Really, zonisamide? You couldn't just let this one slide? Phenobarbital already has dibs on blood dyscrasias and I'm struggling to like you as it is. Why did you go and have to do THIS to dogs, too??
If you've been a TidBit Tuesday reader for awhile you'll know I struggle to love zonisamide. Yes, it has it's place in movement disorder management. Yes, it can be a wonderful anticonvulsant. in some dogs. But in my hands, in my experience, it either hasn't worked well or I've seen undesirable side effects that I've attributed to zonisamide. And it is a Sulfa antibiotic. So, there's that worry, too.
New this week, we can read about 4 dogs with blood dyscrasias likely secondary to zonisamide administration.
Dog 1: 7 year old Shih Tzu. Presented for vomiting, lethargy and fever. He had received Zonisamide (ZNS) for 400 days at a dose of 5 mg/kg q12h. Severe leukopenia with neutropenia, monocytopenia and lymphopenia were noted along with an elevated ALP, ALT, hypocalcemia, hypochloremia, hyponatremia, and hyperbilirubinemia. ZNS was discontinued and antimicrobials were started. 19 days later, the leukopenia was resolved.
Dog 2: 1 year old Siberian Husky. Presented for a history of groaning, and appearing tense. He had received ZNS for 29 days at a dose of 17 mg/kg q12h. On presentation the dog was also febrile, had a leukopenia with neutropenia, and increased ALP and hypoalbuminemia. Zonisamide was discontinued and the leukopenia persisted through 40 days. On day 180 from discontinuation, the WBC was within the reference range.
Dog 3: 9 yr old Miniature Poodle. She presented for lethargy, anorexia, labored breathing and reluctance to walk. She had received zonisamide for 20 days at a dose of 8.5 mg/kg q12h. No fever was noted on presentation however overnight a fever developed. Severe leukopenia with neutropenia was documented after the zonisamide was discontinued (within 24 hours, I think) along with increased ALP activity and hyponatremia. Leukopenia and neutropenia resolved by day 6.
Dog 4: 5 year old Miniature Poodle. He presented for vomiting, lethargy and anorexia as well as fever. ZNS was started 1,196 days prior to presentation at a dose of 8.4 mg/kg q12h. Again, CBC showed a leukocytosis with neutropenia and mild thrombocytopenia. Serum biochemistry showed increased ALP, hyponatremia, hypokalemia, hypochloremia and hypercholesterolemia. Zonisamide was discontinued and leukopenia improved within 2 days, and normal by day 3.
The authors attributed the blood dyscrasia to an idiosyncratic drug reaction. Idiosyncratic, of course, means that it is unpredictable in scope and severity and not reliably related to dose. Other idiosyncratic reactions to ZNS include hepatopathies, skin eruptions and rental tubular acidosis. Perhaps all of these reactions are because this is a sulfonamide derived anticonvulsant? Discontinuing the drug is the best way to try to reverse the blood dyscrasia. I found it interesting that in one of the cases they continued phenobarbital (a drug also known to have a risk of idiosyncratic blood dyscrasia) and the bone marrow was still able to regenerate.
Key point: If you find an abnormal CBC for a pet receiving ZNS, please consider an idiosyncratic blood dyscrasia and discontinue the drug (safely).
Reference: https://doi.org/10.1111/vec.13222
Have a great week and thanks for reading!