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Octreotide: Drug information

Octreotide: Drug information
(For additional information see "Octreotide: Patient drug information" and see "Octreotide: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Bynfezia Pen [DSC];
  • Mycapssa;
  • SandoSTATIN;
  • SandoSTATIN LAR Depot
Brand Names: Canada
  • Octreotide Acetate Omega;
  • SandoSTATIN;
  • SandoSTATIN LAR
Pharmacologic Category
  • Antidiarrheal;
  • Antidote;
  • Somatostatin Analog
Dosing: Adult
Acromegaly

Acromegaly:

Note: For use in patients with persistent disease following surgery or in whom surgery is not appropriate (Ref). May use the long-acting IM depot formulation as initial therapy (Ref) or may consider 1 or 2 doses of SubQ octreotide to assess tolerability prior to starting the long-acting IM depot (Ref). If clinical and/or biochemical response is inadequate at maximum dosage of octreotide, consider alternative agents or starting combination therapy (Ref).

IM (depot): Initial: 20 mg intragluteally every 4 weeks for 3 months; after initial 3 months, adjust dose as necessary based on clinical response. Dosage titration example provided from the manufacturer's labeling:

Growth hormone (GH) ≤1 ng/mL, insulin-like growth factor 1 (IGF-1) normal, and symptoms controlled: Reduce octreotide depot to 10 mg every 4 weeks.

GH >1 to ≤2.5 ng/mL, IGF-1 normal, and symptoms controlled: Maintain octreotide depot at 20 mg every 4 weeks.

GH >2.5 ng/mL, IGF-1 elevated, and/or symptoms uncontrolled: Increase octreotide depot to 30 mg every 4 weeks. If GH, IGF-1, or symptoms remain uncontrolled, may increase dose to 40 mg every 4 weeks. Dosages >40 mg are not recommended by the manufacturer; however, in some cases, individualized doses up to 60 mg every 4 weeks have been used successfully in partial responders (Ref).

SubQ: Initial: 50 mcg 3 times daily; titrate to achieve target GH and IGF-1 levels. Usual effective dose: 100 mcg 3 times daily; range: 300 to 1,500 mcg/day. Doses above 300 mcg/day rarely result in additional benefit; if increased dose fails to provide additional benefit, the dose should be reduced.

Oral: Note: For long-term maintenance treatment in patients who respond to and tolerate treatment with injectable octreotide or lanreotide.

Initial: 20 mg twice daily; adjust dose in 20 mg/day increments every 2 to 4 weeks as necessary based on clinical response as follows (Ref):

60 mg/day: Administer as 40 mg every morning and 20 mg every evening.

80 mg/day: Administer as 40 mg twice daily (maximum: 80 mg/day).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Carcinoid crisis, prevention and treatment

Carcinoid crisis, prevention and treatment (off-label use):

IR octreotide solution:

Prevention:

Note: Consider use prior to invasive procedures in patients with carcinoid syndrome. Octreotide IR solution should be readily available during any surgical procedure in case hemodynamic instability occurs (Ref).

Patients controlled with octreotide IM (depot) 20 to 30 mg every 4 weeks: SubQ: 250 to 500 mcg within 1 to 2 hours prior to procedure (Ref).

Somatostatin analogue-naive patients (Ref):

IV bolus: 500 to 1,000 mcg 1 to 2 hours prior to procedure.

or

SubQ: 500 mcg 1 to 2 hours prior to procedure.

Treatment:

Intraoperative use for carcinoid crisis with hypotension: IV: 500 to 1,000 mcg bolus, repeat at 5-minute intervals until symptoms are controlled or 500 to 1,000 mcg bolus followed by 50 to 200 mcg/hour continuous infusion during the procedure (Ref).

Postoperative use for patients requiring intraoperative therapy: IV: 50 to 200 mcg/hour continuous infusion for 24 hours, followed by resumption of the preoperative treatment schedule (Ref).

Carcinoid syndrome

Carcinoid syndrome:

Note: The North American Neuroendocrine Tumor Society (NANETS) guidelines suggest that the long-acting depot may be appropriate as initial therapy (ie, without prior SubQ octreotide as stated in the US labeling) (Ref). For patients experiencing breakthrough symptoms while taking the long-acting depot, supplementary doses of SubQ octreotide may be necessary.

IM (depot):

Initial: 20 mg intragluteally every 4 weeks (Ref) or 20 to 30 mg intragluteally every 4 weeks (Ref).

Titration: Dose may be modified based on response as follows:

May decrease to 10 mg every 4 weeks after 2 months if initially responsive to 20 mg dose.

Increase to 30 mg every 4 weeks if symptoms are inadequately controlled after 2 months. Note: The US labeling states that higher doses are not recommended; however, if frequent supplementary SubQ doses are needed (eg, ≥3 to 4 times/week), may consider further increasing the dose by 10 mg every 4 weeks, or maintaining the same dose and reducing the dosing interval to every 3 weeks, up to a maximum off-label dose of 60 mg every 4 weeks (Ref).

SubQ, IV: Initial: 100 to 600 mcg/day in 2 to 4 divided doses. If additional symptom control is needed, may increase by doubling the dose every 3 to 4 days until symptoms are controlled; usual range: 50 to 750 mcg/day. Experience with doses above 750 mcg/day is limited; however, may consider a continuous SubQ infusion of 1,000 to 2,000 mcg/day off label in patients who remain symptomatic on intermittent doses (Ref).

Diarrhea associated with acute graft-versus-host disease

Diarrhea associated with acute graft-versus-host disease (off-label use):

Note: Use in combination with other appropriate agents (eg, corticosteroids) for the management of acute graft-versus-host disease (GVHD) (Ref).

IV: 500 mcg every 8 hours; discontinue within 24 hours of diarrhea resolution to avoid ileus. Maximum duration of therapy if diarrhea is not resolved: 7 days (Ref).

Diarrhea associated with chemotherapy, refractory

Diarrhea associated with chemotherapy, refractory (off-label use):

Low grade or uncomplicated, persistent: SubQ: 100 to 150 mcg 3 times daily (Ref).

Severe or complicated:

IV, SubQ: Initial: 100 to 150 mcg 3 times daily; may increase to 500 to 2,000 mcg IV or SubQ 3 times daily (Ref).

or

IV infusion: 25 to 50 mcg/hour (Ref).

Duration of therapy: Discontinue therapy within 24 hours of resolution of diarrhea to reduce the risk of ileus (Ref).

Fistulas, high-output, gastroenteropancreatic

Fistulas, high-output, gastroenteropancreatic (off-label use):

Note: Reserve use for patients with fistula output >1 to 1.5 L/day; in patients with enterocutaneous fistula, avoid use if barriers to spontaneous closure (eg, distal obstruction, Crohn disease) are present (Ref).

SubQ: 100 mcg 3 times daily; discontinue and consider alternative agents if fistula output does not decrease after 3 to 5 days (Ref).

Gastroenteropancreatic neuroendocrine tumors, functional, gastrin-secreting, refractory

Gastroenteropancreatic neuroendocrine tumors, functional, gastrin-secreting (gastrinoma, Zollinger-Ellison syndrome), refractory (alternative agent) (off-label use):

Note: May be used to control symptoms of hormone hypersecretion (eg, ulcers, heartburn, diarrhea) refractory to first-line therapy. The NANETS guidelines suggest that the long-acting depot may be appropriate as initial therapy (ie, without prior SubQ octreotide) (Ref). For patients experiencing breakthrough symptoms while taking the long-acting depot, supplementary doses of SubQ octreotide may be necessary.

IM (depot):

Initial: 20 mg intragluteally every 4 weeks (Ref) or 20 to 30 mg intragluteally every 4 weeks (Ref).

Titration: Dose may be modified based on response as follows:

May decrease to 10 mg every 4 weeks after 2 months if initially responsive to 20 mg dose.

Increase to 30 mg every 4 weeks if symptoms are inadequately controlled after 2 months. Note: The US labeling states that higher doses are not recommended; however, if frequent supplementary SubQ doses are needed (eg, ≥3 to 4 times/week), may consider further increasing the dose by 10 mg every 4 weeks, or maintaining the same dose and reducing the dosing interval to every 3 weeks, up to a maximum off-label dose of 60 mg every 4 weeks (Ref).

SubQ: Initial: 100 mcg every 12 hours; may increase to 200 mcg every 12 hours (Shojamanesh 2002) or 100 to 500 mcg in 2 to 4 divided doses (usual dose: 150 mcg 3 times daily) (Ref). If additional symptom control is needed, may increase by doubling the dose every 3 to 4 days until symptoms are controlled; may also consider a continuous SubQ infusion of 1,000 to 2,000 mcg/day (Ref).

Gastroenteropancreatic neuroendocrine tumors, functional, vasoactive intestinal peptide-secreting

Gastroenteropancreatic neuroendocrine tumors, functional, vasoactive intestinal peptide-secreting (VIPomas):

Note: May be used to control symptoms of hormone hypersecretion (eg, diarrhea). The NANETS guidelines suggest that the long-acting depot may be appropriate as initial therapy (ie, without prior SubQ octreotide as stated in the US labeling) (Ref). For patients experiencing breakthrough symptoms while taking the long-acting depot, supplementary doses of SubQ octreotide may be necessary.

IM (depot):

Initial: 20 mg intragluteally every 4 weeks (Ref) or 20 to 30 mg intragluteally every 4 weeks (Ref).

Titration: Dose may be modified based on response as follows:

May decrease to 10 mg every 4 weeks after 2 months if initially responsive to 20 mg dose.

Increase to 30 mg every 4 weeks if symptoms are inadequately controlled after 2 months. Note: The US labeling states that higher doses are not recommended; however, if frequent supplementary SubQ doses are needed (eg, ≥3 to 4 times/week), may consider further increasing the dose by 10 mg every 4 weeks, or maintaining the same dose and reducing the dosing interval to every 3 weeks, up to a maximum off-label dose of 60 mg every 4 weeks (Ref).

SubQ, IV: Initial: 200 to 300 mcg/day in 2 to 4 divided doses. If additional symptom control is needed, may increase by doubling the dose every 3 to 4 days until symptoms are controlled; usual range: 150 to 450 mcg/day. Doses >450 mcg/day are rarely required; however, may consider a continuous SubQ infusion of 1,000 to 2,000 mcg/day off label in patients who remain symptomatic on intermittent doses (Ref).

Gastroenteropancreatic neuroendocrine tumors, metastatic, tumor control

Gastroenteropancreatic neuroendocrine tumors, metastatic, tumor control (off-label use):

Note: May be used to control tumor growth in patients with unresectable, metastatic, well-differentiated NETs with a high tumor burden (including thymus and lung NETs) (Ref). The NANETS guidelines suggest that the long-acting depot may be appropriate as initial therapy (ie, without prior SubQ therapy) (Ref). For patients with functional tumors who are experiencing breakthrough symptoms while taking the long-acting depot, supplementary doses of SubQ octreotide may be necessary.

IM (depot): 30 mg intragluteally every 4 weeks until tumor progression or death (Ref).

or

IM (depot):

Initial: 20 to 30 mg intragluteally every 4 weeks (Ref).

Titration: If frequent supplementary SubQ doses are needed (eg, ≥3 to 4 times/week), may increase the dose by 10 mg every 4 weeks, or maintain the same dose and reduce the dosing interval to every 3 weeks (Ref).

Dosage range: 20 to 60 mg every 4 weeks.

SubQ: Initial: 100 to 500 mcg in 2 to 4 divided doses (usual dose: 150 mcg 3 times daily). If additional symptom control is needed, may increase by doubling the dose every 3 to 4 days until symptoms are controlled; may also consider a continuous SubQ infusion of 1,000 to 2,000 mcg/day (Ref).

With lutetium Lu 177 dotatate treatment: IM (depot): 30 mg once following each lutetium Lu 177 dotatate dose (administer between 4 to 24 hours after the lutetium Lu 177 dotatate dose) for 4 doses and then continue 30 mg once a month after lutetium Lu 177 dotatate is completed (Ref). Rescue doses (dose not specified) of short-acting octreotide may be used in between for symptomatic management (for diarrhea or flushing), but discontinue at least 24 hours before each lutetium Lu 177 dotatate dose.

Gastroesophageal variceal hemorrhage, acute

Gastroesophageal variceal hemorrhage, acute (off-label use):

Note: For use in patients with varices or at risk for varices who have upper GI bleeding; treatment should not be delayed pending confirmation of the source of bleeding. In patients with cirrhosis and active variceal bleeding, administer prophylactic antibiotics for up to 7 days (Ref).

IV: Initial: 50 mcg bolus, followed by continuous infusion of 50 mcg/hour for 2 to 5 days; may repeat bolus in first hour if hemorrhage is not controlled (Ref).

Hepatorenal syndrome type 1 or acute kidney injury, treatment

Hepatorenal syndrome type 1 or acute kidney injury, treatment (adjunctive agent) (off-label use):

Note: Used in combination with midodrine and albumin in patients who cannot receive norepinephrine or terlipressin (Ref).

SUBQ: Initial: 100 mcg 3 times daily; may increase to 200 mcg 3 times daily until midodrine is discontinued (goal to increase mean arterial pressure by ~10 to 15 mm Hg from baseline) (Ref).

IV: 50 mcg/hour as a continuous infusion until midodrine is discontinued. Note: Some experts prefer continuous infusion over SUBQ injection (Ref).

Hypoglycemia, sulfonylurea-induced

Hypoglycemia, sulfonylurea-induced (adjunctive agent) (off-label use):

Note: Use in combination with IV dextrose for initial treatment of intentional overdose (Ref); may also use for refractory, unintentional single-episode hypoglycemia occurring during therapeutic use of sulfonylureas (Ref). The SUBQ route is preferred over IV except in cases where peripheral circulation may be compromised (Ref). Administration via IV bolus and IV infusion have also been described (Ref). Optimal care decisions should be made based upon patient-specific details; consultation with a poison control center or clinical toxicologist is recommended.

SUBQ, IV: 50 to 100 mcg as a single dose; may repeat every 6 hours if needed (Ref). Note: In patients with recurrent hypoglycemia, a continuous IV infusion (eg, up to 125 mcg/hour) may be required (Ref). Usual duration is 24 hours; however, may need to be extended if hypoglycemia persists (Ref).

Malignant bowel obstruction

Malignant bowel obstruction (off-label use):

Note: For use in patients who are not candidates for surgery or who have inoperable obstruction(Ref).

SubQ: 200 to 900 mcg/day in 2 to 3 divided doses (Ref) or 300 mcg/day by continuous SubQ infusion (Ref). Note: Patients who respond to SubQ injections may be converted to IM depot injections (eg, 30 mg IM every 4 weeks) for maintenance therapy (Ref).

Thymic epithelial malignancies, advanced

Thymic epithelial malignancies, advanced (off-label use):

SubQ: 500 mcg 3 times daily; evaluate after 2 months. Patients with remission (complete or partial) continued octreotide for up to a maximum of 12 months; patients with stable disease continued octreotide and also received prednisone for up to 12 months or until disease progression or unacceptable toxicity (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function:

Oral, parenteral: No initial or maintenance dosage adjustments are likely necessary for any degree of kidney dysfunction, although clearance is reduced and dosage modifications may be necessary in patients with end-stage kidney disease (ESKD) receiving dialysis (Ref).

Hemodialysis, intermittent (thrice weekly): Dialysis removal unknown; some removal is expected based on physicochemical properties (Ref):

SUBQ, IV: There are no specific dosage adjustments recommended by the manufacturer; however, clearance is reduced by ~50%. Consider initiation at the low end of the normal range; titrate based on tolerability and response (Ref).

IM (depot): Initial: 10 mg intragluteally every 4 weeks; may titrate based on tolerability and response (Ref).

Oral: Initial: 20 mg once daily; titrate if needed every 2 to 4 weeks based on tolerability and clinical response in 20 mg/day increments up to 80 mg/day. Refer to indication-specific adult dosing section for more specific titration recommendations (Ref).

Peritoneal dialysis:

SUBQ, IV: No dosage adjustment provided by manufacturer; clearance is reduced by ~50%. Consider initiation at the low end of the normal range and titrate based on efficacy and tolerability (Ref).

IM (depot): Initial: 10 mg intragluteally every 4 weeks; titrate based on tolerability and response (Ref).

Oral: Initial: 20 mg once daily; titrate if needed every 2 to 4 weeks based on tolerability and clinical response in 20 mg/day increments up to 80 mg/day. Refer to indication-specific adult dosing section for more specific titration recommendations (Ref).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Close monitoring of response and adverse reactions (eg, glucose dysregulation) due to drug accumulation is important.

Oral, parenteral: There are no data available on removal by CRRT (has not been studied); however, some removal is expected based on physicochemical characteristics. No initial or maintenance dosage adjustments are likely necessary (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, glucose dysregulation) due to drug accumulation is important.

IV, SUBQ: There are no data available on removal by PIRRT (has not been studied); however, some removal is expected based on physicochemical characteristics. Consider initiation at the low end of the normal range; titrate based on tolerability and response (Ref).

IM (LAR): There are no data available on removal by PIRRT (has not been studied); consider reducing initial dose to 10 mg every 4 weeks; titrate based on tolerability and response (Ref).

Oral: There is no data available on removal by PIRRT (has not been studied); consider reducing initial dose to 20 mg once daily. Titrate if needed every 2 to 4 weeks based on tolerability and clinical response in 20 mg/day increments up to 80 mg/day. Refer to indication-specific adult dosing section for more specific titration recommendations (Ref).

Dosing: Hepatic Impairment: Adult

Injection solution: There are no dosage adjustments provided in the manufacturer’s labeling. Half-life is prolonged and total body clearance is decreased in patients with cirrhosis and fatty liver disease.

LAR depot suspension: Patients with established cirrhosis of the liver: IM: Initial: 10 mg IM every 4 weeks; titrate based upon response.

Delayed-release capsule: There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Pediatric

(For additional information see "Octreotide: Pediatric drug information")

Note: Unless otherwise specified, all pediatric dosing based on use of the immediate-release injection solution (non-long-acting). Dosing is presented in multiple formats (eg, mcg/kg/hour, mcg/kg/day, mcg/kg/dose); use extra precaution.

Chylothorax, acquired

Chylothorax, acquired (eg, postoperative): Limited data available; efficacy results variable; optimal dose not established (Ref): Infants and Children: Continuous IV infusion: Reported range: 1 to 4 mcg/kg/hour; in one report, octreotide was initiated and maintained at fixed rate of 3 mcg/kg/hour; other reports describe initiation of therapy at the lower end of a dosing range and titration; usual duration of therapy: 7 days (Ref).

Diarrhea

Diarrhea: Very limited data available; reported dosing highly variable: Note: In pediatric patients, octreotide has been used to manage refractory cases of diarrhea due to multiple etiologies including GVHD, chemotherapy induced, and congenital secretory syndromes; use has been described in a small trial, several case reports and by some centers. A dose-response relationship has not been established. SubQ administration is the usual route; however, the IV route has been used in some cases (Ref).

Infants, Children, and Adolescents:

Intermittent SubQ: Usual initial dose: 1 to 10 mcg/kg/dose every 8 to 12 hours; doses should begin at the low end of the range and be titrated to effect; reported range: 1 to 49 mcg/kg/day (Ref); a higher dose of 60 mcg/kg/day has been reported (Ref). In adults, a maximum dose of 500 mcg/dose has been recommended for GVHD (Ref).

Continuous IV infusion: Note: Typically IV infusion reserved for patients failing intermittent dosing: Initial: 1 mcg/kg/hour (Ref); some patients may require titration; doses up to 49 mcg/kg/day have been reported (Ref).

Esophageal varices; gastrointestinal bleed

Esophageal varices; gastrointestinal bleed: Limited data available: Infants, Children, and Adolescents: IV: Initial: 1 to 2 mcg/kg bolus followed by 1 to 2 mcg/kg/hour continuous IV infusion; titrate infusion rate to response; taper dose by 50% every 12 hours when no active bleeding occurs for 24 hours; may discontinue when dose is 25% of initial dose (Ref).

Hyperinsulinemic hypoglycemia

Hyperinsulinemic hypoglycemia: Limited data available: Note: Not first-line therapy (diazoxide suggested for initial management) (Ref). Dosing should be individualized to patient response to achieve and maintain target serum glucose concentrations (typically >70 mg/dL) (Ref).

Daily dosing: Infants, Children, and Adolescents: SubQ:

Intermittent SubQ: Initial: 5 mcg/kg/day in divided doses every 6 to 8 hours; titrate to response, 5 mcg/kg/day increments have been used; usual reported effective range: 5 to 25 mcg/kg/day in divided doses; maximum daily dose: 35 mcg/kg/day (Ref).

Continuous SubQ infusion: Initial: 5 mcg/kg/day delivered over 24 hours; titrate to response, 5 mcg/kg/day increments have been used; usual reported effective range: 5 to 25 mcg/kg/day; maximum daily dose: 35 mcg/kg/day (Ref).

Monthly dosing: Long-acting depot formulation; conversion from SubQ (daily) to IM (monthly): Very limited data available:

Note: Not for initial management; for administration by a health care professional; in pediatric trials, initial doses (7) were administered in an inpatient facility. Due to the delayed onset of therapeutic levels with the long-acting IM formulation, overlap with SubQ octreotide therapy (intermittent or continuous infusion) along with IM therapy is necessary:

Children and Adolescents: Long-acting formulation (Sandostatin LAR): IM: Calculate patient's cumulative 31-day SubQ dose, which will equal the monthly IM dose; administer this dose every 4 weeks. Continue with SubQ octreotide therapy for 2 months after starting IM long-acting formulation (first 2 IM depot doses) then discontinue prior at the time of the third IM dose; monitor patient closely for hypoglycemia while receiving both IM (long-acting) and SubQ octreotide (Ref).

Hypothalamic obesity

Hypothalamic obesity (from cranial insult): Limited data available; efficacy results variable: Children ≥8 years of age and Adolescents: SubQ: Initial: 5 mcg/kg/day divided into 3 daily doses; dose may be increased bimonthly at 5 mcg/kg/day increments to a maximum of 15 mcg/kg/day divided into 3 daily doses; dosing based on small trials which showed insulin suppression, decreased caloric intake, and BMI stabilization or decrease; trials were limited to a 6 month duration; long-term effects are unknown (Ref).

Sulfonylurea overdose

Sulfonylurea overdose: Limited data available: Dosing in pediatric patients based on experience in adult patients; pediatric-specific reports are sparse (Ref). Infants, Children, and Adolescents: SubQ: 1 to 1.25 mcg/kg/dose every 6 hours; repeat as needed based upon blood glucose concentrations (Howland 2011); children generally need only a single dose (Ref). Note: Although octreotide use is strongly advocated as a first-line therapy, indications and dosing for octreotide are not firmly established (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no pediatric specific recommendations; clearance is decreased by 50% in adult patients with severe renal failure requiring dialysis; based on experience in adult patients, consider dosing adjustment.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling. Half-life is prolonged and total body clearance is decreased in adult patients with cirrhosis and fatty liver disease; based on experience in adult patients, use with caution, dosing adjustment suggested.

Dosing: Older Adult

Injection solution, LAR depot suspension: Refer to adult dosing. Elimination half-life is increased by 46% and clearance is decreased by 26%; dose adjustment may be required. Dosing should generally begin at the lower end of dosing range.

Delayed-release capsule: Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Delayed Release, Oral, as acetate:

Mycapssa: 20 mg

Kit, Intramuscular:

SandoSTATIN LAR Depot: 10 mg, 20 mg, 30 mg

Solution, Injection:

SandoSTATIN: 50 mcg/mL (1 mL); 100 mcg/mL (1 mL); 500 mcg/mL (1 mL)

Generic: 50 mcg/mL (1 mL); 100 mcg/mL (1 mL); 200 mcg/mL (5 mL); 500 mcg/mL (1 mL); 1000 mcg/mL (5 mL)

Solution, Injection [preservative free]:

Generic: 100 mcg/mL (1 mL); 500 mcg/mL (1 mL)

Solution Pen-injector, Subcutaneous:

Bynfezia Pen: 2500 mcg/mL (2.8 mL [DSC]) [contains phenol]

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Intramuscular:

SandoSTATIN LAR: 10 mg, 20 mg, 30 mg

Generic: 10 mg, 20 mg, 30 mg

Solution, Injection:

SandoSTATIN: 50 mcg/mL (1 mL); 100 mcg/mL (1 mL)

SandoSTATIN: 200 mcg/mL ([DSC]) [contains phenol]

Generic: 50 mcg/mL (1 mL); 100 mcg/mL (1 mL); 200 mcg/mL (5 mL); 500 mcg/mL (1 mL)

Administration: Adult

Delayed-release capsule: Oral: Take with a glass of water at least 1 hour before or 2 hours after a meal. Swallow capsules whole; do not crush or chew the capsules.

Injection solution:

Ampule, syringe, vial: SubQ, IV: Administer SubQ or IV; IV administration may be IV push (undiluted over 3 minutes), intermittent IV infusion (over 15 to 30 minutes), or continuous IV infusion (off-label route). In emergency situations (eg, carcinoid crisis), octreotide may be given as a rapid IV bolus. When administering SubQ use the concentration with smallest volume to deliver dose to reduce injection-site pain. Rotate injection site; may bring to room temperature prior to injection.

Prefilled pen: SubQ: Bring to room temperature ~20 to 30 minutes prior to administration. Administer SubQ into abdomen, front middle thigh, or back/outer area of upper arm. Rotate injection site; administer at least 2 inches away from previous injection site. Refer to manufacturer's labeling for additional administration instructions (including priming of pen).

LAR depot suspension: IM: Administer IM intragluteal (avoid deltoid administration); alternate gluteal injection sites to avoid irritation. For IM administration only; do not administer LAR depot suspension (Sandostatin LAR) IV or SubQ; must be administered immediately after mixing.

Administration: Pediatric

Parenteral: Only Sandostatin injection may be administered IV and SubQ; Sandostatin LAR Depot may only be administered IM

SubQ: Use the concentration with smallest volume to deliver dose to reduce injection site pain; rotate injection site; may bring to room temperature prior to injection

IV infusion: Dilute Sandostatin injection and infuse over 15 to 30 minutes or over 24 hours as a continuous infusion; in emergency situations, may be administered undiluted by direct IV push over 3 minutes; allow solution to come to room temperature before administration

IM: Administer into gluteal area only; avoid deltoid injections due to significant pain and discomfort at injection site

Usual Infusion Concentrations: Adult

IV infusion: 500 mcg in 250 mL (concentration: 2 mcg/mL) of D5W or NS

Use: Labeled Indications

Acromegaly:

Delayed-release capsule: Long-term maintenance treatment of acromegaly in patients who have responded to and tolerated treatment with octreotide or lanreotide.

Injection solution: To reduce blood levels of growth hormone and insulin-like growth factor 1 in patients with acromegaly who have had inadequate response to or cannot be treated with surgical resection and/or pituitary irradiation.

LAR depot suspension: Long-term maintenance treatment of acromegaly in patients with an inadequate response to surgery and/or radiotherapy, or for whom surgery/radiotherapy is not an option.

The Endocrine Society and the Acromegaly Consensus Group suggest use of a first-generation, long-acting somatostatin analogue (eg, lanreotide, octreotide) as first-line therapy in patients with persistent disease despite surgical resection or in whom surgery is not appropriate. Alternative agents are suggested for patients with mild disease postoperatively. Preoperative use of somatostatin analogues is also suggested in select patients to reduce surgical risk from severe comorbidities, although there is conflicting evidence regarding the long-term benefit of this strategy (ACG [Melmed 2018]; ES [Katznelson 2014]).

Carcinoid syndrome:

Injection solution: Management of symptoms of carcinoid syndrome (diarrhea and flushing) in patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

LAR depot suspension: Long-term treatment of severe diarrhea and flushing episodes associated with carcinoid syndrome in patients with metastatic GEP-NETs.

Gastroenteropancreatic neuroendocrine tumors, functional, vasoactive intestinal peptide-secreting (VIPomas):

Injection solution: Treatment of profuse watery diarrhea associated with vasoactive intestinal peptide-secreting GEP-NETs (VIPomas).

LAR depot suspension: Long-term treatment of profuse watery diarrhea associated with VIPomas.

Limitations of use: According to the manufacturer's labeling, the effects of octreotide (injection solution and LAR depot suspension) on tumor size, growth rate, and development of metastases in patients with carcinoid syndrome and VIPomas have not been determined. However, according to the North American Neuroendocrine Tumor Society consensus guidelines for surveillance and medical management of midgut neuroendocrine tumors (NETs), somatostatin analogues (including octreotide LAR) are appropriate initial therapy in most patients with unresectable metastatic midgut NETs for inhibition of tumor growth based on demonstrated antiproliferative effects (NANETS [Strosberg 2017a]; Rinke 2009).

Use: Off-Label: Adult

Carcinoid crisis, prevention and treatment; Diarrhea associated with acute graft-versus-host disease; Diarrhea associated with chemotherapy, refractory; Fistulas, high-output, gastroenteropancreatic; Gastroenteropancreatic neuroendocrine tumors, functional, gastrin-secreting (gastrinoma, Zollinger-Ellison syndrome), refractory; Gastroenteropancreatic neuroendocrine tumors, metastatic, tumor control; Gastroesophageal variceal hemorrhage, acute; Hepatorenal syndrome type 1 or acute kidney injury, treatment; Hypoglycemia, sulfonylurea-induced; Malignant bowel obstruction; Thymic epithelial malignancies, advanced

Medication Safety Issues
Sound-alike/look-alike issues:

Mycapssa may be confused with capsaicin, Mycamine, Mylanta.

Octreotide may be confused with lanreotide, pasireotide.

SandoSTATIN may be confused with SandIMMUNE, SandoSTATIN LAR, sargramostim, simvastatin.

Adverse Reactions (Significant): Considerations
Cholelithiasis and related complications

Biliary tract disease, ranging from asymptomatic increases in gallbladder sludge (Ref) to complicated symptoms, some of which led to cholecystectomy, have been associated with somatostatin analogs (Ref). In clinical trials, asymptomatic biliary sludge generally resolved without treatment (Ref). Cholecystectomy was required in ~6% of patients to manage symptomatic cholelithiasis (Ref). Increased liver enzymes have occurred in pediatric patients; however, no statistically significant difference in gallbladder pathology and/or episodes of severe hepatitis occurred. Increased liver enzymes resolved within 4 to 8 weeks without withdrawal of treatment (Ref).

Mechanism: Time-related; inhibition of prandial cholecystokinin release elicits defects in biliary and GI transit time producing an increase in the concentration of prolithogenic bile factors. The change in biliary lipid composition is also promoted by the increased acidotic and static environment with slower GI transit time (Ref). Additionally, prandial relaxation of the sphincter of Oddi has been associated with favorable conditions promoting stone formation (Ref).

Onset: Varied; most biliary tract abnormalities occur after ≥1 year of therapy with an average time to detection of 3 years (Ref); however, a case report cites development of symptoms within 5 days of octreotide initiation and administration of contrast media (Ref). Less than 2% of biliary complications are linked to therapy duration of ≤1 month.

Risk factors:

• Longer duration of treatment (ie, ≥1 year)

• Coadministration of contrast media (Ref)

• Diabetes (Ref)

• High non-HDL cholesterol (Ref)

• High triglycerides (Ref)

• Metabolic syndrome (Ref)

• Obesity (Ref)

• Treatment for acromegaly (Ref)

• Withdrawal of therapy

Glucose dysregulation

The effect of somatostatin analogs on glucose homeostasis is controversial. The risks of glucose deterioration or improvement are similar, as glucose metabolism may be more closely associated with the underlying pathophysiology of acromegaly (Ref). Octreotide alters the balance between the counter-regulatory hormones, insulin, glucagon, and growth hormone (GH), which may result in hypoglycemia, hyperglycemia, or overt diabetes mellitus. One study cites worsening of glycemic status in 15% of participants with impaired glucose tolerance (IGT) or diabetes mellitus (DM) at treatment initiation; another source cites an improvement in glucose metabolism in 43% patients with preexisting DM (Ref). Poor response to octreotide in the treatment of acromegaly resulted in an ~25% risk of glucose deterioration (Ref). When used in children for GI bleeding, there were no changes in glucose regulation (Ref). There are case reports of octreotide success in the treatment of hypoglycemia (Ref).

Mechanism: Dose-related; inhibition of glucagon and insulin secretion can produce glucose dysregulation (Ref).

Onset: Varied; one study found initial worsening of glycemia at the beginning of therapy, but treatment of acromegaly produced stabilization (Ref). Conversely, other studies showed worsening of glycemia after 12 months, but again was attributed to poor control of acromegaly (Ref).

Risk factors:

• Higher dose or higher dosing frequency (more somatostatin receptors may be affected) (Ref)

• Acromegaly (Ref)

• Baseline IGT or DM (Ref)

• High GH levels (Ref)

Necrotizing enterocolitis

Necrotizing enterocolitis (NEC) has been reported primarily in neonates, infants, and children <2 years old; estimated reported incidence is uncommon (Ref). A lack of controlled trials in this population and the presence of predisposing conditions are barriers to an accurate estimation of risk (Ref). Conversely, successful use in a premature low birth weight neonate with contraindications to surgery for NEC has also been reported (Ref).

Mechanism: Dose-related; increase in splanchnic arteriolar resistance decreasing GI blood flow and secretions inhibits natural protective GI defenses (Ref).

Onset: Varied; ranges from within 15 days to 2 months (Ref).

Risk factors:

• Dose escalation (Ref)

• Rotavirus infection at therapy initiation (Ref)

• Preexisting risk factors for NEC (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions vary by route of administration and dosage form; generally lower incidences were seen with oral formulation. Frequency of cardiac, endocrine, and gastrointestinal adverse reactions was generally higher in patients with acromegaly.

>10%:

Cardiovascular: Hypertension (≤13%), sinus bradycardia (19% to 25%)

Dermatologic: Alopecia (1% to 13%), diaphoresis (21%)

Endocrine & metabolic: Hyperglycemia (2% to 27%), hypothyroidism (1% to 12%)

Gastrointestinal: Abdominal distress (≤61%), abdominal pain (≤44%), biliary tract disease (52% to 63%; length of therapy dependent; including acute cholecystitis [1%], jaundice [≤1%], ascending cholangitis, cholestatic hepatitis, and pancreatitis), biliary obstruction (duct dilatation: 12%), cholelithiasis (5% to 38%) (table 1), constipation (≤21%), diarrhea (≤61%), flatulence (≤38%), gallbladder sludge (24%), nausea (≤61%), upper abdominal pain (8% to 11%), vomiting (≤21%)

Octreotide: Adverse Reaction: Cholelithiasis

Drug (Octreotide)

Comparator (Pituitary Surgery)

Dose

Dosage Form

Indication

Number of Patients (Octreotide)

Number of Patients (Pituitary Surgery)

38%

5%

20 mg

Injectable suspension, for gluteal intramuscular use

Acromegaly

76

64

13%

N/A

10 mg/20 mg/30 mg

Injectable suspension, for gluteal intramuscular use

Acromegaly

261

N/A

5%

N/A

N/A

Delayed-release oral capsules

Acromegaly

155

N/A

Hematologic & oncologic: Anemia (≤15%)

Immunologic: Antibody development (25%; to octreotide; no efficacy change)

Local: Pain at injection site (2% to 50%)

Nervous system: Dizziness (5% to 12%), fatigue (1% to 11%), headache (6% to 33%)

Neuromuscular & skeletal: Arthralgia (1% to 26%), asthenia (1% to 22%)

Respiratory: Flu-like symptoms (1% to 20%)

1% to 10%:

Cardiovascular: Bradycardia (2%), cardiac arrhythmia (≤9%), cardiac conduction disturbance (1% to 10%; including prolonged QT interval on ECG and ST segment changes), edema (1% to 4%), flushing (1% to 4%), tachycardia (≤2%)

Dermatologic: Pruritus (1% to 4%)

Endocrine & metabolic: Decreased free T4 (1%), diabetes mellitus (1%), goiter (2% to 8%), hypoglycemia (2% to 4%), increased thyroid stimulating hormone level (1%)

Gastrointestinal: Abdominal distention (7%), dyspepsia (4% to 8%), fecal discoloration (4% to 6%), gastritis, gastroesophageal reflux disease, gastrointestinal motility disorder, hemorrhoids, malabsorption (fat: 1% to 4%), steatorrhea (4% to 6%), tenesmus (4% to 6%), xerostomia

Genitourinary: Pollakiuria (1% to 4%), urinary tract infection (1% to 4%)

Hematologic & oncologic: Bruise (1% to 4%)

Infection: Cold symptoms (1% to 4%), influenza (7%)

Local: Hematoma at injection site (1% to 4%)

Nervous system: Depression (1% to 4%)

Neuromuscular & skeletal: Back pain (1% to 6%)

Ophthalmic: Blurred vision (1% to 4%), visual disturbance (1% to 4%)

Respiratory: Nasopharyngitis (7%), upper respiratory tract infection (5%)

<1%:

Cardiovascular: Chest pain, heart failure, hypertensive crisis, ischemia, orthostatic hypotension, palpitations, Raynaud's disease, syncope, thrombophlebitis

Dermatologic: Cellulitis, skin rash, urticaria

Endocrine & metabolic: Adrenocortical insufficiency, amenorrhea, decreased libido, diabetes insipidus, galactorrhea not associated with childbirth, gynecomastia, infrequent uterine bleeding, iron deficiency, menstrual disease (polymenorrhea), pituitary apoplexy, weight loss

Gastrointestinal: Appendicitis, gastric ulcer, gastrointestinal hemorrhage, intestinal obstruction, intestinal polyps, peptic ulcer

Genitourinary: Hematuria, vaginitis

Hematologic & oncologic: Basal cell carcinoma of skin, petechia, polyp (gallbladder)

Hepatic: Hepatitis, increased liver enzymes

Hypersensitivity: Hypersensitivity reaction

Nervous system: Amnesia, anxiety, Bell's palsy, neuritis, paranoid ideation, seizure, vertigo

Neuromuscular & skeletal: Arthritis, increased creatine phosphokinase in blood specimen, joint effusion, myalgia, tremor

Ophthalmic: Increased intraocular pressure

Otic: Hearing loss, otitis

Renal: Nephrolithiasis

Respiratory: Dyspnea, epistaxis, pneumonia, status asthmaticus

Miscellaneous: Nodule (pulmonary)

Postmarketing:

Cardiovascular: Acute myocardial infarction, aneurysm, arterial thrombosis (arm), atrial fibrillation, facial edema

Endocrine & metabolic: Vitamin B12 deficiency

Gastrointestinal: Abdominal swelling, necrotizing enterocolitis (Chandran 2020)

Hematologic & oncologic: Breast carcinoma, pancytopenia, thrombocytopenia (Demirkan 2000)

Hepatic: Liver steatosis

Hypersensitivity: Anaphylactic shock, nonimmune anaphylaxis (Azkur 2011)

Nervous system: Aphasia, hemiparesis, intracranial hemorrhage, migraine, paresis, suicidal tendencies

Ophthalmic: Glaucoma, retinal thrombosis, scotoma

Otic: Deafness

Renal: Increased serum creatinine, renal failure syndrome, renal insufficiency

Respiratory: Pneumothorax (aggravated), pulmonary hypertension (Arevalo 2003)

Contraindications

Hypersensitivity to octreotide or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Abnormal Schillings test: Chronic treatment has been associated with abnormal Schillings test; monitor vitamin B12 levels.

• Cardiovascular events: Complete atrioventricular block has been reported in patients receiving IV therapy during surgical procedures; most causes occurred with continuous IV infusion at higher than recommended doses. Safety of continuous IV infusion has not been established in patients receiving octreotide for approved indications.

• Hypothyroidism: Suppresses secretion of TSH; monitor for hypothyroidism.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with heart failure or concomitant medications that alter heart rate or rhythm; bradycardia, conduction abnormalities, and arrhythmia have been observed in acromegalic and carcinoid syndrome patients. Cardiovascular medication requirements may change.

• Excessive GI fluid loss: In patients with conditions associated with excessive GI fluid loss receiving TPN, concomitant use of octreotide may reverse fluid losses and cause increases in serum zinc; monitor zinc levels (manufacturer's labeling).

• Hepatic impairment: Use caution in patients with hepatic impairment; dosage adjustment may be required in patients with established cirrhosis.

• Neuroendocrine tumors: Prophylactic cholecystectomy is recommended in patients with GI or pancreatic neuroendocrine tumors undergoing abdominal surgery if octreotide treatment is planned (Oberg 2004).

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be required in patients receiving dialysis.

Concurrent drug therapy issues:

• QTc-prolonging agents: Octreotide may enhance the adverse/toxic effects of other QTc-prolonging agents.

Dosage form specific issues:

• LAR depot suspension: Mild to moderate injection-site pain (usually lasting 1 hour) may occur with the LAR depot suspension. Do not use LAR depot suspension formulation for the treatment of sulfonylurea-induced hypoglycemia (Dougherty 2010).

• Vehicle used in LAR depot suspension (polylactide-co-glycolide microspheres): Has rarely been associated with retinal artery occlusion in patients with abnormal arteriovenous anastomosis (eg, patent foramen ovale).

Special populations:

• Older adult: Dosage adjustment may be necessary; significant increases in elimination half-life have been observed in older adults.

• Pediatric: Postmarketing cases of serious and fatal events, including hypoxia and necrotizing enterocolitis, have been reported with octreotide use in children (usually with serious underlying conditions), particularly in children <2 years of age. In studies with octreotide LAR depot suspension, the incidence of cholelithiasis in children is higher than the reported incidences for adults and efficacy was not demonstrated.

Other warnings/precautions:

• Appropriate use: Use of octreotide for the treatment of delayed and/or prolonged hypoglycemia due to sulfonylurea overdose: The onset of hypoglycemia typically occurs within 8 to 12 hours of a sulfonylurea overdose (Boyle 1993; Dougherty 2010; Lung 2011; Spiller 1997; Spiller 2006); however, the onset may be delayed for up to 24 hours. In rare cases, hypoglycemia may develop >24 hours after ingestion. Episodes of prolonged hypoglycemia (>13 hours) have been reported following sulfonylurea overdosage; adequate duration of monitoring and treatment must be provided when octreotide is used for this indication.

• Radiolabeled diagnostic evaluations: Therapy with the octreotide injection solution formulation should be withheld 24 hours prior to administration of radiolabeled somatostatin analogs; the LAR depot suspension formulation should be withheld at least 2 months before administration of radiolabeled somatostatin analogs (Oberg 2004).

Warnings: Additional Pediatric Considerations

Serious and some fatal adverse effects have been reported in pediatric patients including NEC, hypoxia, and pancreatitis, and during administration of IV doses bradycardia has been reported; most severe adverse events or death were observed in neonates, infants, and children <2 years of age; direct causality with octreotide was not established due to complex patient comorbidities (Church 2017; FDA 2007; Testoni 2015). Use in neonates, including term and preterm, should be done with extreme caution and reserved for refractory cases; consider avoiding use if patient has other risk factors for NEC (Testoni 2015).

Metabolism/Transport Effects

None known.

Drug Interactions

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

Antacids: May decrease the serum concentration of Octreotide. 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

Digoxin: Octreotide may enhance the bradycardic effect of Digoxin. Octreotide may increase the serum concentration of Digoxin. 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

Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Octreotide. Risk C: Monitor therapy

Hormonal Contraceptives: Octreotide may decrease the serum concentration of Hormonal Contraceptives. Management: Women should use an alternative non-hormonal method of contraception or a back-up method when octreotide is combined with hormonal contraceptives. Risk D: Consider therapy modification

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Octreotide. 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

Lisinopril: Octreotide may increase the serum concentration of Lisinopril. 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

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

Telotristat Ethyl: Octreotide may decrease the serum concentration of Telotristat Ethyl. Management: Administer short-acting octreotide at least 30 minutes after administration of telotristat ethyl and monitor for decreased telotristat ethyl efficacy. Risk D: Consider therapy modification

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Food Interactions

Octreotide may alter absorption of dietary fats; administering octreotide delayed-release capsules with food decreases AUC and Cmax by 90%. Management: Administer injections between meals to decrease GI effects; administer delayed-release capsules on an empty stomach at least 1 hour before or at least 2 hours after meals.

Reproductive Considerations

Pregnancy testing prior to administration of octreotide long-acting formulations is suggested to minimize potential fetal exposure (Abucham 2017).

Because normalization of insulin-like growth factor 1 and growth hormone may restore fertility in premenopausal patients with acromegaly, patients who could become pregnant should use adequate contraception during treatment.

Octreotide may be used for patients with acromegaly who are trying to conceive; discontinue once pregnancy is confirmed (ESE [Luger 2021]). The Endocrine Society suggests 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 (ES [Katznelson 2014]).

Pregnancy Considerations

Octreotide crosses the placenta and can be detected in the newborn at delivery (Caron 1995; Fassnacht 2001; Maffei 2010).

Data concerning use in pregnancy are limited. Based on available case reports of patients with acromegaly who received normal doses of octreotide during pregnancy, an increased risk of congenital malformations has not been observed (Abucham 2017; Vialon 2020).

If treatment for acromegaly is required during pregnancy for worsening symptoms (eg, headaches or evidence of tumor growth), short-acting octreotide may be considered. Titrate to the lowest effective dose. Monitoring of insulin-like growth factor 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 octreotide in pregnant patients with gastroenteropancreatic neuroendocrine tumors is limited (Le 2009; Naccache 2011; Pistilli 2012).

Breastfeeding Considerations

Octreotide is present in breast milk.

Information related to octreotide use in breastfeeding women is limited (Colao 1997; Maffei 2010). In a case report, a woman was taking octreotide SubQ in doses up to 2,400 mcg/day prior to and throughout pregnancy. Octreotide was measurable in the colostrum in concentrations similar to those in the maternal serum (Maffei 2010); however, oral absorption of octreotide is considered to be poor (Battershill 1989). 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.

Dietary Considerations

Schedule injections between meals to decrease GI effects. Administer oral capsules at least 1 hour before or 2 hours after a meal. May alter absorption of dietary fats.

Monitoring Parameters

Acromegaly:

Initial:

Injection solution: Measure serum growth hormone (GH) every 1 to 4 hours for 8 to 12 hours post dose or a single measurement of serum insulin-like growth factor 1 (IGF-1) 2 weeks after initiation or dosage adjustment.

LAR depot suspension: Serum GH and IGF-1 at 3 months (prior to next dose).

Delayed-release capsule: Serum IGF-1 every 2 weeks initially and during dosage adjustment.

Maintenance:

Injection solution, LAR depot suspension: Serum GH and IGF-1 every 3 to 6 months.

Delayed-release capsule: Serum IGF-1 every month or as indicated.

Carcinoid: 5-HIAA, plasma serotonin and plasma substance P.

VIPomas: Vasoactive intestinal peptide.

Chronic therapy: Thyroid function (baseline and periodic); vitamin B12 level; blood glucose, glycemic control and antidiabetic regimen (patients with diabetes mellitus) should be assessed following initiation, then periodically or following dosage adjustments; cardiac function (heart rate, ECG); zinc level (patients with excessive GI fluid loss maintained on TPN); biliary tract abnormality monitoring if clinically indicated; routine gallbladder ultrasound is not considered necessary (ES [Katznelson 2014]).

Cardiac monitoring (patients receiving IV)

Reference Range

Vasoactive intestinal peptide: <75 ng/L; levels vary considerably between laboratories

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])

Mechanism of Action

Octreotide mimics natural somatostatin by inhibiting serotonin release and the secretion of gastrin, VIP, insulin, glucagon, secretin, motilin, and pancreatic polypeptide. Decreases growth hormone (GH) and IGF-1 in acromegaly. Octreotide provides more potent inhibition of GH, glucagon, and insulin as compared to endogenous somatostatin. Also suppresses LH response to GnRH, secretion of thyroid-stimulating hormone and decreases splanchnic blood flow.

Pharmacokinetics

Duration:

SubQ (injection solution): 6 to 12 hours.

IM (LAR depot suspension): Following a single injection, a steady concentration is achieved within 2 to 3 weeks and maintained for an additional 2 to 3 weeks; steady-state levels are achieved after 3 injections administered at 4-week intervals.

Oral (delayed-release capsule): Complete elimination after ~48 hours in patients who achieve steady-state levels.

Absorption:

SubQ (injection solution): Rapid and complete.

IM (LAR depot suspension): Released slowly (via microsphere degradation in the muscle).

Oral (delayed-release capsule): Limited; rate and extent of absorption decreased by 90% when taken with food.

Distribution: Vd: 13.6 L (21.6 ± 8.5 L in acromegaly).

Protein binding: 65%, primarily to lipoprotein (41% in acromegaly).

Metabolism: Extensively hepatic.

Bioavailability: SubQ (injection solution): 100%; IM (LAR depot suspension): 60% to 63% of SubQ dose. Oral: ~0.5% compared to SubQ (Brayden 2020; Tuvia 2012).

Half-life elimination:

SubQ (injection solution): 1.7 to 1.9 hours; Increased in elderly patients; Cirrhosis: Up to 3.7 hours; Fatty liver disease: Up to 3.4 hours; Renal impairment: Up to 3.1 hours.

Oral (delayed-release capsule): Healthy adults: 2.7 hours; Adults with acromegaly: 3.2 to 4.5 hours; End-stage renal disease (ESRD) requiring dialysis: 7.09 hours.

Time to peak, plasma: SubQ (injection solution): 0.4 hours (0.7 hours acromegaly); IM (LAR depot suspension): Transient peak occurs 1 hour after injection, then steady plateau is reached after 2 to 3 weeks; Oral: 1.75 to 2.5 hours.

Excretion: Urine (32% as unchanged drug).

Clearance: Healthy adults: 7 to 10 L/hour; Adults with acromegaly: 18 L/hour; Decreased in patients with ESRD requiring dialysis.

Pharmacokinetics: Additional Considerations

Altered kidney function: Elimination and clearance are prolonged; clearance may be reduced by about 50% in patients with severe renal failure.

Hepatic function impairment: Patients with liver cirrhosis showed prolonged elimination of the drug with t½ increasing and clearance decreasing after SubQ administration.

Older adult: There is a 46% increase in the half-life of the drug and a 26% decrease in clearance after SubQ administration.

Pricing: US

Capsule, delayed release (Mycapssa Oral)

20 mg (per each): $126.47

Kit (SandoSTATIN LAR Depot Intramuscular)

10 mg (per each): $3,906.12

20 mg (per each): $5,117.69

30 mg (per each): $7,663.37

Solution (Octreotide Acetate Injection)

50 mcg/mL (per mL): $5.40

100 mcg/mL (per mL): $4.08 - $11.93

200 mcg/mL (per mL): $16.32 - $23.85

500 mcg/mL (per mL): $17.88 - $59.63

1000 mcg/mL (per mL): $57.60 - $119.25

Solution (SandoSTATIN Injection)

50 mcg/mL (per mL): $16.61

100 mcg/mL (per mL): $32.21

500 mcg/mL (per mL): $155.37

Solution Prefilled Syringe (Octreotide Acetate Subcutaneous)

50 mcg/mL (per mL): $4.80

100 mcg/mL (per mL): $9.48

500 mcg/mL (per mL): $47.64

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.

Brand Names: International
  • Cryostatin (CR, DO, GT, HN, MX, NI, PA, SV);
  • Gasterina (AR);
  • Minoctre (CL);
  • Nomactril (MX);
  • Octide (ID);
  • Octostat (LK);
  • Octrayne (PT);
  • Octrestatin (UA);
  • Octride (CN, CO, IN, LK, PH);
  • Oktra (UA);
  • Otide (IN);
  • Proclose (CR, DO, GT, HN, MX, NI, PA, SV);
  • Sandostatin (AE, AR, AT, AU, BB, BD, BG, BH, BR, CH, CL, CN, CY, CZ, DE, DK, EE, EG, ES, FI, GB, GR, HK, HN, HR, ID, IE, IL, IN, IQ, IR, IS, JO, JP, KR, KW, LB, LK, LT, LU, LV, LY, MT, MY, NO, NZ, OM, PE, PH, PK, PL, PY, QA, RO, RU, SA, SE, SG, SI, SK, SY, TH, TR, TW, UA, UY, VE, YE);
  • Sandostatin LAR (AE, BG, BH, CU, CY, EE, EG, HR, ID, IL, IS, JP, KR, LB, LK, LT, LU, LV, MT, MY, PE, PH, PY, RO, SA, SG, SI, SK, TH, UY, VN);
  • Sandostatina (MX, PT);
  • Sandostatina LAR (CO);
  • Sandostatina Treoject (IT);
  • Sandostatine (BE, FR, NL);
  • Sandostatine LAR (NL);
  • Siroctid (AT, BE, FR, PL);
  • Treoject (EG)


For country code abbreviations (show table)
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