RABIPUR Powder and solvent for solution for injection Ref.[27698] Active ingredients: Rabies vaccine

A protective immune response may not be elicited in all vaccinees.

In case of acute diseases requiring treatment, patients should not be vaccinated until at least 2 weeks after recovery. The presence of a minor infection should not result in the deferral of vaccination.

Hypersensitivity reactions (PEP only)

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. Rabipur contains the excipient polygeline, residues of chicken proteins (e.g., ovalbumin), human serum albumin, and may contain traces of antibiotics (see section 2). In instances in which individuals have developed clinical symptoms of anaphylaxis such as generalized urticaria, upper airway (lip, tongue, throat, laryngeal or epiglottal) oedema, laryngeal spasm or bronchospasm, hypotension or shock, following exposure to any of these substances, the vaccination should only be administered by personnel with the capability and facilities to manage anaphylaxis post-vaccination.

Central nervous system effects

Encephalitis and Guillain-Barré syndrome have been temporally associated with the use of Rabipur (see also section 4.8). A patient’s risk of developing rabies must be carefully considered, before deciding to discontinue immunization.

Route of administration

Rabies vaccine must not be given by intra-gluteal injection or subcutaneously, as the induction of an adequate immune response may be less reliable.

Unintentional intravascular injection may result in systemic reactions, including shock. Do not inject intravascularly.

Anxiety-related reactions

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 fainting.

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).

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.

Available clinical data support concomitant administration of Rabipur with inactivated Japanese encephalitis (JE) vaccine and conjugated MenACWY meningococcal vaccine in adult subjects; limited data are available in the paediatric population.

Almost all adult subjects achieved an adequate immune response (Rabies Viral Neutralizing Antibodies (RVNAs) ≥ 0.5 IU/ml) within 7 days after the end of a primary series of three injections of Rabipur when given concomitantly with inactivated JE vaccine according to either a rapid or the conventional PrEP schedule by the intramuscular route. From day 57 after vaccination a faster decline in immune response to rabies was observed in individuals vaccinated concomitantly with JE vaccine according to the rapid PrEP schedule compared with the concomitant conventional PrEP schedule and the rabies only conventional PrEP schedule. At day 366, percentages of subjects with RVNA concentration ≥0.5 IU/mL were 68%, 76%, and 80% for vaccine groups rabies/JE accelerated, rabies/JE conventional, and rabies conventional, respectively.

All adult subjects achieved an adequate immune response (RVNAs ≥ 0.5 IU/ml) within 28 days after the end of a primary series of three injections of Rabipur when given concomitantly with conjugated MenACWY vaccine according to the recommended conventional schedule by the intramuscular route.

Concomitant vaccines should always be administrated at separate injection sites and preferably contralateral limbs.

Pregnancy

No cases of harm attributable to use of Rabipur during pregnancy have been observed.

Rabipur may be administered to pregnant women when post-exposure 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.

Breastfeeding

While it is not known whether Rabipur enters breast milk, no risk to the breast-feeding 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.

Fertility

Non clinical reproductive and developmental toxicity studies have not been performed.

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. Mild allergic reactions to Rabipur (i.e. hypersensitivity), including rashes (very common) and urticaria (common) may occur after vaccination. These reactions are usually mild in nature and typically resolve within a few days.

Very rare cases with symptoms of Encephalitis and Guillain-Barré Syndrome have been reported following Rabipur vaccination.

In clinical trials, the most commonly reported solicited adverse reactions were injection site pain (30-85%) or injection site induration (15-35%). Most injection site reactions were not severe and resolved within 24 to 48 hours.

Tabulated list of adverse reactions

Adverse reactions considered as being at least possibly related to vaccination have been categorised by frequency. Frequencies are defined as follows: 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).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

In addition to reports in clinical trials, worldwide voluntary reports of adverse reactions received for Rabipur since market introduction are included in the list. These reactions are reported voluntarily from a population of uncertain size and have been chosen for inclusion due to their seriousness, frequency of reporting, causal relationship to Rabipur, or a combination of these factors.

Table 5. Adverse reactions reported in clinical trials and in postmarketing surveillance:

^* Additional adverse reactions from spontaneous reporting

Paediatric population

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

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

In the absence of compatibility studies, Rabipur must not be mixed in the same syringe with other medicinal products.