This information is intended for use by health professionals

1. Name of the medicinal product

Human Varicella-Zoster Immunoglobulin 250mg solution for injection

2. Qualitative and quantitative composition

Human Varicella-Zoster Immunoglobulin Ph.Eur. contains human protein, 40-180 g/L of which at least 95% is IgG. The concentration of specific IgG to Varicella Zoster is at least 100 IU/mL in nominal 250 mg vials. The correct volume to give 250mg is overprinted on the label.

This product is prepared from plasma from screened donors. Donors are selected from the USA.

For excipients, see section 6.1.

3. Pharmaceutical form

Solution for injection.

4. Clinical particulars
4.1 Therapeutic indications

Prophylaxis against varicella zoster virus (VZV) infection in at risk patients exposed to varicella (chickenpox) or herpes zoster:

1. pregnant women with negative VZV immune status especially up to early in the third trimester

2. neonates whose mothers develop varicella infection within 7 days before and 7 days after delivery

3. neonates whose mothers have no history of varicella and/or a negative immune status

4. premature infants <28 weeks of gestation or newborns with low birth weight

5. adults and children with no history of varicella and/or a negative immune status, receiving immunosuppressive therapy including steroids, cytostatic agents, radiotherapy, recent stem cell transplantation, or who have congenital or acquired immunodeficiency disorders and are not receiving replacement therapy with immunoglobulin.

Notes on use of Human Varicella-Zoster Immunoglobulin

Whenever possible, contacts without a definite history of chickenpox should be screened for antibody by a sensitive test (e.g. ELISA, radioimmunoassay or immunofluorescence). There is no need to test neonates for antibody.

If antibodies to VZV are detectable, Human Varicella-Zoster Immunoglobulin is generally NOT needed. The following infants will possess maternal antibody and do NOT require Human Varicella-Zoster Immunoglobulin.

(i) Infants born more than seven days after the onset of maternal chickenpox.

(ii) Infants whose mothers have a positive history of chickenpox and/or a positive antibody result.

(iii) Infants whose mothers develop zoster (shingles) before or after delivery.

4.2 Posology and method of administration

Posology

≥15 IU/kg body weight as soon as possible, ideally within 3 days but within 10 days maximum.

Alternative dose levels for treatment are as follows:

0 - 5 years

6 - 10 years

11 - 14 years

15 years and older

250 mg (1 vial)

500 mg (2 vials)

750 mg (3 vials)

1000 mg (4 vials)

The correct volume of solution to give a dose of 250mg is overprinted on the label.

If a second exposure to chickenpox occurs three weeks or more after the first dose of Human Varicella-Zoster Immunoglobulin, a second dose is required.

Method of administration

Human Varicella-Zoster Immunoglobulin should be administered via the intramuscular route. The usually recommended sites for adults are the buttock, thigh or deltoid; for infants the lateral aspect of the thigh is preferable. If a large volume (>2 mL for children or >5 mL for adults) is required, it is recommended to administer this in divided doses at different sites.

If intramuscular administration is contraindicated (bleeding disorders), the injection can be administered subcutaneously. However, it should be noted that there are no clinical efficacy data to support administration by the subcutaneous route.

4.3 Contraindications

Hypersensitivity to any of the components.

Hypersensitivity to human immunoglobulins.

4.4 Special warnings and precautions for use

Ensure that Human Varicella-Zoster Immunoglobulin is not administered into a blood vessel, because of the risk of shock.

True hypersensitivity reactions are rare.

Human Varicella-Zoster Immunoglobulin contains a small quantity of IgA. Individuals who are deficient in IgA have the potential for developing IgA antibodies and may have anaphylactic reactions after administration of blood components containing IgA. The physician must therefore weigh the benefit of treatment with Human Varicella-Zoster Immunoglobulin against the potential risks of hypersensitivity reactions.

Rarely, Human Varicella-Zoster Immunoglobulin can induce a fall in blood pressure with anaphylactic reaction, even in patients who have tolerated previous treatment with human immunoglobulin.

Suspicion of allergic or anaphylactic type reactions requires immediate discontinuation of the injection. In case of shock, standard medical treatment for shock should be implemented.

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 the 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) and for the non-enveloped hepatitis A and parvovirus B19 viruses.

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 Human Varicella-Zoster Immunoglobulin 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.

4.5 Interaction with other medicinal products and other forms of interaction

Live attenuated virus vaccines

Immunoglobulin administration may interfere with the development of an immune response to live attenuated virus vaccines, such as rubella, mumps and varicella, for a period of up to 3 months. After administration of this product, 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 5 months.

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 tests.

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 antiglobulin test (Coomb's test).

4.6 Pregnancy and lactation

The safety of this medicinal product for use in human pregnancy has not been established in controlled clinical trials. 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.

4.7 Effects on ability to drive and use machines

No effects on ability to drive and use machines have been observed.

4.8 Undesirable effects

There are no robust data on the frequency of undesirable effects from clinical trials. The following undesirable effects have been reported with intramuscular immunoglobulins.

MedDRA Standard System Organ Class

Undesirable effects

Immune system disorders

Hypersensitivity, anaphylactic shock

Nervous system disorders

Headache

Cardiac disorders

Tachycardia

Vascular disorders

Hypotension

Gastrointestinal disorders

Nausea, vomiting

Skin and subcutaneous tissue disorders

Skin reaction, erythema, itching, pruritus

Musculoskeletal, connective tissue and bone disorders

Arthralgia

General disorders and administration site conditions

Fever, malaise, chill

At injection site: swelling, pain, erythema, induration, warmth, pruritus, rash, itching

For safety with respect to transmissible agents, see Section 4.4.

4.9 Overdose

Consequences of an overdose are not known.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: immune sera and immunoglobulins:

Human varicella immunoglobulin ATC code: J06B B03.

Human Varicella-Zoster Immunoglobulin contains mainly immunoglobulin G (IgG) with a specifically high content of antibodies against varicella-zoster virus.

5.2 Pharmacokinetic properties

Human Varicella-Zoster Immunoglobulin for intramuscular administration is bioavailable in the recipient's circulation after a delay of 2-3 days.

Human Varicella-Zoster Immunoglobulin has a half-life of about 3-4 weeks. This half-life may vary from patient to patient.

IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.

5.3 Preclinical safety data

Human Varicella-Zoster Immunoglobulin is a preparation of human plasma proteins, so safety testing in animals is not particularly relevant to the safety of use in man. Acute toxicity studies in rat and mouse showed species specific reactions which bear no relevance to administration in humans. Repeated dose toxicity testing and embryo-fetal toxicity studies are impracticable due to induction of, and interference with antibodies to human protein.

6. Pharmaceutical particulars
6.1 List of excipients

Sodium chloride

Glycine

Sodium acetate trihydrate

Sodium hydroxide

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

Stored at 2°C-8°C:

2 years.

Stored at 25°C:

1 week.

6.4 Special precautions for storage

Human Varicella-Zoster Immunoglobulin should be stored in the original vial at 2°C to 8°C. Keep vial in the outer carton in order to protect from light.

. Storage for up to one week at ambient temperatures (25°C) in the original container is not detrimental.

DO NOT FREEZE.

6.5 Nature and contents of container

Neutral borosilicate glass vial (Type I Ph.Eur.) with overseal consisting of a halobutyl rubber wad (Type I Ph.Eur.), clear lacquered aluminium skirt and flip-off polypropylene cap.

6.6 Special precautions for disposal and other handling

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

The colour can vary from colourless to pale-yellow and is either clear or slightly opalescent. Do not use solutions which are cloudy or have deposits .

Any used product or waste material should be disposed of in accordance with local requirements.

7. Marketing authorisation holder

Bio Products Laboratory Limited

Dagger Lane

Elstree

Hertfordshire

WD6 3BX

United Kingdom.

Tel: +44 (0)20 8957 2200

Fax: +44 (0)20 8957 2608

Email: [email protected]

8. Marketing authorisation number(s)

PL 08801/0013

9. Date of first authorisation/renewal of the authorisation

July 1995

10. Date of revision of the text

October 2014

Version Code: GZS9

POM