SEPHIENCE Oral powder Ref.[115495] Active ingredients: Sepiapterin

Treatment with Sephience must be initiated and supervised by a physician experienced in the treatment of PKU.

Posology

The recommended dose (mg/kg/day) of Sephience to be administered orally once daily is based on age and body weight (see Table 1). The maximum recommended dose is 60 mg/kg/day. The recommended dose of Sephience in patients ≥2 years of age is 60 mg/kg/day. However, the dose may be adjusted to a lower dose if the treating physician considers it necessary or appropriate.

Table 1. Recommended dose based on patient's age and body weight:

Tables 2 to 5 below provide dosing information by age group for patients weighing 16 kg or less at different doses (7.5, 15, 30, and 60 mg/kg/day).

Table 2. Recommended dose of Sephience oral powder in sachet by body weight in paediatric patients aged less than 6 months:

Table 3. Recommended dose of Sephience oral powder in sachet by body weight in paediatric patients aged 6 months to less than 12 months:

Table 4. Recommended dose of Sephience oral powder in sachet by body weight in paediatric patients aged 12 months to less than 2 years:

Table 5. Recommended dose of Sephience oral powder in sachet by body weight in paediatric patients aged 2 years and older:

^* Instead of four 250 mg sachets, one full 1 000 mg sachet can be mixed with 36 mL of water or apple juice. This mixture should be administered with a syringe, according to the administered dose volume detailed in Table 5.

Recommended dose of Sephience oral powder in sachet by body weight for patients 2 years and older and weighing 16 kg or more

The recommended dose is 60 mg/kg/day.

For maintenance doses greater than or equal to 1 000 mg, the calculated daily dose should be rounded to the nearest multiple of 250 mg or 1 000 mg, as appropriate. For instance, a calculated dose of 1 251 to 1 374 mg should be rounded down to 1 250 mg corresponding to 1×250 mg sachet and 1×1 000 mg sachet. A calculated dose of 1 375 to 1 499 mg should be rounded up to 1 500 mg corresponding to 2×250 mg sachets and 1×1000 mg.

Missed dose

A missed dose should be taken as soon as possible. The normal dosing schedule should be resumed the following day.

Discontinuation of treatment

In the pivotal Phase 3 clinical study, a threshold of 15% or greater reduction in blood phenylalanine (Phe) levels was utilised for determination of response.

No controlled efficacy and safety data are available in patients who do not experience a reduction of 15% or greater reduction in blood Phe levels after receiving sepiapterin for 14 days.

The determination of responsiveness for a patient with PKU and the discontinuation of the medicinal product is at the discretion of the treating physician.

Special populations

Elderly

The safety and efficacy of Sephience in patients 65 years of age and older have not been established. Caution should be exercised when prescribing in patients 65 years of age and older.

Renal impairment

The safety and efficacy of Sephience in patients with renal impairment have not yet been established. No data are available (see section 5.2).

Hepatic impairment

The safety and efficacy of Sephience in patients with hepatic impairment have not yet been established. No data are available (see section 5.2).

Paediatric population

In the Phase 3 clinical studies of Sephience, some paediatric patients experienced hypophenylalaninaemia including some patients with multiple low blood Phe levels (see section 4.8).

Method of administration

Oral use.

Sephience should be administered once daily with a meal, using mg/kg dosing.

Sephience oral powder comes in individual sachets of 250 mg or 1 000 mg and should be mixed in water, apple juice, or a small amount of soft food such as apple sauce and jams.

Sephience is intended for long-term use.

Patients weighing less than 16 kg

Sephience should be mixed with water or apple juice (9 mL for each 250 mg sachet; 36 mL for each 1 000 mg sachet), and a portion of this mixture corresponding to a required dose should be administered orally via an oral dosing syringe. The preparation should be mixed well for at least 30 seconds until uniform and free of lumps, before drawing into the dosing syringe. Once mixed, the dose should be administered immediately. If not administered immediately, the liquid mixture can be administered within 6 hours or 24 hours, when stored at room temperature (below 25°C) or in a refrigerator (2°C-8°C), respectively. The preparation should be mixed once again for at least 30 seconds, before administration. The syringe should be rinsed with additional water or juice (at least 15 mL) to remove any residual and swallowed immediately.

Patients weighing 16 kg or more

Sephience should be mixed with water or apple juice (9 mL for each 250 mg sachet; 20 mL for each 1 000 mg sachet) or soft foods (2 tablespoons total). The preparation should be mixed well for at least 30 seconds with water or apple juice and for at least 60 seconds with soft foods until uniform and free of lumps. Once mixed, administer the dose immediately. If not administered immediately, the liquid and soft food mixtures can be administered within 6 hours or 24 hours when stored at room temperature (below 25°C) or in a refrigerator (2°C-8°C), respectively. The liquid mixture and soft food mixtures should be mixed once again for at least 30 seconds and 60 seconds, respectively, before administration. The container should be rinsed with additional water or juice (at least 15 mL) to remove any residual and swallowed immediately.

Administration via enteral feeding tube:

Sephience oral powder may be administered via an enteral feeding tube 6 Fr or 8 Fr after mixing with water. The manufacturer's instructions for the feeding tube should be followed prior to administering the medicinal product. For instructions on preparation of Sephience before administration, see section 6.6.

No specific antidote is available for overdose with Sephience. Treatment of overdose with Sephience should consist of supportive medical care including monitoring of vital signs and observation of the clinical status of the patient.

2 years.

After reconstitution:

Each dose should be administered immediately after reconstitution. The reconstituted solution should be discarded if not used within 24 hours when stored in a refrigerator (2°C-8°C) or within 6 hours below 25°C.

This medicinal product does not require any special temperature storage conditions.

Store in the original package in order to protect from light.

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

Heat-sealed laminated aluminium foil sachet: Polyethylene terephthalate, white extruded polyethylene (polyester/foil bond), aluminium foil (moisture barrier), and heat-sealed ionomeric resin (adhesive).

Each carton contains 30 unit-dose sachets.

No special requirements for disposal.

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

Instructions for administration via enteral feeding tube:

1) Ensure that the enteral feeding tube (size 6 Fr or 8 Fr) is free from obstruction before administration.

2) Flush the enteral feeding tube with 10 mL of water.

3) Administer the required dose of Sephience oral powder within 30 minutes of mixing (see section 4.2).

4) Flush the enteral feeding tube with at least 5 mL (6 Fr tube) or 15 mL (8 Fr tube) of water and administer the flush.

This medicinal product is compatible for use with silicone and polyurethane enteral feeding tube.