Byeta Long
Byeta Long: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Byetta Long
ATX code: A10BX04
Active ingredient: Exenatide (Exenatide)
Producer: Amylin Ohio LLC (USA); Wetter Pharma-Fertigung, GmbH & Co. KG. (Vetter Pharma-Fertigung, GmbH & Co. KG) (Germany)
Description and photo update: 2019-11-07
Prices in pharmacies: from 10959 rubles.
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Byeta Long is a hypoglycemic agent.
Release form and composition
Byetta Long is produced in powder form for preparing a suspension for subcutaneous (s / c) administration of prolonged action: almost white or white; solvent - colorless or with a yellow / brown tinge transparent liquid (set - powder in an amount corresponding to 2 mg of exenatide, in a glass transparent vial of 3 ml, closed with a chlorobutyl rubber stopper and an aluminum cap with a polypropylene cap, and a solvent in a dose of 0.65 ml in a glass transparent syringe with a volume of 1.5 ml with a polypropylene plunger with a bromobutyl rubber plunger and a Luer lock connector; in a sealed blister strip packaging 1 set, including 1 bottle of powder, 1 syringe with solvent, 1 adapter and 2 sterile needles; in a cardboard box with control of the first opening 4 blisters;pen-syringe - in the front chamber of the pen-pen contains powder in an amount corresponding to 2 mg of exenatide, in the back chamber of the transparent glass cartridge built into the pen-pen - solvent at a dose of 0.65 ml; in a sealed blister strip packaging 1 syringe pen with 1 sterile needle; in a cardboard box with first opening control 4 contour packs and 1 spare sterile needle. Each pack also contains instructions for the use of Byetta Long). Each pack also contains instructions for the use of Byetta Long). Each pack also contains instructions for the use of Byetta Long).
1 dose of powder (1 set or 1 syringe pen) contains:
- active substance: exenatide - 2 mg;
- additional components: sucrose, polymer 50:50 DL 4AP [copoly- (D, L-lactide-glycolide)].
The composition of the solvent: polysorbate 20, sodium carmellose, sodium dihydrogen phosphate monohydrate, sodium chloride, sodium hydrogen phosphate heptahydrate, water for injection; additionally for a pen-syringe - 1 M sodium hydroxide solution.
Pharmacological properties
Pharmacodynamics
Exenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist, exhibiting some of the antihyperglycemic effects inherent in GLP-1. The amino acid sequence contained in Exenatide overlaps with that of human GLP-1. In vitro studies have shown that the active substance binds to the GLP-1 receptors and stimulates them, and the mechanism of its action involves cyclic adenosine monophosphate (cAMP) and / or other intracellular signal transduction pathways.
Exenatide glucose-dependently helps to increase the production of insulin by β-cells of the pancreas. The decrease in insulin production occurs against the background of a decrease in blood glucose levels. If the active substance was used in combination with thiazolidinedione and / or metformin, the frequency of episodes of hypoglycemia did not exceed that recorded in the placebo group with thiazolidinedione and / or metformin. This may be due to a glucose-dependent insulinotropic mechanism of action.
Exenatide inhibits the production of glucagon, the level of which is inadequately increased in patients with type 2 diabetes mellitus (DM). Decreasing the level of glucagon in the blood reduces the rate at which glucose is released by the liver. But at the same time, Exenatide does not lead to disruption of the normal secretion of glucagon and other hormones caused by a decrease in blood glucose levels. Byetta Long helps to slow down gastric emptying, which reduces the rate at which glucose enters the bloodstream. The use of the product helps to reduce the amount of food consumed as a result of reduced appetite and increased satiety.
Exenatide provides improved glycemic control due to long-term decreases in fasting blood glucose and postprandial glucose in patients with type 2 diabetes. In contrast to endogenous GLP-1, the pharmacodynamic and pharmacokinetic profiles of Byetta Long allow the drug to be used once every 7 days. In the course of a pharmacodynamic study of Exenatide in patients with type 2 diabetes, in response to intravenous (iv) bolus administration of glucose, the restoration of phase I insulin secretion and improvement of phase II were demonstrated.
In two studies (24 and 30 weeks long), Byeta Long at a dose of 2 mg once every 7 days was compared with Exenatide taken twice a day (Byetta's drug). In both studies, a decrease in the content of glycosylated hemoglobin (HbA 1c) in the blood was recorded already during the first measurement - 4 or 6 weeks after the start of the study. In patients receiving the drug, there was a statistically significant decrease in the level of HbA 1c compared with patients in the group of exenatide taken twice a day. Both groups also showed a decrease in body weight from baseline, but the difference between the groups was not statistically significant.
An additional decrease in HbA 1c levels and a sustained decrease in body weight were recorded for at least 52 weeks in patients who completed the 30-week controlled phase and the 22-week extended uncontrolled phase of the study.
In a 26-week study, Byetta Long at a dose of 2 mg resulted in a more effective reduction in HbA 1c concentration, a statistically significant decrease in mean body weight, and a less frequent occurrence of episodes of hypoglycemia compared with once daily insulin glargine. Also, in a 26-week double-blind study, Byetta Long was shown to be superior to pioglitazone and sitagliptin, which are taken at maximum daily doses while taking metformin, to reduce HbA 1c levels relative to baseline.
In the process of all studies of the drug Byetta Long, a decrease in body weight relative to the initial values was recorded.
Drug therapy also resulted in a significant decrease in fasting plasma / serum glucose. This decrease was noted already 4 weeks after the start of treatment. In addition, a decrease in the level of postprandial glucose was recorded. The improvement in fasting blood glucose was stable over 52 weeks of treatment.
In the course of drug studies, a decrease in systolic blood pressure (SBP) by 2.9–4.7 mm Hg was observed. Art. relative to the original values. The achieved improvement in SBP was noted within 52 weeks of therapy.
Pharmacokinetics
The absorption rates of Exenatide provide the ability of Byetta Long to last for a long time.
In the course of studies on the use of the drug at a dose of 2 mg once every 7 days, the average level of exenatide content exceeded the minimum effective level (~ 50 pg / ml) already 2 weeks after the start of the course, a further increase in the mean plasma concentration of exenatide in the blood was observed for another 6 –7 weeks. The content of the active substance in the following weeks was noted at the level of 300 pg / ml, which confirmed the achievement of an equilibrium state. Stationary concentration (C ss) of exenatide was observed when it was used in the 1 time per 7 days regimen with the smallest fluctuations between the maximum and minimum levels.
The average apparent volume of distribution (V d) of the active substance after subcutaneous administration of 1 dose is 28 liters.
According to the results of preclinical studies, exenatide is excreted mainly by the kidneys through glomerular filtration with further proteolytic degradation. The average apparent active substance clearance is 9 l / h. Doses of Exenatide do not affect these pharmacokinetic parameters. After completion of treatment with Byetta Long, the mean plasma concentration of the agent in the blood falls below the detection limit after approximately 10 weeks.
Pharmacokinetic characteristics of Exenatide are not clinically influenced by race, sex and body weight of the patient.
Indications for use
The use of Byetta Long is recommended for type 2 diabetes as an adjunct treatment to metformin, thiazolidinedione, sulfonylurea derivatives, a combination of metformin and a sulfonylurea derivative or thiazolidinedione and metformin, subject to inadequate glycemic control (in the case of using these drugs at maximum tolerated doses).
Contraindications
- Type 1 diabetes or diabetic ketoacidosis;
- severe lesions of the gastrointestinal tract (GIT) with concomitant gastric paresis;
- severe renal impairment and end-stage renal failure [with creatinine clearance (CC) below 30 ml / min]; impaired renal function of moderate severity (due to very limited experience with the use of the drug in patients of this category);
- acute pancreatitis or a history of pancreatitis;
- personal / family history of medullary thyroid cancer;
- combined use with insulin (the drug is not a substitute for insulin);
- syndrome of multiple endocrine neoplasia (MEN) type 2;
- age up to 18 years;
- pregnancy and lactation;
- hypersensitivity to any of the constituents of Byetta Long.
Byeta Long, instructions for use: method and dosage
The drug Byeta Long is injected n / a into the abdomen, thighs or forearms at any time of the day, regardless of the meal.
The recommended dose of a hypoglycemic agent is 2 mg once every 7 days.
In the case of a transfer of a patient from the use of Exenatide 2 times a day (Byetta's drug) to Byetta Long treatment, it is possible to observe a short-term increase in blood glucose levels, which in most cases takes place within 14 days after the start of therapy.
With the combined use of the drug with thiazolidinedione, metformin, or with a combination of these agents, it is possible not to adjust the initial dose of thiazolidinedione and / or metformin. If Byetta Long is prescribed in combination with a sulfonylurea derivative, it may be necessary to reduce the dose of the latter to reduce the risk of hypoglycemia.
Byeta Long should be administered 1 time in 7 days, on the same day of the week. If necessary, you can change the day of administration of the drug, but the next dose in this case should be administered no earlier than 24 hours after the previous injection.
If you miss a dose, you need to enter it as soon as possible, and then use Byetta Long as usual. It is not necessary to carry out two injections of the drug within one day.
Treatment with the drug does not require additional self-monitoring of blood glucose levels, however, such control may be necessary to change the dose of the drug, which is a sulfonylurea derivative.
At the beginning of the use of other hypoglycemic agents after the completion of the course of treatment by Byetta Long, it is necessary to take into account the prolonged effect of the drug.
The hypoglycemic agent is intended for independent use by patients. A pen or injection kit is used once and by only one patient. Before preparing the suspension, it must be ensured that the solvent is transparent and does not contain visible particles. The suspension obtained from the powder cannot be stored; it must be used immediately for administration.
You cannot use a previously frozen preparation.
The patient or a person caring for him and who does not have medical education should carefully study the rules for self-injection of the drug and strictly follow the recommendations set out in the manual for using the Byetta Long syringe pen / kit attached to the drug.
Side effects
The most common adverse events recorded during drug therapy were nausea and diarrhea. Nausea, which was the most common side effect, was observed in most patients at the beginning of the course, and later in the course of treatment, the frequency of this side effect gradually decreased. Most of the disorders that developed during the use of the hypoglycemic agent were mild or moderate.
During the use of the drug Byeta Long, the following undesirable effects were recorded:
- metabolism and nutritional disorders: very often (≥ 1/10) - hypoglycemia¹ (with combined treatment with a sulfonylurea preparation; most of the episodes of hypoglycemia recorded in clinical studies were mild and were eliminated after oral intake of carbohydrates); often (≥ 1/100 and <1/10) - decreased appetite¹; infrequently (≥ 1/1000 and <1/100) - dehydration¹;
- nervous system: often - dizziness¹, headache¹; infrequently - dysgeusia¹, drowsiness¹;
- immune system: rarely (≥ 1/10 000 and <1/1000) - anaphylactic reaction¹;
- skin and subcutaneous tissues: often - hives and / or itching ¹; infrequently - hyperhidrosis¹, alopecia¹; with an unspecified frequency (according to reports, it is not possible to establish the frequency of occurrence of adverse reactions) - abscesses at the injection site and cellulite², macular and papular rash², angioedema²;
- Gastrointestinal tract: very often - diarrhea¹, nausea¹; often - dyspepsia, vomiting, flatulence, bloating, abdominal pain, constipation, gastroesophageal reflux disease; infrequently - belching, intestinal obstruction; with unspecified frequency - acute pancreatitis²;
- kidneys and urinary tract: infrequently - functional disorders of the kidneys¹;
- laboratory parameters: with unspecified frequency - increased international normalized ratio (INR);
- general disorders and complications at the injection site: often - fatigue¹, asthenia¹, itching / erythema at the injection site¹; infrequently - a rash at the injection site¹ (in order to prevent the development of a reaction at the injection site, new sites should be selected for each subsequent injection); rarely - a feeling of anxiety¹.
¹ Frequency established based on a database of completed long-term studies on the safety and efficacy of extended-release Exenatide.
² Frequency established based on spontaneous reporting using Byetta Long.
Overdose
Symptoms of an overdose of a hypoglycemic agent, in accordance with the results of clinical studies of Exenatide, used twice a day, are severe nausea and vomiting, as well as a rapid decrease in blood glucose. If an overdose is suspected, supportive symptomatic treatment is prescribed.
special instructions
Byetta Long should not be used as a first-line treatment for type 2 diabetes if glycemic control is insufficient during exercise and an appropriate diet.
The drug should not be administered intramuscularly (i / m) or intravenously (i / v).
One dose of a hypoglycemic agent contains practically no sodium (less than 1 mmol sodium).
With the introduction of clinically significant dosages of the drug to laboratory animals, an increase in the frequency of C-cell thyroid tumors was revealed in comparison with the control group. Based on the results of preclinical and clinical studies, a similar threat of C-cell tumors (including medullary cancer) of the thyroid gland in humans cannot be excluded. A biological tumor marker for medullary cancer is the serum level of calcitonin in the blood. The feasibility of routine monitoring of the concentration of this hormone in serum or ultrasound examination (US) of the thyroid gland in order to early detection of medullary cancer in patients receiving therapy with Byetta Long has not been determined. Patients with medullary cancer typically have serum calcitonin levels> 50 ng / L. When,when the serum calcitonin content is elevated, the patient needs to undergo additional examination. Patients with thyroid nodules identified during a physical examination or tomography of the neck are also subject to further examination.
In the period of post-registration use of Byetta Long, there were reports of impaired renal function, such as an increase in serum creatinine levels, renal failure, worsening of chronic renal failure, acute renal failure. Sometimes in such cases it was necessary to prescribe hemodialysis. A number of these phenomena could be triggered by the resulting dehydration due to diarrhea and / or vomiting and / or due to the use of drugs that disrupt water metabolism or renal function, which may include diuretics, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme (ACE) inhibitors. When symptomatic treatment was prescribed and the drug that caused these effects was discontinued, the impaired renal function was restored. The nephrotoxicity of Exenatide has not been confirmed in studies.
On the background of therapy with Byetta Long, in rare cases, the development of acute pancreatitis was recorded, usually resolving after the appointment of supportive treatment. However, the appearance of hemorrhagic or necrotizing pancreatitis and / or death was extremely rare. The characteristic symptoms of acute pancreatitis are persistent, intense pain in the abdomen. If you suspect the development of this complication, drug treatment should be discontinued.
With the use of Exenatide, cases of rapid body weight loss have been noted - at a rate of more than 1.5 kg per week. Such weight loss can lead to negative results, and therefore, this side effect requires careful monitoring of the symptoms of cholelithiasis.
Influence on the ability to drive vehicles and complex mechanisms
The study of the influence of Exenatids on the ability to drive vehicles and other mechanisms was not carried out. In the case of using Byetta Long in combination with a sulfonylurea preparation while driving or working with complex mechanisms, it is recommended to take precautions to prevent hypoglycemia.
Application during pregnancy and lactation
Women of reproductive age should use reliable contraception during treatment. Due to the fact that Byeta Long has a long elimination period, drug therapy must be completed at least three months before the onset of the planned pregnancy.
Data on the use of the drug by women during pregnancy are limited. Reproductive toxicity has been found in preclinical animal studies.
There is no evidence to support the ability of exenatide to be excreted in breast milk.
During pregnancy and lactation, Byetta Long treatment is contraindicated.
Pediatric use
In patients under 18 years of age, the use of Byeta Long is contraindicated due to the lack of data confirming the safety and efficacy of drug therapy in children and adolescents.
With impaired renal function
It was found that in patients who received Byetta Long at a dose of 2 mg, in the presence of mild and moderate renal dysfunction, an increase in the systemic level of Exenatide exposure by 23 and 74%, respectively, may be observed, compared with individuals with normal renal function.
In the presence of a mild degree of impairment of renal function (CC 50-80 ml / min), the dose of Byetta Long does not need to be adjusted, with moderate severity (30-50 ml / min) - the use of the drug is not recommended due to limited clinical experience, with a severe degree violations (CC below 30 ml / min) or end-stage renal failure treatment is contraindicated.
For violations of liver function
In patients with impaired liver function, the pharmacokinetic study of the drug was not performed. Since Byeta Long is eliminated primarily by the kidneys, liver dysfunction is likely to have no effect on blood levels of Exenatide.
In the presence of liver disease there is no need to adjust the dose of the drug.
Use in the elderly
Data on elderly patients are limited, however, according to the available data, no significant changes in the level of Exenatide exposure are expected with increasing age to 75 years.
When Exenatide was used 2 times a day at a dose of 0.01 mg in patients with type 2 diabetes at the age of 75–85 years, there was an increase in AUC (area under the pharmacokinetic curve) by about 36% compared with that in patients 45–65 years old, which, presumably caused by weakening of kidney function in old age.
Elderly patients using Byetta Long do not need to change the dose, but the likelihood of a decrease in renal function with age must be taken into account.
Drug interactions
- oral drugs (drugs that are sensitive to the rate of gastric emptying): a clinically significant decrease in the rate and degree of absorption of these drugs is not expected, as a result of which a change in their doses is not required;
- paracetamol (at a dose of 1000 mg): after 14 weeks of treatment with Byetta Long, there were no significant changes in the AUC of paracetamol taken on an empty stomach or after meals, when compared with the control period; the maximum concentration (C max) of paracetamol after meals and on an empty stomach decreased by 5 and 16%, respectively, and the time to reach the maximum concentration (T max) increased from approximately 1 hour in the control period to 1.3 hours (after meals) and 1.4 hours (on an empty stomach);
- sulfonylurea preparations: the risk of hypoglycemia is aggravated, a change in the dose of these drugs may be required.
The results of the studies on the interaction, recorded when prescribing Exenatide 2 times a day at a dose of 0.01 mg:
- warfarin: when taking warfarin 35 minutes after injection of exenatide, an increase in T max was observed by about 2 hours; no clinically significant changes in C max or AUC were observed, there were reports of an increase in INR; at the initial stage of therapy with Byetta Long, if it is used simultaneously with warfarin and / or coumarin derivatives, it is necessary to monitor INR values;
- inhibitors of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), including lovastatin at a dose of 40 mg once a day: there was a decrease in C max and AUC of lovastatin by 28 and 40%, respectively, as well as an increase in T max on average up to 4 hours compared with the indicators observed when taking lovastatin alone; during 30-week placebo-controlled studies with the combined use of Exenatide and HMG-CoA reductase inhibitors, no persistent changes in lipid metabolism were recorded; it is not required to adjust the doses of these funds, but if necessary, control the lipid profile;
- levonorgestrel (0.15 mg) and ethinyl estradiol (0.03 mg): there was no change in the C max / C min and AUC values of these substances after taking an oral contraceptive, of which they were components, 1 hour before the administration of Exenatide; when using a combined contraceptive 35 minutes after the introduction of exenatide, no changes in AUC were recorded, however, there was a decrease in C max of levonorgestrel by 27–41%, ethinyl estradiol by 45%, as well as an increase in T max by 2–4 hours as a result of a decrease in the rate of gastric emptying; a decrease in the C max value is not clinically significant, therefore, a change in the dose of oral contraceptives is not required;
- lisinopril and digoxin: there was no clinically significant effect on the C max or AUC of these substances, but there was an increase in T max by approximately 2 hours.
Analogs
The analogues of Byeta Long are Trulicity, Victoza, Byeta, Lixumia, etc.
Terms and conditions of storage
Store in its original packaging in a place protected from light, out of reach of children, at a temperature of 2–8 ° C, without freezing. After opening the pack, the drug can be stored in it in sealed blisters for no more than four weeks at a temperature not exceeding 30 ° C.
The shelf life of the syringe pen is 2 years, the kit is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Byeta Long
Reviews of Byeta Long from patients on medical sites are practically not found, due to the fact that the drug was registered by the Ministry of Health of Russia only in 2017. Experts, on the other hand, speak of Exenatide as an effective antidiabetic agent for patients with type 2 diabetes and a body mass index over 35 kg / m², who could not achieve target glycemic indicators only against the background of monotherapy with metformin / thiazolidinedione, or with a combination of these drugs or a combination of metformin with sulfonylurea preparations (when using these drugs in the maximum tolerated doses). The advantages of long-acting Exenatide therapy also include the cardiovascular safety established in the course of clinical studies and the low frequency of administrations - 4-5 injections per month. The latter, according to experts,can help increase patient adherence to treatment.
The price of Byeta Long in pharmacies
The price of Byetta Long, a powder for preparing a suspension for subcutaneous administration of prolonged action (2 mg / 0.65 ml), can be 12,100-13,155 rubles. per package containing 4 syringe pens.
Byeta Long: prices in online pharmacies
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Drug name Price Pharmacy |
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Byetta Long 2 mg powder for suspension for subcutaneous administration of prolonged action 4 pcs. 10959 RUB Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
