LITAINENG®（Octreotide Acetate Injection）
LITAINENG®（Octreotide Acetate Injection）
LITAINENG®（Octreotide Acetate Injection）
LITAINENG®（Octreotide Acetate Injection）
【Ingredient】
1. The main component of this product is: octreotide acetate
Chemical name: D-Phenylalanyl-L-Carbamyl-L-Phenylalanyl-D-Tryptophanyl-L-Lysyl-L-Thionyl-N — [2-Hydroxy-1-Hydroxymethyl) Propyl] -Cysteamine(2→7) Cyclodisulfide acetate
Chemical structural formula:
Molecular formula: C49H66N10010S2·XC2H402
Molecular weight: 1019.26· X60.02
2.Excipients: lactic acid, mannitol, sodium bicarbonate, CO2, water for injection.
【Appearance】
1. The main component of this product is: octreotide acetate
Chemical name: D-Phenylalanyl-L-Carbamyl-L-Phenylalanyl-D-Tryptophanyl-L-Lysyl-L-Thionyl-N — [2-Hydroxy-1-Hydroxymethyl) Propyl] -Cysteamine(2→7) Cyclodisulfide acetate
Chemical structural formula:
Molecular formula: C49H66N10010S2·XC2H402
Molecular weight: 1019.26· X60.02
2.Excipients: lactic acid, mannitol, sodium bicarbonate, CO2, water for injection.
【Appearance】
This product is a colorless clear liquid
【Indication】
1. Emergency treatment of esophagogastric variceal bleeding due to cirrhosis, in combination with special treatment (such as endoscopic sclerotherapy).
2. To prevent postoperative complications of the pancreas.
3. Relieve symptoms and signs associated with gastrointestinal endocrine tumors. There is evidence that this product is effective against the following tumors: carcinoid tumors with carcinoid syndrome; VIP tumors; and pancreatic hyperglycaemia. The effective rate of this product for the following tumors is about 50% (limited cases have been treated with this product so far): gastrinoma/Zollinger-Ellison syndrome, insulinoma, growth hormone-releasing factor tumor.
4. Patients with acromegaly who have failed surgery, radiation therapy, or dopamine receptor agonist therapy can control symptoms and reduce the concentrations of growth hormone (GH) and growth hormone mediator C. It is also indicated for patients with acromegaly who are inoperable or unwilling to undergo surgery, as well as for patients with intermittent periods when radiation therapy has not yet taken effect.
【Strength】
【Indication】
1. Emergency treatment of esophagogastric variceal bleeding due to cirrhosis, in combination with special treatment (such as endoscopic sclerotherapy).
2. To prevent postoperative complications of the pancreas.
3. Relieve symptoms and signs associated with gastrointestinal endocrine tumors. There is evidence that this product is effective against the following tumors: carcinoid tumors with carcinoid syndrome; VIP tumors; and pancreatic hyperglycaemia. The effective rate of this product for the following tumors is about 50% (limited cases have been treated with this product so far): gastrinoma/Zollinger-Ellison syndrome, insulinoma, growth hormone-releasing factor tumor.
4. Patients with acromegaly who have failed surgery, radiation therapy, or dopamine receptor agonist therapy can control symptoms and reduce the concentrations of growth hormone (GH) and growth hormone mediator C. It is also indicated for patients with acromegaly who are inoperable or unwilling to undergo surgery, as well as for patients with intermittent periods when radiation therapy has not yet taken effect.
【Strength】
1 ml:0.1 mg (calculated as octreotide)
【Dosage and administration】
Usage: subcutaneous injection, intravenous drip.
Dosage: 1. Esophageal and gastric variceal bleeding
Continuous intravenous drip of 0.025 mg/hour. Up to 5 days of treatment, it may be diluted with normal saline or glucose.
2. Prevention of complications after pancreatic surgery
0.1 mg subcutaneously three times daily for 7 days; the first injection was administrated at least 1 hour before surgery.
3. Gastroenteropancreatic endocrine tumors
The initial dose is 0.05 mg subcutaneously once or twice daily, then gradually increased to 0.2 mg three times daily according to tolerability and efficacy.
4. Acromegaly
The initial dose is 0.05 to 0.1 mg subcutaneously every 8 hours, adjusted according to monthly assessments of circulating GH concentration, clinical response, and tolerability. The optimal dose for most patients is 0.2 to 0.3 mg/day, and the maximum dose should not exceed 1.5 mg/day. The dose may be reduced as appropriate after several months of treatment guided by monitoring of plasma GH levels. After 1 month of treatment with HUMIRA, if GH concentration decreased and clinical symptoms did not improve, drug withdrawal should be considered.
【Adverse reactions】
1. Local reactions to injection, including pain, needling or burning sensation at the injection site, with redness and swelling. These phenomena rarely exceed 15 minutes. Local discomfort can be reduced by bringing the solution to room temperature before injection.
2. Gastrointestinal reactions, including loss of appetite, nausea, vomiting, cramping abdominal pain, flatulence, loose stools, diarrhea, and steatorrhea. In rare cases, gastrointestinal reactions may resemble acute intestinal obstruction with progressive severe epigastric pain, abdominal tenderness, muscular tension, and abdominal distension.
3. Long-term use can lead to the formation of gallstones.
4. Because this product inhibits the release of GH, trypsin, and insulin, it may cause disorders in blood glucose regulation. Hypoglycemia has been observed in a small number of patients with persistent hyperglycemia because it can reduce patients’ glucose tolerance after the meal.
5. Others: Acute pancreatitis has been reported in a few cases and may gradually disappear after drug withdrawal; rarely, alopecia has been reported in patients treated with octreotide acetate; pancreatitis may also occur in patients who have used this product for a long time and develop gallstones; individual patients develop liver dysfunction, including slowly occurring hyperbilirubinemia with slightly increased alkaline phosphatase, gamma-glutamyltransferase, and transaminases.
【Contraindication】
It is contraindicated in patients allergic to octreotide or any of the excipients in this product.
【Precautions】
1. Because GH-secreting pituitary tumors may sometimes spread and cause serious complications, the patient should be carefully observed, and if there are signs of tumor spread, switching to other treatments should be considered.
2. For long-term use, gallbladder ultrasonography should be performed every 6 to 12 months.
3. Patients with insulin-dependent diabetes or diabetes should be closely monitored for blood glucose levels.
4. For diabetic patients receiving insulin therapy, the insulin dosage may be reduced after administration of this product.
5. Multiple injections at the same site in a short period of time were avoided.
6. In the treatment of gastroenteropancreatic endocrine tumors, occasional uncontrolled symptoms occur resulting in rapid recurrence of severe symptoms.
【Use in pregnant and lactating women】
There is no experience and this product should be used only if absolutely necessary.
【Pediatric use】
There is limited experience with this product in children.
【Geriatric use】
There is no evidence that the tolerance of elderly patients to this product is reduced, so there is no need to reduce the dose of this product.
【Drug-drug interaction】
This product can reduce the intestinal absorption of cyclosporine and delay the absorption of cimetidine.
【Overdose】
Patients with overdose should be treated symptomatically.
【Pharmacology and toxicology】
Pharmacological effects:
Octreotide is a synthetic octapeptide compound that is a tetradecapeptide human somatostatin analogue. The pharmacological effects of octreotide are similar to those of natural hormones, but it strongly inhibits the effects of growth hormone, glucagon, and insulin. Similar to somatostatin, octreotide also inhibits LH response to GnRH, decreases splanchnic blood flow, and inhibits the secretion of 5-HT, gastrin, vasoactive intestinal peptide, chymotrypsin, motilin, and glucagon.
Toxicology studies:
Genotoxicity: No genotoxicity was observed in laboratory studies.
Reproductive toxicity: Octreotide was administered to rats and rabbits at doses equivalent to 16 times the highest human dose based on body surface area, with no effect on fertility and fetuses.
Carcinogenicity: Mice were subcutaneously injected with octreotide at doses up to 2 mg/kg/day (approximately 8 times the human exposure based on body surface area) for 85 to 89 weeks, and no carcinogenicity was observed. Rats were subcutaneously injected with octreotide at the highest dose of 1.25 mg/kg/day (approximately 10 times the human exposure based on body surface area), sarcomas and squamous cell tumors were observed at the injection site, with incidences of 27% and 12% in male and female animals, respectively, and 8 to 10% in the vehicle control group. However, after 5 years of continuous use of octreotide in humans, no tumorigenesis occurred at the injection site. At the highest dose, the incidence of uterine adenomas was 15% in females, 7% in saline, and 0% in vehicle controls. The development of uterine adenomas in females may be related to estrogen levels in older animals.
【Pharmacokinetics】
It is poorly absorbed orally and is rapidly and completely absorbed after subcutaneous and intravenous administration. After subcutaneous injection, maximum plasma concentrations are reached in 30 minutes and the elimination half-life is 100 minutes. After intravenous injection, it reaches the maximum level at 4 minutes and its elimination is biphasic with half-lives of 10 and 90 minutes, respectively. The volume of distribution of the drug is 6 liters, the overall clearance is 160 ml/min, and the plasma protein binding is 65%.
【Storage】 Protect from light and store at 2 to 8℃. It should be used within the shelf life.
【Package】 Glass ampoule, 5 vials/small box.
【Shelf life】 24 months.
【Executive standard】 Chinese Pharmacopoeia (2015) Volume II
【Approval No.】 GYZZ H20051507
【Dosage and administration】
Usage: subcutaneous injection, intravenous drip.
Dosage: 1. Esophageal and gastric variceal bleeding
Continuous intravenous drip of 0.025 mg/hour. Up to 5 days of treatment, it may be diluted with normal saline or glucose.
2. Prevention of complications after pancreatic surgery
0.1 mg subcutaneously three times daily for 7 days; the first injection was administrated at least 1 hour before surgery.
3. Gastroenteropancreatic endocrine tumors
The initial dose is 0.05 mg subcutaneously once or twice daily, then gradually increased to 0.2 mg three times daily according to tolerability and efficacy.
4. Acromegaly
The initial dose is 0.05 to 0.1 mg subcutaneously every 8 hours, adjusted according to monthly assessments of circulating GH concentration, clinical response, and tolerability. The optimal dose for most patients is 0.2 to 0.3 mg/day, and the maximum dose should not exceed 1.5 mg/day. The dose may be reduced as appropriate after several months of treatment guided by monitoring of plasma GH levels. After 1 month of treatment with HUMIRA, if GH concentration decreased and clinical symptoms did not improve, drug withdrawal should be considered.
【Adverse reactions】
1. Local reactions to injection, including pain, needling or burning sensation at the injection site, with redness and swelling. These phenomena rarely exceed 15 minutes. Local discomfort can be reduced by bringing the solution to room temperature before injection.
2. Gastrointestinal reactions, including loss of appetite, nausea, vomiting, cramping abdominal pain, flatulence, loose stools, diarrhea, and steatorrhea. In rare cases, gastrointestinal reactions may resemble acute intestinal obstruction with progressive severe epigastric pain, abdominal tenderness, muscular tension, and abdominal distension.
3. Long-term use can lead to the formation of gallstones.
4. Because this product inhibits the release of GH, trypsin, and insulin, it may cause disorders in blood glucose regulation. Hypoglycemia has been observed in a small number of patients with persistent hyperglycemia because it can reduce patients’ glucose tolerance after the meal.
5. Others: Acute pancreatitis has been reported in a few cases and may gradually disappear after drug withdrawal; rarely, alopecia has been reported in patients treated with octreotide acetate; pancreatitis may also occur in patients who have used this product for a long time and develop gallstones; individual patients develop liver dysfunction, including slowly occurring hyperbilirubinemia with slightly increased alkaline phosphatase, gamma-glutamyltransferase, and transaminases.
【Contraindication】
It is contraindicated in patients allergic to octreotide or any of the excipients in this product.
【Precautions】
1. Because GH-secreting pituitary tumors may sometimes spread and cause serious complications, the patient should be carefully observed, and if there are signs of tumor spread, switching to other treatments should be considered.
2. For long-term use, gallbladder ultrasonography should be performed every 6 to 12 months.
3. Patients with insulin-dependent diabetes or diabetes should be closely monitored for blood glucose levels.
4. For diabetic patients receiving insulin therapy, the insulin dosage may be reduced after administration of this product.
5. Multiple injections at the same site in a short period of time were avoided.
6. In the treatment of gastroenteropancreatic endocrine tumors, occasional uncontrolled symptoms occur resulting in rapid recurrence of severe symptoms.
【Use in pregnant and lactating women】
There is no experience and this product should be used only if absolutely necessary.
【Pediatric use】
There is limited experience with this product in children.
【Geriatric use】
There is no evidence that the tolerance of elderly patients to this product is reduced, so there is no need to reduce the dose of this product.
【Drug-drug interaction】
This product can reduce the intestinal absorption of cyclosporine and delay the absorption of cimetidine.
【Overdose】
Patients with overdose should be treated symptomatically.
【Pharmacology and toxicology】
Pharmacological effects:
Octreotide is a synthetic octapeptide compound that is a tetradecapeptide human somatostatin analogue. The pharmacological effects of octreotide are similar to those of natural hormones, but it strongly inhibits the effects of growth hormone, glucagon, and insulin. Similar to somatostatin, octreotide also inhibits LH response to GnRH, decreases splanchnic blood flow, and inhibits the secretion of 5-HT, gastrin, vasoactive intestinal peptide, chymotrypsin, motilin, and glucagon.
Toxicology studies:
Genotoxicity: No genotoxicity was observed in laboratory studies.
Reproductive toxicity: Octreotide was administered to rats and rabbits at doses equivalent to 16 times the highest human dose based on body surface area, with no effect on fertility and fetuses.
Carcinogenicity: Mice were subcutaneously injected with octreotide at doses up to 2 mg/kg/day (approximately 8 times the human exposure based on body surface area) for 85 to 89 weeks, and no carcinogenicity was observed. Rats were subcutaneously injected with octreotide at the highest dose of 1.25 mg/kg/day (approximately 10 times the human exposure based on body surface area), sarcomas and squamous cell tumors were observed at the injection site, with incidences of 27% and 12% in male and female animals, respectively, and 8 to 10% in the vehicle control group. However, after 5 years of continuous use of octreotide in humans, no tumorigenesis occurred at the injection site. At the highest dose, the incidence of uterine adenomas was 15% in females, 7% in saline, and 0% in vehicle controls. The development of uterine adenomas in females may be related to estrogen levels in older animals.
【Pharmacokinetics】
It is poorly absorbed orally and is rapidly and completely absorbed after subcutaneous and intravenous administration. After subcutaneous injection, maximum plasma concentrations are reached in 30 minutes and the elimination half-life is 100 minutes. After intravenous injection, it reaches the maximum level at 4 minutes and its elimination is biphasic with half-lives of 10 and 90 minutes, respectively. The volume of distribution of the drug is 6 liters, the overall clearance is 160 ml/min, and the plasma protein binding is 65%.
【Storage】 Protect from light and store at 2 to 8℃. It should be used within the shelf life.
【Package】 Glass ampoule, 5 vials/small box.
【Shelf life】 24 months.
【Executive standard】 Chinese Pharmacopoeia (2015) Volume II
【Approval No.】 GYZZ H20051507