Chronic toxicity of the anticonvulsant zonisamide in Beagle dogs*1

Walker, Robin M.; DiFonzo, C.J.; Barsoum, N. J.; Smith, Graham; Macallum, Grace E.

doi:10.1016/0272-0590(88)90158-3

Cited by 29 publications

(40 citation statements)

References 6 publications

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“…Thirteen of the 14 study dogs were treated with 10 mg/kg zonisamide orally twice a day as an add‐on therapy (Matsumoto and others 1983, Walker and others 1988, Boothe and others 2005, Saito and others 2005). Previous anticonvulsive medication was continued unchanged until the individual expected seizure interval passed through without an ictus and then was gradually reduced if appropriate.…”

Section: Methodsmentioning

confidence: 99%

Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs

Klopmann¹,

Rambeck²,

Tipold³

2007

J of Small Animal Practice

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Section: Methodsmentioning

confidence: 99%

Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs

Klopmann¹,

Rambeck²,

Tipold³

2007

J of Small Animal Practice

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“…A previous canine study revealed that plasma C min were stable for the first 26 weeks when zonisamide was administered repeatedly at a daily dose of 10, 30, and 75 mg/kg. In dogs receiving the highest dose, however, it increased another 30% beyond that expected from the dose increase (Walker et al. , 1988).…”

Section: Trough Concentrations Of Zonisamide In Plasma Whole Bloodmentioning

confidence: 97%

Steady-state pharmacokinetics of zonisamide in plasma, whole blood, and erythrocytes in dogs

Fukunaga¹,

Saito

Muto

et al. 2010

Journal of Veterinary Pharmacology and Therapeutics

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mentioning

confidence: 99%

“…Side effects, including ataxia, lethargy and vomiting, were mild and transient and never warranted discontinuation [3,11]. A study on the chronic toxicity of ZNS in dogs, using over 7 times the recommended dose for a duration of 52 weeks, revealed mild effects on the liver only that were not associated with any significant clinical signs [12].The purpose of this report is to describe the findings in a dog with severe hepatopathy that developed following initiation of ZNS monotherapy and resolved after discontinuation of ZNS with supportive care.A 9-year old female spayed Rottweiler (36 kg) presented to the Neurology Service of the Veterinary Teaching Hospital (VTH), North Carolina State University for investigation and treatment of generalised cluster seizures that began 36 hr prior to presentation.The patient had no significant clinical history and was upto-date with standard vaccinations and parasite treatment and prevention. Current medication consisted of carprofen (2.1 mg/kg, PO, q 24 hr (Rimadyl; Pfizer)) and a glucosamine-containing joint supplement (1 tablet q 24hr (Glyco-Flex II; Vetri-Science Laboratories)) for treatment of bilateral coxofemoral joint osteoarthritis, phenylpropanolamine (1.4 mg/kg, PO, q 24 hr (Proin 50 Chewable Tablets; PRN Pharmacal)) for treatment of urinary incontinence and famotidine (0.6 mg/kg, PO, q 12 hr (Famotidine Tablets USP; Ivax Pharmaceuticals Ireland)) for treatment of an episode of vomiting.…”

mentioning

confidence: 99%

“…Nevertheless, this may become very useful once more canine-specific data on therapeutic ZNS blood levels are available. Based on the lack of signs of toxicity with chronic administration of much higher doses than chosen for this patient [12], it appears unlikely that a dosedependant toxicity has occurred in this dog. The dog was administered general supportive therapy for liver disease.…”

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confidence: 99%

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Possible Drug-Induced Hepatopathy in a Dog Receiving Zonisamide Monotherapy for Treatment of Cryptogenic Epilepsy

Schwartz

Muñana

Olby

2011

The Journal of Veterinary Medical Science

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ABSTRACT. A 9-year old female spayed Rottweiler was diagnosed with cryptogenic epilepsy and started on zonisamide monotherapy (8.3 mg/kg, PO, q 12 hr). Three weeks after the 1st dose of zonisamide the dog presented for vomiting, inappetence and icterus. Serum biochemistry showed marked elevation of liver enzymes, consistent with hepatocellular damage and cholestasis. No underlying cause for liver disease was identified and a drug-induced hepatopathy was suspected. Zonisamide was discontinued and replaced by potassium bromide. Supportive therapy consisted of intravenous fluids, antiemetics, antibiotics and hepatoprotectants. The dog made a complete recovery and serial serum biochemical examinations showed complete normalisation of liver parameters 8 weeks after discontinuation of zonisamide. Based on a human Drug-induced Liver Injury Diagnostic Scale, the likelihood for zonisamide-induced hepatopathy was classified as "possible". Veterinary practitioners and owners should be educated about the potential for an idiosyncratic drug reaction to zonisamide. If signs of hepatotoxicity are recognised early and zonisamide is discontinued, complete recovery is possible.KEY WORDS: antiepileptic drug, canine, idiosyncratic drug reaction, liver, seizure.J. Vet. Med. Sci. 73(11): 1505-1508, 2011 The sulfonamide derivate zonisamide (ZNS) is a new generation antiepileptic drug (AED) that was introduced into the Japanese market in 1989 and received licensure in the US and Europe in 2000 and 2005, respectively. While the US and European approval is limited to use as an add-on AED for humans with partial seizures, the Japanese license includes utilisation as mono-and adjunctive therapy for partial and generalised seizures [5].With blockage of voltage-sensitive sodium channels and T-type calcium channels, ZNS possesses a unique mode of action among the currently available AEDs. There is evidence that ZNS also exhibits direct effects on synthesis, release and degradation of the neurotransmitters glutamate, gamma aminobutyric acid (GABA), dopamine, serotonin and acetylcholine, thereby promoting synaptic inhibition. Furthermore, ZNS has been ascribed neuroprotective effects. To date it remains uncertain as to whether the direct effects on neurotransmitters and the neuroprotective properties play a role in the clinical use as an AED [1].In contrast to many of the newly developed anticonvulsants, ZNS has a sufficiently long serum elimination halflife in dogs, to allow maintenance of therapeutic blood levels by means of twice daily dosing [2,9]. This feature in particular has raised interest in using ZNS for treatment of canine epilepsy, and assessment of its use as add-on medication in cases of refractory epilepsy provided promising results with good rates of responders [3,11].Throughout the reports on the use of ZNS in dogs, the drug appears to have a favourable adverse effect profile. Side effects, including ataxia, lethargy and vomiting, were mild and transient and never warranted discontinuation [3,11]. A study on the chronic toxici...

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Chronic toxicity of the anticonvulsant zonisamide in Beagle dogs*1

Cited by 29 publications

References 6 publications

Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs

Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs

Steady-state pharmacokinetics of zonisamide in plasma, whole blood, and erythrocytes in dogs

Possible Drug-Induced Hepatopathy in a Dog Receiving Zonisamide Monotherapy for Treatment of Cryptogenic Epilepsy

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