Topical Agents (Toxicity)

5-Fluorouracil (5-FU) is available as an ointment (1% or 5%) or topical solution (1%, 2%, or 5%). It is used in the treatment of skin cancers and solar keratoses in people. Most exposures result from accidental ingestion, although occasionally 5-FU is used extra-label in pets. Ingestion in dogs and cats leads to the onset of signs within a few hours. 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 severe vomiting, which may progress to bloody vomiting and diarrhea. Signs often progress to severe tremors, ataxia, and seizures. In cats and dogs, 5-FU may be converted to fluorocitrate and interfere with the Kreb’s cycle, which may be one cause of seizures and ataxia. Generally, 5-FU destroys rapidly dividing cells, affecting the GI tract, liver, kidneys, CNS, and bone marrow. The mortality rate among dogs ingesting 5-FU is high.

All 5-FU exposures in pets should be treated aggressively. Treatment consists primarily of symptomatic and supportive care. Emesis should be induced, and the animal given activated charcoal and a cathartic if it is asymptomatic and the ingestion has occurred within 1 hr. Symptomatic animals (eg, vomiting or seizuring) should be stabilized first. The GI tract should be protected with sucralfate (1 g in large dogs, 0.5 g in small dogs, PO, tid) and inhibitors of gastric acid secretion such as cimetidine. Diazepam may be used initially to control seizures and tremors, but in severe cases it is usually not effective, and other anticonvulsants such as pentobarbital (3–15 mg/kg, IV slowly to effect) or phenobarbital (3–30 mg/kg, slowly IV to effect) can be used. Constant-rate infusion using diazepam or barbiturates has successfully controlled severe seizures. If this also fails to control CNS signs, gas anesthetics (eg, isoflurane) and propofol (4–6 mg/kg, IV, or as a continuous drip at 0.6 mg/kg/min) can be tried. IV fluids should be given, and body temperature monitored. Monitoring electrolytes, serum chemistries (liver-specific enzymes and renal function), and CBC is usually required for ~2 wk. Surviving dogs may show evidence of bone marrow suppression later. For severe neutropenia in dogs, administration of filgrastim or granulocyte colony-stimulating factor at 4–6 mcg/kg, SC, may be useful.

Calcipotriene, used to treat psoriasis in people, is available as an ointment or cream (0.005% or 50 mcg/g). Calcipotriene is a novel structural analogue of calcitriol (1,25-dihydroxycholecalciferol), the most active metabolite of cholecalciferol (vitamin D₃). Accidental ingestion of 40–60 mcg/kg of calcipotriene in dogs has been associated with life-threatening hypercalcemia. Clinical signs usually occur within 24–72 hr of ingestion and include anorexia, vomiting, diarrhea, polyuria and polydipsia, depression, and weakness. Serum calcium is usually increased within 12–24 hr and may remain above normal for weeks. This is usually accompanied by an increase in serum phosphorus concentration and calcium phosphorus product and soft-tissue mineralization. Acute renal failure as evidenced by increased BUN and creatinine levels, coma, and death occur in severe or untreated cases.

Treatment of calcipotriene toxicosis involves standard decontamination (emesis induction, administration of activated charcoal and a cathartic) and reduction of serum calcium concentrations by saline diuresis, furosemide, and corticosteroids, with or without salmon calcitonin treatment ( see Hypercalcemia in Dogs and Cats). Concurrent use of pamidronate (1.3–2 mg/kg diluted in saline and given IV over 2 hr) in dogs may be a useful adjunctive therapy. Calcipotriene toxicosis cases usually require monitoring of serum calcium, phosphorus, BUN, and creatinine for several days or even weeks. Signs of renal failure are managed with ongoing supportive fluids.