Baeta, 250 µg/ml 1.2 ml syringe pen cartridges

Baeta is a hypoglycemic drug. Exenatide (exendin-4) is an incretin mimetic and is a 39-amino acid amidopeptide.

Incretins such as glucagon-like peptide-1 (GFP-1) increase glucose-dependent insulin secretion, improve β-cell function, inhibit inadequately elevated glucagon secretion and slow gastric emptying after they enter the general bloodstream from the gut. Exenatide is a potent incretin mimetic that causes increased glucose-dependent insulin secretion and has other hypoglycemic effects inherent to incretins to improve glycemic control in patients with type 2 diabetes.

The amino acid sequence of exenatide partially matches that of human GFP-1, causing it to bind to and activate human GFP-1 receptors, resulting in enhanced glucose-dependent insulin synthesis and secretion from pancreatic β-cells involving cyclic AMP and/or other intracellular signaling pathways. Exenatide stimulates insulin release from β-cells in the presence of elevated glucose concentrations.

Exenatide differs from insulin, sulfonylurea derivatives, D-phenylalanine derivatives and meglitinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors in chemical structure and pharmacological action.

Exenatide improves glycemic control in patients with type 2 diabetes through the following mechanisms.

In hyperglycemic states, exenatide increases glucose-dependent insulin secretion from pancreatic β-cells. This insulin secretion stops as blood glucose concentrations decrease and approach normal, thereby reducing the potential risk of hypoglycemia.

Insulin secretion during the first 10 minutes (in response to a rise in glycemia), known as the “first phase of insulin response,” is specifically absent in patients with type 2 diabetes. In addition, loss of the first phase of the insulin response is an early disruption of β-cell function in type 2 diabetes. Administration of exenatide restores or significantly enhances both the first and second phases of insulin response in patients with type 2 diabetes.

In patients with type 2 diabetes mellitus against a background of hyperglycemia, administration of exenatide suppresses excessive glucagon secretion. However, exenatide does not disrupt the normal glucagon response to hypoglycemia.

The administration of exenatide has been shown to decrease appetite and food intake; it suppresses gastric motility, leading to delayed gastric emptying.

In patients with type 2 diabetes, therapy with exenatide in combination with metformin, thiazolidinedione and/or sulfonylurea drugs leads to decrease of fasting blood glucose concentration, postprandial blood glucose and HbA1c index, thereby improving glycemic control in these patients.

Indications

Monotherapy:
Type 2 diabetes as monotherapy in addition to diet and exercise to achieve adequate glycemic control.

Combination therapy:
type 2 diabetes as adjunctive therapy to metformin, a sulfonylurea derivative, thiazolidinedione, a combination of metformin and a sulfonylurea derivative, or metformin and thiazolidinedione if adequate glycemic control is not achieved.

Active ingredient

Composition

1 ml contains exenatide 250 µg.

The excipients:

Sodium acetate trihydrate,

glacial acetic acid,

mannitol,

methacresol,

water d/i.

How to take, the dosage

Into the thigh, abdomen, or forearm.

The starting dose is 5 mcg administered 2 times/day at any time during a 60-minute period before a morning and evening meal. The drug should not be administered after a meal. If an injection of the drug is missed, treatment is continued without changing the dose.

In 1 month after the start of treatment, the dose of the drug can be increased to 10 mcg 2 times a day.

When co-administered with metformin, thiazolidinedione or a combination of these drugs, the initial dose of metformin and/or thiazolidinedione may not be changed. If Baeta is combined with sulfonylurea derivatives, a dose reduction of the sulfonylurea derivative may be required to reduce the risk of hypoglycemia.

Interaction

The drug Baeta® should be used with caution in patients taking oral drugs that require rapid absorption from the gastrointestinal tract, because Baeta® may cause delayed gastric emptying. Patients should be advised to take oral drugs, the effect of which depends on their threshold concentration (e.g., antibiotics), at least 1 h before exenatide administration. If such drugs must be taken with food, they should be taken during those meals when exenatide is not administered.

The concomitant administration of digoxin (at a dose of 0.25 mg once daily) with Baeta® decreases the Cmax of digoxin by 17% and increases the Tmax by 2.5 h. However, the overall pharmacokinetic effect at equilibrium is not altered.

The AUC and Cmax of lovastatin were decreased by approximately 40 and 28%, respectively, and Tmax was increased by approximately 4 h on administration of Baeta®. Co-administration of Baetal® with HMG-CoA reductase inhibitors was not accompanied by changes in blood lipid composition (HDL-cholesterol, LDL-cholesterol, total cholesterol and triglycerides).

In patients with mild to moderate arterial hypertension stabilized by lisinopril (5-20 mg/day), Baeta® did not alter the AUC and Cmax of lisinopril at equilibrium. Tmax of lisinopril at equilibrium was increased by 2 h. There were no changes in mean daily MAP and DAP.

It was noted that when warfarin was administered 30 min after Baetal®, the Tmax was increased by approximately 2 h. No clinically significant changes in Cmax and AUC were observed.

The use of Baeta® in combination with insulin, D-phenylalanine derivatives, meglitinides or alpha-glucosidase inhibitors has not been studied.

Special Instructions

Intravenous or intravenous administration is not recommended.

Baet should not be used if particles are found in the solution or if the solution is cloudy or stained.

An antibody to exenatide may appear on therapy with Baetal. However, this does not affect the frequency and types of side effects reported.

Patients should be informed that treatment with Baeta may result in decreased appetite and/or body weight and that there is no need to change the dosing regimen because of these effects.

Patients should read the “Syringe Pen Guide” included with the drug before starting treatment with Baeta.

Contraindications

Side effects

Adverse reactions that occurred more frequently than occasional are listed according to the following gradation: very common – ≥10%, common – ≥1%, but

Digestive system disorders: very often – nausea, vomiting, diarrhea; often – decreased appetite, dyspepsia, gastroesophageal reflux; sometimes – abdominal pain, abdominal bloating, belching, constipation, impaired taste sensation, flatulence.

CNS disorders: frequently – dizziness, headache; rarely – somnolence.

Endocrine system disorders: very often – hypoglycemia (in combination with sulfonylurea derivatives); often – trembling sensation, weakness, hyperhidrosis.

Allergic reactions: rarely – rash, itching, angioedema; extremely rare – anaphylactic reaction.

Others: often – skin reaction at the injection site; rarely – dehydration (associated with nausea, vomiting and/or diarrhea). Several cases of increased clotting time (INR) have been reported with concomitant use of warfarin and exenatide, which was sometimes accompanied by bleeding.

In view of the fact that the incidence of hypoglycemia increases when coadministering Baeta with sulfonylurea derivatives, it is necessary to consider reducing the dose of sulfonylurea derivatives when the risk of hypoglycemia increases. Most episodes of hypoglycemia were mild to moderate in intensity and were managed with oral carbohydrate intake.

In general, side effects were mild to moderate in intensity and did not lead to treatment withdrawal. Most commonly, reported nausea of mild to moderate intensity was dose-dependent and decreased over time without interfering with activities of daily living.

Overdose

Symptoms: severe nausea and vomiting, as well as rapid development of hypoglycemia (if the dose is 10 times higher than the maximum recommended).

Treatment: symptomatic therapy, including parenteral administration of glucose in case of severe hypoglycemia.

Pregnancy use

The drug is contraindicated in pregnancy and during breastfeeding.