Lubiprostone

Class: GI Drugs, Miscellaneous
VA Class: GA900
Chemical Name: (–) - 7 - [(2R,4aR,5R,7aR) - 2 - (1,1 - difluoropentyl) - 2 - hydroxy - 6 - oxooctahydrocyclopenta[b]pyran - 5 - yl]heptanoic acid
Molecular Formula: C₂₀H₃₂F₂O₅
CAS Number: 136790-76-6
Brands: Amitiza

Introduction

Bicyclic fatty acid; selectively activates intestinal ClC-2 chloride channels and increases intestinal fluid secretion.^{1 2 3 4 5 6}

Uses for Lubiprostone

Chronic Idiopathic Constipation

Management of chronic idiopathic constipation in adults.^{1 2 4 5 9}

Irritable Bowel Syndrome with Constipation in Women

Treatment of irritable bowel syndrome (IBS) with constipation in women ≥18 years of age.^{1 7 8}

Lubiprostone Dosage and Administration

Administration

Oral Administration

Administer orally with food and water.^{1 2 9}

Dosage

Adults

Periodically assess need for continued therapy.^{1 4}

Chronic Idiopathic Constipation

Oral

24 mcg twice daily.^{1 2 4}

May reduce dosage to 24 mcg daily in patients experiencing severe nausea.¹

Irritable Bowel Syndrome with Constipation in Women

Oral

8 mcg twice daily.¹

Special Populations

No special population recommendations at this time.¹

Cautions for Lubiprostone

Contraindications

• 
  

  Known hypersensitivity to lubiprostone or any ingredient in the formulation.⁹

  
  


• 
  

  Known or suspected mechanical GI obstruction.¹

  
  

Warnings/Precautions

Warnings

GI Obstruction

Thoroughly evaluate patients with symptoms suggestive of mechanical GI obstruction to confirm absence of such obstruction prior to initiating lubiprostone therapy.^{1 9} (See Contraindications under Cautions.)

Fetal/Neonatal Morbidity and Mortality

Women of childbearing potential should have a negative pregnancy test prior to receiving lubiprostone and should use an effective method of contraception during therapy with the drug.^{1 9}

General Precautions

GI Effects

Dose-dependent nausea may occur.¹ Symptoms may be reduced by coadministration with food and water.¹

Possible diarrhea (may be severe).¹

Do not prescribe lubiprostone to patients with severe diarrhea.¹

Respiratory Effects

Possible dyspnea (may result in discontinuance of the drug).¹

Onset of symptoms (e.g., sensation of chest tightness, difficulty in breathing) generally occurs within 30–60 minutes after taking the first dose.¹ Symptoms usually resolve within a few hours; however, frequently recur with subsequent doses.¹

Specific Populations

Pregnancy

Category C.^{1 2} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether distributed into human milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.^{1 6}

Geriatric Use

Geriatric patients with chronic idiopathic constipation experienced a lower incidence (18 versus 29%) of associated nausea than the overall study population.¹

Experience in those ≥65 years of age with IBS with constipation was insufficient to determine whether they respond differently from younger adults.¹

Hepatic Impairment

Not studied in patients with hepatic impairment.^{1 9}

Renal Impairment

Not studied in patients with renal impairment.^{1 9}

Common Adverse Effects

Chronic idiopathic constipation: Nausea,^{1 2 4 5} diarrhea,^{1 2 5} headache,^{1 2 4 5 9} abdominal distention,¹ abdominal pain,^{1 2} flatulence,^{1 2} vomiting,¹ dizziness,¹ edema,¹ loose stools,¹ abdominal discomfort (including abdominal tenderness, abdominal rigidity, GI discomfort),¹ dyspepsia,¹ chest discomfort/pain,¹ dyspnea,¹ fatigue.¹

IBS with constipation in women: Nausea,¹ diarrhea,¹ abdominal pain,¹ abdominal distention.¹

Interactions for Lubiprostone

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4 in vitro.¹ Does not induce CYP1A2, CYP2B6, CYP2C9, or CYP3A4 in vitro.¹ Pharmacokinetic interactions unlikely with drugs metabolized by these CYP isoenzymes.¹

Not metabolized by isoenzymes.¹

Highly Protein-bound Drugs

Pharmacokinetic interaction unlikely.¹

Lubiprostone Pharmacokinetics

Absorption

Bioavailability

Low systemic bioavailability following oral administration with peak plasma concentrations usually attained within 1.1 hours.^{1 4}

Food

High-fat meal may reduce peak plasma concentration but does not affect extent of absorption (AUC).¹

Distribution

Extent

Minimal distribution beyond GI tissues.¹

Lubiprostone crosses the placenta in animals; not known whether crosses the placenta in humans.¹

Not known whether distributed into human milk.¹

Plasma Protein Binding

Approximately 94%.¹

Elimination

Metabolism

Rapidly and extensively metabolized, probably in the stomach and jejunum, by processes mediated by carbonyl reductase.^{1 4} CYP isoenzymes not involved in metabolism of the drug.¹

Elimination Route

Excreted in the urine (about 60%) within 24 hours and in feces (about 30%) within 168 hours.^{1 2 4}

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).¹

ActionsActions

• 
  

  Bicyclic fatty acid; selectively activates intestinal ClC-2 chloride channels; increases intestinal chloride and fluid secretion without affecting serum sodium and potassium concentrations.^{1 2 3 4 6} Activates the ClC-2 chloride channel which is located on the apical (luminal) membrane of the human intestinal epithelium, independent of the actions of protein kinase A.¹

  
  


• 
  

  Increases intestinal motility by increasing intestinal fluid secretion, consequently increasing the passage of stool and alleviating symptoms of chronic idiopathic constipation.^{1 2 3 4 5}

  
  


• 
  

  May stimulate recovery of mucosal barrier function by restoring tight junction protein complexes in the intestine.^{1 8}

  
  


• 
  

  Delays gastric emptying,^{2 3} which may result in nausea.^{1 2}

  
  

Advice to Patients

• 
  

  Advise patients to take the drug twice daily (morning and evening) with food and water.¹

  
  


• 
  

  Importance of advising patients to swallow capsules whole without chewing or breaking apart.¹

  
  


• 
  

  Importance of advising patients that nausea may occur; administer with food and water to reduce nausea.¹ Advise patients to contact a clinician if nausea becomes severe.¹

  
  


• 
  

  Clinicians and patients periodically should assess the need for continued treatment.¹

  
  


• 
  

  Importance of advising patients that diarrhea may occur.¹ Advise patients to notify a clinician⁹ and not to take lubiprostone if they experience severe diarrhea.¹

  
  


• 
  

  Importance of advising patients that dyspnea may occur; advise patients to notify clinician if dyspnea becomes severe.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Advise pregnant women of risk to the fetus.¹ Importance of using effective method of contraception.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Lubiprostone

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	8 mcg	Amitiza	Sucampo
		24 mcg	Amitiza	Sucampo

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Amitiza 24MCG Capsules (TAKEDA PHARMACEUTICALS): 30/$126.99 or 90/$359.97

Amitiza 8MCG Capsules (TAKEDA PHARMACEUTICALS): 60/$246 or 180/$679.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions March 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Sucampo Pharmaceuticals, Inc. Amitiza (lubiprostone) capsules prescribing information. Bethesda, MD; 2008 Apr.

2. Anon. Lubiprostone (Amitiza) for chronic constipation. Med Lett Drugs Ther. 2006; 48:47-8. [PubMed 16770297]

3. Camilleri M, Bharucha AE, Ueno R 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. [PubMed 16603730]

4. McKeage K, Plosker GL, Siddiqui MAA. Lubiprostone. Drugs. 2006; 66:873-9. [PubMed 16706562]

5. Anon. Lubiprostone. Drugs R&D. 2005; 6:245-8.

6. Sucampo Pharmaceuticals, Bethesda, MD: Personal communication.

7. Anon. Lubiprostone (Amitiza) for irritable bowel syndrome with constipation. Med Lett Drugs Ther. 2008; 50:53-4.

8. Johanson JF, Drossman DA, Panas R et al. Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2008; 27:685-96. [PubMed 18248656]

9. Food and Drug Aministration. FDA patient information sheet: Lubiprostone capsules (marketed as Amitiza). Available at the FDA website. Accessed 2008 Oct 6.

More Lubiprostone resources

• Lubiprostone Side Effects (in more detail)
• Lubiprostone Dosage
• Lubiprostone Use in Pregnancy & Breastfeeding
• Lubiprostone Support Group
• 59 Reviews for Lubiprostone - Add your own review/rating

• Lubiprostone MedFacts Consumer Leaflet (Wolters Kluwer)


• Lubiprostone Professional Patient Advice (Wolters Kluwer)


• lubiprostone Advanced Consumer (Micromedex) - Includes Dosage Information


• Amitiza Prescribing Information (FDA)


• Amitiza Consumer Overview

Compare Lubiprostone with other medications

• Constipation, Chronic
• Constipation, Drug Induced
• Irritable Bowel Syndrome