General

Pronunciation:
ok-tree-oh-tide

Trade Name(s)

• Bynfezia Pen
• Mycapssa
• SandoSTATIN
• SandoSTATIN LAR 
• SandoSTATIN LAR Depot

Ther. Class.

antidiarrheals

hormones

Indications

• IV IM Subcut Treatment of the following:
  • Symptoms (flushing and diarrhea) associated with metastatic carcinoid tumors;
  • Profuse, watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas);
  • Acromegaly in patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses.
• PO Long-term maintenance treatment of acromegaly in patients who have responded to and tolerated treatment with octreotide or lanreotide.

Unlabeled Use(s):

• Management of diarrhea associated with chemotherapy or graft-versus-host disease.
• Gastroesophageal variceal hemorrhage.

Action

• Suppresses secretion of serotonin and gastroenterohepatic peptides.
• Increases absorption of fluid and electrolytes from the GI tract and increases transit time.
• Decreases levels of serotonin metabolites.
• Also suppresses growth hormone, insulin, and glucagon.

Therapeutic Effect(s):

• Normalization of growth hormone and insulin-like growth factor 1 levels and maintenance of these levels.
• Control of severe flushing and diarrhea associated with metastatic carcinoid tumors and VIPomas.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability. Well absorbed following subcut administration and IM administration of depot form. Food reduces rate and extent of oral absorption.

Distribution: Some distribution to extravascular tissues.

Metabolism and Excretion: Extensive hepatic metabolism; 32% excreted unchanged in urine.

Half-life: 1.5 hr.

TIME/ACTION PROFILE (control of symptoms)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity.

Use Cautiously in:

• Gallbladder disease (↑ risk of stone formation);
• Renal impairment (dose ↓ may be necessary);
• Hyperglycemia or hypoglycemia (changes in blood glucose may occur);
• Fat malabsorption (may be aggravated);
• OB:   Safety not established in pregnancy;
• Lactation:  Safety not established in breast feeding;
• Rep:  Premenopausal women (may ↑ fertility and ↑ risk of pregnancy);
• Pedi:   Safety and effectiveness of depot injection and oral formulation not established in children.

Adverse Reactions/Side Effects

CV: edema, atrioventricular block, bradycardia, hypertension, orthostatic hypotension, palpitations, QT interval prolongation

Derm: ↑ sweating, flushing

EENT: sinusitis, visual disturbances

Endo: hyperglycemia, hypoglycemia, hypothyroidism

GI: ILEUS, PANCREATITIS, abdominal pain, cholelithiasis, diarrhea, nausea, vomiting, cholecystitis, fat malabsorption, flatulence

GU: urinary tract infection

Local: injection-site pain

MS: arthralgia

Neuro: headache, dizziness, drowsiness, fatigue, weakness.

Misc: ↓ vitamin B₁₂  levels

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• May alter requirements for  insulin  or  oral hypoglycemic agents.
• May ↓ levels of  cyclosporine  and  digoxin ; closely monitor levels and adjust dose of cyclosporine and digoxin as needed.
•  Beta blockers,  digoxin,  diltiazem,  ivabradine, and  verapamil  may ↑ risk of bradycardia.
•  Proton pump inhibitors,  H₂  receptor antagonists, and  antacids  may ↓ absorption and levels of orally administered octreotide; may need to ↑ dosage of oral octreotide.
• May ↑ levels of  lisinopril ; closely monitor BP.
• May ↓ levels of  levonorgestrel ; advise patient to use nonhormonal contraceptive or a backup method while receiving octreotide.
• May ↑ levels of  bromocriptine ; may need to ↓ dose of bromocriptine.
• May ↓ effectiveness of  lutetium Lu 177 dotatate ; discontinue ≥4 wk prior to each dose of lutetium Lu 177 dotatate.

Route/Dosage

Carcinoid Tumors

Subcut IV (Adults): 100–600 mcg/day in 2–4 divided doses during first 2 wk of therapy (range 50–1500 mcg/day).

IM (Adults): Sandostatin LAR– 20 mg every 4 wk for 2 mo; dose may be further adjusted.

VIPomas

Subcut IV (Adults): 200–300 mcg/day in 2–4 divided doses during first 2 wk of therapy (range 150–750 mcg/day).

IM (Adults): Sandostatin LAR– 20 mg every 2 wk for 2 mo; dose may be further adjusted.

Acromegaly

Subcut IV (Adults): 50–100 mcg 3 times daily; titrate to achieve growth hormone levels <5 ng/mL or IGF-1 levels <1.9 units/mL (males) or <2.2 units/mL (females) (usual effective dose = 100–200 mcg 3 times daily).

IM (Adults): Sandostatin LAR– 20 mg every 4 wk for 3 mo, then adjusted on the basis of growth hormone levels.

PO (Adults): 20 mg twice daily initially; titrate based on IGF-1 levels obtained every 2 wk by 20 mg/day. If maintenance dose = 60 mg/day, administer as 40 mg in am and 20 mg in pm; if maintenance dose = 80 mg/day, administer as 40 mg twice daily (not to exceed 80 mg/day).

Renal Impairment 
PO (Adults): End-stage renal disease– 20 mg once daily initially; titrate based on IGF-1 levels obtained every 2 wk by 20 mg/day. If maintenance dose = 40 mg/day, administer as 20 mg twice daily; if maintenance dose = 60 mg/day, administer as 40 mg in am and 20 mg in pm; if maintenance dose = 80 mg/day, administer as 40 mg twice daily (not to exceed 80 mg/day).

Diarrhea Associated With Chemotherapy (off-label)

Subcut IV (Adults): 100–150 mcg subcut every 8 hr; may ↑ to 500–1500 mcg subcut or IV every 8 hr for severe diarrhea.

Subcut (Children): 1–10 mcg/kg every 8–12 hr.

Diarrhea Associated With Graft-Versus-Host Disease (off-label)

IV (Adults): 500 mcg every 8 hr; do not continue for longer than 7 days (discontinue within 24 hr of diarrhea resolution).

Subcut (Children): 1–10 mcg/kg every 8–12 hr.

Gastroesophageal Variceal Hemorrhage (off-label)

IV (Adults): 25–100 mcg bolus (may repeat in 1st hr if hemorrhage uncontrolled), followed by continuous infusion of 25–50 mcg/hr for 2–5 days.

IV (Children): 1–2 mcg/kg bolus, followed by continuous infusion of 1–2 mcg/kg/hr; taper dose by 50% every 12 hr when no active bleeding for 24 hr; discontinue when dose is 25% of initial dose.

Availability (generic available)

Delayed release capsules: 20 mg

Solution for injection: 50 mcg/mL, 100 mcg/mL, 200 mcg/mL, 500 mcg/mL, 1000 mcg/mL, 2500 mcg/mL (prefilled pen)

Suspension for injection (depot): 10 mg/6 mL, 20 mg/6 mL, 30 mg/6 mL

Assessment

• Assess frequency and consistency of stools and bowel sounds throughout therapy.

• Monitor pulse and BP prior to and periodically during therapy.
• Assess patient's fluid and electrolyte balance and skin turgor for dehydration.
• Monitor diabetic patients for signs of hypoglycemia. May require reduction in requirements for insulin and sulfonylureas and treatment with diazoxide.
• Assess for gallbladder disease; assess for pain and monitor ultrasound examinations of gallbladder and bile ducts prior to and periodically during prolonged therapy.

Lab Test Considerations:

Monitor growth hormone, IGF-1 in patients with acromegaly, 5-HIAA (urinary 5-hydroxyindoleacetic acid), plasma serotonin, and plasma substance P in patients with carcinoid tumors; plasma vasoactive intestinal peptide (VIP) in patients with VIPoma; and free T₄  and serum glucose concentrations prior to and periodically during therapy in all patients taking octreotide. Measure IGF-1 every two wks after starting  Bynfezia Pen  or with dose change.

• Monitor quantitative 72-hr fecal fat and serum carotene determinations periodically for possible drug-induced aggravations of fat malabsorption.
• May cause a slight ↑ in liver enzymes.
• Monitor thyroid function before starting  Bynfezia Pen. May cause ↓ serum thyroxine (T₄ ) concentrations.
• Monitor glycemic control for all patients with diabetes and adjust antidiabetic treatment as necessary for hyperglycemia and hypoglycemia.
• Monitor vitamin B₁₂  levels during therapy with  Bynfezia Pen.

Implementation

• Do not confuse Sandostatin (octreotide) with Sandimmune (cyclosporine).

• PO Administer with water on an empty stomach, at least 1 hr before a meal or at least 2 hr after a meal.  DNC: Swallow capsules whole; do not open, crush or chew. 
• Solution is clear and colorless; do not use solution that is cloudy, discolored, or contains particulate matter. Ampules should be refrigerated but may be stored at room temperature for the days they will be used. Discard unused solution.
• Subcut Administer the smallest volume needed to achieve required dose to prevent pain at injection site. Rotate injection sites; avoid multiple injections in same site within short periods of time. Preferred injection sites are the hip, thigh, or abdomen.
  • Administer injections between meals and at bedtime to avoid GI side effects.
  • Allow medication to reach room temperature prior to injection to minimize local reactions at injection site. Rotate injection sites at least 2 in. away from last injection site.
  • Withdraw  Bynfezia Pen  yearly for about 4 wk from patients who have received irradiation to assess disease activity. If growth hormone or IGF-1 levels increase and signs and symptoms recur, may resume  Bynfezia Pen  at the dose used at the time of  Bynfezia Pen  discontinuation.
• IM 

  Mix IM solution by adding diluent included in kit. Administer immediately after mixing into the gluteal muscle. Avoid using deltoid site due to pain of injection.

  • Patients with carcinoid tumors and VIPomas should continue to receive subcut dose for 2 wk following switch to IM depot form to maintain therapeutic level.

Patient/Family Teaching

• Explain purpose of octreotide to patient.
• May cause dizziness, drowsiness, or visual disturbances. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to change positions slowly to minimize orthostatic hypotension.
• Advise patient to notify health care professional if signs and symptoms of gallstones, hyperglycemia, hypoglycemia, thyroid function abnormalities, or irregular heartbeat.
• Rep:  Inform females of reproductive potential that therapy with octreotide may result in improved fertility. Caution patient to use contraception to prevent unintended pregnancy. Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
• Home Care Issues:

  Instruct patient administering octreotide at home on correct technique for injection, storage, and disposal of equipment. Advise patient to read  Instructions for Use  before starting therapy and with each Rx refill in case of changes.

  • Instruct patient to administer octreotide exactly as directed. If a dose is missed, administer as soon as possible, then return to regular schedule. Do not double doses.

Evaluation/Desired Outcomes

• Decrease in severity of diarrhea and improvement of electrolyte imbalances in patients with carcinoid or VIP-secreting tumors.
• Relief of symptoms and suppressed tumor growth in patients with pituitary tumors associated with acromegaly.
• Management of diarrhea in patients with AIDS.
• Growth hormone levels <5 ng/mL or IGF-I levels within normal reference ranges for age and sex in patients treated for acromegaly.