References

  1. LINZESS (linaclotide) [prescribing information]. Madison, NJ: AbbVie Inc.; 2018.
  2. Data on file. Forest Laboratories, LLC.
  3. American Gastroenterological Association. IBS in America: Survey summary findings. December 2015. Bethesda, MD: American Gastroenterological Association; 2015.
  4. Ford AC, Moayyedi P, Lacy BE, et al. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(Suppl 1):S2-S26.
  5. Brandt LJ, Prather CM, Quigley EMM, Schiller LR, Schoenfeld P, Talley NJ. Systematic review on the management of chronic constipation in North America. Am J Gastroenterol. 2005;100(suppl 1):S5-S21.
  6. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. National Digestive Diseases Information Clearinghouse. Irritable bowel syndrome. Bethesda, MD: National Institutes of Health; 2013. NIH publication 13-693.
  7. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. National Digestive Diseases Information Clearinghouse. Constipation. Bethesda, MD: National Institutes of Health; 2013. NIH publication 13-2754.
  8. Colace (docusate sodium) [product information]. Stamford, CT: Purdue Products LP.
  9. Miralax (polyethylene glycol) [product information]. Whippany, NJ: Bayer AG.
  10. Dietary reference intakes: electrolytes and water. National Academies Press website. http://nationalacademies.org/hmd/~/media/Files/Activity%20Files/Nutrition/DRI-Tables/9_Electrolytes_Water%20Summary.pdf. Accessed April 2020.
  11. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480-1491.
  12. Howden LM, Meyer JA. Age and Sex Composition: 2010. Washington, DC: US Census Bureau; 2011.
  13. Mertz H. Review article: visceral hypersensitivity. Aliment Pharmacol Ther. 2003;17(5):623-633.
  14. Agrawal A, Houghton LA, Reilly B, Morris J, Whorwell PJ. Bloating and distension in irritable bowel syndrome: the role of gastrointestinal transit. Am J Gastroenterol. 2009;104(8):1998-2004.
  15. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Müller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45(suppl 2):II43-II47.
  16. Shaheen NJ, Hansen RA, Morgan DR, et al. The burden of gastrointestinal and liver diseases, 2006. Am J Gastroenterol. 2006;101(9):2128-2138.
  17. Harris LA, Hansel S, DiBaise J, Crowell MD. Irritable bowel syndrome and chronic constipation: emerging drugs, devices, and surgical treatments. Curr Gastroenterol Rep. 2006;8(4):282-290.
  18. Wald A, Talley JT, Grover S. Pathophysiology of irritable bowel syndrome. Up To Date website: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-irritable-bowel-syndrome-in-adults?search=clinicalmanifestations-and-diagnosis-of-irritable-bowel-syndrome-in-adults&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Accessed April 2020.
  19. IQVIA Total Patient Tracker (TPT). February 2018.
  20. Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, doubleblind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012;107(11):1702-1712.
  21. Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012;107(11):1714-1724.
  22. Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32(9):920-924.
  23. Lembo AJ, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011;365(6):527-536.
  24. Garg K, Tripathi CD. Management of constipation. J Int Med Sci Acad. 2013;26(3):173-175.
  25. Feng B, Kiyatkin ME, La JH, et al. Activation of guanylate cyclase-C attentuates stretch responses and sensitization of mouse colorectal afferents. J Neurosci. 2013;33(23):9831-9839.
  26. Eutamene H, Bradesi S, Larauche M, et al. guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain. Neurogastroenterol Motil. 2010;22(3):312-e84.
  27. IQVIA Total Patient Tracker. July 2019. Data are subject to change.
  28. IQVIA, NPA Audit. July 2019. Data are subject to change.
  29. IQVIA Patient Insights, New To Brand. July 2019. Data are subject to change.

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE

LINZESS is contraindicated in patients less than 2 years of age; in nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration.

Contraindications

  • LINZESS is contraindicated in patients less than 2 years of age due to the risk of serious dehydration.
  • LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Warnings and Precautions

Risk of Serious Dehydration in Pediatric Patients Less Than 2 Years of Age

  • LINZESS is contraindicated in patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated GC-C agonism which was associated with increased mortality within the first 24 hours due to dehydration. There was no age-dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established.

Diarrhea

  • Diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients, and in <1% of 72 mcg LINZESS-treated CIC patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.

Common Adverse Reactions (incidence ≥2% and greater than placebo)

  • In IBS-C clinical trials: diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
  • In CIC trials of a 145 mcg dose: diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal distension (3% vs 2%). In a CIC trial of a 72 mcg dose: diarrhea (19% vs 7% placebo) and abdominal distension (2% vs <1%).
LINZESS® (linaclotide) is indicated in adults for the treatment of both irritable bowel syndrome with constipation (IBS‑C) and chronic idiopathic constipation (CIC).
If you are a patient, and have any questions, please discuss them with your doctor or healthcare professional. For additional information about LINZESS, call AbbVie Medical Information at 1-800-678-1605.
Please see additional Important Safety Information throughout, including Boxed Warning.
Please see full Prescribing Information, including Boxed Warning, or visit https://www.rxabbvie.com/pdf/linzess_pi.pdf.

IMPORTANT SAFETY INFORMATION

More
 

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE

LINZESS is contraindicated in patients less than 2 years of age; in nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration.

Contraindications

  • LINZESS is contraindicated in patients less than 2 years of age due to the risk of serious dehydration.
  • LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Warnings and Precautions

Risk of Serious Dehydration in Pediatric Patients Less Than 2 Years of Age

  • LINZESS is contraindicated in patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated GC-C agonism which was associated with increased mortality within the first 24 hours due to dehydration. There was no age-dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established.

Diarrhea

  • Diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients, and in <1% of 72 mcg LINZESS-treated CIC patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.

Common Adverse Reactions (incidence ≥2% and greater than placebo)

  • In IBS-C clinical trials: diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
  • In CIC trials of a 145 mcg dose: diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal distension (3% vs 2%). In a CIC trial of a 72 mcg dose: diarrhea (19% vs 7% placebo) and abdominal distension (2% vs <1%).
LINZESS® (linaclotide) is indicated in adults for the treatment of both irritable bowel syndrome with constipation (IBS‑C) and chronic idiopathic constipation (CIC).
If you are a patient, and have any questions, please discuss them with your doctor or healthcare professional. For additional information about LINZESS, call AbbVie Medical Information at 1-800-678-1605.
Please see additional Important Safety Information throughout, including Boxed Warning.
Please see full Prescribing Information, including Boxed Warning, or visit https://www.rxabbvie.com/pdf/linzess_pi.pdf.