Posology : מינונים

4.2      Posology and method of administration

Therapy should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency.

The medicinal product should be administered via the subcutaneous (SC) route. The dose and dose regimen are dependent on the indication.

The dose may need to be individualized for each patient dependent on the pharmacokinetic (PK) and clinical response. Dose based on bodyweight may require adjustment in underweight or overweight patients. The following dose regimens are given as a guideline.

Posology

Replacement therapy
Patients naïve to immunoglobulin therapyThe dose required to achieve a trough level of 6 g/L is of the order of 0.4 to 0.8 g/kg body weight per month. The dose interval to maintain steady-state levels varies from 2-to-4 weeks.

IgG trough levels should be measured and assessed in conjunction with the incidence of infection.
To reduce the rate of infection, it may be necessary to increase the dose and aim for higher IgG trough levels (> 6 g/L).
At the initiation of therapy, it is recommended that the treatment intervals for the first infusions be gradually prolonged from a 1-week dose to up to a 3-or 4-week dose. The cumulative monthly dose of IG 10% should be divided into 1-week, 2-week etc. doses according to the planned treatment intervals with HyQvia.

Patients previously treated with Intravenous immunoglobulin (IVIg)
For patients switching directly from IVIg, or who have a previous IVIg dose that can be referenced, the medicinal product should be administered at the same dose and at the same frequency as their previous IVIg treatment. If patients were previously on a 3-week dosing regimen, increasing the interval to 4-weeks can be accomplished by administering the same weekly equivalents.

Patients previously treated with subcutaneous immunoglobulin (SCIg)

The initial dose of the medicinal product is the same as for SCIg treatment but may be adjusted to 3-or 4-weeks interval. The first infusion should be given one week after the last treatment with the previous immunoglobulin.

Paediatric population

Replacement therapy
The dosing schedule for children and adolescents (0 to 18 years) is the same as for adults. The dosing is based on body weight and adjusted to the clinical outcome. Currently, available data are described in sections 4.8, 5.1 and 5.2.

Method of administration

The medicinal product is for subcutaneous use only, do not administer intravenously.
Each vial of IG 10% is supplied with the appropriate corresponding quantity of rHuPH20 (see section 6.5). The full contents of the rHuPH20 vial should be administered regardless of whether the full content of the IG 10% vial is administered.

The 2 components of the medicinal product must be administered sequentially through the same subcutaneous needle beginning with the rHuPH20 followed by IG 10%.

Example: Patient is prescribed 110 grams (g) of HyQvia: This will require 3 vials of 30 g and 1 vial of 20 g for the total dose of 110 g/1100 mL of the IG 10% component of HyQvia. The volume of rHuPH20 will be (3 x 15 mL + 1 x10 mL) = 55 mL. If the dose is greater than 120 g, HyQvia may be administered over multiple days in divided doses with 48-to 72-hours between doses to allow absorption of infusion fluid at the infusion site(s).

Infusion site leakage can occur during or after subcutaneous administration of immunoglobulin, including HyQvia. Consider using longer needles (12 mm or 14 mm) and/or more than one infusion site. Any change of needle size would have to be supervised by the treating physician.

Home-treatment

In case subcutaneous infusion of HyQvia is used for home treatment, therapy should be initiated and monitored by a physician experienced in the guidance of patients for home treatment. The patient or a caregiver must be instructed in infusion techniques, the use of an infusion pump or syringe driver, the keeping of a treatment diary, recognition of possible severe adverse reactions and measures to be taken in case these occur.

HyQvia can be administered in a full therapeutic dose at up to 3 infusion sites up to every 4-weeks.
Adjust the frequency and number of infusion sites, considering volume, total infusion time, and tolerability so that the patient receives the same weekly equivalent dose. If a patient misses a dose, administer the missed dose as soon as possible and then resume scheduled treatments as applicable.

Device-assisted infusion

The IG 10% component should be infused using a pump. The rHuPH20 may be hand-pushed or infused by a pump. A 24-gauge needle may be required to allow patients to infuse at flow rates of 300 mL/hr/infusion site. However, needles with smaller diameters may be used if slower flow rates are acceptable. For the 1.25 mL rHuPH20 vial size use an 18-to 22-gauge needle to withdraw the contents of the vial to prevent stopper push through or coring; for all other vial sizes a needle or needle-less device may be used to withdraw the contents of the vial.

Infusion site

The suggested site(s) for the infusion of the medicinal product are the middle to upper abdomen and thighs. If 2 sites are used, the 2 infusion sites should be on contra lateral sides of the body. If using three infusion sites, the sites should be at least 10 cm apart. Avoid bony prominences, or scarred areas.
The product should not be infused at or around an infected or acutely inflamed area due to the potential risk of spreading a localized infection. Avoid at least 5 cm away from the umbilicus.

Infusion rate

It is recommended that the rHuPH20 component be administered at a constant rate and that the rate of administration of the IG 10% should not be increased above the recommended rates, particularly when the patient has just started with HyQvia therapy.

First, the full dose of rHuPH20 solution is infused at a rate of 1 to 2 mL/minute (or 60 mL/hr to 120 mL/hr) per infusion site or as tolerated. Within 10 minutes of the rHuPH20, start the infusion of the full dose per site of IG 10% through the same subcutaneous needle set.

The following infusion rates of the IG 10% are recommended per infusion site.

Table 1 : The recommended infusion rates of the IG 10% per infusion site 
Subjects < 40 kg                                Subjects ≥ 40 kg
Subsequent                                   Subsequent
First 2 infusions                              First 2 infusions
Interval/                                2 to 3 infusions                             2 to 3 infusions (mL/hour/infusion                              (mL/hour/infusion
Minutes                                (mL/hour/infusion                             (mL/hour/infusion site)                                          site) site)                                         site)
10 minutes                   5                       10                         10                10 10 minutes                   10                      20                         30                30 10 minutes                   20                      40                         60               120 10 minutes                   40                      80                        120               240 Remainder
80                     160                        240                300 of infusion

If the patient tolerates the initial infusions at the full dose per site and maximum rate, an increase in the rate of successive infusions may be considered at the discretion of the physician and the patient.

For instructions on the handling and preparation of the medicinal product before administration, see section 6.6.