Posology : מינונים

5        DOSAGE AND ADMINISTRATION

5.1      Recommended Dosage
Administer ADAKVEO 5 mg/kg by intravenous infusion over a period of 30 minutes at Week 0, Week 2, and every 4 weeks thereafter.
If a dose is missed, administer ADAKVEO as soon as possible.
If ADAKVEO is administered within 2 weeks after the missed dose, continue dosing according to the patient's original schedule.
If ADAKVEO is administered more than 2 weeks after the missed dose, continue dosing every 4 weeks thereafter.
ADAKVEO may be given with or without hydroxyurea.


5.2      Preparation and Administration
ADAKVEO should be prepared and administered by a healthcare professional.
Preparation
•     Use aseptic technique to prepare the solution for infusion.
•     Calculate the dose (mg) and the total volume (mL) of ADAKVEO solution required, and the number of ADAKVEO vials needed based on the patient’s actual body weight.
o Prepare 5 mg of ADAKVEO per kg of actual body weight.
•     Calculate the volume of ADAKVEO to be used according to the following equation: 5 mg patient′s body weight (kg) x prescribed dose �     � kg
Volume (mL) =
10 mg concentration of ADAKVEO �        � mL


Dilution
Dilute ADAKVEO in 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a total volume of 100 mL for intravenous infusion as follows:
1. Obtain the number of vials required. One vial is needed for every 10 mL of ADAKVEO.
2. Bring vials to room temperature for a maximum of 4 hours prior to the start of preparation (piercing the first vial).
3. Visually inspect the vials.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
• ADAKVEO is clear to opalescent, colorless or may have a slightly brownish-yellow tint.
• Do not use if particles are present in the solution.
4. Obtain a 100 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection infusion bag/container.
• Infusion bags/containers must be made of either polyvinyl chloride (PVC), polyethylene (PE), or polypropylene (PP).
5. Remove a volume of 0.9% Sodium Chloride Injection or 5% Dextrose Injection from the infusion bag/container that is equal to the required volume of ADAKVEO solution.
6. Withdraw the necessary amount of ADAKVEO solution and dilute by adding to the infusion bag/container containing 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
• The volume of ADAKVEO added to the infusion bag/container should not exceed 96 mL 7. Gently invert the infusion bag to mix the diluted solution. DO NOT SHAKE.
8. Single-dose vials. Discard unused portion.

Storage Conditions of the Diluted Solution
Chemical and physical in-use stability, from the start of preparation of the diluted solution for infusion until end of infusion, has been demonstrated for up to 8 hours at room temperature (up to 25°C) and at 2°C to 8°C for up to 24 hours overall.
From a microbiological point of view, the diluted solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, including 4.5 hours at room temperature (up to 25°C) from the start of preparation to completion of the infusion, unless dilution has taken place in controlled and validated aseptic conditions.

Administration
•   Administer ADAKVEO diluted solution by intravenous infusion over a period of 30 minutes through an intravenous line, which must contain a sterile, nonpyrogenic 0.2-micron inline filter.
•   No incompatibilities have been observed between ADAKVEO and infusion sets composed of PVC, polyethylene (PE- lined PVC), polyurethane (PU), and in-line filter membranes composed of polyethersulfone (PES, neutral and positively charged), positively charged polyamide (PA), and polysulphone (PSU).
•   Do not mix or coadminister with other drugs through the same intravenous line.
•   After administration of ADAKVEO, flush the line with at least 25 mL of 0.9% Sodium Chloride injection or 5% Dextrose Injection.
•   Dispose of any unused product or waste material in accordance with local requirements.



5.3    Management of Infusion-Related Reactions
No dose reductions are recommended. Management for infusion-related reactions for ADAKVEO is described in Table 1.

Table 1: Recommended Management for Infusion-Related Reactions
Severity of Adverse Reaction                                     Recommendation Mild to moderate infusion-related reactions                      •   Temporarily interrupt the infusion or slow the rate of infusion
•   Initiate symptomatic treatmenta (e.g., acetaminophen,
nonsteroidal anti-inflammatory drugs (NSAIDs),
opioids, antihistamines, intravenous fluids, and/or oxygen therapy)
•   For subsequent infusions, consider premedication and/or reduce the infusion rate
Severe infusion-related reactions                                •   Discontinue infusion •   Institute appropriate medical carea
•   Consider permanent discontinuation of ADAKVEO aExercise caution with the use of corticosteroids in patients with sickle cell disease unless clinically indicated (e.g., treatment of anaphylaxis).

6          DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/10 mL (10 mg/mL) as a clear to opalescent, colorless to slightly brownish-yellow solution in a single- dose vial.