Tolfedine 4% Injection (Canada)

Tolfenamic Acid

for dogs and cats

FOR VETERINARY USE ONLY

DIN: 4%: 02238924

6 mg: 02231278

20 mg: 02238077

60 mg: 02231279

Active Ingredient

Each TOLFEDINE Tablet contains:

Tolfenamic Acid: 6 mg, 20 mg or 60 mg.

Each mL of TOLFEDINE 4% injection contains:

Tolfenamic Acid: 40 mg/mL (with 1% W/V of benzyl alcohol as a preservative).

PRESENTATION:

TOLFEDINE Tablets:

Boxes containing 2 blisters of 10 Tablets of 6 mg.

Boxes containing 12 blisters of 8 Tablets of 20 mg.

Boxes containing 12 blisters of 8 tablets of 60 mg.

TOLFEDINE Injectable: 30 mL bottles

Tolfedine 4% Injection Indications

TOLFEDINE is recommended for the alleviation of inflammation and pain associated with osteoarthritis in dogs with hip dysplasia; as an aid in the treatment of upper respiratory diseases and as symptomatic treatment of fever in cats.

Pharmacology

NON-STEROIDAL ANTI-INFLAMMATORY, ANALGESIC, ANTIPYRETIC AGENT

Tolfenamic acid (N-(2-methyl-3-chlorophenyl) anthranilic acid) is a non steroidal anti-inflammatory agent (NSAID), which belongs to the fenamate group. Tolfenamic acid is a potent inhibitor of cyclo-oxygenase enzyme, thus inhibiting the synthesis of important inflammatory mediators such as thromboxane (Tx)B₂ and prostaglandin (PG)E₂. It acts not only by inhibiting prostaglandin synthesis, but it also has a direct antagonistic action on its receptors. The anti-inflammatory activity of Tolfenamic acid was evaluated in various animal models of inflammation. It was found that it is 4 times more potent than phenylbutazone in a rat model study. TOLFEDINE shows marked analgesic and anti-pyretic properties. It is well absorbed by the oral route and shows a complete bio-availability even in the presence of food.

After oral administration, efficient blood levels are rapidly reached (C_MAX is reached within 1 to 2 hours in fasted animals, or 2 to 4 hours when administered with the meal) and maintained sufficiently high to exert a satisfactory anti-inflammatory action for at least 24 to 36 hours.

TOLFEDINE is known to be highly effective each time it is important to reduce inflammation, fever and pain in dogs and cats.

Dosage - Mode Of Administration

Dogs: On the first day of treatment, administer TOLFEDINE Injection by subcutaneous or intramuscular injection, at a dosage of 4 mg/kg Tolfenamic acid, and continue with TOLFEDINE Tablets at the same dosage, for 2 to 4 more days. The treatment may be repeated once a week as required, or as recommended by the veterinarian, at the rate of one administration per day for 3 to 5 days.

Cats: Administer orally, 4 mg/kg Tolfenamic acid per day, for 3 to 5 days, or as recommended by the veterinarian.

Contraindications

This drug is contraindicated in the presence of gastro-duodenal ulcers or severe renal, cardiac or hepatic disorders. It is also contraindicated in animal with dehydration, hypovolemia, hypotension, as it increases the risk of renal toxicity. TOLFEDINE should not be used within 24 hours of treatment with any of the following drugs: Other NSAID’s, corticosteroids, amino-glycosid antibiotics or other drugs with significant renal toxicity potential and anti coagulants. Animals with a hypersensitivity to Tolfenamic acid or with a known sensitivity to non steroidal anti-inflammatory drugs or animals with coagulative disorders should not be treated with this drug.

Side Effects

Gastro-intestinal intolerance which is generally reversible upon withdrawal of the drug.

Tolfedine 4% Injection Caution

Do not exceed the prescribed dosage. Although studies in laboratory animals have not shown effects on the reproduction, it is not advised to prescribe this drug to breeding, pregnant or lactating animals, since no studies were conducted in dogs and cats to support those uses. Treatment should be discontinued prior to elective surgery.

NOTE: Gastro-intestinal, renal and hepatic function should be monitored periodically in animals on a long-term therapy. Treated animals should be monitored for the occurrence of side effects. Adverse reactions considered typical of NSAIDs include gastro-intestinal ulceration, renal toxicity and hematological abnormalities. NSAIDs present a greater risk in animals under 6 weeks of age or in aged, debilitated or sick animals. Tolfedine should be used with caution in these cases; careful clinical monitoring is advised. In the event of gastro-intestinal signs (e.g. loss of appetite, vomiting, diarrhea or melena), or adverse drug reactions (e.g. lethargy, behavioral changes, abnormal bleeding), treatment should be discontinued.

Toxicology

In controlled clinical trials, TOLFEDINE was well tolerated at twice the therapeutic dose for 10 days, which is at least twice the recommended duration of treatment. No gastro-intestinal lesions were present. In another controlled clinical trial, the tolerance of TOLFEDINE was evaluated in dogs during a long-term scheme of treatment (4mg/kg_BW/day, 3 days a week for 13 weeks) by the mean of clinical, haemato-biochemical and endoscopic monitorings, and of histological examinations. The general tolerance of TOLFEDINE was good with this long duration dose regimen. Indeed neither haematological nor biochemical disorders nor digestive impairments were recorded during the study. Chemical assays (HPLC) attested that there was no accumulation of the drug in treated dogs. Endoscopic examinations revealed that the mucosa lesions were not drastically severe and were reversible: indeed only very slight superficial loss of substance or erosions were observed after 4 weeks of treatment. There was no deep or active ulceration, as it was often reported as NSAIDs side effect. This dose regimen planning 4 days of wash-out between each period of 3 days of administration is a long-term therapeutic scheme which can be used safely in dogs.

Storage

Vétoquinol N.-A. Inc., 2000, ch. Georges, Lavaltrie, QC, Canada, J5T 3S5

423140 1009 B

CPN: 1234063.8