KUTAKVIG

INSTRUCTION for medical use of the medicinal product CUTAQUIG (CUTAQUIG)

Composition:

Active substance: human normal immunoglobulin;

1 ml of the injection solution contains 165 mg of human normal immunoglobulin,

corresponding to a total protein content containing > 95% IgG;

IgG subclass distribution (approximate values): IgG1 – 71%, IgG2 – 25%, IgG3 – 3%,

IgG4 – 2%. Maximum IgA content – not more than 300 μg/ml;

Excipients: maltose, polysorbate 80, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless liquid which may become slightly opalescent or pale yellow during storage.

Pharmacotherapeutic group. Immune sera and immunoglobulins. Human normal immunoglobulin for extravascular administration. ATC code J06BA01.

Immunological and biological properties.

Pharmacodynamics.

Human normal immunoglobulin primarily contains immunoglobulin G (IgG) with a broad spectrum of antibodies against infectious disease pathogens.

Human normal immunoglobulin contains antibodies present as IgG in the healthy population. It is typically derived from pooled plasma of at least 1000 donors. It has an IgG subclass distribution nearly proportional to that in natural human plasma. Appropriate doses of this medicinal product can restore extremely low levels of immunoglobulin G to the normal range.

In a clinical study, a total of 75 patients (37 adults, 12 children aged [≥2 and <6], 14 children aged [≥6 and <12], 12 children aged [≥12 and <17]) with primary immunodeficiency syndromes were treated with CUTAQUIG for up to 64 weeks.

The mean weekly dose per patient was 0.187 g/kg in adult patients, 0.150 g/kg in children aged [≥2 and <6], 0.164 g/kg in children aged [≥6 and <12], and 0.170 g/kg in children aged [≥12 and <17]. Patients received a total of 4462 weekly injections of CUTAQUIG.

No serious bacterial infections were reported during either the accumulation/elimination period or the treatment effect period in patients receiving CUTAQUIG in the clinical study.

CUTAQUIG was evaluated in 38 pediatric patients (26 children [aged 2 to <12 years] and 12 children [aged 12 to <16 years]) with primary immunodeficiency. No special dosing requirements were needed in pediatric patients to achieve desired serum IgG levels.

An additional study was a prospective, open-label, multicenter Phase III safety follow-up study with one parallel group, which included 27 patients (17 adults, 2 children aged [≥2 and <6 years], 4 children aged [≥6 and <12 years], 4 children aged [≥12 and <17 years]) with primary immunodeficiency. Of these, 21 patients had previously participated in the reference study and 6 patients were newly enrolled. Patients previously included in the reference study were followed for up to 4.5 years, while new patients were followed for 12 months. Patients received CUTAQUIG on a weekly schedule (25 patients) or once every two weeks (2 patients). The mean actual dose of CUTAQUIG administered was 0.127 g/kg in children aged [≥2 and <6 years], 0.210 g/kg in children aged [≥6 and <12 years], 0.160 g/kg in children aged [≥12 and <17 years], and 0.166 g/kg in adult patients. Patients received a total of 2777 injections (2740 weekly and 37 every two weeks). One serious bacterial infection, bacteremia/sepsis, was reported.

For monitoring safety, tolerability, and efficacy of CUTAQUIG, a prospective, open-label, multicenter Phase III study with three parallel groups included 64 PID (Primary Immunodeficiency) patients (59 adults, 1 child aged [≥2 and <6 years], 2 children aged [≥6 and <12 years], 2 children aged [≥12 and <17 years]), aged 5 to 74 years.

After completion of a 4-week stabilization period, patients transitioned to a 24-week treatment observation period and were assigned to one of 3 cohorts:

• Cohort 1 evaluated increased injection volume per injection site up to a maximum of 100 ml/site;
• Cohort 2 evaluated increased injection rate per injection site up to a maximum of 100 ml/hour/site or the maximum rate achievable using an infusion pump;
• Cohort 3 evaluated CUTAQUIG administered once every two weeks, equivalent to twice the weekly dose based on patient body weight (mg/kg).

The primary endpoint was to compare overall trough IgG levels following weekly injections versus injections every two weeks, and to evaluate the safety and tolerability of increased injection volumes and increased injection rates at each injection site, as well as dosing once every two weeks.

Overall, patients received 1338 injections (386 in cohort 1, 396 in cohort 2, 556 in cohort 3). In cohort 1 (n = 15, adults), the mean maximum achieved injection volume per site was 69.4 ml/site, with a maximum volume of 108 ml/site. One-third of patients (5/15; 33.3%) received ≥90% of the intended maximum volume of 100 ml/site, another third received between 50% and <90% of the intended maximum, and one-third received <50% of the intended maximum. The median maximum achieved rate per patient was 56.9 ml/hour, ranging from 34.0 ml/hour to 94.7 ml/hour.

In cohort 2 (n = 15, 13 adults, 1 child aged [≥6 and <12], 1 child aged [≥12 and <17]), the mean maximum achieved injection rate per site was 42.1 ml/hour/site, with a maximum rate of 67.5 ml/hour/site. 73.3% of patients reached a maximum injection rate of <50% of the intended maximum rate of 100 ml/hour/site, while the remaining 26.7% reached between 50% and 75% of the intended maximum rate. The median maximum achieved rate per patient was 135.0 ml/hour, ranging from 51.4 ml/hour to 192.0 ml/hour.

In cohort 3 (n = 34, 31 adult patients, 1 child aged [≥2 and <6], 1 child aged [≥6 and <12], 1 child aged [≥12 and <17]), a decrease in mean overall trough IgG levels was observed with dosing every two weeks (9.927 [2.0146] g/l) compared to weekly dosing (10.364 [1.9632] g/l) (p = 0.0017; 1-sided 97.5% lower confidence limit [LCL] = -0.799). The median maximum achieved rate per patient was 93.5 ml/hour, ranging from 24.3 ml/hour to 145.9 ml/hour.

The mean actual dose of CUTAQUIG administered per body weight was 0.143 g/kg in cohort 1, 0.157 g/kg in cohort 2, and 0.256 g/kg in cohort 3, respectively.

During the study, no serious bacterial infections were reported, and the overall rate of serious bacterial infections was 0.00 per patient-year (upper limit of 98% CI [alternative method] = 0.135 [0.614 in cohort 1, 0.602 in cohort 2, and 0.244 in cohort 3]).

Pediatric patients

No differences in pharmacodynamic properties of the drug were observed between adult and pediatric patients.

Pharmacokinetics.

In a Phase III clinical study, a pharmacokinetic (PK) sub-study was conducted in 37 patients with primary immunodeficiency syndrome (PIS). Blood samples for PK analysis were collected before switching to CUTAQUIG (profile: PKIV), after the 11th injection of CUTAQUIG (first SC profile: PKsc1), and after the 28th injection of CUTAQUIG (second SC profile: PKsc2).

The objective of the PK sub-study was to compare areas under the PK curves (AUCs) after intravenous (IV) and subcutaneous (SC) administration, using a dose correction factor (DCF) of 1.5. Population PK modeling was used to estimate PK parameters and perform simulations.

Absorption and distribution

After subcutaneous administration of CUTAQUIG, peak serum levels are reached approximately 2 days after injection.

Due to gradual absorption, subcutaneous immunoglobulin administration (SCIG) results in flatter profiles and smaller fluctuations at steady state compared to intravenous immunoglobulin administration (IVIG): mean maximum concentration (Cmax) was lower after SCIG (13.2 + 3.4 g/l and 13.5 + 3.7 g/l for PKsc1 and PKsc2, respectively) than after IVIG (18.0+4.5 g/l).

Accordingly, mean trough serum IgG and IgG subclass levels were higher after SC administration (11.5 and 11.7 g/l for PKsc1 and PKsc2, respectively; overall range from 6.5 to 18.9 g/l) compared to the overall range at the end of the IVIG period (10.1 g/l; range: 6.5 to 14.3 g/l). Calculated bioavailability after SC administration was 75%, corresponding to a dose correction factor of 1.3 based on body weight to achieve equivalent AUC exposure after SCIG and IVIG.

PK modeling and simulations based on data from the clinical study with weekly administration of CUTAQUIG indicate that a dose adjusted for body weight without a correction factor for lower bioavailability with SC administration is sufficient to maintain systemic IgG exposure within the therapeutic range for dosing intervals up to 1 week, as well as for more frequent than weekly administration (e.g., daily). Longer dosing intervals (especially with lower baseline IgG levels) increase the risk of IgG levels falling below the minimum level of 5 g/l.

Example: Assuming a baseline IgG level of 4.0 g/l and switching from IVIG to SCIG with a dose ratio coefficient of 1.0, it was predicted that the proportion of patients with IgG levels falling below the minimum level of 5 g/l would increase by 4% with a 2-week dosing interval compared to 1.4% with dosing intervals ≤Q1W (once weekly).

Elimination

IgG and IgG complexes are degraded in cells of the reticuloendothelial system. The mean half-life of IgG after administration of CUTAQUIG in patients with PIS was estimated to be approximately 16 (9.2**–**36.3) days, as calculated in the population PK model, assuming zero (absent) endogenous IgG production.

Pediatric patients

No clinically significant differences were observed between pharmacokinetic parameters in adult and pediatric patients with PIS.

PK modeling and simulation based on data from the clinical study with weekly administration of CUTAQUIG indicate that a dose adjusted for body weight is sufficient to maintain systemic IgG exposure within the therapeutic range, independent of age.

Preclinical safety data

Immunoglobulins are normal components of human plasma. Preclinical data revealed no special hazard for humans based on standard pharmacological safety and local tolerability studies.

Since clinical experience does not provide evidence of carcinogenic or mutagenic potential of immunoglobulins, no experimental studies in heterogeneous species have been conducted.

Clinical characteristics.

Indications.

As replacement therapy in adults and children (aged 0–18 years) in the following conditions:

• primary immunodeficiency syndrome (PIS) with impaired antibody production (see section "Special instructions");
• secondary immunodeficiencies in severe or recurrent infections when antimicrobial therapy is ineffective and specific antibody deficiency (SAD)* or serum IgG levels ˂ 4 g/L have been established.

* SAD – inability to achieve at least a 2-fold increase in IgG antibody titers to pneumococcal polysaccharide vaccine and polypeptide antigen.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients listed in the sections "Composition" and "Special instructions".

Kutakvig must not be administered intravenously.

The drug must also not be administered intramuscularly in cases of severe thrombocytopenia and other hemostatic disorders.

Interaction with other medicinal products and other types of interactions.

Live antiviral vaccines

Administration of immunoglobulin may temporarily reduce the efficacy of live antiviral vaccines against measles, rubella, mumps, and varicella for a period of 6 weeks to 3 months. An interval of 3 months should be maintained between administration of this medicinal product and vaccination with live antiviral vaccines. In the case of measles vaccination, this suppression may last up to 1 year. Therefore, antibody status should be checked in patients receiving measles vaccine.

Blood glucose testing

Kutakvig contains maltose, which may be incorrectly interpreted (detected) as glucose by certain blood glucose monitoring systems. Due to the risk of falsely elevated glucose readings, only those glucose monitoring systems specifically designated for accurate blood glucose measurement should be used when monitoring or controlling blood glucose levels in diabetic patients.

Pediatric population

The interactions listed above apply to both adults and children.

Special precautions for use.

The medicinal product is manufactured from plasma of human donors.

Each 6 ml vial contains 1 g of normal human immunoglobulin.

Each 10 ml vial contains 1.65 g of normal human immunoglobulin.

Each 12 ml vial contains 2 g of normal human immunoglobulin.

Each 20 ml vial contains 3.3 g of normal human immunoglobulin.

Each 24 ml vial contains 4 g of normal human immunoglobulin.

Each 48 ml vial contains 8 g of normal human immunoglobulin.

It is strongly recommended to record the name and batch number of the product each time Cutaquig is administered, in order to allow traceability between the patient's condition and administration of a specific batch.

Cutaquig is intended for subcutaneous use only. If accidentally administered intravascularly, the patient may develop shock.

The recommended infusion rate specified in the section "Dosage and administration" must be strictly observed. Close monitoring of the patient is required throughout the entire administration period to detect any symptoms.

Adverse reactions may occur more frequently in patients receiving normal human immunoglobulin for the first time, in rare cases when switching from replacement therapies to normal human immunoglobulin, and after long intervals since the last injection.

Complications can often be avoided if:

• the product is initially administered slowly (see section "Dosage and administration");
• close monitoring of the patient is ensured for any symptoms throughout the entire injection period. In particular, patients who have not previously been treated with normal human immunoglobulin, patients switching from an alternative immunoglobulin product, and patients with a prolonged interval since the last injection should be closely observed during the first injection and for at least one hour thereafter to detect any adverse symptoms promptly. All other patients should be monitored for at least 20 minutes after administration of the product.

If an adverse reaction occurs, the infusion rate should be reduced or the injection stopped. If an allergic or anaphylactic reaction is suspected, the injection must be stopped immediately. Treatment required depends on the nature and severity of the adverse reaction. In case of shock, standard anti-shock therapy should be initiated.

Hypersensitivity

True allergic reactions are rare and are most likely to occur in patients with antibodies to immunoglobulin A (IgA), who should be treated with extreme caution. Patients with anti-IgA antibodies, for whom subcutaneous administration of IgG products remains the only treatment option, should receive Cutaquig therapy only under strict medical supervision.

Normal human immunoglobulin may occasionally cause a drop in blood pressure with anaphylactic reaction, even in patients who have previously been treated with normal human immunoglobulin.

Thromboembolism

Arterial and venous thromboembolic complications, such as myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism, have been associated with the use of immunoglobulins. Patients should have adequate hydration prior to administration of immunoglobulins. Caution should be exercised in patients with pre-existing risk factors for thrombotic complications (such as advanced age, arterial hypertension, diabetes mellitus, history of vascular disease or thrombotic events, acquired or inherited thrombophilic disorders, prolonged immobilization, severe hypovolemia, or conditions increasing blood viscosity).

Patients should be informed about the early symptoms of thromboembolic complications, such as difficulty breathing, pain and swelling in a limb, focal neurological symptoms, and chest pain, and advised to seek immediate medical attention if such symptoms occur.

Aseptic Meningitis Syndrome (AMS)

Aseptic meningitis syndrome has been reported in association with subcutaneously administered immunoglobulin therapy; symptoms usually begin within several hours to 2 days after treatment. Discontinuation of immunoglobulin therapy may lead to resolution of AMS within a few days without sequelae.

Patients should be informed about early symptoms, including severe headache, neck stiffness, drowsiness (lethargy), fever, photophobia, nausea, and vomiting.

Renal dysfunction / renal failure

Cases of severe adverse renal reactions have been reported in patients receiving immunoglobulin therapy, particularly with products containing sucrose (Cutaquig does not contain sucrose). Severe adverse reactions include acute renal failure, acute tubular necrosis, proximal tubular nephropathy, and osmotic nephrosis.

Factors increasing the risk of renal complications include pre-existing renal insufficiency, diabetes mellitus, hypovolemia, concomitant therapy with nephrotoxic medicinal products, age over 65 years, sepsis, increased blood viscosity, and paraproteinemia.

Hemolysis

IgG products may contain blood group antibodies that can act as hemolysins and cause in vivo coating of erythrocytes with immunoglobulin, resulting in a positive direct antiglobulin test (direct Coombs test), and rarely may cause hemolysis.

Patients receiving immunoglobulin products should be monitored for clinical signs and symptoms of hemolysis.

Effect on serological testing

Following administration of immunoglobulin, transient increases in passively transferred antibodies in the patient's blood may lead to false-positive results in serological testing.

Passive transfer of antibodies to erythrocyte antigens, such as A, B, D, may affect certain serological tests for anti-erythrocyte antibodies, such as the direct antiglobulin test (DAT, direct Coombs test).

Transmission of microorganisms

Standard measures for prevention and reduction of infections transmitted via medicinal products manufactured from human blood or plasma include donor selection, screening of individual donor blood samples and plasma pools for specific infectious markers, and use of effective viral inactivation/removal methods during manufacturing. Nevertheless, when prescribing medicinal products derived from human blood or plasma, transmission of infectious agents cannot be completely excluded. This also applies to unknown or emerging viruses and other pathogenic microorganisms.

The measures taken are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV).

The effectiveness of these measures may be limited against non-enveloped viruses, such as hepatitis A virus (HAV) and parvovirus B19.

There is reassuring clinical experience regarding the lack of transmission of hepatitis A or parvovirus B19 with immunoglobulins, and it is assumed that antibody content plays an important role in viral safety.

Paediatric population

The special precautions and warnings listed above apply to both adults and children.

Maltose content

This medicinal product contains a maximum of 90 mg of maltose as an excipient per 1 ml of solution. Maltose may interfere with blood glucose measurements, leading to falsely elevated glucose readings and, consequently, inappropriate (unjustified) insulin administration, which may result in life-threatening hypoglycemia and potentially fatal outcomes. Additionally, true hypoglycemic episodes may remain untreated if masked by falsely elevated glucose readings (see section "Interaction with other medicinal products and other forms of interaction").

Sodium content

This medicinal product contains 33.1 mg of sodium per 48 ml vial of solution for injection and 13.8 mg of sodium per 20 ml vial of solution for injection, equivalent to 1.7% and 0.7% respectively of the WHO recommended maximum daily intake of sodium for adults (2 g).

Special instructions for use and disposal

The medicinal product should be brought to room temperature or body temperature before use.

The product should be inspected visually for the presence of particulate matter (solid particles) and discoloration prior to administration.

Solutions that are cloudy or contain a precipitate must not be used.

Any unused medicinal product or waste material must be disposed of in accordance with local requirements.

Use during pregnancy or breastfeeding.

Pregnancy

The safety of this medicinal product in pregnant women has not been established in controlled clinical trials; therefore, it should be administered with caution to pregnant women and women who are breastfeeding. Immunoglobulin products have been shown to cross the placenta, particularly during the third trimester of pregnancy. Clinical experience with immunoglobulin use suggests that harmful effects on pregnancy, the fetus, or the newborn are not expected.

Breastfeeding

Immunoglobulins are excreted in breast milk and may contribute to protecting the infant against pathogenic microorganisms entering through mucous membranes.

Fertility

Clinical experience with immunoglobulin use indicates that harmful effects on fertility are not expected.

Ability to influence the ability to drive and use machines.

The ability to drive and operate machinery may be impaired if adverse reactions related to Cutaquig occur. Patients experiencing adverse reactions during treatment should wait until these reactions have completely and definitively resolved before driving or operating machinery.

Method of Administration and Dosage

Replacement therapy should be initiated and monitored under the supervision of a physician experienced in the management of immunodeficiency.

Dosage

The dose and dosing regimen depend on the indication.

Replacement Therapy

This medicinal product should be administered subcutaneously.

In replacement therapy, the dose should be individually adjusted for each patient according to pharmacokinetic characteristics and clinical response (treatment outcomes). Cutaquig can be administered at regular intervals, ranging from daily administration to once every two weeks. The dosing regimens presented below are provided as recommendations.

The dosing regimen should ensure achievement of a minimum IgG level (measured immediately before the next infusion) of at least 5–6 g/L and maintain this parameter within the age-appropriate reference range for serum IgG. A loading (initial) dose of not less than 0.2–0.5 g/kg (1.2–3.0 mL/kg) body weight may be required. This dose may need to be divided into several infusions administered over several days, with a maximum daily dose of 0.1–0.15 g/kg.

Replacement Therapy in Primary Immunodeficiency Syndromes (as indicated in the “Indications” section)

After reaching stable IgG levels, maintenance doses are administered at regular intervals to achieve a cumulative (total) monthly dose of approximately 0.4–0.8 g/kg (2.4–4.8 mL/kg). Different anatomical sites (locations) may be required for each individual dose.

Minimum IgG levels should be measured and evaluated together with the frequency of infections. Dose increases may be necessary to reduce infection frequency and achieve higher minimum IgG levels.

Replacement Therapy in Secondary Immunodeficiencies (as indicated in the “Indications” section)

The recommended dose should be administered at regular intervals (approximately once weekly) to achieve a cumulative (total) monthly dose of approximately 0.2–0.4 g/kg (1.2–2.4 mL/kg). Different anatomical sites (locations) may be required for each individual dose.

Minimum IgG levels should be measured and evaluated together with the frequency of infections. The dose should be adjusted as needed to achieve optimal protection against infections. Dose increases may be required for patients with persistent infections; dose reduction may be considered for patients without infections.

Elderly Patients

Since the dose is based on body weight and adjusted according to treatment response and diagnosis, the dose for elderly patients is considered not to differ from that for patients aged 18 to 65 years. In a clinical study, Cutaquig was evaluated in 17 patients over 65 years of age. No special dosing was required to achieve desired serum IgG levels.

Method of Administration

For subcutaneous use only.

When treatment is administered at home, initiation and monitoring of subcutaneous infusions must be performed by a physician experienced in managing home-treated patients. The patient and/or caregiver should be informed and trained on how to use the infusion device, how to perform the infusion procedure, how to carry out aseptic techniques, how to maintain a treatment diary, and how to recognize and respond to serious adverse reactions.

Cutaquig can be administered at the following sites: abdomen, thigh, upper arm, and lateral thigh.

Infusion Rate

Adjustment of infusion rate and volume per infusion site should be based on patient tolerance.

The recommended initial infusion rate is 15 mL/hour/site for patients who have not previously received subcutaneous immunoglobulin therapy. For patients already receiving subcutaneous immunoglobulin therapy and switching to Cutaquig, initial infusions should be administered at the previously used rate. In subsequent infusions, if well tolerated (see section “Special Warnings and Precautions for Use”), the infusion rate may be gradually increased by approximately 10 mL/hour/site every 2–4 weeks for adults (body weight ≥ 40 kg) and up to 10 mL/hour/site every 4 weeks for pediatric patients (body weight < 40 kg) (see section “Pharmacodynamics”).

After the patient tolerates initial infusions at full volume per site and at the maximum rate, further increases in infusion rate may be considered until the maximum infusion rate of 67.5 mL/hour/site for adults and 25 mL/hour/site for pediatric patients is reached (see section “Pharmacodynamics”).

More than one infusion device may be used simultaneously.

Infusion Volume per Infusion Site

The amount of product administered at a specific site may vary. In children, the infusion site may be changed for every 5–15 mL. In adults, doses exceeding 30 mL may be divided according to patient preference. There are no limitations on the number of infusion sites. Infusion sites should be at least 5 cm apart from each other.

Children

The dose for children (aged 0–18 years) does not differ from that for adults, as the dose for each indication is based on body weight and adjusted according to treatment response as per the indications for replacement therapy.

Overdose

The consequences of overdose are unknown.

Adverse reactions.

Summary of safety profile

Unwanted reactions such as chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia (joint pain), low blood pressure, and moderate back pain may occur occasionally.

Rarely, normal human immunoglobulins may cause a sudden drop in blood pressure and, in individual cases, anaphylactic shock, even when the patient has not shown hypersensitivity to previous administrations of the drug.

Reactions at the injection site: swelling, pain, redness, induration, sensation of warmth, bruising, and rash may occur frequently. The frequency of such reactions usually decreases with ongoing treatment.

For information on the safety regarding transmission of infectious agents, see section "Special precautions for use".

List of adverse reactions in tabular form

Data on the clinical safety of Kutakvig in patients with primary immunodeficiency are based on a pivotal, open-label, prospective, multicenter, single-arm phase III study (n = 75, 4462 infusions), a prospective, open-label, multicenter, single-arm phase III study (n = 27, 2777 infusions), and an open-label, multicenter, phase III study with three parallel groups (n = 64, 1338 infusions).

The table below is organized according to System Organ Classes (SOC) and Preferred Terms (PT) of the Medical Dictionary for Regulatory Activities (MedDRA).

The frequency of adverse reactions per patient was assessed according to the following conventional categories: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are listed in order of decreasing severity.

Frequency of adverse reactions per patient and per infusion in clinical studies with Kutakvig

The following adverse reactions have been identified during post-marketing use of Kutavig. Because these adverse reactions are reported voluntarily from an undefined population size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

This list does not include reactions that were already reported in clinical trials with Kutavig:

The following additional adverse reactions have been reported during post-marketing experience with subcutaneous administration of immunoglobulin products: facial swelling, tremor, pallor, bronchospasm, dyspnea (difficulty breathing), cough, diarrhea, urticaria, rash, hyperemia (flushing), feeling of warmth, feeling of cold, asthenia (general weakness), influenza-like illness, malaise, injection site pain, sensation of throat tightness, aseptic meningitis.

Pediatric population

The frequency, type, and severity of adverse reactions in children are expected to be the same as in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

After first opening of the vial, the medicinal product should be used immediately.

Storage conditions.

Store at a temperature of 2 to 8 °C. Do not freeze.

Keep the vial in the outer carton to protect from light.

Keep out of reach of children.

During the shelf life, the product may be stored at room temperature (below 25 °C) for up to 9 months without the need for refrigeration during this period; the product must be discarded if not used after storage outside the refrigerator.

Incompatibilities.

Due to lack of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Packaging. 6 ml, 10 ml, 12 ml, 20 ml, 24 ml, or 48 ml of solution for injection in a vial.
1 vial in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

1. Octapharma AB
2. Octapharma Pharmazeutika Produktionsges.m.b.H.

Manufacturer's address and location of business operations.

1. Lars Forssells Gata 23, Stockholm, 11275, Sweden
2. Oberlaaer Strasse 235, 1100 Vienna, Austria