Pasireotide
Also known as: Signifor, Signifor LAR, SOM230, pasireotide diaspartate, pasireotide pamoate
Synthetic somatostatin analog; cyclohexapeptide; multi-receptor somatostatin ligand (SSTR1/2/3/5 agonist); pituitary-directed antisecretory agent
What it is
Pasireotide (Signifor, Signifor LAR) is an injectable medication FDA-approved for Cushing's disease — a dangerous hormonal condition caused by a pituitary tumor making too much ACTH, triggering excess cortisol. It is also approved for acromegaly not controlled by surgery. Unlike older somatostatin drugs, it uniquely targets multiple hormone receptors, making it effective where other analogs fail.
The scientific side
pasireotide is a synthetic cyclohexapeptide analog of somatostatin distinguished from first-generation analogs by its uniquely broad receptor-binding profile. While octreotide and lanreotide bind predominantly to somatostatin receptor subtypes 2 and 5 (SSTR2, SSTR5), pasireotide binds with high affinity to SSTR1, SSTR2, SSTR3, and SSTR5 — a pharmacological advantage that underlies its efficacy in conditions where SSTR5 predominates, particularly ACTH-secreting corticotroph adenomas causing Cushing's disease (PMIDs: 22850776, 26808354, 35670988). In Cushing's disease, ACTH-secreting pituitary tumors express SSTR5 as the dominant subtype; pasireotide's high-affinity binding to SSTR5 suppresses ACTH secretion from these tumors, thereby reducing downstream adrenal cortisol production and normalizing urinary free cortisol (PMIDs: 39526050, 30535260, 35670988). This mechanism is not shared by octreotide or lanreotide, which lack sufficient SSTR5 affinity to effectively suppress ACTH, explaining why pasireotide is the only somatostatin analog formally indicated for Cushing's disease. In acromegaly, pasireotide activates SSTR2 and SSTR5 on pituitary somatotroph adenomas to suppress excess growth hormone (GH) secretion and normalize insulin-like growth factor-1 (IGF-1) levels; SSTR1 and SSTR3 co-activation may contribute additional antisecretory and antiproliferative signaling via Gi protein-coupled reduction of adenylyl cyclase activity and inhibition of downstream proliferative cascades (PMIDs: 26808354, 26017304, 25260838). Pasireotide's receptor engagement also induces cytostatic effects on tumor cells, with data from the PAOLA Phase III trial showing tumor volume reductions in a proportion of acromegaly patients inadequately controlled on first-generation analogs. The long-acting release formulation (Signifor LAR) uses pamoate microspheres for monthly IM depot delivery, providing sustained plasma concentrations without the peaks and troughs of subcutaneous dosing (PMIDs: 26017304, 26808354). A distinct and clinically important consequence of pasireotide's multi-receptor activity is its pronounced suppression of insulin secretion — mediated by SSTR5 activation on pancreatic beta cells — which leads to hyperglycemia or new-onset diabetes mellitus in a large proportion of treated patients, a safety signal not seen to the same degree with SSTR2-selective analogs (PMIDs: 22850776, 35670988, 41489578).
Class: Synthetic somatostatin analog; cyclohexapeptide; multi-receptor somatostatin ligand (SSTR1/2/3/5 agonist); pituitary-directed antisecretory agent
Administration & storage
- Administration
- Subcutaneous injection (Signifor SC): inner thigh or abdomen; rotate injection sites; self-administered by patientDeep intramuscular injection into the gluteal muscle (Signifor LAR): administered by a healthcare professional only; alternating buttocks at each visit
- Storage
- Signifor SC ampules: store at room temperature (up to 30°C); protect from light. Signifor LAR kit: refrigerate at 2–8°C until use; remove from refrigerator 30 minutes before preparation to allow warming; do not freeze. Reconstituted Signifor LAR must be administered immediately after preparation.
- Cautions
- Hyperglycemia and new-onset diabetes mellitus: occurs in approximately 73% of patients on pasireotide SC in trials; SSTR5-mediated suppression of pancreatic beta-cell insulin secretion is the primary driver — this is more severe than with octreotide/lanreotide. Blood glucose monitoring is mandatory at initiation. Antidiabetic therapy should be started or intensified promptly. (PMIDs: 22850776, 35670988),Cholelithiasis: somatostatin receptor activation reduces gallbladder contractility; gallstones develop with chronic use; baseline and periodic ultrasound surveillance recommended,Bradycardia and QT interval prolongation: monitor ECG at baseline and during treatment; use with caution in patients with bradycardia, pre-existing cardiac disease, or concomitant QT-prolonging drugs,Adrenal insufficiency risk in Cushing's disease: rapid normalization of cortisol can unmask relative adrenal insufficiency; monitor for signs (fatigue, hypotension) and consider dose reduction if UFC falls below the lower limit of normal,Liver function: pasireotide may cause transient elevations in liver enzymes; assess LFTs at baseline and periodically,Breastfeeding: high molecular weight (~1047 Da) and peptide nature make significant breast milk transfer unlikely, but manufacturer recommends against use in nursing mothers,Gastrointestinal: nausea, diarrhea, and abdominal discomfort are common early adverse effects; typically mild to moderate and transient,Injection site reactions: erythema, pain, and induration reported at SC injection sites; site rotation mitigates cumulative reactions
Legal & regulatory status
FDA-approved as Signifor (pasireotide diaspartate) subcutaneous injection in December 2012 for adults with Cushing's disease for whom pituitary surgery is not an option or has not been curative. FDA-approved as Signifor…
Pasireotide is not explicitly listed on the WADA Prohibited List as a performance-enhancing substance. As a pituitary-acting somatostatin analog, it suppresses rather than augments growth hormone and IGF-1 levels, and…
Pasireotide (Signifor and Signifor LAR) has been reviewed and authorized by Health Canada. Signifor SC is approved for Cushing's disease and Signifor LAR for acromegaly, consistent with the FDA indications. Canadian…
What it's studied for
- Cushing's disease — reduction of urinary free cortisol and ACTH Phase III RCT
- Acromegaly inadequately controlled on first-generation somatostatin analogs — Phase III (PAOLA trial) Phase III RCT
- Acromegaly — medical therapy review and treatment landscape Systematic review / narrative review
- Cushing's disease — new treatment targets and pituitary-directed therapies Mixed (Phase II and observational)
- Neuroendocrine tumors (NETs) and carcinoid — exploratory use Phase II RCT
Safety signals
- Hyperglycemia and new-onset diabetes mellitus
- Cholelithiasis (gallstone formation) and biliary complications
- Bradycardia and QT interval prolongation
- Adrenal insufficiency (relative) in Cushing's disease
- Gastrointestinal adverse effects (nausea, diarrhea, abdominal pain)
- Injection site reactions
- Drug exposure in breastfeeding — manufacturer contraindication
Contraindications
About these dose ranges
Dose ranges below reflect commonly reported community protocols. Where published research cites a specific dose, the PMID is linked. Doses without citations are not clinical recommendations — they reflect what practitioners and researchers commonly report using.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Unspecified | 600–900 µg subcutaneous injection | — | Adults with Cushing's disease (Signifor SC) | Research |
| Unspecified | 40–60 mg intramuscular injection | — | Adults with acromegaly (Signifor LAR IM depot) | Research |
| subcutaneous injection | 600 µg SC BID, titrated to 900 µg SC BID based on UFC response and tolerability | twice daily (BID) | Adults with Cushing's disease for whom pituitary surgery is not an option or has not achieved remission | |
| deep intramuscular injection (gluteal muscle) | 40 mg IM depot, titrated to 60 mg IM depot every 28 days based on GH/IGF-1 response | once every 28 days | Adults with acromegaly with inadequate biochemical control on first-generation somatostatin analogs (octreotide LAR or lanreotide) |