Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. Park eto nenlMdcn,SolNtoa nvriyCleeo eiie eu,Korea Seoul, Medicine, of College University National Seoul Medicine, Internal of ment 7 6 5 Korea South 4 3 Korea South Seoul, Hospital, 2 University National Seoul Institute, Research 1 PhD MD, Lee, Kun Sang PhD rash MD, skin Jung, of Keun-Hwa risk the reduces MD that lamotrigine MD Jang, for Yoonhyuk protocol novel titration situations. various the rapid in of new lamotrigine value of A the application demonstrate available findings the widen These could Conclusion rash which skin administration lamotrigine, idiosyncratic lamotrigine for experienced of reaching protocol (6.9%) weeks until induction two ( 2 dose tolerance only weeks stepwise-incremental after analyzed, 2 a patients patients at administer studied 29 hospital. visit then Of of tertiary follow-up and Results (age single first drug patients a days. adult the the at 11 33 of time before within for enrolled dose first dose protocol prospectively the subthreshold titration therapeutic We for rapid a full Methods administration and with dose the novel mg. lamotrigine starting starts a 200 started the protocol of of and if safety new dose rash epilepsy and Our daily skin with efficacy a a diagnosed the reach of were investigated issue to We who critical days 18-85) rapid. a 11 too has only is it takes rate but that escalation drugs, lamotrigine the antiepileptic used or widely high most too the is of one is Lamotrigine Aims Abstract 2020 27, April 4 3 2 1 Shin Jang risk Yoonhyuk the reduces that rash lamotrigine skin for of protocol titration rapid new A nttt fAlryadCiia muooy eu ainlUiest eia eerhCne;Depart- Center; Research Medical University National Seoul Immunology, Korea Clinical South and Seoul, Allergy Health, of Mental Institute for Center Korea National South Neurology, Seoul, of Hospital, Department University National Seoul, Seoul Medicine, Neurosurgery, of of Department College University Hallym Hospital, Heart Korea Sacred South Kangnam Suwon, Neurology, Medicine, of of Department School University Korea Ajou South Neurology, Seoul, of Hospital, Department University National Seoul Center, Biomedical Disease Rare Center, Epilepsy Comprehensive Neurotherapeutics, for Laboratory Neurology, of Department ainlCne o etlHealth Mental for Medicine Center of National School Hospital Graduate Heart and Sacred Medicine Kangnam of School University Ajou Hospital University National Seoul 4 ogWnSi,MD Shin, Yong-Won , 1 1 yyo Chang Hyeyeon , iYugJung Ki-Young , 1 agu Moon Jangsup , 1* agu on D PhD MD, Moon, Jangsup , 1 1 4 5 1 o Chu Kon , y ynKang Ryun Hye , yyo hn,MD Chang, Hyeyeon , yn-lPr,M,PhD MD, Park, Kyung-Il , ± 1 as.I diin hrpui ocnrto a ece nmr hn75% than more in reached was concentration therapeutic a addition, In days). 3 aa Kim Narae , 1 n agKnLee Kun Sang and , 1 1,2,* onTeLee Soon-Tae , 6 y-ynKn D PhD MD, Kang Hye-Ryun , aa i,PhD Kim, Narae , 1 1 8 a-onKim Tae-Joon , iYugJn,M,PhD MD, Jung, Ki-Young , 1 1 enHaJung Keun-Hwa , 1 a-onKm MD Kim, Tae-Joon , 2 i-u Jun Jin-Sun , 7 onTeLe D PhD MD, Lee, Soon-Tae , 1 o h,M,PhD MD, Chu, Kon , 1 Kyung-Il , 3 Yong-Won , 3 i-u Jun, Jin-Sun , 1 1 , , Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. oe n ai irto rtclfrlmtiieta ae ny1 ast ec al oeo 0 mg. 200 of a if dose of rash daily safety a skin and reach a efficacy to the of days investigated issue 11 We critical only rapid. takes a too that has is lamotrigine rate it Methods for escalation but protocol the drugs, titration or antiepileptic rapid high used and too novel widely is most dose the starting the of one is Lamotrigine psychiatric to Aims lead and can seizures protocol frequent this including duration, Abstract indications titration various the for reducing By prescription maintenance rash. usual lamotrigine diseases. the skin in reach of to increase days risk eleven an the only takes increasing that without protocol titration dose lamotrigine taking new safer, a introduce be We to escalation slower dose. the adds: maintenance be if study or usual to this high the recommends What too reach protocol is to titration dose weeks conventional starting 8 the the than if Thus, more reactions rapidly. adverse too cutaneous made of is risk high a has subject: Lamotrigine this about known already is What E-mail: +82-2-3672-7553 Fax: +82-2-2072-2923/ Tel: Korea 110-744, Seoul Jongno-gu, Daehak-ro, Hospital, 101 University National Seoul Neurology, of Department PhD MD, Lee, Kun Sang and Email: 82-2-3672-7553 + +82-2-2072-1878/Fax: Korea Tel.: South 110-744, Seoul Jongno-gu, Daehak-ro, Hospital, 101 University National Seoul Neurology, of Department PhD MD, Chu, Kon protocol Correspondence: titration lamotrigine Rapid head: Running 1 figures: of Number 2 tables: of Number 30 references: of 2300 Number manuscript: the for count word 183 Total abstract: the for count word Total 81 title: the for study. count this Character to equally contributed authors These * Korea South 8 eateto erlg,SolNtoa nvriyHsia elhaeSse aga etr Seoul, Center, Gangnam System Healthcare Hospital University National Seoul Neurology, of Department [email protected] [email protected] 2 Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. xabzpn) nyeihbtn E vlri cd,o rlcnrcpie rhdee xeine drug assessment experienced ever Clinical had carbamazepine, or 2018. phenobarbital, contraceptives November excluded. oral (phenytoin, to were or 2016 AEDs rashes acid), July enzyme-inducing (valproic from prescribed AED Hospital enzyme-inhibiting University been oxcarbazepine), National lamotrigi- ever started Seoul had and at epilepsy who time with Patients first diagnosed the were for who administration 18-85) (age ne patients adult enrolled prospectively We maintenance enrollments usual Patient the reach to the days rash. with eleven skin Method prevented only we of takes Here, be risk titration. that the could the increasing protocol lamotrigine of without titration duration to dose lamotrigine the response shorten new consequently in a would rash which introduce protocol, skin induction idiosyncratic tolerance rapid the significant tolerance that a oral showing drug-na¨ıve hypothesized patients, slow risk We high The rash. (HLA) the skin reactions. antigen to the leukocyte applied cutaneous human in then severe was of reduction achieved allopurinol allopurinol-induced type successfully of certain the with been protocol and a associated Jung induction has of before.[23] strongly presence drug rashes the is drug certain experienced to which a never according but to patients intraperitoneal risk tolerance classified high or at colleagues concept, intravenous were same na¨ıve the who drug- patients via the in protocol even with stepwise-incremental Various Likewise, rituximab a chemotherapy, reached.[13] 22] and in by is route.[21, phenytoin, even desensitized Moreover, acids, dose successfully desensitized.[14-20] valproic safely therapeutic oxcarbazepine, also be carbamazepine, was full to including proven the rashes, been antigen until skin have drug to phenobarbital, dose the prone of stepwise-incremental protocol dose are a administration suboptimal that a by administer AEDs achieved of administration be to the can with then allergies too start and drug to made have is strategy is who more main patients escalation The taking in adjustment.[12] the safer, drug dose.[9-11] a if be of maintenance to or induction risk usual slower Tolerance high The the be too reach reaction.[8] to is to adverse recommended rate.[3] weeks dose idiosyncratic has retention 8 starting an protocol than 7] titration highest inducing the conventional rash.[6, of if the the skin risk increase Thus, has life-threatening high rapidly.[9] rashes potentially a and skin the has However, choice lamotrigine-induced 5] lamotrigine been of disorder.[4, of AED, has bipolar aromatic drug administration as an such lamotrigine the disorders As of psychiatric is epilepsy.[1, hindrance for with it option major children useful patients, and the a adults also epilepsy both is in elderly lamotrigine Moreover, (AED) in drug antiepileptic Especially first-line used 2] widely a is Lamotrigine could which lamotrigine, situations. for various protocol in Introduction induction lamotrigine tolerance of novel application the available of the value widen the demonstrate findings These visit follow-up first administration Conclusion the lamotrigine before of weeks rash 2 skin after idiosyncratic patients ( experienced weeks (6.9%) full two 2 the only at with analyzed, reaching patients starts until 29 protocol dose Of stepwise-incremental new started a Our and administer hospital. epilepsy then tertiary Results with and single days. diagnosed drug 11 a were within the at dose who of therapeutic time 18-85) dose first (age subthreshold the patients a for adult administration 33 lamotrigine enrolled prospectively We ± as.I diin hrpui ocnrto a ece nmr hn7%o studied of 75% than more in reached was concentration therapeutic a addition, In days). 3 3 Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. aorgn oe10m i)js fe h diitaino rpaoo u onwydansdpostural propranolol. diagnosed and newly lamotrigine to withholding due after propranolol day of next patient administration (BSA the other the subsided body The after rash levetiracetam. whole The just to the syndrome. bid) AED on tachycardia lamotrigine mg the rash (on changing 100 14 maculopapular day after dose acute-onset on disappeared lamotrigine 18%) experienced (BSA lesion leg 2) skin one ID and The arms (Patient 1 bid). the the on mg rash before 100 mild rash relatively dose skin a had idiosyncratic 1) experienced ID 6.9%) (Patient patient 29, aromatic titration of an (2 rapid patients taken lamotrigine Two had after patients occurrence the rash skin of lamotrigine Idiosyncratic before None AED common. an most taken followed the had previously. 51.7%), (24.1%) being AED, (15, patients diagnosis levetiracetam Seven common with 27.6%). most the (8, administration, was epilepsy epilepsy and generalized electroencephalogram lobe video (44.8%), idiopathic temporal hours males by Twenty-four patients; years]. were Thus, all 36-45 agreement. for patients range, an performed [interquartile Thirteen years without were 2). 34 times patients (Table was two 3 age analyzed disqualified; than median were ultimately more the (12%) lamotrigine were patients omitted (88%) four patients study, patients two current twenty-nine and the follow-up, in to enrolled lost were were who patients 33 the Of characteristics Patient for analyzed used was was titration USA) Texas, rapid LLC., lamotrigine Result (StataCorp the 14 STATA after test. and a signed-rank before and Tregs pairs analysis, matched the Wilcoxon ( of the weeks proportion with 2 drugs. the the of of after induction difference and tolerance The titration the rapid after lamotrigine cells Treg the total before the cells 1 T the helper of CD4+ days) among cells (Treg) sorting titration T cell the fluorescence-activated after 2.5mg evaluated and We below before Doses pharmacy. cells decision. hospital T on the clinician’s regulatory bid the at the of mg and protocol medicine to day, analysis 100 powdered according sorting a reaching as day, twice cell titrated prepared every to Fluorescence-activated given was and dose escalated was dose lactose was previous dose saccha the dose the same day, with next times the mixed 11th the 1.5-2 were 4, the and to day After mg, escalated induction From 11. 0.1 was hours. tolerance day of lamotrigine 12 rapid dose of every the a dose dose for with daily previous schedule started the 11-day protocol times an The the 1.5-2.5 following Figure). from patients 1, out (Table the dropped protocol to were prescribed discretion. patients was own Also, Lamotrigine their disqualified protocol visit. on were induction doses scheduled patients consecutive tolerance a two The rapid to of Lamotrigine administration. doses appear lamotrigine three not omitted of did they weeks they when the until 2 when study rash using beyond skin study calculated a rash the was of skin occurrence from lesion the of skin as occurrence defined the was the of outcome primary extent The The 1 chart. Terminologythe surface 4.0. Common body version the Browder to (CTCAE) & according Lund Events evaluated were Adverse events adverse for Cutaneous Criteria 1 phone. by the researcher before the event ( to weeks adverse two any after clinic experienced outpatient patient the visit obtained to 1605- asked was were No consent Patients (IRB informed University Written National 03220256). Seoul patients. (NCT the ClinicalTrials.gov all of at from Board registered Review was Institutional and the 121-764), by approved was study This st olwu.Tescnayotoewstesvrt ftesi ah h aorgn eu ee,and level, serum lamotrigine the rash, skin the of severity the was outcome secondary The follow-up. st p olwu ii eas omrsuishv eosrtdteices ftepretg of percentage the of increase the demonstrated have studies former because visit follow-up -value < 0 a osdrda ttsial significant. statistically as considered was .05 ( AS nlsst vlaetepooto fregulatory of proportion the evaluate to analysis FACS) st 4 olwu ii,te eeifre orpr h issue the report to informed were they visit, follow-up ± as rmtepooo ne.We the When onset. protocol the from days) 3 st olwu ii Tbe2.One 2). (Table visit follow-up > 5)o a 7(on 17 day on 95%) ± 3 Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. h tr aiglmtiiewudb xoe ossandrs fsiuefrnal w otsutlthe until required months often two are nearly AEDs for other seizure of of patients prescription Conventionally, risk combined sustained administration. Therefore, respectively) to levels. lamotrigine times/week, therapeutic exposed of 2 the be weeks reach would and 2 lamotrigine lamotrigine level times/week within lamotrigine taking (5 respectively) (serum start baseline concentration mcg/mL, range who therapeutic at patients 5.5 therapeutic the Two seizures and reaching the patients. frequent by 4.6 measured reduction to with the seizure rapidly 23) of significant and three-quarters experienced rise than 14 to more 1 ID levels in the (Patient reached serum At was lamotrigine time. concentration short patients. the therapeutic two fairly allows latter first a the protocol the in in in titration patients refinement drug two protocol new culprit further and the The by celecoxib, not bid, preventable and was mg been (roxithromycin lamotrigine have 150 drug the could 1 causative to and rash potentially the lamotrigine patient skin a beyond of the of rash escalation think administration We skin experienced dose the respectively). encountered be the patients after patients not rash after these 3 may skin rash of Additional lamotrigine experienced skin one that rash. population, experienced Furthermore, suggesting skin Korean patient propranolol, the (23/102).[25] the one of of 22.5% in administration cause to lamotrigine the con- true titration, after up after the the rapid just reactions be to rash during adverse to compared skin rash cutaneous reported when idiosyncratic skin of reactions been experienced rate adverse patients has the the cutaneous which than Our of days of lower day. (2/29) 11 terms was per 6.9% in in which mg Only day safer 200 protocol. per was of titration mg dose protocol ventional 200 maintenance titration the reaches the new and than reach The titration doubles safer to for and reactions. weeks and day required adverse 8 per faster time cutaneous to mg severe the be up 25 without reduces could requiring of dramatically weeks, dose that protocol two a lamotrigine rapid to with for starts one every protocol protocol conventional it titration The new protocol. titration a conventional demonstrated after Treg we of Here, that observed and was 0.64) proportion (SD Treg the % Discussion the of (p=0.333). 4.64 alteration induction was after significant tolerance patients. titration statistically 10 lamotrigine the and No in the 0.93). before titration before after Treg (SD rapid 4.00% of lamotrigine cells was the percentage titration after the T the and of before CD4+ value performed mean was total The cells Treg the the of among analysis FACS cells T therefore, up; regulatory protocol flared 6%) titration necrosis. of (BSA epidermal none proportion thigh toxic However, and or discontinuation. The the hand syndrome after Stevens-Johnson the soon therefore, on experienced disappeared 28; patients rash rash day the skin The on of the stopped. painkiller thigh rash days, were the the the as celecoxib 9 on added and lamotrigine, After was rash lamotrigine celecoxib reason. and skin Afterward, orthopedic bid). mild medications by mg very an weeks, cold 100 induced a for (on two the patient continuously reported was nearly prescribed withholding the 5) rash was for After ID lamotrigine to the day (Patient the occurrence. given patient whether a neck rash were other day. twice unclear roxithromycin the the The a mg was subsided. and before below twice 100 it chlorpheniramine, days body mg at but bromhexine, 3 150 maintained whole bid), since (codeine, was to the body, mg drugs lamotrigine lamotrigine neck, almost 100 cold of of the on lamotrigine common dosage on dose rash (on the rash the maculopapular 24 While maculopapular increasing a day lamotrigine. a after experienced on had just 91%) 4) 3) 19 ID (BSA ID day (Patient (Patient on patient patient 41%) One One (BSA 10.3%). legs 5, and (77.2%) and patients arms, 4, 17 3, them, ID weeks. Among (Patient 2 2.07). within 1 (SD mcg/mL)[24] the mcg/mL (2.5-15 Beyond level 3.85 serum was therapeutic level the lamotrigine reached serum successfully the of value mean 1 the assessment At long-term and level lamotrigine Serum st olwu ii,tesrmlmtiielvlwscekdi 2ptet 7.% Tbe2.The 2). (Table (75.9%) patients 22 in checked was level lamotrigine serum the visit, follow-up st olwu ii t2wes( weeks 2 at visit follow-up st olwu ii,2wes( weeks 2 visit, follow-up ± as,adlydostsi ahapae ntrepatients three in appeared rash skin delayed-onset a days), 3 5 ± as fe aorgn diitain the administration, lamotrigine after days) 3 st olwu visit; follow-up Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. ecnr htw aera h ora’ oiino susivle nehclpbiainadar that affirm and publication Statement ethical Availability in guidelines. involved Data those issues with on consistent position is Journal’s the report read this have we that confirm We Statement Publication interests. Ethical of conflict no pharmacy declare center authors We trial The (0420170820). Clinical SNUH Fund the Interests Research at of Cho Hospital Conflicts Sook University Yoon and National pharmacy. Jang hospital Seoul Won the Hong the and of by support the supported appreciate was study near This the indications. in various trial of larger for escalation a prescription in dose Acknowledgements investigated lamotrigine prompt be in should safety, require increase protocol noticeable who the an with seizures of future. to validation days in frequent and lead 11 lamotrigine with refinement can to additional for patients Thus, protocol titration in protocol this of helpful induction Moreover, duration extremely AEDs. tolerance the be rapid reduced bid) will successful significantly mg which It a 100 epilepsy. (beyond demonstrated with dose the study patients daily increase our higher may a conclusion, refinement to In protocol lamotrigine Further increasing patients. for Subsequent investigated. of strategies design. number be and open-label should larger and protocol, cell/basophil uncontrolled a the its mast in of and and patients safety conducted of be cells number the small should T for the could studies by drug-specific Thus, cells, future. limited Treg of AEDs. is the total study in the alteration This the investigated against The of be against immunity that induction. should protocol not the titration tolerance tolerance cells, after desensitization had the Treg functions our the had antigen-specific to that are already the mattered did of studies in patients have percentage The which former the reactions, the induction. AED the which patients, immune induction, tolerance of but cells, some the tolerance the cells, T studies of in after immune memory other Tregs difference protocol naive the total with fundamental the the the the result after targets of from different induction and proportion come the the before could shows of cells discrepancy This increase T the alterations. CD4+ having meaningful desensitization total proportion any the the demonstrate assessed We among investigated. not being cells worth is Treg desensitization induction rapid of tolerance this, of the mechanism with applying exact by line lamotrigine. the However, achieved In receiving be patients.[23] start be can high-risk who 29, desensitization to lamotrigine in patients cells,[13, the to to allopurinol thought Treg that tolerance of protocol demonstrated drug-specific is that administration al. increasing demonstrates it et first study by Jung drug-na¨ıve the but our patients. in or during effective understood, useful response be was basophil also fully protocol could and induces not it normally cell that 28] is which have mast so antibiotics.[27, dose, 30] desensitization the and they incremental AEDs reducing of of and including by step mechanism doses, achieved drugs, the at The many therapeutic increasing antigen by to symptoms.[29] full drug refined response fewer to the be in have can increases of rashes who protocols skin incremental dose patients Desensitization avoiding in stepwise suboptimal at drug by a successful a followed with been to intervals, start tolerance time protocols when temporary effective fixed The induce be hypersensitivity.[26] protocols also drug can Desensitization allergies, experienced drug. drug new of state. prevention a manic the starting a for disorders developed of psychiatric originally of stage other management protocols, from acute acute Desensitization conversion an the the in in during useful disorder patients therapy be epilepsy bipolar bridging can severe as of protocol in such duration this useful the Moreover, extremely shorten lamotrigine. be will to would AEDs it protocol and currnet seizures, the frequent Thus, with period. titration the during 6 Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. nPtet ihOcraeieIdcdSi ah io td.PdarcNuooy21;5:207-14. 51: 2014; Desensitization Neurology of Trial Pediatric and Study. Genotypes Pilot Antigen Leukocyte A Human Rash: J. Skin Lee M, Oxcarbazepine-Induced Lee With E-S, Patients Medicine Kang in Nature H, Yu tolerance. B, Lee induce to 14. strategies refining S126-S37.e1. inflammation: 736. 125: Edwin allergic 2010; 18: Immunology for SS, 2012; Clinical Therapies and Robert CA. Allergy Akdis of R, Journal 13. Alan allergy. MP, Drug 40: R. John 1999; Solensky DA, Epilepsia SD, Khan Michael Children. 12. and MD, Adults J Joseph in Sci JB, Considerations Neurological Martin Risk/Benefit 985-91. J MCB, Rash: Can Frank Lamotrigine-Associated Lamotrigine. HG, T. with Alan Treated S14-S18. Patients 11. Pediatric 25: 1998; and Neurologiques Adult Sci in The Des Rash rash. Can AM. skin John lamotrigine-related of 10. incidence 1037-42. S-y. the Lang 33: influencing W-q, 1999; Factors pharmacotherapy JW. Jia Seizure of Sander D-h, GE, Annals analysis. Huang Mawer cohort C-l, IC, postmarketing Wong Tian and J-t, 9. meta-analysis Zhang Current X-s, 52-61. Huang rash: K. S-y, 25: skin Chu Yu 2015; lamotrigine-related K-Y, W-H, population. a Jung Xu Korean K-H, of J, a Jung Risk Xiong in S-T, 629-30. X-q, reactions Lee Wang 118: The drug J, 2017; 8. KH. adverse Moon Immunology Jung & H-S, cutaneous Asthma Park ST, severe Allergy, Y-S, lamotrigine-induced Lee of Chang and JW, Annals T-B, 01 Shin Kim TJ, 31: J-W, the Jung HLA-A* Kim in B-K, JA, eruption Kim e161-e67. maculopapular Lim 56: lamotrigine-induced 7. JI, 2015; with Byun Epilepsia associated JS, population. is Sunwoo orean haplotype K, K 0102 Chu w* HK, 2402/C Park of HLA-A* Journal J, independent British depression: Moon trials. bipolar 6. randomised of five treatment from 4-9. data for 194: patient Lamotrigine 2009; individual Psychiatry GM. Comparative of an Goodwin meta-regression LJ. lamotrigine: JR, and Hirsch with meta-analysis Calabrese CW, depression 242. JR, 6: bipolar Geddes Bazil 2015; 408-15. 5. of SR, Pharmacology 67: Management in Resor 2010; Frontiers LK. neurology J, stabilizer. Bhatt of mood Sims NB, Archives antiepileptic epilepsy. Poovanpallil M, with KS, adults Whalen Prabhavalkar older 4. J, in drugs Pierro antiepileptic R, 10 of Buchsbaum 2017; effectiveness H, reviews systematic Arif of epilepsy: 3. database for Cochrane monotherapy drug The Antiepileptic data. AG. participant Marson individual 12. 1255-60. C, of Smith 42: Tudur meta-analysis 2001; J, network Weston Epilepsia a M, Drug. Sudell Antiepileptic SJ, First Nevitt of 2. Effectiveness MJ. K.C, Brodie P, K, Kwan K.C. H-R. 1. J, the J.M, reviewed K-Y. P, data. authors All K-I. clinical study. J, collected the K-H. References supervised S.K.L L, S.K.L. and K, S-T. and T-J. K.C, J.M, K.C. J.M, manuscript. J, funding. Y.J, the and K-Y. manuscript. data. materials revised P, the provided and K-I. analyzed S.K.L. concepts L, J.M. and study and S-T. provided N.K., H.C, S.K.L Y.J, S, and manuscript. Y-W. the revised J., and J-S. wrote J.M. and Y.J, reasonable upon author Contributions corresponding the Author from available are study this of findings request. the support that data The 7 Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. rtcl tr ihads f1. gbdfrtefis n eodwesaddul tt 5gbdi the in bid 25mg to it double and weeks conventional second The and first lamotrigine. the of for dose bid daily mg the 12.5 indicates of dose box a the with inside start titration. number protocols lamotrigine The of of paper protocols. protocols position titration 844-52. EAACI The Cernadas 68: an P, 2013; – Whitaker Figure. Allergy B, reactions 41: Schnyder Group. hypersensitivity A, 2011; Interest Desensitization drug Romano Allergy Allergy P, delayed M. Demoly Drug Experimental in JHC, the Castells & Desensitization Gooi AJ. Clinical M, W, Bircher Aberer century. Sancho-Serra K, JSR, 21st Brockow D, K, the Scherer Sloane in 30. J, art Fernandez the of H, state Chong 1679-89. Hypersen- 2019. allergy: L, Other Seizure drug Fanning and Literature. for A, Rashes Current regimens ML. of Liu Wagner Review XB, A Zhang 29. Drugs: T, Antiepileptic Truong with PC, Associated Schalock Reactions C, sitivity Monteleone R, approaches 1140-48. and Mani 58: reactions 28. 2013; hypersensitivity Antibiotic diseases E. infectious Swiatlo Clinical GD, desensitization. Marshall 2006; to CA, Immunology Muzny Clinical DP, and Legendre Psychiatric Allergy 27. in in Opinion Rash Current S-Y. allergy. Bhang drug Study. 476-81. E, for Cohort 6: Desensitization Park Retrospective M. K-Y, Castells A Lee 26. S-W, Korea: 174-79. Choi in 9: Y, Lamotrigine 2012; Kim Receiving Investigation K-W, Psychiatry Patients Drug Kim 347-63. Adolescent Therapeutic J-H, Nonpsychiatric 25: PN. K-U, Ahn 2003; Patsalos and Min Monitoring H-J, T, Tomson S-H, Tak Drug G, Therapeutic Cho Kramer 25. Drugs. K, M, Antiepileptic Lee Bialer Newer DJ, C, the Berry Genetics of Ahn D, Monitoring Y-S, Battino typing. SI, Kim HLA Johannessen by K-W, 24. hypersensitivity Joo 807. allopurinol-induced K-H, prevent Clini- 17: Oh to 2015; and to H-W, Medicine strategy Allergy in Park effective reactions of An D-K, Hypersensitivity Journal H-R. Kim Nal- UA. Kang J-W, HJ, cases. Matulonis Jung Legere 413 SM, TM, in 23. Laidlaw Campos desensitization 574-80. DI, rapid ST, 122: Hong of 2008; Berlin NA, Immunology safety Barrett JJ, cal and IF, Rao Outcomes Hsu desensitization. RI, DE, after chemotherapy: Palis Sloane cells NM, SN, Treg Tennant of lamshetty desensitization MC, 478-80. number rituximab Castells 132: rapid in 2013; Successful Increase 22. Immunology E. Clinical Karaoz syndrome: and I, nephrotic Allergy Eser with of Z, patient Journal Uyan with G, adolescent Gacar child an N, in a asthma Yologlu and M, in Allergy Aydogan child. desensitization 21. 3-month-old a Phenytoin in 225-27. K. desensitization Pentobarbital 25: Watanabe A. 2004; Dioun T, B, proceedings 121-23. Dodson Negoro MJ, 29: Butte T, 2007; 20. Development Ikuta and A, Brain epilepsy. Okumura desen- localization-related Phenytoin S, symptomatic dilution K. 385-88. Itomi Watanabe ester 11: succinimidyl T, 2007; carboxyfluorescein Negoro 19. Neurology desensitization. using J, Paediatric response Natsume and of cell H, Journal hypersensitivity T Kurahashi European acid specific assay. T, Valproic antigen Kubota by T. I, monitored Gilboa Tsuge sitization A, D, 1076-78. Okumura Shmoeli 57: 18. L, 2015; Neurology Horev Child Y, & Tal Medicine Developmental O, DESENSITISATION. Toker BY MANAGED 17. CARBAMAZEPINE 509-10. TO 333: 1989; REACTIONS Lancet ADVERSE The P. Eames DESENSITI- BY 16. MANAGED 753. CARBAMAZEPINE 325: TO 1985; REACTIONS Lancet ADVERSE The R. SATION. Newton H, Smith 15. 8 ceeo h ovninladrpdlamotrigine rapid and conventional the of Scheme Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. 1 0 gbd20mg 200 mg 150 mg 100 mg 50 mg 30 mg 20 mg 10 mg 5 Lt. mg 2.5 F/45 dose daily Total mg 1.25 mg 0.35 1 Combined Diagnosis hours. 12 every Sex/Age = q12h bid day; mg a 100 twice bid = mg bid 75 bid mg 50 bid mg 25 ID bid mg 15 bid tion mg 10 bid induc- mg 5 bid ance mg 2.5 q12h toler- mg –1-1.5 q12h ter mg 0.5-0.75 hours. af- q12h epilepsy 12 mg every 0.1-0.25 = q12h with day; a twice = tients bid Dose pa- of sponse re- cal Clini- 2. Table hours. 12 every = q12h day; a twice = bid 11- 10 9 8 7 lamotrigine 6 for protocol induction Tolerance 5 1. Table 4 lamotrigine for 3 protocol induction Tolerance 2 1. Table decision. 1 clinician’s the lamotrigine to reaching for according day, Day same protocol titrated every the dose is induction 4, previous Tolerance dose day the the From 1. times 11, Table 1.5-2 hours. day to 12 After escalated every 0.1 11. is dose for of dose day previous dose is weeks, daily on the a two the protocol bid times with and conventional to mg day, 1.5-2.5 starts This one 100 a to protocol every day. twice escalated titration given mg per is rapid is 50 200mg Our dose dose by of next inhibitor. increased dose the or is maintenance and inducer mg, dose the P cytochrome reach daily taking to the not weeks week, patients 8 fifth to the From up requiring weeks. fourth and third tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table OLE tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table AED d) (14 + tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table LMT) after (days rash Skin Idiosyncratic 9 * . auoaua/8- (100 + Maculopapular/18(-) - 6.9 tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table 1 at level LMT st FU tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table 1 beyond rash Skin LMT) after (days st FU tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table pe/BSA(%) Ty- Rash tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table factor ing Trigger- Potential ¶

tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table bid) mg rash) at dose (daily rash to related tion tinua- discon- LMT Table 2. Clini- cal re- pneof sponse pa- tients with plpyaf- epilepsy ter toler- ance induc- tion

0.5

Follow- pwith up LMT (months) Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. 1F2 G E / 8 - - - Lt. IGE N/A F/72 Lt. M/27 Lt. F/59 - 18 Rt. 17 M/32 LEV Lt. 16 F/29 Lt. 15 F/23 IGE 14 M/34 Rt. F/24 13 Lt. F/36 12 Lt. M/60 11 Lt. M/31 10 Lt. F/71 9 F/56 8 Lt. (17 + 7 F/44 Bilat. 6 F/31 Rt. 5 F/62 IGE 4 M/20 3 2 tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table TLE OLE FTLE TLE TLE TLE TLE TLE TLE TLE TLE TLE TLE TLE tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table E / 18 - - N/A - LEV tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table . 22 19 - 9 - 9 - 8 - 8 - 8 - 8 - 8 - - 3.8 8 - 2.1 - - - - - 4.6 - - 4.7 N/A - - - - N/A - - N/A - 0.3 - - 4.1 - (37 + 5.1 - - (24 + 5.2 - (19 + 9.4 - 4.2 - - d) tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table 10 / Maculopapular/ - N/A tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table < . 20 - - 0.1 tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table d) d) d) tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table Maculopapular/6Celecoxib Maculopapular/91Roxithromycin (150 + Maculopapular/41(-) tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table > 95Propranolol

§ + tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table bid) mg (100 + bid) mg (100 + bid) mg (100 + bid) mg ++ Table 2. Clini- cal re- pneof sponse pa- tients with plpyaf- epilepsy ter toler- ance induc- tion

0.5

1

0.5 0.5 Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. 9M3 G . 32 - 29 - 27 24 24 - 23 - - - - 3.2 - - 2.4 - - - 4.6 - - IGE 3.6 Rt. 2.6 - M/39 3.4 Bilat. F/18 - ETX IGE - 29 F/34 Lt. - M/26 CLZ IGE 28 LEV M/24 Rt. 27 M/26 JAE 26 IGE M/34 25 F/49 Bilat. 24 M/20 IGE 23 M/35 22 F/22 21 20 19 tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table FLE TLE TLE TLE FLE tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table E . 31 - 25 23 - - - 4.7 - - LEV 5.5 - 2.6 - LEV - LEV tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table . 30 27 - - - 1.6 - N/A - - tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table 11 tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table

tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table

tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table Table 2. Clini- cal re- pneof sponse pa- tients with plpyaf- epilepsy ter toler- ance induc- tion Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. rash. the before days 9 for tered minis- coad- was coxib ele- SSC- rash; the before days 3 for tered minis- coad- were ithromycin rox- and ramine, pheni- chlor- ine, bromhex- ++Codeine, rash; the before day one for tered minis- coad- was nolol pra- +Pro- chart. surface body der Brow- & Lung the udsing late calcu- was rash skin of extent ¶ onset; rigine lamot- of 3) days (14 weeks 2 within rash of dence inci- the as defined was rash skin cratic iosyn- *Id- eral; bilat- Bilat., left; Lt., right; Rt., epilepsy; sence ab- nile juve- JAE, epilepsy; tal occipi- OLE, epilepsy; poral totem- fron- FTLE, epilepsy; lobe ral tempo- TLE, epilepsy; lobe frontal FLE, epilepsy; alized gener- pathic idio- IGE, azepam; clon- CLZ, imide; sux- etho- ETX, etam; tirac- leve- LEV, rigine; lamot- LMT, up; follow- FU, area; surface body BSA, drug; tic antiepilep- AED, tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table The ± rash. the before days 9 for tered minis- coad- was coxib ele- SSC- rash; the before days 3 for tered minis- coad- were ithromycin rox- and ramine, pheni- chlor- ine, bromhex- ++Codeine, rash; the before day one for tered minis- coad- was nolol pra- +Pro- chart. surface body der Brow- & Lung the udsing late calcu- was rash skin of extent ¶ onset; rigine lamot- of 3) days (14 weeks 2 within rash of dence inci- the as defined was rash skin cratic iosyn- *Id- eral; bilat- Bilat., left; Lt., right; Rt., epilepsy; sence ab- nile juve- JAE, epilepsy; tal occipi- OLE, epilepsy; poral totem- fron- FTLE, epilepsy; lobe ral tempo- TLE, epilepsy; lobe frontal FLE, epilepsy; alized gener- pathic idio- IGE, azepam; clon- CLZ, imide; sux- etho- ETX, etam; tirac- leve- LEV, rigine; lamot- LMT, up; follow- FU, area; surface body BSA, drug; tic antiepilep- AED, tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table The ± rash. the before days 9 for tered minis- coad- was coxib ele- SSC- rash; the before days 3 for tered minis- coad- were ithromycin rox- and ramine, pheni- chlor- ine, bromhex- ++Codeine, rash; the before day one for tered minis- coad- was nolol pra- +Pro- chart. surface body der Brow- & Lung the udsing late calcu- was rash skin of extent ¶ onset; rigine lamot- of 3) days (14 weeks 2 within rash of dence inci- the as defined was rash skin cratic iosyn- *Id- eral; bilat- Bilat., left; Lt., right; Rt., epilepsy; sence ab- nile juve- JAE, epilepsy; tal occipi- OLE, epilepsy; poral totem- fron- FTLE, epilepsy; lobe ral tempo- TLE, epilepsy; lobe frontal FLE, epilepsy; alized gener- pathic idio- IGE, azepam; clon- CLZ, imide; sux- etho- ETX, etam; tirac- leve- LEV, rigine; lamot- LMT, up; follow- FU, area; surface body BSA, drug; tic antiepilep- AED, tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table The ± rash. the before days 9 for tered minis- coad- was coxib ele- SSC- rash; the before days 3 for tered minis- coad- were ithromycin rox- and ramine, pheni- chlor- ine, bromhex- ++Codeine, rash; the before day one for tered minis- coad- was nolol pra- +Pro- chart. surface body der Brow- & Lung the udsing late calcu- was rash skin of extent ¶ onset; rigine lamot- of 3) days (14 weeks 2 within rash of dence inci- the as defined was rash skin cratic iosyn- *Id- eral; bilat- Bilat., left; Lt., right; Rt., epilepsy; sence ab- nile juve- JAE, epilepsy; tal occipi- OLE, epilepsy; poral totem- fron- FTLE, epilepsy; lobe ral tempo- TLE, epilepsy; lobe frontal FLE, epilepsy; alized gener- pathic idio- IGE, azepam; clon- CLZ, imide; sux- etho- ETX, etam; tirac- leve- LEV, rigine; lamot- LMT, up; follow- FU, area; surface body BSA, drug; tic antiepilep- AED, tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table The ± rash. the before days 9 for tered minis- coad- was coxib ele- SSC- rash; the before days 3 for tered minis- coad- were ithromycin rox- and ramine, pheni- chlor- ine, bromhex- ++Codeine, rash; the before day one for tered minis- coad- was nolol pra- +Pro- chart. surface body der Brow- & Lung the udsing late calcu- was rash skin of extent ¶ onset; rigine lamot- of 3) days (14 weeks 2 within rash of dence inci- the as defined was rash skin cratic iosyn- *Id- eral; bilat- Bilat., left; Lt., right; Rt., epilepsy; sence ab- nile juve- JAE, epilepsy; tal occipi- OLE, epilepsy; poral totem- fron- FTLE, epilepsy; lobe ral tempo- TLE, epilepsy; lobe frontal FLE, epilepsy; alized gener- pathic idio- IGE, azepam; clon- CLZ, imide; sux- etho- ETX, etam; tirac- leve- LEV, rigine; lamot- LMT, up; follow- FU, area; surface body BSA, drug; tic antiepilep- AED, tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table The 12 ± rash. the before days 9 for tered minis- coad- was coxib ele- SSC- rash; the before days 3 for tered minis- coad- were ithromycin rox- and ramine, pheni- chlor- ine, bromhex- ++Codeine, rash; the before day one for tered minis- coad- was nolol pra- +Pro- chart. surface body der Brow- & Lung the udsing late calcu- was rash skin of extent ¶ onset; rigine lamot- of 3) days (14 weeks 2 within rash of dence inci- the as defined was rash skin cratic iosyn- *Id- eral; bilat- Bilat., left; Lt., right; Rt., epilepsy; sence ab- nile juve- JAE, epilepsy; tal occipi- OLE, epilepsy; poral totem- fron- FTLE, epilepsy; lobe ral tempo- TLE, epilepsy; lobe frontal FLE, epilepsy; alized gener- pathic idio- IGE, azepam; clon- CLZ, imide; sux- etho- ETX, etam; tirac- leve- LEV, rigine; lamot- LMT, up; follow- FU, area; surface body BSA, drug; tic antiepilep- AED, tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table The ± rash. the before days 9 for tered minis- coad- was coxib ele- SSC- rash; the before days 3 for tered minis- coad- were ithromycin rox- and ramine, pheni- chlor- ine, bromhex- ++Codeine, rash; the before day one for tered minis- coad- was nolol pra- +Pro- chart. surface body der Brow- & Lung the udsing late calcu- was rash skin of extent ¶ onset; rigine lamot- of 3) days (14 weeks 2 within rash of dence inci- the as defined was rash skin cratic iosyn- *Id- eral; bilat- Bilat., left; Lt., right; Rt., epilepsy; sence ab- nile juve- JAE, epilepsy; tal occipi- OLE, epilepsy; poral totem- fron- FTLE, epilepsy; lobe ral tempo- TLE, epilepsy; lobe frontal FLE, epilepsy; alized gener- pathic idio- IGE, azepam; clon- CLZ, imide; sux- etho- ETX, etam; tirac- leve- LEV, rigine; lamot- LMT, up; follow- FU, area; surface body BSA, drug; tic antiepilep- AED, tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table The ± rash. the before days 9 for tered minis- coad- was coxib ele- SSC- rash; the before days 3 for tered minis- coad- were ithromycin rox- and ramine, pheni- chlor- ine, bromhex- ++Codeine, rash; the before day one for tered minis- coad- was nolol pra- +Pro- chart. surface body der Brow- & Lung the udsing late calcu- was rash skin of extent ¶ onset; rigine lamot- of 3) days (14 weeks 2 within rash of dence inci- the as defined was rash skin cratic iosyn- *Id- eral; bilat- Bilat., left; Lt., right; Rt., epilepsy; sence ab- nile juve- JAE, epilepsy; tal occipi- OLE, epilepsy; poral totem- fron- FTLE, epilepsy; lobe ral tempo- TLE, epilepsy; lobe frontal FLE, epilepsy; alized gener- pathic idio- IGE, azepam; clon- CLZ, imide; sux- etho- ETX, etam; tirac- leve- LEV, rigine; lamot- LMT, up; follow- FU, area; surface body BSA, drug; tic antiepilep- AED, tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table The ± rash. the before days 9 for tered minis- coad- was coxib ele- SSC- rash; the before days 3 for tered minis- coad- were ithromycin rox- and ramine, pheni- chlor- ine, bromhex- ++Codeine, rash; the before day one for tered minis- coad- was nolol pra- +Pro- chart. surface body der Brow- & Lung the udsing late calcu- was rash skin of extent ¶ onset; rigine lamot- of 3) days (14 weeks 2 within rash of dence inci- the as defined was rash skin cratic iosyn- *Id- eral; bilat- Bilat., left; Lt., right; Rt., epilepsy; sence ab- nile juve- JAE, epilepsy; tal occipi- OLE, epilepsy; poral totem- fron- FTLE, epilepsy; lobe ral tempo- TLE, epilepsy; lobe frontal FLE, epilepsy; alized gener- pathic idio- IGE, azepam; clon- CLZ, imide; sux- etho- ETX, etam; tirac- leve- LEV, rigine; lamot- LMT, up; follow- FU, area; surface body BSA, drug; tic antiepilep- AED, tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table The ±

rash. the before days 9 for tered minis- coad- was coxib ele- SSC- rash; the before days 3 for tered minis- coad- were ithromycin rox- and ramine, pheni- chlor- ine, bromhex- ++Codeine, rash; the before day one for tered minis- coad- was nolol pra- +Pro- chart. surface body der Brow- & Lung the udsing late calcu- was rash skin of extent ¶ onset; rigine lamot- of 3) days (14 weeks 2 within rash of dence inci- the as defined was rash skin cratic iosyn- *Id- eral; bilat- Bilat., left; Lt., right; Rt., epilepsy; sence ab- nile juve- JAE, epilepsy; tal occipi- OLE, epilepsy; poral totem- fron- FTLE, epilepsy; lobe ral tempo- TLE, epilepsy; lobe frontal FLE, epilepsy; alized gener- pathic idio- IGE, azepam; clon- CLZ, imide; sux- etho- ETX, etam; tirac- leve- LEV, rigine; lamot- LMT, up; follow- FU, area; surface body BSA, drug; tic antiepilep- AED, tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table The ± AED, antiepilep- tic drug; BSA, body surface area; FU, follow- up; LMT, lamot- rigine; LEV, leve- tirac- etam; ETX, etho- sux- imide; CLZ, clon- azepam; IGE, idio- pathic gener- alized epilepsy; FLE, frontal lobe epilepsy; TLE, tempo- a lobe ral epilepsy; FTLE, fron- totem- poral epilepsy; OLE, occipi- tal epilepsy; JAE, juve- nile ab- sence epilepsy; Rt., right; Lt., left; Bilat., bilat- eral; *Id- iosyn- cratic skin rash was defined sthe as inci- dence frash of within 2 weeks (14 days

)of 3) lamot- rigine onset; ¶ extent fskin of rash was calcu- late udsing the Lung & Brow- der body surface chart. +Pro- pra- nolol was coad- minis- tered o one for day before the rash; ++Codeine, bromhex- ine, chlor- pheni- ramine, and rox- ithromycin were coad- minis- tered o 3 for days before the rash; SSC- ele- coxib was coad- minis- tered o 9 for days before the rash.

Table 2. Clini- cal re- pneof sponse pa- tients with plpyaf- epilepsy ter toler- ance induc- tion

The ± Posted on Authorea 27 Apr 2020 — CC BY 4.0 — https://doi.org/10.22541/au.158801938.89997370 — This a preprint and has not been peer reviewed. Data may be preliminary. tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table 13 tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table

tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table

tion induc- ance toler- ter af- epilepsy with tients pa- of sponse re- cal Clini- 2. Table Table 2. Clini- cal re- pneof sponse pa- tients with plpyaf- epilepsy ter toler- ance induc- tion