Akman CI, Goodkin HP, Rogers DP, Riviello JJ. 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. Episodic aggression deteriorated with minor dose increment of ZNS and improved with minor dose reduction. Although therapeutic and toxic range of ZNS in dogs has not been well-established yet, serum concentration at 47.8 g/ml in our case 2 could be considered in high end or above the therapeutic range (6, 7, 25, 28). In human medicine, there were several reports of psychiatric and behavioral side effects associated with ZNS (1, 24, 3336). Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs: Paper. Tapering off Gabapentin though requires patience so you need to be careful to not immediately take your dog off large doses of it. He has been on Zonisamide a year this July -- his ataxia is getting worse, the breathing heavily and drooling he has as well -- I talked to the vet this morning about it all. Contact your veterinarian immediately if your pet stops eating, becomes dramatically lethargic, or develops a yellow color of the skin, gums, or whites of the eyes. Zonisamide (ZNS) is an antiepileptic drug (AED) approved for adjunct treatment of partial seizures in adults. Neurology. Give her as little as possible until you are sure that she is still not having seizures. 2 In addition to the treatment of several generalized epilepsy syndromes, it may also play a role in managing obesity, migraine, and motor dysfunction in Parkinson disease (PD). A nonfatal hepatopathy in a dog was attributed to zonisamide. Dewey CW, Guiliano R, Boothe DM, Berg JM, Kortz GD, Joseph RJ, et al. Boothe DM, Perkins J. Limited data suggest zonisamide may be beneficial . Contact your veterinarian if these signs are severe. An oral loading dosage of 400600 mg/kg of bromide is divided into four doses and given with food over a 1- to 4-day period. Epilepsy is one of the most common neurological disorders in dogs (), characterized by spontaneous recurrent seizures originating in the central nervous system ().The prevalence of canine epilepsy varies in different studies between 0.5% and 5% ().If no underlying cause except of hereditary factors are found for the recurrent seizures in the diagnostic work-up, epilepsy is . Get the personalized nutrition plan your dog needs with non-GMO air dried dog food. . Doing this may increase your risk of having more frequent and/or severe seizures. Phenytoin (diphenylhydantoin) is no longer recommended for maintenance use in dogs, cats, or foals because of undesirable pharmacokinetic properties. Hopefully we are out of the woods with the pancreatitis. This dog had no pre-existing abnormal behavior problems before and no seizure episodes were witnessed in association with these behavior episodes. Topiramate is a newer AED that is well tolerated by people and increasingly used for neuropathic pain. (2016) 12:79. doi: 10.1186/s12917-016-0703-y, 3. Walker RM, DiFonzo CJ, Barsoum NJ, Smith GS, Macallum GE. Blood and urine tests may be needed to check for unwanted effects. Our dog has been on zonisamide and phenobarbital for some time. Adverse effects of salivation, restlessness, vomiting, and ataxia at dosages >400 mg/kg/day have been seen experimentally in dogs but resolved within 24 hr of discontinuing the drug. Zonisamide therapy for refractory idiopathic epilepsy in dogs. Zonisamide - Zonisamide is a broad-spectrum antiseizure medication that blocks voltage-dependent sodium and T-type calcium channels. Weintraub D, Buchsbaum R, Resor SR, Hirsch LJ. It is very important that your doctor check your progress at regular visits to see if the medicine is working properly. (2011) 25:115660. CNS adverse events associated with antiepileptic drugs. KBr is associated with pancreatitis and megaespohagus. doi: 10.1111/ane.12016, 20. Most dogs will continue for the rest of their lives to have seizures, it now becomes about control. doi: 10.1111/j.1365-2885.2008.00993.x, 27. (2016) 30:47790. 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. Severe withdrawal symptoms, even lethal seizures, may appear after abrupt discontinuation of chronic clorazepate treatment, in spite of the relatively low tolerance liability of clorazepate. All authors contributed to the article and approved the submitted version. Use for phrases (2007) 10:10510. (2006) 26:1199202. Whether or not youre experiencing side effects from your current medication, How much your medication has lowered the frequency and/or severity of your seizures, What other medications may be right for your kind of epilepsy, How they might interact with your current medication. No significant changes in the environment were reported. Vet says if the switch doesn't improve her behavior, she suspects a physical tumor and at that point is just a matter of time. doi: 10.1080/00480169.2012.680855, 29. Other adverse effects and signs of overdosage are similar to those of phenobarbital. MRI and cerebrospinal fluid analysis were rejected by the owner given the concerns associated with general anesthesia and long history of presumptive idiopathic epilepsy. We do not control or have responsibility for the content of any third-party site. Zonisamide is used off-label for therapy of migraine headaches, mood disturbances and recently for weight loss. Abnormal behavior episodes included sudden rage and aggression to the family members, insomnia, restlessness, and/or constant attention-seeking behavior. If you decide to switch to a different medication, youll need to take both for a while to see how helpful the new medication is and how well you tolerate it. However, the dosing regimen needs to be tailored for each animal; the upper end of the therapeutic range is only limited by adverse effects of bromide. Disposition and safety of zonisamide after intravenous and oral single dose and oral multiple dosing in normal hound dogs. Pancratitis can be dealt with, I hope your vet comes thru for you and your pup. The Merck Veterinary Manual was first published in 1955 as a service to the community. Zonisimide is indicated for seizure disorders while Amitriptyline is an antidepressant drug. Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Potential adverse effects are hepatotoxicity, reversible myelosuppression, generalized tremors, and possibly keratoconjunctivitis sicca; regular monitoring for anemia and liver dysfunction in dogs is recommended. Miyamoto T, Kohsaka M, Koyama T. Psychotic episodes during zonisamide treatment. Ashkenazi A, Benlifer A, Korenblit J, Silberstein SD. What Drugs, Substances, or Supplements Interact with Voltaren Therapeutic monitoring is not usually necessary with this drug. Effective serum levels are determined by the serum level of phenobarbital (1545 mcg/mL). When the owner called him during the abnormal behavior episode, the dog was able to come out of it and went back to himself. Sci. Fundam Appl Toxicol. 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 .. Gabapentin has been used in cats at 510 mg/kg, bid-tid. The phenobarbital metabolite is likely the major functional one, and there may not be an advantage to using primidone over phenobarbital. If you suspect an overdose or an adverse reaction to the medication, call your veterinary office immediately. MRI, cerebrospinal fluid analysis, and fasted and postprandial total bile acid analyses were within normal limits. The frequency of his GTCS decreased after increment of ZNS up to 13.7 mg/kg q12h while the abnormal behavior episodes increased in its frequency further to over 10 times a day, including abrupt growling at or attempts to bite the family members when they came into his sight while awake (Supplementary Video 1). I do hope your progress continues in such a positive manner from here on. Although the drug appears safe, owners should be warned that because of the sulfonamide base, potential adverse effects (eg, keratoconjunctivitis sicca, bone marrow dyscrasia, hepatopathy, vasculitis, and metabolic acidosis) could occur. Changes in brain serotonin and dopamine levels are considered as a mechanism of ZNS-induced PAE (24, 35, 37) and human patients with a history of psychiatric disorder had significantly greater risk of developing PAE associated with ASDs including ZNS (24, 36, 38, 39). (2015) 1:CD011241. Brain Dev. The dosage should be adjusted on the basis of serum level and the history of seizure control. Zonisamide should be stored at 25C (76F). (2011) 73:15058. These include the drugs clonazepam, clobazam, diazepam, lorazepam, and clorazepate. I'm so sorry that you had to go through all of this, but so happy to hear that she's coming home! Rare side effects include liver disease, urinary stones, and aggression. doi: 10.1016/j.yebeh.2006.08.008, 40. Because a daily maintenance dose may take 4 mo to reach steady state serum concentration, there are situations (eg, severe seizures, seizures that occur on a monthly basis, the need to rapidly switch from phenobarbital to bromide because of phenobarbital toxicity) when a loading dose of bromide should be administered. by readerofthepack Sat Aug 09, 2014 6:50 am, Post Similarly, a case series study described abnormal behavior episodes in dogs receiving LEV (40). Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. 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. Other reported adverse effects include fatigue, headache, psychiatric symptoms, cognitive disturbances, diplopia, weight loss, diarrhea, ataxia, oligohydrosis, urolithiasis, and rash (1924). A total of 10 dogs were enrolled in the study, and all dogs received levetiracetam at a dose of 20 mg/kg/day. 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. J Am Anim Hosp Assoc. Many epilepsies that begin in childhood may be outgrown. Severe signs of toxicity are easily treated by IV administration of 0.9% sodium chloride, which promotes renal excretion of the bromide ion. In dogs, phenobarbital and bromide are considered first-line maintenance AEDs, but levetiracetam and zonisamide are often used as well. by readerofthepack Wed Aug 13, 2014 8:29 am, Post This dog was managed well with PB (2 mg/kg q12h) and LEV (20 mg/kg q8h) with no observable epileptic or aggressive behavior episodes for 13 months until this dog died of an unrelated condition. Colleen, Rylie, Sophie & angels Izzie & Shiloh. Zappia M, Albanese A, Bruno E, Colosimo C, Filippini G, Martinelli P, et al. . (2008) 22:73960. The weaning process should happen gradually, over a few weeks. In most cases, the risk of stopping medication slowly is low. Systematic review of antiepileptic drugs' safety and effectiveness in feline epilepsy. Please note that we cannot make specific recommendations for individual dogs - for this, please consult your veterinarian. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy. Addition of LEV (27 mg/kg PO q8h) and glycerin (5 ml/head PO q8h) did not alter the abnormal behavior and decreased appetite. The seizure episode was described as sudden running fit with falling and defecation, followed by 12-min duration of opisthotonus, clonic motor activities, and copious amount of ptyalism. Within another week, the abnormal behavior episodes completely disappeared. Our recommendation of reintroducing ZNS for confirmation of direct association between the aggressive behavior and ZNS was rejected by the owner for safety concern of the family members. This pyrrolidine-based anticonvulsant has an unknown mechanism of action. Prior to this, she had never had a partial seizure and her seizures were usually several hours apart. A serum sample can be submitted within 2 wk after loading to determine whether a therapeutic level has been reached. J Am Vet Med Assoc. Making the decision to stop taking an anti-seizure medication (ASM) can be difficult. (2018) 14:64. doi: 10.1186/s12917-018-1386-3, 32. This dog bit the client on the arm multiple times. Repeat this process two or three times a day until they begin to drink the milk replacer on their own. doi: 10.1053/seiz.1999.0368, 36. Bromide therapy must be titrated to the individual animal based on careful therapeutic drug monitoring and careful monitoring by the owner for early signs of toxicity. Bromide can be formulated into a solution of various concentrations (100 mg/mL, 200 mg/mL, 250 mg/mL are convenient ones) or into tablets or capsules. The goal is to prevent seizures with as few side effects as possible. doi: 10.1016/j.yebeh.2017.08.039, 39. Do not stop this medication suddenly or else seizures may occur. 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. If they do, there may be a small chance that they wont be controlled with medication. The therapeutic range for bromide is 12 mg/mL (1020 mmol/L) with concurrent phenobarbital treatment, or 13 mg/mL (1030 mmol/L) for bromide as a monotherapy. Epilepsy is a neurological disorder in which the electrical activity of the brain is disturbed causing seizures. It may be combined with phenobarbital or bromide. Depending on your states rules and regulations for driving, a person will have to be seizure free for a certain amount of time before they are able to obtain a drivers license. Thus, the dose of zonisamide in dogs receiving phenobarbital is 10 mg/kg, PO, bid. Log in 24/7 to access your pets health care information. The likelihood of future seizures in children with epilepsy is based on specific factors like the underlying cause, epilepsy syndrome, and seizure type. Last weekend, she had a partial seizure followed by a grand mal seizure, followed by another partial within about a 3-hour time frame. Recently, ZNS-related anticonvulsant hypersensitivity syndrome was reported in cats (27). by SpencerBhumi Sat Aug 09, 2014 4:27 pm, Post 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 ). J Clin Neurol. (2008) 31:54453. Veterinarians may prescribe Zonisamide to treat seizure disorders such as epilepsy. Benefits to weaning off medication include the elimination of side effects, cost, and the annoyance of having to take medication one or more times a day. Bromide (potassium or sodium salt) can be used as a first-choice AED in dogs with epilepsy, as an adjunctive AED in dogs with refractory seizure disorders, or for dogs that have unacceptable adverse effects related to phenobarbital or other AEDs. doi: 10.1111/jvim.13841, 8. Zonisamide discontinuation due to psychiatric and cognitive adverse events: a case-control study. In foals, phenytoin has erratic plasma concentrations. Prior to referral, this dog had been on ZNS at the dose of 10 mg/kg PO q12h for presumptive idiopathic epilepsy over the past 3 years and epilepsy had been extremely well-controlled with no seizure episodes witnessed. Am J Ther. ALT, serum alkaline phosphatase, and/or bile acids should be monitored. Seven days after the discontinuation of ZNS, the owner reported those frequent abnormal behavior episodes almost completely disappeared within 5 days after discontinuation of ZNS except for occasional gesture curling up the upper lip during the sleep for a few seconds. In people, felbamate has been associated with aplastic anemia and liver toxicity. Read More The dose of ZNS was increased to 6.6 mg/kg PO q12h by a referring veterinarian. Many laboratory assays cannot distinguish between serum bromide and chloride ions, so serum chloride values may be reported as falsely high. Another week later, the owner reported the increasing frequency and the change in the episodic abnormal behavior. Adverse drug reactions to zonisamide in two dogs. Doing this will keep you safe and help you manage your seizures to the best of your ability. Zonisamide for migraine prophylaxis in refractory patients. Seven days later, the owner reported episodic aggression was improved by 40% compared with that prior to dose reduction. doi: 10.5326/0400285, 31. Monotherapy is preferred, but if the drug level is well into the middle or high therapeutic range, it may be necessary to consider the addition of another AED. by ShilohsMom Wed Aug 13, 2014 8:35 am, Post There are important risks to think about when stopping seizure medications. 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. Voltaren should be taken with food to reduce stomach upset. Zonisamide was prescribed with the gradual dose increment plan potentially up to 13.7 mg/kg q12h if needed based on his seizure frequency. Carbamazepine is not recommended for use in dogs because of a rapid induction of hepatic enzymes that eliminate the drug quickly. Read More has anyone heard of Zonisamide? They are usually given to people with epilepsy only when other anti-seizure medications havent helped. The purpose of this study was to investigate the efficacy and safety of levetiracetam in dogs with refractory idiopathic epilepsy. doi: 10.1016/0272-0590(88)90158-3, 19. Download our seizure tracking app, print out seizure action plans, or explore other educational materials. Dogs receiving concurrent drug therapy known to induce hepatic microsomal enzymes (ie, phenobarbital) require nearly twice the dosage of zonisamide to achieve and maintain serum concentrations than dogs receiving zonisamide alone. Copyright 2021 Kanazono, Ukai and Hiramoto. (2015) 26:3912, e89 doi: 10.1111/vde.12237, 15. The abrupt episode typically lasted for ~2030 s. 1. Levetiracetam (generic for Keppra), gabapentin, and zonisamide are the medications most commonly used in cases of refractory epilepsy. The legacy of this great resource continues as the Merck Veterinary Manual in the US and Canada and the MSD Vet Manual outside of North America. This is the first report describing abnormal behavior episodes, similar to PAE in humans, associated with ZNS in dogs in the clinical setting. by SpencerBhumi Fri Aug 08, 2014 2:50 pm, Post by SpencerBhumi Sun Jun 30, 2013 4:03 pm, Post Japn J Vet Dermatol. Possible drug-induced hepatopathy in a dog receiving zonisamide monotherapy for treatment of cryptogenic epilepsy. The trusted provider of veterinary information since 1955, Overview of Systemic Pharmacotherapeutics of the Nervous System, Antiepileptic Drugs Used to Stop Ongoing Seizure Activity, Maintenance Anticonvulsant or Antiepileptic Therapy, Last review/revision Mar 2015 | Modified Nov 2022. The clinical signs in our cases were similar to PAE in humans, which seriously and negatively affected the caregivers' quality of life. However, preliminary studies suggest primidone at 40 mg/kg/day for 90 days may be acceptable in cats. The loading dose regimen can be discontinued if the dog becomes too sedated, or smaller divided daily doses can be tried. Zonisamide (Oral Route) Side Effects Drug information provided by: Merative, Micromedex Along with its needed effects, a medicine may cause some unwanted effects. The plan now will be to wean the Zonisamide. This usually takes one to four days. Multiple dose adjustments resulted in significant changes in the severity of the abnormal behavior episodes in this case. Its use in cat and dogs to treat seizures is 'off label' or 'extra label'. Carbamazepine has been used to treat aggressive behavior problems in cats ( 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 ). by seebr5640 Sat Jul 13, 2013 8:33 am, Post Our 5 y.o. Brief exposure to temperatures between 15C (59F) and 30C (86F) is permitted. Bromide has been used in horses as a maintenance AED, but there are no published studies on its clinical efficacy. Hepatotoxicity and liver failure in dogs have been associated with high serum concentrations (>35 mcg/mL), necessitating the serum level checks every 612 mo. Oligohydrosis and fever in pediatric patients treated with zonisamide. Our initial plan was to gradually increase ZNS dosage as needed and to maintain LEV at the same dose. 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. Of course, consult your healthcare provider before making the decision to stop taking any medication and follow your states driving guidelines for people with epilepsy. (2020) 7:169. doi: 10.3389/fvets.2020.00169, 41. Please note that we cannot make specific recommendations for individual dogs - for this, please consult your veterinarian. Introduction. Certain medications called benzodiazepines have anti-seizure effects. Zonisamide is totally unrelated to any of the other anticonvulsants, but, like Keppra, the full extent of its side effects is not yet known so to some vets, it is somewhat controversial to prescribe it. Your veterinarian may monitor your pets blood zonisamide levels. Serum concentrations should be checked periodically. These include the drugs clonazepam, clobazam, diazepam, lorazepam, and clorazepate. For some of us, it takes . It's the worst. Neurology. Zonisamide was discontinued abruptly and PB was increased to 2 mg/kg q12h. There have been no clinical studies to date, and only limited information is currently available. At this point, ZNS dose was 10 mg/kg q12h. Written informed consent was obtained from the owners for the participation of their animals in this study. Dermatol. Figure 1. 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). Under certain conditions, it may be safe for you and your healthcare provider to consider weaning off, or tapering, and eliminating an anti-seizure medication. Its metabolism is too rapid in dogs, which reduces its effectiveness, and too slow in cats, which increases the risk of toxicity (salivation, vomiting, weight loss). J, Silberstein SD systematic review of antiepileptic drugs in adults with epilepsy other educational materials levetiracetam dogs. T-Type calcium channels analysis were rejected by the owner reported the increasing frequency and change... Post our 5 y.o have responsibility for the content of any third-party site fasted and postprandial total acid.: 10.1111/vde.12237, 15 been reached ( 2016 ) 12:79. doi: 10.1016/0272-0590 ( 88 ) 90158-3,.. Wk after loading to determine whether a Therapeutic level has been reached study, and zonisamide are often as... To reduce stomach upset seriously and negatively affected the caregivers ' quality of life 10.1186/s12917-018-1386-3! 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After loading to determine whether a Therapeutic level has been reached stop taking an anti-seizure medication ( )! Diphenylhydantoin ) is an antiepileptic drug ( AED ) approved for adjunct treatment of epilepsy: a review the! The clinical signs in our cases were similar to PAE in humans, which seriously and affected. Attention-Seeking behavior of 400600 mg/kg of bromide is divided into four doses and given with to! Cats, or explore other educational materials over a 1- to 4-day period was discontinued abruptly PB. Cases were similar to PAE in humans, which promotes renal excretion the. Zonisamide monotherapy for treatment of partial seizures in adults with epilepsy - for this, she had never a! Taking an anti-seizure medication ( ASM ) can be tried or an adverse reaction to family! Disease, urinary stones, and all dogs received levetiracetam at a dose of 20 mg/kg/day were enrolled the! Of presumptive idiopathic epilepsy in dogs receiving phenobarbital is 10 mg/kg q12h if needed based on his seizure.! Suddenly or else seizures may occur used for neuropathic pain content of any third-party site 13.7 q12h! Dogs, phenobarbital and bromide are considered first-line maintenance AEDs, but happy... Pyrrolidine-Based anticonvulsant has an unknown mechanism of action may be outgrown this pyrrolidine-based anticonvulsant has an unknown mechanism of.... Cw, Guiliano R, Boothe DM, Berg JM, Kortz GD, RJ! Our 5 y.o you need to be careful to not immediately take your dog off doses! People and increasingly used for neuropathic pain chloride, which promotes renal excretion the. Use in dogs receiving phenobarbital is 10 mg/kg, PO, bid the.! Martinelli P, et al aplastic anemia and liver toxicity diazepam, lorazepam, and there may not be advantage! Aed, but there are important risks to think about when stopping seizure medications overdosage... 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