Summary of product characteristics

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Rispoval IBR-Marker Vivum, Lyophilisate and diluent for suspension for injection for cattle

Rispoval IBR-Marker Live (for UK and Ireland only)

Rispoval Marker Vivo Attenuato (for Italy only)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Composition for 2 ml dose:

Active Substance: Freeze-dried pellet Bovine Herpes Virus type 1 (BoHV-1), strain Difivac (gE-negative), modified live (attenuated) virus	min. 105.0 CCID50* max. 107.0 CCID50*
Excipient(s): Diluent Water for injections	2 ml
* CCID50 = Cell culture infective dose 50%

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Lyophilisate and diluent for suspension for injection.

Lyophilisate: Slightly coloured freeze-dried pellet.

Diluent: Clear, colourless solution.

4. CLINICAL PARTICULARS

4.1 Target species

Cattle

4.2 Indications for use, specifying the target species

For active immunisation of cattle against Infectious Bovine Rhinotracheitis (IBR), to reduce virus shedding and clinical signs including, in female cattle, abortions associated with BoHV-1 infection. A reduction of abortion associated with BoHV-1 infections has been demonstrated during the second trimester of gestation upon challenge 28 days after vaccination. Vaccinated cattle can be differentiated from field virus infected animals due to the marker deletion, unless the cattle were previously vaccinated with a conventional vaccine or infected with field virus.

Onset of immunity:

7 days after a single dose via intranasal administration or 21 days after a single dose via intramuscular administration as demonstrated in seronegative calves.

Duration of immunity following vaccination before 3 months of age:

After intranasal vaccination of calves aged 2 weeks or older without maternally derived antibodies, immunity lasts until at least 3 months of age, when the animals should be revaccinated via intramuscular injection.

A proportion of young calves may have maternally derived antibodies to BoHV-1, which may affect the immune response to vaccination. Consequently, the protection afforded by the vaccine may not be complete until the revaccination at 3 months of age.

Duration of immunity following vaccination at or after 3 months of age:

6 months.

Additional information on protection from abortion afforded by combined vaccination of Rispoval IBR-Marker Vivum with Rispoval IBR-Marker Inactivatum: prevention of abortion has been demonstrated during the third trimester of gestation upon BoHV-1 challenge applied 86 days after a single dose booster vaccination using Rispoval IBR-Marker Inactivatum, which was administered 6 months after a single dose primary vaccination using Rispoval IBR-Marker Vivum.

4.3 Contraindications

Do not use in unhealthy animals.

4.4 Special warnings for cattle

The presence of maternal antibodies can influence the efficacy of the vaccination. Therefore it is recommended to ascertain the immune status of calves before vaccination is started.

4.5 Special precautions for use

Special precautions for use in animals

In some cases, the vaccine virus may be excreted after intranasal administration from vaccinated animals. After intranasal administration of a 10-fold overdose, the vaccine virus was detected for up to 9 days after vaccination. In very young calves and in rare cases, vaccine virus was excreted until day 18 post intramuscular vaccination with a 10-fold overdose. Exceptional transmission of the virus from intranasally-vaccinated animals to non-vaccinated in-contact animals may occur due to the nature of the vaccine even though no verified data available would indicate that spreading of the vaccine virus occurs in a group of animals.

It is recommended to vaccinate all the cattle in the herd.

Special precautions to be taken by the person administering the veterinary medicinal product to animals

In case of accidental self-injection, seek medical advice immediately and show the package leaflet or the label to the physician.

4.6 Adverse reactions (frequency and seriousness)

When injected intramuscularly in very rare cases minor, transient swelling up to 3 cm which generally subsides within 7 days may occur at the injection site. Following intranasal inoculation slight transient, serous nasal discharge may occur in rare cases for up to 7 days.

In very rare cases allergic reactions may occur as with other vaccines, therefore vaccinates should be observed for approximately. 30 minutes following immunisation. In those cases, antiallergics should be administered.

The frequency of adverse reactions is defined using the following convention:

- very common (more than 1 in 10 animals displaying adverse reactions during the course of one treatment)

- common (more than 1 but less than 10 animals in 100 animals)

- uncommon (more than 1 but less than 10 animals in 1,000 animals)

- rare (more than 1 but less than 10 animals in 10,000 animals)

- very rare (less than 1 animal in 10,000 animals, including isolated reports).

4.7 Use during pregnancy, lactation or lay

Can be used during pregnancy and lactation.

4.8 Interaction with other medicinal products and other forms of interaction

Immunosuppressive substances, i.e. corticosteroids or Bovine Virus Diarrhoea modified live vaccines, should be avoided in a period of 7 days prior to and after vaccination as this may impair the development of the immunity.

Interferon sensitive products should not be applied intranasally following 5 days after intranasal vaccination.

No information is available on the safety and efficacy of this vaccine when used with any other veterinary medicinal product. A decision to use this vaccine before or after any other veterinary medicinal product therefore needs to be decided on a case by case basis.

4.9 Amounts to be administered and administration route

Posology

The dose for cattle, over 2 weeks of age, is 2 ml of the reconstituted vaccine for intranasal inoculation and/or intramuscular injection.

The vaccination scheme consists of basic immunisation and booster vaccinations.

Basic immunisation:

Calves of 2 weeks to 3 months of age at first vaccination

The first vaccination should be applied intranasally, followed by a second vaccination intramuscularly at 3 months of age.

A proportion of young calves may have maternally derived antibodies to BoHV-1, which may affect the immune response to vaccination. Consequently, the protection afforded by the vaccine may not be complete until the revaccination at 3 months of age.As an extra precaution in situations of high challenge with BoHV-1, maternal antibody positive animals that have been initially vaccinated at around 2 weeks of age may be given an additional vaccination between the first vaccination and vaccination at 3 months of age. This additional vaccination may be given via either intranasal or intramuscular administration and may be given from 3 weeks after the first vaccination.

Cattle at 3 months of age or older at first vaccination

Animals should be given one intramuscular vaccination.

To prevent abortions associated with BoHV-1 female cattle require a primary course of two intramuscular doses of Rispoval IBR-Marker Vivum 3-5 weeks apart or alternatively a primary course of a single intramuscular dose of Rispoval IBR-Marker Vivum followed 6 months later by a single dose booster using Rispoval IBR-Marker Inactivatum. In order to cover the main abortion risk period, it is recommended that the second dose of the primary course of two intramuscular doses of Rispoval IBR-Marker Vivum or the single dose booster using Rispoval IBR-Marker Inactivatum is administered no later than by the start of the second trimester of each pregnancy.

Beef cattle and fattening bulls are vaccinated preferably just prior to housing (crowding) or at transfer to new groups, while taking into account the interval needed for the onset of protection following the basic vaccination scheme.

Cattle at immediate risk of IBR

In the case of known high BoHV-1 infection pressure, the first dose in cattle (including pregnant females) should be administered intranasally in order to stimulate local immunity, followed 3 – 5 weeks later by the second dose administered intramuscularly to complete the primary vaccination course.

Booster vaccinations:

Animals should be given a single dose booster vaccination 6 months after their initial vaccination course. Animals initially vaccinated with Rispoval IBR-Marker Vivum may be given a single dose booster vaccination with either Rispoval IBR-Marker Vivum to provide 6 months of protection or Rispoval IBR-Marker Inactivatum to provide a duration of immunity of 12 months of protection. Thereafter, single dose booster vaccinations should be administered every 6 months (if using Rispoval IBR-Marker Vivum) or every 12 months (if using Rispoval IBR-Marker Inactivatum).

Method of administration

The freeze-dried product should be reconstituted aseptically just prior to use. The vaccine is prepared as follows:

For 10 and 50 dose vials approx. 4 ml of the respective diluent are transferred to the vial containing the freeze-dried pellet and then mixed.

The reconstituted virus fraction is finally transferred back into the respective remaining diluent and mixed well. The product is then ready for use.

The needles and syringes used for application of the vaccine must not be sterilised by chemical disinfectants as this may impair the efficacy of the vaccine.

The vaccine is injected aseptically via the intramuscular route (2 ml) or sprayed into the nostrils (1 ml per nostril during aspiration) with the intranasal applicator available from Zoetis. Once resuspended the vaccine remains potent for max. 8 hours when product is withdrawn sterile and the vaccine is refrigerated.

Vaccination schemes summary

From 2 weeks to 3 months of age

Rispoval IBR-Marker vaccine used		Revaccination intervals
Primary vaccination
First dose, from 2 weeks of age (route of administration)	Second dose, at 3 months of age (route of administration)	Interval to next booster vaccination (vaccine and route of administration)	All subsequent booster vaccinations (vaccine and route of administration)
Vivum (intranasal)	Vivum (intramuscular)	6 months (Vivum, intramuscular)	6 months (Vivum, intramuscular)
Vivum (intranasal)	Vivum (intramuscular)	6 months (Inactivatum, subcutaneous)	12 months (Inactivatum, subcutaneous)

From 3 months of age

Rispoval IBR-Marker vaccine used	Revaccination intervals
Primary vaccination (number of doses and route of administration)	Interval to first booster vaccination (vaccine and route of administration)	All subsequent booster vaccinations (vaccine and route of administration)
Vivum (one dose, intramuscular)	6 months (Vivum, intramuscular)	6 months (Vivum, intramuscular)
Vivum (one dose, intramuscular)	6 months (Inactivatum, subcutaneous)	12 months (Inactivatum, subcutaneous)
Inactivatum (two doses, subcutaneous, with 3-5 week interval)	6 months (Inactivatum, subcutaneous)	6 months (Inactivatum, subcutaneous)

For female cattle for protection against abortion:

Rispoval IBR-Marker vaccine used	Revaccination
Vaccination schedule (number of doses and route of administration) recommended to be applied no later than by the start of second trimester of pregnancy
Vivum (two doses, intramuscular, with 3-5 weeks interval)	Inactivatum (one dose, subcutaneous) recommended to be applied no later than by the start of the second trimester of each pregnancy
Vivum (one dose, intramuscular) followed by Inactivatum (one dose, subcutaneous), with 6 months interval
Inactivatum (two doses, subcutaneous, with 3-5 week interval)

For vaccination in known high BoHV-1 infection pressure:

Rispoval IBR-Marker vaccine used	Revaccination intervals
Primary vaccination (number of doses and route of administration)	Interval to first booster vaccination (vaccine and route of administration)	All subsequent booster vaccinations (vaccine and route of administration)
Vivum (one dose, intranasal), followed by Vivum (one dose, intramuscular) with 3-5 weeks interval	6 months (Vivum, intramuscular, OR Inactivatum, subcutaneous)	6 months (Vivum, intramuscular) OR 12 months (Inactivatum, subcutaneous)

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

After intranasal administration of a 10-fold overdose, a transient hyperthermia (> 39.5°C) was observed in some calves for up to 3 consecutive days. After intramuscular administration of a 10-fold overdose, a transient hyperthermia (> 39.5°C) was observed in some calves for up to 4 consecutive days. In another study, a transient (one day) slight serous ocular discharge was observed in some calves after intramuscular administration of a 10-fold overdose.

Otherwise reactions after administration of an overdose of the vaccine are not different from those observed after the single dose.

4.11 Withdrawal period(s)

Zero days.

5. IMMUNOLOGICAL PROPERTIES

Live viral vaccine.

ATCvet code: QI02AD01

The vaccine induces immunity in cattle against clinical respiratory symptoms caused by the Infectious Bovine Rhinotracheitis (IBR) virus. After a single dose vaccination, a significant reduction of virus shedding duration has been demonstrated upon challenge. After two doses of vaccine, the intensity and duration of clinical symptoms as well as the titre and duration of virus shedding are significantly reduced following infection. As with other vaccines, vaccination may not completely prevent but does reduce risk of infection. The product induces in vaccinated cattle antibodies, which are detected in the serum neutralisation test and in conventional ELISA tests. With specific test kits these antibodies can be differentiated - due to the lack of antibodies against gE - from those of field virus infected animals or animals vaccinated with conventional vaccines.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Dextran stabiliser solution

Minimum essential medium with Earle´s Salts

HEPES 2M solution

6.2 Incompatibilities

Do not mix with any other veterinary medicinal product, except diluent supplied for use with the product.

6.3 Shelf life

Shelf-life of the veterinary medicinal product as packaged for sale: 36 months

Shelf-life after reconstitution according to directions: 8 hours

6.4. Special precautions for storage

Store in a refrigerator (+2°C to +8°C). Protect from frost, heat or light.

6.5 Nature and composition of immediate packaging

Not all pack sizes may be marketed.

6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products

Dispose of waste material by boiling, incineration or immersion in an appropriate disinfectant approved for use by the competent authorities.

7. MARKETING AUTHORISATION HOLDER

Zoetis UK Limited

5th Floor, 6 St. Andrew Street

London

EC4A 3AE

8. MARKETING AUTHORISATION NUMBER

Vm 42058/4126

9. DATE OF FIRST AUTHORISATION

10 February 1999

10. DATE OF REVISION OF THE TEXT

July 2015

16 September 2015