注射用生长抑素说明书(24号令格式)-英文
Instructions of Somatostatin for Injection
【Drug Name】
Generic name: Somatostatin for Injection
English name: Somatostatin for Injection
Chinese Pinyin: Zhusheyong Shengzhangyisu
Ingredient: Essential ingredient of the product is somatostatin.
Chemical name: L-alanyl-glycyl-L-cysteinyl-L-lysyl-L-asparagyl-L-phenylalanyl-L- phenylalnyl-L-tryptophyl-L-lysyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-cysteine (cyclic 3-14 disulfide)
Structural formula:
Ala-G ly-C ys-Lys-Asn-P he-P he-Trp-Lys-Thr-P he-Thr-S er-C
Molecular formula: C76H 104N 18O 19S 2
Molecular weight: 1637.88
Excipients: mannitol
【Appearance 】The product is white freeze-dried loosen blocky material.
【Indications 】
Somatostatin is indicated for:Severe acute haemorrhage from oesophageal varices;Severe acute haemorrhage from gastric or duodenal ulcers,or accompanying acute erosive or haemorrhagic gastritis; Adjuvant treatment in pancreatic, biliary and intestinal fistulae;Prophylaxis and treatment of postoperative complications following pancreatic surgery;Adjuvant treatment in diabetic ketoacidosis.
【Specifications 】(1)0.25mg (2)3.0mg (All calculated on somatostatin)
【Administration and Dosage】
Somatostatin is given intravenously,by slow bolus injection (3 to 5 minutes) of 250μg or by continuous infusion at a rate of 250μg/hour (equivalent of approximately 3.5μg/kg body weight/hour).The lyophilised powder should be reconstituted with the physiological sodium chloride solution immediately prior to use.
For continuous infusion one 3 mg somatostatin should be used to prepare a 12 hours infusion. The solution may be either saline or 5% dextrose and should be adjusted to guarantee an outflow of 250μg somatostatin / hour. The use of a perfusion syringe is recommended.
Treatment of severe acute bleeding from the upper gastro-intestinal tract, including from oesophageal varices:It is recommended to start by a slow intravenous injection of 250μg of somatostatin as loading dose, then immediately followed by an intravenous infusion at a rate of 250μg/h. In case of interruption of more than 3 to 5 minutes between two infusions, an additional slow i.v. injection of 250μg is recommended to insure a continuous treatment.Once the haemorrhage has stopped (usually in less than 12 to 24 hours), treatment should be continued for 48-72 hours in order to avoid rebleeding. Treatment up to 120 hours has been routinely performed in this indication.
Adjuvant treatment in pancreatic, biliary and intestinal fistulae:A continuous infusion of somatostatin at a rate of 250μg/h is recommended until closure of the fistula (2-20
days). This infusion should be performed in addition to total parenteral nutrition. Once the fistula has been closed, treatment should be continued for 1 to 3 days and stopped progressively in order to avoid rebound effect.
Prophylactic treatment of postoperative complications following pancreatic surgery: Somatostatin is administered at the beginning of the surgical intervention at a rate of 250μg /h and treatment is continued for 5 days.
Adjuvant treatment in diabetic ketoacidosis:In patients with ketoacidosis, infusion of 100-500μg/h of somatostatin associated with insulin therapy (bolus of 10 I.U. +infusion of 1-4.8 I.U./h)was capable of restoring euglycemia within 4 hours and resolving acidosis within 3 hours.
【Adverse Reactions】
Nausea, vertigo and flushing have been reported rarely. Nausea and vomiting have been reported when the infusion rate is greater than 50μg/min.
【Contraindications 】
Somatostatin is contra-indicated In states of proven hypersensitivity to somatostatin.
【Warnings 】
(1) Due to its inhibitory effect on the secretion of insulin and glucagon, the administration of somatostatin can, at the onset of treatment, lead to a transient fall in blood glucose level. Caution is, therefore, called for in insulin-dependent diabetic patients in whom blood glucose should be measured every 3-4 hours. Simultaneous administration of insulin-requiring sugars should, if possible, be avoided. If necessary, insulin should be administered.
(2) It should be used under the direction of doctors.
【Pregnancy and nursing mothers】Prohibit use in pregnancy and nursing mothers.
【Pediatric Use】Safety have not been established in pediatric patients.
【Geriatric Use】Safety have not been established in elderly patients.
【Drug interactions】
Since somatostatin lengthens the time of hexobarbital induced sleep and potentiates the action of pentetrazol, somatostatin should not be administered concomitantly with these drugs or with drugs exerting the same effects.
Physical incompatibilities with other drugs have not been tested, therefore
somatostatin should be administered alone in the syringe and in infusion solutions.
【Overdosage 】
There are no reported instances of severe toxic reactions caused by over-dosage in humans.
【Pharmacology and Toxicology】
Somatostatin for injection is a synthetic cyclic 14 amino-acid peptide, which is
identical in structure and action to natural somatostatin.
By i.v. infusion in humans, somatostatin causes inhibition of Growth Hormone,
Thyroid Stimulating Hormone, Insulin and Glucagon secretion as well as inhibition of gastric acid secretion. It also affects the absorption, motility, splanchnic blood flow and trophic functions of the gastro-intestinal tract.Physiologically, somatostatin is found mainly in the gastrointestinal tract and in the hypothalamus.
Somatostatin inhibits the release of gastrin, gastric acid and pepsin which supports its
indication in the treatment of upper G.I. haemorrhage. Furthermore, somatostatin is capable of reducing remarkably splanchnic blood flow without causing significant variations in the systemic arterial pressure, which proves to be valuable for the management of oesophageal variceal haemorrhage.
Somatostatin reduces both pancreatic endocrine and exocrine secretion which makes it effective in the prophylaxis and treatment of postoperative complications of pancreatic surgery.
The positive effect of somatostatin in the management of diabetic ketoacidosis can be ascribed to its suppression activity of glucagon secretion.
【Pharmacokinetics 】
In healthy persons the plasma level of endogenous somatostatin is low, generally well under 175 ng/L.
Following i.v. administration, somatostatin shows a very short plasma half-life which, as measured by radioimmunoassay, lies between 1.1 and 3 minutes in normal subjects, between 1.2 and 4.8 minutes in subjects with liver disease, between 2.6 and 4.9 minutes in subjects with chronic renal failure.
Following an i.v. infusion at a rate of 75μg/h, the plateau level was obtained within 15 minutes and reached 1250ng/L. The metabolic clearance rate was around 1 L/min. and the half-life around 2.7 min.
After i.v. injection of 2μg of I thyrosine somatostatin, urinary excretion contained 40% of the radioactivity after 4 hours and 70% after 24 hours.
Somatostatin is rapidly metabolized in the liver through the action of endopeptidases and aminopeptidases, resulting in cleavage between the N-terminus and the cyclized portion of the molecule.
【Storage 】Store between 2°C to 8°C in a light resistant closed space.
【Packing 】In glass tube vial. 1 vial/box.
【Expiry date】
【Quality standard No.】
【License No.】 (1) Guo Yao Zhun Zi
(2) Guo Yao Zhun Zi
【Manufacturer 】 125