Pharmacology Update
Lubiprostone Capsules (Amitiza™)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.
A new agent with a unique mechanism of action has been approved for the treatment of chronic constipation. Lubiprostone is an activator of the chloride channels in the apical membrane of the gastrointestinal epithelium. It is marketed by Sucampo Pharmaceuticals and Takeda Pharmaceuticals America as Amitiza™.
Indications
Lubiprostone is indicated for the treatment of chronic idiopathic constipation in adult patients.1
Dosage
The recommended dose is 24 µg twice daily with food.1
Potential Advantages
Lubiprostone increases the number of spontaneous bowel movements with a different mechanism of action compared to traditional laxatives. No protein binding interactions or drug-drug interactions involving CYP isoenzymes are expected.
Potential Disadvantages
About one third of patients report nausea and 8.7% discontinue treatment due to nausea. Diarrhea is reported in 13.2% of patients and 3.4% reported severe diarrhea and 2.2% discontinued treatment.1
Comments
Lubiprostone is a selective type 2 chloride channel activator. This action on the apical intestinal membrane leads to increased intestinal fluid secretion which softens the stool, promotes spontaneous bowel movement, and reduces abdominal discomfort, pain, and bloating.2,3 The drug was evaluated in 2 studies (n = 479) in mainly Caucasian female patients with chronic idiopathic constipation defined as < 3 spontaneous bowel movements per week. Lubiprostone administration resulted in a median increase of 3.5-3.8 spontaneous bowel movements at week 1 compared to 1.5 for placebo. The median increase was 3 vs 1.5 at week 4. In open-label studies patients have been treated for 6-12 months, lubiprostone appears to continue to improve symptoms.1,3 Nausea and diarrhea are the most common adverse events. Nausea appears to be dose-dependent and is reduced with administration with food. The rate is lower in men than in women (13.2% vs 18.6%). Approximately 9% of patients discontinue treatment due to nausea. The rate of lubiprostone-induced diarrhea does not appear to be dose-dependent. Lubiprostone is contraindicated in patients with a history of or presence of mechanical obstruction. The wholesale cost of lubiprostone is about $5 per day.
Clinical Implications
Lubiprostone offers an effective and apparently safe drug for the treatment of chronic idiopathic constipation. There are currently no comparative studies with other drugs such as laxatives or tegaserod. Lubiprostone should be reserved for patients in whom traditional agents have not been effective.
References
1. Amitiza Product Information. Sucampo Pharmaceuticals, Inc. March 2006.
2. Camilleri M et al. Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2006;290:G942-947.
3. Lubiprostone: RU 0211, SPI 0211. Drugs R.D. 2005;6:245-248.
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