Table Of ContentIn memoriam
Jerome Z. Litt, M.D.
26 th
EDITION
Neil H. Shear, MD, FRCPC, FACP
Professor of Dermatology and
Clinical Pharmacology and Toxicology
University of Toronto, Canada
CRC Press
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reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or
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CONTENTS
Introductory notes vii
Drug profiles: generic names A–Z 1
Descriptions of important reactions 361
Drugs that cause important reactions 367
Main classes of drugs 401
Class reactions 407
ACE inhibitors 407
Antiarrhythmics 409
Antibiotics, imidazole 411
Antibiotics, macrolide 412
Anticonvulsants 413
Antidepressants, tricyclic 416
Antihistamines (H1) 417
Antimalarials 418
Antipsychotics 420
Antiretrovirals 422
Benzodiazepines 424
Beta blockers 425
Biologics 426
Bisphosphonates 431
Calcium channel blockers 432
Cephalosporins 434
Corticosteroids, topical 435
Disease-modifying antirheumatic drugs (DMARDS) 437
DPP-4 inhibitors 442
Epidermal growth factor receptor (EGFR) inhibitors 443
Fluoroquinolones 446
Non-steroidal anti-inflammatory drugs (NSAIDS) 448
Proton pump inhibitors (PPI) 451
Statins 453
TNF inhibitors 454
Tyrosine-kinase inhibitors 457
Genetic tables 461
Concordance of synonyms and trade names with
generic names 473
v
A Note from the Editor
Patients frequently ask about their prescribed drug: “Is it safe?” This text is meant to help all prescribers, dispensers and
patientsunderstandwhattheriskofharmmightbe;whetheritisfromadrugreactionorinteraction,Litt’sD.E.R.M.isthego-
to information source. How does this information help answer the unanswerable? Simply put, safety is a process, not a
question.
Withtherightinformationathandasafeenvironmentcanthrive;themostup-to-daterelevantdatahelppeelawayback-
groundnoisefromaseeminglyinfinitenumberofsources.Thisneweditionaddsadditionalsupporttoariskmanagement
environment,andwewillcontinuetoprovidethemostup-to-dateandrelevantinformation;soweincludeknowngenetic
risks that are associated with drug reactions and can be screened prior to drug therapy. I look forward to feedback and
suggestions.
Litt’s D.E.R.M. is more than a text. It is part of a community of resources to make prescribing safe and to help optimize
therapy.
Tothatendrememberthattheon-lineinformationisalmostdoublewhatyouseeinthetext.Andittooiskeptup-to-date!
FormeinmypracticeIaminlovewiththeLittapp–aneasyportaltotheonlinedatabase,particularlyifyouaremoving
betweenvariousworkspaces.Onepatientonthreecriticaldrugsdevelopedarashonday8oftreatment;theLittappgave
meeasyaccesstothelikelihoodofanexathematousrashforeach,andIcouldprovideaclearandthoughtfuldirectionforthe
immediate future.
The“2020DrugReactionoftheYear”formeisallopurinol-inducedSCAR(severecutaneousadversereaction).Bothtoxic
epidermalnecrolysisandDReSS are too oftendueto allopurinolexposure;more horrific to me is that in many casesthis
shouldneverhavehappened.Thereisasimplegenetictest(HLA-B*58:01)thatcanandshouldbedoneinpatientswitha
southAsianbackground;thistestingisavailableandknowntopreventSCAR.Whatwillittaketomakedrugsafetyarealityin
clinicalpractice?Idonotmeanthisasarhetoricalquestion.LetussaythatsomethingMUSTbedonetochangethemindsetof
prescribers and to put safety first.
Neil H. Shear, M.D., F.R.C.P.C., F.A.C.P.
Litt’s Drug Eruption & Reaction Manual – at a glance
This26theditionhasbeenrevisedandupdatedthroughouttopresentaquickclinicalreferenceguidetoadversedrugreac-
tions(ADRs),sideeffects,druginteractionsandothersafetyinformationforprescriptionandover-the-countermedications.
There is also material on reactions caused by classes of drugs, enabling you to see at a glance whether a reaction is
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), which is updated continually. Space in the manual is, unfortunately, constrained.
vii
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,thereisaheightenedriskofangioedemawiththeuseofACEinhibitors(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.
viii
Contents of the book, and how to use them
1. TheA–Z
The major portion of the manual lists in alphabetical order the 1500 most consulted and most important generic
drugs,biologics,andsupplements,andtheadversereactionsthatcanarisefromtheiruse.Ifyoudonotfindadrugin
themainA–Zlistingunderthenameyouknowitby,youcanturntotheconcordanceofsynonymsandtradenamesto
find the generic name it will be listed under.
Trade(Brand)name(s)arelistedalphabetically.Whentherearemanytradenames,theten(orso)mostcommonly
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.
Pregnancy category: for new drugs approved on or after 30 June 2015 this field gives (where available) a brief
summaryofthefullstatementreflectingtheriskforpregnantwomenasgivenintheprescribingguidelines;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
underthefollowingcategories:Skin,Hair,Nails,Mucosal;Cardiovascular,Central Nervous System,Endo-
crine/Metabolic, Gastrointestinal/Hepatic, Genitourinary, Hematologic, Local, Neuromuscular/Skeletal,
Ocular,Otic,Renal,Respiratory,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 [17]
Angioedema (<10%) [5]
This means that we have 28 journal articles referring to occurrence of AGEP (acute generalized exanthematous
pustulosis);17articlesmentioningtheoccurrenceofanaphylaxis;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.
ix
