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Indications:
•Metastatic carcinoid tumors
•Vasoactive intestinal peptide-secreting tumors (VIPomas)
•Acromegaly
•Post high risk pancreatic surgery
•Emergency management of bleeding esophageal varices
•Severe secretory diarrhea in AIDS patients
•UROD (Ultrarapid Opiate Detoxification) in anesthesia
Usual Dose:
Octostatin® (octreotide acetate) maybe administered subcutaneously or intravenously. Subcutaneous injection is the usual route of administration of Octostatin® for control of symptoms. Pain with subcutaneous administration may be reduced by using the smallest volume that will deliver the desired dose. Octostatin® is stable in sterile isotonic saline solutions or sterile solutions of dextrose 5% in water for 24 hours.In emergency situations (e.g.: carcinoid crisis) it may be given by rapid bolus.The initial dosage is usually 50 mcg administered twice or three times daily.
Acromegaly
Dosage may be initiated at 50 mcg Octostatin® (octreotide acetate) t.i.d. Beginning with this low dose may permit adaptation to adverse gastrointestinal effects for patients who will require higher doses. The dose most commonly found to be effective is 100 mcg Octostatin® (octreotide acetate) t.i.d., but some patients require up to 500 mcg t.i.d. for maximum effectiveness.
Metastatic carcinoid Tumors
The suggested daily dosage of octreotide acetate during the first 2 weeks of therapy ranges from 100–600 mcg/day Octostatin® (octreotide acetate) in 2–4 divided doses (mean daily dosage is 300 mcg).
VIPomas
Daily dosages of 200–300 mcg Octostatin® (octreotide acetate) in 2–4 divided doses are recommended during the initial 2 weeks of therapy (range 150–750 mcg) to control symptoms of the disease.
Emergency management of bleeding esophageal varices
To control bleeding, a loading dose of 25 mcg Octostatin® (octreotide acetate) was given, followed by an infusion of 50 mcg/hr.Treatment continued through the fifth hospital day following the initial bleeding episode. Definitive endoscopic therapy usually is performed shortly after hemostasis is achieved.
Post high risk pancreatic surgery
For prophylaxis of complications,Octostatin® (octreotide acetate) administered 100 mcg three times daily and maintained for seven days, it administered one hour before surgery by subcutaneous injection.
Severe secretory diarrhea in AIDS patients
100 mcg Octostatin® (octreotide acetate) subcutaneous injection, 3 times a day; can be titrated up to as high as 750 mcg Octostatin® (octreotide acetate) daily.
UROD ( Ultrarapid Opiate Detoxification ) in anesthesia
Anesthesia is maintained with propofol, methohexital, or inhalational agents. UROD has been modified resulting in a safe and an effective general anesthetic that results in hemodynamically stable withdrawal without manifestation of central nervous system hyperarousal. Residual withdrawal signs and symptoms may include opioid craving,sympathetic hyperactivity, muscle pain, bone pain, nausea, vomiting, diarrhea, and insomnia.Octreotide is used to control postdetoxification diarrhea.
100 mcg Octostatin® (octreotide acetate) Intravenous infusion before induction of anesthesia.
Pediatric use: Experience with octreotide acetate in the pediatric population is limited.
Mechanism Of Action:
Octreotide is a synthetic octapeptide analog of somatostatin, with similar effects, but a prolonged duration of action. Its major effects include inhibition of the release of pituitary growth hormone. Octreotide also suppresses the secretion of serotonin and the endocrine secretions of the pancreas, stomach, and intestine (including gastrin, vasoactive intestinal peptide, insulin, glucagon, secretin, motilin, and pancreatic polypeptide and TRH stimulated release of TSH).
Octreotide also has a direct antiproliferative action in non-clinical models, probably by blocking the action of epidermal growth factor (EGF). The inhibition of gut hormones by octreotide acts to slow gastrointestinal transit time and to regulate water and electrolyte transport across the gut (watery diarrhea).This likely explains the symptomatic benefit derived from this drug in patients with carcinoid tumors and VIPomas (vasoactive intestinal peptide-secreting tumors). Octreotide also decreases splanchnic blood flow ande suppresses LH response to GnRH.
Pharmacokinetics:
After subcutaneous injection, Octostatin® (octreotide acetate) is absorbed rapidly and completely from the injection site. Intravenous and subcutaneous doses were found to be bioequivalent. In blood, the distribution into the erythrocytes was found to be negligible and about 65% was bound in the plasma in a concentrationindependent manner. Binding was mainly to lipoprotein and, to a lesser extent, to albumin. There was no information about crossing blood brain barrier .
Metabolism : Slowly catabolized to inactive fragments, there was Inactive metabolites but no information about active metabolites.
Excretion: Mainly by kidneys, about 32% of the dose is excreted unchanged into the urine.t ½ a for subcutaneous injection is 100 min and for Intravenous injection 90 min .
Precautions and Contraindications:
Octostatin® is contraindicated in patients with hypersensitivity to octreotide or to any component of the formulation.
In insulin dependent diabetics, reduction of insulin requirements may result following initiation of octreotide therapy.
Pregnancy and breast feeding
It is not known if octreotide is carcinogenic or mutagenic. Its safe use in pregnancy or its effects on fertility have not been established. Breast feeding is not recommended due to the potential secretion into breast milk.
Adverse Reactions:
Cardiovascular: Conduction abnormality,QT prolongation,arrhythmia,bradycardia,edema,worsening cardiac failure,flushing .
Nervous system: Sleep disturbances,visual disturbances, dizziness,depression,headache,fatigue,weakness
Dermatologic: Acne,pruritus,hair loss
Endocrine: Hypothyroidism
Gastrointestinal: Nausea,vomiting,abdominal pain,steatorrhea,B12 malabsorption ,stomatitis,constipation,flatulence
Hepatobiliary: Biliary tract abnormalities (gallstones)
Injection site: Pain, redness, swelling
Other: Arthralgia,muscle cramps,flu symptoms,fever,fatigue
Drug Interactions:
•Diazoxide,Sulfonylureas,Beta blockers,Insulin MECHANISM: transient hyper-or hypoglycemia caused by octreotide.
MANAGEMENT: monitor blood sugar
•Drugs metabolized by cyp 450 (terfenadine etc) MECHANISM: somatostatin inhibits metabolism via p450 MANAGEMENT: caution
•Drugs prolonging QT (droperidol,sparfloxacin, etc) MANAGEMENT: avoid concomitant usage
•Cimetidine MANAGEMENT: caution
•Bromocriptine MANAGEMENT: caution
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