Drug Eruption and Interactions - PHARMACEUTICAL REVIEW

INTRODUCTION
Any drug can cause any rash.
An adverse drug reaction (ADR) – or an adverse drug
event (ADE) – describes any unwanted, unpleasant, noxious,
or harmful consequence associated with the use of medications
that have been administered in standard doses by the
proper route for the purposes of prophylaxis, diagnosis, or
treatment. This definition does not include abuse, overdose,
withdrawal, or error of administration. It appears that most
ADRs are related to the dose. Death is the ultimate adverse
drug event.
ADRs, major problems in drug therapy, are a few of the
leading causes of morbidity and mortality in health care and
they should be considered in the differential diagnosis of a
wide variety of medical disorders.
More and more people – primarily the older population –
are taking more and more prescription and over-the-counter
medications. New drugs are appearing in the medical
marketplace on an almost daily basis. More and more drug
reactions – in the form of cutaneous eruptions – are developing
from all drugs. It has been reported that more than
100,000 hospitalized people in the United States alone died
in 1999 as a result of medications.
While most adverse drug reactions are relatively mild, and
many disappear when the drug is either stopped or when the
dose has changed, other adverse drug reactions are often
more serious and longer lasting. Cutaneous drug eruptions
can mimic almost any inflammatory dermatosis. While most
eruptions are mild and self-limited, severe and life-threatening
eruptions do occur, as seen with the Stevens-Johnson
syndrome and toxic epidermal necrolysis.
About five percent of hospital admissions in the United
States are estimated to be for treatment of adverse drug
reactions. Also, each time a person is hospitalized, the risk of
having at least one adverse drug reaction is about fifteen percent;
and as many as one-third of all emergency department
and urgent care center visits are drug related.
ADRs are underreported and thus are an underestimated
cause of morbidity and mortality. The incidence and severity
of ADRs can be influenced by patient-related specific factors:
age, sex, disease, genetic factors, geographic factors, and by
drug-related factors: type of drug, route of administration
(intramuscular, intravenous and topical administrations are
more likely to cause hypersensitivity reactions; oral medications
are less likely to result in drug hypersensitivity), duration
of therapy, dosage, and bioavailability, as well as by
interactions with other drugs. More drugs – and more combinations
of drugs – are being used to treat patients than ever
before, and it has been estimated that fatal ADRs are the
third or fourth leading cause of death in the US.
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The terms ‘drug allergy,’ ‘drug hypersensitivity,’ and ‘drug
reaction’ are often used interchangeably. Drug allergy is
restricted specifically to a reaction mediated by IgE; drug
hypersensitivity is an immune-mediated response to a drug
agent in a sensitized patient; and drug reactions comprise all
adverse events related to drug administration, regardless of
etiology.
Adverse drug reactions have been arbitrarily classified
into six types:
1. Dose-related (e.g. Digoxin toxicity)
2. Non-dose-related (e.g. Immunological reactions)
3. Dose-related and Time-related (e.g. Corticosteroids)
4. Time-related (e.g. Tardive dyskinesia)
5. Withdrawal (e.g. Opiate or beta-blocker withdrawal)
6. Unexpected failure of therapy (e.g. Inadequate dosage
of an oral contraceptive)
Physicians in all specialties are often perplexed by the nature
of some of these problems. The few sources that are available
to identify the causes of many of these side effects cannot
be accessed by proprietary (Trade, Brand) names.
This Manual is a Drug Eruption Reference guide that
describes and catalogues the adverse cutaneous side effects
of more than 1000 commonly prescribed and over-thecounter
generic drugs (more than 50 of which are new to
this edition). All drugs have been listed and indexed by both
their Generic and Trade (Brand) names for easy accessibility.
As a result of space constraints, several of the Generic
drugs from earlier editions have been extirpated either
because they have been withdrawn from the marketplace or
that they are rarely if ever prescribed now. These, please
note, are still available – and always will be – on the website –
www.drugeruptiondata.com.
In addition to adverse cutaneous reactions, there are
many severe, hazardous interactions that are known to
occur between two or more drugs. I have incorporated only
the highly, clinically significant drug interactions that can trigger
potential harm, and that could be life-threatening. These
interactions are predictable and well documented in controlled
studies; they should be avoided. This subdivision
denoting hazardous interactions has been omitted from
those drugs where no such interactions have been reported.
For each drug, I have listed all the known adverse side
effects – in the form of drug reactions – that can result from
the use of the matching drug.
Appropriate references (author, journal or book, volume,
date and page) for each side effect of every drug have been
cited. Where there is more than one reference to a specific