Species safety: dogs

The MDR1 (ABCB1-1Δ) mutation

MDR1 (ABCB1) is a gene mutation found in some breeds, mostly herding dogs (Collie, Australian Shepherd, Shetland Sheepdog and others). In these dogs some drugs reach the brain easily: loperamide can cause neurotoxicity even at normal doses, while ivermectin and other macrocyclic lactones do so at doses above the heartworm-prevention dose (e.g. for mange). A genetic test identifies it.

Source: Washington State University, Washington Animal Disease Diagnostic Laboratory: MDR1 in Dogs ↗

Source: Mealey KL et al. Pharmacogenetics 2001;11:727-33 (ivermectin sensitivity in Collies, MDR1 deletion)

• Dogs with this mutation are more sensitive to some medicines. It is most common in Collies, Australian Shepherds (also the miniature), long-haired Whippets, McNabs and Silken Windhounds; it also occurs in Shetland Sheepdogs, German Shepherds, Old English Sheepdogs, Border Collies, herding-breed crosses and mixed breeds.
• Ivermectin, milbemycin, moxidectin and selamectin are safe at the label doses of heartworm and parasite prevention; for other formulations and doses the veterinarian sets the dose. The labels of milbemycin and moxidectin products note a narrower safety margin in Collies and related breeds.
• Loperamide should be avoided in dogs with the mutation; acepromazine, butorphanol, some chemotherapy drugs, ciclosporin, maropitant and ondansetron need a dose adjusted by the veterinarian.
• A genetic test (for example Washington State University's MDR1 test) shows whether a dog carries the mutation.

In the reference: Milbemycin oxime, Moxidectin

Non-steroidal anti-inflammatories (NSAIDs)

Source: Metacam (meloxicam) SPC, EMA: not with other NSAIDs or glucocorticosteroids

• Human NSAIDs (ibuprofen, naproxen, diclofenac) are toxic to dogs; their doses are in the list below.
• Veterinary NSAIDs only at the label dose. Never give two NSAIDs together, or an NSAID with a corticosteroid.

In the reference: Ibuprofen, Naproxen, Diclofenac, Meloxicam

Medicines and substances that are toxic or dangerous in dogs

From the reference's data: toxicity records and critical contraindications for dogs, each with its source.

Toxic

• Diclofenac: No acute ingestion threshold has been published.
  In studies, 3 mg/kg twice daily for 4 days caused deep stomach ulcers and raised kidney values, and 1 mg/kg a day for 4 weeks severe gut damage; the old oral LD50 is 59 mg/kg. Dogs recycle diclofenac through bile, and even eye drops have caused stomach erosions. Gels and creams licked or chewed are the usual exposure.

  Source: EMA CVMP 2003
• Ibuprofen: Nervous-system signs from about 400 mg/kg.
  Old age, kidney disease, dehydration or corticosteroids lower the thresholds; repeated low doses (8 mg/kg a day) have caused ulcers without visible signs.

  Source: Dunayer 2004 (ASPCA APCC)
• Naproxen: Half-life in dogs is about 74 hours (enterohepatic recirculation), so small doses accumulate; one 220 mg tablet matters even for a large dog.
  Repeated 5.6 mg/kg for a week caused black stool and pallor.

  Source: DeClementi 2013 (ASPCA APCC)
• Theobromine: Doses are theobromine and caffeine together.
  Content per gram: milk chocolate about 2.3 mg, dark 5-8 mg, baking chocolate 13-16 mg, cocoa powder 20-28 mg, white chocolate almost none. Signs start at 6-12 hours and last long (theobromine half-life in dogs about 17.5 hours).

  Source: MSD Vet Manual: chocolate
• Xylitol: Hypoglycaemia can begin within 30-60 minutes (up to 12-18 hours with chewing gum); liver failure can follow at 9-72 hours without hypoglycaemia first.
  Found in sugar-free chewing gum and sweets, some peanut butters and oral liquids.

  Source: MSD Vet Manual: xylitol

Overdose risk / use with caution

• Acetylsalicylic acid: Aspirin is used in dogs only at low doses set by a veterinarian (for example against blood clots); human tablets are often stronger than a dose for a dog.
  Repeated doses damage the stomach at moderate amounts (25 mg/kg three times a day caused erosions in half of dogs within 2 days); 100-300 mg/kg a day for 1-4 weeks causes poisoning.

  Source: MSD Vet Manual 2024
• Gabapentin: Sugar-free liquid medicines, including oral gabapentin solutions and syrups, often contain xylitol, which is toxic to dogs.
  Check the excipients before giving a liquid formulation to a dog.

  Source: A critical contraindication in the reference (product label)
• Ketoprofen: Ketoprofen is authorised for dogs in the EU (veterinary injection and tablets, EU Union Product Database).
  Human tablets, capsules and gels hold far more than a dose for a dog and are no substitute; an accidental ingestion of one should be checked by a veterinarian. No ingestion threshold has been published (single-dose LD50 studies: about 500 mg/kg).

  Source: EMA CVMP 1995
• Paracetamol (acetaminophen): Paracetamol is used in dogs at veterinary doses (in the UK a paracetamol and codeine product is authorised for dogs).
  Above them the liver is mainly affected; methaemoglobinaemia from about 200 mg/kg. Dry eye has been reported after 40 mg/kg. Repeated dosing harms at lower doses.

  Source: MSD Vet Manual 2024

When the label names the species only in general

If the leaflet says only „animals" or „animals, birds" and gives no separate dose for dogs or cats, treat the dose for that species as not established by the label.

What registration means

In Georgia veterinary medicines are registered by the National Food Agency. There are two routes: national registration (composition, quality control, safety and efficacy data for each species) and recognition of a medicine already registered in another country. In the EU, the UK and the US a new medicine needs target-species safety and field efficacy studies, while a generic is registered on documents and bioequivalence. Registration means the medicine is authorised for the species and dose on its label; using it in another species is the veterinarian's responsibility.

What the labels mean

• Toxic This species has no veterinary use at a proper dose.
• Use with caution Allowed by the label, but the safety margin is narrow; follow the dose and age exactly.
• Overdose risk Used at a proper dose; an overdose is dangerous.

Sources

• Washington State University, Washington Animal Disease Diagnostic Laboratory: MDR1 in Dogs · waddl.vetmed.wsu.edu ↗
• Mealey KL et al. Pharmacogenetics 2001;11:727-33 (ivermectin sensitivity in Collies, MDR1 deletion)
• Metacam (meloxicam) SPC, EMA: not with other NSAIDs or glucocorticosteroids
• Code on Food/Feed Safety, Veterinary and Plant Protection (matsne.gov.ge).
• The list: the reference's toxicity records and contraindications, each with its own source behind (i).