Insudive^® (Solution) Instructions for Use

Marketing Authorization Holder

PSK Pharma, LLC (Russia)

ATC Code

A10BJ06 (Semaglutide)

Active Substance

Semaglutide

Dosage Forms

	Insudive®	Solution for subcutaneous administration 0.25 mg/0.5 mg/1 dose: pre-filled pen 1.5 ml with single-use needles (6 pcs.)
		Solution for subcutaneous administration 1 mg/1 dose: pre-filled pen 3 ml with single-use needles (4 pcs.)

Dosage Form, Packaging, and Composition

Solution for subcutaneous administration colorless or with a slight brownish tint, transparent.

** For the 0.25 mg/dose or 0.5 mg/dose pen one pre-filled pen with a volume of 1.5 ml contains 2 mg of semaglutide.

Excipients: disodium phosphate dihydrate, propylene glycol, phenol, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), water for injections.

1.5 ml (0.25 mg/1 dose or 0.5 mg/1 dose) – cartridges, built into single-use multi-dose pens for multiple injections (1) with 6 single-use needles – cardboard packs.

The pack may be equipped with a first-opening control label.

Solution for subcutaneous administration colorless or with a slight brownish tint, transparent.

** For the 1 mg/1 dose pen one pre-filled pen with a volume of 3 ml contains 4 mg of semaglutide.

Excipients: disodium phosphate dihydrate, propylene glycol, phenol, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), water for injections.

3 ml (1 mg/1 dose) – cartridges, built into single-use multi-dose pens for multiple injections (1) with 4 single-use needles – cardboard packs.

The pack may be equipped with a first-opening control label.

Clinical-Pharmacological Group

Hypoglycemic agent. Glucagon-like peptide-1 (GLP-1) receptor agonist

Pharmacotherapeutic Group

Drugs for the treatment of diabetes mellitus; hypoglycemic drugs, other than insulins; glucagon-like peptide-1 (GLP-1) analogues

Pharmacological Action

Hypoglycemic agent.

Semaglutide is a GLP-1 receptor agonist produced by recombinant DNA biotechnology using a Saccharomyces cerevisiae strain followed by purification.

Semaglutide is a GLP-1 analogue with 94% homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor. The GLP-1 receptor is the target for native GLP-1.

GLP-1 is a physiological hormone that has multiple effects on blood glucose regulation, appetite, and the cardiovascular system. The effects on blood glucose concentration and appetite are specifically mediated by GLP-1 receptors located in the pancreas and brain. Pharmacological concentrations of semaglutide reduce blood glucose concentration and body weight through a combination of the effects described below. GLP-1 receptors are also present in specific areas of the heart, blood vessels, immune system, and kidneys, where their activation may have cardiovascular and microcirculatory effects.

Unlike native GLP-1, the prolonged half-life of semaglutide (about 1 week) allows for subcutaneous administration once a week. Binding to albumin is the main mechanism of the long action of semaglutide, which reduces its renal excretion and protects it from metabolic breakdown. In addition, Semaglutide is stable against degradation by the dipeptidyl peptidase-4 enzyme. Semaglutide reduces blood glucose concentration through glucose-dependent stimulation of insulin secretion and suppression of glucagon secretion. Thus, when blood glucose concentration increases, insulin secretion is stimulated and glucagon secretion is suppressed. The mechanism of glycemic reduction also includes a slight delay in gastric emptying in the early postprandial phase. During hypoglycemia, Semaglutide reduces insulin secretion and does not reduce glucagon secretion.

Semaglutide reduces total body weight and fat mass by reducing energy intake. This mechanism involves an overall reduction in appetite, including enhanced satiety signals and weakened hunger signals, as well as improved control of food intake and reduced food cravings. Insulin resistance is also reduced, possibly due to weight loss. In addition, Semaglutide reduces the preference for high-fat food. Animal studies have shown that Semaglutide is taken up by specific areas of the brain and enhances key satiety signals and attenuates key hunger signals. By acting on isolated areas of brain tissue, Semaglutide activates neurons associated with satiety and suppresses neurons associated with hunger.

In clinical studies, Semaglutide had a positive effect on blood lipids, reduced systolic blood pressure, and reduced inflammation.

In animal studies, Semaglutide suppressed the development of atherosclerosis, preventing further progression of aortic plaques and reducing inflammation in plaques.

Pharmacokinetics

The half-life of semaglutide is approximately 1 week. T_max in plasma was from 1 to 3 days after drug administration. AUC was reached after 4-5 weeks of single weekly use. After subcutaneous administration of semaglutide at doses of 0.5 mg and 1 mg, its mean steady-state concentrations in patients with type 2 diabetes were about 16 nmol/L and 30 nmol/L, respectively. Exposure for semaglutide doses of 0.5 mg and 1 mg increases proportionally to the administered dose. Similar exposure is achieved with subcutaneous administration of semaglutide into the anterior abdominal wall, thigh, or shoulder. The absolute bioavailability of semaglutide after subcutaneous administration was 89%. The mean volume of distribution of semaglutide in tissues after subcutaneous administration to patients with type 2 diabetes was approximately 12.5 L. Semaglutide was largely bound to plasma albumin (> 99%). Semaglutide is metabolized by proteolytic cleavage of the protein backbone and subsequent beta-oxidation of the fatty acid side chain. The gastrointestinal tract and kidneys are the main routes of elimination for semaglutide and its metabolites. Two-thirds of the administered dose of semaglutide is excreted by the kidneys, one-third through the intestines. Approximately 3% of the administered dose is excreted by the kidneys as unchanged semaglutide. In patients with type 2 diabetes, the clearance of semaglutide was about 0.05 L/h. With an elimination half-life of approximately 1 week, Semaglutide will be present in the systemic circulation for approximately 5 weeks after administration of the last dose of the drug.

Indications

Type 2 diabetes mellitus as monotherapy; combination therapy with other oral hypoglycemic drugs in patients who have not achieved adequate glycemic control with previous therapy; combination therapy with insulin in patients who have not achieved adequate glycemic control with semaglutide and metformin therapy.

To reduce the risk of major cardiovascular events in patients with type 2 diabetes and high cardiovascular risk – as an addition to standard treatment of cardiovascular diseases.

Some drugs containing Semaglutide are used only for weight control (in addition to a low-calorie diet and physical activity), including weight loss and maintenance, in adults with an initial BMI ≥ 30 kg/m² (obesity), or ≥ 27 kg/m² but < 30 kg/m² (overweight) in the presence of at least one weight-related comorbidity, such as dysglycemia (prediabetes or type 2 diabetes), hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease.

ICD codes

Dosage Regimen

Administer subcutaneously into the abdomen, thigh, or shoulder. Rotate injection sites with each administration. Use once a week, on the same day each week. The time of day can be changed if necessary, provided the interval between two doses is at least 3 days (>72 hours).

For the treatment of type 2 diabetes mellitus, initiate therapy with a dose of 0.25 mg once weekly for 4 weeks. This starting dose is for treatment initiation and is not effective for glycemic control. After 4 weeks, increase the dose to 0.5 mg once weekly. If additional glycemic control is needed after at least 4 weeks at 0.5 mg, the dose can be increased to 1 mg once weekly. The maximum recommended dose is 1 mg once weekly.

For cardiovascular risk reduction in patients with type 2 diabetes, the recommended maintenance dose is 1 mg once weekly. Follow the same dose escalation schedule (0.25 mg → 0.5 mg → 1 mg) to minimize gastrointestinal adverse reactions.

If a dose is missed and the next scheduled dose is more than 2 days away (>48 hours), administer the missed dose as soon as possible. If the next dose is due within 1-2 days, skip the missed dose and administer the next dose on the regular day. Do not administer a double dose to make up for a missed one.

Select the appropriate pre-filled pen for the prescribed dose. The 0.25 mg/0.5 mg pen delivers doses of 0.25 mg or 0.5 mg. The 1 mg pen delivers a dose of 1 mg. Always use a new, sterile single-use needle for each injection. Attach the needle immediately before use. Inspect the solution visually before administration; it should be clear and colorless. Do not use if particulate matter or discoloration is present.

Adverse Reactions

Immune system disorders rarely – anaphylactic reactions.

Metabolism and nutrition disorders very common – hypoglycemia when used in combination with insulin or a sulfonylurea derivative; common – hypoglycemia when used in combination with other oral hypoglycemic drugs, decreased appetite.

Nervous system disorders: common – dizziness, uncommon – dysgeusia.

Eye disorders common – complications of diabetic retinopathy.

Cardiac disorders: increased heart rate.

Gastrointestinal disorders very common – nausea, diarrhea; common – vomiting, abdominal pain, abdominal distension, constipation, dyspepsia, gastritis, gastroesophageal reflux disease, belching, flatulence.

Hepatobiliary disorders common – cholelithiasis; frequency unknown – cholangitis, cholestatic jaundice.

Local reactions reactions at the injection site.

General disorders fatigue.

Investigations common – increased lipase activity, increased amylase activity, weight loss.

Contraindications

Personal or family history of medullary thyroid carcinoma; multiple endocrine neoplasia type 2; type 1 diabetes mellitus; diabetic ketoacidosis; pregnancy and breastfeeding; age under 18 years; severe hepatic impairment; end-stage renal failure (creatinine clearance <15 ml/min); chronic heart failure class IV (according to NYHA classification).

With caution

In patients with renal impairment and in patients with a history of pancreatitis.

Use in Pregnancy and Lactation

Use is contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

No dose adjustment is required in patients with hepatic impairment. Experience with the use of semaglutide in patients with severe hepatic impairment is lacking, use is contraindicated.

Use in Renal Impairment

No dose adjustment is required in patients with renal impairment. Experience in patients with end-stage renal disease is lacking (creatinine clearance <15 ml/min), use is contraindicated.

Pediatric Use

Use is contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Experience with the drug in patients aged 75 years and older is limited.

Special Precautions

Use is contraindicated in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. The drug does not replace insulin.

The use of GLP-1 receptor agonists may be associated with adverse gastrointestinal reactions. This should be considered when treating patients with renal impairment, as nausea, vomiting, and diarrhea can lead to dehydration and worsening of renal function.

Cases of acute pancreatitis have been observed with the use of GLP-1 receptor agonists. Patients should be informed about the characteristic symptoms of acute pancreatitis. Caution should be exercised in patients with a history of pancreatitis.

Patients receiving the drug in combination with a sulfonylurea derivative or insulin may have an increased risk of hypoglycemia.

Caution should be exercised when using semaglutide in patients with diabetic retinopathy receiving insulin therapy. Such patients should be under constant observation and receive treatment in accordance with clinical guidelines.

In the post-marketing period of use of another GLP-1 analogue, liraglutide, cases of medullary thyroid carcinoma were noted. The available data are insufficient to establish or exclude a causal relationship between the occurrence of medullary thyroid carcinoma and the use of GLP-1 analogues. The patient should be informed about the risk of medullary thyroid carcinoma and about the symptoms of a thyroid tumor (appearance of a lump in the neck, dysphagia, dyspnea, persistent hoarseness). A significant increase in plasma calcitonin concentration may indicate medullary thyroid carcinoma (in patients with medullary thyroid carcinoma, plasma calcitonin concentrations are usually >50 ng/L). If an increase in plasma calcitonin concentration is detected, the patient should be further examined. Patients with thyroid nodules detected during physical examination or thyroid ultrasound should also be further examined. The use of semaglutide in patients with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia syndrome type 2 is contraindicated.

Effect on ability to drive vehicles and operate machinery

Semaglutide has no or negligible influence on the ability to drive and use machines. Patients should be cautioned to take precautions to avoid hypoglycemia while driving and operating machinery, especially when used in combination with a sulfonylurea derivative or insulin.

Drug Interactions

The delay in gastric emptying with the use of semaglutide may affect the absorption of concomitant oral medications. Semaglutide should be used with caution in patients taking oral medications that require rapid absorption in the gastrointestinal tract.

Substances added to the drug may cause degradation of semaglutide. Do not mix with other medicines, including infusion solutions.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.