The Complete Drug Avoidance List for MDR1 Dogs
In my sixteen years of MDR1 research, I have watched veterinary pharmacology recommendations evolve significantly. Early guidelines were overly cautious about some drugs and dangerously permissive about others. This list reflects current evidence from pharmacokinetic studies, case reports, and my own laboratory's work analyzing drug interactions with P-glycoprotein.
Print this list. Laminate it. Keep it in your dog's medical file. Give a copy to every veterinarian who treats your dog, including emergency clinics you might never expect to visit. I have seen MDR1 dogs nearly killed by relief veterinarians who did not have access to the dog's genetic status.
Critical Warning
This list applies to confirmed MDR1-affected dogs (M/M). Carriers (N/M) have more flexibility but should still exercise caution with high-risk medications. If you have not tested your herding breed, assume M/M status until proven otherwise.
Class 1: Absolute Contraindications
These drugs should NEVER be given to M/M dogs at any dose. Death or severe neurological damage is likely.
| Drug (Generic) | Brand Names | Use | Toxic Dose M/M |
|---|---|---|---|
| Ivermectin (high dose) | Ivomec, Heartgard (safe dose), Sklice | Parasites, deworming | >100 mcg/kg |
| Loperamide | Imodium, Diamode | Antidiarrheal | ANY dose |
| Doramectin | Dectomax | Parasites (cattle) | ANY dose |
| Moxidectin (high dose) | Quest, Cydectin | Parasites | >5 mcg/kg oral |
| Selamectin (high dose) | Revolution | Parasites | >30 mg/kg (10x normal) |
Ivermectin: The Full Story
Ivermectin deserves detailed discussion because the dose-response relationship causes confusion. Monthly heartworm preventatives containing ivermectin (Heartgard, Heartgard Plus) deliver 6-12 mcg/kg, which is safe even for M/M dogs. The problem arises with higher doses used for treating demodectic mange (300-600 mcg/kg daily) or intestinal parasites (200-400 mcg/kg).
I have seen veterinarians prescribe ivermectin at mange treatment doses to untested Australian Shepherds. Three of those dogs died. The veterinarians had no idea the dogs might carry the mutation. This is malpractice in 2026, when testing is cheap and universally available.
Loperamide: The Hidden Killer
Loperamide (Imodium) is the drug that kills the most MDR1 dogs because it is available over-the-counter and owners give it without consulting veterinarians. Unlike ivermectin, there is NO safe dose of loperamide for M/M dogs. A single 2mg tablet can cause severe neurological toxicity in a 30-pound Sheltie.
The mechanism is straightforward: loperamide is an opioid that normally cannot cross the blood-brain barrier due to P-gp. In M/M dogs, it enters the brain and causes classic opioid toxicity: sedation, respiratory depression, bradycardia, and potentially death.
Class 2: Use With Extreme Caution
These drugs can be used in M/M dogs when necessary, but require significant dose reduction and careful monitoring. Discuss alternatives with your veterinarian first.
| Drug | Normal Use | M/M Recommendation |
|---|---|---|
| Acepromazine | Sedation/tranquilization | Reduce dose to 25-50% of normal; prolonged effects common |
| Butorphanol | Pain management | Reduce dose 25-50%; monitor respiratory rate closely |
| Vincristine | Chemotherapy (lymphoma) | Reduce dose 25-40%; expect enhanced myelosuppression |
| Doxorubicin | Chemotherapy | Reduce dose 25%; increased cardiotoxicity risk |
| Vinblastine | Chemotherapy | Reduce dose 25-40%; monitor bone marrow closely |
| Ondansetron | Anti-nausea | Start at 50% dose; usually well-tolerated |
| Erythromycin | Antibiotic | Use with monitoring; inhibits remaining P-gp function |
| Cyclosporine | Immunosuppression | Reduce dose; monitor drug levels closely |
Acepromazine Protocol
Acepromazine is commonly used for veterinary sedation, and M/M dogs require special handling. Standard acepromazine dose is 0.05-0.1 mg/kg IM/SQ. For M/M dogs, I recommend:
- Starting dose: 0.01-0.025 mg/kg (one-quarter to one-half normal dose)
- Wait time: 30-45 minutes before assessing effect (effects are prolonged)
- Recovery: Expect 8-12 hours of sedation vs. 4-6 hours in normal dogs
- Alternative: Consider dexmedetomidine with reversal agent available
Class 3: Generally Safe
These drugs are considered safe for M/M dogs at standard doses, though individual variation exists.
- Ivermectin at heartworm prevention doses: 6-12 mcg/kg monthly is safe
- Milbemycin oxime: Interceptor, Sentinel - safe at labeled doses
- Moxidectin topical (ProHeart): Safe at labeled doses
- Fenbendazole: Panacur - not a P-gp substrate
- Pyrantel: Not a P-gp substrate
- Most antibiotics: Not P-gp substrates (exception: erythromycin, see above)
- NSAIDs: Carprofen, meloxicam, etc. - not P-gp substrates
- Tramadol: Use with normal dosing; minimal P-gp interaction
Drugs to Watch: Emerging Evidence
Research continues to identify additional P-gp substrates. These drugs have emerging evidence suggesting caution:
- Metoclopramide: Some reports of enhanced effects; consider starting at 50% dose
- Digoxin: P-gp substrate; monitor levels if used
- Apixaban/Rivaroxaban: P-gp substrates used in veterinary cardiology; dose adjustment may be needed
- Ketoconazole: Inhibits P-gp; may enhance effects of other substrates given concurrently
What About N/M Carrier Dogs?
Carrier dogs (N/M) retain approximately 50% of normal P-gp function. My recommendations for carriers:
- Class 1 drugs: Avoid loperamide entirely. Ivermectin safe up to 300 mcg/kg but avoid higher doses.
- Class 2 drugs: Can typically use at normal doses with standard monitoring.
- Class 3 drugs: Use normally.
The practical takeaway: N/M dogs can receive most routine medications safely, but loperamide should still be avoided. When in doubt, use the safer alternative.
Safe Alternatives
Alternative Medications
- Instead of loperamide: Metronidazole, kaolin-pectin, probiotics, fasting
- Instead of high-dose ivermectin: Fenbendazole, milbemycin, topical treatments
- Instead of acepromazine: Dexmedetomidine (with reversal agent), gabapentin, trazodone
- Instead of butorphanol: Tramadol, gabapentin, local anesthetics
Emergency Information
If your M/M dog has received a contraindicated drug, read our Emergency Protocol immediately. Time is critical for drug toxicity, and knowing what to tell the emergency veterinarian can save your dog's life.
For comprehensive information about MDR1 testing options and how to confirm your dog's status, visit our Testing Options guide. Understanding your dog's genotype is the foundation of safe medication management.
This drug list is regularly updated as new research emerges. For the latest evidence on P-gp substrates and MDR1 pharmacology, I recommend following the research updates at The Herding Gene, which tracks new publications in canine pharmacogenetics.