Idiosyncratic Adverse Effects Research Articles

Paranoid psychosis after a single parenteral dose of indomethacin administered for headache diagnosis: A case and review of the literature

Background: Indomethacin is a non-steroidal anti-inflammatory used to diagnose and treat hemicrania continua and paroxysmal hemicrania. Treatment can be complicated by gastrointestinal adverse effects; less commonly reported are idiosyncratic neuropsychiatric adverse effects with indomethacin. Methods: A 50-year-old male with lateralized brief attacks of headache associated with cranial autonomic symptoms was administered a single 200 mg dose of intramuscular indomethacin. Within an hour, he developed acute psychosis, with paranoid delusions and verbal and physical aggression lasting 5 h, followed by recovery to baseline. We used search terms “indomethacin psychosis,” “indomethacin psychiatric,” “indomethacin side effects,” “non-steroidal anti-inflammatory psychosis,” and “non-steroidal anti-inflammatory psychiatric” within PubMed to identify previous reports and literature in this area. Results: Neuropsychiatric adverse effects of indomethacin have been reported since 1965 in a dose-dependent manner, usually with oral courses. They may be more common in the elderly, postpartum women and postoperative patients. Conclusion: Neuropsychiatric adverse effects should be considered in headache medicine, particularly in at-risk groups when indomethacin is administered. Patients, particularly those at highest risk, should be counseled about the risk of neuropsychiatric side effects on indomethacin which may be dose-dependent and are generally reversible on stopping the drug.

Genetic abnormality of cytochrome-P2C9*3 allele predisposes to epilepsy and phenytoin-induced adverse drug reactions: genotyping findings of cytochrome-alleles in the North Indian population

BackgroundThis research aims to study the association of genetic polymorphism in genes coding for CYP2C9 and CYP2C19 in phenytoin-induced dose-related toxicity and to assess if the presence of allele CYP2C9*3 plays a role in phenytoin-induced idiosyncratic adverse effects. Current observational case control study included 142 patients with phenytoin-induced adverse drug reactions (ADRs) and 100 controls. All these patients underwent genotyping to determine the type of CYP2C9 allele [CYP2C9*1, CYP2C9*2 or CYP2C9*3) and CYP2C19 allele (CYP2C19*1, CYP2C19*2 or CYP2C19*3] by real-time polymerase chain reaction (RT-PCR) using Applied Biosystems (ABI) 7500 Real-Time PCR System (USA).ResultsPresence of homozygous status for allele CYP2C9*3 was associated with significantly higher risk of phenytoin-induced dose-dependent ADRs, dose-independent ADRs, gum hyperplasia, and skin rash. Presence of heterozygous status for allele CYP2C9*3 was associated with significantly higher risk of phyenytoin-induced dose-dependent ADRs and dose-independent ADRs. Presence of either heterozygous or homozygous status for CYP2C9*2 and CYP2C19*2 did not have any bearing on dose-related side effects. None of the patients showed CYP2C19*3 allele.ConclusionVariant alleles of CYP2C9*3 are significantly overexpressed among patients with phenytoin-induced ADRs, thereby suggesting the role for CYP2C9 genotype testing to predict risk of phenytoin-related ADRs.

Finding Predictors of Azathioprine-Induced Pancreatitis in Patients With Inflammatory Bowel Disease.

Azathioprine (AZA)-induced pancreatitis (AIP) is a common, idiosyncratic adverse effect whose incidence and risk factors data in inflammatory bowel disease (IBD) patients are not fully clarified. We aimed to establish the incidence, clinical course and identify risk factors for AIP. A retrospective study including all IBD patients on AZA between January 2013 and July 2020 was conducted. Patients with AIP were considered. Azathioprine-induced pancreatitis occurred in 33 patients (7.5%; 442 patients on AZA). The mean time receiving AZA until AIP was 25 days, with a mean dose of 88 mg. All patients had a mild course of disease, which resolved with suspension of AZA and with no complications. Smoking (P = 0.02), single daily dose of AZA (P < 0.001), and concomitant budesonide (P = 0.001) were risk factors for AIP. In multivariate analysis, concomitant treatment with budesonide (odds ratio, 5.3; P = 0.002) and single daily dose of AZA (odds ratio, 3.8; P = 0.002) were the only predictors of AIP. Although AIP was a relatively common adverse effect, it presented a mild course in all patients. Smoking, concomitant use of budesonide, and single-dose regimen of AZA should be avoided in IBD patients treated with AZA.

Acute Hypoxic Respiratory Failure /Hyperammonemic encephalopathy in the setting of concurrent use of valproic acid and topiramate

Valproic acid (VPA) is widely used for the treatment of epilepsy, migraine, and a variety of psychiatric symptoms, including bipolar disorder, borderline personality disorder, and alcohol withdrawal. Valproate is associated with severe idiosyncratic adverse effects, the most notable being valproate-induced hyperammonemic encephalopathy (VHE). Topiramate is also a broad-spectrum anticonvulsant that is also extensively used for migraine prophylaxis, as a mood stabilizer, and for alcohol dependency. There is increased occurrence of VHE when valproate is used with other medications like phenytoin, phenobarbital, and topiramate. We report a young patient who was on valproic acid and topiramate and developed metabolic encephalopathy with hypoxic respiratory failure with review of the causes and management of the hyperammonemic encephalopathy. We believe that clinicians should be aware of possible hyperammonemic encephalopathy in any patient who is taking valproic acid and presenting with impaired consciousness and cognitive decline. We also underline the importance of early recognition and high index of suspicion of encephalopathy related to hyperammonemia.

Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats.

The study objective was to investigate the prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. The medical records of two veterinary referral clinics from 2007 to 2017 were searched for cats fulfilling the inclusion criteria of a diagnosis of epilepsy, treatment with phenobarbitone and available follow-up information on the occurrence of adverse effects. Follow-up information was obtained from the medical records of the primary veterinarian and referral institutions and a questionnaire completed by the cats' owners. Seventy-seven cats met the inclusion criteria. Fifty-eight were affected by idiopathic epilepsy and 19 by structural epilepsy. One or more of the following adverse effects were reported in 47% of the cats: sedation (89%); ataxia (53%); polyphagia (22%); polydipsia (6%); polyuria (6%); and anorexia (6%). Logistic regression analyses revealed significant associations between adverse effect occurrence and both phenobarbitone starting dosage and administration of a second antiepileptic drug (AED). For each 1 mg/kg q12h increment of phenobarbitone, the likelihood of adverse effects increased 3.1 times. When a second AED was used, the likelihood of adverse effects increased 3.2 times. No association was identified between epilepsy aetiology and adverse effect occurrence. An idiosyncratic adverse effect, characterised by severe neutropenia and granulocytic hypoplasia, was diagnosed in one cat. This resolved following phenobarbitone discontinuation. The prevalence of phenobarbitone-associated adverse effects was 47%. Sedation and ataxia were most common. These are type A adverse effects and are predictable from phenobarbitone's known pharmacological properties. In the majority of cases, adverse effects occurred within the first month of treatment and were transient. Idiosyncratic (type B) adverse effects, which were not anticipated given the known properties of the drug, occurred in one cat. Increased phenobarbitone starting dosage and the addition of a second AED were significantly associated with the occurrence of adverse effects.

End-of-life care in the immune checkpoint inhibitor era.

e24003 Background: Immune checkpoint inhibitors (ICI) can lead to durable responses in some patients with advanced non-small cell lung cancer (NSCLC) with less toxicity than chemotherapy. However, ICI can cause idiosyncratic adverse effects and radiographic responses can be difficult to interpret, making prognostication difficult and potentially impeding a timely transition to hospice. Our purpose was to explore end of life (EOL) outcomes in NSCLC patients treated with ICI. Methods: Retrospective data were collected on all patients with NSCLC started on ICI at single center (2014-2018) and who died before last known follow-up. EOL outcomes included hospitalizations, ICU admissions, timing/location of hospice referral and death. Charts were reviewed to identify barriers to hospice referrals or enrollment. Outcomes were compared to published data of similar cohort (2008-2010) from same institution treated with chemotherapy. Results: Out of 143 patients who died, 83 (58%) had internal hospice referral by cancer center; 15 (11%) were referred by external provider. Hospitalization frequency was associated with higher likelihood of internal hospice referral (p 0.04). Internal hospice referral was not associated with differences in age, sex, race, ethnicity, smoking history, cancer subtype, treatment response/toxicity, or overall survival. Internal hospice referral was associated with decreased rates of death on the hospital floor (p &lt; 0.001) and the intensive care unit (ICU, p &lt; 0.001). When compared to chemotherapy cohort, there was similar rate of hospice referral (68% vs. 74%, p 0.33) but higher rates of starting new systemic therapy within 30 days of death (17% vs. 6%, p 0.001) and last dose within 14 days of death (13% vs. 5%, p 0.005). Other EOL outcomes (hospitalization frequency, death in ICU) were similar, although ICI cohort trended towards a lower rate of death on the floor than chemotherapy cohort (16% vs. 25%, p 0.06). Barriers to hospice referral were not well documented by providers but lack of family support for home EOL care was a common reason patients declined hospice. Conclusions: ICI was associated with a higher rate of systemic treatment at EOL as compared to a historical chemotherapy cohort, although the rates of hospice referral and other outcomes were similar.

Switching from traditional sodium channel blockers to lacosamide in patients with epilepsy

PurposeLacosamide (LCM) is a recently developed sodium channel blocker (SCB), which acts mainly on the slow activation state in sodium channels. Although LCM shares a range of dose-dependent adverse effects with traditional SCBs, it has several advantages in that it does not induce hepatic drug metabolizing enzymes and has less risk of drug interactions and idiosyncratic adverse effects. MethodsWe retrospectively analyzed the efficacy and tolerability of switching from traditional SCBs to LCM. The reason for the switch was classified as insufficient efficacy, adverse effects, or concern about metabolic derangement, resulting in conditions such as atherosclerosis and osteoporosis, with long-term use of traditional SCBs. ResultsSeventy-five patients were switched to LCM from traditional SCBs. The overall rate of successful switching was high (81.3%, 61/75 patients). However, the success rate was strongly dependent on the reason for the switch; patients with insufficient efficacy on SCBs had less chance of a successful switch (71.8%, 28/39 patients) than those with adverse effects (89.5%, 17/19) or concerns about metabolic derangement (94.1%, 16/17, p = 0.038). Patients with insufficient efficacy were significantly younger (p = 0.004) and had a higher chance of drug-resistant epilepsy (p = 0.004) than those in the other two groups. ConclusionsOur study shows that switching from traditional SCBs to LCM is usually successful and the likelihood of a successful switch is higher in patients when the reason for the switch is adverse effects or concerns about metabolic derangement on traditional SCBs.

Topiramate-induced angle closure glaucoma in a case of chronic migraine

Topiramate is an oral sulfamate medication used primarily for epilepsy and migraine. The tolerability profile with its lack of significant metabolic side effects makes it a favorable drug for patients with comorbid lifestyle illnesses. Topiramate-induced angle closure is an idiosyncratic reaction and can occur in otherwise normal eyes with normal anterior chamber angles. Ocular examination before starting topiramate cannot identify eyes at risk. Prompt cessation of therapy alone can result in rapid resolution of most of these adverse effects, whereas failure to recognize can lead to permanent visual problems. The internists should be aware of the documented side effects of topiramate, particularly when presented with simultaneous bilateral acute angle-closure glaucoma. Neurologists initiating therapy with topiramate should also educate the patients of its potential side effects and importance of reporting back immediately in case of any visual disturbance. Prompt cessation of topiramate is the mainstay of treatment. Supportive treatment in the form of oral and topical antiglaucoma drugs to reduce the intraocular pressure (IOP), topical steroids to bring down the inflammation, and topical cycloplegics to retract the ciliary processes thus bringing down the IOP has been recommended, but a few would warrant laser iridotomy or surgical iridectomy. We report a case of topiramate-induced angle closure glaucoma in a young female being managed as a case of chronic migraine, highlighting the importance of increasing the awareness of this rare, idiosyncratic adverse effect of topiramate and the need for timely intervention to avoid irreversible visual loss.

Risk factors for seizures and antiepileptic drug-associated adverse effects in high-grade glioma patients: A multicentre, retrospective study in Hong Kong.

AimThe aim of this present study was to determine the frequency, as well as risk factors, for seizures and antiepileptic drug (AED)-associated adverse effects among high-grade glioma (HGG) patients.Patients and MethodsA multicentre, retrospective study of adult Chinese Hong Kong patients from three neurosurgical centres diagnosed with supratentorial HGG between 1 January 2001 and 31 December 2010 was performed.ResultsA total of 198 patients, with a mean age of 55 years (range: 18–88) and a mean follow up of 15 months, was recruited. Most suffered from glioblastoma multiforme (GBM) (63 per cent) followed by anaplastic astrocytoma (25 per cent). Median overall survival for patients with GBM was 8 months, and 11 months for those with grade III gliomas. Prophylactic AED was prescribed in 165 patients (83 per cent), and 64 per cent of patients were continued until end of life or last follow up. A total of 112 patients (57 per cent) experienced seizures at a mean duration of 8 months postoperatively (range: 1 day–75 months). Independent predictors for seizures were a diagnosis of GBM [adjusted odds ratio (OR): 2.33, 95 per cent confidence interval (CI): 1.21–4.52] and adjuvant radiotherapy (adjusted OR: 2.97, 95 per cent CI: 1.49–6.62). One-fifth of patients (21 per cent) experienced AED adverse effects, with idiosyncratic cutaneous reactions and hepatotoxicity most frequently observed. An independent predictor for adverse effects was exposure to aromatic AED, such as phenytoin, carbamazepine and phenobarbital (adjusted OR: 3.32, 95 per cent CI: 1.32–8.40).ConclusionsAntiepileptic drug prescription for primary seizure prophylaxis is both pervasive and prolonged for HGG patients. Seizures occur frequently, but most were delayed and none were life threatening. Judicious prescription of AED is required, especially when a significant proportion of patients experience adverse effects. Patients with a diagnosis of GBM and exposure to radiotherapy are at risk. We suggest, contrary to present practice, that primary seizure prophylaxis be given only during the perioperative period and resumed when they occur. We also recommend avoidance of aromatic AED due to their association with idiosyncratic adverse effects.

Drug induced diseases (DID): Need for more awareness & research.

Drug induced diseases (DID): Need for more awareness & research.

Antiepileptic drugs toxicity: A case of toxic epidermal necrolysis in patient with phenytoin prophylaxis post-cranial radiation for brain metastases

BackgroundTreatment of epilepsy with antiepileptic drugs (AED) is effective and remains the principal mode of management. A group of adverse effects and drug toxicity can develop immediately or later in the course of treatment. AEDs also have the potential of precipitating idiosyncratic adverse effects including serious cutaneous, hematological and hepatic events. Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse reactions are related to or caused by a variety of medications including AEDs, they carry a high mortality and morbidity rate, accurate diagnosis and rapid treatment may improve the prognosis. ObjectiveTo characterize the clinical features and methods of differentiating Stevens–Johnson syndrome from toxic epidermal necrolysis using a case study and to identify other factors that may contribute to this critical illness. ConclusionClinical knowledge of potential sever adverse reaction of AEDs is essential and may overcome treatment failure with major impact on health-related quality of life in people with epilepsy.

Repression of oxidative stress/reactive metabolite regulated gene expression is associated with conversion of carbamazepine into a hepatotoxicant in LPS and DSS rat models

Idiosyncratic hepatotoxicity accounts for many drug failures in the clinic and is a leading cause for black-boxed and withdrawn drugs. This toxicity has proven difficult to predict preclinically, but correlates with oxidative stress/reactive metabolites (OS/RM). As noted previously for antiepileptic compounds, many drugs causing idiosyncratic adverse drug effects are detected by OS/RM gene expression responses in the rat. In the present study, two immune activation models, low dose lipopolysaccharide (1 mg/kg IV) and 5% dextran sulphate sodium (DSS) in drinking water, were examined to determine if either would convert the non-toxic idiosyncratic toxicant carbamazepine (225 mg/kg) into a rat hepatotoxicant at 24 hours. Using the low dose LPS model, about 1/3 of the carbamazepine-treated rats either showed robust ALT and AST elevations with histopathological evidence of hepatotoxicity, or died. Rats in this LPS/carbamazepine group were subdivided based on ALT values into non-responders, responders or robust responders. Whereas most carbamazepine-induced mRNAs were repressed by LPS across all rats in this group, the OS/ RM genes aflatoxin aldehyde reductase (Afar) and glutathione transferase Ya (Gstya) were repressed only in the robust responder subgroup; it is unclear whether repression of these genes contributes to or results from hepatotoxicity. The OS/RM gene microsomal epoxide hydrolase (mEphx) showed repression across all rats. NAD(P)H: menadione oxidoreductase (Nmor) is an OS/RM-responsive gene that is also induced by LPS, confounding interpretation of its changes. After pretreatment with 5% DSS at 24 hours or for 5 days, using a protocol that reportedly produces increased endotoxin absorption, carbamazepine was not converted to a hepatototoxicant in any rats. Instead, DSS produced a pronounced (2- to 6-fold) and selective potentiation of carbamazepine induction of OS/RM-responsive mRNAs. The lack of repressive effects of DSS on these mRNAs or in converting carbamazepine to a hepatotoxicant was not due to desensitization of endotoxin responses since LPS was at least as effective when administered to DSS-pretreated rats. OS/RM gene repression may contribute to development of hepatotoxicity of carbamazepine in immune activation models.

Hepatitis and Pancreatitis Associated with the Use of Trimetropim Sulfamethoxazole: A Case Report

Purpose/Introduction: Trimetropim sulfamethoxazole (TMP-SMX) is a widely prescribed antibiotic. Both hepatitis and pancreatitis are uncommon side effects, and reports in non-immunosuppressed patients are rare. To our knowledge, there are only two previous case reports of concomitant hepatitis and pancreatitis occurring in an inmunocompetent patient. Case Presentation: A 65-year-old male with previous history of coronary artery disease, hypertension and dyslipidemia presented to the emergency room with abdominal pain, jaundice and a skin rash. The patient had been started on TMP-SMX for otitis media two weeks before arriving to the emergency department. During this period of time, the patient presented with nausea, vomiting, weight loss and fever. On physical examination, he was found to be jaundice, and a generalized non-pruritic macular rash was noticed. There was no history of alcohol use. On admission, liver function test and pancreatic markers were elevated. ALT peaked to 510, AST to 445 U/L, total and direct bilirubin to 19 and 8.9 mg/dL respectively, lipase to 578 U/L and amylase 102 U/L, albumin was decreased and coagulation studies were normal, and remained normal during and after hospitalization. Other causes of pancreatitis were rule out. Triglycerides were within normal limits and calcium and SPEP were normal. Acute viral hepatitis, CMV and EBV serology were negative, and titers of autoimmune markers were normal. Abdominal CT did not show hepatic or pancreatic abnormalities, and the abdominal ultrasound did not show gallstones or dilation of the intrahepatic ducts. Upper endoscopy showed esophagitis and gastritis. Pancreatitis and hepatitis were managed with fluid resuscitation and supportive care. The patient improved clinically, a decrease in lipase and aminotransferase was noted during hospitalization and a gradual decrease of bilirubin occurred after hospitalization. Discussion: Clinical observation is an important tool to identify adverse effects from medications. In this particular case, we have a Naranjo score of six (probable drug reaction). The mechanism of idiosyncratic adverse effects to TMP-SMX is not clearly understood, but inmuno-allergic mechanisms have been proposed. This case underlines the importance of considering commonly used medications as the causative event of severe medical conditions.

Pregabalin: latest safety evidence and clinical implications for the management of neuropathic pain.

Used mainly for the management of neuropathic pain, pregabalin is a gabapentinoid or anticonvulsant that was initially developed as an antiepileptic agent. After more than a decade of experience with pregabalin, experience and studies have shown that the adverse effect profile of pregabalin is well tolerated for the management of neuropathic pain and other conditions. Its use is associated with benign central nervous system and systemic adverse effects, and there are very limited metabolic, idiosyncratic or known teratogenic adverse effects. Along with its efficacy in particular neuropathic pain conditions, pregabalin's safety led it to be one of the first pharmacotherapies considered for the management of neuropathic pain. This review discusses the use of pregabalin as well as its potential adverse effects, including the most commonly noted features of sedation, dizziness, peripheral edema and dry mouth. Although other adverse effects may occur, these appear to be uncommon. The review also discusses the clinical implications of pregabalin's use for the clinician.

AMPA receptor inhibitors for the treatment of epilepsy: the role of perampanel

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the postsynaptic membrane are involved in fast excitatory signaling in the brain and their activation may lead to the firing of action potentials. Talampanel and perampanel were the first noncompetitive AMPA receptor antagonists to be tested as add-on drugs in patients with refractory partial seizures, and were found to be effective in improving seizure control. Due to an unfavorable kinetic and tolerability profile, talampanel clinical development in the field of epilepsy was discontinued early while perampanel has been recently approved in Europe and the USA as adjunctive therapy for adults with partial seizures with or without secondary generalization. The recommended perampanel starting dose is 2 mg/day once daily, which can be increased up to the recommended maintenance dose of 4–8 mg/day. Increments should be of 2 mg/day and based on clinical response and tolerability. Titration should be performed at 1-week intervals or at lower speed and a 12-mg daily dose should be considered after careful evaluation. To date, no serious and/or idiosyncratic adverse effects have been associated with this agent. Most frequently reported adverse effects are dizziness, ataxia, aggression, irritability, vertigo, somnolence, fatigue, headache and gait disturbance. Weight increase is the only non-neurological adverse effects associated with perampanel.

Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy

The aim of treating epilepsy is to control or at least decrease seizures without producing unacceptable adverse effects that impair quality of life. Antiepileptic drugs (AEDs) have been considered amongst the drugs most frequently associated with fatal suspected adverse drug reactions. Physicians must therefore be as familiar with safety and tolerability data of AEDs as they are with the expected therapeutic effects. AEDs may cause dose-related adverse effects (i.e. drowsiness, fatigue, dizziness, blurry vision and incoordination) that, in most cases, may be obviated by lowering the dosage, reducing the number of drugs or switching to a better tolerated AED. AEDs also have the potential of precipitating idiosyncratic adverse effects (i.e. serious cutaneous, haematological and hepatic events), which are more common in children and usually require withdrawal of the AED. Although occurrence of idiosyncratic adverse effects can only rarely be predicted or prevented, there are known risk factors that can help in identifying patients at high risk. Occurrence of an idiosyncratic event in a close relative, a concomitant autoimmune disease, co-treatment with specific drugs, history of a previous allergic drug reaction, starting treatment with high doses and rapid titration have all been associated with a higher risk of idiosyncratic adverse effects. New AEDs have been developed in the last two decades with the aim of improving the benefit-risk balance of AED therapy. Available evidence suggests that the newer AEDs are no more effective but may be somewhat better tolerated than older molecules. We performed a literature review with the aim of evaluating safety and tolerability of second- and third-generation AEDs in children. A PubMed search was conducted with the purpose of identifying English-language studies published between 1 January 1989 and 1 January 2011 that reported any adverse event having occurred in children with epilepsy in whom second- and third-generation AEDs were administered.

Drug safety evaluation of pregabalin

Introduction: Pregabalin is an anticonvulsant with one known mechanism of action which is used most specifically in the management of neuropathic pain.Areas covered: The adverse effect profile of this medication from controlled, randomized studies as well as open and long-term studies is described with consideration of the evidence-based results for pregabalin's clinical use.Expert opinion: Pregabalin is a mostly well tolerated medication for the management of neuropathic pain and other conditions. Pregabalin use is associated with benign central nervous system and systemic adverse effects with very limited metabolic, idiosyncratic, or teratogenic adverse effects. Understanding of these adverse effects is essential for the clinician treating the patient and for the patient receiving treatment. Sedation, dizziness, peripheral edema, and dry mouth are the most prevalent adverse events experienced in all clinical populations. Other adverse effects are rare, but are discussed.

Current progress in pharmacogenetics.

The study of genetic variation has the potential to aid understanding of the mechanisms underlying the observed inter-individual variation in drug response and by which idiosyncratic adverse effects occur. In this review, we outline current progress in pharmacogenetics using examples to highlight both mechanisms of influence of polymorphisms and research strategies for their detection. In the final sections we discuss contemporary challenges for both researchers and clinicians.

Drug safety evaluation of zonisamide for the treatment of epilepsy

Introduction: Zonisamide is a broad spectrum antiepileptic drug with multiple mechanisms of action which has been recently approved in the US and Europe as an adjunctive therapy for refractory partial seizures in adults.Areas covered: The adverse effect profile of this drug from controlled, randomized studies and open and long-term studies and case reports is described herein.Expert opinion: Zonisamide has several CNS dose-dependent, metabolic and idiosyncratic adverse effects. Knowledge of these effects is essential for the prevention or minimization of several of them. For example, treatment-emergent adverse events may be prevented by slow titration; incidence of kidney stones may be reduced through an increase in fluid intake and avoidance of concomitant treatment with topiramate and/or ketogenic diet; and oligohydrosis may be prevented by hydratation and avoidance of hot temperatures. An accurate selection of patients can be useful for the prevention of some adverse effects. Psychiatric disturbances are mainly observed in predisposed subjects and patients with a previous allergic episode to sulfonamide-containing drugs are at a higher risk for developing a skin rash.

ANTIEPILEPTIC DRUGS

The goal of epilepsy treatment is no seizures and no side effects. Antiepileptic drugs (AEDs) are the mainstay of treatment. Chronic use, however, often leads to serial drug changes over time, exposing patients with epilepsy (PWE) to recurrent risks due to adverse effects (AEs) and drug interactions. Both unwanted acute and chronic AEs may occur that are usually dose-related, suggested by AED pharmacology, and addressed with appropriate use of serum drug concentrations. Idiosyncratic AEs can pose significant health issues for PWE and be lifesaving with early identification. AED pharmacokinetics and pharmacodynamic properties serve as the foundation for anumber of drug interactions. Hepatic enzyme systems may facilitate AED interaction with other coadministered medication through induction or inhibition of drug metabolism and result in AEs or seizures from drug interactions. A working knowledge of AED pharmacology is an essential component of good clinical practice to help clinicians predict potential AEs and DIs in the treatments of PWE.