Version July 2025
Note: In patients with diabetes mellitus, optimize antidiabetic therapy prior to initiating therapy. Correct hypokalemia and hypomagnesemia prior to initiating therapy.
Acromegaly:
Note: For use in patients who have persistent disease despite surgical resection (or in whom surgery is not appropriate), normal glucose tolerance, and inadequate response to first-line therapy (Ref).
IM (Signifor LAR): Initial: 40 mg once every 4 weeks.
Dosage adjustment: May increase to 60 mg once every 4 weeks after ≥3 months if growth hormone and/or insulin-like growth factor-1 (IGF-1) levels have not normalized (maximum: 60 mg once every 4 weeks) (Ref). If adverse reactions occur or IGF-1 level decreases below the lower limit of normal, decrease dosage (temporarily or permanently) in 20 mg decrements.
Missed dose: If a dose is missed, dose may be given up to but no later than 2 weeks prior to the next dose.
Cushing disease:
SUBQ (Signifor): Initial: 0.6 or 0.9 mg twice daily.
Dosage adjustment: May increase dose in increments of 0.3 mg twice daily (eg, from 0.6 mg twice daily to 0.9 mg twice daily) every 3 months if 24-hour urinary free cortisol (UFC) levels have not normalized, up to 1.2 mg twice daily (Ref). If adverse reactions occur, temporarily decrease dose by 0.3 mg twice daily. Recommended maintenance dosage range: 0.3 to 0.9 mg twice daily. Note: Maximum 24-hour UFC reductions are usually observed within 2 months of treatment (Ref).
IM (Signifor LAR): Initial: 10 mg once every 4 weeks.
Dosage adjustment: May increase dose after 4 months if 24-hour UFC levels have not normalized (maximum: 40 mg once every 4 weeks). If adverse reactions occur, may interrupt therapy (temporarily or permanently) or decrease to a previously tolerated dose.
Missed dose: If a dose is missed, dose may be given up to but no later than 2 weeks prior to the next dose.
Note: If hypocortisolism occurs (including low serum cortisol levels and/or symptoms of adrenal insufficiency), consider temporarily reducing the dose or interrupting/discontinuing pasireotide therapy and initiating glucocorticoid replacement therapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Acromegaly:
Signifor LAR:
Prior to initiation:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate hepatic impairment (Child-Pugh class B): Initial: 20 mg once every 4 weeks (maximum: 40 mg once every 4 weeks).
Severe hepatic impairment (Child-Pugh class C): Avoid use.
During therapy: Permanently discontinue therapy if signs/symptoms of clinically significant hepatic impairment occur.
Cushing disease:
Signifor:
Prior to initiation:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Initial: 0.3 mg twice daily (maximum: 0.6 mg twice daily)
Severe impairment (Child-Pugh class C): Use not recommended.
During therapy:
If ALT increases >3 times ULN or baseline value: Recheck ALT during recommended timeframe per recommendations in manufacturer's labeling for confirmation. If ALT level confirmed or increasing, interrupt therapy and investigate potential cause.
If any liver test ≥5 times ULN (with a normal baseline) OR >5 times the baseline value (with an abnormal baseline): Interrupt therapy and monitor liver tests more frequently per recommendations in manufacturer's labeling. If values return to normal or near normal, therapy may be reinitiated with extreme caution/monitoring only if another likely cause for hepatic effects is discovered.
Signifor LAR:
Prior to initiation:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate hepatic impairment (Child-Pugh class B): Initial: 10 mg once every 4 weeks (maximum: 20 mg once every 4 weeks).
Severe hepatic impairment (Child-Pugh class C): Avoid use.
During therapy: Permanently discontinue therapy if signs/symptoms of clinically significant hepatic impairment occur.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults for the immediate release (IR) and long-acting release (LAR) products unless otherwise indicated.
>10%:
Cardiovascular: Hypertension (8% to 15%), peripheral edema (10% to 14%)
Dermatologic: Alopecia (2% to 18%)
Endocrine & metabolic: Diabetes mellitus (IR: 6% to 20%; LAR: 21% to 31%), elevated glycosylated hemoglobin (5% to 12%), hypercholesterolemia (6% to 11%), hyperglycemia (29% to 47%), hypoglycemia (3% to 15%)
Gastrointestinal: Abdominal distension (5% to 12%), abdominal pain (8% to 25%), cholelithiasis (10% to 33%), decreased appetite (9% to 11%), diarrhea (IR: 58% to 59%; LAR: 16% to 39%), increased serum amylase (IR: 2%; LAR: 1% to 20%), increased serum lipase (IR: 6% to 9%; LAR: 1% to 30%), nausea (IR: 46% to 58%; LAR: 3% to 21%), upper abdominal pain (6% to 12%)
Hematologic & oncologic: Prolonged partial thromboplastin time (IR: 47%), prolonged prothrombin time (IR: 2% to 33%; LAR: 1%)
Hepatic: Increased gamma-glutamyl transferase (9% to 12%), increased serum alanine aminotransferase (≤14%), increased serum aspartate aminotransferase (≤14%)
Infection: Influenza (6% to 11%)
Local: Injection-site reactions (IR: 17% to 18%; LAR: 2% to 7%)
Nervous system: Anxiety ( IR: 6% to 11%), asthenia (IR: 6% to 16%), fatigue (10% to 27%), headache (IR: 28% to 29%; LAR: 3% to 19%), insomnia (IR: 4% to 14%)
Neuromuscular & skeletal: Back pain (5% to 11%), increased creatine phosphokinase in blood specimen (LAR: 13%), myalgia (5% to 12%)
Respiratory: Nasopharyngitis (6% to 16%)
1% to 10%:
Cardiovascular: Atrioventricular block (LAR: 6%), hypotension (6% to 8%), prolonged QT interval on ECG (1% to 6%), sinus bradycardia (3% to 10%)
Dermatologic: Pruritus (IR: 7% to 9%), xeroderma (IR: 6%)
Endocrine & metabolic: Adrenocortical insufficiency (2% to 7%), decreased cortisol, hyperuricemia (LAR: 7%), hypokalemia (IR: 5% to 7%), hypothyroidism (IR: 4%), impaired glucose tolerance, weight loss (LAR: 5%)
Gastrointestinal: Cholecystitis (LAR: 1%), cholestasis (LAR: 4%), constipation (5% to 9%), flatulence (LAR: 5%), pancreatitis (LAR: ≤1%), vomiting (3% to 10%)
Hematologic & oncologic: Anemia (3% to 6%)
Nervous system: Dizziness (2% to 10%), vertigo (IR: 5% to 8%)
Neuromuscular & skeletal: Arthralgia (6% to 10%), limb pain (5% to 7%)
Respiratory: Cough (LAR: 5%), upper respiratory tract infection (LAR: 7%)
<1%: Endocrine & metabolic: Diabetic ketoacidosis
Frequency not defined: Hepatic: Increased serum bilirubin
Postmarketing:
Cardiovascular: Bradycardia
Endocrine & metabolic: Ketoacidosis (includes patients without a history of diabetes)
Gastrointestinal: Cholangitis, fecal discoloration, steatorrhea
There are no contraindications listed in the manufacturer's labeling.
Canadian labeling: Hypersensitivity to pasireotide or any component of the formulation; moderate or severe hepatic impairment (Child-Pugh B or C); uncontrolled diabetes (HbA1c ≥8%) despite receiving anti-diabetic therapy; NYHA Class III to IV heart failure; cardiogenic shock; second- or third-degree atrioventricular (AV) block, sinoatrial block, sick sinus syndrome (unless patient has a functioning pacemaker); severe bradycardia; congenital long QT syndrome or baseline QTc interval ≥500 ms.
Concerns related to adverse effects:
• Cardiac disorders: Bradycardia and QT prolongation have been observed with therapy. Use with caution in patients with preexisting cardiac disease, patients with risk factors for bradycardia (eg, high-grade heart block, history of significant bradycardia, receiving concomitant drugs known to cause bradycardia), and/or patients at risk for QT prolongation (eg, congenital long QT, recent myocardial infarction (MI), heart failure, unstable angina, hypokalemia, hypomagnesemia, receiving concomitant drugs known to cause QT prolongation). Correct hypokalemia and/or hypomagnesemia prior to therapy and monitor during therapy.
• Cholelithiasis: Cholelithiasis and complications of cholelithiasis (eg, cholecystitis, cholangitis, pancreatitis) requiring cholecystectomy have been reported; monitor periodically for cholelithiasis; discontinue and treat appropriately if suspected.
• Hepatic effects: Increased liver enzymes have been reported.
• Hyperglycemia/diabetes/ketoacidosis: Inhibition of insulin and glucagon secretion may affect glucose regulation, leading to hyperglycemia (sometimes severe). Cases of ketoacidosis have been reported in patients with or without a history of diabetes; patients with predisposing factors, including acute illness, infection, pancreatic disorders (eg, pancreatic malignancy, pancreatic surgery), and alcohol abuse may be at greater risk. Exacerbation of glycemia occurred in the majority of patients during the initial months of therapy, including patients with normal glucose levels at baseline; diabetes and prediabetes has also been observed. Patients with poor baseline glycemic control are at higher risk of developing severe hyperglycemia. If hyperglycemia occurs, initiation or dosage adjustment of antidiabetic therapy is recommended; if uncontrolled hyperglycemia persists despite antidiabetic therapy, consider dosage reduction or discontinuation of pasireotide. Following discontinuation of pasireotide, continued monitoring of blood glucose may be required if hypoglycemia is a risk. Assess patients presenting with signs and symptoms consistent with severe metabolic acidosis for ketoacidosis; discontinue pasireotide and promptly treat patients if ketoacidosis is suspected.
• Hypocortisolism: Suppression of the adrenocorticotropic hormone from therapy may lead to hypocortisolism in Cushing disease.
• Hypothyroidism: Decreases (slight) in thyroid function have been observed during therapy.
• Pituitary hormone deficiency (anterior): May cause inhibition of anterior pituitary hormones. Patients who have undergone transsphenoidal surgery and pituitary irradiation are at an increased risk for deficiency.
Disease-related concerns:
• Diabetes mellitus: Exacerbation of glycemia commonly occurs with pasireotide use.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
Other warnings/precautions:
• Malabsorption of dietary fats: Somatostatin analogs reversibly inhibit secretion of pancreatic enzymes and bile acids which may lead to the malabsorption of dietary fats and symptoms of abdominal bloating, loose stools, steatorrhea, stool discoloration, and weight loss. Evaluate patients experiencing new or worsening symptoms for possible exocrine insufficiency and manage as clinically appropriate.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous, as diaspartate [strength expressed as base]:
Signifor: 0.3 mg/mL (1 mL); 0.6 mg/mL (1 mL); 0.9 mg/mL (1 mL)
Suspension Reconstituted ER, Intramuscular, as pamoate [strength expressed as base]:
Signifor LAR: 10 mg (1 ea); 30 mg (1 ea); 20 mg (1 ea); 40 mg (1 ea); 60 mg (1 ea)
No
Solution (Signifor Subcutaneous)
0.3 mg/mL (per mL): $421.82
0.6 mg/mL (per mL): $421.82
0.9 mg/mL (per mL): $421.82
Suspension Reconstituted ER (Signifor LAR Intramuscular)
10 mg (per each): $24,025.28
20 mg (per each): $24,025.28
30 mg (per each): $24,025.28
40 mg (per each): $24,025.28
60 mg (per each): $24,025.28
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous, as diaspartate [strength expressed as base]:
Signifor: 0.3 mg/mL (1 mL)
Suspension Reconstituted ER, Intramuscular, as pamoate [strength expressed as base]:
Signifor LAR: 10 mg (1 ea); 30 mg (1 ea); 20 mg (1 ea); 40 mg (1 ea); 60 mg (1 ea)
In Canada, patients prescribed Signifor must be enrolled in the Access Program for Signifor (Novartis Canada).
IM: Signifor LAR: Administer only by IM injection into the left or right gluteus immediately after reconstitution.
SUBQ: Signifor: Administer only by SUBQ injection into the top of the thigh or abdomen (excluding the navel and waistline). Do not inject into inflamed or irritated skin. Alternate the injection site.
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Signifor: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/200677s003lbl.pdf#page=18
Signifor LAR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/203255s004lbl.pdf#page=27
Acromegaly (Signifor LAR): Treatment of acromegaly in patients who have had an inadequate response to surgery and/or for whom surgery is not an option.
Cushing disease (Signifor and Signifor LAR): Treatment of Cushing disease in patients for whom pituitary surgery is not an option or has not been curative
Pasireotide may be confused with lanreotide, octreotide
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Androgens: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Antidiabetic Agents: May increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor
Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Bromocriptine: Somatostatin Analogs may increase serum concentration of Bromocriptine. Somatostatin Analogs may also delay bromocriptine absorption and time to maximum plasma concentrations. Risk C: Monitor
Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider Therapy Modification
Codeine: Somatostatin Analogs may decrease active metabolite exposure of Codeine. Specifically, the concentrations of the active metabolite morphine may be reduced. Risk C: Monitor
Copper Cu 64 Dotatate: Coadministration of Somatostatin Analogs and Copper Cu 64 Dotatate may alter diagnostic results. Management: Imaging with copper Cu 64 dotatate positron emission tomography (PET) should be performed just prior to dosing with somatostatin analogs. If on somatostatin analogs, stop long-acting agents 28 days before, and short-acting agents 2 days before, imaging. Risk D: Consider Therapy Modification
CycloSPORINE (Systemic): Somatostatin Analogs may decrease serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
Etrasimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Fexinidazole: Bradycardia-Causing Agents may increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid
Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider Therapy Modification
Gallium Ga 68 Dotatate: Coadministration of Somatostatin Analogs and Gallium Ga 68 Dotatate may alter diagnostic results. Specifically, a false negative PET scan may occur if Gallium GA 68 Dotatate is used during treatment with somatostatin analogs. Management: It is recommended to image with gallium Ga 68 dotatate positron emission tomography (PET) just prior to dosing with long-acting somatostatin analogs. Short-acting somatostatin analogs can be used up to 24 hours before imaging with gallium Ga 68 dotatate. Risk D: Consider Therapy Modification
Gallium Ga 68 Dotatoc: Coadministration of Somatostatin Analogs and Gallium Ga 68 Dotatoc may alter diagnostic results. Management: Imaging with gallium Ga 68 dotatoc positron emission tomography (PET) should be performed just prior to dosing with long-acting somatostatin analogs. Short-acting somatostatin analogs can be used up to 24 hours before imaging with gallium Ga 68 dotatoc. Risk D: Consider Therapy Modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Herbal Products with Glucose Lowering Effects: May increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor
Hypoglycemia-Associated Agents: May increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor
Ivabradine: Bradycardia-Causing Agents may increase bradycardic effects of Ivabradine. Risk C: Monitor
Lacosamide: Bradycardia-Causing Agents may increase AV-blocking effects of Lacosamide. Risk C: Monitor
Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of Landiolol. Risk X: Avoid
Lutetium Lu 177 Dotatate: Somatostatin Analogs may decrease therapeutic effects of Lutetium Lu 177 Dotatate. Specifically, the therapeutic effect of Lutetium Lu 177 Dotatate may be diminished if the timing of Somatostatin Analog administration is not carried out as recommended. Management: Discontinue long-acting somatostatin analogs at least 4 weeks and short-acting octreotide at least 24 hours prior to lutetium Lu 177 dotatate dose. Administer short and long-acting octreotide during treatment as recommended. See full interaction monograph Risk D: Consider Therapy Modification
Macimorelin: Coadministration of Somatostatin Analogs and Macimorelin may alter diagnostic results. Risk X: Avoid
Maitake: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Midodrine: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Monoamine Oxidase Inhibitors: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Opioid Agonists: May decrease analgesic effects of Somatostatin Analogs. Opioid Agonists may increase analgesic effects of Somatostatin Analogs. Risk C: Monitor
Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Pegvisomant: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Pegvisomant: Somatostatin Analogs may increase adverse/toxic effects of Pegvisomant. Specifically, this combination may increase the risk for significant elevations of liver enzymes. Risk C: Monitor
Ponesimod: Bradycardia-Causing Agents may increase bradycardic effects of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider Therapy Modification
Prothionamide: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Quinolones: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Quinolones may decrease therapeutic effects of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor
Salicylates: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Selective Serotonin Reuptake Inhibitor: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider Therapy Modification
Siponimod: Bradycardia-Causing Agents may increase bradycardic effects of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider Therapy Modification
Fertility may be improved with treatment in patients who may become pregnant following normalization of serum cortisol in patients with Cushing disease, and normalization of insulin-like growth factor 1 and growth hormone in patients with acromegaly. Pasireotide may be used for patients with acromegaly who are trying to conceive; discontinue once pregnancy is confirmed (ESE [Luger 2021]). The Endocrine Society acromegaly guidelines recommend patients who may become pregnant use adequate contraception during treatment, and suggest discontinuing long-acting formulations of somatostatin analogs approximately 2 months prior to a planned pregnancy; short-acting octreotide may be used until conception if needed for the treatment of acromegaly (ES [Katznelson 2014]).
Information related to the use of pasireotide is insufficient to recommend its use for the treatment of acromegaly during pregnancy (ESE [Luger 2021]). If treatment for acromegaly is required during pregnancy for worsening symptoms (eg, headaches or evidence of worsening tumor), alternative agents are recommended. Monitoring of insulin-like growth factor 1 (IGF-1) and/or growth hormone (GH) is not recommended during pregnancy, as an active placental GH variant present in maternal blood limits the usefulness of the results (ES [Katznelson 2014]; ESE [Luger 2021]). Information related to the use of pasireotide is also insufficient to recommend its use for the treatment of Cushing syndrome in pregnant patients (ESE [Luger 2021]).
It is not known if pasireotide is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
ECG at baseline (also consider continued monitoring during treatment; in patients receiving Signifor LAR who are at high risk of QT prolongation, repeat 21 days after injection); serum potassium and magnesium (prior to and periodically during therapy); pituitary function (eg, thyroid-stimulating hormone, free thyroxine, growth hormone [GH], insulin-like growth factor-1 [IGF-1], gonadal function; baseline then periodically); adrenal function (including signs/symptoms of adrenal insufficiency; prior to and periodically during therapy); heart rate (patients with cardiac disease and/or risk factor for bradycardia); cholelithiasis (periodically during therapy; in patients receiving Signifor, perform gall bladder ultrasonography at baseline and every 6 to 12 months during therapy).
Glycemic parameters: FBG and HbA1c prior to initiation; blood glucose weekly for the first 2 to 3 months and periodically thereafter as appropriate; monitor blood glucose weekly following dose increases for several weeks (eg, for 2 to 4 weeks in patients receiving Signifor, and for 4 to 6 weeks in patients receiving Signifor LAR). If glucose tolerance is consistently normal after 3 months of monitoring, may consider reduced monitoring (eg, HbA1c every 3 to 6 months [Coopmans 2019]). Following discontinuation of pasireotide, continued monitoring of blood glucose may be required if hypoglycemia is a risk.
Liver function tests:
Signifor LAR: Prior to initiation, 2 to 3 weeks after initiation, then monthly for 3 months and as clinically indicated; during therapy, discontinue if clinically significant liver impairment develops and monitor liver function until resolution.
Signifor: Prior to initiation, 1 to 2 weeks after initiation, then monthly for 3 months, then every 6 months thereafter; more frequent testing may be necessary:
If ALT normal at baseline and ALT increases 3 to 5 times ULN on therapy: Repeat ALT within 1 week
If ALT normal at baseline and ALT increases >5 times ULN on therapy: Repeat ALT within 48 hours
If ALT abnormal at baseline and ALT increases 3 to 5 times baseline values on therapy: Repeat ALT within 1 week
If ALT abnormal at baseline and ALT increases >5 times ULN on therapy: Repeat ALT <1 week
Note: ALT levels should be done in a laboratory capable of same-day results; if ALT levels are confirmed or rising, interrupt therapy and investigate cause.
During therapy, if any liver test ≥5 times ULN (with a normal baseline) OR >5 times the baseline value (with an abnormal baseline), interrupt therapy and monitor ALT, AST, alkaline phosphatase, and total bilirubin weekly or more frequently. If values return to normal or near normal, therapy may be reinitiated with extreme caution/monitoring only if another likely cause for hepatic effects discovered.
Acromegaly: Serum GH and IGF-1 levels at 3 months (prior to dosage adjustment) and as clinically indicated.
Cushing disease: Urinary free cortisol (24-hour) at 4 months (prior to dosage adjustment) and as clinically indicated.
Acromegaly: Age-normalized serum insulin-like growth factor 1 (IGF-1) and a random growth hormone (GH) <1 mcg/L (SI: <1 ng/mL) correlate with control of acromegaly; consider targeting postoperative GH level <0.4 mcg/L (SI: <0.4 ng/mL) if ultra-sensitive GH assay is available; use of the same IGF-1 and GH assay in the same patient throughout management is suggested (ACG [Melmed 2018]; ES [Katznelson 2014]).
Cushing disease: Morning serum cortisol level <5 mcg/dL (SI: <138 nmol/L) or urinary free cortisol level <10 to 20 mcg/day (SI: <28 to 56 nmol/day) (ES [Nieman 2015]).
Pasireotide is a cyclohexapeptide somatostatin analog, which is a peptide inhibitor of multiple endocrine, neuroendocrine, and exocrine mechanisms. In patients with Cushing disease, pasireotide binds to somatostatin receptor (sst1-5), with high affinity for the sst1, sst2, sst3 subtypes, and highest affinity for the sst5 subtype, resulting in inhibition of ACTH secretion which leads to decreased cortisol secretion. In patients with acromegaly, pasireotide binds to sst2 and sst5, resulting in decreased GH and IGF-1.
Distribution: Vd: >100 L
Protein binding: 88%
Metabolism: Primarily eliminated as unchanged drug hepatically (via biliary excretion)
Half-life elimination: Subcutaneous: ~12 hours
Time to peak, plasma: Subcutaneous: 0.25 to 0.5 hours
Excretion: Feces (~40% to 56%, primarily as unchanged drug); urine (~6% to 10%, primarily as unchanged drug)
Hepatic function impairment: AUCinf was increased by 12%, 56%, and 42% and Cmax was increased by 3%, 46%, and 33%, respectively, in mild, moderate, and severe hepatic impairment (Child-Pugh class A, B, and C).
