Ketolin®

Product Group	:	Anti-Inflammatory
Pharmaceutical Form	:	Solution for Injection
Active Ingredient	:	Ketoprofen
Target Type	:	Cattle, Horse
Package Form	:	50 - 100 - 250 ml

For Animal Use Only

Composition - Pharmacological Properties
Indications – Usage
Undesirable Effects – Warnings

For Animal Use Only

KETOLİN

Solution for Injection

Non-Steroid Anti-Inflammatory and Analgesic

COMPOSITION

Ketolin Solution for Injection is a clear, colorless or pale straw colored solution containing 100 mg of Ketoprofen per 1 ml and 10 mg of Benzyl alcohol as an antimicrobial preservative.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamic properties

Ketoprofen is a non-steroidal anti-inflammatory drug. In addition to its anti-inflammatory effect, it also has antipyretic and analgesic effects. Not all modes of action are fully known. The pharmacological mechanism of action of ketoprofen is based on partial inhibition of prostaglandin and leukotrine synthesis by acting on cyclo-oxygenase and lipoxygenase. Ketoprofen also suppresses bradykinin formation and platelet aggregation, stabilizes the cell membranes of lysosomes, which inhibits the release of lysosomal enzymes that mediate tissue destruction.

Pharmacokinetic properties

After intravenous injection to horses, the half-life is approximately 1 hour, the volume of distribution is approximately 0.17 l/kg, and the clearance is approximately. It is 0.3 l/kg. After intramuscular injection in cattle and swine, ketoprofen is rapidly absorbed, with a maximum plasma concentration of approximately 11 micrograms/ml achieved in ½ to 1 hour. The mean absorption time is approximately 1 hour, and the plasma half-life is 2 - 2 ½ hours. The bioavailability after intramuscular injection is 90-100% in cattle and pigs. In case of repeated injection at 24-hour intervals, ketoprofen exhibits linear and constant kinetics as the above parameters remain unchanged. Approximately 95% of ketoprofen is bound to plasma proteins.

AREA OF USE / INDICATIONS

Ketolin Solution for Injection is used

In cattle: in supportive treatment of birth-related paralysis, with appropriate etiological treatment, alleviating pain and fever in bacterial respiratory tract infections, supporting recovery in acute clinical mastitis, including acute endotoxic mastitis caused by Gram-negative bacteria, with appropriate etiological treatment. It is used in alleviating breast edema due to osteoarticular and musculo-skeletal system pain, facilitating postpartum standing up.

In horses: in diseases affecting the osteoarticular and musculoskeletal system related to acute pain and inflammation: lameness of traumatic origin, arthritis, osteitis, knee swelling, tendinitis, bursitis, naviculitis, laminitis, myositis.

It is also used in the symptomatic treatment of postoperative inflammation, colic and fever.

USAGE AND DOSAGE

In cattle:

It is administered intramuscularly or intravenously at a dose of 3 mg/kg body weight/day (practically 3 ml per 100 kg body weight per day) for up to 3 days.

In horses:

It is administered intravenously at a dose of 2.2 mg/kg bw/day (practically 1 ml per 45 kg bw) for 3-5 days. It should not be repeated unless confirmed clinically as necessary and appropriate in cases of colic.

In intramuscular applications, no more than 5 ml should be applied to one area.

It should be applied 10-30 minutes before the intervention to reduce post-operative pain.

To avoid overdose, appropriate injector should be used and body weight should be calculated exactly.

SPECIAL CLINICAL INFORMATION AND SPECIAL WARNINGS FOR TARGET SPECIES

The use of the product in animals younger than 6 weeks old and elderly animals involves more risks. If use is mandatory in this group of animals, the dose should be reduced and the animals should be kept under observation. Avoid intravenous administration.

Do not exceed the specified dose and time.

It should be used with caution in dehydrated, hypovolemic and low blood pressure animals due to possible increased renal toxicity.

Additional application in colic cases should be done only if the decision is made after clinical examination. During the treatment, care should be taken to ensure that the animals have sufficient drinking water.

Use during pregnancy, lactation and ovulation

Safety studies in pregnant experimental animals (rat, mouse, rabbit) and pregnant cows did not show any teratogenic or embryotoxic effects of ketoprofen.

The product can be applied to pregnant and lactating cows.

The use of ketoprofen in pregnant mares is not recommended since the effects of ketoprofen on fertility, pregnancy and fetus have not been studied.

UNDESIRED EFFECTS (FREQUENCY AND SEVERITY)

Very rarely, the following symptoms may occur;

• Temporary irritation in repetitive intramuscular applications,

• Gastric and intestinal irritation or ulceration, kidney intolerance (due to the suppression of prostaglandin synthesis by ketoprofen)

• Temporary loss of appetite after repeated administration in pigs

• Allergic reactions

The following conversion is used to report the frequency of side effects;

- Very common (more than 1 in 10 animals)

- 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 in 10,000 animals)

DRUG INTERACTIONS

This product should not be used concomitantly with glucocorticoids and other NSAID products or within 24 consecutive hours.

It should not be administered concomitantly with diuretics, nephrotoxic drugs and anticoagulants.

Ketoprofen is highly bound to plasma proteins, so its binding may be affected by other drugs that are highly bound to plasma proteins, such as ankicoagulants, or ketoprofen affects the protein binding of these products.

Ketoprofen may inhibit platelet aggregation and cause gastrointestinal ulceration. Therefore, it should not be used concomitantly with other drugs with this effect.

SYMPTOMS OF OVERDOSE, PRECAUTIONS AND ANTIDOTE

No clinical side effects were observed in the application of 5 times the recommended dose in horses for 15 days and in cattle 5 times the recommended dose for 5 days. Ketoprofen can cause hypersensitivity reactions and serious damage to the gastric mucosa. In this case, treatment should be discontinued and symptomatic therapy should be applied. Overdose of NSAIDs can cause gastrointestinal ulceration, protein loss, hepatic and renal damage. In tolerance studies in swine, erosive and/or ulcerative lesions were observed in the glandular and aglandular regions of the stomach, with 3 times the therapeutic dose (9 mg/kg) – 3 days of administration and 9 days of administration at the treatment dose (3 mg/kg). Early signs of toxicity are loss of appetite, soft stools and diarrhea.

WITHDRAWAL WARNINGS FOR FOOD PRODUCING ANIMALS

Withdrawal period: During the treatment and after the last drug administration, cattle should not be sent to slaughter until 4 days later. Withdrawal period for cow's milk is “0” days.

CONTRAINDICATIONS

Do not use in animals known to be sensitive to any substance in its composition.

Do not use in animals with significant liver, heart and kidney function loss.

Do not not use in animals with gastrointestinal lesion, hemorrhagic diathesis, blood dyscrasia.

Do not use in foals less than one month old.

Do not administer with other NSAIDs or 24 hours before or after the administration of this group of drugs.

GENERAL PRECAUTIONS

Consult your veterinarian before use and in case of unexpected effects. Keep out of reach of children. Keep away from foodstuffs.

PRECAUTIONS TO BE TAKEN AND RECOMMENDATIONS FOR PHYSICIANS

In case of accidental self-injection, seek medical treatment immediately and show your doctor the label/package of the product. Persons sensitive to ketoprofen or other excipients should not come into contact with the product. Avoid contact with eyes and skin. In case of contact, wash the area with plenty of water. If sensitivity persists in contact areas, consult a doctor. Wash your hands after use.

STORAGE CONDITIONS AND SHELF LIFE

Shelf life is 2 years from the date of manufacture. Opened package should be consumed within 28 days after first use. It should be stored in its original package below 25°C, protected from sunlight, without being refrigerated or frozen.