Release form, composition and packing Byetta
Solution for subcutaneous injection is colorless and transparent. 1 mL of 250 mcg exenatide. Excipients: sodium acetate trihydrate, glacial acetic acid, mannitol, m-cresol, water, d / and.
Clinico-pharmacological group: hypoglycemic agents.
Pharmacological action
Hypoglycemic medication. Exenatide (eksendin-4) is a mimetic inkretina and a 39-amino acid amidopeptidom. Inkretiny, such as glucagon-like peptide-1 (GLP-1), glyukozozavisimuyu increase insulin secretion, improve the function of beta cells, inhibit glucagon secretion increased inadequate and slow gastric emptying after getting into the bloodstream from the intestine. Exenatide is a potent mimetics inkretina, which causes increased insulin secretion glyukozozavisimoy and provides other hypoglycemic effects of inherent inkretinam that allows you to improve glycemic control in patients with type 2 diabetes mellitus.
Amino acid sequence of exenatide partially corresponds to the sequence of human GLP-1, resulting in it binds to and activates the receptor GLP-1 in humans, which leads to increased glyukozozavisimogo synthesis and secretion of insulin from beta cells of the pancreas, with the participation of cyclic AMP and / or other intracellular signaling ways. Exenatide stimulates insulin release from beta cells in the presence of elevated concentrations of glucose.
On the chemical structure and pharmacological action exenatide differs from insulin, sulfonylureas, D-phenylalanine derivatives, and meglitinidov, biguanides, thiazolidinediones and alpha-glucosidase inhibitors.
Exenatide improves glycemic control in patients with type 2 diabetes mellitus through the following mechanisms. At hyperglycemic states exenatide enhances insulin secretion glyukozozavisimuyu of beta cells of the pancreas. This secretion of insulin stops the lowering of blood glucose concentrations and bringing it closer to the norm, thereby decreasing the potential risk of hypoglycemia.
Insulin secretion during the first 10 minutes, known as the "first phase insulin response, specifically absent in patients with type 2 diabetes mellitus. In addition, the loss of first phase insulin response is an early dysfunction of beta cells in diabetes mellitus type 2. Introduction Exenatide restores or greatly enhances both the first and second phase insulin response in patients with type 2 diabetes mellitus. In patients with type 2 diabetes against the background of hyperglycemia introduction of exenatide suppresses excessive secretion of glucagon. However, exenatide does not disturb the normal glucagon response to hypoglycemia.
It was shown that the introduction of exenatide leads to a decrease in appetite and decrease food intake, inhibits the motility of the stomach, which slows down its emptying.
In patients with type 2 diabetes therapy exenatide in combination with metformin and / or a sulfonylurea leads to a decrease in the concentration of fasting blood glucose, postprandial blood glucose, as well as measure HbA1c, thereby improving glycemic control in these patients.
Pharmacokinetics
Suction
After subcutaneous injection exenatide at a dose of 10 mg in patients with type 2 diabetes mellitus exenatide rapidly absorbed and reaches the average C max by 2.1 hours, which amounts to 211 pg / ml, AUCo-inf was 1036 pg x hr / ml. Under the action of exenatide AUC increases proportionally with increasing doses of 5 micrograms to 10 micrograms, with no observed proportional increase Smah. Same effect was observed when s / c infusion exenatide in the abdomen, hip or forearm.
Distribution
Vd exenatide after subcutaneous injection of 3.28 liters. Metabolism and excretion of Exenatide is derived mainly through glomerular filtration with subsequent proteolytic decay. Exenatide clearance is 9.1 l / h. End T1 / 2 is 2.4 h. These pharmacokinetic characteristics Exenatide does not depend on the dose. Measured concentrations of exenatide determined for approximately 10 hours after dosing.
Pharmacokinetics in special clinical situations
Patients with mild or moderate, impaired renal function (creatinine clearance 30-80 ml / min), exenatide clearance was not significantly different from clearance in patients with normal renal function, and therefore correction of the dose is not required. However, in patients with end-stage renal failure on dialysis, the average clearance was reduced to 0.9 l / h (compared with 9.1 l / h in healthy subjects). Because exenatide is mainly excreted by the kidneys, it is believed that liver dysfunction does not alter the concentration of exenatide in the blood. Age does not influence the pharmacokinetic characteristics of exenatide. Therefore, elderly patients do not require correction of the dose.
Exenatide pharmacokinetics in children has not been studied. Between men and women in clinically important differences in the pharmacokinetics of exenatide is not observed.
Exenatide pharmacokinetics in representatives of different races virtually unchanged. Dose adjustment taking into account the ethnic origin do not want to spend. Not observed a significant correlation between body mass index (BMI) and pharmacokinetics of exenatide. Dose adjustment taking into account the BMI of conduct is not required.
Statement
Type 2 diabetes as adjunctive therapy to metformin, sulfonylureas, thiazolidinediones, a combination of metformin and sulfonylureas, or metformin and tiazoldindiona in case of failure to reach adequate glycemic control.
Dosing regimen
The drug is administered sc in the thigh, abdomen or upper arm. The initial dose is 5 mg, is administered 2 times a day, at any time during the 60-minute period before the morning and evening meals. Should not be given the drug after meals.
In the case of pass the injection treatment is continued without changing the dose. 1 month after starting treatment dose can be increased to 10 mg 2 times a day. At a joint appointment with metformin, thiazolidinediones, or with a combination of these drugs, starting dose of metformin and / or thiazolidinediones can not be changed. In the case of a combination drug Byetta with derivatives of sulfonylurea may need to decrease the dose of sulfonylurea derivatives to reduce the risk of hypoglycemia.
Side effect
Adverse reactions are more common than in isolated cases are listed in accordance with the following scale: very common (≥ 10%), frequent (≥ 1% but <10%),> 0.1% but <1%)> 0.01% but <0.1%), rarely (<0.01%).
From the digestive system: Very common - nausea, vomiting, diarrhea, and often - loss of appetite, indigestion, gastroesophageal reflux, and sometimes - abdominal pain, bloating, belching, constipation, impaired sense of taste, flatulence.
CNS: Frequently - dizziness, headache, rarely - drowsiness.
From the endocrine system: very often - hypoglycemia (in combination with sulfonylureas), and often - the feeling tremors, weakness, hyperhidrosis.
Allergic reactions: seldom - a rash, itching, angioedema, is extremely rare - anaphylactic reaction.
Other: often - a skin reaction at the injection site, rarely - dehydration (associated with nausea, vomiting and / or diarrhea). Several reported cases increasing clotting time (INR), while the application of warfarin and exenatide, which is sometimes accompanied by bleeding. Because frequency of hypoglycemia increases when the joint appointment of the drug Byetta with sulfonylureas, there should be reduction of the dose sulfonylureas increases the risk of hypoglycemia.
Most episodes of hypoglycemia, the intensity was weak or moderate, were stopped and oral intake of carbohydrates. In general, side effects from the intensity was weak or moderate and did not lead to the abolition of the treatment. Most frequently recorded nausea of mild or moderate intensity was dose dependent and decreased with time, not interfering with daily activities.
Contraindications
type 1 diabetes mellitus or the presence of diabetic ketoacidosis;
severe renal insufficiency (creatinine clearance <30 ml / min);
the presence of severe gastrointestinal illness associated with gastroparesis;
pregnancy;
Lactation (breastfeeding);
Children up to age 18 (safety and efficacy in children has not been established);
hypersensitivity to the drug.
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation.
Use in renal impairment
The drug is contraindicated in severe renal insufficiency (creatinine clearance <30 ml / min).
Cautions
Not recommended w / or / m administration. The drug Byetta should not be used if the solution is detected particles or if the solution is cloudy or has a stain. During therapy with the drug Byetta may appear antibodies to exenatide.
However, this does not affect the frequency and types of recorded side effects. Patients should be informed that treatment with Byetta may lead to a decrease in appetite and / or body weight, and that because of these effects is not necessary to modify the dosing regimen.
Patients before starting treatment with Byetta should familiarize themselves with the drug attached to the "Guidelines on the use of syringe-pen." Results of experimental studies in preclinical studies in mice and rats revealed no carcinogenic effects exenatide. When rats dose, in doses 128 times higher than the dose in humans, noted a numerical increase in C-cell adenomas of the thyroid gland without any signs of malignancy, which was associated with increased longevity in experimental animals receiving exenatide.
Overdose
In case of overdose (dose 10 times higher than the maximum recommended dose) were observed following symptoms: severe nausea and vomiting and rapid development of hypoglycemia.
Treatment: symptomatic therapy, including parenteral administration of glucose in the case of severe hypoglycemia.
Solution for subcutaneous injection is colorless and transparent. 1 mL of 250 mcg exenatide. Excipients: sodium acetate trihydrate, glacial acetic acid, mannitol, m-cresol, water, d / and.
Clinico-pharmacological group: hypoglycemic agents.
Pharmacological action
Hypoglycemic medication. Exenatide (eksendin-4) is a mimetic inkretina and a 39-amino acid amidopeptidom. Inkretiny, such as glucagon-like peptide-1 (GLP-1), glyukozozavisimuyu increase insulin secretion, improve the function of beta cells, inhibit glucagon secretion increased inadequate and slow gastric emptying after getting into the bloodstream from the intestine. Exenatide is a potent mimetics inkretina, which causes increased insulin secretion glyukozozavisimoy and provides other hypoglycemic effects of inherent inkretinam that allows you to improve glycemic control in patients with type 2 diabetes mellitus.
Amino acid sequence of exenatide partially corresponds to the sequence of human GLP-1, resulting in it binds to and activates the receptor GLP-1 in humans, which leads to increased glyukozozavisimogo synthesis and secretion of insulin from beta cells of the pancreas, with the participation of cyclic AMP and / or other intracellular signaling ways. Exenatide stimulates insulin release from beta cells in the presence of elevated concentrations of glucose.
On the chemical structure and pharmacological action exenatide differs from insulin, sulfonylureas, D-phenylalanine derivatives, and meglitinidov, biguanides, thiazolidinediones and alpha-glucosidase inhibitors.
Exenatide improves glycemic control in patients with type 2 diabetes mellitus through the following mechanisms. At hyperglycemic states exenatide enhances insulin secretion glyukozozavisimuyu of beta cells of the pancreas. This secretion of insulin stops the lowering of blood glucose concentrations and bringing it closer to the norm, thereby decreasing the potential risk of hypoglycemia.
Insulin secretion during the first 10 minutes, known as the "first phase insulin response, specifically absent in patients with type 2 diabetes mellitus. In addition, the loss of first phase insulin response is an early dysfunction of beta cells in diabetes mellitus type 2. Introduction Exenatide restores or greatly enhances both the first and second phase insulin response in patients with type 2 diabetes mellitus. In patients with type 2 diabetes against the background of hyperglycemia introduction of exenatide suppresses excessive secretion of glucagon. However, exenatide does not disturb the normal glucagon response to hypoglycemia.
It was shown that the introduction of exenatide leads to a decrease in appetite and decrease food intake, inhibits the motility of the stomach, which slows down its emptying.
In patients with type 2 diabetes therapy exenatide in combination with metformin and / or a sulfonylurea leads to a decrease in the concentration of fasting blood glucose, postprandial blood glucose, as well as measure HbA1c, thereby improving glycemic control in these patients.
Pharmacokinetics
Suction
After subcutaneous injection exenatide at a dose of 10 mg in patients with type 2 diabetes mellitus exenatide rapidly absorbed and reaches the average C max by 2.1 hours, which amounts to 211 pg / ml, AUCo-inf was 1036 pg x hr / ml. Under the action of exenatide AUC increases proportionally with increasing doses of 5 micrograms to 10 micrograms, with no observed proportional increase Smah. Same effect was observed when s / c infusion exenatide in the abdomen, hip or forearm.
Distribution
Vd exenatide after subcutaneous injection of 3.28 liters. Metabolism and excretion of Exenatide is derived mainly through glomerular filtration with subsequent proteolytic decay. Exenatide clearance is 9.1 l / h. End T1 / 2 is 2.4 h. These pharmacokinetic characteristics Exenatide does not depend on the dose. Measured concentrations of exenatide determined for approximately 10 hours after dosing.
Pharmacokinetics in special clinical situations
Patients with mild or moderate, impaired renal function (creatinine clearance 30-80 ml / min), exenatide clearance was not significantly different from clearance in patients with normal renal function, and therefore correction of the dose is not required. However, in patients with end-stage renal failure on dialysis, the average clearance was reduced to 0.9 l / h (compared with 9.1 l / h in healthy subjects). Because exenatide is mainly excreted by the kidneys, it is believed that liver dysfunction does not alter the concentration of exenatide in the blood. Age does not influence the pharmacokinetic characteristics of exenatide. Therefore, elderly patients do not require correction of the dose.
Exenatide pharmacokinetics in children has not been studied. Between men and women in clinically important differences in the pharmacokinetics of exenatide is not observed.
Exenatide pharmacokinetics in representatives of different races virtually unchanged. Dose adjustment taking into account the ethnic origin do not want to spend. Not observed a significant correlation between body mass index (BMI) and pharmacokinetics of exenatide. Dose adjustment taking into account the BMI of conduct is not required.
Statement
Type 2 diabetes as adjunctive therapy to metformin, sulfonylureas, thiazolidinediones, a combination of metformin and sulfonylureas, or metformin and tiazoldindiona in case of failure to reach adequate glycemic control.
Dosing regimen
The drug is administered sc in the thigh, abdomen or upper arm. The initial dose is 5 mg, is administered 2 times a day, at any time during the 60-minute period before the morning and evening meals. Should not be given the drug after meals.
In the case of pass the injection treatment is continued without changing the dose. 1 month after starting treatment dose can be increased to 10 mg 2 times a day. At a joint appointment with metformin, thiazolidinediones, or with a combination of these drugs, starting dose of metformin and / or thiazolidinediones can not be changed. In the case of a combination drug Byetta with derivatives of sulfonylurea may need to decrease the dose of sulfonylurea derivatives to reduce the risk of hypoglycemia.
Side effect
Adverse reactions are more common than in isolated cases are listed in accordance with the following scale: very common (≥ 10%), frequent (≥ 1% but <10%),> 0.1% but <1%)> 0.01% but <0.1%), rarely (<0.01%).
From the digestive system: Very common - nausea, vomiting, diarrhea, and often - loss of appetite, indigestion, gastroesophageal reflux, and sometimes - abdominal pain, bloating, belching, constipation, impaired sense of taste, flatulence.
CNS: Frequently - dizziness, headache, rarely - drowsiness.
From the endocrine system: very often - hypoglycemia (in combination with sulfonylureas), and often - the feeling tremors, weakness, hyperhidrosis.
Allergic reactions: seldom - a rash, itching, angioedema, is extremely rare - anaphylactic reaction.
Other: often - a skin reaction at the injection site, rarely - dehydration (associated with nausea, vomiting and / or diarrhea). Several reported cases increasing clotting time (INR), while the application of warfarin and exenatide, which is sometimes accompanied by bleeding. Because frequency of hypoglycemia increases when the joint appointment of the drug Byetta with sulfonylureas, there should be reduction of the dose sulfonylureas increases the risk of hypoglycemia.
Most episodes of hypoglycemia, the intensity was weak or moderate, were stopped and oral intake of carbohydrates. In general, side effects from the intensity was weak or moderate and did not lead to the abolition of the treatment. Most frequently recorded nausea of mild or moderate intensity was dose dependent and decreased with time, not interfering with daily activities.
Contraindications
type 1 diabetes mellitus or the presence of diabetic ketoacidosis;
severe renal insufficiency (creatinine clearance <30 ml / min);
the presence of severe gastrointestinal illness associated with gastroparesis;
pregnancy;
Lactation (breastfeeding);
Children up to age 18 (safety and efficacy in children has not been established);
hypersensitivity to the drug.
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation.
Use in renal impairment
The drug is contraindicated in severe renal insufficiency (creatinine clearance <30 ml / min).
Cautions
Not recommended w / or / m administration. The drug Byetta should not be used if the solution is detected particles or if the solution is cloudy or has a stain. During therapy with the drug Byetta may appear antibodies to exenatide.
However, this does not affect the frequency and types of recorded side effects. Patients should be informed that treatment with Byetta may lead to a decrease in appetite and / or body weight, and that because of these effects is not necessary to modify the dosing regimen.
Patients before starting treatment with Byetta should familiarize themselves with the drug attached to the "Guidelines on the use of syringe-pen." Results of experimental studies in preclinical studies in mice and rats revealed no carcinogenic effects exenatide. When rats dose, in doses 128 times higher than the dose in humans, noted a numerical increase in C-cell adenomas of the thyroid gland without any signs of malignancy, which was associated with increased longevity in experimental animals receiving exenatide.
Overdose
In case of overdose (dose 10 times higher than the maximum recommended dose) were observed following symptoms: severe nausea and vomiting and rapid development of hypoglycemia.
Treatment: symptomatic therapy, including parenteral administration of glucose in the case of severe hypoglycemia.
No comments:
Post a Comment