Octreotide (Sandostatin) is an analog of naturally occurring somatostatin. It inhibits the secretion of hormones including growth hormone, insulin, glucagon, secretin, motilin, and pancreatic polypeptide.

Octreotide (Sandostatin) Uses:

• Acromegaly:

  • Injection solution:
    • To reduce blood levels of growth hormone (GH) & insulin-like growth factor 1 (IGF-1) in patients with inadequate response to or who cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses.
    • The therapy goal is to achieve normalization of GH & IGF-1 levels.
  • LAR depot suspension:
    • With a goal of therapy to reduce GH and IGF-1 levels to normal, Long-term maintenance treatment of acromegaly in patients with an inadequate response to surgery & radiotherapy (or for whom surgery/radiotherapy are not options).
    • It is suggested by Endocrine Society that use of a somatostatin analog in select patients preoperatively to reduce surgical risk from severe comorbidities and as initial adjuvant therapy in patients with persistent, significant disease (ie, moderate to severe signs/symptoms of growth hormone excess and without local mass effects) postoperatively.
    • For patients with mild disease postoperatively, Alternative agents are suggested.

• Carcinoid tumors:

  • Injection solution:
    • In patients with metastatic carcinoid tumors, management of symptoms (diarrhea and flushing).
  • LAR depot suspension:
    • With metastatic carcinoid tumors, Long-term treatment of severe diarrhea and flushing episodes associated.

• Vasoactive intestinal peptide-secreting tumors:

  • Injection solution:
    • Profuse watery diarrhea treatment associated with vasoactive intestinal peptide-secreting tumors (VIPomas).
  • LAR depot suspension:
    • Long-term treatment of profuse watery diarrhea associated with VIPomas.
• Limitations of use:
  • In patients with carcinoid syndrome and VIPomas, the effects of octreotide (injection solution and LAR depot suspension) on tumor size, rate of growth, and development of metastases have not been determined.

• Off Label Use of Octreotide in Adults:

  • Carcinoid crisis (prevention)
  • Diarrhea (refractory or persistent) associated with chemotherapy
  • Diarrhea associated with graft-versus-host disease (GVHD)
  • Gastroenteropancreatic neuroendocrine tumors (metastatic)
  • Gastroesophageal variceal hemorrhage
  • Hepatorenal syndrome
  • Malignant bowel obstruction
  • Sulfonylurea-induced hypoglycemia
  • Thymoma/thymic malignancies (advanced)
  • Zollinger-Ellison syndrome
  • Cushing's syndrome (ectopic)
  • Hypothalamic obesity
  • Postgastrectomy dumping syndrome
  • Small bowel fistulas

Octreotide (Sandostatin) Dose in Adults

Octreotide (Sandostatin) Dose in the treatment of Acromegaly:

SubQ, IV:

• Initial:
  • 50 mcg 3 times/day.
  • Titrate to achieve growth hormone (GH) levels <5 ng/mL or insulin-like growth factor 1 (IGF-1) levels <1.9 units/mL in males and <2.2 units/mL in females.
• Usual effective dose:
  • 100 mcg 3 times/day.
• Range:
  • 300 to 1,500 mcg/day.
  • Doses above 300 mcg/day rarely result in additional benefit.
  • The dose should be reduced if the increased dose fails to provide additional benefit.
• Note:
  • In patients who have received irradiation, should be withdrawn yearly for a 4week interval (8 weeks for depot injection).
  • Resume if levels increase and signs/symptoms recur.

IM depot injection:

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

Dosage adjustment for acromegaly:

• After 3 months of depot injections, the dosage may be continued or modified as follows:

  • GH ≤1 ng/mL, IGF-1 normal, and symptoms controlled:
    • Reduce octreotide depot to 10 mg IM every 4 weeks
  • GH ≤2.5 ng/mL, IGF-1 normal, and symptoms controlled:
    • Maintain octreotide depot at 20 mg IM every 4 weeks
  • GH >2.5 ng/mL, IGF-1 elevated, and/or symptoms uncontrolled:
    • Increase octreotide depot to 30 mg IM every 4 weeks.
  • If GH, IGF-1, or symptoms remain uncontrolled, the dose may be increased to 40 mg every 4 weeks.
  • Dosages >40 mg are not recommended by the manufacturer.
  • however, individualized doses up to 60 mg every 4 weeks have been used successfully in partial responders in some cases.

Note:

• Consider combination therapy with pegvisomant or a dopamine agonist if clinical & biochemical response is inadequate at the max dosage of octreotide.

Octreotide (Sandostatin) Dose in the treatment of Carcinoid tumors:

SubQ, IV:

• Initial 2 weeks:
  • In 2-4 divided doses, 100-600 mcg/day.
• Usual range:
  • 50-750 mcg/day (some patients may require up to 1,500 mcg/day).
  • Experience with doses above 750 mcg/day is limited.

IM depot injection:

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

Note:

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

Dosage adjustment for carcinoid tumors:

• After 2 months of depot injections, the dosage may be continued or modified as follows:
  • If symptoms are inadequately controlled, increase to 30 mg IM every 4 weeks
  • Decrease to 10 mg IM every 4 weeks, for a trial period, if initially responsive to 20 mg dose
  • Dosage >30 mg is not recommended

Octreotide (Sandostatin) Dose in the prevention of Carcinoid crisis (off-label):

• Immediate release octreotide solution (Oberg 2004):

  • Patients controlled with octreotide IM (depot) 20 to 30 mg:
  • SubQ:
    • Prior to the procedure, 250-500 mcg within 1-2 hours.

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

• IV bolus:
  • Prior to the procedure, 500-1000 mcg 1-2 hours or
• SubQ:
  • Prior to procedure 500 mcg 1-2 hours

Intraoperative use for carcinoid crisis with hypotension:

IV:

• 500 to 1,000 mcg bolus, repeat at 5-minute intervals until symptoms are controlled or IV:
  • During the procedure, 500-1,000 mcg bolus followed by 50-200 mcg/hour continuous infusion.

Postoperative dose (if supplemental doses required during the procedure):

IV:

• Followed by resumption of the preoperative treatment schedule, 50-200 mcg/hour continuous infusion for 24 hours.

Octreotide (Sandostatin) Dose in the treatment of Diarrhea (off-label):

• IV:
  • Initial:
  • Every 8 hours, 50-100 mcg.
  • Increase by 100 mcg/dose at 48-hour intervals.
• Max dose:
  • 500 mcg every 8 hours

Octreotide (Sandostatin) Dose in the treatment of refractory diarrhea associated with chemotherapy (off-label):

• Low grade or uncomplicated:

  • SubQ:
  • Every 8 hours, 100-150 mcg.

• Severe:

  • Initial:
  • SubQ:
    • Every 8 hours, 100-150 mcg.
    • Every 8 hours, may increase to 500 to 1500 mcg IV or SubQ (Kornblau 2000)

• Complicated:

  • IV, SubQ:
  • Initial:
    • 100-150 mcg 3 times/day or IV Infusion:
    • 25-50 mcg/hour.
    • May escalate to 500 mcg 3 times/day until controlled (Benson 2004)

Octreotide (Sandostatin) Dose in the treatment of Diarrhea associated with acute graft-versus-host disease (GVHD) (off-label):

• IV:

  • Every 8 hours, 500 mcg.
  • To avoid ileus, discontinue within 24 hours of diarrhea resolution.
  • Max duration of therapy if diarrhea is not resolved:
    • 7 days (Kornblau 2000)

Octreotide (Sandostatin) Dose in the treatment of Gastroenteropancreatic neuroendocrine tumors, metastatic (off-label):

IM (depot):

• Until tumor progression or death, 30 mg every 4 weeks (Rinke 2009) or

SubQ:

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

IM (depot):

• Assure tolerability by initiating with the SubQ formulation for 3-7 days (and continue with SubQ for the first ~14 days after the initial IM depot dose).

• Then initiate IM (depot):

  • •  20-30 mg every 28 days (SubQ doses of 200 to 600 mcg/day should receive 20 mg IM and SubQ doses of 750-1,500 mcg/day should receive 30 mg IM).

• IM (depot) range:

  • 20-60 mg every 28 days (Oberg 2004).

• With lutetium Lu 177 dotatate treatment:

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

Octreotide (Sandostatin) Dose in the treatment of Gastroesophageal variceal hemorrhage (off-label):

Note:

• For up to 7 days, Empiric IV prophylactic antibiotics should be administered to patients with cirrhosis and active variceal bleeding.
• Vasoactive therapy should be given to patients with varices or at risk for having varices who have upper GI bleeding.
• IV bolus:
  • For 2-5 days, 50 mcg, followed by continuous IV infusion of 50 mcg/hour.
  • If hemorrhage not controlled, may repeat bolus in the first hour.

Octreotide (Sandostatin) Dose in the treatment of Hepatorenal syndrome (off-label):

SubQ:

• Initial:
  • 100 mcg 3 times daily.
  • May increase to 200 mcg 3 times daily (with a goal to increase mean arterial pressure [MAP] by at least 15 mm Hg from baseline).

Octreotide (Sandostatin) Dose in the treatment of Malignant bowel obstruction (off-label):

• SubQ:
•  In 2-3 divided doses, 200-900 mcg/day or 300 mcg/day by continuous SubQ infusion.

Octreotide (Sandostatin) Dose in the treatment of Sulfonylurea-induced hypoglycemia (off-label):

Note:

• Although octreotide use has been advocated as first-line therapy, indications & dosing for octreotide are not firmly established (Glatstein 2012).
• With dextrose-alone therapy, Octreotide may reduce the incidence of recurrent hypoglycemia seen (Fasano 2008).
• In addition, although subcutaneous administration is the preferred route, administration via intravenous bolus and intravenous infusion has also been described in the literature.
• Based on patient-specific details, Optimal care decisions should be made.
• Repeat dosing, dose-escalation, or the initiation of a continuous infusion may be required in patients who experience recurrent hypoglycemia.
• The duration of treatment may exceed 24 hours.
• SubQ:
  • 50-75 mcg.
  • Based on blood glucose concentrations, repeat every 6 hours as needed.
• IV:
  • Doses up to 125 mcg/hour have been used successfully (McLaughlin 2000)

Octreotide (Sandostatin) Dose in the treatment of advanced Thymoma/thymic malignancies, (off-label):

• SubQ:
  • 500 mcg 3 times daily.
  • Evaluate after 2 months, patients with remission (complete or partial) continued octreotide for up to a max of 12 months.
  • Patients with stable disease continued octreotide and also received prednisone for up to 12 months or until disease progression or unacceptable toxicity (Loehrer 2004).

Octreotide (Sandostatin) Dose in the treatment of Vasoactive intestinal peptide tumors (VIPomas):

SubQ, IV:

• Initial 2 weeks:
  • In 2-4 divided doses, 200-300 mcg/day.
  • Titrate dose based on response/tolerance.
• Range:
  • 150-750 mcg/day (doses >450 mcg/day are rarely required)

IM depot injection:

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

Note:

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

• Dosage adjustment for VIPomas:

  • The dosage may be continued or modified after 2 months of depot injections as follows:
  • If symptoms are inadequately controlled, increase to 30 mg IM every 4 weeks
  • If initially responsive to 20 mg dose, decrease to 10 mg IM every 4 weeks, for a trial period.
  • Dosage >30 mg is not recommended

Octreotide (Sandostatin) Dose in the treatment of Zollinger-Ellison syndrome (off-label):

Note:

• Until complete disease remission, or until significant disease progression or unacceptable toxicity, continue treatment.

SubQ:

• Initial:
  • 100 mcg every 12 hours.
  • Every 12 hours, may increase to 200 mcg (based upon fasting blood sugars).
• IM (depot):
  • 30 mg once a month (after tolerating 2-4 weeks of short-acting regimen).
• Note:
  • Continue subcutaneous formulation for the first 2 weeks of initiation of depot injection (Shojamanesh 2002).

Octreotide (Sandostatin) Dose in Childrens

Note:

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

Octreotide (Sandostatin) Dose in the treatment of Acquired Chylothorax (eg, postoperative):

• Infants and Children:

  • Continuous IV infusion:

    • Reported range:
      • 1-4 mcg/kg/hour/
      • Octreotide was initiated and maintained at a fixed rate of 3 mcg/kg/hour in one report.
      • Other reports describe the initiation of therapy at the lower end of a dosing range and titration.
    • Usual therapy duration:
      • 7 days.

Octreotide (Sandostatin)Dose in the treatment of Diarrhea:

Note:

• In pediatric patients, octreotide has been used to manage refractory cases of diarrhea due to multiple etiologies including GVHD, chemotherapy-induced, and congenital secretory syndromes.
• Use has been described in a small trial, several case reports & by some centers.
• A dose-response relationship has not been established.
• SubQ administration is the usual route.
• However, the IV route has been used in some cases.

• Infants, Children, and Adolescents:

  • Intermittent SubQ:

    • Usual initial dose:
      • 1-10 mcg/kg/dose every 8-12 hours.
      • Doses should begin at the low end of the range & be titrated to effect.
    • Reported range:
      • 1-49 mcg/kg/day.
      • A higher dose of 60 mcg/kg/day has been reported.
      • For GVHD, in adults, a max dose of 500 mcg/dose has been recommended.

  • Continuous IV infusion:

Note:

• Typically IV infusion reserved for patients failing intermittent dosing:
  • • Initial:
    • 1 mcg/kg/hour.
    • Some patients may require titration.
    • Doses up to 49 mcg/kg/day have been reported.

Octreotide (Sandostatin) Dose in the treatment of Esophageal varices; gastrointestinal bleed:

• IV:

  • Initial:
  • 1-2 mcg/kg bolus followed by 1-2 mcg/kg/hour continuous IV infusion.
  • Titrate infusion rate to the response.
  • Taper dose by 50% every 12 hours when no active bleeding occurs for 24 hours.
  • May discontinue when the dose is 25% of the initial dose (Al-Hussaini 2012; Eroglu 2004).

Octreotide (Sandostatin) Dose in the treatment of Hyperinsulinemic hypoglycemia:

Note:

• Not first-line therapy (diazoxide suggested for initial management).
• Dosing should be individualized to patient response to achieve & maintain target serum glucose concentrations (typically >70 mg/dL).

• Daily dosing:

  • SubQ:

    • Intermittent SubQ:
      • Initial:
        • In divided doses, 5 mcg/kg/day every 6-8 hours.
        • Titrate to response, 5 mcg/kg/day increments have been used.
      • Usual reported effective range:
        • In divided doses, 5-25 mcg/kg/day.
      • Max daily dose:
        • 35 mcg/kg/day (Demirbilek 2017; Shah 2017).
    • Continuous SubQ infusion:
      • Initial:
        • 5 mcg/kg/day delivered over 24 hours.
        • Titrate to response, 5 mcg/kg/day increments have been used.
      • Usual reported effective range:
        • 5-25 mcg/kg/day.
      • Max daily dose:
        • 35 mcg/kg/day.

• Monthly dosing:

  • Long-acting depot formulation; conversion from SubQ (daily) to IM (monthly):

Note:

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

  • Children and Adolescents:

    • Long-acting formulation (Sandostatin LAR): IM:

      • Calculate the patient's cumulative 31-day SubQ dose, which will equal the monthly IM dose.
      • Every 4 weeks, administer this dose.
      • Continue with SubQ octreotide therapy for 2 months after starting IM long-acting formulation (first 2 IM depot doses) then discontinue prior at the time of the third IM dose.
      • While receiving both IM (long-acting) and SubQ octreotide, monitor patients closely for hypoglycemia.

Octreotide (Sandostatin) Dose in the treatment of Hypothalamic obesity (from cranial insult):

• Children ≥8 years of age and Adolescents:

  • SubQ:
    • Initial:
    • Divided into 3 daily doses, 5 mcg/kg/day.
    • The dose may be increased bimonthly at 5 mcg/kg/day increments to a max of 15 mcg/kg/day divided into 3 daily doses.
    • Dosing based on small trials which showed insulin suppression decreased caloric intake & BMI stabilization or decrease.
    • Trials were limited to a 6-month duration.
    • Long-term effects are unknown (Lustig 1999; Lustig 2003; Lustig 2011).

Octreotide (Sandostatin) Dose in the treatment of Sulfonylurea overdose:

• Dosing in pediatric patients based on experience in adult patients.
• Pediatric-specific reports are sparse (Glatstein 2010; Howland 2011).

• Infants, Children, and Adolescents:

  • SubQ:
    • Every 6 hours, 1-1.25 mcg/kg/dose.
    • Based on blood glucose concentrations, repeat as needed (Howland 2011).
    • Children generally need only a single dose.
  • Note:
    • Although octreotide use is strongly advocated as a first-line therapy, indications & dosing for octreotide are not firmly established (Glatstein 2012).

Pregnancy Risk Category: B

• Octreotide crosses with the placenta at delivery and can be detected in newborns.
• Data concerning the use of opiates during pregnancy are not available.
• No congenital malformations were found in case reports of acromegalic mothers who received normal doses octreotide throughout pregnancy.
• Short-acting octreotide might be an option if acromegaly treatment is needed during pregnancy due to worsening symptoms (eg headaches, evidence of tumor growth).
• It is not recommended to monitor insulin-like growth factors 1 (IGF-1), and growth hormone (GH), during pregnancy. A maternally-produced active placental GH variant limits the usefulness (Endocrine Society).
• Women with acromegaly should use appropriate contraception as normalization of IGF-1 or GH can restore fertility.
• The Endocrine Society recommends that long-acting formulations containing somatostatin analogues be stopped approximately two months before a planned pregnancy.
• Short-acting octreotide can be used up to the point of conception if necessary.

Octreotide (Sandostatin) use during breastfeeding:

• Breast milk contains oxreotide.
• Limited information is available on octreotide use by breastfeeding women.
• A case report revealed that a woman had been taking SubQ in high doses of up to 2,400 mcg/day prior to and during pregnancy.
• The colostrum contained octreotide in a concentration similar to that found in the maternal serum.
• However, oral absorption is poor for octreotide (Battershill 1989).
• When deciding whether to breastfeed during therapy, you should consider the risks to infants, the benefits to breastfeeding, and the benefits to the mother, according to the manufacturer.

Octreotide (Sandostatin) Dose in Kidney Disease:

• Regular injection (solution):

  • Mild to severe impairment:
    • In the manufacturer’s labeling, there are no dosage adjustments provided.
  • Severe impairment requiring dialysis:
    • In the manufacturer’s labeling, there are no specific dosage adjustments provided.
    • however, a dosage adjustment may be needed since clearance is reduced by ~50%.

• Depot injection:

  • Mild to severe impairment:
    • No initial dosage adjustment is necessary.
  • Severe impairment requiring dialysis:
    • Initial dose:
    • 10 mg IM every 4 weeks.
    • Titrate based upon response (clearance is reduced by ~50%)

Octreotide (Sandostatin) Dose in Liver Disease:

Regular injection (solution):

• In the manufacturer’s labeling, there are no dosage adjustments provided.
• In patients with cirrhosis and fatty liver disease, the half-life is prolonged, and total body clearance is decreased.

Depot injection:

• Patients with established cirrhosis of the liver:
• Initial dose:
• 10 mg IM every 4 weeks.
• Titrate based upon response.

---

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

Common Side Effects of Octreotide (Sandostatin):

• Cardiovascular:

  • Sinus Bradycardia
  • Hypertension

• Central Nervous System:

  • Fatigue
  • Headache
  • Dizziness
  • Pain

• Dermatologic:

  • Pruritus
  • Skin Rash
  • Alopecia

• Endocrine & Metabolic:

  • Hyperglycemia
  • Hypothyroidism

• Gastrointestinal:

  • Abdominal Distress
  • Diarrhea
  • Loose Stools
  • Nausea
  • Abdominal Pain
  • Flatulence
  • Cholelithiasis
  • Gallbladder Sludge
  • Constipation
  • Vomiting
  • Biliary Obstruction
  • Upper Abdominal Pain

• Hematologic & Oncologic:

  • Anemia

• Immunologic:

  • Antibody Development

• Local:

  • Pain At Injection Site

• Neuromuscular & Skeletal:

  • Back Pain
  • Arthropathy
  • Myalgia
  • Musculoskeletal Pain

• Respiratory:

  • Upper Respiratory Tract Infection
  • Flu-Like Symptoms
  • Sinusitis

Less Common Side Effects Of Octreotide (Sandostatin):

• Cardiovascular:

  • Cardiac Conduction Disturbance
  • Cardiac Arrhythmia
  • Edema
  • Flushing

• Central Nervous System:

  • Depression

• Endocrine & Metabolic:

  • Goiter
  • Hypoglycemia

• Gastrointestinal:

  • Abdominal Distention
  • Abnormal Stools
  • Dyspepsia
  • Fecal Discoloration
  • Steatorrhea
  • Tenesmus
  • Malabsorption

• Genitourinary:

  • Pollakiuria
  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Bruise

• Infection:

  • Cold Symptoms

• Local:

  • Hematoma At Injection Site

• Neuromuscular & Skeletal:

  • Arthralgia
  • Asthenia
  • Tremor

• Ophthalmic:

  • Blurred Vision
  • Visual Disturbance

• Respiratory:

  • Epistaxis

Side effects of Octreotide (Sandostatin) (Frequency not known):

• Cardiovascular:

  • Pulmonary Embolism

• Central Nervous System:

  • Cerebrovascular Disease
  • Malignant Hyperthermia

• Hematologic & Oncologic:

  • Rectal Hemorrhage

• Hepatic:

  • Ascites

• Respiratory:

  • Pleural Effusion

Contraindications to Octreotide (Sandostatin):

• Hypersensitivity to octreotide and any component of the formulation

Warnings and precautions

• Test for abnormal Schillings:

  • Chronic treatment is possible for abnormal Schillings tests
  • monitor vitamin B levels.

• Cholelithiasis

  • May cause gallbladder dysfunction (inhibits gallbladder contractility, decreases bile secretion),
  • Cholelithiasis can be diagnosed by examining patients.
  • Cholelithiasis has been reported as well as complications of cholelithiasis, such as cholangitis, cholecystitis and pancreatitis that require cholecystectomy.
  • If you suspect that someone is using the drug, stop and treat it accordingly.
  • The incidence of gallbladder stones and biliary sludge rises when the therapy lasts more than 12 months.
  • If octreotide treatment has been planned, patients with GI and pancreatic neuroendocrine tumours are recommended to have prophylactic cholecystectomy (Oberg 2004).

• Regulation of Glucose

  • Somatostatin analogs can affect glucose regulation.
  • Type I diabetes may lead to severe hypoglycemia.
  • Hyperglycemia can occur in patients with diabetes type II or without.
  • There may be changes in insulin and other hypoglycemic medications.
  • Patients with insulinomas may experience hypoglycemia worsening by Octreotide.
  • Take care.

• Reactions from the local community:

  • The depot formulation may cause mild to moderate pain at the injection site (usually lasting one hour).

• Hypothyroidism:

  • Reduces the secretion TSH.
  • Hypothyroidism should be monitored.

• Pancreatitis

  • This may alter the absorption rate of dietary fats.
  • Be on the lookout for signs of pancreatitis.

• Cardiovascular disease

  • Patients with heart disease or concomitant medication that alters heart rate or rhythm should be cautious.
  • Bradycardia, conduction abnormalities, and arrhythmia were observed in patients with acromegalic or carcinoid syndrome.
  • There may be changes in the requirements for cardiovascular medication.

• Excessive fluid loss:

  • Patients with severe fluid loss may be able to reduce their excess fluid.
  • Patients on total parenteral nourishment (TPN) should be monitored for any elevations in zinc levels.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious
  • Patients with cirrhosis may need to adjust their dosage.

• Renal impairment

  • Patients with impaired renal function should be cautious.
  • Patients on dialysis may need to adjust their dosage.

Octreotide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
Androgens	May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol.
Antidiabetic Agents	May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
Antidiabetic Agents	Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Bradycardia-Causing Agents	May enhance the bradycardic effect of other Bradycardia-Causing Agents.
Bretylium	May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents.
Bromocriptine	Somatostatin Analogs may increase the serum concentration of Bromocriptine. Somatostatin Analogs may also delay bromocriptine absorption and time to maximum plasma concentrations.
Codeine	Somatostatin Analogs may decrease the metabolism of Codeine. The formation of two major codeine metabolites (morphine and norcodeine) may be impaired by somatostatin analogs.
Herbs (Hypoglycemic Properties)	May enhance the hypoglycemic effect of HypoglycemiaAssociated Agents.
Hypoglycemia-Associated Agents	May enhance the hypoglycemic effect of other HypoglycemiaAssociated Agents.
Ivabradine	Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine.
Lacosamide	Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide.
Maitake	May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Midodrine	May enhance the bradycardic effect of Bradycardia-Causing Agents.
Monoamine Oxidase Inhibitors	May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Pegvisomant	Somatostatin Analogs may enhance the adverse/toxic effect of Pegvisomant. Specifically, this combination may increase the risk for significant elevations of liver enzymes.
Pegvisomant	May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Prothionamide	May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Quinolones	May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use.
Ruxolitinib	May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible.
Salicylates	May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Selective Serotonin Reuptake Inhibitors	May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Terlipressin	May enhance the bradycardic effect of Bradycardia-Causing Agents.
Tofacitinib	May enhance the bradycardic effect of Bradycardia-Causing Agents.
Risk Factor D (Consider therapy modification)
Ceritinib	Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs.
CycloSPORINE (Systemic)	Somatostatin Analogs may decrease the serum concentration of CycloSPORINE (Systemic).
Gallium Ga 68 Dotatate	Somatostatin Analogs may diminish the therapeutic effect of Gallium Ga 68 Dotatate. Specifically, a false negative PET scan may occur if Gallium GA 68 Dotatate is used during treatment with somatostatin analogs. Management: Imaging with gallium Ga 68 dotatate positron emission tomography (PET) should be performed just prior to dosing with long-acting somatostatin analogs. Short-acting somatostatin analogs can be used up to 24 hours before imaging with gallium Ga 68 dotatate.
Lutetium Lu 177 Dotatate	Somatostatin Analogs may diminish the therapeutic effect of Lutetium Lu 177 Dotatate. Specifically, the therapeutic effect of Lutetium Lu 177 Dotatate may be diminished if the timing of Somatostatin Analog administration is not carried out as recommended. Management: Discontinue long-acting somatostatin analogs at least 4 weeks and short-acting octreotide at least 24 hours prior to each lutetium Lu 177 dotatate dose. Administer short- and long-acting octreotide during treatment as recommended. See full monograph.
Sincalide	Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.
Siponimod	Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia.
Telotristat Ethyl	Octreotide may decrease the serum concentration of Telotristat Ethyl. Management: Administer short-acting octreotide at least 30 minutes after administration of telotristat ethyl and monitor for decreased telotristat ethyl efficacy.
Risk Factor X (Avoid combination)
Macimorelin	Somatostatin Analogs may diminish the diagnostic effect of Macimorelin.

Monitoring Parameters:

Acromegaly:

Initial:

• Short-acting formulation:

  • To evaluate responsiveness to therapy, measure serum growth hormone (GH) every 1-4 hours for 8-12 hours post-dose or a single measurement of serum insulin-like growth factor 1 (IGF-1) 2 weeks after initiation or dosage adjustment.

• Long-acting formulation:

  • Serum GH & IGF-1 (at 3 months prior to next dose)

Maintenance:

• Serum GH & IGF-1 every 3-6 months

Carcinoid:

• 5-HIAA, plasma serotonin & plasma substance P

VIPomas:

• Vasoactive intestinal peptide

Chronic therapy:

• Thyroid function (baseline and periodic).
• Vitamin B 12 levels.
• Blood glucose, glycemic control, and antidiabetic regimen (patients with diabetes mellitus) should be assessed following initiation, then periodically or following dosage adjustments.
• Cardiac function (heart rate, ECG).
• Zinc level (patients with excessive fluid loss maintained on TPN).
• Gallbladder monitoring if clinically indicated, routine gallbladder ultrasound is not considered necessary (Endocrine Society [Katznelson 2014])

How to administer Octreotide (Sandostatin)?

Regular injection formulation:

• Administer SubQ or IV.
• IV administration may be IV push (undiluted over 3 mins), intermittent IV infusion (over 15-30 mins), or continuous IV infusion (off-label route).
• In emergency situations (eg, carcinoid crisis), octreotide may be given as a rapid IV bolus.

• SubQ:

  • To deliver dose to reduce injection site pain, use the concentration with the smallest volume.
  • Rotate injection site.
  • Prior to injection, it may bring to room temperature.

Depot formulation (Sandostatin LAR):

• Administer IM intragluteal (avoid deltoid administration).
• To avoid irritation, alternate gluteal injection sites.
• For IM administration only.
• Do not administer depot formulation (Sandostatin LAR) intravenously or subcutaneously.
• It must be administered immediately after mixing.

Mechanism of action of Octreotide (Sandostatin):

• It mimics natural somatostatin and inhibits serotonin production, as well as secretion gastrin, VIP insulin, glucagon secretion, motilin, secretin, and pancreatic polypeptide.
• In acromegaly, decreases in growth hormone and IGF-1.
• Octreotide has a greater ability to inhibit growth hormones, glucagon and insulin than endogenous somatostatin.
• It suppresses the LH response to GnRH and secretion thyroid-stimulating hormonal.

Duration of action:

• SubQ:
  • 6-12 hours.
  • Steady-state levels are achieved after 3 injections when using Sandostatin LAR Depot formulation (3 months of therapy)

Absorption:

• SubQ:
  • Rapid & complete.
• IM (depot formulation):
  • Released slowly (via microsphere degradation in the muscle)

Protein binding:

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

Metabolism:

• Extensively hepatic

Bioavailability:

• SubQ:
• 100%.
• IM:
• 60%-63% of SubQ dose

Half-life elimination:

• 1.7-1.9 hours.
• Increased in elderly patients.
• Cirrhosis:
  • Up to 3.7 hours.
• Fatty liver disease:
  • Up to 3.4 hours.
• Renal impairment:
  • Up to 3.1 hours

Time to peak plasma concnetration:

• SubQ:
  • 0.4 hours (0.7 hours acromegaly).
• IM:
  • 1 hour

Excretion:

• Urine (32% as unchanged drug)

Clearance:

• Adults:
• 10 L/hour.
• Adults with acromegaly:
• 18 L/hour

International Brands of Octreotide:

• SandoSTATIN
• SandoSTATIN LAR Depot
• Ocphyl
• Octreotide Acetate Omega
• SandoSTATIN
• SandoSTATIN LAR
• Cryostatin
• Nomactril
• Octide
• Octostat
• Octrestatin
• Octride
• Oktra
• Proclose
• Sandostatin
• Sandostatin LAR
• Sandostatina
• Sandostatina LAR
• Sandostatine
• Sandostatine LAR
• Treoject

Octreotide Brand Names in Pakistan:

Octreotide Injection 20 mg/ml
Sandostatin Lar	Novartis Pharma (Pak) Ltd

 

Octreotide Acetate Injection 30 mg/ml
Sandostatin Lar	Novartis Pharma (Pak) Ltd

 

Octreotide Injection 0.1 mg/ml
Asterotide	Hoffman Health Pakistan Ltd.
Hatide	Hygeia Pharmaceuticals
Hatide	Hygeia Pharmaceuticals
Jintrotide	Accurate Medical Suppliers
Sandostatin	Novartis Pharma (Pak) Ltd

 

Octreotide Acetate Injection 0.05 mg/ml
Sandostatin	Novartis Pharma (Pak) Ltd