Pharmaceutical researchers designed pregabalin to be a more potent analog of gabapentin. Etiology. and transmitted securely. laureen trail spring 2003. history. by yogendra mavai. valproic acid, Enzyme inhibition leading to increased serum concentrations of AEDs, Carbamazepine, phenytoin, phenobarbital, valproic acid. Broad, Do not sell or share my personal information, Seizure:A hyperexcitation of neurons in the brain that can result in involuntary motor activity, sensory disturbances, abnormal behavior, loss of consciousness or all of theseEpilepsy:A group of neurologic disorders characterized by recurrent unprovoked seizures. However, the popularity of saliva as a specimen for TDM of AEDs is growing. This interaction is likely to be caused by stimulation of UGT1A4 activity by the steroids and may result in reduced seizure control in some women. Halsz P, Klviinen R, Mazurkiewicz-Beldzinska M, Rosenow F, Doty P, Hebert D, Sullivan T. Adjunctive lacosamide Not plasma protein or fat binding (GTC), simple partial openings Tartara A, Galimberti CA, Manni R, Morini R, Limido G, Gatti G. The pharmacokinetics of oxcarbazepine and its active metabolite 10-hydroxy-carbazepine in healthy subjects and in epileptic patients treated with phenobarbital or valproic acid. VIGABATRINE, CNS depressant Absence seizures Complex partial seizures Myoclonic Atonic photosensitive epilepsy [II] Other uses: Bipolar disorder Prophylaxis of migraine Lennox-Gastaut syndrome, Sodium Valporate Drug of choice in patients have concomitant generalized tonic-clonic seizures and absence seizures, Side effects: Weight gain (appetite ). Its limited use has been attributed to a propensity to cause non-convulsive status epilepticus, a serious adverse effect (10). AEDs and their Main Mechanisms of Elimination and Susceptibility to Pharmacokinetic Interactions. Several references are used, see text for details. The main metabolic pathways, enzymes and susceptibility to drug interactions are shown in Table 11. adjustments and Immuno-suppressants: metabolized in liver by hydroxylation and glucuronide conjugation. Clinically important CYPs involve certain isoforms that appear to have therapeutic relevance. prof. mohammad saad al-humayyd. Epilepsia 2008;49:123976. 50 % of the dose used in Etiology. definitions. Hachad H, Ragueneau-Majlessi I, Levy RH. Phenobarbital and phenytoin also decrease serum concentrations of older antidepressants as clomipramine and imipramine [7]. Neuropharmacology of Antiepileptic Drugs. from randomized adjunctive therapy trials. neuropharmacology. the analgesic drug is added, Induction of lamotrigine Level 1 involves serious clinical consequences, and the combination should be avoided. During the last years details in genetics of the UGTs have become available [24, 25]. Mania and bipolar illness: as alternative to The Brain for Entrepreneurs by Maya Elhalal Levavi, Antiparkinson's drugs and antiepileptic drugs, Anti epileptics-pharmacology and guidelines, R C Patel Institute of Pharmaceutical Education and Research , Shirpur, obstructedlabour-120719105413-phpapp01.pptx. GIT - Epigastric pain, nausea and vomiting: Skin rashes (may progress to Steven Johnson syndrome ) Somnolence Blurred vision Diplopia Ataxia, Levetiracetam Pharmacokinetics : Taken orally ( tablets or solutions) Not metabolized & excreted unchanged in urine Does not affect liver enzymes Drug interactions are minimal, Levetiracetam Mechanism of action Unknown Therapeutic Uses Adjunctive therapy in : Partial seizures Generalized tonic-clonic seizures Monotherapy Myoclonic seizures, Side effects Ataxia Dizziness Somnolence Pin & needles sensation in extremities Blurred vision, Topiramate Rapidly absorbed Half-life 2 hours Linear metabolism in liver Excreted by kidney, Clinical Uses Has a broad spectrum of activity As adjunctive therapy in adult & pediatric patients with refractory partial seizures. channels (different site from benzodiazepines) component of Valproate, Cimetidine, Isoniazid inhibits metabolism Focal, Generalized Antiepileptic drugs (AEDs) are widely used as long-term adjunctive therapy or as monotherapy in epilepsy and other indications and consist of a group of drugs that are highly susceptible to interactions. metabolism, reduction in .is that branch of, 1993 felbamate (FBM), gabapentin (GBP), Cellular Mechanisms of Seizure Generation, AEDs: Molecular and Cellular Mechanisms Overview, Drug Metabolizing Enzymes: UDP- Glucuronyltransferase (UGT), AED Inducers: The Cytochrome P-450 Enzyme System, AED Inhibitors: The Cytochrome P-450 Enzyme System, Potential Target Range of AED Serum Concentrations, Comparative Pharmacokinetics Of Traditional AEDs. Most people must continue taking antiepileptic drugs for their entire lives. Since 1990, many new antiseizure medications have been launched. definition of epilepsy. The availability of more automated immunoassays for measuring these drugs, as well as the expected development and introduction of more assays by manufacturers, will allow larger numbers of laboratories to perform in-house TDM of the newer AEDs. try to find a cause. GABAA receptor mediated like other Barbiturates Approved in the U.S. for Lennox-Gastaut syndrome, rufinamide has very complicated metabolism pathways and a high potential for drug-drug interactions. concentrations giving rise to skin Adverse effects Updated knowledge regarding drug interactions is important to predict the potential for harmful or lacking effects involving AEDs. Antiepileptic Drug An antiepileptic drug (AED) is a drug which decreases the frequency and/or severity of seizures in people with epilepsy Treats the symptom of seizures, not the underlying epileptic condition Does not prevent the development of epilepsy in individuals who have acquired a risk for seizures (e.g., after head trauma . definitions. GTCS and SPS Overall, TDM is useful especially in renal insufficiency, pregnancy, and cases with suspected drug-drug interactions. Long-acting forms such as Carbatrol or Tegretol-XR can be given once a day. AEDs=Antiepileptic drugs. firing frequencies Disclosure: The author has nothing to disclose. Generalized, PHENYTOIN Patsalos PN, Berry DJ, Bourgeois BF, Cloyd JC, Glauser TA, Johannessen SI, Leppik IE, Tomson T, Perucca E. Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Many laboratories, however, send out samples to reference laboratories. Antiepileptic drugs (AED) are medications given to control epileptic seizures and convulsions. The serum concentrations of lamotrigine should therefore be closely monitored, and this interaction is of major importance, as lamotrigine is often a preferred choice of drug in female patients (Level 1 interaction, according to [76]). it is a chronic medical condition produced by sudden changes in the electrical, ANTIEPILEPTIC DRUGS - . highly bound to plasma proteins A synergistic pharmacodynamic interaction between lamotrigine and valproic acid has, however, been demonstrated in an open cross-over study with 20 adult patients with refractory complex partial seizures The dose of both drugs, however, may need to be reduced to minimize the risk of intolerable side effects [115]. Barbiturates Oxcarbazepine induces the metabolism of OCs, ethinyl estradiol and levonorgestrel, as their AUCs were reduced by 47 %, accompanied by a 45 % decrease in their half-lives, by concomitant administration of oxcarbazepine (maintenance dose 1200 mg/day) as studied in healthy women [83] (Level 1 interactions). Bourg V, Lebrun C, Chichmanian R M, Thomas P, Frenay M. Nitroso-urea-cisplatin-based chemotherapy associated with valproate: increase of haematologic toxicity. Many drugs other than AEDs affect carbamazepine metabolism. Anticonvulsant or antiepileptic drugs - . Patients taking a typical dose of felbamate have serum/plasma concentrations of 3060 mg/L, but children clear the drug 2065% faster than adults. Mechanism of action involves reducing low threshold Ca2+ Inhibits phenobarbitone Rufinamide increases the clearance of OCs caused by weak enzyme induction, as shown by a reduction in plasma concentrations of ethinyl estradiol and norethindrone of 22 % and 14 %, respectively [35, 87]. Stiripentol is extensively metabolized through four main pathways, and it exhibits non-linear kinetics [62] (Table 11). ataxia, vertigo, diplopia, nystagmus are the most history. channel current (T-type channel) in thalamus Contin M, Riva R, Albani F, Baruzzi A. In a study with 22 women using lamotrigine (on average 350 mg/day) and OCs and 30 women on lamotrigine (on average 350 mg/day) without OCs, lamotrigine serum concentrations were reduced by more than 50 %, from 28 to 13 mol/L [100, 101]. Substrate and inducer of Valproic acid increases rufinamide concentrations by about 70 %, especially in children compared to patients without valproic acid as comedication, and this finding may be explained by inhibition of carboxylesterases [35]. abnormalities, impairment of learning and Findings from pharmacokinetic modeling indicate that rufinamide may slightly increase the metabolism of carbamazepine and lamotrigine (less than 20 %) [35]. valproic acid, Pharmacokinetic Principles Absorption: entry of drug into the blood Essentially complete for all AEDs Exception = gabapentin with saturable amino acid transport system. Blocks T-type Ca2+ channels Therapeutic Uses [I] Epilepsy: It is effective for all forms of epilepsy e.g. Carbamazepine should be prescribed in the modified-release preparation as this reduces side Ca++: Adverse effects Seizure. = ED 5O% /TD 50% Therapeutic range of AED serum concentrations Limited data Broad generalization Individual differences, Steady State and Half Life From Engel, 1989 American Epilepsy Society 2011. metformin, pioglitazone, Carbamazepine, Tran A, Vauzelle-Kervroedan F, Rey E, Pous G, dAthis P, Chiron C, Dulac O, Renard D, Olive G. Effect of stiripentol on carbamazepine plasma concentration and metabolism in epileptic children. Grapefruit juice may also inhibit CYP3A4, and has a modest elevating effect on serum carbamazepine concentrations. For female patients, possible interactions between AEDs and OCs are of major importance, as a large portion (>50 %) of patients lack knowledge and information [74, 75]. epilepsy. Recently, interactions between lamotrigine and OCs have been closely investigated. Carbamazepine (600 mg/day) increases the clearance of ethinyl estradiol and norethindrone by 127 % and 69 %, respectively [77]. Furthermore, some individuals show good clinical response at levels above or below the standard reference range. valproic acid, A synergistic Lennox-gastaut syndrome Acute intoxication - coma, convulsions and 1The National Center for Epilepsy, Sandvika, and Department of Pharmacology, Oslo University Hospital, Oslo, Norway, 2Department of Pharmacy, Faculty of Health Sciences, Oslo University College, Oslo, Norway, Postal address: Pilestredet 50, N-0167 Oslo, Norway. Laboratorians need to be aware of the key clinical and pharmacokinetic properties of these AEDs in order to optimize their TDM. Felbamate cardiovascular collapse. prof. mohammad saad al-humayyd. Teratogenicity: spina Laboratorians would do well to recognize this trend and evaluate new assays carefully so that they can best help clinicians understand the clinical utility of the results. seizures with or without generalization. Not metabolized in humans Several references are used, see text for details and selected reviews, [7-13] and the spc of the various drugs. Addition of simvastatin to healthy volunteers taking carbamazepine lead to a 75-82 % decrease in the AUC of simvastatin treated compared to controls, possibly by induction of CYP 3A4 [79]. Drowsiness, behavioral alterations, mental Therapeutic drug monitoring of antiepileptic drugs by use of saliva. Hyper-glycaemia. Polytherapy and the potential for interactions with other drugs increase with increasing age, and the elderly is the largest group with newonset epilepsy having a considerable risk of interactions with commonly prescribed drugs [7]. Should be done when documenting a serum concentration when a patient is well controlled. The UGTs are in general less substrate specific, and even though many genetic polymorphisms have been identified, no clear polymodal distribution in genotypes has been identified as for the CYP families. Absence and myoclonic or akinetic epilepsy . by: dr mehran homam. Zhou SF. Hirsutism: At high concentrations: Drug treatment of epilepsy in elderly people: focus on valproic acid. In vitro studies suggest a potential for interactions with most drug classes metabolized by CYP3A4, 1A2, 2C19. Fattore C, Cipolla G, Gatti G, Limido GL, Sturm Y, Ber-nasconi C, Perucca E. Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women. Mechanism of action weiping zhang department of pharmacology weiping601@zju.edu.cn. Enzyme-inducing AEDs increase the clearance of tiagabine by 50-65 % and subsequently, reduce the half-life on average from 7 hours to 2-5 hours [48]. Clinical and pharmacokinetic observations on sodium valproate - a 5-year follow-up study in 100 children with epilepsy. Uses: Partial (simple and complex) and secondarily generalized, Benzodiazepines Monitoring the free-drug fraction of stiripentol would appear to be beneficial, but no methods have been reported to date. The importance of drug interactions in epilepsy therapy. Date: JUN.1.2013 Furthermore, seizures by nature occur irregularly and unpredictably, making diagnosis difficult. Pack AM, Davis AR, Kritzer JY, Camus A. Antiepileptic drugs: Are women aware of interactions with oral contraceptives and potential teratogenicity? The newer AEDs are less susceptible to cause pharmacokinetic interactions than the older drugs, but may often be affected by other AEDs or drug classes. Tiagabine: Interferes with GABA re-uptake therapeutic failure, important accelerates AV conduction, of action: Dose: Pharmacological actions: Verrotti A, Coppola G, Parisi P, Mohn A, Chiarelli F. Bone and calcium metabolism and antiepileptic drugs. antiepileptic drugs and dosage implications. The names of the drugs c.. . drowsiness, amnesia, visual field Absorbed orally page 157-168 troleandomycin, Inhibition of carbamazepine phenytoin, but response is slow to develop. Before Another reason that TDM of the newer AEDs has been challenging is that homogeneous immunoassays have only recently become available on standard chemistry analyzers. Valproic acid is a broad enzyme inhibitor, including CYPs, UGTs and epoxide hydrolase, and inhibits the metabolism of lamotrigine (glucuronidation), phenobarbital (oxidation), the metabolite 10,11-epoxide of carbamazepine (epoxide hydrolase), and ethosuximide (oxidation) leading to increased serum concentrations of the inhibited drugs and consequently, an increased risk of toxicity [9, 55]. Seizure Saliva is also a viable specimen type for zonisamide TDM. ventilation Based upon comparative studies and evidence-based guidelines, newer AEDs are considered to be as efficacious as the older drugs and better tolerated. Myoclonic phenobarbital, kainic acid), 3 STATES This is an open access article distributed under the terms of the Creative Commons Attribution License (, Inhibition of lamotrigine The purpose of the present review is to focus upon clinically relevant interactions between AEDs and AEDs in combination with other important therapeutic drug classes, with emphasis on pharmacokinetic interactions. If valproic acid is added to carbamazepine, neurotoxic signs may develop due to an increase in the serum concentration of its epoxide metabolite caused by inhibition of the epoxide hydrolase [12]. hippocrates(400 b c)- on the sacred disease bromides(1957) phenobarbital(1912), ANTIEPILEPTIC DRUGS - . No interactions between OCs and gabapentin, levetiracetam, pregabalin, tiagabine, vigabatrin and zonisamide have been reported [68-73]. heartburn Levy RH, Loiseau P, Guyot M, Blehaut HM, Tor J, Moreland TA. Elimination varies with dose first order to zero order Pharmacokinetics of stiripentol in normal man: evidence of nonlinearity. These are divided into first-, second-, and third-generation AEDs. Tonic Clonic 4. Consequently, other than to assess patient compliance or to evaluate possible drug overdose, there is little benefit in monitoring vigabatrin. Idiopathic. * Effect of probenecid on the pharmacokintics of carbamazepine in healthy subjects. and psychosis . In status epilepticus, IV . irinotecan, methotrexate, The older AEDs may cause interactions involving enzyme induction or inhibition, affecting new AEDs as well as other drugs like anticoagulants, OCs, other CNS-active drugs, immunosuppressants, antimicrobal drugs as isoniazid or macrolides. In Girls polycystic Kim K, Oh S, Park P, Park J. CYP3A4 added as a second drug, A reduction in phenobarbital By 1994, however, clinicians identified cases of aplastic anemia, some of which progressed to severe liver failure, that were associated with felbamate therapy. Level 3 refers to interactions where dosage adjustments are usually not necessary. Adverse effects 5. Interactions between oxcarbazepine and carbamazepine, phenytoin and valproic acid were investigated in a controlled study with 43 patients and showed that oxcarbazepine did not affect any of the drugs, while induction by carbamazepine and phenytoin decreased the AUC of the main metabolite, 10-OH-carbazepine, (MHD) by 40 % and 29 %, respectively [45]. pharmacology 6th edition AEDs=Antiepileptic drugs. sedative action. Your evaluation may include: A neurological exam. Metabolism of zonisamide is affected by drugs that induce or inhibit CYP enzyme activity. Trigeminal and related neuralgias Oxcarbazepine. nature of epilepsy. Effect of felbamate on phenytoin and carbamazepine serum concentrations. Introduction. Vigabatrin: Irreversibly inhibits GABA transaminase Antiepileptic Drugs - . Teratogenicity (or phenobarbital, the contents by NLM or the National Institutes of Health. The past 20 years have seen the introduction of 14 newer AEDs for treatment of seizure disorders. of oral contraceptives with >50 Overall, clinical use of the drug is limited, and therefore so is experience with TDM. Luna-Torts C, Fedrowitz M, Lscher W. Several major antiepileptic drugs are substrates for human P-glycoprotein. These anticonvulsants were the mainstays of seizure treatment until the 1990s, when . Rivers F, O'Brien TJ, Callaghan R. Exploring the possible interaction between anti-epilepsy drugs and multidrug efflux pumps; Lscher W, Schmidt D. Experimental and clinical evidence for Uses: The effects of carbamazepine on the pharmacokinetics of phenobarbital and primidone are somewhat variable. Metabolized in liver by hydroxylation and glucoronide Perucca E. Clinical pharmacology and therapeutic use of the new antiepileptic drugs. often incomplete, but it is the drug of choice. Fulminant hepatitis (very rare0 The present review is based on published articles and searches in PubMed and Google Scholar from July 2008 to May 2010, in addition to references from the included articles. Multiple mechanisms of action : definition of epilepsy. drugs. protein In higher doses (up to 400 mg/day), however, a modest inducing effect was seen with a 18-33 % increase in oral clearance [85] (Level 1 interaction). metronidazol, doses if required maximum dose 100 mg/day channels at high firing frequencies, of antiepileptic drugs anticonvulsant - Symptoms of ED include. Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Complex partial seizure Glutamate and aspartate inhibition: By directly blocking Na+ channels - Adverse effects: Levetiracetam. Relevant pharmacokinetics The drug exhibits: increased metabolism over time (auto-induction); drug-drug interactions with CYP enzyme inducers and inhibitors; and impaired clearance in renal failure. Frscher W, Eichelbaum M, Gugler R, et al. disproportionately high plasma EpilepsyDrug therapyClinical pharmacologyReview. Approved in Europe in 2001, stiripentol has yet to be approved in the U.S. immunosuppressant to avoid affecting the efficacy, Newer AEDs have a less potential for pharmacokinetic interactions than older AEDs, but they are susceptible to interactions, since they are often used as adjunctive therapy with older AEDs. Focal TDM of topiramate is valuable because individuals' metabolism is quite variable. Furthermore, the central nervous system adverse effects of carbamazepine may be potentiated by lamotrigine and by oxcarbazepine [12, 37]. CONTD. memory, hyperactivity in children, mental Pharmacodynamic interactions are interactions at the site of action of the drugs and may involve synergistic or antagonistic alteration, and they are not possible to measure and evaluate, as no alterations in pharmacokinetics and consequently, serum concentrations are observed. :), Lecture 1 adithan diuretics july 22, 2016 mgmcri, Mahatma Gandhi Medical College & Hospital. conjugation Effective in partial, GTCS and absence seizures Interactions between antiepileptic drugs and herbal medicines. HHS Vulnerability Disclosure, Help Inherited abnormality in the C.N.S. Mechanism: 75% bound to plasma of valproate and lamotrigine in healthy subjects. Many consider them the drugs of choice for Phenytoin, epilepsy. Bethesda, MD 20894, Web Policies it is a chronic medical condition, Antiepileptic Drugs - . drugs may reduce risk of Lamotrigine's pharmacokinetics are well understood, but fairly complex. GABA-facilitatory Lacosamide, newer agent antibiotics: Each isoform is identified by three terms representing families and subfamilies. glutamate Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Valproate) Regulatory bodies in Europe and North America require bioequivalence between generic and innovator drugs with regard to area under the plasma concentration-time curve (AUC) and peak plasma concentration (C max); strict cutoff values have been defined. dependent calcium channels This involves various CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP3A4), UGTs and epoxide hydrolase. Anderson GD. Inhibition of calcium channel function. The interactions with older AEDs are thoroughly described in earlier reviews [8-12]. erythromycin, Pregabalin has predictable pharmacokinetics with no reported drug-drug interactions and minimal binding to serum proteins; however, renal failure patients generally take lower dosages. Researchers have proposed a reference range of 520 mg/L for epilepsy therapy. The other older AEDs with enzyme-inducing properties also affect antipsychotic drugs (Level 2 interactions). Elger C, Halsz P, Maia J, Almeida L, Soares da-Silva P. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment Anti-Epileptic Drugs - authorSTREAM Presentation. seizures only in infants Clinically significant drug-drug interactions involving lacosamide are also uncommon. Uses: GTCS, SP and CPS as supplement drug in refractory cases, and can cross BBB Effect of felbamate on clobazam and its metabolite kinetics in patients with epilepsy. Indications Phenytoin prolongs the inactivated state of contraceptive effect, Avoid the combination (or use on 6. Valproic acid inhibits the metabolism of amitriptyline and nortriptyline and increases their total AUC by 42 %, as studied in healthy subjects [89]. Oxcarbazepine is a weak inhibitor of CYP2C19 and may increase the serum concentration of phenytoin and phenobarbital [61]. Antiepileptic drugsbest practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Pisani F, Oteri G, Russo MF, Di Perri R, Perucca E, Richens A. for partial-onset seizures: Efficacy and safety results from a randomized antibiotics are added, Avoid macrolide antibiotics that An increase in the warfarin levels - Sachdeo R, Wagner M L, Sachdeo S, Shumaker R C, Lyness W H, Rosenberg A, Ward D, Perhach JL. The clinical importance of felbamate is, however, limited because of the diminished use of the drug during the last years due to toxic effects. Valproate and Usually given 0.2 to 0.5 mg/kg body weight IV followed by repeated In recent studies of children and adults with refractory epilepsy, 64 % used polytherapy with two or more AEDs, and 35 % of the adults suffered from CNS-related comorbid conditions, resulting in a considerable risk of interactions [5, 6]. Ragueneau-Majlessi I, Levy RH, Janik F. Levetiracetam does not alter the pharmacokinetics of an oral contraceptive in healthy women. Deoxybarbiturate relaxation, causing a Blocks voltage-dependent sodium channels Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. May TW, Rambeck B, Jrgens U. Lacosamide does not seem to be involved in pharmacokinetic interactions and will not be discussed further [31, 32]. 7. GABA Antiepileptic drugs (AEDs) are the mainstay in the treatment of epilepsy, one of the most common serious chronic neurological disorders. Fetal Hydantoin Syndrome Adverse effects- mild sedation, nervousness, For example, TDM of oxcarbazepine often focuses on its active metabolite, 10-hydroxycarbazepine. Benzodiazepines, ethosuximide, lamotrigine, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, zonisamide, valproic acid, Doxycycline, In a recent sur-vey of 471,873 persons carried out in Denmark, 5,426 were found to be receiving AEDs, which corresponds to a prevalence of 1.1% (1). Specific combinations and clinical implications of major clinical importance that should be remembered are summarized in Table 44 (Level 1 and 2 interactions). Anti-epileptic drugs for pediatrics are a diverse collection of anticonvulsant drugs used for the symptomatic treatment of seizure disorders. Well-known interactions and newly established interactions of clinical importance will be highlighted. * Abbreviations: GC, gas chromatography; HPLC, high-performance liquid chromatography; LC-MS/MS, liquid chromatography-tandem mass spectrometry. The basic assumption of TDM is that the measured drug concentration correlates with the concentration at the target site of its action, usually an ion channel or neurotransmitter transporter in the brain, and therefore with the therapeutic effect. could be bilaterally symmetrical, DRUGS: i.v. and monitor closely, Level 2: Dosage Epilepsy is one of the most common neurological diseases; its first-line treatment is the administration of antiepileptic drugs (AEDs). Gum hypertrophy and Gingival hyperplasia. The newer second- and third generation AEDs is less interacting than the older drugs, which results in less complicated therapeutic outcomes and complications for the patients [13]. clonazepam) Other highly protein-bound drugs, as salicylates and naproxen, displace tiagabine from serum proteins and slightly decrease the total serum concentration [109]. Perucca E, Gidal BE, Baltes E. Effects of antiepileptic comedication ADR: Rash, antiseizure drug Pharmacodynamic and pharmacokinetic interactions of psychotropic drugs with antiepileptic drugs. treatment. A noted clinical pharmacologist, Emilio Perucca, MD, PhD, has promoted the concept of "individual therapeutic concentrations" for AEDs, wherein a patient is treated until good seizure control is achieved (8). Today, most reference laboratories employ high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for measuring levels of newer-generation AEDs. 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