Posology : מינונים

4.2        Posology and method of administration

Treatment with vosoritide should be initiated and directed by a physician appropriately qualified in the management of growth disorders or skeletal dysplasias.

Posology

Voxzogo is given as a daily subcutaneous injection. The recommended dose is based on the patient's weight and is approximately between 15-30 µg/kg, where the higher dose is given to smallest children, see Table 1.

The dose can be administered using either mL graduated syringes or Unit (U) graduated syringes (see Table 1). The measurements for the Unit graduated syringes are equivalent to mL as follows: 0.1 mL = 10 Units. For practicality reasons and to account for weight-related PK changes (see section 5.2), the following dosing is recommended.

Table 1: Single dose volumes by body weight in mL and Units (U) volumes 
Body            Dose        Vosoritide 0.4 mg         Vosoritide 0.56 mg       Vosoritide 1.2 mg weight
(mg)        solvent (water for         solvent (water for       solvent (water for (kg)                   injections): 0.5 mL        injections): 0.7 mL      injections): 0.6 mL concentration:             concentration:           concentration:
0.8 mg/mL                  0.8 mg/mL                2 mg/mL

Daily injection volume
 mL          Units          mL           Units       mL          Units 
4         0.12 mg    0.15 mL       15 U

5         0.16 mg    0.20 mL       20 U
6-7        0.20 mg    0.25 mL       25 U

8-11       0.24 mg    0.30 mL       30 U

12-16          0.28 mg                               0.35 mL        35 U 
17-21          0.32 mg                               0.40 mL        40 U 
22-32          0.40 mg                               0.50 mL        50 U

33-43          0.50 mg                                                        0.25 mL       25 U 
44-59          0.60 mg                                                        0.30 mL       30 U

60-89          0.70 mg                                                        0.35 mL       35 U 
≥ 90       0.80 mg                                                        0.40 mL       40 U 
Duration of treatment
Treatment with this medicinal product should be stopped upon confirmation of no further growth potential, indicated by a growth velocity of < 1.5 cm/year and closure of epiphyses.

Missed dose
If a dose of vosoritide is missed, it can be administered within 12 hours. If more than 12 hours have passed since the original dosing schedule, the missed dose should NOT be administered.
Patients/caregivers should be advised to continue with the next scheduled dose the following day.

Growth monitoring
Patients should be monitored and assessed regularly every 3-6 months to check body weight, growth and physical development. Dose should be adjusted according to the patient’s body weight (see Table 1).

Special populations

Patients with renal or hepatic impairment
The safety and efficacy of vosoritide in patients with renal or hepatic impairment has not been evaluated.

Paediatric population
The safety and efficacy of Voxzogo in children less than 4 months of age is limited. Currently available data are described in sections 4.8, 5.1 and 5.2, but no recommendation on a posology can be made.

Method of administration

Voxzogo is for subcutaneous single use only. This medicinal product must be administered within 3 hours of reconstitution, see section 6.3.

Prior to injecting, a healthcare professional should:
•      train caregivers on the preparation and subcutaneous injection of this medicinal product.
•      train caregivers and patients to recognise signs and symptoms of decreased blood pressure.
•      inform caregivers and patients what to do in the event of symptomatic decreases in blood pressure.

Patients and caregivers should be instructed to rotate sites for subcutaneous injections. Recommended injection sites on the body include the front middle of the thighs, the lower part of the abdomen except for 5 cm directly around the navel, top of the buttocks or the back of the upper arms. The same injection area should not be used on two consecutive days. Voxzogo should not be injected into sites that are red, swollen, or tender.

Patients should be well hydrated at the time of injection. It is recommended patients eat a light snack and drink an adequate amount of fluid (e.g., water, milk, juice, etc.) about 30 minutes before injecting.
This is to reduce the signs and symptoms of potential decreases in blood pressure (dizziness, fatigue and/or nausea) (see section 4.4, Blood pressure effects).

If possible, this medicinal product should be injected at approximately the same time each day.

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