SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

AT, BE, DE, DK, EL, ES, FR, HU, IE, IT, LV, NL, PL, PT, SK, UK:

Rifen 100 mg/ml Solution for Injection for Horses, Cattle and Swine

CZ: Rifen 100 mg/ml - solution for inj.

SE: Rifen vet. 100 mg/ml solution for injection

FI: Ketovet vet 100 mg/ml – Solution for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml contains:

Active substance:

Ketoprofen 100 mg

Excipients:

Benzyl alcohol (E1519) 10 mg

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection.

Clear, colourless to brownish-yellowish solution

4. CLINICAL PARTICULARS

4.1 Target species

Horse, cattle, swine

4.2 Indications for use, specifying the target species

Horse

Diseases affecting the osteoarticular and muscular-skeletal system associated with acute pain and inflammation:

• Osteitis, spavin

• Tendinitis, bursitis

• Naviculitis

• Laminitis

• Myositis

Ketoprofen is also indicated for post-surgical inflammation, symptomatic therapy of colic and fever.

Cattle

Diseases associated with inflammation, pain or fever:

• Respiratory diseases

• Mastitis

• Osteoarticular and muscular-skeletal disorders such as lameness, arthritis and to ease uprise post parturition

• Injuries

Swine

Diseases associated with inflammation, pain or fever:

• Treatment associated with the Postpartum Dysgalactia Syndrome/Mastitis Metritis Agalactia (MMA) Syndrome

• Respiratory tract infections

• Symptomatic treatment of fever

For the short-term relief of post operative pain associated with minor soft tissue surgery such as castration in piglets.

Where necessary ketoprofen should be combined with appropriate antimicrobial therapy.

4.3 Contraindications

Do not use in case of hypersensitivity to the active substance, or to any of the excipients. Do not use in animals suffering from gastrointestinal lesions, haemorrhagic diathesis, impaired hepatic, renal or cardiac function. Do not use with other NSAID drugs concurrently or within 24 hours of each other.

4.4 Special warnings for each target species

Treatment of piglets with ketoprofen before castration reduces post operative pain for 1 hour. To obtain pain relief during surgery co-medication with an appropriate anaesthetic/sedative is needed.

4.5 Special precautions for use

Avoid intra-arterial injection. Do not exceed recommended dose or period of treatment. Special care should be taken when administering the product to animals with severe dehydration, hypovolaemia and hypotension as there is a potential risk of increased renal toxicity.

The use of ketoprofen is not recommended in foals under the age of 15 days. Use in animals less than 6 weeks of age or in aged animals may involve additional risk. If such use cannot be avoided, animals may require a reduced dosage and careful management. See point 4.7 regarding the use of the product in pregnant mares and sows.

Sufficient drinking water must be supplied at all times during treatment.

In colic, a subsequent dose may be given only after a thorough re-examination.

In case of accidental self-injection, seek medical advice immediately and show the package leaflet or the label to the physician. People with known hypersensitivity to ketoprofen or benzyl alcohol should avoid contact with the veterinary medicinal product.

Avoid splashes on the skin and eyes. Rinse thoroughly with water should this occur. If irritation persists seek medical advice. Wash hands after use.

4.6 Adverse reactions (frequency and seriousness)

Due to the mechanism of action of NSAIDs (inhibition of prostaglandin synthesis), gastric and intestinal irritation or ulceration or renal intolerance may occur even after appropriate use.

Intramuscular injections may occasionally cause transient irritation.

Repeated administration to swine may result in reversible inappetence.

Allergic reactions may occur very rarely. In this case the treatment should be stopped.

4.7 Use during pregnancy, lactation

Pregnancy:

The safety of ketoprofen has been investigated in pregnant laboratory animals and cattle and no adverse effects were noted. The product can be used in pregnant cows.

In absence of studies on swine use only according to the benefit/risk assessment by the responsible veterinarian. Do not use in pregnant mares.

Lactation:

Can be used in lactating cows.

4.8 Interaction with other medicinal products and other forms of interaction

The product must not be administered in conjunction with, or within 24 hours of administration ofother NSAIDs and glucocorticoids. Concurrent administration of diuretics, nephrotoxic drugs and anticoagulative drugs should be avoided.

Ketoprofen is highly bound to plasma proteins, and may displace or be displaced by other highly protein bound medicines, such as anticoagulants with the possibility of consequent toxic effects due to the unbound fraction of the drug. Due to the fact that ketoprofen may inhibit platelet aggregation and cause gastrointestinal ulceration, it should not be used with other medicines that have the same profile of adverse drug reactions.

4.9 Amounts to be administered and administration route

Horse:

2.2 mg ketoprofen/kg body weight/day intravenously once daily for up to 3 to 5 consecutive days, i.e. 1 ml per 45 kg body weight.

In order to treat colic one injection is normally sufficient. A second administration of ketoprofen requiresa reassessment of the patient’s clinical status. See point 4.5, Special precautions for use.

Cattle:

3 mg ketoprofen/kg body weight/day intravenously or deep intramuscularly once daily for up to 3 consecutive days,i.e. 3 ml per 100 kg body weight.

Swine:

3 mg ketoprofen/kg body weight as a single deep intramuscular injection, i.e. 3 ml per 100 kg body weight (= 0.03 ml/kg).

For reduction of post-operative pain the product should be injected 10 - 30 minutes before surgical intervention. Particular care should be taken with regard to the accuracy of dosing including the use of an appropriate dosing device (i.e.: low dose syringe) and proper determination of body weight.

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

Overdose with NSAIDs can lead to gastrointestinal ulceration, loss of proteins, hepatic and renal impairment. In tolerance studies performed in pigs up to 25 % of the animals treated at three times the maximum recommended dose (9 mg/kg) for three days or at the recommended dose (3 mg/kg) for triple the maximum recommended time (9 days) showed erosive and/or ulcerative lesions in both the aglandular (pars oesophagica) and glandular parts of the stomach. Early signs of toxicity include loss of appetite and pasty faeces or diarrhoea. If overdose symptoms are observed, symptomatic treatment should be initiated. The occurrence of ulcers is dose dependent to a limited extent.

4.11 Withdrawal period(s)

Meat and offal: 4 days

Milk (cattle): Zero hours

5. PHARMACOLOGICAL PROPERTIES

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

ATCvet code:QM01AE03

5.1 Pharmacodynamic properties

Ketoprofen is a non-steroidal anti-inflammatory drug. In addition to the anti-inflammatory effect, it also exerts an anti-pyretic and analgesic effect. The pharmacological mechanism of action of ketoprofen is based on the inhibition of the cyclo-oxygenase and lipoxygenase. Ketoprofen also prevents the formation of bradykinin and stabilises the cell membranes of lysosomes, which inhibits the release of lysosomal enzymes that mediate tissue destruction.

Ketoprofen is rapidly absorbed after intramuscular administration. Maximum plasma concentration is reached within 30 to 60 minutes. Absolute bioavailability after intramuscular administration in cattle and swine is 90 - 100%, in the horse 70%. The volume of distribution and clearance are approximately 0.17 L/kg and 0.3 L/kg respectively. Linear kinetics prevails.

The plasma half-life after intramuscular administration is 2 to 3 hours. Ketoprofen binds 95% to plasma proteins and is metabolised by reduction to the secondary alcohol. It is excreted rapidly, mainly via the urine i.e. 80% of the dose administered are eliminated within 12 hours. The reduced ketoprofen metabolite prevails in cattle, the glucuronidated conjugate in horses.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

- Benzyl alcohol (E1519)

- Arginine

- Citric acid monohydrate (for pH adjustment)

- Water for injection

6.2 Incompatibilities

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.

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: 28 days

6.4 Special precautions for storage

Keep the glass vial in the outer carton in order to protect from light.

After first opening the immediate packaging do not store above 25 °C.

6.5 Nature and composition of immediate packaging

50 ml, 100 ml, 10 x 50 ml, 10 x 100 ml

Amber glass vials type II, with brombutyl rubber stopper type I and aluminium caps.

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

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

Richter Pharma AG

Feldgasse 19

4600 Wels

Austria

8. MARKETING AUTHORISATION NUMBER

Vm 22080/4001

9. DATE OF FIRST AUTHORISATION

Date:12 March 2010

10. DATE OF REVISION OF THE TEXT

Date:April 2013

Approved:16/08/2013