medicinal product is essentially 'sodium-free'.

ECALTA may be diluted with sodium-containing solutions (see section 6.6) and this should be considered in relation to the total sodium from all sources that will be administered to the patient.

Polysorbate

ECALTA contains Polysorbate 80. Polysorbates may cause allergic reactions and can have an effect on the heart and blood circulation (e.g., irregular or abnormal heartbeat, or low blood pressure). Risk minimization by lowering the rate of infusion is to be considered.

Anidulafungin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 isoenzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A). Of note, in vitro studies do not fully exclude possible in vivo interactions.

Drug interaction studies were performed with anidulafungin and other medicinal products likely to be co-administered. No dosage adjustment of either medicinal product is recommended when anidulafungin is co-administered with ciclosporin, voriconazole or tacrolimus, and no dosage adjustment for anidulafungin is recommended when co-administered with amphotericin B or rifampicin.

Paediatric population

Interaction studies have only been performed in adults.

Pregnancy

There are no data from the use of anidulafungin in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3).

ECALTA is not recommended during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus.

Breast-feeding

It is unknown whether anidulafungin is excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of anidulafungin in milk.

A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Ecalta therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

For anidulafungin, there were no effects on fertility in studies conducted in male and female rats (see section 5.3).

Not relevant.

Summary of the safety profile

Infusion-related adverse reactions have been reported with anidulafungin in clinical studies, including rash, pruritus, dyspnoea, bronchospasm, hypotension (common events), flushing, hot flush, and urticaria (uncommon events), summarized in Table 1 (see section 4.4).

Tabulated list of adverse reactions

The following table includes, the all-causality adverse reactions (MedDRA terms) from 840 subjects receiving 100 mg anidulafungin 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, undesirable effects are presented in order of decreasing seriousness.

Table 1. Table of Adverse Reactions:

^* See section 4.4.

Paediatric population

The safety of anidulafungin was investigated in 68 paediatric patients (1 month to <18 years) with invasive candidiasis including candidaemia (ICC) in a prospective, open-label, non-comparative paediatric study (see section 5.1). The frequencies of certain hepatobiliary adverse events, including alanine aminotransferase (ALT) increased and aspartate aminotransferase (AST) increased appeared at a higher frequency (7-10%) in these paediatric patients than has been observed in adults (2%). Although chance or differences in underlying disease severity may have contributed, it cannot be excluded that hepatobiliary adverse reactions occur more frequently in paediatric patients compared to adults.

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.

This medicinal product must not be mixed with other medicinal products or electrolytes except those mentioned in section 6.6.