Pasireotide

Summary

Pasireotide (Signifor) is a second-generation somatostatin analogue approved for Cushing's disease (subcutaneous formulation) and acromegaly (long-acting release intramuscular formulation, Signifor LAR). It has a broader receptor binding profile than octreotide, with particular potency at SSTR5, making it effective in conditions driven by ACTH or GH excess.

Mechanism of Action

Binds with high affinity to somatostatin receptors (SSTR1, SSTR2, SSTR3, SSTR5), particularly SSTR5, suppressing secretion of ACTH from corticotroph adenomas, as well as GH and IGF-1 from somatotroph adenomas; also inhibits glucagon and insulin secretion.

Routes of Administration

Goals & Uses

• Reduction of GH and IGF-1 levelsHormonal ControlHigh
• Management of neuroendocrine tumorsOncologyModerate
• Treatment of Cushing's diseaseEndocrine DisorderHigh
• Treatment of acromegalyEndocrine DisorderHigh
• Reduction of ACTH secretionHormonal ControlHigh

Contraindications

• Severe hepatic impairment (Child-Pugh C)HepaticHigh
• Significant bradycardia or conduction abnormalitiesCardiacModerate
• Hypersensitivity to pasireotide or excipientsAllergyHigh
• Uncontrolled Diabetes MellitusMetabolic / EndocrineModerate

Adverse Effects

• Injection site reactionsLocalCommon
• CholelithiasisHepatobiliaryCommon
• Hyperglycemia / diabetes mellitusMetabolicCommon
• Adrenal insufficiencyEndocrineUncommon
• QT prolongationCardiovascularUncommonExtended QT interval on ECG
• DiarrheaGastrointestinalCommonLoose or frequent stools

Drug Interactions

• Antidiabetic agentsModerate
• CyclosporineModerate
• QT-prolonging drugs (e.g., antiarrhythmics, fluoroquinolones)Moderate
• Bromocriptine / dopamine agonistsLow

Population Constraints

• Moderate hepatic impairment (Child-Pugh B)HepaticRelative
• PregnancyReproductive SafetyRelative
• Patients with diabetes or pre-diabetesMetabolicRelative
• Pediatric patientsAgeRelative
• LactationReproductiveRelative

Regulatory Status

• European UnionApprovedApproved: Cushing's disease (subcutaneous), Acromegaly (LAR), Cushing's disease (LAR) - approved in some EU member statesEMA approval through centralized procedure; marketed by Recordati.
• United StatesApprovedApproved: Cushing's disease (subcutaneous; adults not amenable to pituitary surgery or for whom surgery has failed), Acromegaly (LAR; adults who have had inadequate response to surgery and/or for whom surgery is not an option)Signifor approved December 2012; Signifor LAR approved December 2014 by FDA.
• United KingdomApprovedApproved: Cushing's disease (subcutaneous), Acromegaly (LAR)Approved via MHRA following EU centralized procedure; retained post-Brexit.

FDA approved subcutaneous pasireotide (Signifor) for Cushing's disease in December 2012. FDA approved pasireotide LAR (Signifor LAR) for acromegaly in December 2014. EMA approved both formulations in the EU. Signifor LAR is also approved for Cushing's disease in some jurisdictions.

Evidence & Sources

No sources recorded yet.