Based on our risk assessment we recommend that your patient receives a course of post-exposure rabies vaccination with r
Virus Reference Department 61 Colindale Avenue London NW9 5EQ
T +44 (0)20 8327 6204 F +44 (0)20 8200 1569 www.gov.uk/phe
Ref: KEB/Rabies/08947111P April 2015 Dear Colleague Re: Based on our risk assessment we recommend that your patient receives a course of post-exposure rabies vaccination with rabies immunoglobulin (RIG). Information on rabies vaccine and RIG can be found in the green book “Immunisation against Infectious Disease” (https://www.gov.uk/government/publications/rabies-the-green-bookchapter-27). This letter provides additional information on the correct administration of rabies vaccine and RIG and should remain with the product. Rabies immunoglobulin (RIG) Dosage and volume of RIG The recommended dose of RIG is 20 IU/kg, and the volume needed to administer this dose needs to be calculated. RIG batches from the same manufacturer do vary in potency. It is therefore critical to know the weight of the patient and the potency of the RIG. The volume required for your patient should have already been provided to you. If not, the description of the potency is indicated on the vial of Berirab P and is 150 IU/ml i.e. 300 IU/pre-filled syringe. If the volume required is more than 2ml then this will need to be delivered using multiple injections. Partial volumes can be calculated by estimating that each mark on the syringe is equivalent to 0.2ml. Administration of RIG RIG should be infiltrated into the depth of the wound and around the site of the wound if possible. If this is difficult, then RIG can be given in the anterolateral thigh. Where more than 2mls is to be given the immunoglobulin should be given at different sites. Vaccine and RIG must never be given at the same anatomical site, but can be given on the same day. RIG is not given after seven days post initiation of rabies PEP vaccine (or to an individual who is already partially immunised).
The RIG used in this country is sourced from overseas human donors following rabies vaccination, and is not from UK donors. Rabies vaccine Dose and schedule of vaccine The recommended UK schedule for unimmunised individuals is 1.0 ml vaccine (1 complete vial) at the following intervals: 0, 3, 7, 14, 28-30, with day 0 being the day of first vaccine administration (this is NOT necessarily the day of the exposure). If a dose of vaccine is missed, or timing has been compromised, the next vaccine should be given as soon as possible, and considered as the missed dose, and subsequent intervals readjusted. The first three doses of vaccine can be given plus/minus 1 day of the scheduled date if vaccination on the scheduled date is not possible (and to allow for administration that would be on a Saturday or Sunday). The 5 th final dose of rabies vaccine should not be given before day 26. Administration of vaccine The vaccine should be administered intramuscularly in the deltoid muscle, with each sequential dose given in alternate arms. We recommend that you start in the non-dominant arm. Advice on vaccination of individuals with bleeding disorders can be found in the Green Book page 27. Storage of vaccine and RIG The supplied RIG and vaccine should be stored within the cold chain until use, and should be used as soon as possible after receipt. If you have any further questions about using rabies vaccine or RIG for your patient that are not covered here or in the green book please contact the Rabies Office at Colindale on 0208 327 6204. Please note the advice given is based on the available information. It remains the responsibility of registered healthcare professionals prescribing, supplying or administering medicines to check the medicine is appropriate for the patient. This includes checking doses, contraindications and drug interactions. The clinician should be aware of potential side effects and communicate these to the patient. Yours faithfully
Dr Kevin E Brown MD MRCP FRCPath MA MSc Deputy Director, Virus Reference Department E:
[email protected]
STORAGE AND STABILITY
Berirab P is to be stored at +2 C to +8 C (refrigerator). Do not freeze! Keep container in the outer carton in order to protect its contents from light. Berirab P must not be used after the expiry date given on the pack and container. Once the container has been opened the contents have to be used imme diately. Keep out of the reach and sight of children! Any unused product or waste material should be disposed of in accord ance with local requirements.
CSL Behring PACKAGE INSERT Read all of this leaflet carefully before you start taking this medicine. Keep this leaflet. You may need to read it again. If you have further questions, ask your doctor or pharmacist. This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
—
—
—
QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml contains: Active ingredients Human protein thereof immunoglobulin with antibodies to rabies virus
—
100— 170 mg at least 95 % at least 150 IU
Berirab® P Solution for injection for intramuscular use
Other ingredients Aminoacetic acid (glycine), sodium chloride, HCI or NaOH (in small amounts for pH adjustment), water for injections
Active ingredient: Human rabies immunoglobulin PHARMACOTHERAPEUTIC GROUP
PHARMACEUTICAL FORM AND PRESENTATIONS
Pharmaceutical form Solution for injection for intramuscular use Berirab P is a clear solution. The colour can vary from colourless to paleyellow up to light-brown during shelf life. Presentations Pack of 1 ampoule with 2 ml containing at antibodies Pack of 1 prefilled syringe with 2 ml containing antibodies Pack of 1 ampoule with 5 ml containing at antibodies Pack of 1 prefilled syringe with 5 ml containing antibodies Pack of 1 ampoule with 10 ml containing at antibodies Not all pack sizes may be marketed.
least 300 lU of rabies at least 300 IU of rabies least 750 lU of rabies at least 750 IU of rabies least 1500 IU of rabies
Immune sera and immunoglobulins, human rabies immunoglobulin ATC-code: JO6B B05 THERAPEUTIC INDICATIONS
Post-exposure prophylaxis of rabies infection after • exposure to scratches, bites or other injuries caused by a suspected rabid animal • mucous membrane contamination with infectious tissue or saliva of a suspected rabid animal • contact of mucous membranes or newly skin injury with rabies live attenuated vaccine e.g. vaccination baits. Human rabies immunoglobulin must always be used in combination with a rabies vaccine. National and/or WHO guidelines regarding protection against rabies should be observed.
MARKETING AUTHORIZATION HOLDER
CONTRAINDICATIONS
CSL Behring GmbH Emil-von-Behring-Str. 76 35041 Marburg Germany
Because of the life-threatening risk due to rabies, there are no contraindi cations to the administration of rabies immunoglobulin. SPECIAL WARNINGS AND PRECAUTIONS FOR USE
DATE OF LAST REVISION
Ensure that Berirab P is not administered into a blood vessel because of the risk of shock. True hypersensitivity reactions are rare. Berirab P contains a small quantity of IgA. Individuals who are deficient in gA have the potential for develop ing gA antibodies and may have anaphylactic reactions after adminis tration of blood components containing IgA. Rarely human rabies immunoglobulin can induce a fall in blood pressure with anaphylactic reactions, even in patients who had tolerated previous treatment with human immunoglobulin. Therapeutic measures depend on the nature and severity of the event. The current medical standards for shock treatment are to be observed.
May 2008
Patients should be observed for at least 20 minutes after administration of Berirab P.
4
A1291 G26 (20348])
Particularly in cases of inadvertent i.v. injection, patients should be observ ed for longer term (at least 1 hour) after administration. Important information about some of the ingredients of Berirab P This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium free’. Virus safety Standard measures to prevent infections resulting from the use of medi cinal products prepared from humanblood 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 HIV, HBV and HCV, and for the non-enveloped viruses HAV and parvo virus 819. 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 Berirab P 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. Pregnancy and lactation The safety of Berirab P for use in human pregnancy has not been estab lished in controlled clinical trials. Long lasting clinical experience with immunoglobulins does indicate that no harmful effects on the course of pregnancy, on the foetus or the neonate are to be expected.
and the first dose of rabies vaccine should be given as soon as possible after exposure. Additional doses of rabies vaccine should be given accord ing to official guidelines or the manufacturer’s instruction. Rabies prophylaxis exclusively with simultaneous vaccination: recommen ded dose of rabies immunoglobulin is 20 IU Berirab P per kg body weight (bw). Because of the risk of interference with antibody production related to vaccination, neither the dose should be increased nor repeat rabies im munoglobulin be given even if the onset of the simultaneous prophylaxis is delayed. Method of administration Human rabies immunoglobulin should be administered via the intramus cular route. Do not use solutions which are cloudy or contain residues (deposits/ particles). Berirab P is a ready-for-use solution and should be administered at body temperature. Of the total quantity of rabies immunoglobulin, as much as possible should be instilled deeply into and around the wound. The remainder is to be injected i.m. preferably into the vastus lateralis muscle with the patient lying down. If comparatively large total volumes are required, it is advisable to admin ister them in divided doses at different sites. This applies in the case of doses above 2 ml for children up to 20 kg bw and doses above 5 ml for persons above 20 kg bw. In case of simultaneous prophylaxis the immunoglobulin and the vaccine should be administered at contralateral sites of the body.
Effects on ability to drive and use machines No effects on the ability to drive and use machines have been observed.
The immunoprophylaxis should be carried out immediately even in case that suspicion is not clarified if the animal was infected. Wounds should not be primary sewed. Parts of the body that are possibly contaminated and all wounds are to be cleaned immediately with soap or detergent, washed well with water and treated with 70 % alcohol or iodine tincture; this is also true for contamination with vaccine solution from vaccination baits.
INTERACTIONS WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTIONS
In the presence of a coagulation disorder, in the case of which intramus cular injections are contraindicated, Berirab P may be given subcutane ously. Afterwards the injection site should be compressed with a swab.
Vaccinations with live attenuated virus vaccines Immunoglobulin administration may impair the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella vaccines for a period of up to three months. After administration of Berirab P an interval of at least three months should elapse before vaccination with live virus vaccines. In the case of measles, this impairment may persist for up to four months. 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 immunoglobu lin injection may result in misleading positive test results. Passive transmission of antibodies to erythiocyte antigens, e.g., A, B and D may interfere with some serological tests for red cell allo-antibodies (e.g. Coombs test). Incompatibilities In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products, diluents or solvents.
However, it should be noted that there are no clinical efficacy data to support administration by the subcutaneous route. UNDESIRABLE EFFECTS
If you experience reactions, especially those which ate not mentioned in this package insert, please inform your doctor or pharmacist. In rare cases the following adverse reactions may occur: • allergic reactions including fall in blood pressure, dyspnoea, cutaneous reactions, in isolated cases reaching as far as anaphylactic shock, even when the patient has shown no hypersensitivity to previous adminis tration of immunoglobulins. • generalized reactions such as chills, fever, headache, malaise, nausea, vomiting, arthralgia and moderate back pain. • cardiovascular reactions particularly if the product is inadvertently injected intravascularly. Local reactions At the injection site local pain, tenderness or swelling can be observed in rare cases.
POSOLOGY AND METHOD OF ADMINISTRATION
Posology Post-exposure prophylaxis consists of a regimen of one dose of immuno globulin and full courses of rabies vaccination. Rabies immunoglobulin 20348]
2
For safety with respect to transmissible agents, see section “Special warnings and precautions for use”.
3
