Common Adverse Drug-Drug Interactions in Dermatology: Oral Therapies

Abstract

Pharmacotherapy in dermatology can be especially complex and challenging: the wide array of comorbidities that patients present to care with and the spectrum of systemic oral therapies that are commonly prescribed in a standard dermatology practice increase the likelihood of adverse drug-drug interactions. Such interactions can range from neutralized drug efficacy to fatal adverse effects and are most commonly due to the potentiation or antagonism of cytochrome P450 metabolism or competitive renal excretion by an offending drug to affect the pharmacokinetics of concurrently dosed drugs. Drug-drug interactions can contribute to up to 60% of adverse drug reactions seen in the inpatient or immediate discharge setting, representing a potentially significant iatrogenic source of preventable healthcare costs, morbidity, and mortality in patient care.1,2 We review here the most common systemic treatments causing drug-drug interactions in standard dermatology practice.Methotrexate (MTX) acts through inhibition of dihydrofolate reductase and thymidylate synthetase, reducing folate formation and impairing DNA synthesis/repair, respectively. It is used at high doses in standard chemotherapy regimens and at low doses in psoriasis, Crohn disease, rheumatoid arthritis, and other autoimmune conditions. Toxicities, which can occur at all doses, include myelosuppression, hepatotoxicity, renal impairment, and pneumonitis. A near total reliance on renal excretion without production of inactive metabolites makes MTX vulnerable to drug-drug interactions when kidney function is affected. 3 In fact, MTX represents the highest severity of drug-drug interactions of all medications prescribed in the outpatient setting. Drug-drug interactions between systemic oral therapies in dermatology can result in preventable iatrogenic causes of patient morbidity and mortality. Most of these interactions are due to cytochrome P450 or renal excretion interactions. We review here a number of drugs and drug-drug interactions seen in general dermatology, including methotrexate, bexarotene, macrolides, cyclosporine, epinephrine, isotretinoin, spirinolactone, allopurinol, and oral contraceptives.