Posology : מינונים

4.2   Posology and method of administration

Treatment with Evrysdi should be initiated by a physician with experience in the management of SMA.

Posology

The recommended once daily dose of Evrysdi is determined by age and body weight (see Table 1).
Evrysdi is taken orally once a day after a meal at approximately the same time each day.


Table 1. Dosing regimen by age and body weight

Age and body weight                           Recommended daily dose
< 2 months of age                                 0.15 mg/kg
2 months to < 2 years of age                          0.20 mg/kg
≥ 2 years of age (< 20 kg)                            0.25 mg/kg
≥ 2 years of age (≥ 20 kg)                               5 mg

Treatment with a daily dose above 5 mg has not been studied.
Delayed or missed doses
If a planned dose is missed, it should be administered as soon as possible if still within 6 hours of the scheduled dose. Otherwise, the missed dose should be skipped and the next dose should be administered at the regularly scheduled time the next day.

If a dose is not fully swallowed or vomiting occurs after taking a dose of Evrysdi, another dose should not be administered to make up for the incomplete dose. The next dose should be administered at the regularly scheduled time.

Elderly
No dose adjustment is required in elderly patients based on limited data in subjects aged 65 years and older (see section 5.2).

Renal impairment
Risdiplam has not been studied in this population. No dose adjustment is expected to be required in patients with renal impairment (see section 5.2).

Hepatic impairment
No dose adjustment is required in patients with mild or moderate hepatic impairment. Patients with severe hepatic impairment have not been studied and may have increased risdiplam exposure (see sections 5.1 and 5.2).

Paediatric population

Use of Evrysdi for SMA in patients 2 months of age and younger is supported by pharmacokinetic and safety data from paediatric patients 16 days and older (see sections 4.8, 5.1 and 5.2), and pharmacokinetic modeling and simulation to identify the dosing regimen. No data on risdiplam pharmacokinetics are available in patients less than 16 days of age


Method of administration
Oral use.

Evrysdi must be constituted by a healthcare professional (e.g. pharmacist) prior to being dispensed.
It is recommended that a healthcare professional (HCP) discuss with the patient or caregiver how to prepare the prescribed daily dose prior to administration of the first dose.

Evrysdi is taken orally once a day after a meal at approximately the same time each day, using the re- usable oral syringe provided. In infants who are breastfed, Evrysdi should be administered after breastfeeding. Evrysdi should not be mixed with milk or formula milk.

Evrysdi should be taken immediately after it is drawn up into the oral syringe. If it is not taken within 5 minutes, it should be discarded from the oral syringe and a new dose be prepared. If Evrysdi spills or gets on the skin, the area should be washed with soap and water.
The patient should drink water after taking Evrysdi to ensure the medicinal product has been completely swallowed. If the patient is unable to swallow and has a nasogastric or gastrostomy tube in situ, Evrysdi can be administered via the tube. The tube should be flushed with water after delivering Evrysdi.

Selection of the oral syringe for the prescribed daily dose:

Syringe size             Dosing volume                 Syringe markings 1 mL                     0.3 mL to 1 mL                0.01 mL
6 mL                     1 mL to 6 mL                  0.1 mL
12 mL                    6.2 mL to 6.6 mL              0.2 mL


For the calculation of dosing volume, the syringe markings need to be considered. The dose volume should be rounded to the nearest graduation mark on the selected oral syringe.