Octreotide

Contraindications

Hypersensitivity

Cautions

Hepatic or renal impairment may necessitate dosing adjustments

May alter fat absorption in some patients (monitor for pancreatitis)

May decrease vitamin B12 levels (monitor)

Monitor for hypothyroidism (octreotide suppresses secretion of TSH)

Use caution when giving drug to patients with cardiovascular disease

May enhance toxicity of QTc-prolonging agents

Do not use depot formulation in patients with sulfonylurea-induced hypoglycemia

Dosage adjustments may be necessary in the elderly

Females of childbearing age should use adequate contraception because the treatment may restore fertility

Octreotide is a prescription medication used to treat the symptoms of acromegaly, carcinoid tumors, and vasoactive intestinal peptide adenomas. Octreotide belongs to a class of drugs called octapeptides, which work by decreasing the amounts of certain natural substances. These substances may be made in excessive amounts by the body because of certain conditions like tumors.

Octreotide is available in an injectable form to be given directly into a vein (IV) by a healthcare professional. It is also available in an injectable form to be given directly under the skin (subcutaneously) that may be done by the patient after proper training.

A long-acting form of octreotide is available in an injectable form to be given directly into a muscle (IM) by a healthcare professional.

Octreotide immediate-release injection is usually injected 2 to 4 times a day. Octreotide long-acting injection is usually injected once every 4 weeks.

Common side effects of octreotide include bile duct abnormalities, fatigue, headache, and abdominal pain. Octreotide can cause dizziness. Do not drive or operate heavy machinery until you know how octreotide affects you.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known whether octreotide passes into human milk. Because many drugs can pass into human milk, caution should be used when octreotide is given to a nursing woman.

Octreotide

• Store at refrigerated temperatures 2ºC-8ºC (36ºF-46ºF) and store in outer carton in order to protect from light.
• At room temperature, (20ºC-30ºC or 70ºF-86ºF), octreotide is stable for 14 days if protected from light.
• The solution can be allowed to come to room temperature before injection.
• Do not warm artificially (i.e. microwave, stove, oven).
• After initial use, multiple-dose vials should be discarded within 14 days.
• Ampuls should be opened just prior to administration and the unused portion discarded.
• Dispose unused product or waste properly.
• Keep this and all medications out of the reach of children.

Long-acting Octreotide

• Store at refrigerated temperatures between 2°C-8°C (36°F-46°F) and protect from light until the time of use.
• The product kit should remain at room temperature for 30-60 minutes before preparing the drug suspension.
• After preparation, the drug suspension must be given immediately.
• Keep this and all medications out of the reach of children.

Gallbladder Abnormalities

Gallbladder abnormalities, especially stones and/or biliary sludge, frequently develop in patients on chronic Octreotide acetate therapy (see WARNINGS).

Cardiac

In acromegalics, sinus bradycardia (< 50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias developed in 9% of patients during Octreotide acetate therapy (see PRECAUTIONS, General).

Gastrointestinal

Diarrhea, loose stools, nausea and abdominal discomfort were each seen in 34% to 61% of acromegalic patients in U.S. studies although only 2.6% of the patients discontinued therapy due to these symptoms. These symptoms were seen in 5% to 10% of patients with other disorders.

The frequency of these symptoms was not dose-related, but diarrhea and abdominal discomfort generally resolved more quickly in patients treated with 300 mcg/day than in those treated with 750 mcg/day. Vomiting, flatulence, abnormal stools, abdominal distention, and constipation were each seen in less than 10% of patients.

In rare instances, gastrointestinal side effects may resemble acute intestinal obstruction, with progressive abdominal distention, severe epigastric pain, abdominal tenderness and guarding.

Hypo/Hyperglycemia

Hypoglycemia and hyperglycemia occurred in 3% and 16% of acromegalic patients, respectively, but only in about 1.5% of other patients. Symptoms of hypoglycemia were noted in approximately 2% of patients.

Hypothyroidism

In acromegalics, biochemical hypothyroidism alone occurred in 12% while goiter occurred in 6% during Octreotide acetate therapy (see PRECAUTIONS, General). In patients without acromegaly, hypothyroidism has only been reported in several isolated patients and goiter has not been reported.

Other Adverse Events

Pain on injection was reported in 7.7%, headache in 6% and dizziness in 5%. Pancreatitis was also observed (see WARNINGS and PRECAUTIONS).

Other Adverse Events 1% to 4%

Other events (relationship to drug not established), each observed in 1% to 4% of patients, included fatigue, weakness, pruritus, joint pain, backache, urinary tract infection, cold symptoms, flu symptoms, injection site hematoma, bruise, edema, flushing, blurred vision, pollakiuria, fat malabsorption, hair loss, visual disturbance and depression.

Other Adverse Events < 1%

Events reported in less than 1% of patients and for which relationship to drug is not established are listed: Gastrointestinal: hepatitis, jaundice, increase in liver enzymes, GI bleeding, hemorrhoids, appendicitis, gastric/peptic ulcer, gallbladder polyp; Integumentary: rash, cellulitis, petechiae, urticaria, basal cell carcinoma; Musculoskeletal: arthritis, joint effusion, muscle pain, Raynaud's phenomenon; Cardiovascular: chest pain, shortness of breath, thrombophlebitis, ischemia, congestive heart failure, hypertension, hypertensive reaction, palpitations, orthostatic BP decrease, tachycardia; CNS: anxiety, libido decrease, syncope, tremor, seizure, vertigo, Bell's Palsy, paranoia, pituitary apoplexy, increased intraocular pressure, amnesia, hearing loss, neuritis; Respiratory: pneumonia, pulmonary nodule, status asthmaticus; Endocrine: galactorrhea, hypoadrenalism, diabetes insipidus, gynecomastia, amenorrhea, polymenorrhea, oligomenorrhea, vaginitis; Urogenital: nephrolithiasis, hematuria; Hematologic: anemia, iron deficiency, epistaxis; Miscellaneous: otitis, allergic reaction, increased CK, weight loss.

Evaluation of 20 patients treated for at least 6 months has failed to demonstrate titers of antibodies exceeding background levels. However, antibody titers to Octreotide acetate were subsequently reported in three patients and resulted in prolonged duration of drug action in two patients. Anaphylactoid reactions, including anaphylactic shock, have been reported in several patients receiving Octreotide acetate.

Postmarketing Experience

The following adverse reactions have been identified during the postapproval use of Octreotide acetate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal: intestinal obstruction

Hematologic: thrombocytopenia

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• SandoSTATIN
• SandoSTATIN LAR Depot

• Antidiarrheal
• Antidote
• Somatostatin Analog

Mimics natural somatostatin by inhibiting serotonin release, and the secretion of gastrin, VIP, insulin, glucagon, secretin, motilin, and pancreatic polypeptide. Decreases growth hormone and IGF-1 in acromegaly. Octreotide provides more potent inhibition of growth hormone, glucagon, and insulin as compared to endogenous somatostatin. Also suppresses LH response to GnRH, secretion of thyroid-stimulating hormone and decreases splanchnic blood flow.

Absorption

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

Distribution

Vd: 14 L (21.6 ± 8.5 L in acromegaly)

Metabolism

Extensively hepatic

Excretion

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

Time to Peak

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

Regular injection (solution):

Mild to severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling.

Severe impairment requiring dialysis: There are no specific dosage adjustments provided in the manufacturer’s labeling; however, a dosage adjustment may be needed since clearance is reduced by ~50%.

Depot injection:

Mild to severe impairment: No initial dosage adjustment necessary.

Severe impairment requiring dialysis: Initial dose: 10 mg IM every 4 weeks; titrate based upon response (clearance is reduced by ~50%)

Concerns related to adverse effects:

• Abnormal Schillings test: Chronic treatment has been associated with abnormal Schillings test; monitor vitamin B12 levels.

• Cholelithiasis: May impair gallbladder function (inhibits gallbladder contractility and decreases bile secretion); monitor patients for cholelithiasis. The incidence of gallbladder stone or biliary sludge increases with a duration of therapy of ≥12 months. Prophylactic cholecystectomy is recommended in patients with gastrointestinal or pancreatic neuroendocrine tumors undergoing abdominal surgery if octreotide treatment is planned (Oberg 2004).

• Glucose regulation: Somatostatin analogs may affect glucose regulation. In type I diabetes, severe hypoglycemia may occur; in type II diabetes or patients without diabetes, hyperglycemia may occur. Insulin and other hypoglycemic medication requirements may change. Octreotide may worsen hypoglycemia in patients with insulinomas; use with caution.

• Local reactions: Mild to moderate injection-site pain (usually lasting 1 hour) may occur with the depot formulation.

• Hypothyroidism: Suppresses secretion of TSH; monitor for hypothyroidism.

• Pancreatitis: May alter absorption of dietary fats; monitor for pancreatitis.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with heart failure or concomitant medications that alter heart rate or rhythm; bradycardia, conduction abnormalities, and arrhythmia have been observed in acromegalic and carcinoid syndrome patients. Cardiovascular medication requirements may change.

• Excessive fluid loss: May reduce excessive fluid loss in patients with conditions that cause such a loss; periodic monitoring for elevations in zinc levels is recommended in such patients that are maintained on total parenteral nutrition (TPN).

• Hepatic impairment: Use caution in patients with hepatic impairment; dosage adjustment may be required in patients with established cirrhosis.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be required in patients receiving dialysis.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• QTc-prolonging agents: Octreotide may enhance the adverse/toxic effects of other QTc-prolonging agents.

Dosage form specific issues:

• Depot formulation: Do not use depot formulation for the treatment of sulfonylurea-induced hypoglycemia (Dougherty 2010).

• Vehicle used in depot injection (polylactide-co-glycolide microspheres): Has rarely been associated with retinal artery occlusion in patients with abnormal arteriovenous anastomosis (eg, patent foramen ovale).

Special populations:

• Elderly: Dosage adjustment may be necessary; significant increases in elimination half-life have been observed in older adults.

• Females: Therapy may restore fertility; females of childbearing potential should use adequate contraception.

• Pediatric: Postmarketing cases of serious and fatal events, including hypoxia and necrotizing enterocolitis, have been reported with octreotide use in children (usually with serious underlying conditions), particularly in children <2 years of age. In studies with octreotide depot, the incidence of cholelithiasis in children is higher than the reported incidences for adults and efficacy was not demonstrated.

Other warnings/precautions:

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