And here is the information on aspirin. Again, it is pretty easy to see why I don't recommend it either.
- ASA, Acetylsalicylic Acid
- Analgesic; Antipyretic; Platelet Aggregation Reducer; Antiinflammatory
- NSAID used for analgesic, antiinflammatory & antiplatelet effects in a variety of species.
- Contraindicated in patients hypersensitive to it or with active GI bleeds; Relatively contraindicated in patients with bleeding disorders, asthma, or renal insufficiency (but has been used to treat glomerular disease).
- Aspirin has a very long half-life in cats (approx. 30 hours; dose carefully); dogs are relatively sensitive to GI effects (bleeding).
- Low grade teratogen & may delay labor; avoid use in pregnancy.
- Many drug & lab interactions.
Aspirin is used for its analgesic, antipyretic, and antiplatelet effects.
Aspirin inhibits cyclooxygenase (COX-1, prostaglandin synthetase) thereby reducing the synthesis of prostaglandins and thromboxanes (TXA2). These effects are thought to be how aspirin produces analgesia, antipyrexia, and reduces platelet aggregation and inflammation.
Most cells can synthesize new cyclooxygenase, but platelets cannot. Therefore, aspirin can cause an irreversible effect on platelet aggregation. A study in dogs investigating the platelet function effects of various aspirin doses, showed that doses <1 mg/kg/day or at 10 mg/kg/day PO did not have any statistically significant effect on platelet aggregation. Doses of 12 mg/kg/day inhibited platelet function and aggregation (Shearer et al. 2009).
Aspirin has been shown to decrease the clinical signs of experimentally induced anaphylaxis in calves and ponies.
While aspirin does not directly inhibit COX-2, it can modify it to produce, with lipoxygenase (LOX), a compound known as aspirin-triggered lipoxin (ATL), which appears to have gastric mucosal protective actions. This may explain why aspirin tends to have reduced gastric damaging effects when used over time.
Aspirin is rapidly absorbed from the stomach and proximal small intestine in monogastric animals. The rate of absorption is dependent upon factors as stomach content, gastric emptying times, tablet disintegration rates and gastric pH. In cattle, oral dosages of 50 mg/kg did not achieve therapeutic concentrations (Coetzee 2013).
During absorption, aspirin is partially hydrolyzed to salicylic acid where it is distributed widely throughout the body. Highest levels may be found in the liver, heart, lungs, renal cortex, and plasma. The amount of plasma protein binding is variable depending on species, serum salicylate and albumin concentrations. At lower salicylate concentrations it is 90% protein bound, but only 70% protein bound at higher concentrations. Salicylate is excreted into milk but levels appear to be very low. Salicylate will cross the placenta and fetal levels may actually exceed those found in the mother.
Salicylate is metabolized in the liver primarily by conjugation with glycine and glucuronic acid via glucuronyl transferase. Because cats are deficient in this enzymatic pathway, they have prolonged half-lives (27-45 hours) and are susceptible to accumulating the drug. Minor metabolites formed include gentisic acid, 2,3-dihydroxybenzoic acid, and 2,3,5-trihydroxybenzoic acid. Gentisic acid appears to be the only active metabolite, but because of its low concentrations appears to play an insignificant role therapeutically. The rate of metabolism is determined by both first order kinetics and dose-dependent kinetics depending on the metabolic pathway. Serum half-life in dogs is approximately 8 hours, in cats, approximately 38 hours, while in humans it averages 1.5 hours. Generally, steady-state serum levels will increase to levels higher (proportionally) than expected with dosage increases. These effects have not been well studied in domestic animals, however.
The kidneys rapidly excrete salicylate and its metabolites by both filtration and renal tubular secretion. Significant tubular reabsorption occurs which is highly pH dependent. Raising urine pH to 5-8 can significantly increase salicylate excretion. Salicylate and metabolites may be removed using peritoneal dialysis or more rapidly using hemodialysis.
Aspirin is contraindicated in patients demonstrating previous hypersensitivity reactions to it or with bleeding ulcers. It is relatively contraindicated in patients with hemorrhagic disorders, asthma, or renal insufficiency.
Because aspirin is highly protein bound to plasma albumin, patients with hypoalbuminemia may require lower dosages to prevent clinical signs of toxicity. Aspirin should be used cautiously with enhanced monitoring in patients with severe hepatic failure or diminished renal function. Because of its effects on platelets, aspirin therapy should be halted, if possible, one week prior to surgical procedures.
Aspirin must be used cautiously in cats because of their inability to rapidly metabolize and excrete salicylates. Clinical signs of toxicity may occur if dosed recklessly or without stringent monitoring. Aspirin should be used cautiously in neonatal animals; adult doses may lead to toxicity.
The most common adverse effect of aspirin at therapeutic doses is gastric (nausea, anorexia, vomiting) or intestinal irritation with varying degrees of occult GI blood loss occurring. The resultant irritation may result in vomiting and/or anorexia. Severe blood loss may result in a secondary anemia or hypoproteinemia. In dogs, plain uncoated aspirin may be more irritating to the gastric mucosa than either buffered aspirin or enteric-coated tablets. Misoprostol has been shown to reduce GI bleeding and vomiting in dogs receiving aspirin. Hypersensitivity reactions have been reported in dogs although they are thought to occur rarely. Cats may develop acidosis from aspirin therapy.
Salicylates are possible teratogens and have been shown to delay parturition; their use should be avoided during pregnancy, particularly during the later stages. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should be used cautiously as a last resort when the benefit of therapy clearly outweighs the risks.)
Clinical signs of acute overdosage in dogs and cats include: depression, vomiting (may be blood tinged), anorexia, hyperthermia, and increased respiratory rate. Initially, a respiratory alkalosis occurs with a compensatory hyperventilation response. A profound metabolic acidosis follows. If treatment is not provided, muscular weakness, pulmonary and cerebral edema, hypernatremia, hypokalemia, ataxia, and seizures may all develop with eventual coma and death.
There were 1939 single agent exposures to aspirin reported to the ASPCA Animal Poison Control Center (APCC) during 2009-2013. There were 1749 dogs exposed, 712 of which were symptomatic. The most common signs included: vomiting (75%), lethargy (21%), panting (9%), hyperthermia (8%), and bloody vomiting (7%). Of the 177 cats, 54 were symptomatic with 56% vomiting, 22% anorexic, 13% lethargic and 6% with bloody vomiting.
Treatment of acute overdosage initially consists of emptying the gut if ingestion has occurred within 12 hours, giving activated charcoal and an oral cathartic, placing an intravenous line, beginning fluids and drawing appropriate lab work (e.g., blood gases). Some clinicians suggest performing gastric lavage with a 3-5% solution of sodium bicarbonate to delay the absorption of aspirin. A reasonable choice for an intravenous solution to correct dehydration would be dextrose 5% in water. Acidosis treatment and forced alkaline diuresis with sodium bicarbonate should be performed for serious ingestions, but should only be attempted if acid-base status can be monitored. Diuresis may be enhanced by the administration of mannitol (1 – 2 grams/kg/hour). GI protectant medications should also be administered. Seizures may be controlled with IV diazepam. Treatment of hypoprothrombinemia may be attempted by using phytonadione (2.5 mg/kg divided q8-12h) and ascorbic acid (25 mg parenterally) but ascorbic acid may negate some of the urinary alkalinization effects of bicarbonate. Peritoneal dialysis or exchange transfusions may be attempted in very severe ingestions when heroic measures are desired.
The following drug interactions with aspirin have either been reported or are theoretical in humans or animals and may be of significance in veterinary patients. Unless otherwise noted, use together is not necessarily contraindicated, but weigh the potential risks and perform additional monitoring when appropriate.
- Aminoglycosides: Some clinicians feel that aspirin should not be given concomitantly with aminoglycoside antibiotics because of an increased likelihood of nephrotoxicity developing. The actual clinical significance of this interaction is not clear, and the risks versus benefits should be weighed when contemplating therapy.
- Corticosteroids: May increase the clearance of salicylates, decrease serum levels and increase the risks for GI bleeding. One dog study showed no significant difference in gastric mucosal injury when ultra-low dose (0.5 mg/kg/day) aspirin was added to prednisone therapy. Addition of aspirin did increase the incidence of mild, self-limiting diarrhea (Graham et al. 2009).
- Digoxin: In dogs, aspirin has been demonstrated to increase plasma levels of digoxin by decreasing the clearance of the drug.
- Furosemide: May compete with the renal excretion of aspirin and delay its excretion; this may cause clinical signs of toxicity in animals receiving high aspirin doses. Furosemide diuretic effect may be diminished.
- Heparin or Oral Anticoagulants: Aspirin may increase the risks for bleeding.
- Methotrexate: Aspirin may displace MTX from plasma proteins increasing the risk for toxicity.
- NSAIDs: Increased chances of developing GI ulceration exist. Animals that have been on aspirin therapy that will be replaced with a COX-2 NSAID, should probably have a “wash out” period of 3-10 days between stopping aspirin and starting the NSAID (Bill 2008). Another recommendation for cats is a “washout period” of approximately 7-10 days when switching from aspirin to another NSAID (Sparkes et al. 2010).
- Phenobarbital May increase the rate of metabolism of aspirin by inducing hepatic enzymes.
- Probenecid, Sulfinpyrazone: At usual doses, aspirin may antagonize the uricosuric effects of probenecid or sulfinpyrazone.
- Spironolactone: Aspirin may inhibit the diuretic activity of spironolactone.
- Tetracycline: The antacids in buffered aspirin may chelate tetracycline products if given simultaneously; space doses apart by at least one hour.
- Urinary acidifying drugs (e.g., methionine, ammonium chloride, ascorbic acid): Can decrease the urinary excretion of salicylates.
- Urinary Alkalinizing Drugs: (e.g., acetazolamide, sodium bicarbonate) significantly increase the renal excretion of salicylates; because carbonic anhydrase inhibitors (e.g., acetazolamide, dichlorphenamide) may cause systemic acidosis and increase CNS levels of salicylates; toxicity may occur.
- At high doses, aspirin may cause false-positive results for urinary glucose if using the cupric sulfate method (Clinitest®, Benedict’s solution) and false-negative results if using the glucose oxidase method (Clinistix® or Tes-Tape®).
- Urinary ketones measured by the ferric chloride method (Gerhardt) may be affected if salicylates are in the urine (reddish-color produced). Salicylates may interfere with fluorescent methods for determining urine 5-HIAA. Falsely elevated VMA (vanillylmandelic acid) may be seen with most methods used if salicylates are in the urine. Falsely lowered VMA levels may be seen if using the Pisano method.
- Urinary excretion of xylose may be decreased if aspirin is given concurrently. Falsely elevated serum uric acid values may be measured if using colorimetric methods.
- Aspirin can decrease serum concentrations of total T4.
Note: There are no approved FDA-Products/Dosages; all dosages are extra-label.
- To decrease platelet aggregation; as an antithrombotic (extra-label): The ideal aspirin dosage, if any, for prevention of thromboembolism in dogs is unknown (data conflicts, study limitations, etc.) (Smith 2012). Commonly, dosages of 0.5 – 1 mg/kg PO once a day are recommended, but some recommend up to 10 mg/kg PO once a day. A preliminary report demonstrated that platelet activity is increased in dogs with IMHA as compared to normal dogs and that neither low dose aspirin (0.5 mg/kg/day PO) nor individually dosed heparin suppresses platelet thromboxane release in vivo(Stiller et al. 2013).
- As an analgesic/antipyretic/antiinflammatory (extra-label): Anecdotal dosages usually range from 10 – 20 mg/kg of buffered aspirin PO twice daily. Anecdotal antiinflammatory dosages are slightly higher (20 – 30 mg/kg q8-12h), but canine-approved NSAIDs generally have significantly fewer gastrointestinal effects and are usually preferred.
- For analgesia/antipyrexia/antiinflammatory (extra-label): Anecdotal dosage recommendation is usually 10 mg/kg PO every 2-3 days; practically: ½ to one 81 mg tablet (“baby aspirin”) Monday, Wednesday, Friday of each week.
- As an antithrombotic agent (extra-label): Two basic dosage regimens have been recommended, “high dose” and “low dose”; it is unknown if one is superior to the other with regard to efficacy, but “high dose” appears to have a significantly higher risk for causing GI effects. High-dose: As above (10 mg/kg PO q2-3 days; ½ – 1 “baby aspirin” every 2-3 days (M-W-F). Low-dose: 5 mg per cat PO every 3rd day.
- As an analgesic (extra-label): 10 – 20 mg/kg PO once daily (has short duration of activity). (Williams 2000)
Note: All are extra-label.
- Rabbits: 5 – 20 mg/kg PO once daily for low-grade analgesia. (Ivey et al. 2000)
- Mice, Rats, Gerbils, Hamsters: 100 – 150 mg/kg PO q4h. Guinea pigs: 87 mg/kg PO. (Adamcak et al. 2000)
Horses: (NOTE: ARCI UCGFS CLASS 4 DRUG)
- For anti-platelet activity as an adjunctive treatment of laminitis (extra-label): 5 – 10 mg/kg PO q24-48 hours or 20 mg/kg PO every 4-5 days. (Brumbaugh et al. 1999)
- Analgesic effect &/or antipyretic effect.
- Bleeding times if indicated.
- PCV and stool guaiac tests if indicated.
- Contact veterinarian if symptoms of GI bleeding or distress occur (e.g., black, tarry feces; anorexia or vomiting, etc.).
- Because aspirin is a very old drug, formal approvals from the FDA for its use in animals have not been required. There is no listed meat or milk withdrawal times listed for food-producing animals but because there are salicylate-sensitive people, in the interest of public health, this author suggests a minimum of 1 day withdrawal time for either milk or meat.
Aspirin, sometimes known as acetylsalicylic acid or ASA, is the salicylate ester of acetic acid. The compound occurs as a white, crystalline powder or tabular or needle-like crystals. It is a weak acid with a pKa of 3.5. Aspirin is slightly soluble in water and is freely soluble in alcohol. Each gram of aspirin contains approximately 760 mg of salicylate.
Aspirin may also be known as: ASA, acetylsal acid, acetylsalicylic acid, acidum acetylsalicylicum, polopiryna, or salicylic acid acetate; many trade names are available.
Aspirin tablets should be stored in tight, moisture resistant containers. Do not use products past the expiration date or if a strong vinegar-like odor is noted emitting from the bottle.
Aspirin is stable in dry air, but readily hydrolyzes to acetate and salicylate when exposed to water or moist air; it will then exude a strong vinegar-like odor. The addition of heat will speed the rate of hydrolysis. In aqueous solutions, aspirin is most stable at pH’s of 2-3 and least stable at pH’s <2 or >8. Should an aqueous solution be desirable as a dosage form, the commercial product Alka-Seltzer® will remain stable for 10 hours at room temperature in solution.
Compounded preparation stability: Aspirin is hydrolyzed by water to degradative byproducts, acetic acid and salicylic acid.
Effervescent buffered aspirin tablets (Alka-Seltzer®) dissolved in water are demonstrated to be stable for 10 hours at room temperature and for 90 hours if refrigerated (McEvoy 2008). Although pharmacists compound aspirin suspensions in fixed oils, the long-term stability of these preparations has not been determined.
Dosage Forms/Regulatory Status
Note: No known products are FDA-approved for use in animals.
Aspirin Tablets (Enteric-Coated): 81 mg; (OTC). Labeled for use in dogs.
Aspirin Tablets (Buffered, Microencapsulated, Chewable for dogs): 150 mg & 450 mg; Canine Aspirin Chewable Tablets for Small & Medium (150 mg) or Large Dogs® (450 mg); (OTC). Labeled for use in dogs.
Aspirin Tablets 60 grain (3.9 g): Aspirin 60 Grain (OTC & Rx); Rx is labeled for use in horses, cattle, sheep and swine; not for use in horses intended for food or in lactating dairy animals.
Aspirin Boluses 240 grain (15.6 g): Labeled for use in horses, foals, cattle and calves; not for use in lactating animals. Aspirin 240 Grain Boluses, Aspirin Bolus (various); (OTC)
Aspirin Boluses 480 grain (31.2 g). Labeled for use in mature horses, & cattle. Aspirin 480 Grain Boluses (various); (OTC)
Oral Aspirin Gel: 250 mg/mL in 30 mL: Aspir-Flex® Aspirin Gel for Small and Medium Dogs; 500 mg/1 mL in 30 mL: Aspir-Flex® Aspirin Gel for Large Dogs; (OTC). Labeled for use in dogs.
Aspirin Powder: l lb. (various); (OTC); Aspirin Powder Molasses-Flavored 50% acetylsalicylic acid in base; Aspirin USP 204 g/lb. (apple flavored); Acetylsalicylic acid; (OTC)
Aspirin Granules: 2.5 gram per 39 mL scoop (apple and molasses flavor); Arthri-Eze Aspirin Granules®; (OTC); Labeled for use in horses
Aspirin Liquid Concentrate (equiv. to 12% aspirin) for Dilution in Drinking Water in 32 oz. btls.; (OTC). Labeled for addition to drinking water for swine, poultry, beef and dairy cattle
There are no listed meat or milk withdrawal times listed for food-producing animals, but because there are salicylate-sensitive people, in the interest of public health, this author suggests a minimum of 1 day withdrawal time for either milk or meat. For further guidance with determining use and withdrawal times, contact FARAD (see Phone Numbers & Websites in the appendix for contact information).
The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information.
Aspirin, Chewable Tablets: 81 mg (1.25 grain); many trade names, generic; (OTC)
Aspirin, Tablets; plain uncoated; 325 mg (5 grain), & 500 mg (7.8 grain); many trade names, generic; (OTC)
Aspirin Tablets, enteric coated: 81 mg, 165 mg, 325 mg, 500 mg, 650 mg, & 800 mg; many trade names, generic; (OTC)
Aspirin Extended-controlled Release Tablets: 81 mg, 650 mg, 800 mg & 975 mg; many trade names, generic; (OTC)
Aspirin, Tablets; buffered uncoated; 325 mg (5 grain), with aluminum &/or magnesium salts; many trade names, generic; (OTC)
Aspirin Tablets: buffered coated: 325 mg & 500 mg; many trade names, generic; (OTC)
Rectal suppositories, chewing gum and effervescent oral dosage forms are also available commercially for human use.
Monograph revised/updated August 2013.
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Bill, R. (2008). NSAIDs--Keeping up with all the changes. Proceedings: ACVC.
Brumbaugh, G., et al. (1999). The pharmacologic basis for the treatment of laminitis. The Veterinary Clinics of North America: Equine Practice 15:2(August).
Coetzee, J. F. (2013). Assessment and Management of Pain Associated with Castration in Cattle. Veterinary Clinics of North America-Food Animal Practice 29(1): 75-+.
Graham, A. H. & M. S. Leib (2009). Effects of Prednisone Alone or Prednisone with Ultralow-Dose Aspirin on the Gastroduodenal Mucosa of Healthy Dogs. Journal of Veterinary Internal Medicine 23(3): 482-7.
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McEvoy, J., Ed. (2008). AHFS Drug Information. Bethesda, American Society of Health System Pharmacists.
Shearer, L., et al. (2009). Effects of aspirin and clopidogrel on platelet function in healthy dogs. Proceedings: ECVIM. accessed via Veterinary Information Network; vin.com
Smith, S. A. (2012). Antithrombotic Therapy. Topics in Companion Animal Medicine 27(2): 88-94.
Sparkes, A. H., et al. (2010). ISFM AND AAFP CONSENSUS GUIDELINES Long-term use of NSAIDs in cats. Journal of Feline Medicine and Surgery 12(7): 521-38.
Stiller, A., et al. (2013). Effect of Low-Dose Aspirin or Heparin on Platelet-Derived Urinary Thromboxane Metabolite in Dogs with Immune-Mediated Hemolytic Anemia (IMHA). ACVIM Proceedings. accessed via Veterinary Information Network; vin.com
Williams, B. (2000). Therapeutics in Ferrets. Vet Clin NA: Exotic Anim Pract 3:1(Jan): 131-53.
January 1, 2005 (published) | January 1, 2015 (revised)