section name header

Introduction ⬇

AHFS Class:

Generic Name(s):

Octreotide, a somatostatin analog, is a synthetic polypeptide that is pharmacologically related to the natural hormone somatostatin.1,26,29,30 31

Uses ⬆ ⬇

[Section Outline]

Carcinoid Tumors !!navigator!!

Octreotide acetate is used for the symptomatic treatment of patients with metastatic carcinoid tumors to suppress or inhibit the severe diarrhea and flushing episodes associated with the disease and has been designated an orphan drug by FDA for this use.1,26,27,30,31 The drug is available in various preparations for this use, including immediate-release injection formulations for subcutaneous or IV administration, and a long-acting release (LAR) injectable IM suspension for long-term treatment in patients who have responded to and tolerated the immediate-release formulation.1,26,30,31 The effect of octreotide on tumor size and rate of growth and development of metastases has not been determined.1,26

Carcinoid syndrome is characterized by excess serotonin production by a carcinoid tumor; symptoms include flushing, diarrhea, wheezing, occasionally congestive heart failure, and various other manifestations.12 Octreotide may reduce urinary excretion of the principal metabolite of serotonin (5-hydroxyindoleacetic acid, 5-HIAA) and decrease the frequency and severity of diarrhea and facial flushing episodes in patients with this syndrome; most patients appear to experience a substantial reduction (e.g., by 50%) in the frequency and severity of diarrhea and flushing, with complete relief of these manifestations occurring in some patients. 1,3,7,12,14,15,16,26

Octreotide also has been used for the acute management of potentially life-threatening hypotension associated with carcinoid crisis or to prevent carcinoid crisis that might be precipitated by anesthesia, surgery, initiation of chemotherapy, peptide receptor radionuclide therapy, radiologic procedures, stress, or infection.1,3,7,12,14,15,17,19,20,32 Carcinoid crisis is a life-threatening complication of the carcinoid syndrome and may include manifestations such as profound hypotension, arrythmias, hypertension, bronchospasm, prolonged or severe cutaneous flushing, stupor, confusion, and diarrhea.3 19,32 Effective therapy with octreotide reportedly has reversed the hypotension of carcinoid crisis.3,7,12,14,15,17,19,20 At least one patient with severe hypotensive carcinoid crisis while under anesthesia responded rapidly to repeated IV doses of the drug; peripheral blood flow resumed within 30-40 seconds, and systolic blood pressure exceeded 100 mm Hg within 5-10 minutes and remained at this level throughout surgery.12,14,17,19,20 Octreotide also has been administered prophylactically prior to neuroendocrine tumor surgery.3,19,20,32,33 However, the effectiveness of this strategy has been challenged and the North American Neuroendocrine Tumor Society Consensus group states that somatostatin analogs (i.e., octreotide, lanreotide) may be considered when tailored to the diagnosed endocrine syndrome (e.g., gastrinoma, insulinoma, correction of diarrhea), but their role in prevention of carcinoid crisis remains undefined.33

Octreotide long-acting release (LAR) injectable IM suspension is used for the long-term management of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors in patients in whom initial treatment with immediate-release octreotide injection has been shown to be effective and tolerated.26 In a clinical trial of patients with malignant carcinoid syndrome who responded to octreotide injection, patients either continued their octreotide injection regimen (100-300 mcg subcutaneously 3 times daily) or received varying doses of octreotide LAR injectable suspension (10, 20, or 30 mg IM every 28 days).26 Mean daily stool frequency and mean daily flushing episodes were similar for all doses of octreotide LAR suspension and for octreotide injection.26 During this 6-month trial, approximately 50-70% of patients treated with octreotide LAR suspension required supplemental therapy with octreotide injection to control exacerbations of carcinoid symptoms.26 In the extension study that followed, all patients received 12 injections of the LAR formulation at 4-week intervals.26 For those remaining in the extension trial, diarrhea and flushing were similarly well controlled as during the 6-month trial.26 Because malignant carcinoid disease is progressive, a number of deaths (10%) occurred due to disease progression or complications from the underlying disease and an additional 22% of patients prematurely discontinued the drug due to disease progression or worsening of carcinoid symptoms.26

Clinical Perspective

While many patients with metastatic carcinoid tumors may not have serious or debilitating symptoms for months or years, symptoms of carcinoid syndrome, including episodic or permanent flushing, hypotension, palpitations, diarrhea, malnutrition-induced muscle wasting, abdominal pain associated with local mesenteric fibrosis and vascular ischemia, and wheezing secondary to bronchospasm, can develop; occasionally, manifestations of endocardial fibrosis and congestive heart failure occur in later stages of the disease.3,12,14,15,16,19,32 The potential effect, if any, of octreotide on the underlying disease process remains to be fully elucidated, and therapy with the drug in this condition currently should be considered principally symptomatic, although some tumor regression occasionally has been reported.1,2,3,7,12,32 In addition, while sustained relief of flushing and diarrhea may occur with prolonged octreotide therapy, some patients may experience little relief and others may experience a return to pretreatment or near pretreatment severity despite initial relief and continued therapy with the drug.3,7,12,14 Occasionally, some patients may respond to dosage escalation or a switch to another somatostatin analog (e.g., lanreotide). 12 32

Vasoactive Intestinal Peptide-secreting Tumors !!navigator!!

Octreotide is used for the treatment of severe diarrhea associated with vasoactive intestinal peptide (VIP)-secreting tumors (VIPomas) and has been designated an orphan drug by FDA for this use.1,26,27,30,31 The effect of octreotide on tumor size and rate of growth and development of metastases has not been determined.1,26

Octreotide is available in various preparations for this use, including immediate-release injection formulations for subcutaneous or IV administration, and a long-acting release (LAR) injectable IM suspension for long-term treatment in patients who have responded to and tolerated the immediate-release formulation.1,26,30,31

Octreotide has decreased stool volume, electrolyte loss, and plasma VIP concentrations in most patients with such tumors.1,2,3,7,12 The initial therapy for patients with VIP-secreting tumor associated diarrhea is aggressive fluid and electrolyte replacement;3 however, because octreotide may ameliorate the diarrhea, and therefore improve electrolyte abnormalities (e.g., hypokalemia), the need for fluid and electrolyte replacement in such patients may be reduced.1 Although surgical resection of VIP-secreting tumors is the treatment of choice, most patients have metastatic disease that is not amenable to surgery alone.3 In addition, appropriate chemotherapy may not eliminate associated manifestations,3,12 and symptomatic therapy other than octreotide may not consistently provide symptomatic relief.3,7,12 Initiation of octreotide therapy often provides dramatic, rapid (within 12-48 hours) improvement in stool output.3,7,12 Marked biochemical improvement also usually occurs, occasionally to within normal limits, but symptomatic relief of diarrhea can occur without or despite loss of such improvement.3,7,12 Some patients fail to respond symptomatically to therapy with the drug, and response may be only temporary in others.7 In addition, the potential effect, if any, of octreotide on the underlying disease process remains to be fully elucidated, and therapy with the drug in this condition currently should be considered principally symptomatic, although some tumor regression occasionally has been reported.1,2,3,7,12 26

Acromegaly !!navigator!!

Octreotide is used to reduce growth hormone (GH) and insulin-like growth factor 1 (IGF-1) 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).1,30,31 The treatment goal is to achieve normalization of GH and IGF-1 levels.1 Octreotide has been designated an orphan drug by FDA for the treatment of acromegaly.27

Octreotide is available in various preparations for the treatment of acromegaly, including immediate-release injection formulations for subcutaneous or IV administration and a long-acting release (LAR) injectable IM suspension for long-term treatment in patients who have responded to and tolerated the immediate-release formulation; an oral preparation (delayed-release capsules) is also available for use in patients who have responded to and tolerated treatment with octreotide or lanreotide.1,26,29,30 31

The safety and efficacy of octreotide LAR injectable IM suspension in the management of acromegaly have been evaluated in 3 clinical trials.26 In 2 of the trials, a total of 101 patients with acromegaly were treated with octreotide LAR injectable suspension (20 or 30 mg in most patients, range 10-40 mg) IM once every 4 weeks for up to 27 or 28 doses.26 Most of the patients enrolled had achieved a GH level of less than 5 ng/mL during prior treatment with octreotide immediate-release injection (100 or 200 mcg 3 times daily).26 GH and IGF-1 concentrations and clinical symptoms were at least as well-controlled with octreotide LAR injectable suspension as with the immediate-release injection, and the therapeutic effect was maintained throughout the entire duration of the trials.26 Analysis of hormonal response (concentrations of GH and IGF-1) in 88 of the patients showed that treatment with octreotide immediate-release injection was associated with GH concentrations less than 5 ng/mL in 78% of patients, and normal IGF-1 concentrations in 41% of patients.26 Treatment with octreotide LAR injectable suspension was associated with GH concentrations less than 5 ng/mL in 83% of patients, and normal IGF-1 concentrations in 51% of patients.26 GH concentrations less than 2.5 ng/mL were reported in 50% of patients receiving octreotide immediate-release injection, and 34% of patients achieved normal IGF-1 concentrations and GH concentrations less than 2.5 ng/mL.26 Treatment with octreotide LAR injectable suspension was associated with GH concentrations less than 2.5 ng/mL in 47% of patients and normal IGF-1 concentrations and GH concentrations less than 2.5 ng/mL in 42% of patients.26

In the third clinical trial, 151 patients who had GH concentration less than 10 ng/mL (and less than 5 ng/mL in most patients) after treatment with octreotide injection were treated with octreotide LAR injectable suspension for 12 months.26 The initial dose of octreotide LAR suspension was 20 mg IM every 4 weeks for 3 doses; subsequent doses ranged from 10-30 mg every 4 weeks and were based on the degree of GH suppression achieved.26 Response as evaluated by GH and IGF-1 concentrations and clinical symptoms were similar in patients receiving octreotide injection or the LAR suspension.26 Among 122 patients who received all 12 doses of octreotide LAR injectable suspension, a mean GH concentration less than 2.5 ng/mL was reported in 66% of patients, and 57% of patients had normal IGF-1 concentrations and GH concentrations less than 2.5 ng/mL.26

Responses to octreotide LAR injectable suspension have been reported in patients with acromegaly who were partial responders (defined as GH concentration exceeding 5 ng/mL but reduced by more than 50% from pretreatment levels) to octreotide immediate-release injection.26 Among the 25 partial responders to octreotide immediate-release injection who were included in the 3 clinical trials of octreotide LAR injectable suspension, GH concentrations less than 5 ng/mL were achieved in 32% (8/25) of patients, and GH concentrations less than 2.5 ng/mL were achieved in 4% (1/25) of patients.26

The safety and efficacy of octreotide delayed-release capsules in the management of acromegaly have been evaluated in a 9-month, randomized, double-blind, placebo-controlled study (OPTIMAL trial).29,34,36 Patients with active acromegaly who were treated in the prior 6 months with a long-acting injectable somatostatin receptor ligand (i.e., octreotide or lanreotide) as monotherapy at a stable dosage for at least 3 months were included in the study.29,34,36 Baseline IGF-1 levels were 0.80 or 0.84 times the upper limit of normal (ULN) in patients treated with octreotide or placebo, respectively.29 Patients were randomized to oral octreotide capsules (initiated 1 month after the last injection of somatostatin analog) or placebo.34,36 Octreotide was administered at a starting dose of 40 mg and then titrated based on patient response up to a maximum dosage of 80 mg daily.29,34

The primary efficacy endpoint was somatostatin dose-adjusted proportion of patients who maintained their biochemical response, defined as IGF-1 levels ≤ ULN at the end of 9 months of treatment; this was achieved in 58% of octreotide-treated patients compared with 19% of placebo-treated patients.29 Rescue therapy with a somatostatin analog was administered in patients who had IGF-1 levels ≥1.3 times ULN and exacerbation of acromegaly signs and symptoms on two consecutive assessments while treated for at least 2 weeks on a total daily dosage of 80 mg or for other reasons such as adverse reactions or patient's decision.29 Discontinuation occurred in 25% and 67.9% of octreotide and placebo-treated patients, respectively.29,34

Patients who completed the double-blind placebo-controlled OPTIMAL study were eligible to enroll in the open-label extension study.35 All patients entering the open-label extension phase received octreotide 60 mg daily, with the option to increase to 80 mg daily or decrease to 40 mg daily based on biochemical control.35 In an interim analysis, 80% (32/40) of enrolled patients remained in the extension trial at 48 weeks and 10% (4/40) withdrew early due to treatment failure.35 In those responding to oral octreotide at the end of the initial study, 92.6% maintained response, defined as IGF-1 ≤ 1.0 times ULN, at week 48 of the extension trial.35

Clinical Perspective

Acromegaly is caused by excess circulating levels of growth hormone and insulin-like growth factor 1 (IGF-1), typically from a pituitary adenoma.37 Surgical resection of the adenoma is the first-line treatment of choice whenever possible.37 Medical therapy is recommended in patients with persistent disease despite surgical resection.37 The Acromegaly Consensus Group issued a consensus statement in 2018 recommending a first-generation long-acting somatostatin receptor ligand (SRL) such as octreotide long-acting release (LAR) injectable suspension or lanreotide autogel for the first-line medical treatment of patients with persistent disease after surgery; the addition of cabergoline may be considered in patients with IGF-I levels ≤2.5 times the upper limit of normal (ULN).37

In a 2020 update to its acromegaly management guidelines, the Pituitary Society addressed the role of oral octreotide capsules.38 Due to similar efficacy rates observed in clinical trials of octreotide and lanreotide, the Pituitary Society states that switching to the oral octreotide formulation is a suitable option for patients who have demonstrated complete or partial biochemical response to these injectable agents.38 There is no data to support oral octreotide as primary medical therapy in SRL-naïve patients or to support a switch from pasireotide LAR to oral octreotide.38

Other Uses !!navigator!!

Variceal Bleeding

Octreotide has been used in adults and pediatric patients for the treatment of acute variceal bleeding†.43 44,56 The drug is generally administered as a continuous IV infusion for this use, with or without an initial bolus injection.43 44,56 Drug therapies directed at portal pressure reduction and treatment of varices and variceal bleeding include nonselective beta-adrenergic blocking agents, IV vasopressin or terlipressin, and IV somatostatin analogs (e.g., octreotide).43,44 The combination of an IV vasoactive drug (e.g., octreotide, terlipressin) and endoscopic therapy may provide a better treatment response compared to these therapies alone.45 In a meta-analysis of 13 randomized trials of octreotide in patients with acute variceal bleeding, rebleeding was decreased by 37% with octreotide compared to alternative interventions (e.g., placebo, vasopressin, or terlipressin).43 In a second meta-analysis, results were similar.44,58 In a contemporary randomized noninferiority trial of IV octreotide versus somatostatin or terlipressin in patients 16-75 years of age, the primary endpoint of 5-day treatment success, defined as control of bleeding without rescue treatment, rebleeding, or mortality, occurred in 83.8% of patients treated with octreotide, 83.4% of patients treated with somatostatin, and 86.2% of patients treated with terlipressin.45

The American Association for the Study of Liver Diseases (AASLD) recommends initation of IV vasoactive drugs (e.g., octreotide, vasopressin, terlipressin) as soon as acute variceal bleeding is suspected, followed by esophagogastroduodenoscopy within 12 hours, once the patient is hemodynamically stable.44

Hyperinsulinaemic Hypoglycemia

Octreotide injection has been used for the treatment of hyperinsulinaemic hypoglycemia† in adults and children.39,40,41,42 Octreotide (administered by IV or subcutaneous injections every 6 to 8 hours or by continuous subcutaneous infusion) also has been used for the short- or long-term treatment of hyperinsulinism† in children.42 In a small uncontrolled trial, monthly IM injections of octreotide LAR replaced established long-term subcutaneous immediate-release octreotide treatment in 10 diazoxide-resistent children (1.3 to 8.5 years of age).39,42 Metabolic control, hemoglobin A1c, and mean IGF-1 levels were maintained in the usual range and parental general satisfaction was excellent; however, quality of life evaluations were unchanged.39,42 Octreotide also has been used for the treatment of sulphonylurea-induced severe hypoglycemia† in children with accidental poisoning or in adults with treatment-induced hypoglycemia or intentional overdose; such use is primarily based on case reports and small studies in healthy subjects or patients with severe hypoglycemia.41,42 54 Administration of IV octreotide after the first episode of drug-induced hypoglycemia or following recurrent hypoglycemia in such patients may increase serum glucose concentrations, decrease dextrose requirement, and reduce recurrent hypoglycemic events compared with IV dextrose alone.54,55

Hepatorenal Syndrome

Octreotide injection has been used for the treatment of hepatorenal syndrome† in adults and children. 46,47,57,1002 Drugs used to increase effective circulating blood volume and renal blood flow, alone or in combination, include octreotide, terlipressin, albumin, and midodrine.46 In a small randomized controlled trial of patients with cirrhosis and type 1 or severe type 2 hepatorenal syndrome, subcutaneous octreotide 100-200 mcg 3 times daily plus albumin and oral midodrine was compared to IV terlipressin 3-12 mg/24 hours plus albumin.47 A significantly higher rate of renal recovery occurred among those receiving terlipressin (70.4%) compared to those receiving octreotide and midodrine (28.6%).47 The American Association for the Study of Liver Diseases (AASLD) states that although the evidence of efficacy for octreotide in combination with oral midodrine for the treatment of hepatorenal syndrome with acute kidney injury is considered low, a trial of such treatment may be considered when more effective alternatives (i.e., terlipressin, norepinephrine) are not available.1002

Autosomal Dominant Polycystic Liver or Kidney Disease

Octreotide injection has been used for the treatment of autosomal dominant polycystic liver or kidney disease†. 48 Octreotide is designated an orphan drug by FDA for autosomal dominant polycystic liver disease.27 Meta-analysis of randomized trials evaluating patients with these conditions provides some evidence for the effectiveness of somatostain analogs (e.g., octreotide, lanreotide, pasireotide) on total liver or kidney volume (TLV, TKV), although there were differences in trial design and outcomes.48 Signficantly lower rates of TLV growth were observed but TKV-related results were not different; in another meta-analysis, signficantly lower rates of TKV growth rates were observed but not TLV growth rates.48 Interpretation of these meta-analyses are limited by small numbers of patients, lack of control treatments in some trials, inadequate blinding, and variable baseline characteristics and follow-up periods.48

Enterocutaneous Fistulas

Octreotide injection has been used for the treatment of enterocutaneous fistulas†.49,50 Enterocutaneous fistulas are abnormal connections between the GI tract and the skin that arise most commonly after abdominal surgery.49 In a meta-analysis of 8 randomized controlled trials, time to fistula closure was about 6 days shorter with somatostatin analogs (subcutaneous octreotide 100 mcg 3 times daily, IM lanreotide 30 mcg every 10 days, continuous IV infusion of somatostatin) compared to placebo or standard of care such as parenteral nutrition.49 In a second meta analysis of 9 randomized controlled trials, time to fistula closure was also found to be reduced with somatostatin analogs.50

Gastrointestinal Angiodysplastic Lesions

Octreotide injection has been used for the reduction of red blood cell (RBC) transfusions in patients with gastrointestinal angiodysplastic lesions†.51,52 The American College of Gastroenterology states that small bowel angioectasia, also known as angiodysplasias, are the most common cause of small bowel bleeding.51 When there is persistent or recurrent bleeding, or when a lesion cannot be localized, experts state that consideration may be given to medical treatment with somatostatin analogs, iron, or antiangiogenic therapy.51 The recommendation to use somatostatin analogs (e.g., octreotide, lanreotide LAR) in refractory patients is based on case reports, small retrospective studies, and meta-analysis.51 The mean reduction in RBC transfusions was the primary outcome in a meta analysis of 11 studies (1 randomized controlled, 7 prospective, and 3 retrospective cohort studies) of patients with endoscopically diagnosed gastrointestinal angiodysplasias.52 Somatostatin analogs significantly reduced the number of RBC transfusions during a median treatment duration of 12 months and follow-up period of 12 months, correlating with a mean absolute decrease in the number of RBC transfusions from 12.8 during baseline to 2.3 during follow-up.52

Dosage and Administration ⬆ ⬇

[Section Outline]

General !!navigator!!

Pretreatment Screening

Patient Monitoring

Administration !!navigator!!

Octreotide acetate is administered by the subcutaneous, IV, IM, or oral route depending on the specific use.1,26,29,30,31

Octreotide immediate-release injection is administered by subcutaneous injection or by IV injection or infusion for symptom control in patients with acromegaly, carcinoid tumors, or vasoactive intestinal peptide (VIP) tumors.1,30,31 Subcutaneous injection is the usual route of administration; IV administration generally is reserved for emergency situations (e.g., acute management of carcinoid crisis) that require rapid injection.1 31

Octreotide is also available as a long-acting release (LAR) suspension for IM administration in patients with acromegaly, carcinoid tumors, or VIP-secreting tumors who have responded to and tolerated the immediate-release injection.26 Octreotide LAR suspension should not be administered subcutaneously or IV.26 The LAR injectable suspension may be used after tolerance has been established with at least 2 weeks of subcutaneous therapy with immediate-release octreotide.26

Octreotide is also available as delayed-release capsules for the long-term maintenance treatment of acromegaly in patients who have responded to and tolerated treatment with octreotide or lanreotide.29

Subcutaneous Administration

Immediate-release (short-acting) octreotide acetate injection is usually administered subcutaneously.1,30,31 The smallest volume that will deliver the desired dose should be used to minimize pain associated with subcutaneous administration, and the injection site should be rotated in a systematic manner.1 Avoid multiple subcutaneous injections at the same site within short periods of time.1

Patients and/or their caregivers should be instructed carefully regarding proper techniques for sterile subcutaneous injection of the drug.1,30,31

Ampuls, single- or multiple-dose vials, and single-dose syringes should be refrigerated at 2-8°C and protected from light; however, the drug can be stored at 20-30°C for up to 14 days when protected from light.1,30,31 The solution can be allowed to come to room temperature prior to administration; do not warm artificially.1,30,31 Open ampuls or prepare single-dose vials and syringes just prior to administration; discard any unused portion.1,30,31 Multiple-dose vials should be discarded within 14 days.30

IV Administration

Octreotide immediate-release injection may be diluted in 50-200 mL of 0.9% sodium chloride or 5% dextrose injection and infused over 15-30 minutes or administered by IV push over 3 minutes; such solutions are stable for 24 hours.1,30,31 In emergency situations (e.g., carcinoid crisis), octreotide injection may be administered by rapid, direct IV (bolus) injection.1,2,31,32

The manufacturers state that octreotide acetate immediate-release injection should not be added to total parenteral nutrition (TPN) solutions because of the formation of a glycosyl octreotide conjugate that may decrease the product's efficacy, although the clinical value of this administration approach has been debated.1,30,31

Ampuls, single- or multiple-dose vials, and single-dose syringes of the drug should be refrigerated at 2-8°C and protected from light prior to use; the drug can be stored at room temperature (20-30°C) for up to 14 days when protected from light.1,30,31 The solution can be allowed to come to room temperature prior to administration; do not warm artificially.1,30,31 Open ampuls or prepare single-dose vials and syringes just prior to administration; discard any unused portion.1,30,31 Multiple-dose vials should be discarded within 14 days.30 Inspect the drug solution visually prior to administration and do not use if particulates and/or discoloration are observed; use proper sterile technique when preparing and administering the drug.1,30,31

Standardize 4 Safety

Standardized concentrations for octreotide have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care.249 Multidisciplinary expert panels were convened to determine recommended standard concentrations.249 Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.249 For additional information on S4S (including updates that may be available), see [Web].

Table 1. Standardize 4 Safety Pediatric† Continuous Infusion Standards for Octreotide249

Patient Population

Concentration Standard

Dosing Units

Pediatric patients (<50 kg)

2.5 mcg/mL

10 mcg/mL

50 mcg/mL

mcg/kg/hour

IM Administration

Octreotide long-acting release (LAR) injectable suspension is administered by IM injection and must be given under the supervision of a clinician.26 Octreotide suspension should not be administered subcutaneously or IV.26 The LAR formulation is commercially available as a powder that must be reconstitued with the supplied diluent prior to administration.26 The diluent should not be injected directly (i.e., injected without preparing the long-acting suspension).26 Octreotide LAR should remain at room temperature for 30-60 minutes prior to mixing.26 Closely follow mixing and administration instructions in the prescribing information; administer the suspension immediately after mixing.26

Injection into the gluteal muscle is recommended; avoid injection into the deltoid muscle because severe discomfort at the injection site may occur.26 Gluteal injection sites should be rotated to minimize irritation.26

For prolonged storage, octreotide LAR injectable suspension should be refrigerated at 2-8°C and protected from light.26

Oral Administration

Delayed-release octreotide oral capsules should be administered with a glass of water at least 1 hour before a meal or at least 2 hours after a meal.29 The oral preparation must be swallowed whole; do not crush or chew the capsules.29 If the total daily dosage is 60 mg, administer 40 mg in the morning and 20 mg in the evening; if the total daily dosage is 80 mg, administer 40 mg in the morning and 40 mg in the evening.29

Store delayed-release capsules unopened in the original packaging at 2-8°C; do not freeze.29 After first-use, the opened package of capsules may be stored at 20-25°C for up to 1 month.29

Dosage !!navigator!!

Dosage of octreotide acetate is expressed in terms of octreotide.1,26,29

Carcinoid Tumors

Parenteral

Immediate-release octreotide:For the management of symptomatic diarrhea and flushing associated with carcinoid tumors in adults, octreotide therapy should be initiated with immediate-release octreotide injection given subcutaneously,1,30,31 Octreotide dosages ranging from 100-600 mcg daily (mean daily dosage of 300 mcg), given in 2-4 divided doses, have been suggested for the initial 2 weeks of therapy.1,30,31 The manufacturer states that while the median maintenance dosage in clinical studies was approximately 450 mcg daily, clinical and biochemical benefits were obtained with as little as 50 mcg daily in some patients, while others required dosages up to 1500 mcg daily; however, experience with dosages exceeding 750 mcg daily is limited.1,30,31

Octreotide doses of 50-500 mcg, repeated as necessary, have been administered by rapid IV injection for rapid control of hypotension and other manifestations of carcinoid crisis; 17,19,20 prolonged IV infusions (e.g., 50 mcg/hour infused for 8-24 hours) also have been employed for the management of carcinoid crisis.16

When immediate-release octreotide injection is used in combination with telotristat etiprate for carcinoid syndrome diarrhea, octreotide should be administered at least 30 minutes following administration of telotristat etiprate.28

LAR octreotide: Patients should be treated with immediate-release subcutaneous octreotide injection for at least 2 weeks before treatment with the LAR injectable suspension is considered.26 Patients who have responded well to the immediate-release injection may be switched to the LAR suspension at an initial dosage of 20 mg IM once every 4 weeks for 2 months.26 Because of the need for a certain period of time to reach therapeutic levels following initial injection of the LAR formulation, subcutaneous therapy with the immediate-release injection should be continued for at least 2 weeks at the same dosa some patients may require 3-4 weeks of such therapy to prevent exacerbation of disease symptoms.26 After 2 months of therapy with the 20-mg dose, the dosage of LAR octreotide may be increased to 30 mg IM once every 4 weeks if necessary for adequate symptom control.26 Reduction of the dosage to 10 mg IM once every 4 weeks may be attempted in patients who have achieved satisfactory symptom relief with the 20-mg dose.26 Doses above 30 mg have not been evaluated and are not recommended.26 Temporary use of subcutaneous injections of immediate-release octreotide (at the dosage used prior to switching to the long-acting formulation) may be necessary if patients experience exacerbation of symptoms.26

Vasoactive Intestinal Peptide-secreting Tumors

Parenteral

Immediate-release octreotide:For the treatment of severe diarrhea associated with vasoactive intestinal peptide-secreting tumors (VIPomas) in adults, octreotide therapy should be initiated with the immediate-release injection.1,26 The manufacturer recommends an octreotide dosage of 200-300 mcg (range 150-750 mcg) daily, given in 2-4 divided doses, for the initial 2 weeks of therapy.1,26 Dosage should be individualized based on patient response and tolerance, but dosages exceeding 450 mcg daily usually are not required.1,26

LAR octreotide: Patients should be treated with immediate-release octreotide injection for at least 2 weeks before treatment with the LAR injectable suspension is considered.26 Patients who have responded well to the immediate-release injection may be switched to the LAR suspension at an initial dosage of 20 mg IM once every 4 weeks for 2 months.26 Because a certain period of time is needed to reach therapeutic levels following initial injection of the LAR formulation, subcutaneous therapy with the immediate-release injection should be continued for at least 2 weeks at the same dosa some patients may require 3-4 weeks of such therapy to prevent exacerbation of disease symptoms.26 After 2 months of therapy with the 20 mg IM dose, dosage of LAR octreotide may be increased to 30 mg IM once every 4 weeks if necessary for adequate symptom control.26 Reduction of the dosage to 10 mg IM once every 4 weeks may be attempted in patients who have achieved satisfactory symptom relief with the 20-mg dose.26 Doses exceeding 30 mg have not been evaluated and are not recommended.26 Temporary use of subcutaneous injections of immediate-release octreotide (at the dosage used prior to switching to the long-acting formulation) may be necessary when patients experience exacerbation of symptoms.26

Acromegaly

Parenteral

Immediate-release octreotide:When used for the management of acromegaly in adults, treatment with octreotide should be initiated with the immediate-release injection at a dosage of 50 mcg subcutaneously 3 times daily; dosage may be titrated.1,26 Initiation of therapy with a low dosage may permit adaptation to adverse GI effects for patients who will require higher doses.1 Adjustment of the octreotide dosage should be based on insulin growth factor-1 (IGF-1) levels measured at 2 week intervals and/or multiple measurements of growth hormone (GH) concentrations obtained 0-8 hours after subcutaneous injection of the drug, with the goal of normalizing GH and IGF-1 concentrations.1,26 Doses of 100-200 mcg 3 times daily result in a maximum effect in most patients; however, doses of up to 500 mcg 3 times daily may be needed in some patients.1,26 Doses greater than 300 mcg/day seldom result in additional biochemical benefit, and if an increase in dose fails to provide additional benefit, the dose should be reduced.1

If the patient has received pituitary irradiation, withdraw therapy for approximately 4 weeks each year to assess disease activity.1 If GH or IGF-1 levels increase and symptoms recur, resume therapy.1

LAR octreotide: Patients should be treated with immediate-release octreotide injection for at least 2 weeks before treatment with the LAR injectable suspension is considered.26 Patients who respond well to treatment with immediate-release octreotide injection may be switched to the LAR injectable suspension at an initial dosage of 20 mg IM once every 4 weeks for 3 months.26 Subsequent dosage of LAR octreotide is determined based on GH and IGF-1 levels and clinical symptoms.26 In patients with GH concentrations of 2.5 ng/mL or less, normal IGF-1 concentrations, and good symptom control, dosage should be maintained at 20 mg IM once every 4 weeks.26 In patients with a GH concentration of 1 ng/mL or less, normal IGF-1 concentrations, and controlled clinical symptoms, dosage can be reduced to 10 mg IM once every 4 weeks.26 In patients with GH concentrations exceeding 2.5 ng/mL, elevated IGF-1 concentrations, and/or uncontrolled clinical symptoms, the dosage can be increased to 30 mg IM once every 4 weeks.26 In patients who do not respond to a dosage of 30 mg IM once every 4 weeks, dosage may be increased further to 40 mg IM once every 4 weeks; however, doses higher than 40 mg are not recommended.26

If the patient has received pituitary irradiation, withdraw therapy yearly for approximately 8 weeks to assess disease activity.26 If GH or IGF-1 levels increase and symptoms recur, resume therapy.26

Oral

For the long-term maintenance treatment of acromegaly in patients who have responded to and tolerated treatment with parenteral octreotide or lanreotide, the inital dosage of octreotide oral capsules (Mycapssa®) is 20 mg twice daily.29 Subsequent dosage is determined based on IGF-1 concentrations and clinical symptoms monitored every 2 weeks; titration should occur in increments of 20 mg daily.29 The maximum recommended total daily dosage of the oral preparation is 80 mg.29 If IGF-1 levels remain above the upper limit of normal after treatment with the maximum recommended dosage of 80 mg daily or the patient cannot tolerate treatment, consider discontinuing therapy and switching patient to another somatostatin analog.29

Variceal Bleeding

Parenteral

For the treatment of acute variceal bleeding†, octreotide has been administered as an initial IV bolus dose of 50 mcg followed by a continuous IV infusion of 50 mcg/hour for a duration of 2 to 5 days.44 A second bolus dose may be administered within the first hour if bleeding is ongoing.44 In randomized controlled trials, the IV bolus dose range has varied between 0-100 mcg and the continuous IV infusion rates varied between 25-50 mcg/hour; duration of treatment ranged from 8 hours to 7 days.43 Few studies utilized subcutaneous dosing.43,45

In pediatric patients, continuous IV infusion of 1-5 mcg/kg per hour of octreotide appears to be effective, but may require an initial bolus dose.56

Special Populations !!navigator!!

Hepatic Impairment

In patients with established liver cirrhosis, the intial IM dosage of octreotide LAR suspension should be 10 mg every 4 weeks; titrate based upon clinical response and tolerability.26

The manufacturers make no specific dosage recommendations for patients with hepatic impairment requiring octreotide immediate-release injection or oral preparations.1,29

Renal Impairment

The manufacturer states the maintenance dosage of octreotide immediate-release injection may require adjustment in patients with severe renal failure requiring dialysis.1

In patients with renal failure requiring dialysis, the intial IM dosage of octreotide LAR suspension should be 10 mg every 4 weeks; titrate based upon clinical response and tolerability.26 In other patients with renal impairment, the initial IM dosage of octreotide long-acting suspension should be similar to a nonrenal patient (i.e., 20 mg every 4 weeks).26

For patients with end-stage renal disease, the initial dosage of octreotide oral preparation is 20 mg once daily; titrate based on IGF-1 levels, clinical response, and tolerability.29

Geriatric Patients

Geriatric patients may be more sensitive to octreotide due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy; initiate dosage cautiously at the low end of the dosage range.1,26

Cautions ⬆ ⬇

[Section Outline]

Contraindications !!navigator!!

Warnings/Precautions !!navigator!!

Biliary Effects

Octreotide may reduce gallbladder contractility and bile secretion leading to gallbladder abnormalities, especially stones and/or biliary sludge.1,26,29,30,31 In clinical trials of octreotide injection in patients (most of whom had acromegaly or psoriasis) who had not previously received the drug, the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% biliary sludge without stones, 12% biliary duct dilatation).1 26 The incidence of cholelithiasis or biliary sludge was 52% in patients who received octreotide injection for 12 months or longer.1,26,29 The incidence of gallbladder abnormalities appears to be related to duration of exposure to octreotide; it does not appear to be related to age, sex, or dose.1,26 There have been postmarketing reports of cholelithiasis (gallstones) in patients taking somatostatin analogs resulting in complications, including cholecystitis, cholangitis, pancreatitis and requiring cholecystectomy.1,26,29 Monitor patients periodically; discontinue octreotide and treat appropriately if complications of cholelithiasis are suspected.1,26,29

Cardiovascular Effects

Atrioventricular block may occur in patients receving intravenous octreotide.1 Increased risk for higher degree or complete antrioventricular block may occur following intravenous administration during surgical procedures.1 In such cases, the drug was given at higher than recommended doses and/or as a continuous IV infusion.1 The safety of continuous IV octreotide infusion has not been established in patients receiving the drug for the approved indications.1 Consider cardiac monitoring in patients receiving octreotide intravenously.1

Bradycardia, arrhythmias (including tachycardia), and conduction abnormalities have been reported during octreotide therapy in patients with acromegaly or carcinoid syndrome.1,26,29 Sinus bradycardia, conduction abnormalities, or arrhythmias were reported in 25, 10, or 9%, respectively, of patients with acromegaly treated with octreotide immediate-release injection.1,26 In patients with carcinoid syndrome treated with octreotide long-acting suspension, the incidence of sinus bradycardia, conduction abnormalities, or arrhythmias was 19, 9, or 3%, respectively.26 The relationship of these events to octreotide is not established because many of these patients have underlying cardiac disease.1,26 Bradycardia (2%), conduction abnormalities (1%), and arrhythmias/tachycardia (2%) occurred in clinical trials of oral octreotide for the treatment of acromegaly.29 Other electrocardiogram changes observed included QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, early R-wave progression, and nonspecific ST-T wave changes.1,26,29 Dosage adjustments of concomitantly used drugs that have bradycardic effects (i.e., beta-blockers) may be necessary.1,26,29

Risk of Pregnancy

Normalization of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) by octreotide therapy may lead to improved fertility and unintended pregnancy in female patients with acromegaly.1,26,29 Advise female patients of child-bearing potential of such risk.1,26,29

Endocrine Effects

Octreotide alters the balance between the counter-regulatory hormones, insulin, glucagon, and growth hormone, which may result in hypoglycemia, or hyperglycemia, or diabetes mellitus.1,26,29 Hyperglycemia (16%) or hypoglycemia (3%) occured in patients with acromegaly receiving octreotide immediate-release injection, but only in approximately 1.5% of patients receiving the drug for other indications.1 In patients with acromegaly treated with octreotide LAR, hypoglycemia occurred in 2% and hyperglycemia occurred in 15% of patients.26 The incidence of hypoglycemia or hyperglycemia in patients receiving octreotide LAR for the management of carcinoid tumors was 4 or 27%, respectively.26 Increased blood glucose (7%), hypoglycemia (4%), and diabetes mellitus (1%) were reported in clinical trials of oral octreotide for the treatment of acromegaly.29 In patients with concomitant diabetes mellitus, octreotide injection may affect glucose regulation, insulin requirements, and in patients with insulin reserves (i.e., type 2 diabetes mellitus) hyperglycemia may occur; in patients with type 1 diabetes mellitus, hypoglycemia, which may be severe, has been reported.1 Blood glucose levels should be monitored when octreotide treatment is initiated or when the dose is adjusted; adjust diabetes treatment accordingly.1,26,29

Octreotide suppresses secretion of thyroid stimulating hormone (TSH), which may result in hypothyroidism.1,26,29 Biochemical hypothyroidism, goiter, or a need for thyroid replacement therapy occurred in 12, 8, or 4%, respectively, of patients with acromegaly treated with octreotide immediate-release injection.1 In patients with acromegaly treated with octreotide long-acting suspension, hypothyroidism, or goiter each was reported in 2% of patients.26 In those without acromegaly, hypothyroidism has only been reported in isolated patients and goiter has not been reported. 1,26 Hypothyroidism (1%), increased TSH (1%), or decreased free T4levels (1%) were reported in clinical trials of oral octreotide for the treatment of acromegaly.29 Baseline and periodic assessment of thyroid function (TSH, total, and/or free T4) is recommended during chronic octreotide therapy.1,26,29

Immunogenicity

There is a potential for the development of immunogenicity to octreotide.1,26,29 Antibodies to octreotide have been reported in up to 25% of patients receiving the drug.26 These antibodies do not influence the degree of efficacy response to octreotide; however, in 2 patients who received octreotide immediate-release injection for the treatment of acromegaly, the duration of growth hormone suppression following each injection was about twice as long as in patients without antibodies.1,26 It has not been determined whether octreotide antibodies will also prolong the duration of growth hormone suppression in patients treated with the long-acting suspension.26 No octreotide peptide antibodies were detected in 149 patients assessed in the open-label study of the oral preparation (Mycapssa®) throughout 13 months of treatment.29

Dietary Abnormalities

Octreotide may alter absorption of dietary fats in some patients.1,26,29 Depressed vitamin B12 levels and abnormal Schilling's tests have been observed in some patients receiving octreotide; vitamin B12 level monitoring is recommended during chronic drug treatment.1,26,29 Octreotide has been investigated for the reduction of excessive fluid loss † from the GI tract in patients with conditions producing such a loss.26 If such patients are receiving total parenteral nutrition (TPN), serum zinc may rise excessively when the fluid loss is reversed.26 Patients on TPN and octreotide should have periodic monitoring of zinc levels.26

Specific Populations

Pregnancy

There are no adequate and controlled studies of octreotide in pregnant women, and the drug should be used during pregnancy only when clearly needed.1 30,31 In cases with a known outcome, no congenital malformations have been reported among patients with acromegaly exposed to octreotide during the first trimester, including women electing to continue the drug throughout pregnancy.1,30,31 The women were exposed to 100-300 mcg/day of octreotide immediate-release or 20-30 mg once a month of octreotide LAR suspension.1,30,31

Animal reproduction studies conducted with octreotide at doses up to 16 times the highest recommended human dose based on body surface area (BSA) have not revealed evidence of harm to the fetus.1 26,29,30,31 Transient growth retardation of rat offspring was observed at IV octreotide doses of 0.02-1 mg/kg per day which are below the maximum recommended human dose of 1.5 mg/day, based on body surface area; this is possibly a consequence of growth hormone inhibition by octreotide.26,29

There are insufficient data with octreotide LAR suspension in pregnant women to inform drug-associated-risk for major birth defects and miscarriage. 26

Lactation

Octreotide is present in rat milk following subcutaneous injection; however, there is no information regarding the presence of octreotide in human milk.1,26,29,30,31 Consider the benefits of breast-feeding and the importance of octreotide to the woman along with potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.1,26,29,30,31

Females and Males of Reproductive Potential

Normalization of growth hormone and insulin-like growth factor-1 by octreotide therapy may lead to improved fertility and unintended pregnancy in female patients with acromegaly.1,26,29

Pediatric Use

Safety and efficacy of octreotide immediate-release injection, long-acting release (LAR) injectable suspension, and the oral preparation have not been established in pediatric patients.1,26,29,30,31 Controlled clinical trials to evaluate the safety and effectiveness of octreotide injection in pediatric patients younger than 6 years of age have not been performed.1,26 In postmarketing reports, serious adverse events, including hypoxia, necrotizing enterocolitis, and death, have been reported with octreotide use in children, most notably in children under 2 years of age.1,26,29 The majority of these pediatric patients had serious underlying co-morbid conditions and the relationship of such adverse events to octreotide has not been established.1,26,29

Octreotide LAR injectable suspension (40 mg once monthly) has been investigated in a randomized, placebo-controlled study in pediatric patients 6-17 years of age with hypothalamic obesity secondary to cranial insult†.26 Efficacy was not demonstrated and treatment with octreotide was not associated with unexpected adverse events; however, new cholelithiasis was reported in 33% of children receiving octreotide.26

Geriatric Use

Clinical trials of octreotide did not include sufficient numbers of patients 65 years of age or older to determine whether such patients respond differently than younger patients.1,26,29 In a small number of patients 65 years of age or older treated with the oral preparation (Mycapssa®), no overall differences in safety or effectiveness were observed between these patients and younger patients.29 Other reported clinical experience has not identified differences in response between geriatric patients and younger adults, but greater sensitivity of some older individuals cannot be ruled out.1,26,29 Half-life increased by 46% and clearance decreased by 26% following administration of immediate-release octreotide injection in an elderly population.1,26 29 Dosage of octreotide should be selected with caution and generally initiated at the lower end of the dosing range because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1,26

Hepatic Impairment

In patients with liver cirrhosis or fatty liver, octreotide half-life is increased to 3.7 or 3.4 hours, respectively, following subcutaneous administration.1,26,29 The LAR IM suspension has not been studied in patients with hepatic impairment.26 In patients with established liver cirrhosis receiving this preparation, the manufacturer recommends an intial dosage of 10 mg; titrate based upon clinical response and tolerability.26

Renal Impairment

In patients with mild (creatinine clearance 40-60 mL/minute), moderate (creatinine clearance 10-39 mL/minute), or severe (creatinine clearance <10 mL/minute) renal impairment not requiring dialysis, octreotide half-life is increased to 2.4, 3, or 3.1 hours, respectively, compared to those without renal impairment.1 In patients with severe renal failure requiring dialysis, octreotide half-life may be increased necessitating adjustment of the maintenance dosage.1

The long-acting IM suspension has not been studied in patients with renal impairment. 26 In patients with dialysis-dependent renal failure receiving this preparation, the manufacturer recommends an intial dose of 10 mg; titrate based upon clinical response and tolerability.26

In patients with end stage renal disease, the initial dosage of the octreotide oral preparation (Mycapssa®) should be 20 mg once daily; titrate dosage based upon IGF-1 levels, clinical response, and tolerability.29

Common Adverse Effects !!navigator!!

Adverse effects reported in at least 20% of patients receiving octreotide LAR for carcinoid syndrome include back pain, fatigue, headache, abdominal pain, nausea, and dizziness.26

Adverse effects reported in greater than 10% of patients receiving immediate-release octreotide for acromegaly include biliary tract abnormalities (gallstones, biliary sludge, duct dilatation), diarrhea, loose stools, nausea, abdominal discomfort, sinus bradycardia, hyperglycemia, and biochemical hypothryroidism. 1,30,31

Adverse effects reported in at least 20% of patients receiving octreotide LAR for acromegaly include diarrhea, cholelithiasis, abdominal pain, and flatulence. 26

Adverse effects reported in greater than 10% of patients receiving oral octreotide (Mycapssa®) include nausea, diarrhea, headache, arthralgia, asthenia, hyperhidrosis, peripheral swelling, blood glucose increased, vomiting, abdominal discomfort, dyspepsia, sinusitis, and osteoarthritis. 29

Drug Interactions ⬆ ⬇

[Section Outline]

Octreotide is not known to be metabolized by cytochrome P-450 (CYP) isoenzymes or other drug metabolizing enzymes.1,26,29

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes !!navigator!!

Limited data suggest somatostatin analogs may decrease metabolic clearance of drugs metabolized by CYP isoenzymes.1,26,29 The manufacturer states that caution is advised and increased monitoring may be required if octreotide is used concomitantly with drugs with a low therapeutic index (e.g., quinidine) that are primarily metabolized by CYP3A4.1,26,29

Drugs Affecting Gastric Acidity !!navigator!!

Concomitant administration of the oral octreotide preparation (Mycapssa®) with oral esomeprazole resulted in a clinically significant 45% and 41% reduction in octreotide peak plasma concentration and AUC, respectively.29 Increased dosages of the oral preparation of octreotide may be required in patients treated with drugs that alter the pH of the upper GI tract (e.g., other proton pump inhibitors, histamine H2-receptor antagonists, and antacids).29

Insulin and/or Other Antihyperglycemic Agents !!navigator!!

Octreotide inhibits the secretion of insulin and glucagon; possible pharmacologic interaction (hyperglycemia or hypoglycemia) may occur.1,26,29 Monitor blood glucose levels when octreotide treatment is initiated or when the dose is altered.1,26,29 Insulin and/or other antihyperglycemic agent dosage adjustments may be required.1,26,29

Effects on GI Absorption of Drugs !!navigator!!

Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs.1,26,29 Patients receiving drugs to control fluid and electrolyte balance may require dosage adjustments of such drugs.1

Octreotide has been investigated for the reduction of excessive fluid loss† from the GI tract in patients with conditions producing such a loss.26 If such patients are receiving total parenteral nutrition (TPN), serum zinc may rise excessively when the fluid loss is reversed. 26 Patients on TPN and octreotide should have periodic monitoring of zinc levels.26

Drugs Associated with Bradycardia !!navigator!!

Possible pharmacodynamic interaction (additive effect on heart rate reduction) with agents associated with bradycardia (e.g., β-adrenergic blockers, calcium channel blockers); dosage adjustment of the concomitantly administered drug may be necessary.1,26,29

Bromocriptine !!navigator!!

Concomitant administration of parenteral or oral octreotide with bromocriptine may increase the systemic exposure of bromocriptine.1,26,29 In patients with active acromegaly, the combination of bromocriptine 5 mg orally twice daily with octreotide 200 mcg subcutaneously twice daily resulted in improved growth hormone and IGF-1 levels compared to either drug alone.53 Octreotide pharmacokinetics were unchanged; bromocriptine AUC increased approximately 40%.53 Dose adjustment of bromocriptine may be necessary.29

Cyclosporine !!navigator!!

Concomitant administration of octreotide injection with cyclosporine may decrease blood levels of cyclosporine and result in transplant rejection.1,26 Concomitant administration of the oral octreotide preparation (Mycapssa®) with oral cyclosporine resulted in a clinically significant 71 and 62% reduction in cyclosporine peak plasma concentration and AUC, respectively.29 Cyclosporine dose adjustment to maintain therapeutic levels may be required.29

Digoxin !!navigator!!

Concomitant administration of the oral octreotide preparation (Mycapssa®) with digoxin resulted in a 37% reduction in digoxin peak plasma concentration, but no change in AUC.29 Careful assessment of digoxin clinical response should be performed when administered concomitantly with oral octreotide (Mycapssa®).29

Levonorgestrel !!navigator!!

Concomitant administration of the oral octreotide preparation (Mycapssa®) with levonorgestrel resulted in a clinically significant 38 and 24% reduction in levonorgestrel peak plasma concentration and AUC, respectively.29 Decreased bioavailability may potentially diminish the effectiveness of combined oral contraceptives or increase breakthrough bleeding.29 Advise women of child-bearing potential to use an alternative non-hormonal method of contraception or a back-up method when the oral octreotide preparation (Mycapssa®) is used with combined oral contraceptives.29

Lisinopril !!navigator!!

Concomitant administration of the oral octreotide preparation (Mycapssa®) with lisinopril resulted in a clinically significant 1.5- and 1.4-fold increase in lisinopril peak plasma concentration and AUC, respectively.29 Monitor the patient's blood pressure and adjust the lisinopril dosage if needed.29

Lutetium Lu 177 Dotatate !!navigator!!

Octreotide competitively binds to somatostatin receptors and may interfere with the efficacy of lutetium Lu 177 dotatate.1,26 Discontinue parenteral octreotide, at least 24 hours for the immediate-release or 4 weeks for the long-acting suspension, prior to each lutetium Lu 177 dotatate dose.1,26

Telotristat !!navigator!!

Concomitant use of telotristat ethyl and short-acting octreotide decreases systemic exposure to telotristat ethyl and its active metabolite telotristat.28 When immediate-release octreotide acetate (200 mcg by subcutaneous injection) was administered concomitantly with telotristat ethyl (single 500-mg dose) in healthy individuals, mean AUC and peak plasma concentrations of telotristat ethyl decreased by 81 and 86%, respectively.28 In addition, mean AUC and peak plasma concentrations of telotristat were decreased by 68 and 79%, respectively.28 When these drugs are used in combination, the manufacturer of telotristat ethyl states that immediate-release octreotide should be administered at least 30 minutes following administration of telotristat ethyl.28

Other Information ⬆ ⬇

Description

Octreotide is a synthetic octapeptide pharmacologically related to the natural hormone somatostatin; it is also known as a somatostatin analog.1,26,29 Octreotide is a more potent inhibitor of growth hormone (GH), glucagon, and insulin than somatostatin.1,26,29 Octreotide also suppresses luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH), decreases splanchnic blood flow, and inhibits release of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide.1,26,29 Because of the drug's pharmacologic actions, octreotide has been employed to control gastrointestinal and other manifestations associated with a variety of conditions (e.g., flushing and diarrhea associated with metastatic carcinoid tumors, watery diarrhea associated with VIP-secreting adenomas).1,26 Octreotide decreases the concentration of GH and/or insulin-like growth factor 1 (IGF-1) in patients with acromegaly.1,26

Octreotide immediate-release injection (Sandostatin® injection and generic equivalents) is absorbed rapidly and completely following subcutaneous injection; peak concentrations are reached in 0.4 hours (0.7 in those with acromegaly).1,26 IV and subcutaneous doses were found to be bioequivalent.1,26 Octreotide is 65% bound in the plasma (41.2% in those with acromegaly), mainly to lipoprotein and to a lesser extent, to albumin.1,26 The elimination half-life of the drug is 1.7-1.9 hours and approximately 32% of the dose is excreted unchanged in the urine.1,26 The duration of action of immediate-release octreotide is variable but extends up to 12 hours depending on the type of tumor, necessitating multiple daily dosing with this dosage form.1,26

Octreotide half-life is longer (2.4-3.1 hours compared to 1.9 hours) in patients with renal impairment (creatinine clearance ≤ 60 mL/minute); in those requiring dialysis, clearance is reduced by half compared to healthy volunteers.1,26 In patients with liver impairment such as cirrhosis and fatty liver, octreotide half-life is increased to 3.7 and 3.4 hours, respectively.1,26

Octreotide long-acting release (LAR) injectable suspension for IM administration (Sandostatin® LAR Depot) is a long-acting dosage form consisting of microspheres of the biodegradable glucose star polymer, D, L-lactic and glycolic acids copolymer, containing octreotide.26 All of the clinical and pharmacological characteristics of the immediate-release dosage form (Sandostatin® Injection and generic equivalents) are maintained with the added feature of slow release of octreotide from the site of injection, reducing the need for frequent administration.26 This slow release occurs as the polymer biodegrades, primarily through hydrolysis.26 The relative bioavailability of the long-acting suspension compared to the immediate-release solution given subcutaneously was 60-63%.26 Following a single IM injection in healthy volunteers, serum octreotide concentrations reach a transient initial peak within 1 hour which progressively declines for the next 3-5 days.26 Following this decline, octreotide concentrations increase slowly, plateau in approximately 2-3 weeks post-injection, and are maintained over a period of nearly 2-3 additional weeks.26 Following multiple IM injections given every 4 weeks, steady-state octreotide concentrations are achieved after the third injection.26 The long-acting suspension has not been studied in patients with renal or hepatic impairment.26

Octreotide delayed-release capsules (Mycapssa®) are enteric-coated (methacrylate [Acryl-EZE®]) and utilize Transient Permeability Enhancer (TPE®) technology.29 36 The capsules are designed to pass through the stomach intact and disintegrate when it reaches the higher pH of the small intestine where the octreotide-TPE formulation is released into the lumen. 29,36 TPE facilitates paracellular transit across the intestinal wall via transient and reversible opening of the tight junctions between cells, allowing intact octreotide to be absorbed.36 The delayed-release preparation does not cause any chemical or physical change in the active compound and once octreotide reaches the systemic circulation, the metabolism and excretion of octreotide is expected to be identical to that of the immediate-release dosage form (Sandostatin Injection and generic equivalents). 36 In a study designed to assess the duration of Mycapssa®-induced increased intestinal permeability, an increase in paracellular permeability was observed 2 hours after administration and returned to baseline by 5.5 hours after administration; this permeability is completely reversible within this timeframe.29 When comparing a single dose of subcutaneous immediate-release octreotide to a single dose of oral octreotide (Mycapssa®), absorption time was longer, peak concentrations were reached at a median 1.67-2.5 hours (oral) versus 0.5 hours (subcutaneous), and peak octreotide levels were 33% lower in healthy subjects receiving the oral preparation.29 In patients with acromegaly, octreotide concentrations are dose proportional following chronic administration of the oral preparation (40, 60, or 80 mg total daily dose); mean peak plasma concentrations were lower compared to single-dose peak concentrations in healthy subjects.29 Administration of the oral preparation with food decreases the rate and extent of absorption by 90% in healthy subjects.29 In patients with acromegaly, elimination after chronic dosing of the oral preparation was slightly slower than that seen in healthy subjects, with a mean apparent half-life at steady state ranging from 3.2-4.5 hours across all doses (20 mg, 40 mg, 60 mg, and 80 mg).29 Elimination is complete approximately 48 hours after the last dose in patients who have achieved steady-state plasma levels; minimal accumulation (approximately 10%) was observed in patients after repeat administration of the oral preparation.29 In patients with severe renal impairment (estimated glomerular filtration rate 15-19 mL/minute per 1.73 m2), octreotide AUC and half-life are increased, but not to the same extent as matched-controls requiring dialysis.29 In patients with end stage renal disease requiring dialysis, clearance is reduced 46%, AUC is increased 87%, and the half-life increased 85% compared to healthy subjects.29

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

Octreotide Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, delayed-release

20 mg (of octreotide)

Mycapssa®

Almac

Parenteral

Injection

50 mcg (of octreotide) per mL*

Octreotide Acetate Injection

SandoSTATIN®

Novartis

100 mcg (of octreotide) per mL*

Octreotide Acetate Injection

SandoSTATIN®

Novartis

200 mcg (of octreotide) per mL*

Octreotide Acetate Injection

500 mcg (of octreotide) per mL*

Octreotide Acetate Injection

SandoSTATIN®

Novartis

1000 mcg (of octreotide) per mL*

Octreotide Acetate Injection

Parenteral

For injectable suspension, extended-release, for IM use

10 mg (of octreotide)

SandoSTATIN LAR® Depot (supplied with vial adapter, needle, and diluent syringe)

Novartis

20 mg (of octreotide)

SandoSTATIN LAR® Depot (supplied with vial adapter, needle, and diluent syringe)

Novartis

30 mg (of octreotide)

SandoSTATIN LAR® Depot (supplied with vial adapter, needle, and diluent syringe)

Novartis

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Copyright ⬆ ⬇

AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions June 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References ⬆

1. Novartis Pharmaceuticals. Sandostatin® (octreotide acetate) injection prescribing information. East Hanover, NJ; 2022 Oct.

2. Sandoz Pharmaceuticals Corporation. Sandostatin® (octreotide acetate) overview and clinical summary. [SDS-8007] East Hanover, NJ; 1992 Feb.

3. Katz MD, Erstad BL. Octreotide, a new somatostatin analogue. Clin Pharm . 1989; 8:255-73. [PubMed 2653711]

4. Mozell EJ, Woltering EA, O'Dorisio TM. Non-endocrine applications of somatostatin and octreotide acetate: facts and flights of fancy. Dis Mon . 1991; 37(Dec):749-848. [PubMed 1683832]

5. Reichlin S. Somatostatin (first of two parts). N Engl J Med . 1983; 309:1495-1501. [PubMed 6139753]

6. Reichlin S. Somatostatin (second of two parts). N Engl J Med . 1983; 309:1556-63. [PubMed 6140639]

7. Battershill PE, Clissold SP. Octreotide: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in conditions associated with excessive peptide secretion. Drugs . 1989; 38:658-702. [PubMed 2689136]

8. Anon. Somatostatin: hormonal and therapeutic roles. Lancet . 1985; 2:77-8. [PubMed 2861528]

9. Bloom SR, Polak JM. Somatostatin. BMJ . 1987; 295:288-90. [PubMed 2888511]

12. Gordon P, Comi RJ, Maton PN et al. Somatostatin and somatostatin analogue (SMS 201-995) in the treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Intern Med . 1989; 110:35-50. [PubMed 2535688]

14. Kvols LK, Moertel CG, O'Connell MJ et al. Treatment of the malignant carcinoid syndrome. N Engl J Med . 1986; 315:663-6. [PubMed 2427948]

15. Oates JA. The carcinoid syndrome. N Engl J Med . 1986; 315:702-3. [PubMed 2875390]

16. Oberg K, Norheim I, Lundqvist G et al. Treatment of the carcinoid syndrome with SMS 201-995, a somatostatin analogue. Scand J Gastroenterol . 1986; 21(Suppl 119):91-2.

17. Kvols LK, Martin JK, Marsh HM et al. Rapid reversal of carcinoid crisis with a somatostatin analogue. N Engl J Med . 1985; 313:1229-30. [PubMed 2865675]

18. Long RG, Adrian TE, Brown MR et al. Suppression of pancreatic endocrine tumour secretion by long-acting somatostatin analogue. Lancet . 1979; 2:764-7. [PubMed 90860]

19. Kvols LK. Therapeutic considerations for the malignant carcinoid syndrome. Acta Oncologica . 1989; 28:433-8. [PubMed 2663050]

20. Marsh HM, Martin JK, Kvols LK et al. Carcinoid crisis during anesthesia: Successful treatment with a somatostatin analogue. Anesthesiology . 1987; 66:89-91. [PubMed 2432806]

22. Orskov H, Christenson SE, Weeke J et al. Effects of antibodies against octreotide in two patients with acromegaly. Clin Endocrin . 1991; 34:395-8.

23. Christenson SE, Weeke J, Orskov H et al. Long-term efficacy and tolerability of octreotide treatment in acromegaly. Metab Clin Exp . 1992; 41:44-50. [PubMed 1518433]

24. Kwekkeboom DJ, Assies J, Hofland LJ et al. A case of antibody formation against octreotide visualized with 111In-octreotide scintigraphy. Clin Endocrinol . 1993; 39:239-43.

25. Stiles ML, Allen LV, Resztak KE et al. Stability of octreotide acetate in polypropylene syringes. Am J Hosp Pharm . 1993; 50:2356-8. [PubMed 8266962]

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