HIZENTRA SOLUTION FOR SUBCUTANEOUS INJECTION 200G/L [SIN15499P]

Product Info

HIZENTRA SOLUTION FOR SUBCUTANEOUS INJECTION 200G/L

[SIN15499P]

4.1 Therapeutic indications

Replacement therapy in adults and children in primary immunodeficiency syndromes such as:

• congenital agammaglobulinaemia and hypogammaglobulinaemia

• common variable immunodeficiency

• severe combined immunodeficiency and Wiskott-Aldrich syndrome

• IgG subclass deficiencies with recurrent infections

Replacement therapy in myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections.

Immunomodulatory therapy in adults:

• Hizentra is indicated for the treatment of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy after stabilization with IVIg.

4.2 Posology and method of administration

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.

Posology
Adults and children

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 using the subcutaneous route should achieve a sustained level of IgG. 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 divided into smaller doses and 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.

For patients switching from intravenous treatment the monthly dose is divided into smaller doses and administered at repeated intervals (see section “Pharmacokinetic properties” – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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.

Immunomodulatory therapy in CIDP
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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Paediatric population

The posology in children and adolescents 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.

Elderly population
As the dose is given by body weight and adjusted to the clinical outcome of the above mentioned conditions, the dose in the elderly population 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.

Method of administration

For subcutaneous use only.

Home-treatment
Subcutaneous infusion for home treatment must be initiated and monitored by a healthcare professional experienced in the guidance of patients for home treatment. Infusion devices appropriate for subcutaneous administration of immunoglobulins can be used. The patient or a caregiver must be instructed 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.

Infusion rate
Hizentra can be infused using:

• an infusion device, or

• by manual push with a syringe.

The recommended initial infusion rate depends on the individual patient’s needs

Device-assisted infusion
The initial infusion rate should not exceed 20 ml/hour/site.

If well-tolerated (see also section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), 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

Manual push infusion

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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), 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.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Patients with hyperprolinaemia type I or II.
Hizentra must not be given intravascularly.