RABIPUR POWDER AND SOLVENT FOR SOLUTION FOR INJECTION
Active substance(s): INACTIVATED RABIES VIRUS ANTIGEN
NAME OF THE MEDICINAL PRODUCT
Powder and solvent for solution for injection
Rabies vaccine, inactivated
QUALITATIVE AND QUANTITATIVE COMPOSITION
After reconstitution, 1 vial (1.0 ml) contains:
Rabies virus* (Inactivated, strain Flury LEP)……………………………≥ 2.5 IU
* produced on purified chick embryo cells (PCEC)
This vaccine contains residues of polygeline, chicken proteins (e.g., ovalbumin),
human serum albumin, and may contain traces of neomycin, chlortetracycline and
amphotericin B. See sections 4.3 and 4.4.
For excipients see section 6.1.
Powder and solvent for solution for injection.
The powder is white.
The solvent is clear and colourless.
Rabipur is indicated for active immunization against rabies in individuals of all ages.
This includes pre-exposure prophylaxis (i.e. before possible risk of exposure to rabies), in both
primary series and booster dose, and post-exposure prophylaxis (i.e. after suspected or proven
exposure to rabies).
Rabipur is to be used on the basis of official recommendations.
Posology and method of administration
Dosage in adults and children
The recommended single intramuscular (IM) dose is l.0 ml in individuals of all ages.
Pre-exposure Prophylaxis (PrEP)
In previously unvaccinated individuals, an initial course of pre-exposure prophylaxis
consists of three doses (each of l.0 ml) administered IM on days 0, 7 and 21 (or 28).
The individual IM booster dose is 1.0 ml.
Rabipur may be used for booster vaccination after prior immunization with a human diploid cell
rabies vaccine (HDCV).
The need of intermittent serological testing for the presence of antibody ≥ 0.5 IU/ml
and the administration of booster doses should be assessed in accordance with official
Experience shows that reinforcing doses are generally required every 2-5 years.
Post-exposure Prophylaxis (PEP)
Post exposure prophylaxis consists of:
• local treatment of the wound as soon as possible after exposure,
• a course of rabies vaccine and
• administration of rabies immunoglobulin, if indicated
The indication for post-exposure prophylaxis depends on the type of contact with
the suspected rabid animal, as provided in Table 1, Recommended post-exposure
prophylaxis according to type of exposure. Post-exposure immunisation should
begin as soon as possible after exposure.
Table 1: Recommended post-exposure prophylaxis according to type of exposure
Type of exposure to a
of exposure domestic or wilda) animal
suspected or confirmed to
be rabid, or animal
unavailable for testing
Touching or feeding of
Licks on intact skin
Contact of intact skin with
secretions or excretions of a
None, if reliable case history is
rabid animal or human case.
Nibbling of uncovered skin
Administer vaccine immediately b)
Minor scratches or abrasions Stop treatment if animal remains
healthy throughout an observation
period of 10 days c) or is proven to
be negative for rabies by reliable
laboratory using appropriate
Single or multiple
transdermal bitesd) or
scratches, licks on broken
Contamination of mucous
membrane with saliva (i. e.
Exposure to batse)
Administer rabies vaccine
immediately, and rabies
immunoglobulin, preferably as
soon as possible after initiation of
post-exposure prophylaxis. Rabies
immunoglobulin can be injected
up to 7 days after first vaccine
Stop treatment if animal remains
healthy throughout an observation
period of 10 days or is proven to
be negative for rabies by reliable
laboratory using appropriate
Exposure to rodents, rabbits or hares does not routinely require rabies post-exposure
If an apparently healthy dog or cat in or from a low-risk area is placed under
observation, treatment may be delayed.
This observation period applies only to dogs and cats. Except for threatened or
endangered species, other domestic and wild animals suspected of being rabid should
be euthanized and their tissues examined for the presence of rabies antigen by
appropriate laboratory techniques.
Bites especially on the head, neck, face, hands and genitals are category III
exposures because of the rich innervation of these areas.
Post-exposure prophylaxis should be considered when contact between a human and a
bat has occurred, unless the exposed person can rule out a bite or scratch or exposure of
a mucous membrane.
Post-exposure prophylaxis of previously unvaccinated individuals
• 5 dose Essen regimen (1-1-1-1-1): one 1.0 ml IM injection on each of days 0,
3, 7, 14 and 28
4 dose Zagreb regimen (2-1-1): two 1.0 ml IM injections on day 0 (one in
each of the two deltoids or thigh sites) followed by one 1.0 ml IM injection on
each of days 7 and 21.
Post-exposure prophylaxis in previously vaccinated individuals
In previously vaccinated individuals, post-exposure prophylaxis consists of two
doses (each of 1.0 ml) administered IM on days 0, and 3. Rabies immunoglobulin is
not indicated in such cases.
Paediatric individuals receive the same 1.0 ml IM dose as adults.
Geriatric individuals receive the same 1.0 ml IM dose as adults.
In immunocompromised individuals, a complete series of 5 doses according to the
Essen (1-1- 1-1-1) on days 0, 3, 7, 14 and 28) regimen in combination with
comprehensive wound management and local infiltration of rabies immunoglobulin
is required for individuals with category II and III exposure.
Alternatively, two doses of vaccine may be given on day 0, that is, a single dose
of 1.0 ml vaccine should be injected into the right deltoid and another single dose
into the left deltoid muscle. In small children, one dose should be given into the
anterolateral region of each thigh. This would result in a total of 6 doses (2-1-1-1-1
on days 0, 3, 7, 14 and 28).
When feasible, the rabies virus neutralising antibody response should be
measured 2 to 4 weeks (preferably on day 14) following the start of vaccination to
assess the possible need for an additional dose of the vaccine. Immunosuppressive
agents should not be administered during postexposure therapy unless essential for
the treatment of other conditions (see section 4.5).
Method of Administration
For adults and children ≥ 2 years of age, the vaccine should be administered
intramuscular into the deltoid; for children < 2 years, the anterolateral area of the
thigh is recommended.
The vaccine must not be given by intravascular injection, see section 4.4.
Rabies vaccine must not be given by intra-gluteal injection or subcutaneously, see
For instructions on reconstitution of the vaccine before administration, see section 6.6.
Pre-exposure prophylaxis (PrEP)
History of a severe hypersensitivity to the active substance, any of the excipients listed
in section 6.1 or residues in section 2.
Individuals with acute diseases requiring treatment should not be vaccinated until at
least 2 weeks after recovery. Minor infections are not a contraindication to
Post-exposure prophylaxis (PEP)
In view of the almost invariably fatal outcome of rabies, there is no contraindication
to post-exposure prophylaxis, including pregnancy.
Special warnings and precautions for use
Reports of anaphylactic reactions including anaphylactic shock have occurred
following Rabipur vaccination. As with all injectable vaccines, appropriate medical
treatment and supervision should always be readily available in case of a rare
anaphylactic event following the administration of the vaccine.
Patients considered to be at risk of a severe hypersensitivity reaction to the
vaccine or any of the vaccine components should receive an alternative
rabies vaccine if a suitable product is available.
Encephalitis and Guillain-Barré syndrome have been reported to be
temporally associated with the use of Rabipur (see also section 4.8). The
use of corticosteroids to treat adverse reactions such as these may inhibit
the development of immunity to rabies (see section 4.5). A patient's risk of
developing rabies must be carefully considered, before deciding to
Unintentional intravascular injection may result in systemic reactions,
including shock. Do not inject intravascularly. The vaccine must not be
mixed in the same syringe with other medicinal products. If rabies
immunoglobulin is indicated in addition to Rabipur vaccine, then it must
be administered at an anatomical site distant to the vaccination (see section
Anxiety-related reactions, including vasovagal reactions (syncope),
hyperventilation or stress- related reactions, may occur in association with
vaccination as a psychogenic response to the needle injection (see section
4.8). It is important that procedures are in place to avoid injury from
Rabies vaccine must not be given by intra-gluteal injection or
subcutaneously, as the induction of an adequate immune response may be less
Interaction with other medicinal products and other forms of interaction
Immunosuppressive agents can interfere with the development of an
adequate response to the rabies vaccine. Therefore, it is recommended that
serological responses should be monitored in such subjects, and additional
doses administered as necessary (see section 4.2).
All of the rabies immunoglobulin, or as much as anatomically possible (but
avoiding possible compartment syndrome), should be administered into or
around the wound site or sites. The remaining immunoglobulin, if any,
should be injected intramuscularly at a site distant from the site of vaccine
administration to avoid possible interference with simultaneously
administered rabies vaccine.
Other inactivated vaccines may be given at the same time as Rabipur. Concomitant
vaccines should always be administered at separate injection sites and preferably
Fertility, pregnancy and lactation
No cases of harm attributable to use of Rabipur during pregnancy have been
observed. Rabipur may be administered to pregnant women when postexposure prophylaxis is required.
The vaccine may also be used for pre-exposure prophylaxis during
pregnancy if it is considered that the potential benefit outweighs any possible
risk to the foetus.
While it is not known whether Rabipur enters breast milk, no risk to the breastfeeding infant has been identified. Rabipur may be administered to breastfeeding
women when post-exposure prophylaxis is required.
The vaccine may also be used for pre-exposure prophylaxis in breastfeeding women
if it is considered that the potential benefit outweighs any possible risk to the infant.
Non clinical reproductive and developmental toxicity studies have not been
Effects on ability to drive and use machines
No studies have been carried out with Rabipur to assess the effect on the ability to
drive or use machines (see also section 4.8).
Some of the adverse effects described in section 4.8, may affect the ability to drive
and use machines.
Summary of the safety profile
Anaphylactic reactions including anaphylactic shock that are very rare but
clinically severe, and potentially lethal, systemic allergic reactions, can occur
following Rabipur vaccination. Anaphylaxis was not reported during clinical
trials of Rabipur.
The most commonly reported solicited adverse reactions were injection site pain
(30-85%, mainly pain due to injection) or injection site induration (15-35%). Most
injection site reactions were not severe and resolved within 24 to 48 hours after
Mild allergic reactions to Rabipur (i.e. Hypersensitivity), including rashes and
urticaria may occur after vaccination. Rashes may occur in more than 1 in 10 people,
and urticaria may occur in between 1 in 100 and 1 in 10 people. These reactions are
usually mild in nature and typically resolve within a few days.
A small number of people have reported symptoms of encephalitis and GuillainBarré Syndrome following Rabipur vaccination.
Tabulated list of adverse reactions
The following vaccine-related adverse reactions were reported in clinical studies
and during post-marketing surveillance. During post-marketing experience, the
adverse events are reported voluntarily from a population of uncertain size wherein
an estimate of frequency cannot be made. Hence, these events have been chosen
for inclusion due to their seriousness, frequency of reporting, causal relationship to
Rabipur, or a combination of these factors.
Within each frequency grouping, adverse reactions are presented in order of
decreasing seriousness. In addition, the corresponding frequency category using
the following convention (CIOMS III) is also provided for each adverse
reaction: very common (≥1/10); common (≥1/100, <1/10); uncommon
(≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000) and very rare (<1/10,000)
System organ class
Blood and lymphatic
General disorders and
Nausea, vomiting, Diarrhoea,
Abdominal pain / discomfort
Injection site reactions,
Malaise, Fatigue, Asthenia,
* Adverse reactions from spontaneous reporting
Description of selected adverse reactions
Headache and dizziness were majorly reported during the post-marketing
experience where these remained of transient nature and resolved without any
Adverse event rash followed the same post-marketing surveillance experience
where in majority of cases was reported with limited details with no description
provided; however, few cases for rash were reported in association with potential
Injection site reactions were reported variably and primarily included adverse event
terms of injection site pain/ discomfort/ induration/ swelling/ erythema and oedema.
All these had a favorable outcome even if the treatment was started. None of these
qualified as injection-site cellulitis, and hence remained of transient nature. In
general, injection site reactions were commonly reported in clinical trials with
Rabipur and the post marketing data supports this finding.
For the treatment to hypersensitivity (allergic) reactions, reference is made to section
Once initiated, rabies post-exposure prophylaxis should not be interrupted or
discontinued because of local or mild systemic adverse reactions to rabies vaccine.
Frequency, type and severity of adverse reactions in children are expected to be the
same as in adults.
Other special populations
Rabipur has never been studied exclusively in any specific population group such as
elderly, patients with renal impairment, patients with hepatic impairment, and
elderly individuals patients with other diseases or a specific genotype, because the
risk factors remains the same across all populations. However, these special
populations were not specifically excluded from Rabipur clinical trials and no
clinically relevant differences (i.e. in nature, frequency, seriousness or reversibility
of adverse reactions, or need for monitoring) have been specifically observed.
Reporting of suspected adverse reactions
Reporting 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 adverse reactions
via the Yellow Card Scheme at:www.mhra.gov.uk/yellowcard.
No symptoms of overdose are known.
ATC-Code: J07B G01
The minimum rabies virus antibody titre recommended as being proof of an
adequate immune response after vaccination is ≥ 0.5 IU/ml concentration as
specified by the WHO. In healthy vaccinees, this level should be achieved in
most individuals by Day 14 of a postexposure regimen, with or without
simultaneous administration of RIG and irrespective of age.
In clinical trials with previously unimmunised subjects, almost all subjects achieve an
adequate immune response (RVNAs ≥ 0.5 IU/ml) 3 to 4 weeks after the end of a
primary series of three injections of Rabipur when given according to the
recommended schedule by the intramuscular route.
Persistence of adequate immune response (RVNAs ≥ 0.5 IU/ml) for up to 2 years
after immunization with Rabipur without additional booster has been found in clinical
As antibody concentrations slowly decrease, booster doses may be
required to maintain antibody levels above 0.5 IU/ml. The need for and
timing of boosting should be assessed on a case by case basis, taking into
account official guidance (see also section 4.2).
In a clinical trial, a booster dose of Rabipur administered 1 year after primary
immunization elicited a 10-fold or higher increase in Geometric Mean Concentrations
(GMCs) by day 30. It has also been demonstrated that individuals who had previously
been immunised with Human Diploid Cell Vaccine (HDCV) developed a rapid
anamnestic response when boosted with Rabipur.
In clinical studies, Rabipur elicited adequate neutralising antibodies (≥
0.5 IU/ml) in almost all subjects by day 14 or 30 when administered
according to the WHO-recommended 5-dose* (day 0, 3, 7, 14, 28; 1.0
ml each, intramuscular) Essen regimen or to the WHO recommended 4dose (day 0 [2 doses], 7, 21; 1.0 ml each, intramuscular) Zagreb
*Former WHO recommended Essen regimen consisted of 6 doses (day
0, 3, 7, 14, 28, 90; 1.0 ml each, intramuscularly).
Concomitant administration of Human Rabies Immunoglobulin (HRIG) with the first
dose of rabies vaccine caused a slight decrease in GMCs (Essen regimen). However,
this was not considered to be clinically relevant nor statistically significant.
Preclinical safety data
Preclinical data including single-dose, repeated dose and local tolerance studies
revealed no unexpected findings and no target organ toxicity. No genotoxicity,
carcinogenicity and reproductive toxicity studies have been performed.
List of excipients
Water for injection
In the absence of compatibility studies, Rabipur must not be mixed in the same
syringe with other medicinal products.
After reconstitution the vaccine is to be used immediately.
Special precautions for storage
Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the vials in the outer carton in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
The vaccine may not be used after the expiration date given on package and container
Nature and contents of container
1 vial (type I glass) of freeze-dried vaccine with stopper (chlorobutyl)
1 ampoule (type I glass) of Sterile Diluent for reconstitution (1 mL)
with or without injection syringe (polypropylen with polyethylen plunger) with
Not all pack sizes may be marketed
Special precautions for disposal and other handling
The vaccine should be visually inspected both before and after reconstitution for any
foreign particulate matter and or change in physical appearance. The vaccine must not
be used if any change in the appearance of the vaccine has taken place.
The reconstituted vaccine is clear to slightly opalescent and colourless to slightly
The powder for solution should be reconstituted using the solvent for solution
supplied and carefully agitated prior to injection. The reconstituted vaccine should be
During manufacturing, the vial is sealed under vacuum. Therefore to prevent
problems in withdrawing the reconstituted vaccine from the vial after reconstitution
of the vaccine, it is recommended to unscrew the syringe from the needle to eliminate
the negative pressure. After that, the vaccine can be easily withdrawn from the vial. It
is not recommended to induce excess pressure, since over-pressurization will create
the problems in withdrawing the proper amount of the vaccine.
Any unused vaccine or waste material should be disposed of in accordance with local
MARKETING AUTHORISATION HOLDER
GSK Vaccines GmbH
Emil-von-Behring Stra. 76
MARKETING AUTHORISATION NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
Date of first authorisation: 24/09/2003
Date of last renewal: 12/05/2008
DATE OF REVISION OF THE TEXT