Brand names: SandoSTATIN, SandoSTATIN LAR Depot
Drug class: Somatostatin Agonists
- Somatostatin Analogs
VA class: GA208
Chemical name: [R-(R*,R*)]-d-Phenylalanyl-l-cysteinyl-l-phenylalanyl-d-tryptophyl-l-lysyl-l-threonyl-N-[2-hydroxy-1-(hydroxymethyl)propyl]-l-cysteinamide cyclic(2→7)-disulfide acetate (salt)
Molecular formula: C₄₉H₆₆N₁₀O₁₀S₂•× C₂H₄O₂
CAS number: 79517-01-4

Medically reviewed by Drugs.com on Mar 3, 2022. Written by ASHP.

Introduction

Synthetic polypeptide structurally and pharmacologically related to somatostatin (growth hormone [somatropin] release inhibiting factor).

Uses for Octreotide

Carcinoid Tumors

Symptomatic treatment to suppress or inhibit severe diarrhea and flushing associated with carcinoid tumors.

Long-acting suspension is used for long-term management of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors in patients in whom initial treatment with octreotide immediate-release injection has been shown to be effective and tolerated (designated an orphan drug by FDA for this use).

Acute management of potentially life-threatening hypotension associated with carcinoid crisis.

Prophylaxis of carcinoid crisis that might be precipitated by anesthesia, surgery, initiation of chemotherapy, or infection.

Vasoactive Intestinal Peptide-Secreting Tumors

Management of profuse watery diarrhea associated with vasoactive intestinal polypeptide (VIP)-secreting tumors.

Long-acting suspension is used for long-term management of profuse watery diarrhea associated with VIP-secreting tumors in patients who have been treated successfully with octreotide immediate-release injection (designated an orphan drug by FDA for this use).

Acromegaly

Treatment to reduce growth hormone (GH) and insulin-like growth factor I (IGF-I) blood concentrations in patients with acromegaly who have had inadequate responses to or are not candidates for surgical resection, pituitary irradiation, and bromocriptine mesylate (at maximally tolerated doses).

Long-acting suspension is used for long-term therapy in patients who are candidates for medical therapy and who have been treated successfully with immediate-release injection (designated an orphan drug by FDA for this use). Long-acting suspension may be used in patients who are not candidates for surgery or who have had an inadequate response to surgery or patients who have had a suboptimal response to radiation therapy.

Congenital Hyperinsulinism† [off-label]

Has been used in a limited number of neonates and infants to stabilize plasma glucose levels prior to pancreatectomy^{† [off-label]}, to treat recurrent post-operative hypoglycemia^{† [off-label]}, and as an alternative medical treatment to diazoxide for control of hypoglycemia^{† [off-label]}.

Octreotide Dosage and Administration

General

• Octreotide acetate is commercially available as an immediate-release (short-acting) injection for sub-Q or IV administration and as a long-acting (extended-release) suspension for IM administration.

• Clinical and/or biochemical response may diminish to some extent during prolonged therapy.

Carcinoid Tumors

• Measurement of 5-HIAA (urinary 5-hydroxyindole acetic acid), plasma serotonin, or plasma Substance P may be useful in monitoring response to therapy.

Vasoactive Intestinal Peptide-secreting Tumors

• Measurement of VIP (plasma vasoactive intestinal peptide) may be useful in monitoring response to therapy.

Acromegaly

• Measurement of growth hormone (GH) or insulin growth factor (IGF-I [somatomedin C]) may be useful in monitoring response to therapy.

Administration

Administer immediate-release (short-acting) injection sub-Q or IV, as a rapid IV injection or as an IV infusion.

Sub-Q injection is the usual route of administration because of delayed absorption and somewhat prolonged activity, as well as patient convenience.

IV administration generally is reserved for emergency situations (e.g., acute management of carcinoid crisis) in which the drug can be injected rapidly.

Administer long-acting (extended-release) suspension IM; do not administer sub-Q or IV.

Administration of long-acting suspension at intervals >4 weeks is not recommended.

Administer immediate-release injection between meals and at bedtime to minimize adverse GI effects; reducing dietary fat also may decrease adverse GI effects. (See Biliary Effects under Cautions.)

When immediate-release injection is used in combination with telotristat etiprate for carcinoid syndrome diarrhea, administer immediate-release injection ≥30 minutes following administration of telotristat etiprate. (See Specific Drugs under Interactions.)

Sub-Q Administration

To minimize pain, administer smallest volume that will deliver the desired dose; rotate injection site systematically. Avoid multiple injections at the same site within short periods of time.

Daily dosage may be given in 2–4 divided doses.

IM Administration

Administer long-acting (extended-release) suspension IM into the gluteal muscle; alternate injection sites to minimize irritation. Injection into the deltoid muscle results in severe discomfort and is not recommended.

IM administration of long-acting suspension may be used after tolerance established with at least 2 weeks of sub-Q therapy with immediate-release injection.

Must be given under the supervision of a clinician.

Reconstitution

Reconstitute long-acting suspension immediately prior to administration.

Prior to reconstitution, remove long-acting suspension kit from refrigerator and allow it to remain at room temperature for 30–60 minutes. Do not inject provided diluent without preparing long-acting suspension. Closely follow mixing instructions included in the packaging.

IV Infusion

For solution and drug compatibility information, see Compatibility under Stability.

Dilution

Immediate-release injection may be diluted in 50–200 mL of 0.9% sodium chloride or 5% dextrose injection.

Rate of Administration

Dilutions of immediate-release injection may be infused over 15–30 minutes. Alternatively, infuse over 8–24 hours.

IV Injection

For solution and drug compatibility information, see Compatibility under Stability.

For rapid, direct IV injection (IV bolus), immediate-release injection may be administered undiluted.

Direct IV administration is generally reserved for emergencies (e.g., acute management of carcinoid crisis).

Immediate-release injection may be diluted in 50–200 mL of 0.9% sodium chloride or 5% dextrose injection and administered by IV push over 3 minutes.

Dosage

Available as octreotide acetate; dosage expressed in terms of octreotide.

Usual dosages are not well defined because of the wide variation in disease severity and response.

Individualize dosage according to patient response (symptomatic relief, biochemical response) and tolerance.

Initiate therapy with immediate-release injection administered sub-Q. If patient responds well after ≥2 weeks of sub-Q therapy, switch to long-acting (extended-release) suspension administered IM.

Maintain therapy with sub-Q injections of immediate-release injection for at least 2 weeks after initiating therapy with long-acting suspension.

Pediatric Patients

Congenital Hyperinsulinism† [off-label]

IV or Sub-Q

Dosages of 1–40 mcg/kg (immediate-release injection) daily have been used in neonates and infants to stabilize plasma glucose levels prior to pancreatectomy, to treat recurrent post-operative hypoglycemia, and as an alternative medical treatment to diazoxide for control of hypoglycemia; however, experience in pediatric patients is limited.

Adults

General

Sub-Q

Initially, 50–100 mcg (immediate-release injection) 1–3 times daily (usually 50 mcg 2 or 3 times daily). Subsequent dosage may be increased gradually according to patient response and tolerance.

Carcinoid Tumors

Sub-Q

Initiate therapy with 100–600 mcg of immediate-release injection daily (average 300 mcg daily), given in 2–4 divided doses for at least 2 weeks.

Median maintenance dosage (immediate-release injection) in clinical studies was approximately 450 mcg daily, clinical and biochemical benefits were obtained with as little as 50 mcg daily, dosages up to 1500 mcg daily sometimes were required; experience with dosages >750 mcg daily is limited.

When switching to IM injection of long-acting suspension, continue sub-Q injections of immediate-release formulation at the previous dosage during at least the first 2 weeks of therapy with the long-acting suspension; sub-Q therapy (immediate-release injection) may be needed as long as 3–4 weeks to prevent exacerbation of disease symptoms.

Temporary concomitant use of sub-Q therapy with immediate-release injection (at the dosage used prior to switching to the long-acting suspension) may be required to control exacerbation of symptoms that occur during IM therapy with long-acting suspension.

IM

Initially, 20 mg (long-acting suspension) once every 4 weeks for 2 months in patients who have responded well to ≥2 weeks of therapy with immediate-release injection. After 2 months of therapy, dosage may be increased to 30 mg once every 4 weeks if necessary for adequate symptom control. Dose may be decreased to 10 mg every 4 weeks if satisfactory symptom relief is achieved with the 20 mg dose.

Safety and efficacy of doses >30 mg (long-acting suspension) have not been evaluated and are not recommended.

Carcinoid Crisis (Treatment)

Administer immediate-release injection by rapid IV injection or prolonged IV infusion.

IV

50–500 mcg (immediate-release injection) administered by rapid IV injection and repeated as necessary.

Alternatively, 50 mcg/hour (immediate-release injection) infused IV for 8–24 hours.

Carcinoid Crisis (Prophylaxis)

Sub-Q

250–500 mcg (immediate-release injection) 1–2 hours prior to anesthetic induction has been used to prevent carcinoid crisis associated with surgery.

150–250 mcg (immediate-release injection) every 6–8 hours 24–48 hours prior to anesthetic induction or initiation of chemotherapy has been used.

Vasoactive Intestinal Peptide-secreting Tumors

Sub-Q

Initiate therapy with 200–300 mcg of immediate-release injection daily given in 2–4 divided doses for at least 2 weeks.

Dosages range from 150–750 mcg (immediate-release injection) daily during this period; >450 mcg daily usually not required.

When switching to IM injection of long-acting suspension, continue sub-Q injections of immediate-release injection at the previous dosage during at least the first 2 weeks of therapy with the long-acting suspension; sub-Q therapy (immediate-release injection) may be needed as long as 3–4 weeks to prevent exacerbation of disease symptoms.

Temporary concomitant use of sub-Q therapy with immediate-release injection (at the dosage used prior to switching to the long-acting suspension) may be required to control exacerbation of symptoms that occur during IM therapy with long-acting suspension.

IM

Initially, 20 mg (long-acting suspension) once every 4 weeks for 2 months in patients who have responded well to ≥2 weeks of therapy with immediate-release injection. After 2 months of therapy, increase dosage to 30 mg once every 4 weeks if necessary for adequate symptom control. Dose may be decreased to 10 mg every 4 weeks if satisfactory symptom relief is achieved with the 20 mg dose.

Safety and efficacy of doses >30 mg (long-acting suspension) have not been evaluated and are not recommended.

Acromegaly

Initiate therapy with low dosage immediate-release injection administered sub-Q to promote tolerance to adverse GI effects during titration.

Patients responding well to immediate-release injection (based on GH and IGF-I levels) and who tolerate the drug may be switched to the long-acting suspension administered IM.

Sub-Q

Initiate therapy with 150 mcg (immediate-release injection) daily given in 3 divided doses.

Titrate dosage by tolerance, clinical effect, and evaluation of multiple GH levels. Adjust dosage based on GH levels measured at 1- to 4-hour intervals for 8–12 hours after sub-Q injection or alternatively, based on a single IGF-I level measured 2 weeks after initiation of therapy or a dosage change.

300–600 mcg (immediate-release injection) daily given in 3 divided doses generally results in maximum effect; up to 1500 mcg daily given in 3 divided doses may be needed in some cases.

If patient has received pituitary irradiation, withdraw therapy for approximately 4 weeks each year to assess disease activity. If GH or IGF-I levels increase and symptoms recur, resume therapy.

IM

Initially 20 mg (long-acting suspension) once every 4 weeks for 3 months in patients who have responded well to immediate-release injection.

Subsequent doses of long-acting suspension are determined based on GH and IGF-I concentrations and clinical response. (See Table 1.)

GH and IGF-I measurements may be made after 3 monthly IM injections. Adjust dosage based on the mean of 4 GH levels measured at 1-hour intervals taken 4 weeks after the last injection of long-acting suspension or a single IGF-I level measured 4 weeks after the last injection of long-acting suspension.

If clinical and biochemical control is not obtained at a dosage of 30 mg once every 4 weeks, dosage may be increased to 40 mg once every 4 weeks; doses >40 mg are not recommended.

If patient has received pituitary irradiation, withdraw therapy yearly for approximately 8 weeks to assess disease activity. If GH or IGF-I levels increase and symptoms recur, resume therapy.

Prescribing Limits

Adults

General

Maximum recommended dosage has not been established; however, dosages ≥5 times usual (e.g., 1500–3000 mcg daily) have been used, and substantially higher single doses (e.g., up to 120 mg infused IV over 8 hours) reportedly have been administered without serious adverse effect.

Potential long-term effects (e.g., adverse GI and biliary effects) of relatively high dosages have not been fully elucidated. Possibility that clinical and/or biochemical response may diminish to some extent during prolonged therapy should be considered.

Carcinoid Tumors

Sub-Q

Limited experience with daily dosages exceeding 750 mcg (immediate-release injection); dosages up to 1500 mcg daily have been used.

IM

Safety and efficacy of doses >30 mg (long-acting suspension) have not been evaluated and are not recommended.

Vasoactive Intestinal Peptide-secreting Tumors

IM

Safety and efficacy of doses >30 mg (long-acting suspension) have not been evaluated and are not recommended.

Acromegaly

IM

Doses >40 mg (long-acting suspension) are not recommended.

Special Populations

Renal Impairment

Clearance may be reduced substantially in patients with severe renal impairment; dosage reduction may be necessary in patients with renal failure requiring dialysis.

Geriatric Patients

Elimination may be prolonged; dosage adjustment may be necessary.

Cautions for Octreotide

Contraindications

• Known hypersensitivity to octreotide or any ingredient in the formulation.

Warnings/Precautions

Warnings

Biliary Effects

Biliary abnormalities (e.g., cholelithiasis, microlithiasis, sediment, sludge, and dilatation) occur commonly, possibly due to drug-induced alterations in GI fat absorption, inhibited gallbladder contractility, and decreased bile secretion. Acute cholecystitis, ascending cholangitis, biliary obstruction, cholestatic hepatitis, and pancreatitis have been reported rarely. Incidence related to duration of therapy; incidence not apparently related to age, sex, or dose.

If severe abdominal pain develops during therapy, consider the possibility of biliary complications (e.g., cholelithiasis) potentially requiring surgical intervention.

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and anaphylactoid reactions have been reported.

General Precautions

Acromegaly

Monitor closely all patients with growth hormone secreting tumors; tumor expansion may result in serious complications (e.g., visual field defects).

Endocrine Effects

Hypoglycemia or hyperglycemia can occur as a result of altered balance between the counter-regulatory hormones (e.g., insulin, glucagon, growth hormone). Hypoglycemia, sometimes severe, more commonly occurs in patients with type I diabetes mellitus. Hyperglycemia more commonly occurs in nondiabetic patients and those with type II diabetes mellitus. Dosage adjustment may be required for insulin or hypoglycemic agents in patients with diabetes mellitus.

Monitor glucose tolerance and antidiabetic treatment periodically.

Hypothyroidism may result from suppression of secretion of thyroid stimulating hormone (TSH). Perform baseline and periodic assessment of thyroid function (e.g., TSH, total and/or free thyroxine [T₄]). Patients with preexisting thyroid dysfunction may require adjustment in thyroid supplementation.

Cardiovascular Effects

Sinus bradycardia, conduction abnormalities, and arrhythmias reported in patients with acromegaly or carcinoid syndrome. ECG changes (e.g., QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, early R-wave progression, and nonspecific ST-T-wave changes) and worsening of CHF reported. Dose adjustments in drugs with bradycardic effects (e.g., β-adrenergic blocking agents) may be required. (See Specific Drugs under Interactions.)

Nutritional Effects

Decreases in serum vitamin B₁₂ concentrations and abnormal Shilling’s test results reported; monitor vitamin B₁₂ concentrations.

Alterations in GI absorption of dietary fats reported.

Consider possible interference with GI absorption of fat-soluble vitamins.

Excessive increases in serum zinc concentrations may occur if octreotide is used to reduce excessive fluid loss from the GI tract in patients with conditions producing such a loss. Periodic monitoring of zinc levels is recommended in patients with this condition who are receiving concomitant total parenteral nutrition (TPN) and octreotide. (See Specific Drugs under Interactions.)

Antibody Formation

Up to 25% of patients develop antibodies to octreotide.

Antibodies to octreotide do not affect clinical response; some evidence from clinical studies indicates that antibodies to octreotide may be associated with prolonged duration of GH suppression.

Specific Populations

Pregnancy

Category B.

Lactation

Not known whether octreotide is distributed into milk. Caution if used in nursing women.

Pediatric Use

Safety and efficacy of immediate-acting injection not established.

Immediate-release injection has been used in a limited number of neonates and infants with congenital hyperinsulinism^†. Adverse effects mainly involved the GI tract (e.g., steatorrhea, diarrhea, vomiting, abdominal distension). Poor growth, poor weight gain, and tachyphylaxis reported; “catch up” growth followed drug discontinuance. Potential effects of long-term therapy on pediatric growth and development not fully elucidated.

Safety and efficacy of long-acting suspension formulation not established.

Long-acting suspension investigated in pediatric patients 6–17 years of age with hypothalamic obesity^† secondary to cranial insult; new cholelithiasis reported in 33% of children.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults. Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

Prolonged clearance and elimination half-life.

Hepatic Impairment

Prolonged elimination and decreased clearance of immediate-release injection in patients with liver cirrhosis. Prolonged elimination in patients with fatty liver disease.

Long-acting suspension formulation has not been studied in patients with hepatic impairment.

Renal Impairment

Half-life of immediate-release injection increased. Dosage adjustment may be necessary in patients with renal failure requiring dialysis.

Long-acting suspension formulation has not been studied in patients with renal impairment.

Common Adverse Effects

Diarrhea, abdominal pain/discomfort, flatulence, fatty stools (including steatorrhea), nausea, vomiting, gallbladder and biliary tract abnormalities (cholelithiasis, sludge), sinus bradycardia, conduction abnormalities, arrhythmias, and local effects (pain, burning) at the injection site.

Interactions for Octreotide

Associated with alterations in nutrient absorption; may affect absorption of orally administered drugs.

May inhibit CYP3A4 isoenzymes secondary to suppression of growth hormone.

Drugs Metabolized by Hepatic Microsomal Enzymes

Octreotide may inhibit clearance of drugs metabolized by CYP3A4.

Specific Drugs

Octreotide Pharmacokinetics

Absorption

Bioavailability

Following sub-Q injection, immediate-release formulation is rapidly and completely absorbed; peak concentrations are attained in 0.4 hours. Sub-Q and IV doses of immediate-release formulation are bioequivalent.

After IM administration of the long-acting suspension, peak plasma concentration is attained initially within 1 hour, progressively declines to a nadir within 3–5 days, and then slowly increases to a dose proportional peak concentration about 2–3 weeks post injection.

The relative bioavailability of the long-acting suspension given IM compared to the immediate-release injection given sub-Q is 60–63%. Following multiple IM injections of long-acting suspension given every 4 weeks, steady-state octreotide concentrations are achieved after the third injection.

Duration

Duration of action of immediate-release injection is variable but extends up to 12 hours depending upon the type of tumor.

Following administration of long-acting suspension, plateau plasma concentrations are maintained over a period of 2–3 weeks.

Special Populations

In patients with acromegaly, the time to peak plasma concentration is 0.7 hours following administration of immediate-release formulation.

Distribution

Extent

Steady-state volume of distribution is about 13.6 L. Distribution into erythrocytes appears negligible. It is not known whether the drug is distributed into breast milk.

Plasma Protein Binding

Approximately 65% bound to plasma proteins, mainly to lipoprotein and, to a lesser extent, albumin.

Special Populations

In patients with acromegaly, the steady-state volume of distribution is about 21.6 L and the plasma protein binding is 41.2%.

Elimination

Elimination Route

Approximately 32% excreted in urine as unchanged drug.

Half-life

Apparent elimination half-life is 1.7–1.9 hours.

Special Populations

Following administration of the immediate-release injection, elimination half-life of 2.4, 3, or 3.1 hours reported in patients with mild renal impairment (Cl_cr 40–60 mL/minute), moderate impairment (Cl_cr 10–39 mL/minute), or severe impairment (Cl_cr <10 mL/minute), respectively.

In patients with severe renal failure requiring dialysis, clearance of immediate-release injection is decreased by approximately 50% compared with healthy individuals. (See Special Populations under Dosage and Administration.)

Long-acting suspension has not been studied in patients with renal or hepatic impairment.

Elimination of immediate-release injection prolonged in patients with liver cirrhosis; half-life increased to 3.7 hr. Half-life increased to 3.4 hr in patients with fatty liver disease.

In geriatric individuals, the half-life is prolonged by 46%, and the clearance is decreased by 26%.

In patients with acromegaly, disposition and elimination half-life of the drug are similar to healthy individuals.

Stability

Storage

Parenteral

Injection

2–8°C; protect from light.

May store at 20–30°C for up to 14 days if protected from light.

May allow to come to room temperature before administration; do not warm artificially.

Open ampuls just prior to administration; discard unused drug.

Diluted solutions are stable for ≥24 hours.

Parenteral

Injectable Suspension, Extended-release, for IM Use

2–8°C; protect from light.

Product kit should remain at room temperature for 30–60 minutes before preparation of the suspension.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Incompatible in total parenteral nutrition solutions; formation of a glycosyl octreotide conjugate may decrease octreotide efficacy.

Solution Compatibility (Octreotide Immediate-release Injection)

Drug Compatibility (Octreotide Immediate-release Injection)HID

Actions

• Inhibits secretion of anterior pituitary hormones, suppresses pancreatic endocrine and exocrine function, inhibits gastric acid and GI hormone secretion, suppresses serotonin secretion, inhibits GI motility and splanchnic blood flow, and alters GI absorption.

• More potent than somatostatin, inhibits somatropin release to a greater extent than insulin and glucagon release, and has a longer plasma half-life and duration of action relative to somatostatin.

• Suppresses somatropin secretion and the lutropin (luteinizing hormone) response to gonadotropin-releasing hormone (GnRH).

• Has been used to control GI and other manifestations of a variety of conditions (e.g., flushing and diarrhea associated with carcinoid syndrome, watery diarrhea associated with VIP-secreting tumors) because of its inhibitory effects on secretion of serotonin and various gastroenteropancreatic peptides (e.g., gastrin, vasoactive intestinal polypeptide [VIP], insulin, glucagon, secretin, motilin, pancreatic polypeptide).

• Decreases the concentration of growth hormone and/or insulin-like growth factor I (IGF-I, somatomedin C) in patients with acromegaly.

Advice to Patients

• Importance of instructing patient and/or caregiver regarding sterile sub-Q injection technique.

• Importance of advising patients with carcinoid tumors or vasoactive intestinal polypeptide-secreting tumors to closely follow return visit reinjection schedule in order to minimize exacerbation of symptoms.

• Importance of advising patients with acromegaly to closely follow return visit reinjection schedule in order to maintain steady control of GH and IGF-1 levels.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Medical Disclaimer