Clinical relevance of linezolid-associated serotonin toxicity.

OBJECTIVE: To evaluate and review the literature surrounding serotonin toxicity in patients receiving linezolid and determine the clinical relevance of this reaction. DATA SOURCES: Literature was accessed via MEDLINE/PubMed and Google Scholar (both through February 2013) using the search terms linezolid, serotonin syndrome, serotonin toxicity, and adverse reaction. STUDY SELECTION AND DATA EXTRACTION: Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. DATA SYNTHESIS: Linezolid exhibits mild, nonselective inhibition of monoamine oxidase and has been associated with serotonin toxicity when used in combination with other serotonergic agents. Based on published reports, the incidence of linezolid-associated serotonin toxicity is between 0.54% and 18.2%. Our review identified 32 documented cases, including 3 fatalities. Most cases occurred in patients concurrently receiving selective serotonin reuptake inhibitors. Receipt of multiple agents with serotonergic activity seems to increase the risk of serotonin toxicity. Both onset and resolution of symptoms varied from hours to days. CONCLUSIONS: Current Food and Drug Administration recommendations to avoid the use of linezolid in patients receiving select serotonergic agents highlight the need to carefully balance the risk/benefit ratio in this situation. Although linezolid has been available for 12 years, reports of serotonin toxicity with this agent are uncommon. While clinicians should be aware of this potentially severe interaction and closely monitor patients who are receiving linezolid in combination with serotonergic agents, our findings show that linezolid is not contraindicated in this situation.

Ecallantide for treatment of acute attacks of hereditary angioedema.

PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, dosage, administration, adverse effects, and place in therapy of ecallantide, a kallikrein inhibitor for the treatment of hereditary angioedema (HAE), are reviewed. SUMMARY: Ecallantide is the first member of the kallikrein inhibitor class approved for the treatment of acute attacks of HAE. Ecallantide works by binding to kallikrein, preventing the conversion of kininogen to bradykinin, which reduces vascular permeability, thus reducing the swelling associated with acute attacks of HAE. Ecallantide has been studied for the treatment of HAE in three Phase II studies and two Phase III studies. These studies were collectively known as the EDEMA (Evaluation of DX-88's Effect in Mitigating Angioedema) studies. Phase III clinical trials found that ecallantide is superior to placebo in ameliorating patient symptoms associated with acute attacks of HAE at any anatomical site. Ecallantide has a favorable safety profile, with the most common adverse effects being gastrointestinal effects, headache, and injection site reactions. The most severe adverse effects of ecallantide are the risk of anaphylaxis and the possible development of antiecallantide antibodies. A risk evaluation and mitigation strategy program has been approved by the Food and Drug Administration to help ensure the safety and efficacy of ecallantide use. The recommended dose is 30 mg given as three separate subcutaneous injections. CONCLUSION: Ecallantide is a novel agent approved for the treatment of acute attacks of HAE at any anatomical site. It is one of only three medications approved for this indication in the United States, presents a unique mechanism of action, and appears to be safe and effective when used for its labeled indication.