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Indications:  AMITIZA is for Chronic Idiopathic Constipation (CIC) in adults, Opioid-Induced Constipation (OIC) in adults with chronic, non-cancer pain, and Irritable Bowel Syndrome with Constipation (IBS-C) in women ≥ 18 years. Effectiveness in patients taking diphenylheptane opioids has not been established.

Indications

AMITIZA is for Chronic Idiopathic Constipation (CIC) in adults, Opioid-Induced Constipation (OIC) in adults with chronic, non-cancer pain, and Irritable Bowel Syndrome with Constipation (IBS-C) in women ≥ 18 years. Effectiveness in patients taking diphenylheptane opioids has not been established.

Mechanism of action

The science behind AMITIZA

AMITIZA is a locally acting ClC-2 chloride channel activator. AMITIZA promotes fluid secretion into the intestinal lumen.

AMITIZA has a different mechanism of action from other products, such as fiber and laxatives. Watch the mechanism of action video below to get an inside look at the science behind AMITIZA, or read the story for yourself beginning with the role of chloride channels.3

AMITIZA in depth

The role of chloride channels

Chloride channels are key regulators in the intestinal tract, actively transporting chloride ions into the lumen. Sodium ions and fluids passively follow.9-11 By regulating fluid absorption and secretion, chloride channels help regulate fluid balance.12

AMITIZA is a locally acting type 2 chloride channel (ClC-2) activator

Human cell line studies suggest that the biological action of AMITIZA occurs primarily in the apical region of the gastrointestinal epithelium. Here, AMITIZA activates ClC-2 in epithelial cells lining the intestinal tract. Once ClC-2 are activated, the chloride concentration in the intestinal lumen increases. As chloride moves into the intestinal lumen, sodium ions and fluids then passively follow.3,18

By increasing intestinal fluid secretion, AMITIZA increases motility in the intestine, facilitating the passage of stool and alleviating symptoms associated with Chronic Idiopathic Constipation.3

With the activation of ClC-2, AMITIZA:

  • Is able to enhance a chloride-rich intestinal fluid secretion, without altering sodium and potassium concentrations in the serum3
  • Bypasses the antisecretory action of opioids that results from suppression of secretomotor neuron excitability3
  • Stimulates the recovery of the mucosal barrier function and reduces intestinal permeability via the restoration of tight junction protein complexes as seen in ex vivo studies using ischemic porcine intestine*3

The mechanism of action of AMITIZA in IBS-C is not fully understood.

*The role of tight junctions is unclear.

AMITIZA and tight junctions

The mucosal barrier consists of a single layer of columnar epithelium regulated primarily by tight junctions located between cells. Tight junctions act as gate keepers, regulating solutes and macromolecules passing between the apical and basolateral regions of the gut.17

The mechanism of action of AMITIZA in patients with Irritable Bowel Syndrome with Constipation (IBS-C) is not fully understood, but an alteration in the barrier function of the mucosa may be at play in patients with IBS-C.19 While their role in disease remains unclear, damaged or compromised tight junctions are associated with the leaking of luminal contents.17,19

OIC pathophysiology

  • The gastrointestinal (GI) tract is innervated by the largest number of neurons outside of the central nervous system (CNS), and is known as the enteric nervous system (ENS)22
  • Enteric neurons originate from the myenteric and submucosal plexus and regulate digestion in the GI tract22
  • Three major receptors mediate opioid effects (delta, kappa, and mu)23
  • In the GI tract, mu-opioid receptors are localized to functionally distinct enteric neurons and immune cells and they affect motility and secretion15
    • Water and electrolyte secretion are inhibited, resulting in constipation

The mechanism of action of AMITIZA

 

Important Safety Information

AMITIZA (lubiprostone) is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Patients with symptoms suggestive of mechanical gastrointestinal obstruction should be thoroughly evaluated by the treating healthcare provider (HCP) to confirm the absence of such an obstruction prior to initiating AMITIZA treatment.

Patients taking AMITIZA may experience nausea. Concomitant administration of food with AMITIZA may reduce symptoms of nausea.

Avoid use of AMITIZA in patients with severe diarrhea. Patients should be aware of the possible occurrence of diarrhea during treatment. Instruct patients to discontinue AMITIZA and contact their HCP if severe diarrhea occurs.

Syncope and hypotension have been reported with AMITIZA in the postmarketing setting and a few of these adverse reactions resulted in hospitalization. Most reports occurred in patients taking 24 mcg twice daily. Patients should be aware that the risk of syncope and hypotension may be increased with concomitant diarrhea, vomiting, or use of medications known to lower blood pressure. Inform patients that syncope and hypotension may occur within an hour of the first dose or subsequent doses of AMITIZA and generally resolve prior to the next dose, but may recur with repeat dosing. Instruct patients to discontinue AMITIZA and contact their HCP if these reactions occur.

Dyspnea may occur within an hour of first dose. This symptom generally resolves within three hours, but may recur with repeat dosing. Instruct patients to contact their HCP if dyspnea occurs. Some patients have discontinued therapy because of dyspnea.

In clinical trials of AMITIZA (24 mcg twice daily vs placebo; N=1113 vs N=316, respectively) in patients with CIC, the most common adverse reactions (incidence > 4%) were nausea (29% vs 3%), diarrhea (12% vs 1%), headache (11% vs 5%), abdominal pain (8% vs 3%), abdominal distension (6% vs 2%), and flatulence (6% vs 2%).

In clinical trials of AMITIZA (24 mcg twice daily vs placebo; N=860 vs N=632, respectively) in patients with OIC, the most common adverse reactions (incidence > 4%) were nausea (11% vs 5%) and diarrhea (8% vs 2%).

In clinical trials of AMITIZA (8 mcg twice daily vs placebo; N=1011 vs N=435, respectively) in patients with IBS-C, the most common adverse reactions (incidence > 4%) were nausea (8% vs 4%), diarrhea (7% vs 4%), and abdominal pain (5% vs 5%).

Concomitant use of diphenylheptane opioids (e.g., methadone) may interfere with the efficacy of AMITIZA.

The safety of AMITIZA in pregnancy has not been evaluated in humans. Based on animal data, AMITIZA may cause fetal harm. AMITIZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when AMITIZA is administered to a nursing woman. Advise nursing women to monitor infants for diarrhea.

Reduce the dosage in CIC and OIC patients with moderate and severe hepatic impairment. Reduce the dosage in IBS-C patients with severe hepatic impairment.

Indications

AMITIZA (lubiprostone) capsules are indicated for the treatment of Chronic Idiopathic Constipation (CIC) in adults and Opioid-Induced Constipation (OIC) in adults with chronic, non-cancer pain (24 mcg twice daily). The effectiveness in patients with OIC taking diphenylheptane opioids (e.g., methadone) has not been established. AMITIZA is also indicated for Irritable Bowel Syndrome with Constipation (IBS-C) in women ≥ 18 years old (8 mcg twice daily).

Please click here for complete Prescribing Information.

Hide references

  1. Data on file. Takeda Pharmaceuticals.
  2. Brandt LJ, Chey WD, Foxx-Orenstein AE, et al; American College of Gastroenterology Task Force on Irritable Bowel Syndrome. Am J Gastroenterol. 2009;104(suppl 1):S1-S35.
  3. AMITIZA (lubiprostone) Prescribing Information. Sucampo Pharma Americas, LLC.
  4. Brandt LJ, Prather CM, Quigley EM, Schiller LR, Schoenfeld P, Talley NJ. Am J Gastroenterol. 2005;100(suppl 1):S5-S21.
  5. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Gastroenterology. 2006;130:1480-1491.
  6. Drossman DA, Chey WD, Johanson JF, et al. Aliment Pharmacol Ther. 2009;29:329-341.
  7. Johanson JF, Morton D, Geenen J, Ueno R. Am J Gastroenterol. 2008;103:170-177.
  8. Barish CF, Drossman D, Johanson JF, Ueno R. Dig Dis Sci. 2010;55:1090-1097.
  9. Lipecka J, Bali M, Thomas A, et al. Am J Physiol Cell Physiol. 2002;282:C805-C816.
  10. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Physiol Rev. 2002;82:503-568.
  11. Hall JE. Textbook of Medical Physiology. 12th ed. Philadelphia, PA: Saunders Elsevier; 2011:773-788.
  12. Keely SJ, Montrose MH, Barrett KE. In: Yamada T, Alpers DH, Kalloo AN, Kaplowitz N, Owyang C, Powell DW, eds. Textbook of Gastroenterology. 5th ed. West Sussex, England: John Wiley & Sons Ltd; 2009:330-367.
  13. Data on file. Sucampo Pharma Americas, LLC.
  14. Chey WD, Drossman DA, Johanson JF, Scott C, Panas RM, Ueno R. Aliment Pharmacol Ther. 2012;35:587-599.
  15. Patierno S, Anselmi L, Jaramillo I, Scott D, Garcia R, Sternini C. Gastroenterology. 2011;140:618-626.
  16. Hungin APS, Chang L, Locke GR, et al. Aliment Pharmacol Ther. 2005;21:1365-1375.
  17. Moeser AJ, Nighot PK, Engelke KJ, Ueno R, Blikslager AT. Am J Physiol Gastrointest Liver Physiol. 2007;292:G647-G656.
  18. Cuppoletti J, Malinowska DH, Tewari KP, et al. Am J Physiol Cell Physiol. 2004;287:C1173-C1183.
  19. Camilleri M, Gorman H. Neurogastroenterol Motil. 2007;19:545-552.
  20. Higgins PDR, Johanson JF. Am J Gastroenterol. 2004;99:750-759.
  21. National Digestive Diseases Information Clearinghouse (NDDIC). Constipation (2007).
  22. Furness JB, Nguyen TV, Nurgali K, Shimizu Y. In: Yamada T, Alpers DH, Kalloo AN, Kaplowitz N, Owyang C, Powell DW, eds. Textbook of Gastroenterology. 5th ed. Hoboken, NJ: Wiley Blackwell; 2009:15-36.
  23. Sternini C. Am J Physiol Gastrointest Liver Physiol. 2001;281:G8-G15.
  24. Pappagallo M. Am J Surg. 2001;182:11S-18S.
  25. Brock C, Olesen SS, Olesen AE, Frøkjaer JB, Andresen T, Drewes AM. Drugs. 2012;72:1847-1865.

Important Safety Information

AMITIZA (lubiprostone) is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Patients with symptoms suggestive of mechanical gastrointestinal obstruction should be thoroughly evaluated by the treating healthcare provider (HCP) to confirm the absence of such an obstruction prior to initiating AMITIZA treatment.

Patients taking AMITIZA may experience nausea. Concomitant administration of food with AMITIZA may reduce symptoms of nausea.

Avoid use of AMITIZA in patients with severe diarrhea. Patients should be aware of the possible occurrence of diarrhea during treatment. Instruct patients to discontinue AMITIZA and contact their HCP if severe diarrhea occurs.

Syncope and hypotension have been reported with AMITIZA in the postmarketing setting and a few of these adverse reactions resulted in hospitalization. Most reports occurred in patients taking 24 mcg twice daily. Patients should be aware that the risk of syncope and hypotension may be increased with concomitant diarrhea, vomiting, or use of medications known to lower blood pressure. Inform patients that syncope and hypotension may occur within an hour of the first dose or subsequent doses of AMITIZA and generally resolve prior to the next dose, but may recur with repeat dosing. Instruct patients to discontinue AMITIZA and contact their HCP if these reactions occur.

Dyspnea may occur within an hour of first dose. This symptom generally resolves within three hours, but may recur with repeat dosing. Instruct patients to contact their HCP if dyspnea occurs. Some patients have discontinued therapy because of dyspnea.

In clinical trials of AMITIZA (24 mcg twice daily vs placebo; N=1113 vs N=316, respectively) in patients with CIC, the most common adverse reactions (incidence > 4%) were nausea (29% vs 3%), diarrhea (12% vs 1%), headache (11% vs 5%), abdominal pain (8% vs 3%), abdominal distension (6% vs 2%), and flatulence (6% vs 2%).

In clinical trials of AMITIZA (24 mcg twice daily vs placebo; N=860 vs N=632, respectively) in patients with OIC, the most common adverse reactions (incidence > 4%) were nausea (11% vs 5%) and diarrhea (8% vs 2%).

In clinical trials of AMITIZA (8 mcg twice daily vs placebo; N=1011 vs N=435, respectively) in patients with IBS-C, the most common adverse reactions (incidence > 4%) were nausea (8% vs 4%), diarrhea (7% vs 4%), and abdominal pain (5% vs 5%).

Concomitant use of diphenylheptane opioids (e.g., methadone) may interfere with the efficacy of AMITIZA.

The safety of AMITIZA in pregnancy has not been evaluated in humans. Based on animal data, AMITIZA may cause fetal harm. AMITIZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when AMITIZA is administered to a nursing woman. Advise nursing women to monitor infants for diarrhea.

Reduce the dosage in CIC and OIC patients with moderate and severe hepatic impairment. Reduce the dosage in IBS-C patients with severe hepatic impairment.

Indications

AMITIZA (lubiprostone) capsules are indicated for the treatment of Chronic Idiopathic Constipation (CIC) in adults and Opioid-Induced Constipation (OIC) in adults with chronic, non-cancer pain (24 mcg twice daily). The effectiveness in patients with OIC taking diphenylheptane opioids (e.g., methadone) has not been established. AMITIZA is also indicated for Irritable Bowel Syndrome with Constipation (IBS-C) in women ≥ 18 years old (8 mcg twice daily).

Please click here for complete Prescribing Information.