Clinical manifestations

True hypersensitivity adverse drug reactions are great imitators of disease and may present with involvement of any organ system, including systemic reactions such as anaphylaxis

Drug reactions commonly manifest with dermatologic symptoms caused by the metabolic and immunologic activity of the skin

• – The most common dermatologic manifestation of drug reaction is morbilliform rashes

  • Typically, an erythematous (red), maculopapular (flat to bumpy) rash that appears within one to three weeks after drug exposure, originates on the trunk, and eventually spreads to the limbs

  • Urticaria (hives) and swelling may be a typical manifestation of a truly allergic reaction, but it may appear with pseudoallergic reactions as well

• – Rarer severe nonallergic, hypersensitivity cutaneous reactions may also occur

  • For example, erythema multiforme, Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), are severe and life-threatening reactions

  • These represent bullous skin diseases that require prompt recognition because of their association with significant morbidity and mortality

  • These conditions are associated often with development of a fever, blistering lesions, and mucous membrane involvement

Therapy and management

The most important and effective therapeutic measure in managing drug-hypersensitivity reactions is the discontinuation of the offending medication, when possible

Alternative medications with unrelated chemical structures should be substituted where possible

The clinical consequences of medication cessation or substitution should be closely monitored (precipitation of an SSRI or BZ withdrawal)

In the majority of patients, rash symptoms will resolve within two weeks if the diagnosis of drug hypersensitivity is correct

Additional therapy for drug-hypersensitivity reactions is largely supportive and symptomatic (antihistamine)

• – Systemic corticosteroids may speed recovery in severe cases of drug hypersensitivity

• – Topical corticosteroids and oral antihistamines may improve dermatologic symptoms

The severe drug reactions of SJS or TEN require additional intensive therapy where patients should be evaluated and admitted to the hospital

Anaphylactic responses, which include rashes, facial swelling, stridor, or difficulty breathing require prompt and urgent care

• – In an emergency room setting, epinephrine may be injected and systemic steroids administered while airway and vital sign support are ongoing

Posttest self-assessment question and answer

How much different can a generic drug be from its brand name counterpart, based upon individual regulatory tests of bioequivalence?

A. 0%

B. 5%

C. 15%

D. 25%

Answer: D

A generic drug may differ by 21% from the parent brand name product. When switching from a brand name to a generic, some patients may develop new side effects if the generic is actually more bioavailable. Other patients may have a return of psychiatric symptoms if the generic is less bioavailable. In another scenario, a patient may be changed from one generic to another as pharmacies try to purchase the most economical generic available. Take an example where a patient is actually on a generic antidepressant that is 20% more bioavailable than the brand name drug, but a year later is switched by the pharmacy to a new generic that is 10% less bioavailable than the parent brand name drug. This is actually a 30% lessening of antidepressant dose and tempts fate for a psychiatric relapse, even more than the initial brand name-to-generic scenario noted initially. Thankfully, this is often the exception and not the rule. However, clinicians must be astute regarding this relationship in certain acutely relapsing patients.

References

1.Orange Book Annual Preface, Statistical Criteria for Bioequivalence. Approved Drug Products with Therapeutic Equivalence Evaluations, 29th edn. U.S. Food and Drug Administration Center for Drug Evaluation and Research, 2009. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm079068.htm. Accessed August 10, 2009.

2.http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingGenericDrugs/ucm167991.htm. Accessed May 9, 2011.

3.Davit BM, Nwakama PE, Buehler GJ, et al. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration. Ann Pharmacother 2009; 43:1583–97.

4.Riedl MA, Casillas AM. Adverse drug reactions: types and treatment option. Am Fam Phys 2003; 68:1781–91.

Patient file

The Case:

The woman who would not leave her car

The Question:

What to do when obsessive compulsive disorder with poor insight is resistant to treatment

The Dilemma:

Rational subsequent polypharmacy trials may help, but fail to achieve remission