NEXVIADYME Powder for solution for infusion Ref.[50122] Active ingredients: Avalglucosidase alfa

Nexviadyme treatment should be supervised by a physician experienced in the management of patients with Pompe disease or other inherited metabolic or neuromuscular diseases.

Posology

Patients may be pre-treated with antihistamines, antipyretics, and/or corticosteroids to prevent or reduce allergic reactions.

The recommended dose of avalglucosidase alfa is 20 mg/kg of body weight administered once every 2 weeks.

Dose modification for IOPD patients

For IOPD patients who experience lack of improvement or insufficient response in cardiac, respiratory, and/or motor function while receiving 20 mg/kg, a dose increase to 40 mg/kg every other week should be considered in the absence of safety concerns (e.g., severe hypersensitivity, anaphylactic reactions, or risk of fluid overload).

In patients who do not tolerate avalglucosidase alfa at 40 mg/kg every other week (e.g., severe hypersensitivity, anaphylactic reactions, or risk of fluid overload), consider decreasing the dose to 20 mg/kg every other week (see section 4.4).

Special populations

Elderly patients

No dose adjustment is required in patients >65 years.

Hepatic impairment

The safety and efficacy of avalglucosidase alfa in patients with hepatic impairment have not been evaluated and no specific dose regimen can be recommended for these patients.

Renal impairment

No dose adjustment is required in patients with mild renal impairment. The safety and efficacy of avalglucosidase alfa in patients with moderate or severe renal impairment have not been evaluated and no specific dose regimen can be recommended for these patients. (see section 5.2).

Paediatric population (patients 6 months of age and younger)

The safety and efficacy of avalglucosidase alfa in children 6 months of age and younger have not yet been established. There are no data available in patients 6 months of age and younger.

Method of administration

Nexviadyme vials are for single use only and the medicinal product should be administered as an intravenous infusion.

The infusion should be administered incrementally as determined by patient response and comfort. It is recommended that the infusion begins at an initial rate of 1 mg/kg/hour and is gradually increased every 30 minutes if there are no signs of infusion-associated reactions (IARs), in accordance with Table 1. Vital signs should be obtained at each step, before increasing the infusion rate.

Table 1. Infusion rate schedule:

^a For LOPD patients with body weight of 1.25-5 kg a maximum infusion rate of 4.8 mg/kg/hour can be applied.
^b For IOPD patients with body weight of 1.25-5 kg a maximum infusion rate of 9.6 mg/kg/hour can be applied.

In the event of anaphylaxis or severe hypersensitivity reaction or severe IARs, administration of Nexviadyme should be immediately discontinued and appropriate medical treatment should be initiated. In the event of mild to moderate hypersensitivity reactions or IARs, the infusion rate may be slowed or temporarily stopped and/or appropriate medical treatment initiated (see section 4.4).

Symptoms may persist despite temporarily stopping the infusion; therefore, the treating physician should wait at least 30 minutes for symptoms of the reactions to resolve before deciding to stop the infusion for the remainder of the day. If symptoms subside, infusion rate should be resumed for 30 minutes at half the rate, or less, of the rate at which the reactions occurred, followed by an increase in infusion rate by 50% for 15 to 30 minutes. If symptoms do not recur, the infusion rate should be increased to the rate at which the reactions occurred and consider continuing to increase the rate in a stepwise manner until the maximum rate is achieved.

Home infusion

Infusion of Nexviadyme at home may be considered for patients who are tolerating their infusions well and have no history of moderate or severe IARs for a few months. The decision to have a patient move to home infusion should be made after evaluation and upon recommendation by the treating physician. A patient’s underlying co-morbidities and ability to adhere to the home infusion requirements need to be taken into account when evaluating the patient for eligibility to receive home infusion. The following criteria should be considered:

• The patient must have no ongoing concurrent condition that, in the opinion of the physician, may affect patient’s ability to tolerate the infusion.
• The patient is considered medically stable. A comprehensive evaluation must be completed before the initiation of home infusion.
• The patient must have received Nexviadyme infusions supervised by a physician with expertise in management of Pompe patients for a few months that could be in a hospital or in another appropriate setting of outpatient care. Documentation of a pattern of well-tolerated infusions with no IARs, or mild IARs that have been controlled with premedication, is a prerequisite for the initiation of home infusion.
• The patient must be willing and able to comply with home infusion procedures.
• Home infusion infrastructure, resources, and procedures, including training, must be established and available to the healthcare professional. The healthcare professional should be available at all times during the home infusion and a specified time after infusion, depending on patient’s tolerance prior to starting home infusion.

If the patient experiences adverse reactions during the home infusion, the infusion process should be stopped immediately, and appropriate medical treatment should be initiated (see section 4.4). Subsequent infusions may need to occur in a hospital or in an appropriate setting of outpatient care until no such adverse reaction is present. Dose and infusion rate must not be changed without consulting the responsible physician.

For instructions on reconstitution and dilution of medicinal product before administration, see section 6.6.

Excessive infusion rate of Nexviadyme may result in hot flush. In a clinical study, paediatric patients received doses up to 40 mg/kg of body weight once every 2 weeks and no specific signs and symptoms were identifies following the higher doses. For management of adverse reactions, see sections 4.4 and 4.8.

Unopened vials: 4 years.

Reconstituted medicinal product

After reconstitution, chemical, physical, and microbiological in-use stability has been demonstrated for 24 hours at 2°C-8°C. From a microbiological point of view, the reconstituted product should be used immediately. If not used for dilution immediately, in-use storage times and conditions prior to dilution are the responsibility of the user and would normally not be longer than 24 hours at 2°C-8°C.

Diluted medicinal product

After dilution, chemical, physical and microbiological in-use stability has been demonstrated between 0.5 mg/ml and 4 mg/ml for 24 hours at 2°C-8°C, followed by 9 hours at room temperature (up to 25°C) to allow for infusion. Use Aseptic Techniques.

From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2°C-8°C, followed by 9 hours at room temperature (up to 25°C) to allow for infusion.

Store in a refrigerator (2°C-8°C).

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

100 mg of powder for concentrate for solution for infusion in a vial (type I glass) with a stopper (elastomeric rubber), seal (aluminium) and a flip off cap.

Each pack contains 1, 5, 10, or 25 vials.

Not all pack sizes may be marketed.

Vials are for single use only.

Reconstitution:

Aseptic technique should be used during reconstitution.

1. The number of vials have to be determined to be reconstituted based on individual patient’s weight and the recommended dose of 20 mg/kg or 40 mg/kg. Patient weight (kg) × dose (mg/kg) = patient dose (in mg). Patient dose (in mg) divided by 100 mg/vial = number of vials to reconstitute. If the number of vials includes a fraction, it should be rounded up to the next whole number. Example: Patient weight (16 kg) × dose (20 mg/kg) = patient dose (320 mg). 320 mg divided by 100 mg/vial = 3.2 vials; therefore, 4 vials should be reconstituted. Example: Patient weight (16 kg) × dose (40 mg/kg) = patient dose (640 mg). 640 mg divided by 100 mg/vial = 6.4 vials; therefore, 7 vials should be reconstituted.

2. The required number of vials needed for the infusion should be removed from the refrigerator and set aside for approximately 30 minutes to allow them to reach room temperature.

3. Each vial should be reconstituted by slowly injecting 10.0 ml of water for injections (WFI) to each vial. Each vial will yield 100 mg/10 ml (10 mg/ml). Forceful impact of the WFI on the powder and foaming should be avoided. This is performed by slow drop-wise addition of the WFI down the inside of the vial and not directly onto the lyophilised powder. Each vial should be tilted and rolled gently to dissolve the lyophilised powder. It should not be inverted, swirled, or shaken.

4. Immediate visual inspection should be performed on the reconstituted vials for particulate matter and discoloration. If upon immediate inspection particles are observed or if the solution is discoloured, the reconstituted medicinal product should not be used. The solution should be allowed to become dissolved.

Dilution:

5. The reconstituted solution should be diluted in 5% glucose in water to a final concentration of 0.5 mg/ml to 4 mg/ml. See Table 6 for the recommended total infusion volume based on the patient weight.

6. The volume of reconstituted solution from each vial should be slowly withdrawn (calculated according to patient’s weight).

7. The reconstituted solution should be added slowly and directly into the 5% glucose solution. Foaming or agitation of the infusion bag should be avoided. Air introduction into the infusion bag should be avoided.

8. To mix the infusion bag solution, gently invert or massage the infusion bag to mix. It should not be shaken.

9. To avoid administration of inadvertently introduced particles during dose IV preparation, it is recommended to use an in-line, low protein binding, 0.2 μm filter to administer Nexviadyme. After the infusion is complete, the intravenous line should be flushed with glucose 5% in water.

10. Nexviadyme should not be infused in the same intravenous line with other medicinal products.

Table 6. Projected intravenous infusion volumes for Nexviadyme administration by patient weight at 20 and 40 mg/kg Dose:

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