Azithromycin for the Treatment of Gastroparesis (March).

< Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond, VA.
Annals of Pharmacotherapy (Impact Factor: 2.57). 02/2013; DOI: 10.1345/aph.1R541
Source: PubMed

ABSTRACT OBJECTIVE:To evaluate the use of azithromycin for the treatment of gastroparesis.DATA SOURCES:Literature was accessed through PubMed/MEDLINE and Web of Science (both 1966-October 2012) using the terms gastroparesis, diabetic gastroparesis, and azithromycin. Literature was limited to English-language publications. In addition, references from publications identified were reviewed.STUDY SELECTION AND DATA EXTRACTION:All articles published in English identified from the DATA SOURCES: The treatment of gastroparesis depends on the severity of the symptoms, but generally includes dietary modifications, prokinetic medications, and antiemetics. The initial treatment for gastroparesis is a prokinetic agent, and because erythromycin has the greatest effect on gastric emptying, it is often used. Limitations to erythromycin include adverse reactions (nausea, vomiting, and abdominal pain), QTc interval prolongation, CYP3A-associated drug interactions, and tachyphylaxis. Azithromycin, another macrolide, has been shown to increase gastrointestinal motility and may have fewer limitations to its use. Azithromycin has fewer drug interactions, less incidence of QTc interval prolongation, a longer half-life, and fewer gastrointestinal adverse effects. Use of azithromycin may be beneficial in patients with gastric and small bowel dysmotility. Two observational studies have supported its use in gastroparesis, but there have been no controlled studies. All studies published have been performed during testing procedures for gastroparesis; thus, longer-term treatment effects and symptom control need to be studied. There is one ongoing prospective controlled trial with preliminary data available only in abstract form.CONCLUSIONS:Azithromycin may prove to be an alternative prokinetic agent in gastroparesis, but further study is needed before it can be recommended.

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    ABSTRACT: Current therapy for gastroparesis with prokinetic agents is limited by options and side effects. One macrolide, erythromycin (ERY), is associated with possible sudden cardiac death from QT prolongation due to P450 iso-enzyme inhibition. An alternative, azithromycin (AZI), lacks P450 inhibition. We compared the effect on gastric emptying half-times (t½) between AZI and ERY in patients diagnosed with gastroparesis by gastric emptying scintigraphy. Patients stopped medications known to affect gastric emptying prior to the study, and then ingested 1 scrambled egg meal labeled with 18.5-37 MBq of technetium-99m sulfur colloid followed by continuous imaging for 120 minutes, at 1 minute per frame. A simple linear fit was applied to the rate of gastric emptying, and gastric emptying t½ was calculated (normal = 45-90 minutes). At 75-80 minutes, if the stomach had clearly not emptied, patients were given either ERY (n = 60) or AZI (n = 60) 250 mg IV and a new post-treatment gastric emptying t½ was calculated. Comparison of gastric emptying t½ showed a similar positive effect (mean gastric emptying t½ for AZI = 10.4 ± 7.2 minutes; mean gastric emptying t½ for ERY = 11.9 ± 8.4 minutes; p = 0.30). AZI is equivalent to ERY in accelerating the gastric emptying of adult patients with gastroparesis. Given the longer duration of action, better side effect profile and lack of P450 interaction for AZI as compared with ERY, further research should evaluate the long term effectiveness and safety of AZI as a gastroparesis treatment.
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    ABSTRACT: To investigate the effect of azithromycin (AZI) on small bowel activity in patients with gastrointestinal dysmotility (GID). Manometric data on a consecutive series of 21 patients was reviewed. Only those patients with gastroparesis and small bowel dysmotility as defined by antroduodenal manometric criteria were included. Pressure profiles were recorded in three stages: baseline period, fed state and postprandial after administration of erythromycin (ERY) and AZI. The measured parameters included the number and characteristics of activity fronts and migrating motor complexes (MMCs) including duration, amplitude and frequency of contractions. The data were analyzed using repeated measures analysis of variance for comparison of each medication. AZI induced more MMCs in the duodenum with origin of activity fronts in the antrum than did ERY (18 patients with AZI, 10 patients with ERY). No significant difference between AZI and ERY was seen with respect to the amplitude of MMCs or number of cycles per minute. The average duration of activity fronts was longer with AZI compared with ERY (AZI mean 18.5 min, ERY mean 9.7 min, p < 0.02). AZI induces activity fronts in the antrum followed by duodenal contractions more frequently than ERY in patients with GID. AZI potentially promises to be a prokinetic for treatment of small bowel dysmotility.
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