Suprelorin - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

PACKAGE LEAFLET FOR: Suprelorin 4.7 mg implant for dogs

• 1. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND OF THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE, IF DIFFERENT

Marketing authorisation holder :

VIRBAC

1ere avenue 2065 m LID

06516 Carros

FRANCE

Manufacturers responsible for batch release :

VIRBAC

1ere Avenue 2065 m LID

06516 Carros

FRANCE

• 2. NAME OF THE VETERINARY MEDICINAL PRODUCT

Suprelorin 4.7 mg implant for dogs

• 3. STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENT(S)

Suprelorin is a white to pale yellow cylindrical implant containing 4.7 mg deslorelin (as deslorelin acetate).

• 4. INDICATION(S)

For the induction of temporary infertility in healthy, non-castrated, sexually mature male dogs.

• 5. CONTRAINDI­CATIONS

None.

• 6. ADVERSE REACTIONS

Moderate swelling at the implant site was observed observed for 14 days during safety/efficacy studies.

During the treatment period, rare clinical effects have been reported: hair coat disorders (e.g. hair loss, alopecia, hair modification), urinary incontinence, down-regulation associated signs (decrease in testicle size, reduced activity,weight gain). In very rare cases, a testicle may be able to ascend the inguinal ring.

In very rare cases there has been transitory increased sexual interest, increased testicle size and testicular pain immediately after implantation. These signs resolved without treatment.

In very rare cases, a transient behavioural change has been reported with development of aggression (see “Special warnings”).

In humans and animals, testosterone modulates seizure susceptibility. On very rare occasions (<0.01%) transient occurrence of seizure has been reported shortly after implantation, though the casual relationship with the application of the implant has not been established. In some cases, the dog had displayed epileptic seizure prior to the implant administration or was diagnosed as suffering from epilepsy.

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

• – very common (more than 1 in 10 animals treated displaying adverse reaction(s))

• – common (more than 1 but less than 10 animals in 100 animals treated)

• – uncommon (more than 1 but less than 10 animals in 1,000 animals treated)

• – rare (more than 1 but less than 10 animals in 10,000 animals treated)

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

If you notice any serious effects or other effects not mentioned in this leaflet, please inform your veterinary surgeon.

• 7. TARGET SPECIES

Dogs (male).

• 8. DOSAGE FOR EACH SPECIES, ROUTE(S) AND METHOD OF ADMINISTRATION

Administer one implant only, irrespective of the size of the dog (see also “Special warnings”). Repeat treatment every 6 months to maintain efficacy.

Do not use the product if the foil pouch is broken.

One implant should be administered subcutaneously between the shoulder blades of the dog.

• 9. ADVICE ON CORRECT ADMINISTRATION

Disinfection of the implantation site should be undertaken prior to implantation to avoid introduction of infection.

Select the implant site by locating the area of the back midway between the shoulder blades. Avoid injection of the implant into fat, as release of the active substance might be impaired in areas of low vascularisation. If the hair is long, a small area may be clipped, if required.

• 1. Remove Luer Lock cap from the implanter.

• 2. Attach the actuator to the implanter using the Luer Lock connection.

• 3. Lift the loose skin between the shoulder blades. Insert the entire length of the needle subcutaneously.

• 4. Fully depress the actuator plunger and, at the same time, slowly withdraw the needle.

• 5. Press the skin at the insertion site as the needle is withdrawn, and maintain pressure for 30 seconds.

• 6. Examine the syringe and needle to ascertain that the implant has not remained within the syringe or needle, and that the spacer is visible. It may be possible to palpate the implant in situ.

Preloaded implanter

Implant Spacer

The biocompatible implant does not require removal. However, should it be necessary to end treatment, implants may be surgically removed by a veterinarian. Implants may be located using ultrasound.

The actuator can be re-used.

• 10. WITHDRAWAL PERIOD(S)

Not applicable.

• 11. SPECIAL STORAGE PRECAUTIONS

Keep out of the reach and sight of children.

Store in a refrigerator (2°C – 8°C)

Do not freeze

Do not use this veterinary medicinal product after the expiry date which is stated on the carton.

• 12. SPECIAL WARNING(S)

Special warnings

Infertility is achieved from 6 weeks up to at least 6 months after initial treatment. Treated dogs should therefore still be kept away from bitches on heat within the first 6 weeks after initial treatment One out of 75 dogs treated with the veterinary medicinal product during clinical trials mated and tied with a bitch on heat within six months of implantation, but this did not result in pregnancy. Should a treated dog mate with a bitch between 6 weeks and 6 months after treatment, appropriate measures should be taken to rule out the risk of pregnancy.

In rare cases (>0.01 % to < 0.1%), suspected lack of expected efficacy has been reported (in the majority of cases a lack of reduction of testicle size was reported and/or a bitch was mated). Only testosterone levels (i.e. an established surrogate marker of fertility) could definitely confirm a lack of efficacy of the treatment. If lack of treatment efficacy is suspected, then the dog’s implant (e.g. presence) should be checked.

Any mating that occurs more than 6 months after the administration of the veterinary medicinal product may result in pregnancy. However, it is not necessary to keep bitches away from treated dogs following subsequent implantations, provided that the veterinary medicinal product is administered every 6 months.

In certain cases, the implant may be lost from a treated dog. If loss of the first implant is suspected, then this can be confirmed by observing no reduction in scrotal circumference or plasma testosterone levels after 6 weeks from the suspected date of loss, as both should reduce under correct implantation. If loss of the implant is suspected following re-implantation after 6 months, then a progressive increase will be seen in scrotal circumference and/or plasma testosterone levels. In both of these circumstances a replacement implant should be administered.

The ability of dogs to sire offspring following their return to normal plasma testosterone levels, after the administration of the veterinary medicinal product, has not been investigated.

With respect to testosterone levels (an established surrogate marker of fertility), during clinical trials more than 80 % of dogs administered one or more implants, returned to normal plasma testosterone levels (>0.4 ng/ml) within 12 months of implantation. Ninety-eight percent of dogs returned to normal plasma testosterone levels within 18 months of implantation. However, data demonstrating the complete reversibility of clinical effects (reduced testicular size, reduced ejaculation volume, reduced sperm count and reduced libido) including fertility after 6 months, or repeated implantation, are limited. In very rare cases (< 0.01 %) the temporary infertility may last more than 18 months.

During clinical trials, most of the smaller size dogs (<10 kg) maintained suppressed levels of testosterone for more than 12 months following implantation. For very large dogs (>40 kg), data are limited but duration of testosterone suppression was comparable to that seen in medium and large dogs. The use of the veterinary medicinal product in dogs of less than 10 kg or more than 40 kg bodyweight, therefore, should be subject to a risk/benefit assessment performed by the veterinarian.

Surgical or medical castration might have unexpected consequences (i.e. improvement or worsening) on aggressive behaviour. Thus, dogs with sociopathic disorders and showing episodes of intra-specific (dog to dog) and/or inter-specific (dog to another species) aggressions should not be castrated either surgically or with the implant.

Special precautions for use in animals

The use of the veterinary medicinal product in pre-pubertal dogs has not been investigated. It is therefore recommended that dogs should be allowed to reach puberty before treatment with the veterinary medicinal product is initiated.

Data demonstrate that treatment with the product will reduce the libido of the dog.

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

Pregnant women should not administer the veterinary medicinal product. Another GnRH analogue has been shown to be foetotoxic in laboratory animals. Specific studies to evaluate the effect of deslorelin when administered during pregnancy have not been conducted.

Although skin contact with the veterinary medicinal product is unlikely, should this occur, wash the exposed area immediately, as GnRH analogues may be absorbed through the skin.

When administering the veterinary medicinal product, take care to avoid accidental self-injection by ensuring that animals are suitably restrained and the application needle is shielded until the moment of implantation.

In case of accidental self-injection, seek medical advice immediately, with a view to having the implant removed. Show the package leaflet or the label to the physician.

Overdose (symptoms, emergency procedures, antidotes)

No clinical adverse reactions other than those described in the section “Adverse reactions” have been observed following subcutaneous administration of up to 10 times the recommended dose. Histologically, mild local reactions with chronic inflammation of the connective tissue and some capsule formation and collagen deposition have been seen at 3 months after administration following simultaneous subcutaneous administration of up to 10 times the recommended dose.

• 13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE MATERIALS, IF ANY

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. The actuator can be re-used.

• 14. DATE ON WHICH THE PACKAGE LEAFLET WAS LAST APPROVED

Detailed information on this veterinary medicinal product is available on the website of the European

Medicines Agency

• 15. OTHER INFORMATION

The implant is supplied in a pre-loaded implanter. Each pre-loaded implanter is packaged in a sealed foil pouch, which is subsequently sterilised.

Cardboard carton containing either two or five individually foil wrapped implanters that have been sterilised, together with an implanting device (actuator) that is not sterilised. The actuator is attached to the implanter using the Luer Lock connection.

Not all pack sizes may be marketed.

For any information about this veterinary medicinal product, please contact the local representative of the marketing authorisation holder.

Belgie/Belgiqu­e/Belgien VIRBAC BELGIUM NV Esperantolaan 4 BE-3001 Leuven Tél/Tel : +32-(0)16 387 260	Lietuva VIRBAC 1ère avenue 2065 m LID FR-06516 Carros Prancüzija Tel: +33-(0)4 92 08 73 00
PenySnuKa EBnrapun VIRBAC 1ere avenue 2065 m LID FR-06516 Carros OpaH^ua Ten: +33-(0)4 92 08 73 00	Luxembourg/Lu­xemburg VIRBAC BELGIUM NV Esperantolaan 4 BE-3001 Leuven Belgique / Belgien Tél/Tel: +32-(0)16 387 260
Česká republika VIRBAC 1ere avenue 2065 m LID FR-06516 Carros Francie	Magyarország VIRBAC HUNGARY KFT Szent Istvàn krt.11.II/21. HU-1055 Budapest Tel: +36703387177

Tel: +33-(0)4 92 08 73 00

Danmark VIRBAC Danmark A/S Profilvej 1 DK-6000 Kolding Tlf: +45 75521244

Malta VIRBAC 1ère avenue 2065 m LID FR-06516 Carros Franza Tel: + 33-(0)4 92 08 73 00

Deutschland VIRBAC Tierarzneimittel GmbH Rögen 20 DE-23843 Bad Oldesloe Tel: +49-(4531) 805 111	Nederland VIRBAC Nederland BV Hermesweg 15 NL-3771 ND-Barneveld Tel : +31-(0)342 427 127
Eesti VIRBAC 1ere avenue 2065 m LID FR-06516 Carros Prantsusmaa Tel: +33-(0)4 92 08 73 00	Norge VIRBAC Danmark A/S Profilvej 1 DK-6000 Kolding Danmark Tel: + 45 75521244
EMáSa VIRBAC HELLAS A.E. 13o x^M- E.O. A0nvóv – Aapiag EL-14452, MsTapóppoGn Tql: +30 2106219520	Österreich VIRBAC Österreich GmbH Hildebrandgasse 27 A-1180 Wien Tel: +43-(0)1 21 834 260
España VIRBAC ESPAÑA SA Angel Guimerá 179–181 ES-08950 Esplugues de Llobregat (Barcelona) Tel. : + 34-(0)93 470 79 40	Polska VIRBAC Sp. z o.o. ul. Pulawska 314 PL 02–819 Warszawa Tel.: + 48 22 855 40 46
France VIRBAC France 13erue LID FR-06517 Carros Tél : +33-(0)805 05 55 55	Portugal VIRBAC de Portugal Laboratórios LDA R.do Centro Empresarial Ed13-Piso 1– Esc.3 Quinta da Beloura PT-2710–693 Sintra Tel: + 351 219 245 020
Hrvatska VIRBAC 1ere avenue 2065 m LID FR-06516 Carros Francuska Tel: + 33-(0)4 92 08 73 00	Romania VIRBAC 1ere avenue 2065 m LID FR-06516 Carros Franja Tel: + 33-(0)4 92 08 73 00
Ireland VIRBAC 1ere avenue 2065m LID FR-06516 Carros France Tel: + 33-(0)4 92 08 73 00	Slovenija VIRBAC 1ere avenue 2065 m LID FR-06516 Carros Francija Tel : + 33-(0)4 92 08 73 00
Ísland VIRBAC 1ere avenue 2065 m LID FR-06516 Carros Frakkland Sími: + 33-(0)4 92 08 73 00	Slovenská republika VIRBAC 1ere avenue 2065 m LID FR-06516 Carros Francúzsko Tel: + 33-(0)4 92 08 73 00

Italia

VIRBAC SRL

Via Ettore Bugatti, 15

IT-20142 Milano

Tel: + 39 02 40 92 47 1

Kvnpog

VIRBAC HELLAS A.E.

13o x^M- E.O. AOqvo'jv – Aapiag EL-14452, MsTaMoppooq Tq!.: +30 2106219520

Latvija

VIRBAC

1ere avenue 2065 m LID

FR-06516 Carros

Francjia

Tel: +33-(0)4 92 08 73 00

PACKAGE LEAFLET FOR:

Suprelorin 9.4 mg implant for dogs and ferrets

• 1. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND OF THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE, IF DIFFERENT

Marketing authorisation holder:

VIRBAC

Pre avenue 2065 m LID

06516 Carros

FRANCE

Manufacturers responsible for the batch release:

VIRBAC

Pre Avenue 2065 m LID

06516 Carros

FRANCE

• 2. NAME OF THE VETERINARY MEDICINAL PRODUCT

Suprelorin 9.4 mg implant for dogs and ferrets

• 3. STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENT(S)

Suprelorin is a white to pale yellow cylindrical implant containing 9.4 mg deslorelin (as deslorelin acetate).

• 4. INDICATION(S)

For the induction of temporary infertility in healthy, entire, sexually mature male dogs and ferrets.

• 5. CONTRAINDI­CATIONS

None.

• 6. ADVERSE REACTIONS

In dogs: Moderate swelling at the implant site was commonly observed for 14 days during safety/efficacy studies.

During the treatment period, rare clinical effects have been reported: hair coat disorders (e.g. hair loss, alopecia, hair modification), urinary incontinence, down-regulation associated signs (e.g. decrease in testicle size, reduced activity, weight gain). In very rare cases, a testicle may be able to ascend the inguinal ring.

In very rare cases there has been transitory increased sexual interest, increased testicle size and testicular pain immediately after implantation. These signs resolved without treatment.

In very rare cases, a transient behavioural change has been reported with the development of aggression (see “Special warnings”).

In humans and animals, testosterone modulates seizure susceptibility. On very rare occasions (<0.01%) transient occurrence of seizure has been reported shortly after implantation, though the casual relationship with the application of the implant has not been established. In some cases, the dog had displayed epileptic seizure prior to the implant administration or was diagnosed as suffering from epilepsy.

In ferrets: Transient moderate swelling, pruritus and erythema at the implant site were commonly observed during clinical studies.

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

• – very common (more than 1 in 10 animals treated displaying adverse reaction(s))

• – common (more than 1 but less than 10 animals in 100 animals treated)

• – uncommon (more than 1 but less than 10 animals in 1,000 animals treated)

• – rare (more than 1 but less than 10 animals in 10,000 animals treated)

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

If you notice any serious effects or other effects not mentioned in this leaflet, please inform your veterinary surgeon.

• 7. TARGET SPECIES

Dogs (male) and ferrets (male).

• 8. DOSAGE FOR EACH SPECIES, ROUTE(S) AND METHOD OF ADMINISTRATION

Dogs

Administer one implant only, irrespective of the size of the dog (see also “Special warnings”). Repeat treatment every 12 months to maintain efficacy.

Ferrets

Administer one implant only, irrespective of the size of the ferret. Repeat treatment every 16 months to maintain efficacy.

Dogs and ferrets

The implant should be administered subcutaneously between the shoulder blades of the dog or ferret. Do not use the veterinary medicinal product if the foil pouch is broken.

The biocompatible implant does not require removal. However, should it be necessary to end treatment, implants may be surgically removed by a veterinarian. Implants may be located using ultrasound.

• 9. ADVICE ON CORRECT ADMINISTRATION

Dogs

Subcutaneous use.

The recommended dose is one implant per dog, irrespective of the size of the dog (see also “Special warnings”).

Disinfection of the implantation site should be undertaken prior to implantation to avoid introduction of infection. If the hair is long, a small area should be clipped, if required.

The veterinary medicinal product should be implanted subcutaneously in the loose skin on the back between the lower neck and the lumbar area. Avoid injection of the implant into fat, as release of the active substance might be impaired in areas of low vascularisation.

• 1. Remove Luer Lock cap from the implanter.

• 2. Attach the actuator to the implanter using the Luer Lock connection.

• 3. Lift the loose skin between the shoulder blades. Insert the entire length of the needle subcutaneously.

• 4. Fully depress the actuator plunger and, at the same time, slowly withdraw the needle.

• 5. Press the skin at the insertion site as the needle is withdrawn, and maintain pressure for 30 seconds.

• 6. Examine the syringe and needle to ascertain that the implant has not remained within the syringe or needle, and that the spacer is visible. It may be possible to palpate the implant in situ.

Repeat administration every 12 months to maintain efficacy.

Ferrets

Subcutaneous use.

The recommended dose is one implant per ferret, irrespective of the size of the ferret.

Disinfection of the implantation site should be undertaken prior to implantation to avoid introduction of infection. If the hair is long, a small area should be clipped, if required.

It is recommended that the product should be administered under general anaesthesia in ferrets.

The product should be implanted subcutaneously in the loose skin on the back in the intrascapular space. Avoid injection of the implant into fat, as release of the active substance might be impaired in areas of low vascularisation.

• 1. Remove Luer Lock cap from the implanter.

• 2. Attach the actuator to the implanter using the Luer Lock connection.

• 3. Lift the loose skin between the shoulder blades. Insert the entire length of the needle subcutaneously.

• 4. Fully depress the actuator plunger and, at the same time, slowly withdraw the needle.

• 5. Press the skin at the insertion site as the needle is withdrawn, and maintain pressure for 30 seconds.

• 6. Examine the syringe and needle to ascertain that the implant has not remained within the syringe or needle, and that the spacer is visible. It may be possible to palpate the implant in situ.

Tissue glue can be used to close the site of administration if required.

Subsequent implantations should be based on the increase in testis size and/or increase in plasma testosterone concentrations as well as return to sexual activity. See also “Special warnings”.

Preloaded implanter

Implant Spacer

• 10. WITHDRAWAL PERIOD(S)

Not applicable.

• 11. SPECIAL STORAGE PRECAUTIONS

Keep out of the reach and sight of children.

Store in a refrigerator (2°C – 8°C)

Do not freeze.

Do not use after the expiry date which is stated on the carton.

• 12. SPECIAL WARNING(S)

Pregnant women should not administer the veterinary medicinal product. Another GnRH analogue has been shown to be foetotoxic in laboratory animals. Specific studies to evaluate the effect of deslorelin when administered during pregnancy have not been conducted.

Although skin contact with the veterinary medicinal product is unlikely, should this occur, wash the exposed area immediately, as GnRH analogues may be absorbed through the skin.

When administering the veterinary medicinal product, take care to avoid accidental self-injection by ensuring that animals are suitably restrained and the application needle is shielded until the moment of implantation.

In case of accidental self-injection, seek medical advice immediately and show the package leaflet or the label to the physician, with a view to having the implant removed.

Dogs

Infertility is achieved from 8 weeks up to at least 12 months after initial treatment. Treated dogs should therefore still be kept away from bitches on heat within the first 8 weeks after initial treatment.

In 2 out of 30 dogs in the clinical trial infertility was not achieved until approximately 12 weeks after initial treatment, but in most cases these animals were not capable of successfully siring offspring. Should a treated dog mate with a bitch between 8 and 12 weeks after treatment, appropriate measures should be taken to rule out the risk of pregnancy.

Uncommonly, lack of expected efficacy has been reported in dogs (in the majority of reports a lack of reduction in testicle size was reported and/or a bitch was mated). Only testosterone levels (i.e. an established surrogate marker of fertility) could definitely confirm a lack of efficacy of the treatment. If lack of treatment efficacy is suspected, then the dog’s implant (e.g. presence) should be checked.

Any mating that occurs more than 12 months after the administration of the veterinary medicinal product may result in pregnancy. However, it is not necessary to keep bitches away from treated dogs following subsequent implantations for the initial 8 week period, provided that the veterinary medicinal product is administered every 12 months.

In certain cases, the implant may be lost from a treated dog. If loss of the first implant is suspected, then this can be confirmed by observing no reduction in scrotal circumference or plasma testosterone levels after 8 weeks from the suspected date of loss, as both should reduce under correct implantation. If loss of the implant is suspected following re-implantation after 12 months, then a progressive increase will be seen in scrotal circumference and/or plasma testosterone levels. In both of these circumstances a replacement implant should be administered.

The ability of dogs to sire offspring following their return to normal plasma testosterone levels, after the administration of the veterinary medicinal product, has not been investigated.

With respect to testosterone levels (i.e. an established surrogate marker of fertility), during clinical trials 68 % of dogs administered one implant, returned to fertility within 2 years of implantation. 95 % of dogs had returned to normal plasma testosterone levels within 2.5 years of implantation. However, data demonstrating the complete reversibility of clinical effects (reduced testicular size, reduced ejaculation volume, reduced sperm count and reduced libido) including fertility after 12 months, or repeated implantation, are limited. In very rare cases the temporary infertility may last more than 18 months.

Due to limited data, the use of Suprelorin in dogs of less than 10 kg or more than 40 kg bodyweight should be subject to a risk/benefit assessment performed by the veterinarian. During clinical trials with Suprelorin 4.7 mg, the mean duration of testosterone suppression was 1.5 times longer among smaller size dogs (<10 kg) compared with all larger dogs.

Surgical or medical castration might have unexpected consequences (i.e. improvement or worsening) on aggressive behaviour. Thus, dogs with sociopathic disorders and showing episodes of intra-specific (dog to dog) and/or inter-specific (dog to another species) aggressions should not be castrated either surgically or with the implant.

The use of Suprelorin in pre-pubertal dogs has not been investigated. It is therefore recommended that dogs should be allowed to reach puberty before treatment with the veterinary medicinal product is initiated.

Data demonstrate that treatment with the veterinary medicinal product will reduce the libido of the dog.

Ferrets

Infertility (suppression of spermatogenesis, reduced testis size, levels of testosterone below 0.1 ng/ml, and suppression of musky odor) is achieved between 5 weeks and 14 weeks after initial treatment under laboratory conditions. Treated ferrets should therefore still be kept away from jills on heat within the first weeks after initial treatment.

Levels of testosterone remain below 0.1 ng/ml for at least 16 months. Not all parameters of sexual activity have been tested specifically (seborrhoea, urine marking and aggressiveness). Any mating that occurs more than 16 months after the administration of the product may result in pregnancy.

The need for subsequent implantations should be based on the increase in testis size and/or increase in plasma testosterone concentrations and return to sexual activity.

The reversibility of effects and ability of treated hobs to produce offspring subsequently has not been investigated. Therefore, the use of Suprelorin should be subject to a benefit/risk assessment performed by the responsible veterinarian.

In certain cases, the implant may be lost from a treated ferret. If loss of the first implant is suspected, then this can be confirmed by observing no reduction in testis size or plasma testosterone levels as both should reduce under correct implantation. If loss of the implant is suspected following reimplantation, then a progressive increase will be seen in testis size and/or plasma testosterone levels. In both of these circumstances a replacement implant should be administered.

The use of the veterinary medicinal product in pre-pubertal ferrets has not been investigated. It is therefore recommended that ferrets should be allowed to reach puberty before treatment with the veterinary medicinal product is initiated.

Treatment in ferrets should be initiated at the beginning of the breeding season.

The safety after repeated implantations with Suprelorin in ferrets has not been investigated.

The treated hobs may remain infertile up to four years. The veterinary medicinal product should therefore be used prudently in hobs intended for future reproduction.

Dogs: No adverse reactions other than those described in section “Adverse effects” have been observed following subcutaneous administration of up to 6 times the recommended dose. Histologically, mild local reactions with chronic inflammation of the connective tissue and some capsule formation and collagen deposition have been seen at 3 months after administration following simultaneous subcutaneous administration of up to 6 times the recommended dose.

Ferrets: There is no information available in ferrets concerning overdose.

• 13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE MATERIALS, IF ANY

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. The actuator can be re-used.

• 14. DATE ON WHICH THE PACKAGE LEAFLET WAS LAST APPROVED

Detailed information on this veterinary medicinal product is available on the website of the European Medicines Agency

• 15. OTHER INFORMATION