Toxicosis in Animals From Human Topical Agents

Topical antifungal medications, such as clotrimazole, ketoconazole, and miconazole, are available in over-the-counter and prescription creams, ointments, sprays, otic suspensions, and shampoos. They have minimal oral absorption and present limited risk of systemic toxicosis.

Ingestion of topic antifungals can lead to GI upset, which can be managed at home. Supportive veterinary care might be indicated in the rare cases when GI upset is more than mild.

Calcipotriene, used to treat psoriasis in humans, 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 has been associated with life-threatening hypercalcemia in dogs.

Clinical signs of calcipotriene toxicosis usually occur within 24–36 hours after ingestion and include anorexia, vomiting, diarrhea, polyuria/polydipsia, depression, and weakness. Serum calcium is usually increased within 12–24 hours and can remain above normal for days.

Hypercalcemia and hyperphosphatemia can result in soft tissue mineralization, most commonly affecting the kidneys, vasculature (especially the aorta), and the GI tract. Acute kidney injury can occur secondary to mineralization, as evidenced by increased BUN and creatinine concentrations.

Coma and death occur in severe or untreated cases of calcipotriene toxicosis.

Treatment of calcipotriene toxicosis consists of standard decontamination (emesis induction, administration of activated charcoal and a cathartic) and decreasing serum calcium concentrations by saline diuresis and administration of corticosteroids. Bisphosphonates are not typically recommended, because of the short half-life of calcipotriene.

Calcipotriene toxicosis cases usually require monitoring of serum calcium, phosphorus, BUN, and creatinine for several days. Acute kidney injury is managed with ongoing administration of supportive fluids.

Topical corticosteroid preparations come in both over-the-counter and prescription formulations, often in combination with other active ingredients. Clinical signs of corticosteroid toxicosis after ingestion can generally be managed at home and consist of mild vomiting and diarrhea, polyuria/polydipsia, and polyphagia.

Pets that ingest corticosteroid creams should be given free access to water and might need more frequent opportunities to urinate. They should be monitored closely for misadventure, because polyphagia can make them more likely to ingest inappropriate substances.

Betamethasone is a long-acting corticosteroid found in cream and solutions. Although the clinical signs of toxicosis from betamethasone ingestion are the same as with other corticosteroids, they can last much longer, up to 1–3 weeks after exposure.

Because of the potential for immunosuppression, elective surgery in pets that have ingested betamethasone creams should be postponed, when possible.

Estrogens can be found in transdermal patches and transdermal creams. Dogs and cats that ingest ≥ 1 mg/kg of estrogen can develop bone marrow suppression and/or aplastic anemia.

Decontamination after estrogen ingestion includes induction of emesis and administration of activated charcoal within 1–2 hours of exposure. For the recovery of ingested patches, emesis or endoscopic retrieval can be helpful for a longer period of time. Emesis is preferred; endoscopy should be used only when emesis is not possible because of underlying patient conditions or when the patch is not produced with emesis

Animals that ingest a potentially toxic amount of estrogen should have CBCs monitored for 2 weeks. Erythropoietin can be administered to treat aplastic anemia.

Transdermal fentanyl patches are used to treat moderate to severe pain in humans and veterinary patients.

Used fentanyl patches contain as much as half of the initial dose and can cause signs of intoxication in animals. Clinical signs can develop from licking or chewing patches; however, these signs are generally short-lived.

The swallowing of fentanyl patches is more concerning because the signs can be more severe and prolonged. Clinical signs include GI upset, ataxia, depression, miosis, seizures, and hypotension.

CNS signs typically respond rapidly and fully to naloxone. Supportive care can also be beneficial.

Removal of the patch from the GI tract should be attempted. Emesis or endoscopic removal can be attempted in patients not showing clinical signs. Often, patients no longer show clinical signs after naloxone is administered, which facilitates attempts to remove the patch.

5-Fluorouracil (5-FU) is available as an ointment or a topical solution. It is used to treat skin cancers and solar keratoses in humans. In general, 5-FU destroys rapidly dividing cells, affecting the GI tract, liver, kidneys, CNS, and bone marrow.

Initial clinical signs of 5-FU toxicosis include severe vomiting, which can progress to bloody vomiting and diarrhea. Signs often progress to severe tremors, ataxia, and seizures. The mortality rate is high among dogs that ingest 5-FU.

All 5-FU exposures in pets should be treated aggressively. Induction of emesis and administration of activated charcoal should be considered if the patient shows no clinical signs and the ingestion occurred within the previous hour. Administration of GI protectants, such as omeprazole and sucralfate, should be considered.

Diazepam (bolus or CRI) can be used initially to control seizures and tremors; in severe 5-FU exposures, however, it is usually not effective. Levetiracetam has proved to be effective against seizures. If levetiracetam also fails to control CNS signs, phenobarbital, gas anesthesia, and/or propofol should be used.

IV fluids should be administered to maintain hydration and promote renal excretion. Body temperature should be monitored and regulated when indicated.

Up to 2 weeks after exposure to 5-FU, intoxicated patients might develop bone marrow suppression that can last up to 30 days. CBCs should be monitored for at least 2 weeks, or until clinical signs of myelosuppression have resolved.

For severe neutropenia in dogs, broad-spectrum antimicrobials and filgrastim (an injectable agent to treat neutropenia by stimulating bone marrow production of WBCs) might be useful.

Lidocaine is a local anesthetic found in creams, gels, and patches. It can be in a prescription or over-the-counter form and can be combined with other active ingredients.

Cats are more sensitive to lidocaine toxicosis than are dogs. Clinical signs can occur rapidly (< 15 minutes after exposure) and include agitation, depression, cardiac arrhythmias, hypotension, methemoglobinemia, Heinz body anemia, and acidosis.

Hypotension typically responds to fluids; if not, however, vasopressors can be administered. Antiarrhythmics other than lidocaine might be necessary to treat cardiac arrhythmias.

Administration of IV lipids can be helpful for treating the cardiac effects of lidocaine. N-acetylcysteine can be used to treat methemoglobinemia.

Topical minoxidil is available as a foam, solution, or spray. It is labeled for use in humans to regrow hair. An oral tablet is used to treat hypertension in humans.

GI upset is often observed within a few hours after exposure in animals. Cardiac signs can be delayed 12–24 hours. Common clinical signs of minoxidil toxicosis include hypotension, tachycardia, hypothermia, and pleural effusion.

Dogs or cats ingesting a substantial dose of minoxidil should be closely monitored in the hospital. Frequent auscultation, ECG, and peripheral or central blood pressure monitoring should be considered. ECGs can be helpful, especially in dogs, to assess changes in right atrial function.

Pulmonary edema should be treated with furosemide and oxygen. Hypotension can be treated with fluids; however the potential for pulmonary edema should be kept in mind.

Synthetic colloids or pressors such as phenylephrine, dopamine, or vasopressin can be considered for treating refractory hypotension.

Nicotine patches are used by humans to aid in the cessation of smoking. Pets become exposed through either chewing or complete ingestion.

Severe clinical signs of nicotine toxicosis are possible but uncommon. The most common clinical signs are GI upset, lethargy, and transient agitation. Higher doses can result in tremors, seizures, fasciculations, dyspnea, bradycardia, and urinary incontinence.

In cases of ingestion not accompanied by clinical signs, induction of emesis can be considered. Emesis is unlikely to be helpful if the patch was merely chewed.

In general, patients can be monitored at home unless they develop clinical signs that require treatment. Treatment is largely supportive. Antiemetics are helpful for treating GI upset; antacids, however, should be avoided because they can increase the absorption of nicotine.

Atropine at a preanesthetic dosage can be used to treat bradycardia. Benzodiazepines can be administered for agitation, tremors, or seizures.

NSAIDs can be found in creams (including transdermal creams) and ophthalmic solutions, in either over-the-counter or prescription formulations. Many prescription NSAIDs can be compounded in topical formulations and contain many active ingredients.

Doses of concern vary by the type of topical NSAID; however, clinical signs of toxicosis in animals have been documented in cases of either puncturing the tube or bottle and licking the cream off of human skin or grooming fur that has been contaminated by contact with human skin.

Cats are more sensitive to topical NSAID exposure than dogs and are more likely to develop toxicosis by licking cream off of human skin or grooming their fur after contact with human skin, especially if allowed to do so chronically.

Clinical signs of topical NSAID toxicosis are dose dependent and include GI upset, GI ulceration (with perforation as a sequela), and acute kidney injury. CNS signs (depression, coma, seizures) can occur at very high doses.

The treatment of topical NSAID toxicosis depends on the amount ingested. Decontamination can be attempted within the first hour after exposure. Activated charcoal with a cathartic can be administered once. GI signs might require treatment with an antiemetic.

Pets that ingest an ulcerative dose of a topical NSAID should be started on gastroprotectants (omeprazole with or without sucralfate) for 14 days.

Patients that consume a nephrotoxic dose should be fluid-diuresed for 48 hours. Supportive care should be provided, and any pets with suspected GI ulceration should be monitored for bleeding or perforation. Renal values should be monitored for 72 hours. CBC and urine specific gravity monitoring should be considered if indicated by clinical signs.

Salicylates, such as methyl salicylate and salicylic acid, are found in a variety of over-the-counter and prescription products, such as sunscreens, topical pain relievers, and topical wart removal products. Oil of wintergreen contains 98% methyl salicylate.

Clinical signs of salicylate exposure in animals are dose dependent and include GI upset, GI ulceration (with perforation as a sequela), hyperthermia, tachypnea, acidosis, and acute liver injury. Acute kidney injury is rare with salicylates.

Treatment of salicylate exposure depends on the amount ingested. Decontamination can be attempted within the first hour after exposure. Activated charcoal with a cathartic can be administered once to treat doses expected to result in systemic clinical signs.

Acid-base status, PCV, total protein, and serum chemistry should be monitored as needed in cases of salicylate exposure. GI signs might require treatment with an antiemetic. Pets that ingest an ulcerative dose should be started on gastroprotectants (omeprazole with or without sucralfate) for 14 days and misoprostol for 3–5 days.

Fluids can be administered to maintain normal hydration. Supportive care should be provided, and any pets with suspected GI ulceration should be monitored for bleeding or perforation.

Tacrolimus is available as an ointment that is applied to treat atopic dermatitis in humans. It is also available in compounded ophthalmic preparations.

Many ingestions of tacrolimus result in mild GI upset. Some cases are marked by substantial GI upset and abdominal pain. In more severe cases, supportive care with bland diet, probiotics, and fluids should be implemented, along with monitoring for the development of intussusception, especially if tenesmus is present. Intussusception should be surgically corrected.

Tretinoin (available in concentrations from 0.01% to 0.05%) is a derivative of vitamin A applied topically to treat acne in humans.

Acute tretinoin toxicosis is rare and would be expected only with massive overdoses, which are unlikely with the ingestion of topical products.

The most common clinical signs of tretinoin exposure include vomiting and diarrhea, which respond well to supportive care.

Triple antibiotic ointments are available by prescription and over the counter. Common ingredients include bacitracin, clindamycin, erythromycin, gentamicin, mupirocin, neomycin, nystatin, and polymyxin B.

Some triple antibiotic ointments have additional ingredients, such as corticosteroids, pramoxine, or lidocaine, and these should be considered separately.

Generally, exposures to triple antibiotic ointments result in mild GI upset and can be managed at home. Supportive veterinary care might be indicated for GI upset that is more than mild.

Zinc oxide is most commonly found as an ointment or cream, and it is applied as a topical skin protectant (diaper cream, sunscreen), astringent, and bactericidal agent. Most ointments contain 10% and 40% zinc oxide, often in combination with other emollients.

Most acute ingestions of agents that contain zinc oxide can lead to gastric irritation, vomiting, and diarrhea within 2–4 hours after exposure. Rarely, products that contain zinc oxide can cause a hypersensitivity reaction manifested by facial and periocular edema and urticaria.

Hypersensitivity reactions to zinc oxide exposure typically respond well to diphenhydramine. A single dose of a short-acting corticosteroid can be administered for severe cases.

Acute zinc oxide ingestions are generally not expected to result in intravascular hemolysis and acute kidney injury; however, intravascular hemolysis can develop with chronic ingestion, such as when a zinc oxide cream is applied topically to a pet and then ingested off the animal's skin over the course of days to weeks.

• Immelman LM, Goodman IH, Keller N. Transient chemotherapy-induced alopecia after successful reversal of 5-fluorouracil myelosuppression and neurotoxicosis in a 9-month-old dog. Aust Vet J. 2022;100(6):236-242.

• Ivaldi F, Ogdon C, Khan FA. A rare case of vulvar discharge associated with exogenous oestrogen exposure in a spayed Weimaraner bitch. Vet Med Sci. 2022;8(5):1872-1876.

• McLean, Mary Kay, and Safdar A Khan. Toxicology of frequently encountered nonsteroidal anti-inflammatory drugs in dogs and cats: an update. Vet Clin North Am Small Anim Pract. 2018;48(6):969-984.

• Siow JW. Zinc toxicosis in a dog secondary to prolonged zinc oxide ingestion. Open Vet J. 2018;8(4):458-462.

• Tater KC, Gwaltney-Brant S, Wismer T. Topical minoxidil exposures and toxicoses in dogs and cats: 211 cases (2001–2019). J Am Anim Hosp Assoc. 2021;57(5):225-231.

• Also see pet owner content regarding topical zinc oxide poisoning.