pasireotide
Sources réglementaires consultées
Indications approuvées
- Acromégalie de l’adulte insuffisamment contrôlée par un autre analogue de la somatostatine lorsque la chirurgie est impossible ou non curative ; maladie de Cushing de l’adulte lorsque la chirurgie a échoué ou est impossible.
Contre-indications
Absolues
- Hypersensibilité au pasiréotide ou aux excipients.
- Insuffisance hépatique sévère, Child-Pugh C.
Mises en garde cliniques
- Mise en garde majeure · L’hyperglycémie est fréquente et peut être sévère. Évaluer la glycémie/l’HbA1c avant le traitement, surveiller pendant le traitement et adapter les antidiabétiques. — CIMA/AEMPS, ficha técnica 112753013
- Mise en garde majeure · Surveiller la fonction hépatique, le QTc, les électrolytes, la bradycardie, la vésicule biliaire et les signes d’hypocortisolisme. — CIMA/AEMPS, ficha técnica 112753013
Interactions médicamenteuses
- SévèreMédicaments allongeant le QT
Mécanisme: Ils peuvent augmenter le risque d’allongement du QT et d’arythmie.
Recommandation: Envisager des alternatives et surveiller l’ECG et les électrolytes.
CIMA/AEMPS, ficha técnica 112753013
- ModéréeCiclosporine
Mécanisme: Le pasiréotide peut réduire sa biodisponibilité.
Recommandation: Surveiller les concentrations et ajuster la ciclosporine.
CIMA/AEMPS, ficha técnica 112753013
Effets indésirables
Communs (≥1%)
Diarrhée, lithiase biliaire, hyperglycémie et diabète sucré
Rares mais graves
Insuffisance surrénalienne et hépatotoxicité sévère
Grossesse et allaitement
Non recommandé pendant la grossesse ni chez les femmes en âge de procréer sans contraception. L’allaitement doit être interrompu pendant le traitement.
Bibliographie récente (PubMed)
Dumping syndrome is a complex of gastrointestinal symptoms originally studied in peptic ulcer surgery patients. At present, it is most prevalent in patients who underwent bariatric, upper gastrointestinal cancer or anti-reflux surgery. The symptom pattern comprises early and late dumping symptoms. Several management options have been reported including nutritional, pharmacological and surgical approaches. In this study, we aimed to review the current evidence on dumping syndrome definition, diagnosis and treatment, including preliminary data from newer pharmacological studies. Current pathophysiological concepts and analyses of provocative tests has led to a clear definition of dumping syndrome, including both early and late dumping symptoms. The term postbariatric hypoglycemia represents a limited focus on late dumping only. The diagnosis relies on recognition of symptoms and signs in a patient with appropriate surgical history; and can be confirmed by provocative testing or registration of spontaneous hypoglycemia. The initial treatment focuses on dietary intervention, to which meal viscosity enhancers and/or the glycosidase inhibitor acarbose can be added. The most effective therapy is the use of short- or long-acting somatostatin analogues, which is however expensive and entails side effect issues. In case of refractory hypoglycemia, diazoxide or SGLT2 inhibitors can be considered, based on limited evidence. In refractory patients, continuous enteral feeding or (rarely) surgical reinterventions have been advocated, although not supported by solid evidence. Therapies under current evaluation include the broad-spectrum somatostatin analogue pasireotide, GLP-1 receptor antagonists, GLP-1 receptor agonists and administration of stable forms of glucagon are currently under study. Dumping syndrome is a well-defined but probably under-diagnosed complication of upper gastrointestinal, especially bariatric, and surgeries. Diagnosis is confirmed by a provocative test and
Somatotroph adenomas are usually controlled with standard therapy, which can include surgery, medical treatment and radiotherapy. Some tumors have a more aggressive behavior and are refractory to standard therapy. In this review, we summarize the phenotype of these tumors and the current options for their management.
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.
Medical treatment of hypercortisolism may be necessary for a high proportion of patients with Cushing syndrome (CS), including those who are not candidates for curative surgery. It may also be used in the presurgical period when hypercortisolism is severe, as long-term treatment following surgical failure or recurrence after surgery, or while waiting for the effects of pituitary radiation in Cushing disease. Currently available medical treatments include adrenal steroidogenesis inhibitors that block cortisol secretion (ketoconazole, levoketoconazole, metyrapone, osilodrostat, mitotane, and etomidate), drugs that modulate pituitary ACTH secretion (pasireotide and cabergoline), and drugs that block peripheral glucocorticoid receptors (mifepristone). In addition, there are other medical treatments in development that target pituitary signaling pathways, ACTH or its adrenal receptor, or the conversion of cortisol from cortisone by 11ßHSD1. Steroidogenesis inhibitors can be administered using either a titration or a block-and-replace approach. Titration requires adjusting the daily drug dose with the aim of normalizing circulating cortisol levels, whereas the block-and-replace strategy uses higher drug doses to fully suppress endogenous cortisol production, followed by glucocorticoid supplementation. In this review, we summarize the main indications for medical treatment in CS, the mechanism of drug action, efficacy, recommended doses, and safety of the currently available drugs, as well as potential future treatments. We also discuss titration and block-and-replace approaches for control of hypercortisolism and provide recommendations for the use and monitoring of medical treatment in CS, including patients with endogenous hypercortisolism in special situations such as pregnancy, cyclic CS, and mild autonomous cortisol secretion.