Anidulafungin

1).

Treatment with Anidulafungin 100mg Powder for Concentrate for Solution for Infusion should be initiated by a physician experienced in the management of invasive fungal infections. Posology Specimens for fungal culture should be obtained prior to therapy.

Therapy may be initiated before culture results are known and can be adjusted accordingly once they are available. Adult population (dosing and treatment duration) A single 200 mg loading dose should be administered on Day 1, followed by 100 mg daily thereafter.

Duration of treatment should be based on the patient’s clinical response. In general, antifungal therapy should continue for at least 14 days after the last positive culture. There are insufficient data to support the 100 mg dose for longer than 35 days of treatment.

Patients with renal and hepatic impairment No dosing adjustments are required for patients with mild, moderate, or severe hepatic impairment. No dosing adjustments are required for patients with any degree of renal insufficiency, including those on dialysis.

2). 2). 5 mg/kg (not to exceed 100 mg) thereafter. Duration of treatment should be based on the patient's clinical response. In general, antifungal therapy should continue for at least 14 days after the last positive culture. 4). Method of administration For intravenous use only.

77 mg/mL for the final infusion solution. For a paediatric patient, the volume of infusion solution required to deliver the dose will vary depending on the weight of the child. 6). 4 mL/min when reconstituted and diluted per instructions).

4). Anidulafungin 100mg Powder for Concentrate for Solution for Infusion must not be administered as a bolus injection.

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. 4. 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

1. Hypersensitivity to other medicinal products of the echinocandin class.

1).

Treatment with ECALTA should be initiated by a physician experienced in the management of invasive fungal infections. Posology Specimens for fungal culture should be obtained prior to therapy. Therapy may be initiated before culture results are known and can be adjusted accordingly once they are available.

Adult population (dosing and treatment duration) A single 200 mg loading dose should be administered on Day 1, followed by 100 mg daily thereafter. Duration of treatment should be based on the patient’s clinical response. In general, antifungal therapy should continue for at least 14 days after the last positive culture.

There are insufficient data to support the 100 mg dose for longer than 35 days of treatment. 3 Patients with renal and hepatic impairment No dosing adjustments are required for patients with mild, moderate, or severe hepatic impairment.

No dosing adjustments are required for patients with any degree of renal insufficiency, including those on dialysis. 2). 2). 5 mg/kg (not to exceed 100 mg) thereafter. Duration of treatment should be based on the patient’s clinical response.

In general, antifungal therapy should continue for at least 14 days after the last positive culture. 4). Method of administration For intravenous use only. 77 mg/mL for the final infusion solution. For a paediatric patient, the volume of infusion solution required to deliver the dose will vary depending on the weight of the child.

6). 4 mL/min when reconstituted and diluted per instructions). 4). ECALTA must not be administered as a bolus injection.

4). 6 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. 4. 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.

1. Hypersensitivity to other medicinal products of the echinocandin class.

ERAXIS (anidulafungin) is indicated for: • treatment of invasive candidiasis/candidemia in non-neutropenic adult and pediatric patients one month and older (see 14 CLINICAL TRIALS) ERAXIS has not been studied in endocarditis, osteomyelitis, or meningitis due to Candida.

Infections caused by C. krusei have not been studied. Neutropenic patients have not been studied in sufficient numbers to determine the efficacy of the drug in this group (see 14 CLINICAL TRIALS). 1 Pediatrics Pediatrics (>1 month and older): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of ERAXIS in pediatric patients has been established.

Therefore, Health Canada has authorized an indication for pediatric use (see 14 CLINICAL TRIALS).

Pediatrics (<1 month):

The safety and efficacy of ERAXIS in pediatric patients <1 month of age has not been established; therefore, Health Canada has not authorized an indication for use in pediatrics <1 month old. 3 Pharmacokinetics, Special Populations and Conditions).

, Carcinogenesis and Mutagenesis No long - term studies in animals have been performed to evaluate the carcinogenic potential of anidulafungin. For information on animal data, see 16 NON-CLINICAL TOXICOLOGY sections of the Product Monograph.

Hepatic/Biliary/Pancreatic Laboratory abnormalities in liver function tests have been seen in healthy subjects and patients treated with anidulafungin. In some patients with serious underlying medical conditions who were receiving multiple concomitant medications along with anidulafungin, clinically-significant hepatic abnormalities have occurred.

Isolated cases of significant hepatic dysfunction, hepatitis, or hepatic failure have been reported in patients; a causal relationship to anidulafungin has not been established. Patients who develop abnormal liver function tests during anidulafungin therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing anidulafungin therapy.

Immune 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. 1 Pregnant Women Animal studies have shown no selective reproductive toxicity (see 16 NON-CLINICAL TOXICOLOGY).

There are no adequate and well-controlled studies in pregnant women. Therefore, ERAXIS (anidulafungin) should be used during pregnancy only if the potential benefit justifies the risk to the fetus. 2 Breast-feeding Animal studies have shown excretion of anidulafungin in breast milk (see 16 NON-CLINICAL TOXICOLOGY).

It is not known whether anidulafungin is excreted in human breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with anidulafungin should be made taking into account the benefit of breast-feeding to the child and the benefit of anidulafungin to the woman.

3 Pediatrics The safety and efficacy of ERAXIS have not been established in neonates (less than 1 month of age). Nonclinical infection models indicate that higher doses of anidulafungin are needed to achieve adequate CNS penetration (16 NON-CLINICAL TOXICOLOGY), 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.

1 Adverse Reaction Overview Nine hundred and twenty-nine (929) patients received intravenous anidulafungin in clinical trials (672 in Phase 2/3 studies and 257 in Phase 1 studies). Of the 669 Phase 2/3 patients for whom safety data are available, 505 received anidulafungin for ≥ 14 days.

Three studies (one comparative vs fluconazole, two non-comparative) assessed the efficacy of anidulafungin (100 mg) in patients with candidemia and other deep tissue Candida infections. In these three studies [invasive candidiasis/candidaemia (ICC) database], a total of 204 patients received anidulafungin, 119 for ≥ 14 days.

Adverse events were typically mild to moderate and seldom led to discontinuation. Infusion-related adverse events have been reported with anidulafungin, including rash, urticaria, flushing, pruritus, dyspnea, bronchospasm and hypotension.

1 mg/minute. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. 0% of subjects receiving ERAXIS or fluconazole therapy for candidemia/other Candida infections in the comparative study.

ERAXIS® (anidulafungin) - Product Monograph Page 10 of 32 Table 1. 0% of subjects receiving ERAXIS or fluconazole therapy for candidemia/other Candida infections. 4) a Treatment-related AEs are defined as those that are possibly or probably related to study treatment, as determined by the investigator.

1 Clinical Trial Adverse Reactions – Pediatrics The safety of anidulafungin was investigated in 68 pediatric subjects (1 month to < 18 years) with invasive candidiasis, including candidemia (ICC) in a prospective, open-label, non-comparative pediatrics study (see section 14 CLINICAL TRIALS).

The adverse event profile of these 68 pediatric subjects was similar to that observed in adults with ICC; however, 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 pediatric 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 pediatric patients compared to adults. 3 Less Common Clinical […]

ERAXIS is contraindicated in patients who are hypersensitive to anidulafungin or to any ingredient in the formulation, including any non-medicinal ingredient or other echinocandins, or component of the container. 3 Reconstitution. 2 Recommended Dose and Dosage Adjustment Specimens for fungal culture and other relevant laboratory studies (including histopathology) should be obtained prior to therapy to isolate and identify causative organism(s).

Therapy may be instituted before the results of the cultures and other laboratory studies are known. However, once these results become available, antifungal therapy should be adjusted accordingly. A single 200 mg loading dose should be administered on Day 1, followed by 100 mg daily thereafter.

Duration of treatment should be based on the patient’s clinical response. In general, antifungal therapy should continue for at least 14 days after the last positive culture. Renal and Hepatic Impairment No dosing adjustments are required for patients with mild, moderate or severe hepatic impairment.

No dosing adjustments are required for patients with any degree of renal insufficiency, including those on dialysis. Anidulafungin can be given without regard to the timing of hemodialysis (see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions).

Other Special Populations No dose adjustments are required for adult patients based on patient gender, ethnicity, HIV positivity, or geriatric status. (see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions). 5 mg/kg (not to exceed 100 mg) daily dose thereafter.

In general, antifungal therapy should continue for at least 14 days after the last negative culture (defined as the second of two consecutive negative cultures, separated by at least 24 hours, following the last positive culture) and improvement of clinical signs and symptoms of invasive candidiasis including candidemia (ICC).

Switch to an oral antifungal may occur after a minimum of 10 days on anidulafungin intravenous therapy. The efficacy and safety of anidulafungin has not been established in neonates (less than 1 month) (see section 7 WARNINGS AND PRECAUTIONS).

9% Sodium Chloride Injection, USP (normal saline). 9% Sodium Chloride Injection, USP (normal saline) has not been established. The infusion solution must not be frozen. 33 mg/mL. The reconstitution time can be up to 5 minutes. If not used immediately, the reconstituted solution should be stored at 15 - 30 °C for up to 24 hours.

77 mg/ml. The table below provides the volumes required for each dose. 9% Sodium Chloride Injection, USP (normal saline). 4 mL/minute). The infusion solution should be stored at 15 - 30 °C, for up to 48 hours. Do not freeze. For single use only.

Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit. If particulate matter or discolouration are identified, discard the solution.

For further information on storage and stability for the infusion and reconstituted solution, see section 11 STORAGE, STABILITY AND DISPOSAL. 1 mg/minute. 5 OVERDOSAGE As with any overdose, general supportive measures should be utilized as necessary.

During clinical trials a single 400 mg dose of anidulafungin was inadvertently administered as a loading dose. No clinical adverse events were reported. In a study of 10 healthy subjects administered a loading dose of 260 mg followed by 130 mg daily, anidulafungin was well tolerated with no dose ERAXIS® (anidulafungin) - Product Monograph Page 7 of 32 limiting toxicity; 3 of the 10 subjects experienced transient, asymptomatic transaminase elevations (3 x ULN).

During a pediatric clinical trial, one subject received two doses of anidulafungin that were 143% of the expected dose. No clinical adverse reactions were reported. Anidulafungin is not dialyzable. The maximum non-lethal single dose of anidulafungin in rats was 50 mg/kg, a dose which is equivalent to 5 times the recommended daily dose in humans for Candidemia and other Candida infections [100 mg/day] , […]