NULIBRY Powder for solution for injection Ref.[50216] Active ingredients: Fosdenopterin

NULIBRY is to be administered only if the patient has a confirmed genetic diagnosis or presumptive diagnosis of MoCD Type A.

Patients with a presumptive diagnosis of MoCD Type A need to have a genetic test to confirm the diagnosis of MoCD Type A. NULIBRY must be discontinued if the MoCD Type A diagnosis is not confirmed by genetic testing.

Treatment with NULIBRY is to be initiated and supervised in hospital by a healthcare professional experienced in the management of inborn errors of metabolism. NULIBRY is a chronic substrate replacement therapy intended for long-term use.

Posology

Paediatric population less than 1 year of age (by gestational age)

In patients less than one year of age, the recommended dose of NULIBRY is titrated based on gestational age.

For patients less than 1 year of age who are preterm neonates (gestational age <37 weeks), the recommended starting dose of NULIBRY is 0.40 mg/kg/day administered intravenously once daily. The dose is to be titrated to the target dose of 0.90 mg/kg/day over a period of 3 months as shown in Table 1.

For patients less than 1 year of age who are term neonates (gestational age ≥37 weeks), the recommended starting dose of NULIBRY is 0.55 mg/kg/day administered intravenously once daily. The dose is to be titrated to the target dose of 0.90 mg/kg/day over a period of 3 months as shown in Table 1.

Table 1. Starting dose and titration schedule of NULIBRY for patients less than one year of age by gestational age:

Paediatric population from 1 year to less than 18 years of age and adults

The recommended dose of NULIBRY is 0.90 mg/kg (based on actual body weight) administered intravenously once daily.

Missed dose

If a dose is missed, the missed dose is to be administered as soon as possible. The next scheduled dose must be given at least 6 hours after the administration of the missed dose.

Method of administration

NULIBRY is for intravenous use only.

NULIBRY is intended for administration at an infusion rate of 1.5 mL/min after reconstitution with 5 mL of sterile water for injection. Dose volumes below 2 mL may require syringe administration by slow intravenous push.

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

If deemed appropriate by a healthcare professional, NULIBRY may be administered at home by the patient’s caregiver. If NULIBRY is administered by a caregiver/patient, the caregiver/patient must read and follow carefully the detailed “Instructions for the user” on the preparation, administration, storage, and disposal of NULIBRY provided in the carton.

The healthcare professional should calculate and provide the volume of NULIBRY in millilitres (mL) and the number of vials needed for each dose to the caregiver/patient, see section 6.6.

The maximum tolerated dose of NULIBRY has not been established, and there is no known antidote for fosdenopterin. In the event a patient receives a dose of NULIBRY greater than the intended dose, frequent monitoring of vital signs and clinical status is recommended for a minimum of 8 hours after dosing.

Unopened vial:

2 years.

After reconstitution:

Reconstituted NULIBRY may be stored at room temperature (15°C to 25°C) or refrigerated (2°C to 8°C) for up to 4 hours including infusion time. Do not freeze NULIBRY after reconstitution. Do not shake.

Chemical and physical in-use stability has been demonstrated for 4 hours at 2°C to 8°C or 15°C to 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the us would normally not be longer than the above mentioned conditions when reconstitution has taken place in controlled and validated aseptic conditions.

Unopened vial:

Store in a freezer at -25°C to -10°C.

Keep the vial in the outer carton in order to protect from light.

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

10 mL type I clear glass vial with an aluminium seal and butyl rubber stopper.

Pack size of 1 vial.

Each vial is intended for single use only and the excess of unused product must be properly disposed. Sterile water for injection, syringes, needle tips, and alcohol wipes are to be provided to the patient.

Reconstitution

NULIBRY must be reconstituted with 5 mL of sterile water for injections prior to use. Reconstituted NULIBRY must not be shaken nor heated. Aseptic technique is to be used during preparation and these instructions are to be followed:

1. The total dose, number of vials needed, and total reconstituted dose volume based on the patient’s weight and prescribed dose must be determined. Dose volumes can range from 0.4 mL for a 2 kg preterm neonate (0.40 mg/kg/day) to 23.7 mL for a 50 kg adult (0.90 mg/kg/day). See section 4.2. Number of vials to be reconstituted is determined by patient’s dose divided by 9.5 mg/vial (content of one vial). If the number of calculated vials includes a fraction, it should be rounded up to the next whole number.

2. The required number of vials is to be removed from the freezer to allow them to reach room temperature (by rolling each vial gently between your hands for 3 to 5 minutes (do not shake) or by leaving it at room temperature for approximately 30 minutes).

3. Each required NULIBRY vial must be reconstituted with 5 mL of sterile water for injections. Each vial is reconstituted by slowly injecting 5 mL of water for injections to the inside of the wall of each vial. The vial must be gently and continuously swirled until the powder is completely dissolved. The vial must not be shaken. After reconstitution, the final concentration of NULIBRY reconstituted solution is 9.5 mg/5 mL (1.9 mg/mL). Only the volume corresponding to the recommended dose should be administered.

4. Reconstituted NULIBRY is a clear and colourless to pale yellow solution. NULIBRY is to be visually inspected for particulate matter and discoloration prior to administration. NULIBRY must not be used if there are particles present or if the solution is discoloured.

5. The total reconstituted dose is to be administered.

If reconstituted NULIBRY is refrigerated, allow it to come to room temperature before administration by rolling each vial gently between your hands 3 to 5 minutes (do not shake) or by leaving it at room temperature for approximately 30 minutes.

Administration

NULIBRY is intended for administration by a healthcare professional. If deemed appropriate by a healthcare professional, NULIBRY may be administered at home by the patient’s caregiver (see section 4.2). If NULIBRY can be administered by a caregiver/patient, caregiver/patient must read the detailed instructions on the preparation, administration, storage, and disposal of NULIBRY.

NULIBRY is for intravenous use only. NULIBRY must be administered with di(2-ethylhexyl)phthalate (DEHP)-free tubing with a 0.2 micron filter. NULIBRY must not be mixed with other medicinal products (note NULIBRY is reconstituted with sterile water for injections). NULIBRY must not be administered as an infusion with other medicinal products.

NULIBRY is given through a syringe pump at a rate of 1.5 mL per minute.

Dose volumes below 2 mL may require syringe administration through slow intravenous push.

Administration of NULIBRY must be completed within 4 hours of reconstitution.

Disposal of medicinal product and auxiliary components

Any unused medicinal product or waste material including materials used for reconstitution and administration should be disposed of in accordance with local requirements.