lanreotide
Regulatory sources consulted
Approved indications
- Acromegaly not controlled after surgery or radiotherapy or requiring medical treatment; selected adult gastroenteropancreatic neuroendocrine tumors and symptoms associated with neuroendocrine tumors.
Contraindications
Absolute
- Hypersensitivity to lanreotide, somatostatin, related peptides, or excipients.
Clinical warnings
- Major warning · Periodically monitor the gallbladder; stop and treat if cholecystitis, cholangitis, biliary obstruction, or pancreatitis is suspected. — CIMA/AEMPS, ficha técnica 86174
- Major warning · Monitor glucose, thyroid function, and heart rate, especially when starting or changing the dose. — CIMA/AEMPS, ficha técnica 86174
Drug interactions
- ModerateCyclosporine
Mechanism: Lanreotide may reduce its intestinal absorption and bioavailability.
Recommendation: Monitor levels and adjust cyclosporine if needed.
CIMA/AEMPS, ficha técnica 86174
- ModerateBradycardia-inducing drugs
Mechanism: An additive effect on heart rate may occur.
Recommendation: Monitor heart rate and adjust concomitant treatment if appropriate.
CIMA/AEMPS, ficha técnica 86174
Adverse events
Common (≥1%)
Diarrhea, abdominal pain, cholelithiasis, and injection-site reactions
Rare but serious
Cholecystitis, cholangitis, and pancreatitis from biliary complications
Pregnancy and lactation
It is preferable to avoid it during pregnancy. It should not be used while breastfeeding because risk to the infant cannot be excluded.
Recent literature (PubMed)
Somatostatin analogs, such as octreotide, lanreotide, and pasireotide, which function as somatostatin receptor ligands (SRLs), are the main drugs used for the treatment of acromegaly. These ligands are also used as important molecules for radiation therapy and imaging of neuroendocrine tumors. Somatostatin receptors (SSTRs) are canonical G protein-coupled proteins that play a role in metabolism, growth, and pathological conditions such as hormone disorders, neurological diseases, and cancers. Cryogenic electron microscopy combined with the protein structure prediction platform AlphaFold has been used to determine the 3-dimensional structures of many proteins. Recently, several groups published a series of papers illustrating the 3-dimensional structure of SSTR2, including that of the inactive/activated SSTR2-G protein complex bound to different ligands. The results revealed the residues that contribute to the ligand binding pocket and demonstrated that Trp8-Lys9 (the W-K motif) in somatostatin analogs is the key motif in stabilizing the bottom part of the binding pocket. In this review, we discuss the recent findings related to the structural analysis of SSTRs and SRLs, the relationships between the structural data and clinical findings, and the future development of novel structure-based therapies. Insulinomas are rare pancreatic neuroendocrine neoplasms (panNENs - incidence of 1-3 cases per million per year). Most are solitary and do not show signs of malignant spread. Multiple synchronous or metachronous panNENs / insulinomas may occur in multiple endocrine neoplasia type 1 (MEN-1). The diagnosis of an insulinoma requires demonstration of inappropriately high insulin, proinsulin or C-peptide levels for the prevailing hypoglycemia in a 72h fast. Localization of the tumor and exclusion or confirmation of metastatic disease by computed tomography is still the preferred initial option followed by endoscopic ultrasonography (EUS) or MRI. Glucagon-like peptide receptor
Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly. To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs). This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had IGF-I ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0× ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary score, and maintenance of mean 5-sample GH <1.0 ng/mL. The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0× ULN (odds ratio, 126.53; 95% CI, 13.73->999.99; P < .0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (± SE) change in IGF-I of 0.04 ± 0.09× ULN vs 0.83 ± 0.1× ULN (P < .0001); mean (± SE) change in Acromegaly Symptom Diary score of -0.6 ± 1.5 vs 4.6 ± 1.6 (P = .02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) vs 5/18 (27.8%) patients (odds ratio, 16.61; 95% CI, 2.86-181.36; P = .0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs. Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated. The excretion of lanreotide into breastmilk has not been studied. However, because it has a high molecular weight of 1096 daltons it is likely to be poorly excreted into breastmilk and it is a peptide that is likely digested in the infant's gastrointestinal tract, so it is unlikely to reach the clinic