Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: CSL Behring GmbH, Emil-von-Behring-Strasse 76, D-35041 Marburg, Germany
Replacement therapy in adults, children and adolescents (0-18 years) in:
* PSAF = failure to mount at least a 2-fold rise in IgG antibody titre to pneumococcal polysaccharide and polypeptide antigen vaccines.
Immunomodulatory therapy in adults, children and adolescents (0-18 years):
The dose and dose regimen are dependent on the indication.
Therapy should be initiated and monitored under the supervision of a healthcare professional experienced in the treatment of immunodeficiency/CIDP with SCIg.
The medicinal product should be administered via the subcutaneous route.
In replacement therapy the dose may need to be individualised for each patient dependent on the clinical response and serum IgG trough levels. The following dose regimens are given as a guideline.
The dose regimen should achieve a trough level of IgG (measured before the next infusion) of at least 5 to 6 g/l and aim to be within the reference interval of serum IgG for age. A loading dose of at least 0.2 to 0.5 g/kg (1.0 to 2.5 ml/kg) body weight may be required. This may need to be divided over several days. After steady state IgG levels have been attained, maintenance doses are administered at repeated intervals to reach a cumulative monthly dose of the order of 0.4 to 0.8 g/kg (2.0 to 4.0 ml/kg) body weight. Each single dose may need to be injected at different anatomic sites.
Trough levels should be measured and assessed in conjunction with the patient’s clinical response. Depending on the clinical response (e.g. infection rate), adjustment of the dose and/or the dose interval may be considered in order to aim for higher trough levels.
The therapy with Hizentra is initiated 1 week after the last IVIg infusion. The recommended subcutaneous dose is 0.2 to 0.4 g/kg body weight per week administered in 1 or 2 sessions over 1 or 2 consecutive days. The initial subcutaneous dose may be a 1:1 conversion from the previous IVIG dose (calculated as weekly dose).
Example a 1g/kg IVIG dose given every 3 weeks would convert into a 0.33g/kg weekly Hizentra dose. The weekly dose can be divided into smaller doses and administered by desired number of times per week. For dosing every two weeks, double the weekly Hizentra dose.
The dose may need to be adapted to achieve the desired clinical response. Patient’s individual clinical response should be the primary consideration in dose adjustment. In case of clinical deterioration the dose may be increased to the recommended maximum of 0.4g/kg weekly dose.
Hizentra maintenance therapy in CIDP has not been studied for periods longer than 18 months. Individualize the duration of any treatment beyond 18 months based upon the patient’s response and demonstrated need for continued therapy.
Efficacy of Hizentra has been demonstrated over placebo after switching from intravenous immunoglobulins (IVIG). Direct comparative data for Hizentra versus IVIG are not available. Please refer also to section 5.1.
The posology in children and adolescents (0-18 years) is not different to that of adults as the posology for each indication is given by body weight and adjusted to the clinical outcome in replacement therapy indications.
Hizentra was evaluated in 68 paediatric subjects with PID aged 2 to <12 years and in 57 adolescents aged 12 to <18 years. No paediatric-specific dose requirements were necessary to achieve the desired serum IgG levels. Hizentra has not been evaluated in clinical studies in paediatric patients with CIDP who are under the age of 18.
As the dose is given by body weight and adjusted to the clinical outcome of the above mentioned conditions, the dose in elderly is not considered to be different from that in subjects 18 to 65 years of age.
In clinical studies Hizentra was evaluated in 13 subjects with PID >65 years of age and no specific dose adjustments were necessary to achieve the desired serum IgG levels.
In clinical studies Hizentra was evaluated in 61 subjects with CIDP >65 years of age and no specific dose adjustments were necessary to achieve the desired clinical outcome.
For subcutaneous use only.
Subcutaneous infusion for home treatment must be initiated and monitored by a healthcare professional experienced in the guidance of patients for home treatment. The healthcare professional must select the appropriate way of infusion (device-assisted or manual push infusion), based on patient’s individual medical situation and preferences. Infusion devices appropriate for subcutaneous administration of immunoglobulins can be used. The patient or a caregiver must be instructed and trained in the use of infusion devices, the keeping of treatment diary, recognition of and measures to be taken in case of severe adverse reactions.
Hizentra may be infused into sites such as abdomen, thigh, upper arm, and/or lateral hip. More than one infusion device can be used simultaneously. The amount of product infused into a particular site may vary. In infants and children, infusion site may be changed every 5-15 ml. In adults doses may be given up to 50 ml/site. There is no limit to the number of infusion sites. Infusion sites should be at least 5 cm apart.
Hizentra can be infused using:
The recommended initial infusion rate depends on the individual patient’s needs.
The initial infusion rate should not exceed 20 ml/hour/site.
If well-tolerated (see also section 4.4), the infusion rate can then gradually be increased to 35 ml/hour/site for the subsequent two infusions. Thereafter, if the patient tolerates the initial infusions at the full dose per site and maximum rate, an increase in the infusion rate of successive infusions may be considered at the discretion of the patient and based on the healthcare professionals' judgement.
The recommended initial infusion rate should not exceed 0.5 ml/min/site (30 ml/hour/site). If well-tolerated (see also section 4.4), the infusion rate can be increased up to 2.0 ml/min/site (120 ml/hour/site). Thereafter, if the patient tolerates the initial infusions at the full dose per site and maximum rate, an increase in the infusion rate of successive infusions may be considered at the discretion of the patient and based on the healthcare professionals' judgement.
A 24 or larger (i.e. lower gauge number) needle gauge may be required to allow patients to infuse at higher flow rates. Using smaller needles (i.e. higher gauge number) may make it more difficult to manually push Hizentra. Only one infusion site per syringe can be infused. If administration with an additional Hizentra syringe is required, a new sterile injection needle should be used and the infusion site changed.
Consequences of an overdose are not known.
30 months.
Once a vial or the blistered pre-filled syringe has been opened, the solution should be used immediately.
Do not store above 25°C.
Do not freeze.
Keep the vial or the blistered pre-filled syringe in the outer carton in order to protect from light.
For storage conditions after first opening of the medicinal product, see section 6.3.
5, 10 or 20 ml of solution in a vial (type I glass) and 50 ml of solution in a vial (type II glass), with a stopper (halobutyl), a cap (aluminium crimp) and a flip off disc (plastic).
Pack sizes of 1, 10 or 20 vials:
1 g / 5 ml
2 g / 10 ml
4 g / 20 ml
10 g / 50 ml
5, 10 or 20 ml of solution in a pre-filled syringe (cyclo-olefin-copolymer (COC)) blistered with an oxygen absorber pack.
Pack sizes of 1 or 10 pre-filled syringes:
1 g / 5 ml
2 g / 10 ml
4 g / 20 ml
Alcohol swabs, needles and other supplies or equipment are not contained in the pack.
Not all pack sizes may be marketed.
Hizentra comes as a ready-to-use solution in single-use vials or single-use pre-filled syringes. Because the solution contains no preservative, Hizentra should be used/infused as soon as possible after opening the vial or blistered pre-filled syringe.
The medicinal product should be brought to room or body temperature before use.
The solution should be clear and pale-yellow or light-brown. Solutions that are cloudy or have deposits should not be used.
Any unused medicinal product, waste material and the oxygen absorber pack should be disposed of in accordance with local requirements.
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