SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Butagran Equi, 200 mg/g, oral powder for horses.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Per g:

Active substance:

Phenylbutazone 200 mg

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Oral powder.

White powder.

4. CLINICAL PARTICULARS 4.1 Target species

Horses.

4.2 Indications for use, specifying the target species

The product is indicated for the treatment of musculo-skeletal conditions where relief from pain and a reduction in the associated inflammation is required e.g. in lameness associated with osteoarthritic conditions, bursitis, laminitis and soft tissue inflammation, particularly where continued mobility is considered desirable.

It is also of value in limiting post-surgical inflammation, myositis and other soft tissue inflammation.

The product can be used as an anti-pyretic where this is considered advisable e.g. in viral respiratory infections.

4.3 Contraindications

Do not use in known cases of hypersensitivity to the active substance, or to any of the excipients.

Do not use in animals suffering from cardiac, hepatic or renal disease, where there is the possibility of gastrointestinal ulceration or bleeding or where there is evidence of a blood dyscrasia.

4.4 Special warnings for each target species

The clinical effects of phenylbutazone can be evident for at least three days following cessation of therapy. This should be borne in mind when examining horses for soundness.

4.5 Special precautions for use

i. Special precautions for use in animals

Do not exceed the stated dose as the therapeutic index of phenylbutazone is low.

Use in any animal less than 6 weeks of age or in aged animals may involve additional risk. If such use cannot be avoided, animals may require careful clinical management.

Avoid use in any dehydrated, hypovolaemic or hypotensive animal as there is a potential risk of increased renal toxicity. Keep water readily available during the treatment period to avoid dehydration.

NSAIDs can cause inhibition of phagocytosis and hence in the treatment of inflammatory conditions associated with bacterial infections, appropriate concurrent antimicrobial therapy should be instigated.

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

• This product may cause hypersensitivity (allergic) reaction in those sensitised to phenylbutazone, either via skin contact or accidental ingestion.

• People with known hypersensitivity to phenylbutazone should avoid contact with this product.

• If you develop symptoms following exposure, such as a skin rash, you should seek medical advice and show the doctor this warning. Swelling of the face, lips or eyes, or difficulty breathing, are more serious symptoms and require urgent medical attention.

• This product can be irritating to the skin and the eyes. Avoid contact with the eyes. In case of accidental eye contact, irrigate eyes with plenty of clean water. If irritation persists, seek medical advice.

• Care should be taken to avoid inhaling or ingesting the powder. In the event of accidental inhalation or ingestion, seek medical advice and show the product packaging to the doctor.• Wash any exposed skin and hands after use.

4.6 Adverse reactions (frequency and seriousness)

In common with other NSAIDs that inhibit prostaglandin synthesis, there may be gastric and/or renal intolerance. This is usually associated with overdosage and such events are rare (more than 1 but less than 10 animals in 10,000 animals treated). Recovery is usual on cessation of treatment and following the initiation of supportive symptomatic therapy (see 4.10 for further information).

Blood dyscrasia may occur.

Ponies are very sensitive to gastric ulceration with this product, even at therapeutic doses (diarrhoea, ulceration in the mouth and hypoproteinaemia may also be seen).

If adverse reactions occur, treatment should be discontinued and the advice of a veterinarian should be sought.

4.7 Use during pregnancy or lactation

Pregnancy:

Care should be exercised if administered to pregnant mares. Although no adverse effects of phenylbutazone on the foetus or maintenance of pregnancy have been reported during field use, no definitive safety studies have been carried out in the mare.

Foetotoxic effects of phenylbutazone have been recorded in experimental animal species at high dose levels.

Lactation:

The safety of the product in lactating mares has not been demonstrated

If the administration of phenylbutazone to pregnant or lactating mares is considered essential the potential benefits should be weighed against the potential hazard to the mare and/or foal.

Avoid use around time of parturition.

4.8 Interaction with other medicinal products and other forms of interaction

Concurrent administration of potential nephrotoxic drugs should be avoided.

Phenylbutazone is extensively bound to plasma proteins. It may displace other drugs that are highly protein-bound e.g. some sulphonamides, warfarin or it may itself be displaced to produce an increase in non-bound pharmacologically active concentrations, which can lead to toxic effects.

Concurrent therapy with other therapeutic agents should be undertaken with caution due to the risk of metabolic interactions. Phenylbutazone may interfere with the metabolism of other drugs e.g. warfarin, barbiturates, with resultant toxicity.

There is evidence to indicate that the pharmacokinetics of penicillin and gentamicin products may be affected by concurrent administration of products containing phenylbutazone with a possible reduction of therapeutic efficacy, since tissue penetration may be reduced. The distribution of other drugs given concurrently may also be affected.

Do not administer other NSAIDs concurrently or within 24 hours of each other.

Phenylbutazone induces hepatic microsomal enzyme activity.

4.9 Amounts to be administered and administration route

For oral administration.

For each 450 kg of body weight the following dosage guide should be used according to individual response:

Day 1: Two sachets or 10 g of product twice daily (equivalent to 4.4 mg of phenylbutazone/kg of BW on each occasion).

Day 2-4: One sachet or 5 g of product twice daily (equivalent to 2.2 mg of phenylbutazone/kg of BW on each occasion) followed by one sachet or 5 g of product daily (2.2 mg of phenylbutazone/kg of BW daily) or on alternate days as required.

If no response is evident after 4-5 days, discontinue treatment. Hay may delay the absorption of phenylbutazone and so the onset of a clinical effect. It is advisable not to administer hay immediately prior to, or during the administration of the product.

For ease of administration the product may be mixed with a limited quantity of bran or oats.

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

Overdosing may result in gastric and large intestinal ulceration and general enteropathy. Renal papillary damage may also occur with impaired renal function. Subcutaneous oedema, especially under the jaw may become evident due to plasma protein loss.

There is no specific antidote. If signs of possible overdosage occur, treat the animal symptomatically.

4.11 Withdrawal periods

Not for use in horses intended for human consumption.

Treated horses may never be slaughtered for human consumption.

The horse must have been declared as not intended for human consumption under national horse passport legislation.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non-steroids

ATCvet-code: QM01AA01

5.1 Pharmacodynamic properties

Phenylbutazone is a pyrazolone non-steroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory and anti-pyretic activity. These pharmacodynamic effects are achieved by the inhibition of prostaglandin synthetase (cyclo-oxygenase).

5.2 Pharmacokinetic properties

The plasma elimination half-life of phenylbutazone in the horse varies from

3.5 - 8.0 hours. Normally peak plasma levels are achieved approximately 23 hours after administration. Oral bioavailability is high but concurrent feeding of hay can delay the time to peak concentration, decreases the peak plasma concentrations and so delay the onset of a clinical effect.

Phenylbutazone binds heavily to plasma albumin.

Phenylbutazone is metabolised in the liver to oxyphenbutazone, which also has similar pharmacological activity. Further metabolism takes place to gamma-hydroxyphenylbutazone Excretion is mainly via the urine.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Glucose Monohydrate

Hypromellose

Butter vanilla flavour

6.2 Major incompatibilities

Do not mix this product with any other veterinary medicinal product.

6.3 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 3 years. Shelf life after first opening the immediate packaging: use immediately after opening.

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and composition of immediate packaging

- Heat-sealed PET/LDPE/aluminium foil/LDPE laminated sachet of 5 grams of product;

- Heat-sealed aluminium foil/LDPE/paper/LDPE laminated sachet of 5 grams of product.

- Sachets are packed in a cardboard box containing 20 or 100 sachets for single use.

Not all pack sizes may be marketed.

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

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Dopharma Research B.V.

Zalmweg 24

4941 VX Raamsdonksveer The Netherlands

8. MARKETING AUTHORISATION NUMBER

Vm 28365/4004

9. DATE OF THE FIRST AUTHORISATION

08 February 2013

10. DATE OF REVISION OF THE TEXT

January 2018

Approved: 11 January 2018