Association of asthma therapy and Churg-Strauss syndrome: an analysis of postmarketing surveillance data.

BACKGROUND: Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis (AGA), is a rare vasculitis that occurs in patients with bronchial asthma. The nature of the association of CSS with various asthma therapies is unclear. OBJECTIVE: This study investigated the associations of different multidrug asthma therapy regimens and the reporting of AGA (the preferred code for CSS in the coding dictionary for the Adverse Event Reporting System [AERS]) by applying an iterative method of disproportionally analysis to th AERS database maintained by the US Food and Drug Administration. METHODS: The public-release version of the AERS database was used to identify reports of AGA in patients receiving asthma therapy. Reporting of AGA was examined using iterative disproportionality methods in patients receiving > or =1 of the following drug classes: inhaled corticosteroid (ICS), leukotriene receptor antagonist (LTRA), short-acting beta(2)-agonist (SABA), or long-acting beta(2)-agonist (LABA). The Bayesian data-mining algorithm known as the multi-item gamma poisson shrinker was used to determine the relative reporting rates by calculation of the empirical Bayes geometric mean (EBGM) and its 90% CI (EB05 = lower limit and EB95 = upper limit) for each drug. Subset analyses were performed for each drug with different medication combinations to differentiate the relative reporting of AGA for each. RESULTS: A strong association was found between LTRA use and AGA (EBGM = 104.0, EB05 = 95.0, EB95 = 113.8) that persisted with all combinations of therapy studied. AGA was also associated with the ICS, SABA and LABA classes (EBGM values of 27.8, 14.6 and 40.4, respectively). However, the latter associations were mostly dependent on the presence of concurrent LTRA and, to a lesser extemt, oral corticosteroid therapy and became negligible (ie, EB05 < 2) for patients who were not receiving these concurrent treatments. CONCLUSIONS: Differences based on relative reporting were observed in the patterns of association of AGA with LTRA, ICS, and beta(2)-agonist therapies. A strong association between LTRA use and AGA was present regardless of the use of other asthma drugs.

Safety of EMBEda (morphine sulfate and naltrexone hydrochloride) extended-release capsules: review of postmarketing adverse events during the first year.

BACKGROUND: EMBEDA@ (morphine sulfate and naltrexone hydrochloride) extended-release capsules, indicated for management of chronic, moderate-to-severe pain, contain pellets of morphine sulfate with a core of sequestered naltrexone, an opioid antagonist. OBJECTIVE: To review postmarketing adverse event (AE) reports received during first year following approval. METHODS: All postmarketing AEs reported to the manufacturer were reviewed. RESULTS: During the reporting period, approximately 97,000 prescriptions for EMBEDA were dispensed. One hundred eighty-two case reports containing 429 events were reviewed; 33 (18 percent) were reported as serious and 149 (82 percent), as non-serious. Of 429 AEs reported, the most common were drug ineffective (7 percent), headache (6 percent), drug withdrawal syndrome (6 percent), and nausea (4 percent). Seven cases involved oral overdose; of these, two suicide attempts resulted in fatalities. Product tampering was confirmed in six cases; suspected in five. No cases of confirmed tampering resulted in fatality; none resulted in symptoms typically associated with opioid overdose. Three were associated with opioid withdrawal symptoms, suggesting that naltrexone released during tampering potentially blocked the opioid effects. Twenty-five cases involving reported withdrawal or symptoms of withdrawal were reviewed; most were associated with dose interruption, capsule manipulation, history of drug abuse, or intolerance to a new opioid regimen. CONCLUSIONS: Results suggest that the safety profile of EMBEDA is consistent with that of an extended-release morphine formulation. Reports of exposure to tampered product yielded either withdrawal reactions or events not typical of opioid abuse. The clinical effects of EMBEDA in the context of misuse and abuse require further clinical and epidemiological exploration.