Acute and Chronic Adverse Effects of Zonisamide in Dogs

Zonisamide and the Liver

Many of you know of my love-hate relationship with zonisamide. It stems from the lack of published data, and my reliance on personal observation/preference. Well, this is about to change! This week, a colleague at UW published a delightfully large study looking at acute and chronic hepatopathy in dogs receiving zonisamide.

Materials and Methods:
384 dogs were included. 103 dogs met the criteria for monitoring for acute change because they had bloodwork before, and within 3 months of starting the medication. One hundred and seventeen dogs met the criteria for chronic observation because they had biochemical monitoring greater than 3 months from starting zonisamide.

Acute Hepatopathy Results
Two dogs had clinical signs and biochemical changes on bloodwork consistent with acute hepatopathy within the first 3 months of administration. An additional 1 dog had biochemical changes but no clinical signs of hepatic disease. That is an overall incidence of 2.9% (3/103)

Case 1:
15 year old Australian Shephard diagnosed with seizures secondary to a brain mass. Started on Zonisamide and 10 days later, prednisone. The dog became clinically ill 9 days later and her ALT went from 164 U/L to 3162 U/L on day 23. The zonisamide was discontinued, prednisone was continued and 11 days after stopping zonisamide her ALT was 179 U/L. (ALT reference range: 10-125 U/L),
Dose of zonisamide was 6.3 mg/kg PO q12h.

Case 2:
8 year old Mini Schnauzer with cluster seizures. Clinical signs of liver disease started 13 days later and her ALT went from 224 U/L to 2170 U/L in those 13 days. She was treated with supportive care but continued to decline and was humanely euthanized. No necropsy performed. Dose of zonisamide: 7.8 mg/kg PO q12h.

Case 3:
4 year old MC Bulldog. This dog developed biochemical changes consistent with a hepatopathy on bloodwork monitored 15 days after starting zonisamide. The ALT was 186 U/L initially and increased to 896 U/L. Zonisamide was discontinued and the ALT returned to normal (96 U/L) 14 days after stopping. Zonisamide dose: 7.1 mg/kg PO q12h.

Chronic Hepatopathy Results
The report discusses biochemical changes consistent with chronic hepatopathy in a separate 117 dogs. Ten of 117 had an elevation in ALP alone compared to baseline but additional diagnostic testing was not performed (about 8%). Six of 117 (about 5%) dogs had a new mild increase of ALT compared to baseline but not considered a significant elevation in value. No decrease in albumin was noted when increases in ALT and ALP were noted. No clinical signs of a hepatopathy were detected in this group.

Take home message:

  • Zonisamide is pretty darn safe (if you know what to monitor)

  • Monitoring blood work should be performed at 3 weeks and 3 months and then annually when on zonisamide

  • Clinical signs of hepatopathy, while on zonisamide, should prompt you to run a biochemistry and if liver values are abnormal, taper the zonisamide and discontinue it

  • Zonisamide is a sulfa derived anticonvulsant. Remember - use caution in breeds and dogs sensitive to sulfa antibiotics!

  • Only one case was fatal in this study, and another has been reported in the literature, so it can happen but is likely idiosyncratic.

  • This data does not apply to cats!

If you'd like to read more on this groundbreaking study please see the link: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16398

Thanks for reading! As you may have heard I will be out of town April 4-9, speaking at the Austin Vet Conference. My first LIVE conference in over 2 years! Yikes! I hope I remember how to stand up and speak in front of people (you know, instead of in front of my computer screen). Please reach out if you need me but be aware that there may be a delayed response that week. Have a great week!