Active ingredient: Tolfenamic acid 

For oral dosage:

 Pharmacological Properties
Tolfenamic acid (N-(2-methyl-3-chlorophenyl)-acid anthracitic) is a non-steroidal anti-inflammatory drug (NSAID) of the fenamate group. It has anti-inflammatory, analgesic and antipyretic properties. 

The principles of its anti-inflammatory properties are its inhibition of cyclo-oxygenase leading to a reduction of the synthesis of prostaglandins and thromboxanes, important mediators of inflammation. 

In dogs, tolfenamic acid is rapidly absorbed. When one oral dose of 4mg/kg is given, the average maximum plasma concentration (CMax) of 4µg/ml is attained in about one hour. Even when taking tolfenamic acid during a meal, CMax is 2+3 µg/ml. The variations are due to important entero-hepatic recycling of the molecule. 

In cats, the absorption of tolfenamic acid is extremely rapid. When 1 oral dose of 4mg/kg is given, an average plasma concentration (CMax) of 5.6µg/ml is attained in about one hour (TMax). 

Tolfenamic acid is distributed throughout the organs of the body, with large concentrations in the plasma, digestive tract, liver, lungs and kidneys. Contrarily, the concentration in the brain is low. Tolfenamic acid and its metabolites can cross the placental barrier. 

Tolfenamic acid is eliminated from the body with a majority of the molecules unchanged and a minority as inactive metabolites. 

In dogs with renal disease (insufficient function), the elimination of tolfenamic acid is not modified. 

Therapeutic indications

Dogs: Treatment of symptoms of inflammation and pain of osteo-articular and musculo-skeletal disorders.

Cats: Fever. (Manufacturer: Lower urinary syndromes eg. urolithiasis) (BSAVA: upper respiratory tract infection, pain, inflammation) 

Administration

4mg/kg of tolfenamic acid in single doses per day. Either:

-          6mg tablet for 1.5kg animals for up to three days (with food)

-          20mg tablet for 5kg animals for up to three days (with food)

-          60mg tablet for 15kg animals for up to three days (with food)

-          120mg tablet for 30kg animals for up to three days (with food)

(BSAVA: 4 days. Repeated weekly dosing not recommended in cats.)

Prescribe according to this table:

Dr Sing: One of my cases with good feedback of the use of tolfedine from the owner is at: Cocker Rage: Neuter & Tolfedine pain-killer effects. Briefly, this Cocker Spaniel at 9.3 kg was given 30 mg tolfedine post-operation (1/2 of 60 mg tablet) on day 2. He vomited after 10 minutes. So, he did not benefit from the analgesic effect. On Day 3, he traumatise his scrotal area with his e-collar. On Day 6, I examined him and removed his stitches (picture). No more complaints as I had given him a steroidal injection, prednisolone 20 mg SC. Tolfedine is given once a day and must be given with food.    One internet report on the use of tolfedine recommends that for 30 mg, the vet should give 3 x 20-mg tablets instead of half of 60-mg tablet. This is logical. However, the supplier says he  does not know of the existence of 20-mg tablets despite my few reminders. I am reminding him again to get the 20-mg tablets into Singapore.  The Cocker Spaniel might have no problems with the correct dose as half of a 60-mg tablet may not be exactly 30 mg of tolfedine. Sometimes, the Singapore Government charges money for each type of drug being imported and therefore the company may not want to import the 20-mg tolfedine tablets to save some money! I have had no problems post-neuter from a 4-year-old Miniature Schnauzer neutered and given tolfedine post-operation at home. No reports of problems with cats after spay or neuter. I had one problem similar to the Cocker Spaniel in a male Terrier X neutered. He traumatised his scrotal area badly despite wearing an e-collar and had a tolfedine injection before he went home. He was warded and recovered after 1 days. He was given a larger e-collar.   3189. Undescended testicle 3190. Neuter done   3191. Dog traumatises scrotum It is possible that the dosage of 4mg/kg oral, was not sufficient in this Cocker Spaniel as the first dose was vomited out. It was given on an empty stomach. Owners unable to give the prescribed tolfedine orally may also cause the dog to traumatise his surgical area after neutering. The advantage is that it is not a narcotic analgesic (controlled drug).  In general, I find that tolfedine does control post-surgical pain in dog sterilisations. Two other analgesics: Vets may use Rimadryl (Carprofen) or Torbugesic (butorphanol tartrate) as pain-killers for dogs. Rimadryl is a non-steroidal anti-inflammatory (NSAID) like tolfedine. It inhibits the production of COX-2 and other sources of inflammatory prostaglandins. It is used to treat pain and inflammation in joint diseases like arthritis and hip Dysplasia. It is used to treat surgical pain and to reduce fever.   Butorphanol is a centrally acting analgesic. It said to be 4-30 times more potent than morphine and petazocine respectively. It is a potent narcotic agonist analgesic and is used for the relief of moderate to severe pain in the horse. It is a pain-reliever and cough suppressant in many species. Can be used to prevent vomiting in animals undergoing chemotherapy. It is effective but short-lasting especially in cats.

Contra-indications

The use of tolfenamic acid is contra-indicated in animals with cardiac or hepatic diseases. Tolfenamic acid is also unsuitable for animals with ulcers or bleeding in the digestive tract, blood clotting problems (dyscrasia) or hypersensitivity to tolfenamic acid. (BSAVA: do not use on animals with blood clotting problems. Animals with liver disease are susceptible to overdosage due to prolonged metabolism)

Special Precautions

-          The use of tolfenamic acid presents special risks when used in animals less than 6 weeks old. If use is unavoidable, a reduced dosage and clinical monitoring are especially necessary.

-          Do not exceed the recommended dose or duration.

-          Do not use on animals with dehydration, hypovolaemia, and/or hypotension (possibility of increased risk of renal toxicity)

-          Do not give to animals under general anaesthesia.

-          Although tolfenamic acid can be given to animals with chronic renal disease without adjustment of dosage, tolfenamic acid should not be given to animals with acute renal failure.

-          In case of undesirable side effects (anorexia, vomiting, diarrhea, blood in feces) occurring during the treatment, consult a vet promptly.

Use during Pregnancy and Lactation

Although laboratory studies showed no effects of tolfenamic acid on reproduction, use of tolfenamic acid during gestation is inadvisable.

Drug Interactions

Do not give tolfenamic acid within 24 hours of other NSAIDs. (BSAVA: glucocorticoids, nephrotoxic agents). Tolfenamic acid molecules strongly bind to plasma proteins, competing with other NSAIDs.

Overdosage (symptoms, emergency procedures, antidotes)

In dogs, administration of tolfenamic acid for 3 consecutive days (BSAVA: 4 days) a week at 4mg/kg/day up to three months is well tolerated. In case of overdosage, administer symptomatic treatment.

Side effects

Diarrhea and vomiting occur rarely during treatment. Also, a temporary increase in thirst and/or urination may occur. In most cases, these signs disappear spontaneously upon cessation of treatment. (Manufacturer: treatment can continue) (BSAVA: Stop treatment if effects last more than 1-2 days)

Particular Precautions for Elimination of Unused Products/ Packaging

Empty packaging/any remaining product should be disposed of according to the rules on waste disposal.

Tolfedine ® 4% Injectable Solution

 Active ingredient: Tolfenamic acid

Pharmacological Properties

Tolfenamic acid (N-(2-methyl-3-chlorophenyl)-acid anthracitic) is a non-steroidal anti-inflammatory drug (NSAID) of the fenamate group. It has anti-inflammatory, analgesic and antipyretic properties. 

The principles of its anti-inflammatory properties are its inhibition of cyclo-oxygenase leading to a reduction of the synthesis of prostaglandins and thromboxanes, important mediators of inflammation. 

In dogs, tolfenamic acid is rapidly absorbed. When injected, the average maximum plasma concentration (CMax) of 4µm/ml (subcutaneous) and 3µm/ml (intra-muscular) is attained two hours after administration of tolfenamic acid at 4mg/kg (IM and SC) 

In cats, the absorption of tolfenamic acid is extremely rapid. After injection of 4mg/kg of tolfenamic acid, the average maximum plasma concentration (CMax) of 3.9µg/ml is attained in approximately one hour (TMax) 

Tolfenamic acid is distributed throughout the organs of the body, with large concentrations in the plasma, digestive tract, liver, lungs and kidneys. Contrarily, the concentration in the brain is low. Tolfenamic acid and its metabolites can cross the placental barrier. 

Tolfenamic acid is eliminated from the body with a majority of the molecules unchanged and a minority as inactive metabolites. 

In dogs with renal disease (insufficient function), the elimination of tolfenamic acid is not modified. 

Indications

Dogs: Reduction of post-operative pain and treatment of inflammation and pain due to osteo-articular and musculo-skeletal disorders

Cats: Fever 

Contra-Indications

The use of tolfenamic acid is contra-indicated in animals with cardiac or hepatic diseases. Tolfenamic acid is also unsuitable for animals with ulcers or bleeding in the digestive tract, blood clotting problems (dyscrasia) or hypersensitivity to tolfenamic acid. 

Side effects

Diarrhea and vomiting occur rarely during treatment. Also, a temporary increase in thirst and/or urination may occur. In most cases, these signs disappear spontaneously upon cessation of treatment. 

Special Precautions

-          The use of tolfenamic acid presents special risks when used in animals less than 6 weeks old. If use is unavoidable, a reduced dosage and clinical monitoring are especially necessary.

-          Do not exceed the recommended dose or duration.

-          Do not use on animals with dehydration, hypovolaemia, and/or hypotension (possibility of increased risk of renal toxicity)

-          Do not give to animals under general anaesthesia.

-          Although tolfenamic acid can be given to animals with chronic renal disease without adjustment of dosage, tolfenamic acid should not be given to animals with acute renal failure.

-          In case of undesirable side effects (anorexia, vomiting, diarrhea, blood in feces) occurring during the treatment, consult a vet promptly. 

Precautions Particular to Persons Administrating the Product to Animals

Observe aseptic conditions for use of the product. 

Use during Pregnancy and Lactation

Although laboratory studies showed no effects of tolfenamic acid on reproduction, use of tolfenamic acid during gestation is inadvisable. 

Drug Interactions

Do not give tolfenamic acid within 24 hours of other NSAIDs. The tolfenamic acid molecules strongly bind to plasma proteins and will compete with the other NSAID molecules. 

Administration

Reduction of post-operative pain in dogs:

4mg/kg tolfenamic acid is equivalent to 1 injection of 1ml/10kg (IM). As premedication, it is preferably given 1 hour before anaesthesia. 

Treatment of symptoms of inflammation and pain due to osteo-articular and musculo-skeletal disorders in dogs and fever in cats:

4mg/kg of tolfenamic acid which is equivalent to 1 injection of 1ml/10kg (SC or IM, subsequent doses given 48 hours apart) or a single injected dose of 1ml/10kg followed by oral administration. (Manufacturer: oral treatment 24-48 hours after injection, continued 3-5 days, 4mg/kg/day in one dose) 

Do not give IM in cats. 

Overdosage (symptoms, emergency procedures, antidotes)

In case of overdosage, administer symptomatic treatment. 

Particular Caution for Special Animals

For animals which have a low body weight, it is recommended to use an insulin syringe to administer a precise dose. 

Precautions Pertaining to Conservation

After opening, use within 28 days. Do not store at temperatures above 25^oC or in bright light. Keep out of reach of children. 

Particular Precautions for Elimination of Unused Products/ Packaging

Empty packaging and any remaining product should be disposed of according to the rules on waste disposal.
 

P.S. In my observations, tolfedine is effective in relieving pain in most dogs and cats after sterilisations. An injection is given SC. The tablets are taken once a day for 5 days at home. If no vomiting and if the tablets are taken with food, there should be good pain relief. I believe the 4mg/kg injection recommendation for SC after surgery may not give good pain relief in some dogs, from my observations. This is equivalent to 1 ml Tolfedine 4% per 10 kg bodyweight. In the Cocker Spaniel at 9.3 kg, I gave slightly more at 1.4 ml SC instead of around 1 ml. There was pain relief for the next 24 hours. However, the owner gave the half of 60-mg tolfedine tablet at 7 am the next day, on an empty stomach (dog did not in the morning usually). The dog vomited after 10 minutes. So, there was no pain-relief on the 3rd day. The dog started to traumatise its scrotal area using the e-collar which was a specially bigger size.  Each dog is an individual and so it is hard to generalise on the dosage of injectable tolfedine post-sterilisation.    

For joint diseases, it is to be used 3 or 4 days per week, stop for 4 or 3 days and repeat again for 3 months at a time apparently. My associate vet use Rimadryl as pain-relief after sterilisation. Each vet has his own choices. Follow up studies, recording of effects and observations will be best in practice. 
 

The above translation is done for English-vets who may have the French literature in their purchases.  References: BSAVA 2008th Edition's indications compared to the manufactuer's