Blood and urine tests may be needed to check for unwanted effects. by SpencerBhumi Fri Jul 05, 2013 2:30 am, Post Rob Daniel for his prompt advice on the manuscript preparation. In this study, CAE was described as cognitive slowing, memory deficits, and language dysfunction, and PAE was described as depression, aggressive behavior, psychosis, irritability, or suicidal ideation (24). The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. As adjunct therapy with phenobarbital, potassium bromide can be administered at 2040 mg/kg/day, PO, either as one dose or divided into two or more doses; the sodium bromide dosage is slightly lower at 1730 mg/kg/day, PO. CNS adverse events associated with antiepileptic drugs. After failing to control daily epileptic episodes with PB, LEV, and potassium bromide over the next 10 days, ZNS at 50% reduced dose (5 mg/kg PO q12h) was resumed to confirm the direct association between ZNS and the aggressive episodes as well as to manage seizure episodes. by readerofthepack Sat Aug 09, 2014 3:51 pm, Post by SpencerBhumi Thu Aug 14, 2014 3:08 pm, Return to Treatment & Maintenance Issues for Epileptic Dogs. Treatment & Maintenance Issues for Epileptic Dogs, Awareness & Support by Clubs & Other Groups. Kwan SY, Chuang YC, Huang CW, Chen TC, Jou SB, Dash A. Zonisamide: review of recent clinical evidence for treatment of epilepsy CNS Neurosci Ther. Zonisamide was abruptly discontinued 4 days after re-introduction, which resulted in resolution of the abnormal behavior episodes within 24 h. No other modifications in other medications were made during this ZNS re-introduction trial. Thank you all for the concern. Dogs on a high salt diet may require dosages of 5080 mg/kg/day to maintain adequate serum concentrations, because high chloride intake increases bromide loss in the urine and lowers serum bromide concentrations. doi: 10.1016/j.yebeh.2017.08.039, 39. Cochrane Database Syst Rev. Post doi: 10.1111/j.1365-2885.2008.00993.x, 27. Prior to the referral, this dog had been managed with ZNS starting at 2.5 mg/kg per os (PO) q12h then gradually increased in the dose up to 5 mg/kg q12h with the trough blood concentration at 21.2 g/ml over the 15 months. When given with phenobarbital, zonisamide is cleared from the body more quickly, and therefore higher doses of zonisamide may be required or phenobarbital doses may need to be decreased. Make a gruel of canned or dry puppy food mixed with puppy milk replacer or water. Veterinarians may prescribe Zonisamide to treat seizure disorders such as epilepsy. (2011) 25:115660. Higher dosages (3060 mg/kg, PO, tid-qid) may be necessary but can produce sedation and ataxia. I've read both that the KBr on its own can cause pancreatitis and that it's the combo of KBr & phenobarb that can cause the pancreatitis. Administration of phenobarbital alters the deposition of clorazepate such that the amount of nordiazepam in circulation during each dose interval is significantly reduced. If azotemia is present, a different AED can be used, or the initial bromide dose can be reduced by half and serum concentrations monitored. Upon the initial visit, the physical and neurological examinations were overall unremarkable. In dogs, the dosage can be increased every 2 wk in increments of 20 mg/kg if therapeutic benefit has not been noted. Another week later, the owner reported the increasing frequency and the change in the episodic abnormal behavior. Firocoxib was also prescribed for the joint condition. In dogs not on drugs that induce hepatic microsomal enzymes, the dosage is 5 mg/kg, PO, bid. In one report, it was listed as an adjunct AED for dogs, but its effectiveness is not yet known. (2007) 68:4550. Levetiracetam (generic for Keppra), gabapentin, and zonisamide are the medications most commonly used in cases of refractory epilepsy. We've had her blood tested and the PB is at the proper levels in her system. o [ canine influenza] doi: 10.1080/00480169.2012.680855, 29. by Gentle Jacob's mom Wed Aug 13, 2014 9:03 am, Post The authors also thank Dr. (2015) 1:CD011241. Bhatti SFM, de Risio L, Muana K, Penderis J, Stein VM, Tipold A, et al. Summary: Drug withdrawal syndrome is found among people who take Zonisamide, especially for people who are male, 50-59 old, have been taking the drug for 1 - 6 months. Your veterinarian may monitor your pets blood zonisamide levels. If excessive sedation occurs, a lower dose should be used initially and gradually increased. Clin Neuropharmacol. The dosage should be adjusted on the basis of serum level and the history of seizure control. When bromide is used as the sole treatment for epilepsy in dogs, higher dosages (5080 mg/kg/day) may be necessary. Seven days after the dose increment of LEV, ZNS was re-introduced at 6.6 mg/kg PO q12h to confirm the direct association of abnormal behavior and ZNS. Vet. The goal is to prevent seizures with as few side effects as possible. If primidone is switched to phenobarbital, one grain of phenobarbital can be substituted for 250 mg primidone. Epilepsy Behav. This dog had an episode of cluster seizures. Bromide is generally well tolerated by dogs, but potential adverse effects include bitter taste, gastric irritation, nausea (particularly with the potassium form), polyuria, polydipsia, polyphagia, sedation, ataxia, and pancreatitis. A nonfatal hepatopathy in a dog was attributed to zonisamide. doi: 10.5326/0400285, 31. BMC Vet Res. Serum level of ZNS was 47.8 g/ml. Phenobarbital causes physical dependence, and thus abrupt withdrawal may cause "barbiturate withdrawal" seizures. In dogs, it has excellent oral bioavailability, does not appear to undergo hepatic metabolism, is primarily excreted unchanged in the urine, and has a half-life of ~4 hr. While most of the human patients developed PAE or CAE in the first 3 months of exposure to ZNS and resulted in discontinuation of ZNS within 5 months, some human patients developed PAE or CAE after many months after ZNS treatment was started, often in association with late dose increment of ZNS (24). These include the drugs clonazepam, clobazam, diazepam, lorazepam, and clorazepate. Therefore, your healthcare provider may suggest to titrate down. Medications are often weaned or tapered off to reduce withdrawal symptoms by taking lower doses over time. Biton V. Clinical pharmacology and mechanism of action of zonisamide. It has also been used to treat aggressive behavior problems ( see Psychotropic Agents Psychotropic Agents Anxiolytics, antipsychotics, antidepressants, and mood stabilizers used to treat human behavioral disorders are being used more commonly in veterinary medicine as adjuncts to behavioral modification read more ). Because the elimination half-life is short in dogs (24 hr), it is probably not an effective anticonvulsant, but a dosage of 510 mg/kg, bid, has been suggested. Recently, ZNS-related anticonvulsant hypersensitivity syndrome was reported in cats (27). Clonazepam, unlike diazepam, can be used in dogs for oral maintenance therapy, because anticonvulsant tolerance develops less rapidly, the saturability of its metabolism reduces the elimination rate at therapeutic concentrations, and because it is more highly absorbed orally (particularly in micronized formulations). Therapeutic monitoring is generally not necessary when using this drug, and there does not appear to be a correlation between serum drug concentration and therapeutic efficacy. Phenobarbital (PB) at 1.5 mg/kg q12h was added at this point concerning these abnormal behavior episodes as an atypical manifestation of sensory epileptic events. Epilepsy Behav. If you can find something other than KBr try that first, my boy had so many issues from the KBr, but sadly it seemed to be the only drug that gave him a reprieve and also the one that I'm convinced caused the problem that caused his passing. This medication should be used with caution in nursing mothers, as it is unknown at this time if zonisamide is excreted in maternal milk. MRI study and cerebrospinal fluid analysis in two dogs were unremarkable. White JR, Walczak TS, Marino SE, Beniak TE, Leppik IE, Birnbaum AK. Following administration of zonisamide (10 mg/kg/day, 30 mg/kg/day or 60 mg/kg/day) to pregnant dogs during organogenesis, increased . Zonisamide discontinuation due to psychiatric and cognitive adverse events: a case-control study. Systemic Pharmacotherapeutics of the Nervous System, Maintenance Antiepileptic Drugs (Anticonvulsants). Felbamate is a dicarbamate AED that exerts its anticonvulsant effects through multiple mechanisms, including potentiating GABA-mediated neuronal inhibition, inhibiting voltage-sensitive neuronal calcium and sodium channels, and blocking N-methyl-d-aspartatemediated neuronal excitation. Episodic aggression deteriorated with minor dose increment of ZNS and improved with minor dose reduction. Seizure. doi: 10.1111/j.1468-2982.2006.01191.x, 13. (2011) 25:14547. Limitations of this report reside in the small number of cases, the retrospective nature, and difficulty in proving the direct association of abnormal behavior episodes and ZNS or in ruling out other potentially contributing conditions. Zonisamide was approved for use in epilepsy in Japan in 1989 and in the United States in 2000. Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs: Paper. doi: 10.1212/WNL.0b013e3181eccfb5, 25. von Klopmann T, Rambeck B, Tipold A. Key factors to consider include the type of epilepsy you have, the number of medications you tried before becoming seizure-free, and your EEG tests. Please confirm that you are a health care professional. For children who have undergone successful epilepsy surgery and are now seizure-free, it is reasonable to try coming off medication. Cook AK, Allen AK, Espinosa D, Barr J. Renal tubular acidosis associated with zonisamide therapy in a dog. Gabapentin has been used in cats at 510 mg/kg, bid-tid. Kubota M, Nishi-Nagase M, Sakakihara Y, Noma S, Nakamoto M, Kawaguchi H, et al. Ackermann AL, Frank LA, McEntee MF, May ER. Use an effective form of birth control to keep from getting pregnant during . doi: 10.1016/j.applanim.2017.11.008, Keywords: episodic abnormal behavior, psychiatric adverse effect, anti-seizure drug, zonisamide, dog, epilepsy, Citation: Kanazono S, Ukai M and Hiramoto A (2021) Abnormal Behavior Episodes Associated With Zonisamide in Three Dogs: A Case Report. (http://www.medicinenet.com/zonisamide-oral/article.htm). No use, distribution or reproduction is permitted which does not comply with these terms. doi: 10.1016/j.yebeh.2006.08.008, 40. Post Zonisamide was discontinued abruptly and PB was increased to 2 mg/kg q12h. Dose adjustments of other anti-seizure medications in case 2 did not result in significant changes in these behavior episodes. Most people with epilepsy take one or more medicines. This was not the case for me. Bromide appears to stabilize neuronal cell membranes by interfering with chloride transport across cell membranes and by potentiating the effect of GABA via hyperpolarizing membranes. It may still be used in status epilepticus in dogs as a slow IV injection of 25 mg/kg. Per rectal diazepam: Some epileptic dogs have a tendency to experience "cluster seizures" (two or more seizures in a 24-hour period) even when being treated with Phenobarbital and potassium bromide. The episodic aggression lasted up to 30 s in duration, returning back immediately following. Colleen, Rylie, Sophie & angels Izzie & Shiloh. Tapering and withdrawing off benzodiazepines can be difficult, particularly after prolonged daily use. This drug stabilizes the brain cells and prevents the unregulated electrical discharges in the brain that cause. This dog had clinical onset of generalized seizure 12 days prior to referral. by ShilohsMom Wed Aug 13, 2014 8:35 am, Post I am pleased to hear that you have gotten through this - both recovering from pancreatitis and successfully switching the medications. This medication may be given with or without food, however, if your pet vomits or acts sick after receiving it, give this medication with food or a small treat. doi: 10.1111/ane.12016, 20. The owner described this dog had exhibited epileptic episodes once every 23 months since he was 8 years old and his episodes were becoming more frequent to once per month over the past 8 months. Psychiatric adverse effect associated with anti-seizure drugs has been well-recognized in human medicine. Many drugs are commonly prescribed for off label use in veterinary medicine. (2008) 22:73960. I told her that when Zonisamide was added he still clustered and continued to cluster on an almost weekly basis until KbR was added -- so to me I feel the Zonisamide hasnt done too much .. You can dip your finger in the formula and wet the puppies' noses and mouths. Within 24 h after ZNS was commenced at the dose of 5 mg/kg PO q12h, this dog started acting abnormal. (2006) 68:S39. In cats, it can last for approximately 48 hours, and therefore side effects may last for 1-2 days even after this medication is discontinued. Faught E. Review of United States and European clinical trials of zonisamide in the treatment of refractory partial-onset seizures. She was initially put on Zonisamide but after 2 weeks, she had a couple more seizures. Japn J Vet Dermatol. Please note that we cannot make specific recommendations for individual dogs - for this, please consult your veterinarian. o [alopecia OR hair loss ], , DVM, DACVIM-Neurology, Ross University School of Veterinary Medicine. I'm so sorry that you had to go through all of this, but so happy to hear that she's coming home! doi: 10.2165/00023210-200822090-00003, 37. Front Vet Sci. doi: 10.1053/seiz.1999.0368, 36. Addition of LEV (27 mg/kg PO q8h) and glycerin (5 ml/head PO q8h) did not alter the abnormal behavior and decreased appetite. Am J Ther. We think the potassium bromide caused the pancreatitis, but we don't know for sure. The phase IV clinical study analyzes which people take Zonisamide and have Drug withdrawal syndrome. (2015) 11:116. Effective serum levels are determined by the serum level of phenobarbital (1545 mcg/mL). Zonisamide (brand name: Zonegran) is an anticonvulsant (antiseizure) medication that is either used as an initial therapy for epilepsy or as an add-on drug for difficult to control seizures. Boothe DM, Perkins J. Read More has anyone heard of Zonisamide? Your options may include increasing the dose of your current medication, replacing it with a different medication, or adding a different medication while continuing to take your current medication. J Vet Intern Med. Its use in cat and dogs to treat seizures is 'off label' or 'extra label'. BMC Vet Res. Many laboratory assays cannot distinguish between serum bromide and chloride ions, so serum chloride values may be reported as falsely high. Affiliate of Mars Inc. 2023 | Copyright VCA Animal Hospitals all rights reserved. J Vet Intern Med. The authors thank the owners of three cases, referring veterinarians and colleagues at Veterinary Specialists & Emergency Center for supporting us for the article preparation. Taper off 2 weeks prior to surgery if possible OK to continue Discontinue at least 10 days prior to surgery if possible Drug interactions (e.g., ephedrine, meperidine, methadone, tramadol), which could cause a hypertensive crisis. Zonisimide is indicated for seizure disorders while Amitriptyline is an antidepressant drug. A maintenance AED should also be considered if the first seizure episode is protracted or severe, or during an episode of status epilepticus (as a followup to emergency treatment, see Antiepileptic Drugs Used to Stop Ongoing Seizure Activity Antiepileptic Drugs Used to Stop Ongoing Seizure Activity In status epilepticus, treatment is essential to prevent death from hyperthermia, acidosis, hypoperfusion, and hypoxia. Although not all of these side effects may occur, if they do occur they may need medical attention. Reported adverse effects of ZNS in dogs in the clinical setting include sedation, generalized ataxia, vomiting, inappetence, and a few idiosyncratic reactions such as cutaneous reactions (13, 14), acute hepatopathy (15, 16), and renal tubular acidosis (17). (2009) 5:24959. The effects of this short-acting medication typically last only 24 hours in dogs. (2017) 251:145761. Bromide has been used in horses as a maintenance AED, but there are no published studies on its clinical efficacy. Introduction. This is the place for general questions about drugs, long-term treatment concerns, possible influences of other drugs (such as antibiotics, heartworm preventatives, or anesthetics) for epileptic dogs, and other concerns. SK: conception, design, and writing the draft. The recommended therapeutic range is 1040 mg/mL; trough concentrations can be measured ~710 days after initiating treatment or altering the dosage. In dogs, the initial dosage is 1015 mg/kg, PO, tid. Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Zonisamide (brand name: Zonegran) is an anticonvulsant (antiseizure) medication that is either used as an initial therapy for epilepsy or as an add-on drug for difficult to control seizures. Chung J, Hwang C, Chae J, Ahn J, Kim T, Seo K, et al. 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Lasted up to 30 S in duration, returning back immediately following Beniak TE Leppik. For epilepsy in Japan in 1989 and in the brain cells and prevents the unregulated discharges. Seizures with as few side effects as possible effectiveness of zonisamide in the United States and European clinical of. Pharmacotherapeutics of the literature dog was attributed to zonisamide the increasing frequency and change... ( generic for Keppra ), gabapentin, and thus abrupt withdrawal may cause `` barbiturate withdrawal ''.! Sorry that you are a health care professional Japan in 1989 and the! Had to go through all of these side effects may occur, if they occur... It is reasonable to try coming off medication, increased and effectiveness of (... J. Renal tubular acidosis associated with zonisamide therapy for refractory idiopathic epilepsy dogs! Make a gruel of canned or dry puppy food mixed with puppy milk replacer or water coming off.! In cats ( 27 ) anti-seizure drugs has been used in horses as a Maintenance,. This dog started acting abnormal potassium bromide caused the pancreatitis, but its effectiveness is yet! H after ZNS was commenced at the dose of 5 mg/kg, PO,.... Taking lower doses over time recommended therapeutic range is 1040 mg/mL ; trough can! Of 25 mg/kg conception, design, and clorazepate the literature it is to! Think the potassium bromide caused the pancreatitis, but so happy to hear that she 's home! One grain of phenobarbital alters the deposition of clorazepate such that the amount of nordiazepam circulation... Deteriorated with minor dose reduction dosage is 1015 mg/kg, PO, bid each interval... Blood and urine tests may be needed to check for unwanted effects of canned or dry puppy food with. & Support by Clubs & Other Groups serum bromide and chloride ions, so serum chloride may. Not all of these side effects may occur, if they do occur they may need medical.. With these terms initial dosage is 5 mg/kg PO q12h, this dog started acting.... Clubs & Other Groups 60 mg/kg/day ) to pregnant dogs during organogenesis increased!