New Drug Reviews
Lubiprostone (Amitiza) for Chronic Idiopathic Constipation
Am Fam Physician. 2006 Oct 15;74(8):1380-1381.
Lubiprostone (Amitiza) is a prostaglandin derivative that reduces constipation and improves stool consistency by activating specific chloride channels (ClC-2) in the small intestine to increase intestinal fluid secretion and accelerate small intestine and colonic transit time.1–3 It is labeled for the treatment of chronic idiopathic constipation lasting at least 12 weeks.4 Lubiprostone also is being studied for use in constipation-predominant irritable bowel syndrome and postoperative ileus.
|Name||Starting dosage||Dose form||Approximate monthly cost*|
24 mcg twice daily
*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2006.
No significant safety issues have been identified with lubiprostone; however, it was only studied in otherwise healthy adults for 24 weeks or less. It has been studied in healthy patients older than 65 years, and no restrictions exist for use in this population. Lubiprostone use has not been studied in patients with renal or hepatic dysfunction. It should not be given to patients with severe diarrhea. Lubiprostone has shown potential to cause fetal loss in animal studies (e.g., guinea pigs receiving two to six times the recommended dose); it is classified as pregnancy category C.1
Lubiprostone causes nausea, diarrhea, and headache in many patients. Approximately one third (31 percent) of patients receiving lubiprostone 24 mcg twice daily reported having nausea compared with 5 percent of patients receiving placebo. Of the 31 percent, 3 percent reported severe nausea, and 9 percent discontinued treatment because of nausea. Men and patients older than 65 years were less likely to experience nausea (approximately 13 percent and 18 percent, respectively). Diarrhea, which does not appear to be dose-dependent, occurred in approximately one in eight patients (13 percent) compared with 1 percent of patients receiving placebo. Two percent of patients receiving lubiprostone discontinued therapy because of diarrhea.1
Abdominal distension/pain, gas, vomiting, and loose stools also occurred, but less often than nausea and diarrhea. Headache occurred in 13 percent of patients receiving lubiprostone compared with 6 percent of patients receiving placebo. Dizziness, peripheral edema, dyspnea, and arthralgia also occurred more often in patients receiving lubiprostone.1 Despite the increase in intestinal chloride secretion, lubiprostone did not affect serum electrolytes in one study.5
The product labeling and research in abstract form (there is no published research) report that patients treated with lubiprostone experienced a median increase of three or four spontaneous bowel movements per week after one month of treatment compared with a median increase of 1.0 to 1.5 spontaneous bowel movements per week among those in the placebo group.1,6 Full response (i.e., more than four total bowel movements per week) occurred in 72 percent of patients after one week of treatment compared with 49 percent of patients receiving placebo.7 This represents a number needed to treat of approximately four patients. Lubiprostone works quickly; 60 percent of patients will have a spontaneous bowel movement within 24 hours of starting treatment.6–7
Lubiprostone improves stool consistency, straining, and abdominal symptoms.7 Improvement in constipation severity, bloating, and abdominal discomfort is maintained for at least six months after starting treatment.8 Lubiprostone has been studied predominantly in white females. There are no studies comparing lubiprostone with any other drug used for constipation.
A one-month supply of lubiprostone costs approximately $178. This is comparable to the cost of tegaserod (Zelnorm; $194), which also is approved for chronic idiopathic constipation. The cost of lubiprostone is much higher than that of over-the-counter laxatives and polyethylene glycol (Miralax), which often is used off-label for chronic constipation and costs $43 for a dosage of 17 g per day for one month.
Each capsule contains 24 mcg of lubiprostone, and the usual dosage is one capsule twice daily. Nausea can be reduced with dosage reduction to 24 mcg once daily or if taken with food. The dosage also can be reduced to once daily in patients who experience diarrhea or other bothersome gastrointestinal side effects. Patients with a history of mechanical gastrointestinal obstruction should not use lubiprostone. Lubiprostone has not been studied in patients with renal or hepatic impairment; therefore, it is unknown if dosing adjustment is necessary in this population.1
Although bulk or osmotic laxatives are less expensive first options for treating patients with chronic idiopathic constipation, lubiprostone is an alternative for those who do not tolerate or respond to these agents, or in patients older than 65 years in whom tegaserod use is not recommended.
1. Amitiza (lubiprostone) soft gelatin capsules [Prescribing information]. Bethesda, Md.: Sucampo Pharmaceuticals, Inc., 2006. Accessed July 25, 2006, at: http://www.sucampo.com/downloads/2006.02.01_AMITIZA.pdf.
2. Cuppoletti J, Malinowska DH, Tewari KP, Li QJ, Sherry AM, Patchen ML, et al. SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents. Am J Physiol Cell Physiol. 2004;287:C1173–83.
3. Camilleri M, Bharucha AE, Ueno R, Burton D, Thomforde GM, Baxter K, 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:G942–7.
4. Velio P, Bassotti G. Chronic idiopathic constipation: pathophysiology and treatment. J Clin Gastroenterol. 1996;22:190–6.
5. Ueno R, Osama H, Habe T, Engelke K, Patchen M. Oral SP-0211 increases intestinal fluid secretion and chloride concentration without altering serum electrolyte levels [abstract]. Gastroenterology. 2004;126(suppl 2):A–100.
6. Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Phase III patient assessments of the effects of lubiprostone, a chloride channel-2 (ClC-2) activator, for the treatment of constipation. Presented at: American College of Gastroenterology 70th Annual Scientific Meeting; October 31–November 2, 2005; Honolulu, Hawaii. Abstract 899. Am J Gastroenterol. 2005;100(9 suppl):S329–30.
7. Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Phase III study of lubiprostone, a chloride channel-2 (ClC-2) activator for the treatment of constipation: safety and primary efficacy. Presented at: American College of Gastroenterology 70th Annual Scientific Meeting; October 31–November 2, 2005; Honolulu, Hawaii. Abstract 896. Am J Gastroenterol. 2005;100(9 suppl):S328–9.
8. Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Multicenter open-label study of lubiprostone for the treatment of chronic constipation Presented at: American College of Gastroenterology 70th Annual Scientific Meeting; October 31–November 2, 2005; Honolulu, Hawaii. Abstract 903. Am J Gastroenterol. 2005;100(9 suppl):S331
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The series coordinator is Allen F. Shaughnessy, Pharm.D., Tufts University Family Medicine Residency Program, Malden, Mass.
Copyright © 2006 by the American Academy of Family Physicians.
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