Octreotide

Octreotide is used for the treatment of growth hormone producing tumors (acromegaly and gigantism), when surgery is contraindicated, pituitary tumors that secrete thyroid-stimulating hormone (thyrotropinoma),{{citation needed|date=March 2020}} diarrhea and flushing episodes associated with carcinoid syndrome, and diarrhea in people with vasoactive intestinal peptide-secreting tumors (VIPomas). Octreotide is also used in mild cases of glucagonoma when surgery is not an option.Octreotide {{Drugs.com|monograph|octreotide-acetate}}{{cite journal|vauthors=Moattari AR, Cho K, Vinik AI|year=1990|title=Somatostatin analogue in treatment of coexisting glucagonoma and pancreatic pseudocyst: dissociation of responses|journal=Surgery|volume=108|issue=3|pages=581–7|pmid=2168587}}

Octreotide is often given as an infusion for management of acute hemorrhage from esophageal varices in liver cirrhosis on the basis that it reduces portal venous pressure, though current evidence suggests that this effect is transient and does not improve survival.{{cite journal | vauthors = Gøtzsche PC, Hróbjartsson A | title = Somatostatin analogues for acute bleeding oesophageal varices | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD000193 | date = July 2008 | volume = 2008 | pmid = 18677774 | doi = 10.1002/14651858.CD000193.pub3 | pmc = 7043291 }}

{{Further|Octreotide scan}}

Octreotide is used in nuclear medicine imaging by labeling with indium-111 (Octreoscan) to noninvasively image neuroendocrine and other tumours expressing somatostatin receptors.{{Cite web |url=https://www.medscape.com/s/viewarticle/406655_3 |title=Medscape: Octreoscan review |access-date=28 October 2010 |archive-date=12 February 2017 |archive-url=https://web.archive.org/web/20170212162120/http://www.medscape.com/viewarticle/406655_3 |url-status=live }} It has been radiolabeled with carbon-11{{cite journal | vauthors = Chin J, Vesnaver M, Bernard-Gauthier V, Saucke-Lacelle E, Wängler B, Wängler C, Schirrmacher R | title = Direct one-step labeling of cysteine residues on peptides with [(11)C]methyl triflate for the synthesis of PET radiopharmaceuticals | journal = Amino Acids | volume = 45 | issue = 5 | pages = 1097–108 | date = November 2013 | pmid = 23921782 | doi = 10.1007/s00726-013-1562-5 | s2cid = 16848582 }} as well as gallium-68 (using edotreotide), enabling imaging with positron emission tomography (PET).

In June 2020, octreotide (Mycapssa) was approved for medical use in the United States with an indication for the long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide.{{cite web | title=Octreotide Capsules - Our Research | website=Chiasma | date=24 January 2020 | url=https://chiasma.com/octreotide-capsules/ | access-date=30 June 2020 | archive-date=2 July 2020 | archive-url=https://web.archive.org/web/20200702123255/https://chiasma.com/octreotide-capsules/ | url-status=dead }}{{cite press release | title=Chiasma Announces FDA Approval of Mycapssa (Octreotide) Capsules, the First and Only Oral Somatostatin Analog | website=Chiasma | date=26 June 2020 | url=https://ir.chiasma.com/news-releases/news-release-details/chiasma-announces-fda-approval-mycapssar-octreotide-capsules | access-date=30 June 2020 | archive-date=30 June 2020 | archive-url=https://web.archive.org/web/20200630012616/https://ir.chiasma.com/news-releases/news-release-details/chiasma-announces-fda-approval-mycapssar-octreotide-capsules | url-status=dead }} Mycapssa is the first oral somatostatin analog (SSA) approved by the FDA.

Octreotide is also used in the treatment of refractory hypoglycemia or congenital hyperinsulinism in neonates{{cite journal | vauthors = McMahon AW, Wharton GT, Thornton P, De Leon DD | title = Octreotide use and safety in infants with hyperinsulinism | journal = Pharmacoepidemiology and Drug Safety | volume = 26 | issue = 1 | pages = 26–31 | date = January 2017 | pmid = 27910218 | pmc = 5286465 | doi = 10.1002/pds.4144 }} and sulphonylurea-induced hypoglycemia in adults.

Octreotide has not been adequately studied for the treatment of children as well as pregnant and lactating women. The medication is given to these groups only if a risk-benefit analysis is positive.{{cite book|title=Austria-Codex| veditors = Haberfeld H |publisher=Österreichischer Apothekerverlag|location=Vienna|year=2009|edition=2009/2010|isbn=978-3-85200-196-8|language=de}}{{cite book|title=Arzneistoff-Profile| veditors = Dinnendahl V, Fricke U |publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|year=2010|edition=23|volume=8|isbn=978-3-7741-9846-3|language=de}}

The most common adverse effects are headache, hypothyroidism, cardiac conduction changes, gastrointestinal reactions (including cramps, nausea/vomiting and diarrhoea or constipation), gallstones, reduction of insulin release, hyperglycemia{{cite journal | vauthors = Hovind P, Simonsen L, Bülow J | title = Decreased leg glucose uptake during exercise contributes to the hyperglycaemic effect of octreotide | journal = Clinical Physiology and Functional Imaging | volume = 30 | issue = 2 | pages = 141–5 | date = March 2010 | pmid = 20132129 | doi = 10.1111/j.1475-097X.2009.00917.x | s2cid = 5303108 }} or sometimes hypoglycemia, and (usually transient) injection site reactions. Slow heart rate, skin reactions such as pruritus, hyperbilirubinemia, hypothyroidism, dizziness and dyspnoea are also fairly common (more than 1%). Rare side effects include acute anaphylactic reactions, pancreatitis and hepatitis.

Some studies reported alopecia in those who were treated by octreotide.{{cite journal | vauthors = van der Lely AJ, de Herder WW, Lamberts SW | title = A risk-benefit assessment of octreotide in the treatment of acromegaly | journal = Drug Safety | volume = 17 | issue = 5 | pages = 317–24 | date = November 1997 | pmid = 9391775 | doi = 10.2165/00002018-199717050-00004 | s2cid = 25405834 }} Rats which were treated by octreotide experienced erectile dysfunction in a 1998 study.{{cite journal | vauthors = Kapicioglu S, Mollamehmetoglu M, Kutlu N, Can G, Ozgur GK | title = Inhibition of penile erection in rats by a long-acting somatostatin analogue, octreotide (SMS 201-995) | journal = British Journal of Urology | volume = 81 | issue = 1 | pages = 142–5 | date = January 1998 | pmid = 9467491 | doi = 10.1046/j.1464-410x.1998.00520.x | doi-access = }}

A prolonged QT interval has been observed, but it is uncertain whether this is a reaction to the medication or the result of an existing illness.

Octreotide can reduce the intestinal reabsorption of ciclosporin, possibly making it necessary to increase the dose.{{cite book|title=Arzneimittel-Interaktionen | veditors = Klopp T |publisher=Arbeitsgemeinschaft für Pharmazeutische Information|year=2010|edition=2010/2011|isbn=978-3-85200-207-1|language=de}} People with diabetes mellitus might need less insulin or oral antidiabetics when treated with octreotide, as it inhibits glucagon secretion more strongly and for a longer time span than insulin secretion. The bioavailability of bromocriptine is increased; besides being an antiparkinsonian, bromocriptine is also used for the treatment of acromegaly.

Since octreotide resembles somatostatin in physiological activities, it can:

• inhibit secretion of many hormones, such as gastrin, cholecystokinin, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, TSH, and vasoactive intestinal peptide,
• reduce secretion of fluids by the intestine and pancreas,
• reduce gastrointestinal motility and inhibit contraction of the gallbladder,
• inhibit the action of certain hormones from the anterior pituitary,
• cause vasoconstriction in the blood vessels, and
• reduce portal vessel pressures in bleeding varices.

It has also been shown to produce analgesic effects, most probably acting as a partial agonist at the mu opioid receptor.{{cite journal | vauthors = Maurer R, Gaehwiler BH, Buescher HH, Hill RC, Roemer D | title = Opiate antagonistic properties of an octapeptide somatostatin analog | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 79 | issue = 15 | pages = 4815–7 | date = August 1982 | pmid = 6126877 | pmc = 346769 | doi = 10.1073/pnas.79.15.4815 | bibcode = 1982PNAS...79.4815M | doi-access = free }}{{cite journal | vauthors = Allen MP, Blake JF, Bryce DK, Haggan ME, Liras S, McLean S, Segelstein BE | title = Design, synthesis and biological evaluation of 3-amino-3-phenylpropionamide derivatives as novel mu opioid receptor ligands | journal = Bioorganic & Medicinal Chemistry Letters | volume = 10 | issue = 6 | pages = 523–6 | date = March 2000 | pmid = 10741545 | doi = 10.1016/s0960-894x(00)00034-2 }}

Octreotide is absorbed quickly and completely after subcutaneous application. Maximal plasma concentration is reached after 30 minutes. The elimination half-life is 100 minutes (1.7 hours) on average when applied subcutaneously; after intravenous injection, the substance is eliminated in two phases with half-lives of 10 and 90 minutes, respectively.

Octreotide acetate was approved for use in the United States in 1988.{{cite web | title=Sandostatin Lar Depot- octreotide acetate kit | website=DailyMed | date=11 April 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d0b7fe9e-7000-4b79-ba3b-291ce92c14f9 | access-date=16 February 2020 | archive-date=24 March 2021 | archive-url=https://web.archive.org/web/20210324124306/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d0b7fe9e-7000-4b79-ba3b-291ce92c14f9 | url-status=live }}

In January 2020, approval of octreotide acetate in the United States was granted to Sun Pharmaceutical under the brand name Bynfezia Pen for the treatment of:{{cite web | title=Bynfezia Pen- octreotide acetate injection | website=DailyMed | date=19 February 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=20ed4e79-ad4c-426f-859d-83790c00439b | access-date=19 April 2021 | archive-date=19 September 2022 | archive-url=https://web.archive.org/web/20220919055039/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=20ed4e79-ad4c-426f-859d-83790c00439b | url-status=live }}{{cite web | url=https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/213224Orig1s000ltr.pdf | title=Bynfezia Pen letter | publisher=U.S. Food and Drug Administration (FDA) | date=28 January 2020 | access-date=16 February 2020 | archive-date=17 February 2020 | archive-url=https://web.archive.org/web/20200217070012/https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/213224Orig1s000ltr.pdf | url-status=live }} {{PD-notice}}{{cite web | title=Drug Approval Package: Bynfezia | website=U.S. Food and Drug Administration (FDA) | date=1 June 2020 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213224Orig1s000TOC.cfm | access-date=18 April 2021 | archive-date=30 March 2021 | archive-url=https://web.archive.org/web/20210330152034/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213224Orig1s000TOC.cfm | url-status=live }}

• the reduction of growth hormone and insulin-like growth factor 1 (somatomedin C) in adults with acromegaly who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses
• severe diarrhea/flushing episodes associated with metastatic carcinoid tumors in adults
• profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas) in adults

In September 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Mycapssa, intended for the treatment of adults with acromegaly. The applicant for this medicinal product is Amryt Pharmaceuticals DAC.{{cite web | title=Mycapssa: Pending EC decision | publisher=European Medicines Agency | date=16 September 2022 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/mycapssa | access-date=18 September 2022 | archive-date=19 September 2022 | archive-url=https://web.archive.org/web/20220919032025/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/mycapssa | url-status=dead }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Mycapssa was approved for medical use in the European Union in December 2022.{{cite web | title=Mycapssa Product information | publisher=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1690.htm | access-date=3 March 2023}}

In April 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Oczyesa, intended for the maintenance treatment of adults with acromegaly. The applicant for this medicinal product is Camurus AB. Oczyesa is a hybrid medicine of Sandostatin, which has been authorized in the EU since November 1988. Oczyesa contains the same active substance as Sandostatin but as a different salt and is available at a higher strength and in a different pharmaceutical form.{{cite web | title=Oczyesa EPAR | publisher=European Medicines Agency (EMA) | date=25 April 2025 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/oczyesa | access-date=2 May 2025}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

Octreotide has also been used off-label for the treatment of severe, refractory diarrhea from other causes. It is used in toxicology for the treatment of prolonged recurrent hypoglycemia after sulfonylurea and possibly meglitinide overdose. It has also been used with varying degrees of success in infants with nesidioblastosis to help decrease insulin hypersecretion. Several clinical trials have demonstrated the effect of octreotide as acute treatment (abortive agent) in cluster headache, where it has been shown that administration of subcutaneous octreotide is effective when compared with placebo.{{cite journal | vauthors = Matharu MS, Levy MJ, Meeran K, Goadsby PJ | title = Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study | journal = Annals of Neurology | volume = 56 | issue = 4 | pages = 488–94 | date = October 2004 | pmid = 15455406 | doi = 10.1002/ana.20210 | s2cid = 23879669 }}

Octreotide has also been investigated in people with pain from chronic pancreatitis.{{cite journal | vauthors = Uhl W, Anghelacopoulos SE, Friess H, Büchler MW | title = The role of octreotide and somatostatin in acute and chronic pancreatitis | journal = Digestion | volume = 60 | issue = 2 | pages = 23–31 | year = 1999 | pmid = 10207228 | doi = 10.1159/000051477 | s2cid = 24011709 }}

It has been used in the treatment of malignant bowel obstruction.{{cite journal | vauthors = Shima Y, Ohtsu A, Shirao K, Sasaki Y | title = Clinical efficacy and safety of octreotide (SMS201-995) in terminally ill Japanese cancer patients with malignant bowel obstruction | journal = Japanese Journal of Clinical Oncology | volume = 38 | issue = 5 | pages = 354–9 | date = May 2008 | pmid = 18490369 | doi = 10.1093/jjco/hyn035 | doi-access = free }}

Octreotide may be used in conjunction with midodrine to partially reverse peripheral vasodilation in the hepatorenal syndrome. By increasing systemic vascular resistance, these medications reduce shunting and improve renal perfusion, prolonging survival until definitive treatment with liver transplant.{{cite journal | vauthors = Skagen C, Einstein M, Lucey MR, Said A | title = Combination treatment with octreotide, midodrine, and albumin improves survival in patients with type 1 and type 2 hepatorenal syndrome | journal = Journal of Clinical Gastroenterology | volume = 43 | issue = 7 | pages = 680–5 | date = August 2009 | pmid = 19238094 | doi = 10.1097/MCG.0b013e318188947c | s2cid = 19747120 }} Similarly, octreotide can be used to treat refractory chronic hypotension.{{cite web | vauthors = Tidy C | veditors = Cox J | work = Patient.info |title=Hypotension |date=February 2013 |url=https://patient.info/doctor/hypotension |access-date=26 June 2015 |archive-date=28 August 2021 |archive-url=https://web.archive.org/web/20210828194146/https://patient.info/doctor/hypotension |url-status=live }}{{Unreliable medical source|date=September 2024}}

While successful treatment has been demonstrated in case reports,{{cite journal | vauthors = Kilic D, Sahin E, Gulcan O, Bolat B, Turkoz R, Hatipoglu A | title = Octreotide for treating chylothorax after cardiac surgery | journal = Texas Heart Institute Journal | volume = 32 | issue = 3 | pages = 437–9 | year = 2005 | pmid = 16392238 | pmc = 1336729 }}{{cite journal | vauthors = Siu SL, Lam DS | title = Spontaneous neonatal chylothorax treated with octreotide | journal = Journal of Paediatrics and Child Health | volume = 42 | issue = 1–2 | pages = 65–7 | year = 2006 | pmid = 16487393 | doi = 10.1111/j.1440-1754.2006.00788.x | s2cid = 24561126 }} larger studies have failed to demonstrate efficacy in treating chylothorax.{{cite journal | vauthors = Chan EH, Russell JL, Williams WG, Van Arsdell GS, Coles JG, McCrindle BW | title = Postoperative chylothorax after cardiothoracic surgery in children | journal = The Annals of Thoracic Surgery | volume = 80 | issue = 5 | pages = 1864–70 | date = November 2005 | pmid = 16242470 | doi = 10.1016/j.athoracsur.2005.04.048 }}

A small study has shown{{when|date=February 2020}} that octreotide may be effective in the treatment of idiopathic intracranial hypertension.{{cite web | title=Intracranial Hypertension Research Foundation | website=ihrfoundation.org | date=17 May 2011 | url=http://ihrfoundation.org/intracranial/hypertension/info/C172 | archive-url=https://web.archive.org/web/20101219053757/http://ihrfoundation.org/intracranial/hypertension/info/C172 | archive-date=19 December 2010 | url-status=dead | access-date=30 September 2024}}{{Unreliable medical source|date=September 2024}}{{cite journal | vauthors = Panagopoulos GN, Deftereos SN, Tagaris GA, Gryllia M, Kounadi T, Karamani O, Panagiotidis D, Koutiola-Pappa E, Karageorgiou CE, Piadites G | display-authors = 6 | title = Octreotide: a therapeutic option for idiopathic intracranial hypertension | journal = Neurology, Neurophysiology, and Neuroscience | pages = 1 | date = July 2007 | pmid = 17700925 }}

Octreotide has been used experimentally to treat obesity, particularly obesity caused by lesions in the hunger and satiety centers of the hypothalamus, a region of the brain central to the regulation of food intake and energy expenditure.{{cite journal | vauthors = Lustig RH, Hinds PS, Ringwald-Smith K, Christensen RK, Kaste SC, Schreiber RE, Rai SN, Lensing SY, Wu S, Xiong X | display-authors = 6 | title = Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 6 | pages = 2586–92 | date = June 2003 | pmid = 12788859 | doi = 10.1210/jc.2002-030003 | doi-access = free }} The circuit begins with an area of the hypothalamus, the arcuate nucleus, that has outputs to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brain's feeding and satiety centers, respectively.{{cite journal | vauthors = Flier JS | title = Obesity wars: molecular progress confronts an expanding epidemic | journal = Cell | volume = 116 | issue = 2 | pages = 337–50 | date = January 2004 | pmid = 14744442 | doi = 10.1016/S0092-8674(03)01081-X | doi-access = free }}{{cite book | vauthors = Boulpaep EL, Boron WF |title=Medical physiologya: A cellular and molecular approach |publisher=Saunders |location=Philadelphia |year=2003 |page=1227 |isbn=978-0-7216-3256-8}} The ventromedial hypothalamus is sometimes injured by ongoing treatment for acute lymphoblastic leukemia or surgery or radiation to treat posterior cranial fossa tumors. With the ventromedial hypothalamus disabled and no longer responding to peripheral energy balance signals, "Efferent sympathetic activity drops, resulting in malaise and reduced energy expenditure, and vagal activity increases, resulting in increased insulin secretion and adipogenesis."{{cite journal | vauthors = Lustig RH | title = Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and treatment | journal = Frontiers in Endocrinology | volume = 2 | pages = 60 | year = 2011 | pmid = 22654817 | pmc = 3356006 | doi = 10.3389/fendo.2011.00060 | doi-access = free }} "VMH dysfunction promotes excessive caloric intake and decreased caloric expenditure, leading to continuous and unrelenting weight gain. Attempts at caloric restriction or pharmacotherapy with adrenergic or serotonergic agents have previously met with little or only brief success in treating this syndrome." In this context, octreotide suppresses the excessive release of insulin and may increase its action, thereby inhibiting excessive adipose storage. In a small clinical trial in eighteen pediatric subjects with intractable weight gain following therapy for acute lymphoblastic leukemia or brain tumors and other evidence of hypothalamic dysfunction, octreotide reduced body mass index (BMI) and insulin response during glucose tolerance test, while increasing parent-reported physical activity and quality of life (QoL) relative to placebo. In a separate placebo-controlled trial of obese adults without known hypothalamic lesions, obese subjects who received long-acting octreotide lost weight and reduced their BMI compared to subjects receiving placebo; post hoc analysis suggested greater effects in participants receiving the higher dose of the medication, and among "Caucasian subjects having insulin secretion greater than the median of the cohort." "There were no statistically significant changes in QoL scores, body fat, leptin concentration, Beck Depression Inventory, or macronutrient intake", although subjects taking octreotide had higher blood glucose after a glucose tolerance test than those receiving placebo.{{cite journal | vauthors = Lustig RH, Greenway F, Velasquez-Mieyer P, Heimburger D, Schumacher D, Smith D, Smith W, Soler N, Warsi G, Berg W, Maloney J, Benedetto J, Zhu W, Hohneker J | display-authors = 6 | title = A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion | journal = International Journal of Obesity | volume = 30 | issue = 2 | pages = 331–41 | date = February 2006 | pmid = 16158082 | pmc = 1540404 | doi = 10.1038/sj.ijo.0803074 }}

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Bynfezia Pen

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