Version May 2024
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 (ACG [Melmed 2018]).
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) (Colao 2014; Colao 2020; manufacturer’s labeling). 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 (Colao 2012; Petersenn 2017; manufacturer’s labeling). 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 (ES [Nieman 2015]).
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.
>10%:
Cardiovascular: Hypertension (8% to 15%), peripheral edema (10% to 14%)
Dermatologic: Alopecia (2% to 18%)
Endocrine & metabolic: Diabetes mellitus (immediate release: 6% to 20%; long-acting release: 21% to 31%), hypercholesterolemia (6% to 11%), hyperglycemia (29% to 47%), hypoglycemia (3% to 15%), increased gamma-glutamyl transferase (9% to 12%)
Gastrointestinal: Abdominal distension (5% to 12%), abdominal pain (8% to 25%), cholelithiasis (10% to 33%), decreased appetite (9% to 11%), diarrhea (immediate release: 58% to 59%; long-acting release: 16% to 39%), increased serum amylase (immediate release: 2%; long-acting release: 1% to 20%), increased serum lipase (immediate release: 6% to 9%; long-acting release: 1% to 30%), nausea (immediate release: 46% to 58%; long-acting release: 3% to 21%), upper abdominal pain (6% to 12%)
Hematologic & oncologic: Elevated glycosylated hemoglobin (5% to 12%), prolonged partial thromboplastin time (immediate release: 47%), prolonged prothrombin time (immediate release: 2% to 33%; long-acting release: 1%)
Hepatic: Increased serum alanine aminotransferase (≤14%), increased serum aspartate aminotransferase (≤14%)
Infection: Influenza (6% to 11%)
Local: Injection site reactions (immediate release: 17% to 18%; long-acting release: 2% to 7%)
Nervous system: Anxiety (immediate release: 6% to 11%), fatigue (10% to 27%), headache (immediate release: 28% to 29%; long-acting release: 3% to 19%), insomnia (immediate release: 4% to 14%)
Neuromuscular & skeletal: Asthenia (immediate release: 6% to 16%), back pain (5% to 11%), increased creatine phosphokinase in blood specimen (long-acting release: 13%), myalgia (5% to 12%)
Respiratory: Nasopharyngitis (6% to 16%)
1% to 10%:
Cardiovascular: Atrioventricular block (long-acting release: 6%), hypotension (6% to 8%), prolonged QT interval on ECG (1% to 6%), sinus bradycardia (3% to 10%)
Dermatologic: Pruritus (immediate release: 7% to 9%), xeroderma (immediate release: 6%)
Endocrine & metabolic: Adrenocortical insufficiency (2% to 7%), decreased cortisol, hyperuricemia (long-acting release: 7%), hypokalemia (immediate release: 5% to 7%), hypothyroidism (immediate release: 4%), impaired glucose tolerance/prediabetes, weight loss (long-acting release: 5%)
Gastrointestinal: Cholecystitis (long-acting release: 1%), cholestasis (long-acting release: 4%), constipation (5% to 9%), flatulence (long-acting release: 5%), pancreatitis (long-acting release: ≤1%), vomiting (3% to 10%)
Hematologic & oncologic: Anemia (3% to 6%)
Nervous system: Dizziness (2% to 10%), vertigo (immediate release: 5% to 8%)
Neuromuscular & skeletal: Arthralgia (6% to 10%), limb pain (5% to 7%)
Respiratory: Cough (long-acting release: 5%), upper respiratory tract infection (long-acting release: 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
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.
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): $366.88
0.6 mg/mL (per mL): $366.88
0.9 mg/mL (per mL): $366.88
Suspension Reconstituted ER (Signifor LAR Intramuscular)
10 mg (per each): $20,896.10
20 mg (per each): $20,896.10
30 mg (per each): $20,896.10
40 mg (per each): $20,896.10
60 mg (per each): $20,896.10
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 2016 [group 3]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
For IM or SUBQ preparation, NIOSH recommends double gloving, a protective gown, and ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator). Double gloving and a protective gown are required during administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Bromocriptine: Somatostatin Analogs may increase the serum concentration of Bromocriptine. Somatostatin Analogs may also delay bromocriptine absorption and time to maximum plasma concentrations. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect 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 serum concentrations of the active metabolite(s) of Codeine. Specifically, the concentrations of the active metabolite morphine may be reduced. Risk C: Monitor therapy
Copper Cu 64 Dotatate: Somatostatin Analogs may diminish the diagnostic effect of Copper Cu 64 Dotatate. 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 the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect 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: Somatostatin Analogs may diminish the diagnostic effect of Gallium Ga 68 Dotatate. 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: Somatostatin Analogs may diminish the diagnostic effect of Gallium Ga 68 Dotatoc. 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 enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Lutetium Lu 177 Dotatate: Somatostatin Analogs may diminish the therapeutic effect 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: Somatostatin Analogs may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Opioid Agonists: May diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs. Risk C: Monitor therapy
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Pegvisomant: Somatostatin Analogs may enhance the adverse/toxic effect of Pegvisomant. Specifically, this combination may increase the risk for significant elevations of liver enzymes. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect 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 enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect 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 therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect 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 therapy
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect 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 enhance the bradycardic effect 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
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
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 correlate with control of acromegaly; consider targeting postoperative GH level <0.4 mcg/L 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 (<138 nmol/L) or urinary free cortisol level <10 to 20 mcg/day (<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).
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
