Collie with Demodicosis and Suspected Ivermectin Toxicosis
Rocco is a 14-month-old intact male rough-coated Collie, 19.4 kg, referred for generalized demodicosis. Deep skin scrapings confirm numerous Demodex canis mites; he has 12 areas of alopecia and secondary pyoderma. The referring veterinarian started two weeks ago: compounded ivermectin 1% solution at 0.4 mg/kg PO once daily, plus ketoconazole 10 mg/kg PO once daily. This morning the owner reports Rocco is 'walking like he is drunk,' has dilated pupils, is head-pressing, and has fine muscle tremors; he ate normally yesterday. The owner administered the evening doses at 20:00 and again at 08:00 today. The clinic stocks injectable ivermectin 1% (10 mg/mL), afoxolaner and sarolaner chewables, and moxidectin/imidacloprid spot-on. The veterinarian asks you to review the drug history, calculate the doses given, and help plan the next step while she calls the owner back.
1. Calculate the ivermectin dose Rocco received at each administration and explain the likely cause of his neurologic signs. What do you do before the veterinarian returns the call?
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Dose check. 0.4 mg/kg x 19.4 kg = 7.76 mg per dose. A 1% solution is 10 mg/mL, so 7.76 / 10 = 0.78 mL per dose, given twice within 12 hours.
Interpretation. Mydriasis, ataxia, head pressing and tremors after ivermectin at 0.4 mg/kg is a classic toxicosis. The heartworm prophylactic dose is 0.006 mg/kg, so this is roughly 65 times higher. Two factors amplify it: Collies frequently carry the ABCB1 (MDR1) mutation, which reduces P-glycoprotein at the blood-brain barrier, and ketoconazole inhibits P-glycoprotein and CYP3A4, raising ivermectin exposure further. The combination, not ivermectin alone, likely pushed him over the threshold.
Immediate actions. Stop both drugs and record exact times and volumes. Do not induce vomiting - he is already neurologic and the drug is absorbed. Place him in a quiet, padded cage, obtain IV access, start crystalloids, and monitor temperature, glucose and respiratory effort because aspiration is the main killer. Warn the veterinarian about seizure risk and avoid drugs that lower the seizure threshold. There is no antidote; most dogs recover over 24-72 hours with supportive care.
2. Explain the drug interaction to the owner in plain language, and state what genetic test and record-keeping steps you would recommend.
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Explanation. I would say the drug is not wrong in itself, but Rocco's body clears it unusually slowly for two reasons. First, Collies often carry a gene change that lets more drug reach the brain. Second, ketoconazole blocks the same liver and transport pathways, so the ivermectin piled up. Neither drug alone may have been a problem; together they were.
Testing. Recommend ABCB1 (MDR1) genotyping on a cheek swab. A positive result is lifelong and should be flagged on the record, the cage card and any referral letter, because it also affects loperamide, acepromazine and some chemotherapy agents.
Records and consent. Document that both drugs were dispensed extra-label, the exact concentrations and volumes, the owner's report, the advice given, and that the owner was told to stop the drugs. Note the withdrawal-time discussion if the dog is ever intended for breeding or shows. File the compounding pharmacy's certificate of analysis if available; compounding errors in concentration are a real second possibility when a compounded product is involved.
3. Propose an alternative treatment plan for the generalized demodicosis and the monitoring that goes with it.
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Plan. Once Rocco is stable and neurologic signs have resolved, switch class rather than simply lowering the ivermectin dose. An isoxazoline given with food is the most practical option here - afoxolaner at 2.5 mg/kg monthly (about 48 mg for 19.4 kg) or sarolaner at 2-4 mg/kg monthly - and it avoids the P-glycoprotein interaction. Moxidectin/imidacloprid spot-on used off-label weekly is an alternative, but do not stack it with an isoxazoline.
Why not just reduce ivermectin. A lower dose in an ABCB1-affected dog still carries risk, and subtherapeutic miticidal doses breed poor response and owner frustration.
Monitoring. Recheck deep scrapes monthly; continue treatment until two consecutive scrapes are negative four weeks apart. Treat the pyoderma based on cytology and, if deep or recurrent, culture. Warn the owner that isoxazolines carry a labeled neurologic-event warning and to call if tremors or ataxia return. Book a 30-day recheck at dispensing and record the weight so the chewable dose stays accurate as the dog grows.