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Acromegaly
Published in Nadia Barghouthi, Jessica Perini, Endocrine Diseases in Pregnancy and the Postpartum Period, 2021
SRLs include octreotide, lanreotide, and pasireotide. Octreotide and lanreotide are first-generation SRLs that bind with a high affinity to somatostatin receptor (SSTR) 2 subtype. There are multiple octreotide dosage forms, including a rapid-acting octreotide injection, long-acting release (LAR) injection, and a recently FDA-approved delayed-release oral capsule.9,14Lanreotide is a monthly subcutaneous injection.Pasireotide is a second-generation SRL that binds to both SSTR2 and SSTR5. Greater biochemical control has been demonstrated for pasireotide LAR when compared to octreotide LAR. Pasireotide LAR is associated with a higher rate of hyperglycemia and is therefore not an optimal choice for patients with poor glycemic control.13,15For patients on long-acting SRLs, Endocrine Society guidelines recommend transitioning to short-acting octreotide two months before trying to conceive.9 A recent review notes that patients frequently conceive while receiving long-acting SRLs and suggests measuring a human chorionic gonadotropin (hCG) level prior to each injection to minimize fetal exposure.6
Endocrine diseases and pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
The most likely clinical scenario involving acromegaly and pregnancy is pregnancy in a woman previously diagnosed and treated for the disease. She may in fact have been cured by transsphenoidal resection of an adenoma; confirmation of cure rests with sustained suppressibility of GH to oral glucose challenge and normalization of serum IGF-1. If so, pregnancy should be managed as a normal pregnancy. For patients not surgically cured, the most conventional and effective long-term management involves use of a long-acting somatostatin analog, either octreotide or lanreotide. Frequently, treatment with a somatostatin analog normalizes IGF-1 and restores fertility; consequently, pregnancy can occur. The available information about pregnancies occurring in treated women identifies no adverse fetal consequences (44–46). However, because octreotide and lanreotide do cross the placenta (47) and because experience with continuation of these drugs throughout pregnancy is extremely limited, a conservative and mainstream recommendation is to discontinue the somatostatin analog once pregnancy is recognized (40). Symptomatic enlargement of acromegalic pituitary adenomas during pregnancy is an uncommon complication (one reported case) (48); should this be encountered in the first two trimesters, consideration could be given to transsphenoidal resection or to reinstitution of somatostatin analog therapy.
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Lanreotide is used in the treatment of acromegaly resulting from both pituitary and nonpituitary growth hormone–secreting tumors, and for the management of other neuroendocrine tumors such as carcinoid tumors (e.g., carcinoid syndrome) and VIPomas. In the US and Canada, lanreotide is only indicated for the treatment of acromegaly. In the UK, lanreotide is recommended by NICE to treat neuroendocrine (particularly carcinoid) and thyroid tumors (by intramuscular injection), and neuroendocrine (particularly carcinoid) tumors, metastatic gastroenteropancreatic neuroendocrine tumors of the midgut, pancreas or unknown (by deep subcutaneous injection).
The industrial design, translation, and development strategies for long-acting peptide delivery
Published in Expert Opinion on Drug Delivery, 2022
Bin Yang, Ana Gomes Dos Santos, Sanyogitta Puri, Annette Bak, Liping Zhou
Lanreotide, a synthetic therapeutic octapeptide analogue of natural somatostatin, forms a depot upon SC injection for the purpose of SR. The process of this unique self-assembly starts with non-covalent peptide dimerization, followed by formation and growth of an open ribbon, and concluded with the formation of a ribbon closure in the shape of a hollow nanotube with a uniform diameter and wall thickness [48]. At a concentration of 10–15% w/w, the lanreotide semi-solid forms a gel consisting of densely packed nanotubes [49–51]. This nanostructure formation is a reversible process and slowly dissociates in the subcutaneous layer. The release of free active drug from the gel is governed by the intrinsic properties of the peptide and is most likely mediated by passive diffusion of lanreotide from the depot into the surrounding tissues, followed by the absorption into circulation. This peptide has a long terminal half-life (30.1 days) [52]. A 60-mg or 90-mg dose of the lanreotide depot administered every 4 weeks or a 120-mg dose every 6–8 weeks enables satisfactory management of the clinical symptoms [52–55]. Human peptide hormone oxyntomodulin can also self-assemble into nanofibrils and can be reversibly disassembled, releasing active peptide to achieve up to 5 days of desired plasma exposure [56,57].
Pharmacological and safety profile of a prolonged-release lanreotide formulation in acromegaly
Published in Expert Review of Clinical Pharmacology, 2021
Sebastian Neggers, Corin Badiu, Betina Biagetti, Lucie Durand-Gasselin, Anne Petit, Patrick Petrossians, Benjamin Regnault, David Rich, Zulfiya Shafigullina, Sergey Shustov, Anna Vydrych
This study showed that, with a new formulation, it is feasible to maintain concentrations of lanreotide above the efficacy threshold for longer after a single injection. The increase in lanreotide Cmax is approximately twice that seen for lanreotide autogel but did not affect the safety profile of the product. The PK profile of lanreotide PRF suggests that a dosing interval of 12 weeks is achievable, but that further development would be required to match the Ctrough of lanreotide autogel 120 mg. The MTD was not reached as no dose-limiting toxicities were recorded, indicating that doses >360 mg may be tolerated, although this may not be clinically beneficial. Furthermore, the safety and tolerability profile of lanreotide PRF were in line with that of existing lanreotide formulations. Taken together, these data demonstrate the potential impact of an excipient on release kinetics from a depot that could be used to optimize the release properties of any formulation.
Use of octreotide long acting repeatable (LAR) as second-line therapy in advanced neuroendocrine tumors in different clinical settings: an Italian Delphi survey
Published in Expert Opinion on Pharmacotherapy, 2020
Massimo Falconi, Nicola Fazio, Diego Ferone, Annibale Versari
Some of the experts held that continuing octreotide LAR in this scenario might be warranted depending on the degree of SSTR2 positivity in 68 Ga-DOTA-peptide-PET/CT, time and type of progression and control of hormonal symptoms. However, the choice of chemotherapy in second-line is likely related to rapid progression of disease, high disease burden, or severe symptoms, and there is no data in the literature suggesting that continuation of octreotide LAR would augment the effects of chemotherapy. Lastly, it should be highlighted that according to the respective Summaries of Product Characteristics, lanreotide is approved for pancreatic NETs, while octreotide is not approved for pancreatic NETs. This is relevant since chemotherapy is most used in patients with unresectable pancreatic NETs [47], and lanreotide could thus play a potential role in combination with chemotherapy.