GAMMANORM Solution for injection Ref.[27659] Active ingredients: Human normal immunoglobulin G

If Gammanorm is accidentally administered into a blood vessel, patients could develop shock.

The recommended infusion rate stated under section 4.2 must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period.

Certain adverse reactions may occur more frequently in patients who receive human normal immunoglobulin for the first time or, in rare cases, when the human normal immunoglobulin product is switched or when there has been a long interval since the previous infusion.

Potential complications can often be avoided by:

• initially injecting the product slowly (see section 4.2);
• ensuring that patients are carefully monitored for any symptoms throughout the infusion period. In particular, patients naïve to human normal immunoglobulin, patients switched from an alternative immunoglobulin product or when there has been a long interval since the previous infusion should be monitored during the first infusion and for the first hour after the first infusion, in order to detect potential adverse signs.

All other patients should be observed for at least 20 minutes after administration.

In case of adverse reaction, either the rate of administration must be reduced or the infusion stopped. The treatment required depends on the nature and severity of the adverse reaction.

In case of shock, standard medical treatment for shock should be implemented.

Hypersensitivity

True allergic reactions are rare. They can particularly occur in patients with anti-IgA antibodies who should be treated with particular caution. Patients with anti-IgA antibodies, in whom treatment with subcutaneous IgG products remains the only option, should be treated with Gammanorm only under close medical supervision.

Rarely, human normal immunoglobulin can induce a fall in blood pressure with anaphylactic reaction, even in patients who had tolerated previous treatment with human normal immunoglobulin.

Thromboembolism

Arterial and venous thromboembolic events including myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism have been associated with the use of immunoglobulins. Patients should be sufficiently hydrated before use of immunoglobulins.

Caution should be exercised in patients with preexisting risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus and a history of vascular disease or thrombotic episodes, patients with acquired or inherited thrombophilic disorders, patients with prolonged periods of immobilization, severely hypovolaemic patients, patients with diseases which increase blood viscosity).

Patients should be informed about first symptoms of thromboembolic events including shortness of breath, pain and swelling of a limb, focal neurological deficits and chest pain and should be advised to contact their physician immediately upon onset of symptoms.

Aseptic Meningitis Syndrome (AMS)

Aseptic meningitis syndrome has been reported to occur in association with subcutaneous immunoglobulin treatment; the symptoms usually begin within several hours to 2 days following treatment. Discontinuation of immunoglobulin treatment may result in remission of AMS within several days without sequelae.

Patients should be informed about first symptoms which encompass severe headache, neck stiffness, drowsiness, fever, photophobia, nausea, and vomiting.

Important information about some of the ingredients of Gammanorm

This medicinal product contains 25 mg (or 1.1 mmol) sodium per vial of 10 mL, and 60 mg (or 2.61 mmol) sodium per vial of 24 mL, equivalent to 1.25%, and 3%, respectively, of the WHO recommended maximum daily intake of 2 g sodium for an adult. This should be taken into consideration in patients on a controlled sodium diet.

Interference with serological testing

After injection of immunoglobulin the transitory rise of the various passively transferred antibodies in the patient´s blood may result in misleading positive results in serological testing.

Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D may interfere with some serological tests for red cell antibodies for example the direct antiglobulin test (DAT, direct Coombs' test).

Transmissible agents

Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.

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

The measures taken may be of limited value against non-enveloped viruses such as HAV and parvovirus B19.

There is reassuring clinical experience regarding the lack of hepatitis A or parvovirus B19 transmission with immunoglobulins and it is also assumed that the antibody content makes an important contribution to the viral safety.

It is strongly recommended that every time that Gammanorm is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.

Gammanorm does not protect against hepatitis A.

Paediatric population

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

Live attenuated virus vaccines

Immunoglobulin administration may impair for a period of at least 6 weeks and up to 3 months the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella. After administration of this product, an interval of 3 months should elapse before vaccination with live attenuated virus vaccines. In the case of measles, this impairment may persist for up to 1 year. Therefore patients receiving measles vaccine should have their antibody status checked.

Paediatric population

There were no specific or additional interactions observed for the paediatric population.

Pregnancy

The safety of this medicinal product for use in human pregnancy has not been established in controlled clinical trials and Gammanorm should therefore only be given with caution to pregnant women and breast-feeding mothers. Immunoglobulin products have been shown to cross the placenta, increasingly during the third trimester. Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the foetus and the neonate are to be expected.

Breast-feeding

Immunoglobulins are excreted into the milk and may contribute to protecting the neonate from pathogens which have a mucosal portal of entry.

Fertility

Clinical experience with immunoglobulins suggests that no harmful effects on fertility are to be expected.

The ability to drive and operate machines may be impaired by some adverse reactions associated with Gammanorm. Patients who experience adverse reactions during treatment should wait for these to resolve before driving or operating machines.

Summary of the safety profile

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

Rarely human normal immunoglobulins may cause a sudden fall in blood pressure and, in isolated cases, anaphylactic shock, even when the patient has shown no hypersensitivity to previous administration.

Local reactions at infusion sites: swelling, soreness, redness, induration, local heat, itching, bruising and rash, may frequently occur.

Tabulated list of adverse reactions

The safety of Gammanorm administered subcutaneously was evaluated in two studies in 60 subjects with primary immunodeficiency syndromes.

The following table shows an overview of adverse reactions observed in clinical studies, post-marketing safety studies, and from other postmarketing sources, categorized according the MedDRA System Organ Class (SOC), Preferred Term Level (PT) and frequency.

Frequencies have been evaluated according to the following convention: 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).

For spontaneously reported post-marketing adverse reactions the reporting frequency is categorised as not known.

^# See also Section 4.4
^* MedDRA low level term (LLT)

For safety information with respect to transmissible agents, see section 4.4.

Paediatric population

Frequency, type and severity of adverse reactions in children are the same as in adults.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.