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The Contents

• Historical background.

• Actions & therapeutic uses.

• Side effects.

• Contraindication & precautions.

• Routes & Doses.

• Pharmacokinetics.

Historical Background

• In early 1979, a chemist called Dr.Wilfried Bauer synthesized a compound with the research number SMS 201-995. The molecule was given the generic name octreotide, reflecting its structure with eight amino acids .

• Subcutaneous Somatostatin was launched in 1988, and in 1991 it received the Prix Gallen.

• The long-acting formulation, was launched in 1997. This provides patients with a more convenient treatment option via a single injection every 4 weeks.

Actions

• Anterior pituitary

GH

TSH

• Gastrointestinal systemGastrointestinal system• Somatostatin suppresses the release of

gastrointestinal hormones: • Gastrin • Cholecystokinin (CCK) • Secretin • Motilin • Vasoactive intestinal peptide (VIP) • Gastric inhibitory polypeptide (GIP)

• Lowers the rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine.

• Suppresses the release of pancreatic hormones • Inhibits the release of insulin• Inhibits the release of glucagon

• Suppresses the exocrine secretory action of pancreas.

Therapeutic Uses

• Acromegaly.

• Tumors causing diarrhea like metastatic carcinoid & VIPomas.

• Other causes of secretory diarrhea.

• Decrease the GI secretions.

• Insulinoma & correction of hypoglycemic drugs overdosage.

• Varices associated with liver cirrhosis.

Side Effects

• >16%:>16%:

• Endocrine & metabolic: Hyperglycemia .

•  Gastrointestinal: Diarrhea (36% to 58%), abdominal discomfort (5% to 61%), flatulence (<10% to 38%), constipation (9% to 21%), nausea (5% to 61%), cholelithiasis (27%; length of therapy dependent), biliary duct dilatation (12%),loose stools (5% to 61%), vomiting (4% to 21%)

• nervous system: Fatigue (1% to 20%), malaise (16% to 20%), dizziness (5% to 20%), headache (6% to 20%), fever (16% to 20%)

• Cardiovascular: Sinus bradycardia (19% to 25%), chest pain (16% to 20%)

•  Hematologic: Antibodies to octreotide (up to 25%) • Local: Injection pain (2% to 50%; dose and formulation

related) 

• Neuromuscular & skeletal: Backache (1% to 20%), arthropathy (16% to 20%) 

• Respiratory: Dyspnea (16% to 20%), upper respiratory infection (16% to 20%)

•  Miscellaneous: Flu symptoms (1% to 20%)

• 5% to 15%: 5% to 15%: •   Endocrine & metabolic: Hypothyroidism (2% to 12%),

goiter (2% to 8%) 

• Gastrointestinal: Abdominal pain, anorexia, cramping, dehydration, hemorrhoids, tenesmus (4% to 6%), dyspepsia (4% to 15%), steatorrhea (4% to 6%), feces discoloration (4% to 6%), weight loss

 • Cardiovascular: Conduction abnormalities (9% to 10%),

arrhythmia (3% to 9%), hypertension, palpitation, peripheral edema 

• Central nervous system: Anxiety, confusion, depression, hypoesthesia, insomnia

•  Dermatologic: Pruritus, rash

• Genitourinary: UTI, renal calculus •  • Hematologic: Anemia

 • Hepatic: Hepatitis

•  Neuromuscular & skeletal: Arthralgia, leg cramps, myalgia, paresthesia, rigors, weakness

•  Otic: Earache, otitis media  

•  Respiratory: Coughing, pharyngitis, rhinitis, sinusitis

•  Miscellaneous: Allergy, diaphoresis

• 1% to 4%: 1% to 4%:

• Endocrine & metabolic: Hypoglycemia (2% to 4%), hypokalemia, hypoproteinemia, gout, cachexia, menstrual irregularities, breast pain, impotence

•  Gastrointestinal: Colitis, diverticulitis, dysphagia, gastritis, gastroenteritis, gingivitis, glossitis, melena, stomatitis, taste perversion.

• Cardiovascular: Angina, cardiac failure, cerebral vascular disorder, edema, flushing, hematoma, phlebitis, tachycardia 

• Central nervous system: Abnormal gait, amnesia, dysphonia, hallucinations, nervousness, neuralgia, neuropathy, somnolence, tremor, vertigo 

• Dermatologic: Acne, alopecia, bruising, cellulitis.

•   Genitourinary: Incontinence 

• Hematologic: Epistaxis•   Hepatic: Ascites, jaundice•   Local: Injection hematoma•  Skeletal: Hyperkinesia, hypertonia•   Ocular: Blurred vision, visual disturbance•   Otic: Tinnitus•   Renal: Albuminuria, renal abscess•   Respiratory: Bronchitis, pleural effusion,

pneumonia, pulmonary embolism

Contraindication & Precautions

• CONTRAINDICATION: Hypersensitivity to octreotide or any component.

• PRECAUTIONS — Patients must be monitored closely for biliary tract abnormalities, hypothyroidism, and glucose tolerance.

• use with caution in patients with renal impairment and consider dosage modification in patients with severe renal failure requiring dialysis.

• Chronic usage is associated with depressed vitamin B12 levels so we monitor it’s levels in patients receiving long-term therapy.

• Monitor growth hormone in long-term therapy.• Pregnancy: class B

Doses• Dosage should be individualized

according to the patient's response • Secretory diarrhea : I.V., SubQ: Doses of

1-10 mcg/kg every 12 hours have been used in children beginning at the low end of the range and increasing by 0.3 mcg/kg/dose at 3-day intervals. Suppression of growth hormone is of concern when used as long-term therapy.

• Congenital hyperinsulinism: SubQ: Doses of 3-40 mcg/kg/day have been used.

• Acromegaly:  SubQ, I.V.: Initial: 50 mcg 3 times/day; titrate to achieve growth hormone levels <5 ng/mL or IGF-I (somatomedin C) levels <1.9 units/mL in males and <2.2 units/mL in females. Usual effective dose 100 mcg 3 times/day. Range 300-1500 mcg/day.

• Note: Should be withdrawn yearly for a 4 week interval (8 weeks for depot injection) in patients who have received irradiation. Resume if levels increase and signs/symptoms recur.

•   Continuous I.V. infusion rates have ranged from 25-50 mcg/hour for the treatment of esophageal variceal bleeding.

Pharmacokinetics

• After subcutaneous injection, octreotide is absorbed rapidly and completely from the injection site. Peak concentrations of 5.2 ng/mL (100 mcg dose) were reached 0.4 hours after dosing.

• Using a specific radioimmunoassay, intravenous and subcutaneous doses were found to be bioequivalent.

• The elimination of octreotide from plasma had an apparent half-life of 1.7 to 1.9 hours compared with 1-3 minutes with the natural hormone.

• Metabolism: Extensive by the liver

• Elimination: 32% excreted unchanged in urine