Products
Pasireotide is commercially available as an injectable (Signifor, Signifor LAR). It was approved in the EU and many countries in 2012.
Structure and properties
Pasireotide (C59H67N9O9, Mr = 1046.2 g/mol) is present in the drug as pasireotide diaspartate or as pasireotide pamoate. It is a cyclohexapeptide and an analog of the hormone somatostatin. Somatostatin analogs were developed because the endogenous somatostatins themselves have a very short half-life of only a few minutes. In contrast, the half-life of pasireotide is approximately 12 hours.
Effects
Pasireotide (ATC H01CB05) inhibits the release of ACTH (adrenocorticotropin) from neuroendocrine tumors. The effects are due to binding of the drug to several subtypes of the somatostatin receptor (hsst1,2,3,5) and especially to hsst5. Other somatostatin analogs, such as octreotide (Sandostatin), bind with only moderate affinity to hsst5, the major tumor somatostatin receptor.
Indications
- As a 2nd-line agent for the treatment of Cushing’s disease if surgical therapy is not possible.
- For the treatment of acromegaly as a 2nd-line agent.
Dosage
According to the professional information.
Contraindications
- Hypersensitivity
- Severely impaired liver function
Full precautions can be found in the drug label.
Interactions
Pasireotide is a substrate of P-glycoprotein. Accordingly, drug-drug interactions with P-gp inhibitors are possible. Pasireotide could decrease the relative bioavailability of ciclosporin. It should be combined only with caution with drugs that prolong the QT interval. Clinical monitoring of heart rate is recommended in patients receiving pasireotide together with drugs that may induce bradycardia. Finally, dose adjustment of antidiabetic agents may be necessary because pasireotide can increase blood glucose. Pasireotide is excreted predominantly unchanged and is rarely metabolized. It does not interact with CYP450.
Adverse effects
The most common potential adverse effects include diarrhea, nausea, abdominal pain, gallstones, injection site reactions, hyperglycemia, diabetes mellitus, and fatigue. Pasireotide may prolong the QT interval and increase blood glucose levels.
