Beriglobin Injection

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

• Congenital agammaglobulinaemia and hypogammaglobulinaemia, including therapy induced.
• Common variable immunodeficiency.
• Severe combined immunodeficiency.
• IgG subclass deficiencies with recurrent infections.

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

Hepatitis A prophylaxis:

• In travelers who present less than 2 weeks before possible exposure, preferably in combination with vaccination. For long-term hepatitis A prophylaxis, active immunization is recommended.
• In persons exposed less than 2 weeks previously.

Therapy of radiogenic mucositis

Dosage:

The dosage and intervals of infusion are dependent on the indication.

Replacement therapy: The product should be administered via the subcutaneous route. The dosage may need to be individualised for each patient dependent on the pharmacokinetic and clinical response. The following dosage regimens are given as a guideline. The dosage 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 (1,3 to 3,1 ml/kg) bodyweight - divided over several days with a maximal daily dose of 0,1 to 0,15 g/kg body weight and as indicated by the treating doctor - may be required. After steady state IgG levels have been attained, maintenance doses are administered at repeated intervals, ideally weekly, to reach a cumulative monthly dose of about 0,4 to 0,8 g/kg (2,5 to 5,0 ml/kg) bodyweight. Trough levels should be measured in order to adjust the dose and dosage interval.

Hepatitis A prophylaxis: The product is to be administered via the intramuscular route.

• Short-term prophylaxis in travellers who present less than 2 weeks before possible exposure: For stays in endemic areas of less than 3 months a dose of 0,003 to 0,004 g/kg (0,02 ml/kg) bodyweight is recommended to be administered intramuscularly. BERIGLOBIN P can be given in combination with hepatitis A vaccine, but at different sites of the body.
• Hepatitis A prophylaxis in persons exposed less than 2 weeks previously: 0,003 to 0,004 g/kg (0,02 ml/kg) bodyweight administered intramuscularly.

Therapy of radiogenic mucositis: The product is to be administered via the intramuscular route. Initially 10 ml (1600 mg), after 2 days 5 ml (800 mg) and after a further 2 days again 5 ml (800 mg). The treatment can be repeated as often as necessary.

Administration: BERIGLOBIN P is a ready-for use solution and should be administered at body temperature. BERIGLOBIN P is a clear solution. The colour can vary from colourless to pale-yellow up to light brown. Do not use solutions which are cloudy or contain residues (deposits/particles). The product must be inspected visually prior to administration and should not be used if there is any variation of physical appearance.

Method of administration: Depending on the indication, BERIGLOBIN P should be administered via the subcutaneous or intramuscular route. Subcutaneous administration: Subcutaneous infusion should be initiated and monitored by a physician experienced in the treatment of immunodeficiencies and in the guidance of patients for home treatment. The patient will be instructed in the use of a syringe driver, infusion techniques, the keeping of a treatment diary and measures to be taken in case of severe adverse events. The recommended infusion rate is 22 ml/hour. In a clinical study with 53 patients evaluated, during the training phase under supervision of a physician, the infusion rate was increased from initially 10 ml to 22 ml/hour.

Do not inject intravascularly! Note that there is an increased risk of inadvertent intravascular injection in patients who have repeatedly received intramuscular injections. The product should preferably be administered in the abdominal wall, thigh and/or buttocks. No more than 15 ml should be injected into a single site. Doses over 15 ml should be divided and injected into 2 or more sites.

Intramuscular administration: Intramuscular injection must be given by a doctor or nurse. BERIGLOBIN P should preferably be administered ventrogluteally with the patient lying down. If larger doses are required, it is advisable to administer them in divided fractions. This applies in the case of doses above 2 ml for persons up to 20 kg bodyweight and doses above 5 ml for persons above 20 kg bodyweight. Do not inject intravascularly! Note that there is an increased risk of inadvertent intravascular injection in patients who have repeatedly received intramuscular injections. Any unused product or waste material should be disposed of in accordance with local requirements.

Hypersensitivity to any of the components of the product. Beriglobin P must not be administered intramuscularly in cases of disorders of haemostasis.

Do not inject intravascularly! If BERIGLOBIN P is accidentally administered into a blood vessel, patients could develop shock or thromboembolic events. When administering intramuscularly it is recommended to ensure by aspiration that no vessel has been penetrated. The recommended infusion rate stated under u2018DOSAGE AND DIRECTIONS FOR USEu201d should be adhered to.

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 vaccines. After administration of BERIGLOBIN P, an interval of at least 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.

Interference with serological testing: It has to be considered that when serological test results are interpreted, the transitory rise of passively transferred antibodies after immunoglobulin injection may result in positive test results. Passive transmission of antibodies to erythrocyte antigens, e.g., A, B and D, may interfere with some serological tests for red cell allo-antibodies (e.g. Coombs test), reticulocyte count and haptoglobin.

There are no controlled clinical trials on the use in human pregnancy. Therefore, the administration of this medicinal product to pregnant women or breast-feeding mothers should be carefully considered. Long lasting clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy or on the fetus and the neonate are to be expected.

Beriglobin P should not affect your ability to drive and use machines.

In a clinical study with subcutaneous administration in 60 patients the following undesirable effects have been reported. The following standard categories of frequency are used: Very common u2265 1/10 Common u2265 1/100 and < 1/10 Uncommon u2265 1/1 000 and < 1/100 Rare u2265 1/10 000 and < 1/1,000 Very rare < 1/10 000 (including reported single cases)

Body as a whole u2013 general disorders:

Rare: In single cases: Generalised reactions such as chills, fever, headache, malaise, moderate back pain, syncope, dizziness, rash, bronchospasm. Allergic reactions including fall in blood pressure.

Application site disorders:

Very common: Swelling, soreness, redness, induration, local heat, itching, bruising or rash. The frequency declined very rapidly within the first ten infusions, when patients became used to the subcutaneous form of treatment. (In study patients who were treated with subcutaneous immunoglobulin for years before the trial, injection site reactions were not reported.)

Adverse reactions reported from post marketing surveillance are similar to the reactions which have also been observed during the clinical trials. In addition, the following have also been reported during post marketing surveillance:

Cardiovascular disorders, general:

Uncommon: Cardiovascular reactions particularly if the product has been inadvertently injected intravascularly.

Vascular (extracardiac) disorders:

Uncommon: Vascular disorders associated with subcutaneous substitution therapy: There are reports from patients being treated subcutaneously with high doses of immunoglobulins for substitution therapy (e.g. primary immunodeficiency syndrome) of arterial and venous thromboembolic events including myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism.

Body as a whole u2013 general disorders:

Uncommon: Allergic/anaphylactic reactions including dyspnoea, cutaneous reactions, in isolated cases reaching as far as anaphylactic shock, even when the patient has shown no hypersensitivity to previous administration. Generalised reactions such as nausea, vomiting, arthralgia.

There are no known symptoms of overdosage.