(ah-seet-a-min-a-fen) Tylenol®, APAP, Paracetamol
ORAL ANALGESIC, ANTIPYRETIC
Acetaminophen is occasionally used as an oral analgesic in dogs and small mammals. It may be particularly beneficial in dogs with renal dysfunction for the treatment of chronic pain conditions. In situations where moderate pain occurs, it may be used in combination products containing codeine, hydrocodone, or tramadol. See the codeine, hydrocodone and tramadol monographs for more information on the use of acetaminophen combination preparations.
Acetaminophen’s exact mechanism of actions are not completely understood; it produces analgesia and antipyresis via a weak, reversible, isoformnonspecific inhibition of cyclooxygenase (COX-3; Cox-1–v1). Unlike aspirin, it does not possess significant antiinflammatory activity nor inhibit platelet function when given at clinically recommended dosages.
Specific pharmacokinetic information in domestic animals was not located. In humans, acetaminophen is rapidly and nearly completely absorbed from the gut and is rapidly distributed into most tissues. Approximately 25% is plasma protein bound. Dogs apparently exhibit dose dependent metabolism (saturable).
Acetaminophen is contraindicated in cats at any dosage. Severe methemoglobinemia, hematuria, and icterus can be seen. Cats are unable to significantly glucuronidate acetaminophen leading to toxic metabolites being formed and resultant toxicity. Acetaminophen should not be used in ferrets as they may be as sensitive to acetaminophen as are cats. At this time, acetaminophen should not be used in Sugar Gliders or Hedgehogs as its safety has not been determined.
Dogs do not metabolize acetaminophen as well as humans and its use must be judicious. While dogs are not as sensitive to acetaminophen as cats, they may also be susceptible to methemoglobinemia when given high dosages. In dogs, it is generally not recommended to use acetaminophen during the immediate post-operative phase (first 24 hours) due to an increased risk of hepatotoxicity.
Because acetaminophen is not routinely used in veterinary medicine, experience on its adverse effect profile is limited. At suggested dosages in dogs, there is some potential for renal, hepatic, GI, and hematologic effects occurring.
Absolute reproductive safety has not been established, but acetaminophen is apparently relatively safe for occasional use in pregnancy (no documented problems in humans). Animal data was not located. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in 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.)
Acetaminophen is excreted in milk in low concentrations with reported milk:plasma ratios of 0.91 to 1.42 at 1 and 12 hours, respectively. In nursing human infants, no adverse effects have been reported.
Because of the potentially severe toxicity associated with acetaminophen, consultation with an animal poison control center is highly recommended (see appendix). Effects can include methemoglobinemia, liver necrosis, renal effects, facial and paw swelling, and keratoconjunctivitis sicca (KCS). Liver effects are more common in dogs; facial and paw swelling and methemoglobinemia are more common in cats.
There were 1192 exposures to acetaminophen reported to the ASPCA Animal Poison Control Center (APCC) during 2008–2009. In these cases, 1083 were dogs with 187 showing clinical signs, 99 were cats with 47 showing clinical signs, 6 were birds with 1 showing clinical signs, 1 was a pig that showed clinical signs. The remaining 3 cases involved 2 ferrets and 1 lagomorph that showed no clinical signs. Common findings in dogs recorded in decreasing frequency included vomiting, lethargy, methemoglobinemia, edema of the face, elevated ALT, chemosis (conjunctival swelling/edema), and trembling. Common findings in cats recorded in decreasing frequency included methemoglobinemia, cyanosis, lethargy, vomiting, hypothermia, and anorexia.
For overdosage in dogs or cats, standard gut emptying techniques and supportive care should be administered when applicable. Further treatment with acetylcysteine, s-adenosyl methionine (SAMe), oxygen, and blood transfusions may be warranted (Richardson 2000), (Aronson & Drobatz 1996), (Mariani & Fulton 2001), (Steenbergen 2003).
The following drug interactions have either been reported or are theoretical in humans or animals receiving acetaminophen and may be of significance in veterinary patients:
False positive results may occur for urinary 5-hydroxyindoleacetic acid
Note: For dosages of acetaminophen/codeine, and acetaminophen/hydrocodone combination products refer to the codeine and hydrocodone monographs.
As an analgesic:
a) 15 mg/kg PO q8h (Dodman 1992), (McLaughlin 2000)
b) 10 mg/kg PO q12h (Kelly 1995)
c) 10–15 mg/kg PO q12h for 5 days (Gaynor 2008)
d) In the treatment of degenerative myelopathy (in German Shepherds): 5 mg/kg PO (not to exceed 20 mg/kg per day) (Clemmons 1991)
As an analgesic:
a) Using Children’s Tylenol®: 1–2 mg/mL in drinking water. Effective for controlling low-grade nociception. (Huerkamp 2000)
b) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: 1–2 mg/mL in drinking water (Adamcak & Otten 2000)
When used at recommended doses for pain control in otherwise healthy patients, little monitoring should be necessary. However, with chronic therapy, occasional liver, renal and hematologic monitoring may be warranted, particularly when clinical signs occur.
Follow directions carefully; do not exceed dosage or increase dosing frequency. Do not administer to cats or ferrets for any reason. Keep out of reach of children.
A synthetic non-opiate analgesic, acetaminophen (also known as paracetamol) occurs as a crystalline, white powder with a slightly bitter taste. It is soluble in boiling water and freely soluble in alcohol. Acetaminophen is known in the U.K. as paracetamol.
Acetaminophen may also be known as: paracetamol, MAPAP or APAP; many trade names are available.
Acetaminophen products should be stored at temperatures less than 40°C. Do not freeze oral solution or suspension.
VETERINARY-LABELED PRODUCTS: None
The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information.
HUMAN-LABELED PRODUCTS:
There are many different trade names and products of acetaminophen available. The most commonly known trade name is Tylenol®. Acetaminophen is commonly available in 325 mg, 500 mg, 650 mg tablets; 80 mg chewable tablets; 650 mg extended release tablets; 160 mg, 500 mg, & 650 mg caplets; 500 mg gelcaps; 325 mg, & 500 mg capsules, 80 mg and 160 mg sprinkle capsules; 80 mg/0.8 mL drops; 80 mg/2.5 mL, 80 mg/5 mL, 120 mg/5 mL, & 160 mg/5 mL elixirs; 160 mg/5 mL, 500 mg/15 mL, and 100 mg/mL liquids and solutions; 80 mg, 120 mg, 125 mg, 300 mg, 325 mg and 650 mg suppositories. Combinations with other analgesics (aspirin, codeine phosphate, hydrocodone, tramadol, oxycodone or propoxyphene) are also available.