Table Of Content24 th
EDITION
Jerome Z. Litt
Neil H. Shear
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The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device
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CONTENTS
Introduction v
Drug profiles: generic names A–Z 1
Descriptions of important reactions 305
Drugs that cause important reactions 311
Main classes of drugs 345
Classes of drugs that can cause important interactions 351
Class reactions 353
ACE inhibitors 353
Antiarrhythmics 355
Antibiotics, macrolide 357
Anticonvulsants 358
Antidepressants, tricyclic 361
Antihistamines (H1) 362
Antimalarials 363
Antipsychotics 365
Benzodiazepines 367
Beta blockers 368
Biologics 369
Bisphosphonates 374
Calcium channel blockers 375
Cephalosporins 377
Disease-modifying antirheumatic drugs (DMARDS) 378
DPP-4 inhibitors 383
Epidermal growth factor receptor (EGFR) inhibitors 384
Fluoroquinolones 387
Non-steroidal anti-inflammatory drugs (NSAIDS) 389
Proton pump inhibitors (PPI) 392
Statins 394
TNF inhibitors 395
Tyrosine-kinase inhibitors 398
Concordance of synonyms and trade names with
generic names 403
iii
To Vel – my Muse
JZL
Editors’ introductory notes
Anydrughasthepotentialtocauseanadversereaction.Anadversedrugreaction(ADR)isanunwanted,unpleasant,noxious,
orharmfulconsequenceassociatedwiththeuseofamedicationthathasbeenadministeredinastandarddosebytheproper
route, for the purpose of prophylaxis, diagnosis, or treatment. Death is the ultimate adverse drug event.
ADRsareamajorproblemindrugtherapy.Theyarethemostcommonofalliatrogenicillnessesthatcomplicateupto15%
oftherapeuticdrugcourses,andarealeadingcauseofmorbidityandmortalityinhealthcare.ADRsshouldthereforebecon-
sideredinthedifferentialdiagnosisofawidevarietyofmedicaldisorders.Manymorepeople–particularlytheelderly–are
takingmoreandmoreprescriptionandover-the-countermedications.Inaddition,newdrugsareappearinginthemedical
marketplaceonanalmostdailybasis.Itisunsurprising,then,thatmoreandmoredrugreactionsandcutaneouseruptionsare
emerging.
Prevention,diagnosisandtreatmentofadversedrugeventsarebecomingincreasinglycomplex,anditistobeexpectedthat
physiciansinallspecialtiesareoftenperplexedbythenatureofADRs.Tothisend,Inowofferanewandimprovededition
thathasevolvedfromthetreasuredDrugEruptionReferenceManualofpreviouseditions.Ihopethatyouwillfindthisnew
edition informative and valuable.
Enjoy!
Jerome Z. Litt, M.D.
“Is it safe?”
Iamfrequentlyaskedthatbigquestionfromapatient:"Isitsafe?"Thistextismeanttohelpallprescribers,dispensersand
patientsunderstandwhattheriskofharmmightbe;whetheritisfromadrugreactionorinteraction,Litt'sisthego-toinfor-
mationsource.Howdoesthisinformationhelpanswertheunanswerable?Simplyput,safetyisaprocess,notaquestion.With
therightinformationathandasafeenvironmentcanthrive;themostup-to-daterelevantdatahelppeelawaybackground
noisefromaseeminglyinfinitenumberofsources.Thisneweditionaddsadditionalsupporttoariskmanagementenviron-
ment,andwewillcontinuetoprovidethemostup-to-dateandrelevantinformation.Ilookforwardtofeedbackandsugges-
tions. I thank Jerry Litt for this great opportunity and the awesome work of the team at T&F to keep on top of all new
medications that are making the landscape even more complex.
Neil H. Shear, M.D., F.R.C.P.C., F.A.C.P.
Litt’s Drug Eruption & Reaction Manual – at a glance
This 24th edition has been revised and updated throughout to present a quick clinical reference guide to adverse drug
reactions(ADRs),sideeffects,druginteractionsandothersafetyinformationforprescriptionandover-the-countermedica-
tions.Thereisalsomaterialonreactionscausedbyclassesofdrugs,enablingyoutoseeataglancewhether areactionis
common to all the drugs in that particular class, or to a majority of them, or only to a significant few.
The aims of this edition remain:
1. To help medical practitioners make informed and safe decisions when diagnosing and prescribing, and also when
generally seeking information.
2. To help healthcare professionals remain pharmacovigilant.
3. Toprovideallphysicians,lecturers,educatorsandpharmacistswithaneasy-to-useandreliablequickreferencetool.
Thefullandcomprehensivepictureforalldrugs–fromwhichourinformationderives–canbefoundatourwebsitedatabase
(www.drugeruptiondata.com),whichisupdatedcontinually.Spaceinthemanualis,unfortunately,constrained,sofullprofiles
forvariousgenericdrugshavebeeneliminatedfromthisprintmanualbecauseeithertheyhavebeenwithdrawnfromthe
marketplaceortheyarerarely,ifever,prescribedtoday;newtothiseditionarelinkstotheirbasicprofilesinthewebsite
database. Important new drugs added to this edition of the manual are noted with an asterisk.
v
A note on ADRs
The incidence and severity of ADRs are influenced by a number of factors:
1. Patient-related factors:
(cid:127) Age – geriatric, pediatric, adolescent . . . older patients are taking more medications—hence more of a possibility of
developing reactions; pediatric patients have more delicate skins; hormonal changes occur in adolescents . . . All these
factors play roles in the development of possible adverse reactions.
(cid:127) Gender – male or female – and if the latter, then pregnant/breast-feeding/menopausal . . .
(cid:127) Disease – not only the disease being treated, but also other pre-existing health conditions and comorbid diseases. For
example, atopic patients are at increased risk for serious allergic reactions. Also, there would be an increased risk for
hypersensitivity drug reactions if the patient has asthma or lupus erythematosus.
(cid:127) Genetics – a patient could have abnormal drug metabolism by cytochrome P450 due to inheriting abnormal alleles.
(cid:127) Geography – patients living in sunny climes could develop photoxicities from photosensitizing drugs more readily than
those who inhabit cooler, less sunny climates.
2. Drug-related factors:
(cid:127) Type/classofdrug–forexample,thereisaheightenedriskofhypersensitivitywiththeuseofbeta-blockers(seefurtherthe
tables on class reactions).
(cid:127) Durationoftherapy–thelongerapatientmaintainsthetherapy,thegreaterthepossibilitythathe/shecoulddevelopa
reaction.
(cid:127) Dosage – the greater the dosage, the more likely an adverse side effect.
(cid:127) Bioavailability – the extent to and rate at which the drug enters systemic circulation, thereby accessing the site of action.
(cid:127) Interactionswithotherdrugs–forexample,synergisticQTprolongationcanoccurwhentwoQTprolongingagents,such
as erythromycin + ritonavir, are used together.
(cid:127) Routeofadministration–intramuscular,intravenous,subcutaneous,andtopicaladministrationsaremorelikelytocause
hypersensitivity reactions; oral medications are less likely to result in drug hypersensitivity.
Theterms“drugallergy,”“drughypersensitivity,”and“drugreaction”areoftenusedinterchangeably.Drugallergyspecific-
allyreferstoareactionmediatedbyIgE;drughypersensitivityisanimmune-mediatedresponsetoadrugagentinasensitized
patient; and drug reactions comprise all adverse events related to drug administration, regardless of etiology.
Vigilance at point of care:
Whilethepossibilitiesforadversedrugreactionsseemendless,wemustbeonthelookoutforanynewmedication(s)the
patientmightbetaking.Athorough,detailedhistoryofallmedicationsmustbemadeinordertoelicitanyremotepossibility
that the drug in question might be the culprit for the side effect. People do not often realize that the common over-the-
counteranalgesics– aspirin,Tylenol,Advil,Motrin, Naprosyn,andothers – are actuallymedications.Herbals andsupple-
ments such as St. John’s wort, ginkgo biloba, and echinacea can be responsible for various hypersensitivity reactions. For
example, St. John’s wort, in particular, interacts adversely with SSRIs and tricyclic antidepressants.
Contents of the book, and how to use them
1. TheA–Z
Themajorportionofthemanuallistsinalphabeticalorderthe900+genericdrugs,biologics,andsupplements,and
theadversereactionsthatcanarisefromtheiruse.Anasteriskagainsttheentrytitleindicatesthisdrugisnewtothis
edition.IfyoudonotfindadruginthemainA–Zlistingunderthenameyouknowitby,youcanturntotheconcord-
ance of synonyms and trade names to find the generic name it will be listed under. Occasionally a drug has been
omitted from the listing but a cross-reference will link to the profile found in our website database
(www.drugeruptiondata.com).
vi
Trade (Brand) name(s) are then listed alphabetically. When there are many trade names, the ten (or so) most
commonly recognized ones are listed.
Followingthetradenamesis–inparentheses–thelatestnameofthepharmaceuticalcompanythatmarketsthedrug.
Many of the names of the companies have changed from earlier editions of this manual because of acquisitions,
mergers, and other factors in the pharmaceutical industry.
Next appear the Indication(s), the Class in which the drug belongs, and the Half-life of each drug, where known.
Druginteractions:manysevere,hazardousdrug–druginteractionsarerecorded.Onlyclinicallysignificantdruginter-
actionsthathavebeenreportedtotriggerpotentialharmandthatcouldbelifethreateninghavebeenincludedherein
the profile. These interactions are predictable and well documented in controlled studies; they should be avoided.
Pregnancycategory:fornewdrugsapprovedonorafter30June,2015thisfieldgives(whereavailable)abriefsum-
maryofthefullstatementreflectingtheriskforpregnantwomenasgivenintheprescribingguidelines;healthcare
providers are advised to check the individual label where necessary.
An explanation of the categories for older drugs (A, B, C, D and X) can be found on our website
www.drugeruptiondata.com.
AdverseDrugReactions:undereachdrugprofileisalistofrelatedADRs.Theseadverseeventshavebeenclassified
under the following categories: Skin, Hair, Nails, Mucosal, Cardiovascular, Central Nervous System,
Neuromuscular/Skeletal, Gastrointestinal/Hepatic, Respiratory, Endocrine/Metabolic, Genitourinary,
Renal,Hematologic,Otic,Ocular,Local,Other.
Within each category, the reactions are listed alphabetically.Thus, the order of listing does not reflect severity or
frequency in any way.
Theterminologyusedtolistreactionpatternshasbeensimplifiedasfaraspossiblebyeliminating,forthemostpart,
tags such as “like” (as in “-Psoriasis-like”), “-reactivation,” “-syndrome,” “-dissemination,” “-iform,” etc.
Thenumberofreportsisgivenforeachreactioninsquarebrackets.Theincidenceofthemostimportantreactionsis
given in parentheses where indicated (usually from the full prescribing information for the relevant drug). For
example, the profile for Amoxicillin begins:
Skin
AGEP [28]
Anaphylactoid reactions/Anaphylaxis [15]
Angioedema (<10%) [5]
This means that we have 28 journal articles referring to occurrence of AGEP (acute generalized exanthematous
pustulosis);15articlesmentioningtheoccurrenceofanaphylaxis;and5articlesdiscussingangioedema,asreactionsto
AmoxicillinwithintheSkincategory.Allthesearticlesappearonthewebsitewww.drugeruptiondata.comtogether
with links to the article abstracts on PubMed®. Additionally, the incidence of angioedema as a reaction has been
reported as up to 10%.
On some occasions, there are very few adverse reactions to a specific drug. These drugs are still included in the
manual as there is a positive significance in negative findings.
2. Importanteruptions/reactions
i) This section of the manual includes a listing of descriptions of important eruption and reaction patterns. Over 40
eruptions/reactions are described here in alphabetical order, from Acanthosis nigricans to Xerostomia.
ii) Followingthissectionarelistsofalldrugsthathavebeenfoundtocausetheseimportanteruptions/reactions.This
section is a quick look-up tool for drugs that cause important reaction patterns.
(Descriptions of several other reactions, and lists of drugs associated with these reactions, can be found on our
website –www.drugeruptiondata.com.)
iii) Wethenhavealistofthemainclassesofdrugs,from5-HT1agoniststoXanthinealkaloids,asaquickreferenceguide.
iv) Therefollowlistsoftheclassesofdrugsmostlikelytocauseimportantinteractionswithotherdrugs,withthedrugsin
those classes.
v) Wethenhaveanenlargedsectionoftablesofclassreactions,enablingyoutoseeataglancewhetherareactionis
common to all the drugs in that particular class, or to a majority of them, or only to a significant few.
vii
3. TheConcordance
Thefinalpartofthemanualisaconcordancetomatchsynonyms(notedinitalic)andtradenameswiththegeneric
drugname.Ifyouknowonlythesynonymortradename,youcanusethislisttofindthecorrespondinggenericname
to look up in the main A–Z listing section of the book.
viii
Hypertriglyceridemia(2–6%)
ABACAVIR ABATACEPT
Renal
Fanconisyndrome[2]
Tradenames:Epzicom(ViiV),Triumeq(ViiV), Tradename:Orencia(Bristol-MyersSquibb)
Trizivir(ViiV),Ziagen(ViiV) Hematologic Indications:Rheumatoidarthritis,juvenile
Indications:HIVinfectionsincombinationwith Agranulocytosis[3] idiopathicarthritisinpediatricpatients6yearsof
otherantiretrovirals Neutropenia(2–5%) ageandolder
Class:Nucleosideanalogreversetranscriptase Other Class:Disease-modifyingantirheumaticdrug
inhibitor Adverseeffects[4] (DMARD),T-cellco-stimulationmodulator
Half-life:1.5hours Infection(5%) Half-life:1223days
Clinicallyimportant,potentiallyhazardous Clinicallyimportant,potentiallyhazardous
interactionswith:alcohol,arbutamine, interactionswith:adalimumab,anakinra,
argatroban,arsenic,darunavir,ganciclovir, ABALOPARATIDE * certolizumab,denosumab,echinacea,etanercept,
lopinavir,methadone,phenobarbital,phenytoin, golimumab,infliximab,lenalidomide,livevaccines,
proteaseinhibitors,ribavirin,rifampin,tipranavir, natalizumab,pimecrolimus,sipuleucel-T,
Tradename:Tymlos(RadiusHealth)
valganciclovir tacrolimus,TNFantagonists,trastuzumab
Indications:Osteoporosisinpostmenopausal
Pregnancycategory:C Pregnancycategory:C
women
Importantcontra-indicationsnotedinthe Importantcontra-indicationsnotedinthe
Class:Parathyroidhormoneanalog
prescribingguidelinesfor:nursingmothers prescribingguidelinesfor:nursingmothers;
Half-life:<2hours
Note:Epzicomisabacavirandlamivudine; pediatricpatients
Clinicallyimportant,potentiallyhazardous
Triumeqisabacavir,dolutegravirandlamivudine;
interactionswith:noneknown
Trizivirisabacavir,lamivudineandzidovudine. Skin
Pregnancycategory:N/A(Notindicatedfor
Warning:HYPERSENSITIVITYREACTIONS, Basalcellcarcinoma[3]
useinfemalesofreproductivepotential)
LACTICACIDOSISandSEVERE Eczema[2]
Importantcontra-indicationsnotedinthe
HEPATOMEGALY,andEXACERBATIONSOF Herpessimplex(<5%)[3]
prescribingguidelinesfor:pediatricpatients
HEPATITISB Herpeszoster[3]
Warning:RISKOFOSTEOSARCOMA
Hypersensitivity[2]
Skin Malignancies[10]
Cardiovascular
Anaphylactoidreactions/Anaphylaxis(3%) Psoriasis[13]
Orthostatichypotension(<4%)
[3] Rash(4%)[6]
Palpitation(5%)
Exanthems[2] Sjo¨gren’ssyndrome[4]
Tachycardia(2%)
Hypersensitivity(8–9%)[69] Squamouscellcarcinoma[5]
Lipoatrophy[2] Central NervousSystem Vasculitis[2]
Rash(5–7%)[17] Headache(8%) Mucosal
Stevens-Johnsonsyndrome[2] Vertigo(dizziness)(2–10%)
Stomatitis[3]
Toxicepidermalnecrolysis[2] Neuromuscular/Skeletal
Cardiovascular
Cardiovascular Asthenia(fatigue)(3%)
Hypertension(7%)[4]
Myocardialinfarction[9] Gastrointestinal/Hepatic Hypotension[2]
CentralNervous System Abdominalpain(3%) CentralNervousSystem
Abnormaldreams(10%)[2] Nausea(8%)
Fever(5%)[2]
Anxiety(5%) Endocrine/Metabolic Headache(5–18%)[6]
Chills(6%)
Hypercalcemia(3%)[2] Vertigo(dizziness)(9%)[3]
Depression(6%)
Hyperuricemia(25%) Neuromuscular/Skeletal
Fever(6%)[2]
Headache(7–13%)[4] Genitourinary Asthenia(fatigue)[2]
Insomnia[2] Hypercalciuria(11%) Backpain(7%)[2]
Migraine(7%) Urolithiasis(2%) Paininextremities(3%)
Neuropsychiatricdisturbances[3] Local Gastrointestinal/Hepatic
Sleeprelateddisorder(10%) Injection-siteedema(10%) Abdominalpain(5%)
Vertigo(dizziness)(6%)[3] Injection-siteerythema(58%) Diarrhea(5%)[3]
Neuromuscular/Skeletal Injection-sitepain(9%) Dyspepsia(6%)
Asthenia(fatigue)(7–12%)[2] Gastroenteritis[5]
Boneorjointpain(5–6%) Nausea(5%)[2]
Myalgia/Myopathy(5–6%)[2] ABARELIX Vomiting[2]
Gastrointestinal/Hepatic Respiratory
Abdominalpain(6%) See:www.drugeruptiondata.com/drug/id/1011 Bronchitis(<13%)[4]
Diarrhea(7%)[2] Cough(5–8%)
Gastritis(6%) Influenza(5–13%)[2]
Hepatotoxicity[4] Nasopharyngitis(12%)[6]
Nausea(7–19%)[5] Pharyngitis[3]
Vomiting(2–10%) Pneumonia(<5%)[7]
Pulmonarytoxicity[2]
Respiratory
Rhinitis(<5%)[2]
Bronchitis(4%)
Sinusitis(5–13%)[3]
Cough[2]
Tuberculosis[2]
Pneumonia(4%)
Upperrespiratorytractinfection(>10%)
Endocrine/Metabolic [9]
ALTincreased(6%) Genitourinary
ASTincreased(6%)
Urinarytractinfection(5–13%)[10]
Hyperamylasemia(2–4%)
Litt’s Drug Eruption & Reaction ManualB 2018 by Taylor & Francis Group, LLC 1
