By: Mary Locicero, DVM
Emergency Veterinarian
Florida Veterinary Referral Center
5-Fluorouracil (5FU) is a chemotherapy agent used topically as a cream for treating skin cancers and occasionally warts. Common trade names include Efudex, Adrucil or Fluoroplex. When a dog chews on the cream tube and ingests the 5-Fluorouracil it is usually fatal. We have seen three of these cases in our clinic in the past year and out of these, two patients died and the one that survived was hospitalized for 10 days. According to Poison Control, the mortality rate is 85 percent.
Pharmacists are often not aware of the danger this drug poses to pets and do not warn owners of the potential toxicity--they may even tell the owners that it is non-toxic. Sadly, many of these patients arrive at the veterinary clinic hours after ingestion already showing signs of toxicity.
Mode of Action
5-Fluorouracil is a pyrimadine analogue and is considered an antimetabolite. 5-Fluorouracil blocks the enzyme thymidylate sythase, stopping the synthesis of pyrimidine--a nucleotide required for DNA and RNA replication. 5FU inhibits cell division, thus it affects all cells in the body, but most specifically the rapidly dividing cells. In dogs and cats 5FU inhibits cell division, thus it affects all cells in the body, but most specifically the rapidly dividing cells. In dogs and cats 5FU may be converted to fluorocitrate, which interferes with the Kreb's cycle mechanisms of cellular energy production and may be one cause of seizures and neurological signs.
Signs
In dogs, signs have been seen at dosages as low as 8.6 mg/kg, with the minimum lethal dose reported as 20 mg/kg. Initial signs include vomiting and may progress to bloody vomiting, diarrhea, severe abdominal pain and sloughing of the intestinal tract. Signs often progress to severe tremors, ataxia and seizures. Cardiac arrhythmias, respiratory depression and pulmonary edema can also develop. The seizures usually do not respond to diazepam and become uncontrollable. As per Poison Control, once seizures start the dog usually does not survive.
Treatment
The most important procedures for a chance of survival is early decontamination, emesis and oral activated charcoal administration within 2-3 hours of ingestion--beyond that time, 5FU will already be absorbed. After 2 to 3 hours emesis will not be helpful but activated charcoal may be helpful for up to 12-24 hours is there is no vomiting.
Once signs have manifested, treatment includes supportive care, seizure management and airway control if necessary.
*For GI signs: sucralfate, Cerenia, Famotidine or Ranitidine, IV fluids. Do not use Metoclopramide, which can get an excitatory effect.
*Pain control: Opioids
*Seizure control: diazepam is rarely effective. Often Pentobarbital or Phenobarbital need to be added. If these do not work then a CRI of Pentobarbital or Propofol can be tried.
*Airway control: intubation if on CRI or comatose.
*Monitor electrolytes and serum chemistries for liver an renal failure.
*Dogs that are lucky enough to survive may show bone marrow suppression later, so CBC should be monitored closely. If bone marrow suppression develops, filgrastim (Neupogen) can be used to stimulate bone marrow stem cell proliferation.
Because we live in an area that has a large population of geriatric adults and the prevalence of skin cancer in increasing, we will likely see this toxicity again. It is important to educate clients, referring veterinarians and pharmacists of this dangerous drug. The most important chance for survival of the pet is early decontamination so it is important that the animal is brought to a veterinarian immediately and treated quickly.
Sources: Plumb, Donald C., Plumb's Veterinarian Drug Handbook, sixth edition, Blackwell Publishing. pp. 539, 540; Albretsen, Jay, 5-Fluorouracil toxicosis in dogs. Veterinary Medicine, pp.. 270-274, April 2001; Merck & Co., The Merck Veterinary Manual, Whitehouse Station NJ, 2008; 5-Fluorouracil on Right Health internet site; Animal Poison Control conversations.
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