Elephant specific information, if available, is in blue.

Chemistry – An anthranilic acid derivative (fenamate), meclofenamic acid is a white, crystalline powder that is practically insoluble in water. The sodium salt of meclofenamic acid is available commercially for human use. It is freely soluble in water.

 

Storage/Stability/Compatibility – Should be stored in tight, light-resistant packaging at temperatures below 30°C (86°F).

 

Pharmacology – Meclofenamic acid exhibits pharmacologic actions similar to those of aspirin. It is a potent inhibitor of cyclooxygenase, thereby inhibiting the release of prostaglandins. Like aspirin, meclofenamic acid (sodium salt administered IV) has been demonstrated to reduce the cardiovascular and respiratory effects of experimentally in­duced anaphylaxis in ponies and calves by its antagonistic effects at high concentrations on histamine, kinins, and prostaglandins.

 

It also has a transient effect on platelet aggregation, but unlike aspirin, does not appear to affect bleeding times.

 

Pharmacokinetics – Meclofenamic acid is reported to be well absorbed following oral administration, with measurable plasma levels being reached in 30 minutes and peak lev­els in 1-4 hours.

 

In studies done with monkeys, highest meclofenamic acid levels were detected in the plasma, liver, and kidneys. Lower levels were detected in skeletal muscle, fat, spleen, heart, and brain.

At plasma levels of 1 micrograms/ml, the drug was 99.8% bound to al­bumin. It rapidly crosses the placenta, but it is unknown whether it is distributed into milk.

 

The plasma half-life has been reported to range from 1-8 hours in horses. Therapeutic ef­ficacy does not seem to be closely related with blood levels, however, as the onset of ac­tion may take 36-96 hours and significant efficacy may be seen for days following a dose.

 

Meclofenamic acid is metabolized in the liver primarily by oxidation to an active hy­droxymethyl metabolite which may be further oxidized to an inactive metabolite (carboxyl). In humans, meclofenamic acid and its metabolites are then excreted by the kidneys (approx. 70% within 7 days) or eliminated with the feces (20-30%). In horses, meclofenamic acid can be detected in the urine for at least 96 hours following the final dose.

 

Uses/Indications – Meclofenamic acid is used clinically in dogs for the symptomatic relief of symptoms associated with chronic inflammatory disease of the musculoskeletal system; often in an attempt to improve mobility in animals with hip dysplasia or chronic os­teoarthritis.

 

In horses, it is indicated for the “oral treatment of acute or chronic inflammatory diseases involving the musculoskeletal system…” (Package Insert; Arquel®—Parke-Davis). Meclofenamic acid has also been used for the treatment of laminitis, with varying degrees of success.

 

Contraindications/Precautions – The manufacturer states that meclofenamic acid is con­traindicated in animals with “active gastrointestinal, hepatic or renal diseases” (Package Insert; Arquel®—Parke-Davis). Additionally, meclofenamic acid is contraindicated in pa­tients demonstrating previous hypersensitivity reactions to it or salicylates. It is relatively contraindicated in patients with active or historical hemorrhagic disorders, or bronchospas­tic disease. Because meclofenamic acid is highly bound to plasma proteins, patients with hypoproteinemia may require lower dosages to prevent symptoms of toxicity.

 

Meclofenamic acid has been shown to delay parturition in some species and therefore should be avoided during the last stages of pregnancy. It has caused teratogenic effects (minor skeletal abnormalities, delayed ossification) in rodents. Some preliminary studies have shown no effects with regard to either mare or stallion reproductive performance and no gross defects were seen in foals born to mares who received meclofenamic acid during pregnancy. It should, nevertheless, be used in pregnancy only when the potential benefits outweigh the potential risks of therapy.

 

Adverse Effects/Warnings – Adverse reactions are reported to be fairly uncommon in horses. However, hematologic changes (decreased hematocrit/PCV) and GI effects (buccal erosions, diarrhea, colic, anorexia, changes in stool consistency) have been reported. The diarrheal and colic reactions may be more likely in horses that have a heavy infestation of bots (Gasterophilus sp.) With chronic therapy, decreases in plasma protein concentrations may occur.

 

In dogs, vomiting, decreased hemoglobin, leukocytosis, tarry stools, and small intestinal ulcers have all been reported following therapy at usual effective doses. Clients should be counseled with regard to these potential adverse effects and instructed to monitor their animal carefully for symptoms associated with them.

 

In humans, NSAIDs have caused hepatotoxicity and it is recommended that human pa­tients receiving chronic meclofenamate sodium therapy undergo occasional liver function tests. Although it does not appear that this adverse reaction is of major concern in either dogs or horses, the potential for hepatotoxicity does exist.

 

Overdosage – There is very limited information regarding acute overdoses of this drug in humans and no information was located regarding overdoses in domestic animals. Following an acute, massive overdose in humans, generalized CNS stimulation initially occurs, with seizures possible. After this initial phase, acute renal failure may occur with secondary azotemia and anuria.

 

Treatment should follow standard overdose procedures (empty gut following oral inges­tion, etc.). Supportive treatment should be instituted as necessary and IV diazepam used to help control seizures. Because meclofenamic acid may cause renal effects, monitor elec­trolyte and fluid balance carefully and manage renal failure using established guidelines.

 

Drug Interactions – Because meclofenamic acid is highly bound to plasma proteins and may displace other highly bound drugs, increased serum levels and duration of actions of phenytoin, valproic acid, oral anticoagulants, other anti-inflammatory agents, salicy­lates, sulfonamides, and the sulfonylurea antidiabetic agents can occur. If meclofe­namic acid is used concurrently with warfarin, enhanced hypoprothrombinemic effects may transpire.

When aspirin is used concurrently with meclofenamic acid, plasma levels of meclofe­namic acid may decrease as well as a likelihood of increased GI adverse effects (blood loss) developing. Concomitant administration of aspirin with meclofenamic acid is not recommended.

 

Doses –

Horses:

a)   2.2 mg/kg PO once daily for 5-7 days, this equates to two 500 mg packets per 454 kg (1000 lb.) animal daily. If treatment is desired past the 7 days recom­mended, decrease the dosage and increase the dosing interval to obtain the low­est effective dose. The package contents may be added to the daily grain feed ra­tion, a moist feed with molasses added will help to prevent separation of the granules from the feed. (Package Insert; Arquel®, Parke-Davis, 1981)

b)   2.2 mg/kg PO q12h (Jenkins 1987)

 

Monitoring Parameters –

1)   Analgesic/anti-inflammatory efficacy

2)   GI:     appetite, feces (occult blood, diarrhea)

3)   PCV (packed cell volume), hematocrit if indicated or on chronic therapy

4)   WBC’s if indicated or on chronic therapy

 

Client Information/FDA Approval Status – Notify veterinarian if symptoms of GI dis­tress (anorexia, vomiting in dogs, diarrhea, black feces or blood in stool) occur or if the animal becomes depressed. Meclofenamic acid is approved for use in dogs (see note below regarding available dosage forms) and horses (not intended for food). Meclofenamic acid is a veterinary pre­scription (legend) drug.

 

Dosage Forms/Preparations –

 

Veterinary-Approved Products:

   Meclofenamic acid 5% granules in 10 gram packets (500 mg meclofenamic acid/10 gram packet) & scored 10 mg
        & 20 mg tablets; Arquel®   (Fort Dodge)