Linaclotide
Clinical data | |
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Trade names | Linzess |
AHFS/Drugs.com | Monograph |
MedlinePlus | a613007 |
License data |
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Routes of administration | By mouth |
ATC code | |
Legal status | |
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Identifiers | |
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JSmol) | |
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Linaclotide, (sold under the brand name Linzess in the US and Mexico, and as Constella elsewhere)
It is an
It is marketed by
Medical use
Linaclotide is
In June 2023, the indication was expanded in the US to include the treatment of functional constipation.[4][11]
Adverse effects
The US label has a black box warning to not use linaclotide in children less than six years old and to avoid in people from 6 to 18 years old, due to the risk of serious dehydration.[4]
More than 10% of people taking linaclotide have diarrhea. Between 1% and 10% of people have decreased appetite, dehydration, low potassium, dizziness when standing up too quickly, nausea, vomiting, urgent need to defecate, fecal incontinence, and bleeding in the colon, rectum, and anus.[3]
It has not been tested in pregnant women and it is unknown if it is excreted in breast milk.[3]
Pharmacology
Systemic absorption of the globular tetradecapeptide is minimal.[12][13]
Linaclotide, like the
Chemistry
Linaclotide is a hybrid
H–Cys1–Cys2–Glu3–Tyr4–Cys5–Cys6–Asn7–Pro8–Ala9–Cys10–Thr11–Gly12–Cys13–Tyr14–OH
However, the actual structure of linaclotide is not fully specified without the three
A study in discovery synthesis reported that 2 of 14 strategies available to synthesize linaclotide were successful—the successful ones involving
History
The drug was discovered at
Under a partnership agreement announced in 2007, between Forest Laboratories and Microbia, Forest would pay $70 million in licensing fees towards the development of linaclotide, with profits shared between the two companies in the US; Forest obtained exclusive rights to market in Canada and Mexico.[22] By 2010, Microbia had changed its name to Ironwood Pharmaceuticals and had licensed rights to distribute the drug in Europe to Almirall and had licensed Asian rights to Astellas Pharma.[23]
It was approved in the United States and in the European Union in 2012.[7]
Forest was acquired in 2014 and eventually became part of Allergan.[24] Allergan acquired rights from Almirall in 2015,[25] and in 2017, acquired remaining rights in most of the rest of the world, excluding North America, Japan, and China.[26]
Society and culture
Economics
In 2014, Ironwood and Forest then Allergan began running direct-to-consumer advertising which raised sales by 21%; campaigns in 2015 and 2016 raised sales by 27% and 30%.[27]
In 2017, the list price for linaclotide in the US was US$378 for 30 pills; Allergan and Ironwood increased the price of linaclotide to around $414 in 2018.[8]
References
- ^ Oh SA (17 August 2011). "Macrocycle Milestone for Ironwood Pharma". The Haystack. Archived from the original on 27 November 2018. Retrieved 11 February 2017 – via CENBlog.org.
- FDA. Retrieved 22 October 2023.
- ^ a b c d e "UK label: Linaclotide Summary of Product Characteristics". Electronic Medicines Compendium. September 2017. Archived from the original on 15 April 2018. Retrieved 15 April 2018.
- ^ a b c d e f g h i j k "Linzess- linaclotide capsule, gelatin coated". DailyMed. 31 August 2021. Archived from the original on 29 March 2021. Retrieved 12 June 2023.
- ^ "Constella EPAR". European Medicines Agency. 24 May 2023. Archived from the original on 22 June 2021. Retrieved 12 June 2023.
- ^ "Linaclotide - Ironwood Pharmaceuticals". AdisInsight. Archived from the original on 7 October 2017. Retrieved 15 April 2018.
- ^ PMID 25177366.
- ^ a b Nocera J (9 January 2018). "How Allergan Continues to Make Drug Prices Insane". Bloomberg News. Archived from the original on 15 April 2018. Retrieved 15 April 2018.
- ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
- ^ "Linaclotide - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
- ^ "FDA approves first treatment for pediatric functional constipation". U.S. Food and Drug Administration (FDA) (Press release). 12 June 2023. Retrieved 12 June 2023.
- ^ PMID 27099579.
- PMID 24917937.
- ^ PMID 24939497.
- PMID 25177366.
- PMID 33979161.
- ^ S2CID 46150263. Archived from the original(PDF) on 11 February 2017. Retrieved 10 February 2017.
- ^ a b c Withers M (22 September 2004). "Druhunters". Paradigm Magazine, Whitehead Institute. Archived from the original on 28 August 2021. Retrieved 15 April 2018.
- ^ Timmerman L (23 February 2009). "Xconomy: Renewables Aren't Just for Biofuels: Microbia Makes Industrial Chemicals a Bit Greener". Xconomy. Archived from the original on 16 April 2018. Retrieved 15 April 2018.
- S2CID 207494271.
- ^ "Director profile: Mark Currie, Ph.D." MUSC Foundation for Research Development. Archived from the original on 16 April 2018. Retrieved 15 April 2018.
- ^ "Microbia, Forest Laboratories Announce Linaclotide Collaboration". FDA News. 17 September 2007. Archived from the original on 20 August 2016. Retrieved 15 September 2010.
- ^ Pollack, Andrew (13 September 2010). "Drug for Irritable Bowel Achieves Goals in Trial". The New York Times. Archived from the original on 20 December 2011. Retrieved 14 September 2010.
- ^ Jones S, Burdette K, Wieczner J (30 July 2015). "From Actavis to Allergan: One pharma company's wild dealmaking journey". Fortune. Archived from the original on 27 September 2020. Retrieved 15 April 2018.
- ^ "Press release: Allergan Acquires Rights To Ironwoods Constella (Linaclotide) From Almirall In More Than 40 Countr". Allergan. 27 October 2015. Archived from the original on 15 April 2018. Retrieved 15 April 2018.
- ^ "8-K" (PDF). Ironwood. 31 January 2017. Archived from the original (PDF) on 15 April 2018. Retrieved 15 April 2018.
- ^ LaMotta L. "How DTC got things moving for Linzess". BioPharma Dive. Archived from the original on 15 April 2018. Retrieved 15 April 2018.