Medically reviewed by Drugs. Last updated on Dec 30, Initial dose: to mcg per day, IV or subcutaneously, in 2 to 4 divided doses Comments : -The median daily dose was mcg; mean daily dose was mcg. Long-Acting depot formulation Establish tolerability with short acting product for at least 2 weeks before using this formulation : Initial dose: 20 mg, IM intragluteally , at 4 week intervals, for 2 months; continue with dose of regular octreotide for at least 2 weeks at same dose patient was on before the switch After 2 months : -If symptoms are controlled, consider reducing dose to 10 mg every 4 weeks -If symptoms are not adequately controlled, increase to 30 mg every 4 weeks Maximum dose: 30 mg every 4 weeks Comments : -Failure to continue dosing of regular octreotide during a switch to the long acting formulation may exacerbate symptoms; some patients require 3 to 4 weeks of concomitant dosing. Use: Symptomatic treatment of patients with metastatic carcinoid tumors where it suppresses or inhibits the severe diarrhea and flushing episodes associated with the disease. Initial dose: to mcg per day, IV or subcutaneously, in 2 to 4 divided doses Maintenance dose: to mcg per day -Doses above mcg per day are not usually required.
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We report our experience with the use of octreotide as primary or adjunctive therapy in children with various gastrointestinal disorders. A pharmacy database identified patients who received octreotide for gastrointestinal diseases. Indications for octreotide use, dosing, effectiveness, and adverse events were evaluated by chart review. A total of 21 patients 12 males , aged 1 month to 13 years, were evaluated. The child with dumping syndrome responded to octreotide in a week.
Adverse events developed in 4 patients: Q-T interval prolongation and ventricular fibrillation, hyperglycemia, growth hormone deficiency, and hypertension. Octreotide provides a valuable addition to the therapeutic armamentum of the pediatric gastroenterologist for a wide variety of disorders. Serious adverse events may occur and patients must be closely monitored. Octreotide is a synthetic peptide analog of somatostatin with the same pharmacologic effects. Its primary advantages over somatostatin are a longer half-life in the circulation, a higher potency, and good bioavailability after subcutaneous administration.
Consequently, octreotide has largely supplanted somatostatin as a therapeutic agent for several diseases. The effects of somatostatin and octreotide occur as a result of binding to G protein receptors found throughout the body, including the gastrointestinal tract, pancreas, and the central nervous system.
The experience with octreotide for the treatment of gastrointestinal disorders in children is limited, with the vast majority of data in the form of case reports, small case series, or reviews of these reports. A pharmacy database was used to identify all patients up to 18 years of age, who received octreotide Novartis Pharmaceutical, Montreal, Canada at the Alberta Children's Hospital in Calgary, from January to December Patients who received octreotide as primary or adjunctive therapy for gastrointestinal disorders were included.
Exclusion criterion was the use of octreotide as a primary therapy for nongastrointestinal endocrine disorders. A retrospective review of medical records was performed and demographic data were collected. These included age, weight, gender, and underlying medical condition necessitating octreotide use.
Octreotide dosing, duration of use, mode of administration intermittent or continuous , route of administration intravenous IV or subcutaneous SC and adverse effects attributed to octreotide were also recorded.
The effectiveness of octreotide was evaluated by the assessment of certain measurable variables based on the indication for its use. In patients with gastrointestinal bleeding, packed red blood cell requirement during the h period before and h period following administration of octreotide was obtained. Cessation of bleeding was defined as the absence of bleeding for 48 h after the administration of octreotide with stabilization of vital signs and hemoglobin.
Failure of therapy was defined as the persistence of bleeding during octreotide therapy. In patients with pancreatic disorders, data were collected based on imaging ultrasound or computed tomography of abdomen measurements of pseudocyst size, abdominal drain of pancreatic ascites, or serum lipase levels before and during octreotide administration.
For patients with chronic diarrhea, the amount of stool output and total fluid intake were obtained before and during octreotide therapy. In cases of chylothorax, data were collected about chest drain output before and during octreotide administration. For the patient with dumping syndrome, symptomatic response to octreotide therapy was evaluated.
Blood requirements before and during octreotide therapy were compared by paired t -test. The study was approved by the institutional review board. Octreotide was administered to 26 patients. Five of 26 patients were excluded: 3 patients with hyperinsulinemic hypoglycemia and 2 with acromegaly. Clinical and therapeutic characteristics of patients with gastrointestinal disorders on octreotide therapy.
The mean hemoglobin drop at presentation was 3. The mean of the initial octreotide bolus administered was 2. Octreotide infusion rate was tapered by half for 24 h and was stopped when there was no active bleeding. Patient 1 underwent a negative upper endoscopy and colonoscopy.
Meckel's scan was positive and a Meckel's diverticulum was resected. Nonsteroidal anti-inflammatory drug use for joint pains in patient 2 raises the possibility of proximal small intestinal ulceration or erosion in view of negative upper endoscopy. This child with chronic renal failure did not respond to IV proton pump inhibitor and died 48 h after admission due to cardiac arrhythmia, hyperkalemia, and pulmonary edema. Patient 9 had endstage liver disease secondary to prolonged total parenteral nutrition TPN use for short gut, with severe coagulopathy unresponsive to vitamin K injections or fresh frozen plasma and bled persistently despite continuous octreotide infusion for 14 days.
The family preferred palliative management rather than the option of combined liver and bowel transplantation. Six months after the first gastrointestinal bleed, patient 6 experienced recurrent bleeding esophageal varices with no response to octreotide, and needed emergent portacaval shunt with no recurrence of bleeding.
Initially patient 7 with aplastic anemia developed a massive gastrointestinal bleed with oozing from the small intestine that was not controlled with blood products. Octreotide therapy was instituted as outlined in Table 1 and bleeding ceased in 24 h. Therapy was discontinued at 72 h. He developed signs of typhlitis, underwent a right hemicolectomy and had no recurrence of gastrointestinal bleeding. The resected specimen demonstrated extensive cecal necrosis and ulceration.
Patient 8 had recurrence of esophageal variceal bleed on two occasions, one month apart. Injection of gastric varix with cyanoacrylate was performed on day 7 of octreotide therapy and octreotide was successfully weaned. Patients 4, 5, 6, and 8 had sclerotherapy of esophageal varices on day 1 of octreotide. The diarrhea resolved 3 days after initiation of octreotide therapy.
Patient 15 had endoscopic transgastric drainage of infected pseudocyst on day 1 of octreotide therapy. Culture of cyst fluid grew pseudomonas organisms treated by IV antibiotics. Patient 13, a child with traumatic pancreatitis and ascites, developed severe abdominal pain unresponsive to pain control, bowel rest, and TPN. Pain and ascites resolved within 5 days of octreotide therapy. Patients 16, 17, and 18 [ Table 1 ] each developed a chylothorax that required placement of a chest tube within 2—3 weeks after cardiac surgery.
The resolution of chylothorax was confirmed on chest X-ray. Figure 2 demonstrates the dramatic reduction in chest tube drainage after administration of octreotide in each child. Weight was maintained along the 20 th centile.
Patient 21 [ Table 1 ] presented with symptoms suggestive of dumping syndrome that developed 2 months postfundoplication for gastroesophageal reflux disease. Bolus feeding caused a rise of serum glucose from 5. The glucose reduction was associated with onset of lethargy, sweating, and diarrhea. Failure to respond to a continuous feeding led to a trial of octreotide, with alleviation of the symptoms within a week.
Side effects of octreotide developed in 4 of 21 patients. Patient 7 suffered bradycardia that progressed into ventricular fibrillation, and was successfully resuscitated. Electrocardiography demonstrated prolonged corrected Q—T interval Q—Tc of 0. Echocardiogram and serum electrolytes were normal. Repeated electrocardiography, weeks and months after discontinuation of octreotide therapy, persistently showed borderline Q—Tc intervals of 0. Apart from octreotide, there was no obvious predisposing factor to explain the occurrence of the arrhythmia.
The insulin was discontinued with no recurrence of hyperglycemia. Hormonal analysis at the time of hypoglycemia revealed an abnormally low response of serum growth hormone of 1. Provocative growth hormone testing using IV arginine revealed an abnormally low serum growth hormone of 1. Hypertension requiring medical therapy developed in patient 21, 3 weeks after initiation of octreotide therapy.
Extensive workup for organic causes of hypertension was negative. Hypertension was resolved 2 weeks after discontinuation of octreotide therapy. Octreotide alters multiple aspects of gastrointestinal physiology and is a valuable therapeutic addition in the treatment of a variety of gastrointestinal disorders. In adults, octreotide therapy worked in the management of variceal hemorrhage, secretory diarrhea and profound excessive ileostomy losses, gastroenteropancreatic tumors, dumping syndrome, pancreatic and enterocutaneous fistulas, and pancreatitis.
Octreotide significantly reduced the amount of blood transfusions in children with severe gastrointestinal bleeding and hemodynamic instability. Because of its potential to reduce portal blood flow, hepatic venous pressure gradient and azygos blood flow,[ 12 , 13 ] the effectiveness of octreotide in controlling upper gastrointestinal bleed in adults has been largely reported in cases of variceal hemorrhage secondary to portal hypertension.
No data indicate that a higher dose or longer duration is more effective and free of adverse effects. Higher octreotide dose in patient 7 and longer duration of therapy in patient 10 were associated with major adverse effects. While the role of octreotide in the treatment of nonvariceal gastrointestinal mucosal lesions is not well established, it has been successfully used to treat severe nonvariceal bleeding in adults and children.
Octreotide failed to control massive bleeding in a child with a Meckel's diverticulum, Non-steroidal anti-inflammatory drug induced bleeding in chronic renal failure or in a child with hepatic failure induced coagulopathy.
The available data from randomized controlled trials in adults, about the efficacy of octreotide in controlling bleeding peptic ulcers are controversial. It is not a substitute for definitive therapy in these situations.
Historically, pediatric pancreatic pseudocysts have been treated with operative or percutaneous drainage procedures, and occasionally with conservative management. Similar results have been obtained in 4 pediatric case reports. Octreotide inhibited pancreatic secretions and allowed healing of pancreatic duct with the resolution of ascites in 2 of our patients and in a case report.
Octreotide was used to relieve severe pain associated with chronic pancreatitis perhaps by decreasing intraductal pressure caused by pancreatic secretions. So although there may be benefit in administering octreotide in cases of severe pancreatitis, the substantial number of studies in which no benefit could be demonstrated should also be noted.
Diverse therapeutic methods were used and this may be one of the main reasons for the inconsistency of the results. Somatostatin inhibits pancreatic secretion in a dose-dependent way. Other pediatric case reports support this observation. Low doses may be not sufficient, yet high doses decrease splanchnic blood flow and pancreatic perfusion, which could be associated with aggravation of pancreatitis.
However, IV route may be advantageous for acutely ill patients with hypovolemia and circulatory failure when SC absorption of drugs is suboptimal. For the management of complications of pancreatitis, an initial SC dose of 7. Chylothorax may have deleterious effects on the immunologic and nutritional status of patients. Standard management of chylothorax includes medium chain triglyceride-based feeds, bowel rest with TPN, and surgical intervention, in the form of thoracic duct ligation, pleurodesis or placement of pleuroperitoneal shunt, if medical treatment fails.
The mechanism of action of octreotide is not understood.
Therapeutic Applications of Octreotide in Pediatric Patients
We report our experience with the use of octreotide as primary or adjunctive therapy in children with various gastrointestinal disorders. A pharmacy database identified patients who received octreotide for gastrointestinal diseases. Indications for octreotide use, dosing, effectiveness, and adverse events were evaluated by chart review. A total of 21 patients 12 males , aged 1 month to 13 years, were evaluated. The child with dumping syndrome responded to octreotide in a week. Adverse events developed in 4 patients: Q-T interval prolongation and ventricular fibrillation, hyperglycemia, growth hormone deficiency, and hypertension. Octreotide provides a valuable addition to the therapeutic armamentum of the pediatric gastroenterologist for a wide variety of disorders.