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

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.

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. ECALTA can be given without regard to the timing of haemodialysis (see section 5.2).

Other special populations

No dosing adjustments are required for adult patients based on gender, weight, ethnicity, HIV positivity, or elderly (see section 5.2).

Paediatric population (1 month to <18 years) (dosing and treatment duration)

A single loading dose of 3.0 mg/kg (not to exceed 200 mg) should be administered on Day 1 followed by a daily maintenance dose of 1.5 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.

The safety and efficacy of ECALTA have not been established in neonates (<1 month old) (see section 4.4).

Method of administration

For intravenous use only.

ECALTA should be reconstituted with water for injection to a concentration of 3.33 mg/mL and subsequently diluted to a concentration of 0.77 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. For instructions on reconstitution of the medicinal product before administration (see section 6.6).

It is recommended that ECALTA be administered at a rate of infusion that does not exceed 1.1 mg/min (equivalent to 1.4 mL/min when reconstituted and diluted per instructions). Infusion associated reactions are infrequent when the rate of anidulafungin infusion does not exceed 1.1 mg/min (see section 4.4).

ECALTA must not be administered as a bolus injection.

As with any overdose, general supportive measures should be utilised as necessary. In case of overdose, adverse reactions may occur as mentioned in section 4.8.

During clinical trials, a single 400 mg dose of anidulafungin was inadvertently administered as a loading dose. No clinical adverse reactions were reported. No dose limiting toxicity was observed in a study of 10 healthy subjects administered a loading dose of 260 mg followed by 130 mg daily; 3 of the 10 subjects experienced transient, asymptomatic transaminase elevations (≤3 x Upper Limit of Normal (ULN)).

During a paediatric clinical trial, one subject received two doses of anidulafungin that were 143% of the expected dose. No clinical adverse reactions were reported.

ECALTA is not dialysable.

3 years.

Excursions for up to 96 hours at temperatures up to 25ºC are permitted, and the powder can be returned to refrigerated storage.

Reconstituted solution:

Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 24 hours at 25ºC.

From a microbiological point of view, following good aseptic practices, the reconstituted solution can be utilized for up to 24 hours when stored at 25ºC.

Infusion solution:

Do not freeze.

Chemical and physical in-use stability of the infusion solution has been demonstrated for 48 hours at 25ºC.

From a microbiological point of view, following good aseptic practices, the infusion solution can be utilized for up to 48 hours from preparation when stored at 25ºC.

Store in a refrigerator (2°C–8°C).

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

30 mL Type 1 glass vial with an elastomeric stopper (butyl rubber with an inert polymer coating on the product contact surface and lubricant on the top surface for easier machinability, or alternatively bromobutyl rubber with a lubricant) and aluminium seal with flip-off cap.

Pack size of 1 vial.

There are no special requirements for disposal.

ECALTA must be reconstituted with water for injection and subsequently diluted with ONLY sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) glucose for infusion. The compatibility of reconstituted ECALTA with intravenous substances, additives, or medicines other than 9 mg/mL (0.9%) sodium chloride for infusion or 50 mg/mL (5%) glucose for infusion has not been established. The infusion solution must not be frozen.

Reconstitution

Aseptically reconstitute each vial with 30 mL water for injection to provide a concentration of 3.33 mg/mL. The reconstitution time can be up to 5 mins. After subsequent dilution, the solution is to be discarded if particulate matter or discolouration is identified.

Dilution and infusion

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

Adult Patients

Aseptically transfer the contents of the reconstituted vial(s) into an intravenous bag (or bottle) containing either 9 mg/mL (0.9%) sodium chloride for infusion or 50 mg/mL (5%) glucose for infusion to obtain the appropriate ECALTA concentration. The table below provides the dilution to a concentration of 0.77 mg/mL for the final infusion solution and infusion instructions for each dose.

Dilution requirements for ECALTA administration

^A Either 9 mg/mL (0.9%) sodium chloride for infusion or 50 mg/mL (5%) glucose for infusion.
^B Infusion solution concentration is 0.77 mg/mL

The rate of infusion should not exceed 1.1 mg/min (equivalent to 1.4 mL/min when reconstituted and diluted per instructions) (see sections 4.2, 4.4 and 4.8).

Paediatric Patients

For paediatric patients aged 1 month to <18 years, the volume of infusion solution required to deliver the dose will vary depending on the weight of the patient. The reconstituted solution must be further diluted to a concentration of 0.77 mg/mL for the final infusion solution. A programmable syringe or infusion pump is recommended. The rate of infusion should not exceed 1.1 mg/minute (equivalent to 1.4 mL/minute or 84 mL/hour when reconstituted and diluted per instructions) (see sections 4.2 and 4.4).

1. Calculate patient dose and reconstitute vial(s) required according to reconstitution instructions to provide a concentration of 3.33 mg/mL (see sections 2 and 4.2)

2. Calculate the volume (mL) of reconstituted anidulafungin required:

• Volume of anidulafungin (mL) = Dose of anidulafungin (mg) ÷ 3.33 mg/mL

3. Calculate the total volume of dosing solution (mL) required to provide a final concentration of 0.77 mg/mL:

• Total volume of dosing solution (mL) = Dose of anidulafungin (mg) ÷ 0.77 mg/mL

4. Calculate the volume of diluent [5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline)] required to prepare the dosing solution:

• Volume of diluent (mL) = Total volume of dosing solution (mL) – Volume of anidulafungin (mL)

5. Aseptically transfer the required volumes (mL) of anidulafungin and 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline) into an infusion syringe or IV infusion bag needed for administration.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.