Octreotide

Dosage Forms

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

Kit, Intramuscular:

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

Solution, Injection:

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

SandoSTATIN: 200 mcg/mL (5 mL [DSC]) [contains phenol]

SandoSTATIN: 500 mcg/mL (1 mL)

SandoSTATIN: 1000 mcg/mL (5 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); 1000 mcg/mL (5 mL)

Solution, Injection [preservative free]:

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

Pharmacology

Mechanism of Action

Mimics natural somatostatin by inhibiting serotonin release, and the secretion of gastrin, VIP, insulin, glucagon, secretin, motilin, and pancreatic polypeptide. Decreases growth hormone and IGF-1 in acromegaly. Octreotide provides more potent inhibition of growth hormone, 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/Pharmacodynamics

Absorption

SubQ: Rapid and complete; IM (depot formulation): Released slowly (via microsphere degradation in the muscle)

Distribution

V_d: 14 L (21.6 ± 8.5 L in acromegaly)

Metabolism

Extensively hepatic

Excretion

Urine (32% as unchanged drug); Clearance: Adults: 10 L/hour; Adults with acromegaly: 18 L/hour

Time to Peak

Plasma: SubQ: 0.4 hours (0.7 hours acromegaly); IM: 1 hour

Duration of Action

SubQ: 6 to 12 hours; when using Sandostatin LAR Depot formulation, steady-state levels are achieved after 3 injections (3 months of therapy)

Half-Life Elimination

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

Protein Binding

65%, primarily to lipoprotein (41% in acromegaly)

Use in Specific Populations

Special Populations: Renal Function Impairment

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

Special Populations: Hepatic Function Impairment

Patients with liver cirrhosis showed prolonged elimination of the drug with t_½ increasing and clearance decreasing.

Special Populations: Elderly

There is a 46% increase in the half-life of the drug, and a 26% decrease in clearance.

Use: Labeled Indications

Acromegaly:

Injection solution: To reduce blood levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) in patients with inadequate response to or who cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses; goal of therapy is to achieve normalization of GH and IGF-1 levels.

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 are not options) with a goal of therapy to reduce GH and IGF-1 levels to normal.

The Endocrine Society suggests use of a somatostatin analog in select patients preoperatively to reduce surgical risk from severe comorbidities and as initial adjuvant therapy in patients with persistent, significant disease (ie, moderate to severe signs/symptoms of growth hormone excess and without local mass effects) postoperatively. Alternative agents are suggested for patients with mild disease postoperatively (Endocrine Society [Katznelson 2014]).

Carcinoid tumors:

Injection solution: Management of symptoms (diarrhea and flushing) in patients with metastatic carcinoid tumors.

LAR depot suspension: Long-term treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.

Vasoactive intestinal peptide-secreting tumors:

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

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

Limitations of use: The effects of octreotide (injection solution and LAR depot suspension) on tumor size, rate of growth, and development of metastases in patients with carcinoid syndrome and VIPomas have not been determined.

Use: Off Label

Carcinoid crisis (prevention)c

Clinical experience suggests the benefit of octreotide in preventing carcinoid crisis prior to invasive procedures in patients with neuroendocrine tumors Oberg 2004. Additional data may be necessary to further define the role of octreotide in this condition.

Diarrhea (refractory or persistent) associated with chemotherapyc

Clinical experience suggests the utility of octreotide in managing refractory diarrhea associated with chemotherapy Benson 2004, Kornblau 2000. Additional data may be necessary to further define the role of octreotide in this condition.

Diarrhea associated with graft-versus-host disease (GVHD)c

Clinical experience suggests the utility of octreotide in managing diarrhea associated with GVHD Kornblau 2000. Additional data may be necessary to further define the role of octreotide in this condition.

Gastroenteropancreatic neuroendocrine tumors (metastatic)a

Data from a randomized, placebo controlled phase III study supports the use of octreotide LAR in the management of well-differentiated metastatic midgut neuroendocrine tumors Rinke 2009. Data from a randomized phase III study support the use of octreotide LAR depot suspension in combination with lutetium Lu 177 dotatate for the treatment of well-differentiated metastatic neuroendocrine tumors that originate in the midgut Strosberg 2017. Clinical experience also suggests the utility of octreotide in managing gastroenteropancreatic neuroendocrine tumors Oberg 2004.

Gastroesophageal variceal hemorrhageayes

Data from a meta-analysis and controlled trial support the use of octreotide in conjunction with endoscopic treatment for the acute management of gastroesophageal variceal hemorrhage Corley 2001, Seo 2014.

Based on the American Association for the Study of Liver Diseases guidelines on the management of portal hypertensive bleeding in cirrhosis and the British Society of Gastroenterology guidelines on the management of variceal hemorrhage in cirrhotic patients, octreotide is recommended as a first-line option for management of variceal bleeding

Hepatorenal syndromebyes

Data from a small controlled trial in patients with type 1 hepatorenal syndrome (HRS) treated with midodrine, octreotide, and albumin showed significant improvement in renal plasma flow, glomerular filtration rate, and urinary sodium excretion, although the trial included only 13 patients. Retrospective data also suggest improvement in 30-day mortality with the combination of midodrine, octreotide, and albumin. Based on American Association for the Study of Liver Diseases (AASLD) clinical practice guidelines for the management of adult patients with ascites due to cirrhosis, octreotide in combination with midodrine and albumin should be considered for the treatment of type 1 HRS.

Malignant bowel obstructionb

Data from a small randomized study supports the use of octreotide in managing gastrointestinal symptoms due to malignant bowel obstructions in patients with cancer Mercadante 2000. Data from a review and a systematic review also support the use of octreotide in managing symptoms caused by malignant bowel obstructions in patients with cancer Mercadante 2007, Mercadante 2012.

Sulfonylurea-induced hypoglycemiab

Data from a prospective, double-blind, placebo-controlled study supports the use of octreotide in the treatment of sulfonylurea-induced hypoglycemia Fasano 2008. Additional trials may be necessary to further define the role of octreotide in this condition.

Thymoma/thymic malignancies (advanced)b

Data from a small phase II study supports the use of octreotide in the treatment of advanced (invasive, recurrent, or metastatic) thymoma/thymic malignancies Loehrer 2004. Additional trials may be necessary to further define the role of octreotide in this condition.

Zollinger-Ellison syndromec

Data from a limited number of patients in an open label study suggest that octreotide may be beneficial for the treatment of progressive malignant gastrinoma (Zollinger-Ellison syndrome) Shojamanesh 2002.

Additional Off-Label Uses

Cushing's syndrome (ectopic); Hypothalamic obesity; Postgastrectomy dumping syndrome; Small bowel fistulas

Contraindications

Hypersensitivity to octreotide or any component of the formulation

Dosage and Administration

Dosing: Adult

Acromegaly:

SubQ, IV: Initial: 50 mcg 3 times/day; titrate to achieve growth hormone (GH) levels <5 ng/mL or insulin-like growth factor 1 (IGF-1) levels <1.9 units/mL in males and <2.2 units/mL in females. Usual effective dose: 100 mcg 3 times/day; 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. Note: Should be withdrawn yearly for a 4-week interval (8 weeks for depot injection) in patients who have received irradiation. Resume if levels increase and signs/symptoms recur.

IM depot injection: Patients must be stabilized on subcutaneous octreotide for at least 2 weeks before switching to the long-acting depot. Upon switch: 20 mg IM intragluteally every 4 weeks for 3 months, then the dose may be modified based upon response.

Dosage adjustment for acromegaly: After 3 months of depot injections, the dosage may be continued or modified as follows:

GH ≤1 ng/mL, IGF-1 normal, and symptoms controlled: Reduce octreotide depot to 10 mg IM every 4 weeks

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

GH >2.5 ng/mL, IGF-1 elevated, and/or symptoms uncontrolled: Increase octreotide depot to 30 mg IM 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 (Giustina 2009).

Note: If clinical and/or biochemical response is inadequate at maximum dosage of octreotide, consider combination therapy with pegvisomant or a dopamine agonist (Endocrine Society [Katznelson 2014]).

Carcinoid tumors:

SubQ, IV: Initial 2 weeks: 100 to 600 mcg/day in 2 to 4 divided doses; usual range: 50 to 750 mcg/day (some patients may require up to 1,500 mcg/day); experience with doses above 750 mcg/day is limited.

IM depot injection: Patients must be stabilized on subcutaneous octreotide for at least 2 weeks before switching to the long-acting depot. Upon switch: 20 mg IM intragluteally every 4 weeks for 2 months, then the dose may be modified based upon response.

Note: Patients should continue to receive their SubQ injections for the first 2 weeks at the same dose in order to maintain therapeutic levels (some patients may require 3 to 4 weeks of continued SubQ injections). Patients who experience periodic exacerbations of symptoms may require temporary SubQ injections in addition to depot injections (at their previous SubQ dosing regimen) until symptoms have resolved.

Dosage adjustment for carcinoid tumors: After 2 months of depot injections, the dosage may be continued or modified as follows:

Increase to 30 mg IM every 4 weeks if symptoms are inadequately controlled

Decrease to 10 mg IM every 4 weeks, for a trial period, if initially responsive to 20 mg dose

Dosage >30 mg is not recommended

Carcinoid crisis, prevention (off-label use): Immediate release octreotide solution (Oberg 2004):

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

Emergency surgery in somatostatin analog-naïve patients with functional neuroendocrine tumors:

IV bolus: 500 to 1000 mcg 1 to 2 hours prior to procedure or

SubQ: 500 mcg 1 to 2 hours prior to procedure

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

Postoperative dose (if supplemental doses required during procedure): IV: 50 to 200 mcg/hour continuous infusion for 24 hours, followed by resumption of the preoperative treatment schedule.

Diarrhea (off-label use): IV: Initial: 50 to 100 mcg every 8 hours; increase by 100 mcg/dose at 48-hour intervals; maximum dose: 500 mcg every 8 hours

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

Low grade or uncomplicated: SubQ: 100 to 150 mcg every 8 hours (Benson 2004; Kornblau 2000)

Severe: Initial: SubQ: 100 to 150 mcg every 8 hours; may increase to 500 to 1500 mcg IV or SubQ every 8 hours (Kornblau 2000)

Complicated: IV, SubQ: Initial: 100 to 150 mcg 3 times/day or IV Infusion: 25 to 50 mcg/hour; may escalate to 500 mcg 3 times/day until controlled (Benson 2004)

Diarrhea associated with acute graft-versus-host disease (GVHD) (off-label use): 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 (Kornblau 2000)

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

IM (depot): 30 mg every 4 weeks until tumor progression or death (Rinke 2009) or

SubQ: Initial: 100 to 500 mcg 2 to 4 times daily (usually 150 mcg 3 times daily), may increase to response (symptom control) by doubling the dose every 3 to 4 days or a continuous subQ infusion of 1,000 to 2,000 mcg/day (Oberg 2004) or

IM (depot): Assure tolerability by initiating with the SubQ formulation for 3 to 7 days (and continue with SubQ for the first ~14 days after the initial IM depot dose). Then initiate IM (depot): 20 to 30 mg every 28 days (SubQ doses of 200 to 600 mcg/day should receive 20 mg IM and SubQ doses of 750 to 1,500 mcg/day should receive 30 mg IM); IM (depot) range: 20 to 60 mg every 28 days (Oberg 2004).

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 (Strosberg 2017). 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 (off-label use): Note: Empiric IV prophylactic antibiotics should be administered to patients with cirrhosis and active variceal bleeding for up to 7 days. Vasoactive therapy should be given to patients with varices or at risk for having varices who have upper GI bleeding (ASSLD [Garcia-Tsao 2017]; Bajaj 2019).

IV bolus: 50 mcg, followed by continuous IV infusion of 50 mcg/hour for 2 to 5 days; may repeat bolus in first hour if hemorrhage not controlled (Erstad 2001; ASSLD [Garcia-Tsao 2017]; Bajaj 2019; BSG [Tripathi 2015]).

Hepatorenal syndrome (off-label use): SubQ: Initial: 100 mcg 3 times daily; may increase to 200 mcg 3 times daily (with a goal to increase mean arterial pressure [MAP] by at least 15 mm Hg from baseline) (Angeli 1999; Esrailian 2007; Garcia-Tsao 2009; AASLD [Runyon 2012])

Malignant bowel obstruction (off-label use): SubQ: 200 to 900 mcg/day in 2 to 3 divided doses (Mercadante 2007; Mercadante 2012) or 300 mcg/day by continuous SubQ infusion (Mercadante 2000)

Sulfonylurea-induced hypoglycemia (off-label use): Note: Although octreotide use has been advocated as a first line therapy, indications and dosing for octreotide are not firmly established (Glatstein 2012). Octreotide may reduce the incidence of recurrent hypoglycemia seen with dextrose-alone therapy (Fasano 2008). In addition, although subcutaneous administration is the preferred route, administration via intravenous bolus and intravenous infusion have also been described in the literature (Barkin 2013; Braatvedt 1997; Carr 2002; Crawford 2004; Dougherty 2010; Dougherty 2013; Fasano 2008; Graudins 1997; Green 2003; Hung 1997; McLaughlin 2000; Mordel 1998). Optimal care decisions should be made based upon patient-specific details. Repeat dosing, dose escalation, or initiation of a continuous infusion may be required in patients who experience recurrent hypoglycemia. Duration of treatment may exceed 24 hours.

SubQ: 50 to 75 mcg; repeat every 6 hours as needed based upon blood glucose concentrations (Fasano 2008; Smith 2019)

IV: Doses up to 125 mcg/hour have been used successfully (McLaughlin 2000)

Thymoma/thymic 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 (Loehrer 2004).

Vasoactive intestinal peptide tumors (VIPomas):

SubQ, IV: Initial 2 weeks: 200 to 300 mcg/day in 2 to 4 divided doses; titrate dose based on response/tolerance. Range: 150 to 750 mcg/day (doses >450 mcg/day are rarely required)

IM depot injection: Patients must be stabilized on subcutaneous octreotide for at least 2 weeks before switching to the long-acting depot. Upon switch: 20 mg IM intragluteally every 4 weeks for 2 months, then the dose may be modified based upon response.

Note: Patients receiving depot injection should continue to receive their SubQ injections for the first 2 weeks at the same dose in order to maintain therapeutic levels (some patients may require 3 to 4 weeks of continued SubQ injections). Patients who experience periodic exacerbations of symptoms may require temporary SubQ injections in addition to depot injections (at their previous SubQ dosing regimen) until symptoms have resolved.

Dosage adjustment for VIPomas: After 2 months of depot injections, the dosage may be continued or modified as follows:

Increase to 30 mg IM every 4 weeks if symptoms are inadequately controlled

Decrease to 10 mg IM every 4 weeks, for a trial period, if initially responsive to 20 mg dose

Dosage >30 mg is not recommended

Zollinger-Ellison syndrome (off-label use): Note: Continue treatment until complete disease remission, or until significant disease progression or unacceptable toxicity.

SubQ: Initial: 100 mcg every 12 hours; may increase to 200 mcg every 12 hours (based upon fasting blood sugars) (Shojamanesh 2002).

IM (depot): 30 mg once a month (after tolerating 2 to 4 weeks of short-acting regimen). Note: Continue subcutaneous formulation for the first 2 weeks of initiation of depot injection (Shojamanesh 2002).

Dosing: Geriatric

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.

Dosing: Pediatric

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 (eg, postoperative): Limited data available; efficacy results variable; optimal dose not established (Church 2017): 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 (Landvoigt 2006; Mery 2014; Yeh 2013).

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 (Al-Hussaini 2012; Beckman 2000; Couper 1989; Jaros 1988; Pai 2011).

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 (Al-Hussaini 2012; Beckman 2000; Couper 1989; Jaros 1988; Pai 2011); a higher dose of 60 mcg/kg/day has been reported (Al-Hussaini 2012). In adults, a maximum dose of 500 mcg/dose has been recommended for GVHD (ASCO [Benson 2004]).

Continuous IV infusion: Note: Typically IV infusion reserved for patients failing intermittent dosing: Initial: 1 mcg/kg/hour (Beckman 2000); some patients may require titration; doses up to 49 mcg/kg/day have been reported (Pai 2011).

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 (Al-Hussaini 2012; Eroglu 2004).

Hyperinsulinemic hypoglycemia: Limited data available: Note: Not first-line therapy (diazoxide suggested for initial management) (Shah 2017). Dosing should be individualized to patient response to achieve and maintain target serum glucose concentrations (typically >70 mg/dL) (Sperling 2014).

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 (Demirbilek 2017; Shah 2017).

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 (Demirbilek 2017; Hosokawa 2017; Shah 2017).

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 (Le Quan Sang 2012; Shah 2017).

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 (Lustig 1999; Lustig 2003; Lustig 2011).

Sulfonylurea overdose: Limited data available: Dosing in pediatric patients based on experience in adult patients; pediatric-specific reports are sparse (Glatstein 2010; Howland 2011). 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 (Dougherty 2013). Note: Although octreotide use is strongly advocated as a first-line therapy, indications and dosing for octreotide are not firmly established (Glatstein 2012).

Reconstitution

IV infusion: Dilute injection solution in 50 to 200 mL NS or D5W

IM depot: Allow vial and provided diluent-filled syringe to reach room temperature slowly (approximately 30 to 60 minutes). Reconstitute with provided diluent; refer to product labeling for detailed mixing instructions.

Administration

Regular injection formulation: 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.

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.

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

Dietary Considerations

Schedule injections between meals to decrease GI effects. May alter absorption of dietary fats.

Storage

Injection solution: Octreotide is a clear solution and should be stored at refrigerated temperatures between 2°C and 8°C (36°F and 46°F). Protect from light. May be stored at room temperature of 20°C to 30°C (68°F and 86°F) for up to 14 days when protected from light. Stable as a parenteral admixture in NS or D5W for 24 hours. Discard multidose vials within 14 days after initial entry.

LAR depot suspension: Prior to dilution, store at refrigerated temperatures between 2°C and 8°C (36°F and 46°F). Protect from light. Additionally, the manufacturer reports that octreotide suspension may be stored at room temperature of 20°C to 25°C (68°F and 77°F) for up to 10 days when protected from light (data on file [Novartis 2011]). Depot drug product kit may be at room temperature for 30 to 60 minutes prior to use. Use suspension immediately after preparation.

Drug Interactions

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. 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. 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. Exceptions are discussed in separate monographs. Consider therapy modification

Codeine: Somatostatin Analogs may decrease the metabolism of Codeine. The formation of two major codeine metabolites (morphine and norcodeine) may be impaired by somatostatin analogs. Monitor therapy

CycloSPORINE (Systemic): Somatostatin Analogs may decrease the serum concentration of CycloSPORINE (Systemic). Consider therapy modification

Fexinidazole [INT]: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT]. Avoid combination

Gallium Ga 68 Dotatate: Somatostatin Analogs may diminish the therapeutic 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: Imaging with gallium Ga 68 dotatate 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 dotatate. Consider therapy modification

Gallium Ga 68 Dotatoc: Somatostatin Analogs may diminish the therapeutic 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. Consider therapy modification

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

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

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. 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 each lutetium Lu 177 dotatate dose. Administer short- and long-acting octreotide during treatment as recommended. See full monograph. Consider therapy modification

Macimorelin: Somatostatin Analogs may diminish the diagnostic effect of Macimorelin. Avoid combination

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. 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. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. 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. 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. 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. Consider therapy modification

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

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

Adverse Reactions

Adverse reactions vary by route of administration and dosage form. Frequency of cardiac, endocrine, and gastrointestinal adverse reactions was generally higher in patients with acromegaly.

>10%:

Cardiovascular: Sinus bradycardia (19% to 25%), hypertension (≤13%)

Central nervous system: Fatigue (1% to 32%), headache (6% to 30%), dizziness (5% to 20%), pain (4% to 15%)

Dermatologic: Pruritus (18%), skin rash (≤15%), alopecia (13%)

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

Gastrointestinal: Abdominal distress (≤61%), diarrhea (≤61%), loose stools (≤61%), nausea (≤61%), abdominal pain (≤44%), flatulence (≤38%), cholelithiasis (13% to 38%; length of therapy dependent), gallbladder sludge (24%; length of therapy dependent), constipation (9% to 21%), vomiting (4% to 21%), biliary obstruction (duct dilatation: 12%), upper abdominal pain (11%)

Hematologic & oncologic: Anemia (≤15%)

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

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

Neuromuscular & skeletal: Back pain (1% to 27%), arthropathy (8% to 19%), myalgia (≤18%), musculoskeletal pain (5% to 15%)

Respiratory: Upper respiratory tract infection (10% to 23%), flu-like symptoms (1% to 20%), sinusitis (5% to 15%)

1% to 10%:

Cardiovascular: Cardiac conduction disturbance (9% to 10%), cardiac arrhythmia (3% to 9%), edema (1% to 4%), flushing (1% to 4%)

Central nervous system: Depression (1% to 4%)

Endocrine & metabolic: Goiter (≤8%), hypoglycemia (2% to 4%)

Gastrointestinal: Abdominal distention (<10%), abnormal stools (<10%), dyspepsia (4% to 6%), fecal discoloration (4% to 6%), steatorrhea (4% to 6%), tenesmus (4% to 6%), malabsorption (fat: 1% to 4%)

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

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

Infection: Cold symptoms (1% to 4%)

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

Neuromuscular & skeletal: Arthralgia (1% to 4%), asthenia (1% to 4%), tremor (1% to 4%)

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

Respiratory: Epistaxis (1% to 4%)

Frequency not defined:

Cardiovascular: Pulmonary embolism

Central nervous system: Cerebrovascular disease, malignant hyperthermia

Hematologic & oncologic: Rectal hemorrhage

Hepatic: Ascites

Respiratory: Pleural effusion

<1%, postmarketing, and/or case reports: Abdominal swelling, acute myocardial infarction, adrenocortical insufficiency, amenorrhea, amnesia, anaphylactic shock, aneurysm, anxiety, aphasia, appendicitis, arterial thrombosis (arm), arthritis, atrial fibrillation, basal cell carcinoma of skin, Bell's palsy, biliary obstruction, breast carcinoma, cardiac failure, cellulitis, chest pain, cholangitis (ascending), cholecystitis, cholestatic hepatitis, cyanocobalamin deficiency, deafness, decreased libido, diabetes insipidus, diabetes mellitus, dyspnea, facial edema, galactorrhea not associated with childbirth, gastrointestinal hemorrhage, gastrointestinal ulcer, glaucoma, gynecomastia, hematuria, hemiparesis, hemorrhoids, hepatitis, hypersensitivity reaction, increased creatine phosphokinase in blood specimen, increased intraocular pressure, increased liver enzymes, increased serum creatinine, infrequent uterine bleeding, intestinal obstruction, intracranial hemorrhage, iron deficiency, ischemia, jaundice, joint effusion, liver steatosis, menstrual disease (polymenorrhea), migraine, nephrolithiasis, neuritis, nodule (pulmonary), nonimmune anaphylaxis, orthostatic hypotension, otalgia, palpitations, pancreatitis, pancytopenia, paranoid ideation, paresis, petechia, pituitary apoplexy, pneumonia, pneumothorax (aggravated), polyp (gallbladder), prolonged QT interval on ECG, pulmonary hypertension, Raynaud’s disease, renal failure syndrome, renal insufficiency, scotoma, seizure, status asthmaticus, suicidal tendencies, syncope, tachycardia, thrombocytopenia, thrombophlebitis, thrombosis (including retinal vein), urticaria, vaginitis, vertigo, visual field defect, weight loss

Warnings/Precautions

Concerns related to adverse effects:

• Abnormal Schillings test: Chronic treatment has been associated with abnormal Schillings test; monitor vitamin B₁₂ levels.
• Cholelithiasis: May impair gallbladder function (inhibits gallbladder contractility and decreases bile secretion); monitor patients for cholelithiasis. Cholelithiasis and complications of cholelithiasis (eg, cholecystitis, cholangitis, pancreatitis) requiring cholecystectomy have been reported; discontinue and treat appropriately if suspected. The incidence of gallbladder stone or biliary sludge increases with a duration of therapy of ≥12 months. Prophylactic cholecystectomy is recommended in patients with GI or pancreatic neuroendocrine tumors undergoing abdominal surgery if octreotide treatment is planned (Oberg 2004).
• Glucose regulation: Somatostatin analogs may affect glucose regulation. In type I diabetes, severe hypoglycemia may occur; in type II diabetes or patients without diabetes, hyperglycemia may occur. Insulin and other hypoglycemic medication requirements may change. Octreotide may worsen hypoglycemia in patients with insulinomas; use with caution.
• Local reactions: Mild to moderate injection-site pain (usually lasting 1 hour) may occur with the depot formulation.
• Hypothyroidism: Suppresses secretion of TSH; monitor for hypothyroidism.
• Pancreatitis: May alter absorption of dietary fats; monitor for pancreatitis.

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 fluid loss: May reduce excessive fluid loss in patients with conditions that cause such a loss; periodic monitoring for elevations in zinc levels is recommended in such patients that are maintained on total parenteral nutrition (TPN).
• Hepatic impairment: Use caution in patients with hepatic impairment; dosage adjustment may be required in patients with established cirrhosis.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be required in patients receiving dialysis.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• QTc-prolonging agents: Octreotide may enhance the adverse/toxic effects of other QTc-prolonging agents.

Dosage form specific issues:

• Depot formulation: Do not use depot formulation for the treatment of sulfonylurea-induced hypoglycemia (Dougherty 2010).
• Vehicle used in depot injection (polylactide-co-glycolide microspheres): Has rarely been associated with retinal artery occlusion in patients with abnormal arteriovenous anastomosis (eg, patent foramen ovale).

Special populations:

• Elderly: Dosage adjustment may be necessary; significant increases in elimination half-life have been observed in older adults.
• Females: Therapy may restore fertility; females of childbearing potential should use adequate contraception.
• Pediatric: Postmarketing cases of serious and fatal events, including hypoxia and necrotizing enterocolitis (NEC), have been reported with octreotide use in children (usually with serious underlying conditions), particularly in children <2 years of age. In studies with octreotide depot, the incidence of cholelithiasis in children is higher than the reported incidences for adults and efficacy was not demonstrated.

Other warnings/precautions:

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

Monitoring Parameters

Acromegaly:

Initial:

Short-acting formulation: To evaluate responsiveness to therapy, 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.

Long-acting formulation: Serum GH and IGF-1 (at 3 months prior to next dose)

Maintenance: Serum GH and IGF-1 every 3 to 6 months

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 fluid loss maintained on TPN); gallbladder monitoring if clinically indicated, routine gallbladder ultrasound is not considered necessary (Endocrine Society [Katznelson 2014])

Pregnancy

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 is limited. In case reports of acromegalic women who received normal doses of octreotide during pregnancy, no congenital malformations were reported.

If treatment for acromegaly is required during pregnancy for worsening symptoms (eg, headaches or evidence of tumor growth), short-acting octreotide may be considered. 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 (Endocrine Society [Katznelson 2014]).

Because normalization of IGF-1 and GH may restore fertility in women with acromegaly, women of childbearing potential should use adequate contraception during treatment. 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 (Endocrine Society [Katznelson 2014]).

Patient Education

What is this drug used for?

• It is used to treat diarrhea and flushing caused by cancer.
• It is used to treat acromegaly.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Abdominal pain
• Passing gas
• Nausea
• Vomiting
• Flu-like symptoms
• Muscle pain
• Joint pain
• Back pain
• Stuffy nose
• Sore throat
• Constipation
• Diarrhea
• Hair loss
• Injection site pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.
• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.
• Low thyroid level like constipation; difficulty handling heat or cold; memory problems; mood changes; or burning, numbness, or tingling feeling.
• Gallstones like pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; yellow skin; or fever with chills.
• Severe dizziness
• Passing out
• Vision changes
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.
• Slow heartbeat
• Abnormal heartbeat
• Bloating
• Abdominal edema
• Severe loss of strength and energy
• Severe headache
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.