Sejaro^® (Solution) Instructions for Use

Marketing Authorization Holder

Geropharm, LLC (Russia)

ATC Code

A10BX16 (Tirzepatide)

Active Substance

Tirzepatide

Dosage Forms

	Sejaro®	Solution for subcutaneous injection 2.5 mg/dose
		Solution for subcutaneous injection 5 mg/dose
		Solution for subcutaneous injection 7.5 mg/dose
		Solution for subcutaneous injection 10 mg/dose
		Solution for subcutaneous injection 12.5 mg/dose
		Solution for subcutaneous injection 15 mg/dose

Dosage Form, Packaging, and Composition

Solution for subcutaneous injection

2.4 ml – pre-filled pens – cardboard packs /kit with needles – 4 pcs./ – Not specified

Solution for subcutaneous injection

2.4 ml – pre-filled pens – cardboard packs /kit with needles – 4 pcs./ – Not specified

Solution for subcutaneous injection

2.4 ml – pre-filled pens – cardboard packs /kit with needles – 4 pcs./ – Not specified

Solution for subcutaneous injection

2.4 ml – pre-filled pens – cardboard packs /kit with needles – 4 pcs./ – Not specified

Solution for subcutaneous injection

2.4 ml – pre-filled pens – cardboard packs /kit with needles – 4 pcs./ – Not specified

Solution for subcutaneous injection

2.4 ml – pre-filled pens – cardboard packs /kit with needles – 4 pcs./ – Not specified

Clinical-Pharmacological Group

Drug for the treatment of obesity and type 2 diabetes mellitus – an agonist of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors

Pharmacotherapeutic Group

Drugs for the treatment of diabetes mellitus; hypoglycemic drugs, other than insulins; other hypoglycemic drugs, other than insulins

Pharmacological Action

Tirzepatide is a long-acting agonist of GIP and GLP-1 receptors. Both receptors are present on α- and β-endocrine cells of the pancreas, heart, vascular system, immune cells (leukocytes), in the intestine and kidneys. GIP receptors are also present on adipocytes. Furthermore, GIP and GLP-1 receptors are expressed in areas of the brain involved in appetite regulation.

Tirzepatide has high selectivity for human GIP and GLP-1 receptors. Tirzepatide has high affinity for both GIP and GLP-1 receptors.

The activity of tirzepatide on the GIP receptor is similar to that of the native GIP hormone. The activity of tirzepatide on the GLP-1 receptor is lower compared to the native GLP-1 hormone.

Tirzepatide improves glycemic control by reducing blood glucose concentrations both fasting and postprandial in patients with T2DM through several mechanisms.

Tirzepatide reduces body weight and body fat mass. Mechanisms associated with the reduction of body weight and fat mass include reduced food intake through appetite regulation. According to clinical studies, Tirzepatide reduces energy intake and appetite by enhancing feelings of satiety and fullness, as well as blunting the feeling of hunger.

Pharmacokinetics

Tirzepatide consists of 39 amino acids and has an attached C20 diacid fatty acid component that provides albumin binding and prolongs T_1/2. The C_max of tirzepatide is reached 8-72 hours after dose administration. Steady-state exposure is achieved after 4 weeks of once-weekly administration. Tirzepatide exposure increases proportionally with dose. Similar exposure is achieved with subcutaneous administration of tirzepatide in the anterior abdominal wall, thigh, or upper arm. The absolute bioavailability of tirzepatide after subcutaneous administration was 80%.

The mean apparent V_d of tirzepatide at steady state after subcutaneous administration in patients with T2DM is approximately 10.3 L, and in patients with obesity it is 9.7 L.

Tirzepatide has a high degree of binding to plasma albumin (99%). Tirzepatide is metabolized by proteolysis of the peptide backbone, beta-oxidation of the C20 diacid fatty acid component, and amide hydrolysis.

The mean clearance of tirzepatide in the population is about 0.06 L/h, and the T_1/2 is about 5 days.

Tirzepatide metabolites are primarily excreted in urine and feces. Tirzepatide is not detected unchanged in urine or feces.

Indications

Type 2 diabetes mellitus (T2DM): for the treatment of adults with poorly controlled T2DM as an adjunct to diet and physical activity – as monotherapy, if metformin is unsuitable due to intolerance or contraindications; in addition to other medications for the treatment of T2DM.

Weight control: as an adjunct therapy to a reduced-calorie diet and increased physical activity for weight reduction and weight control in adults over 18 years of age with an initial BMI ≥ 30 kg/m² (obesity) or ≥ 27 kg/m² to < 30 kg/m² (overweight) in the presence of at least one weight-related comorbidity (e.g., hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease, prediabetes or T2DM).

ICD codes

Dosage Regimen

Administer subcutaneously into the abdomen, thigh, or upper arm. The injection site should be rotated with each administration. If the patient is also administering insulin, they should administer the tirzepatide injection in a different injection area.

The initial dose is 2.5 mg once a week. After 4 weeks, the dose should be increased to 5 mg once a week. If necessary, dose increases can be made in 2.5 mg increments after at least 4 weeks on the current dose.

The recommended maintenance doses are 5 mg, 10 mg, and 15 mg.

The maximum dose is 15 mg once a week.

When adding tirzepatide to ongoing metformin and/or a sodium-glucose cotransporter-2 inhibitor (SGLT2i), the current dose of metformin and/or SGLT2i does not need to be adjusted.

When adding tirzepatide to existing therapy with sulfonylureas and/or insulin, a reduction in the dose of sulfonylurea or insulin may be considered to reduce the risk of hypoglycemia. Self-monitoring of blood glucose is necessary to adjust the dose of sulfonylurea and insulin. A stepwise approach to insulin reduction is recommended.

Adverse Reactions

Immune system disorders common – hypersensitivity reactions; rare – anaphylactic reaction, angioedema.

Metabolism and nutrition disorders very common – hypoglycemia when used with sulfonylureas or insulin; common – hypoglycemia when used with metformin and an SGLT2 inhibitor, decreased appetite; uncommon – hypoglycemia when used with metformin, weight decrease.

Nervous system disorders common – dizziness; uncommon – dysgeusia.

Cardiac disorders common – increased heart rate, arterial hypotension.

Gastrointestinal disorders: very common – nausea, diarrhea, vomiting, abdominal pain, constipation; common – dyspepsia, abdominal distension, eructation, flatulence, GERD; uncommon – cholelithiasis, acute pancreatitis

Skin and subcutaneous tissue disorders common – hair loss (alopecia).

General disorders and administration site conditions: common – fatigue.

Administration site conditions uncommon – injection site pain.

Investigations common – increased blood lipase, increased blood amylase, increased blood calcitonin.

Contraindications

Hypersensitivity to tirzepatide; personal or family history of medullary thyroid carcinoma (MTC); multiple endocrine neoplasia (MEN) type 2; type 1 diabetes mellitus (T1DM); diabetic ketoacidosis; pregnancy, breastfeeding period; age under 18 years.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and in women of reproductive potential who are not using contraception.

Contraindicated during breastfeeding.

Use in Hepatic Impairment

Dose adjustment is not required in patients with impaired hepatic function. Experience with tirzepatide in patients with severe hepatic impairment is limited. Use Tirzepatide with caution in this category of patients.

Use in Renal Impairment

Dose adjustment is not required in patients with renal impairment, including end-stage renal disease (ESRD). Experience with tirzepatide in patients with severe renal impairment and ESRD is limited. Use Tirzepatide with caution in this category of patients.

Pediatric Use

Safety and efficacy in children and adolescents under 18 years of age have not been established at this time. Data are not available.

Geriatric Use

Dose adjustment in elderly patients is not required. There are only limited data on the use of tirzepatide in patients aged 85 years and older. Tirzepatide should be used with caution in patients aged 85 years and older, as higher sensitivity in some elderly patients cannot be ruled out.

Special Precautions

In rats of both sexes, Tirzepatide caused a dose-dependent and treatment duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) in a two-year study at clinically relevant plasma exposures. It is unknown whether Tirzepatide causes thyroid C-cell tumors, including MTC, in humans, as the relevance of tirzepatide-induced rodent thyroid C-cell tumors to humans has not been definitively established.

Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for the early detection of MTC in patients treated with Tirzepatide. Such monitoring may increase the risk of unnecessary procedures due to the low specificity of the serum calcitonin test and the high background incidence of thyroid disease. Significantly elevated serum calcitonin values may indicate MTC, and in patients with MTC, calcitonin levels are typically >50 ng/L. If serum calcitonin measurement detects an elevation, the patient should be further evaluated. Patients with thyroid nodules detected on physical examination or neck imaging should also undergo further evaluation.

If pancreatitis is suspected, use of tirzepatide should be discontinued. If pancreatitis is confirmed, tirzepatide should not be restarted. In the absence of other signs and symptoms of acute pancreatitis, elevation of pancreatic enzymes is not predictive of acute pancreatitis.

Patients receiving Tirzepatide concomitantly with medications that enhance insulin secretion (e.g., sulfonylureas) or insulin may have an increased risk of hypoglycemia. The risk of hypoglycemia can be reduced by lowering the dose of the insulin secretagogue or insulin itself.

Tirzepatide is associated with gastrointestinal adverse reactions, including nausea, vomiting, and diarrhea. These adverse reactions may lead to dehydration, which can cause worsening of renal function, including acute renal failure. Patients receiving Tirzepatide should be informed of the potential risk of dehydration due to gastrointestinal adverse reactions and take precautions to avoid hypovolemia and electrolyte imbalances. This should be particularly considered in elderly individuals, who may be more susceptible to such complications.

Tirzepatide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis; it should be used with caution in such patients.

Tirzepatide causes gastrointestinal adverse reactions, including nausea, vomiting, and diarrhea. These events can lead to dehydration, which in severe cases can cause acute kidney injury.

In patients treated with GLP-1 receptor agonists, there have been post-marketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis. Some of these events were reported in patients without known pre-existing renal disease. Most of the reported cases occurred in patients who experienced nausea, vomiting, diarrhea, or dehydration. Renal function should be monitored at the start of treatment or upon dose increase of tirzepatide in patients with renal impairment reporting serious gastrointestinal adverse reactions.

If cholelithiasis is suspected, diagnostic investigations of the gallbladder and appropriate clinical follow-up are indicated.

Tirzepatide has not been studied in patients with non-proliferative diabetic retinopathy requiring urgent therapy, proliferative diabetic retinopathy, or diabetic macular edema; it should be used with caution in these patients with appropriate monitoring.

During surgical interventions under general anesthesia or deep sedation in patients receiving GLP-1 receptor agonists, there is a potential risk of pulmonary aspiration due to delayed gastric emptying and the presence of residual gastric contents.

Effect on ability to drive and use machines

When used concomitantly with sulfonylureas or insulin, precautions are recommended to prevent hypoglycemia while driving and operating machinery.

Drug Interactions

Tirzepatide delays gastric emptying and thus may affect the absorption rate of concomitantly administered oral medications. This effect, leading to a reduction in C_max and a delay in median T_max, is most pronounced at the start of tirzepatide treatment.

Based on the results of a study with paracetamol, which was used as a model drug to assess the effect of tirzepatide on gastric emptying, no need for dose adjustment for most concomitantly administered oral medications has been established. However, it is recommended to monitor patients taking oral medications with a narrow therapeutic index (e.g., warfarin, digoxin), especially at the start of tirzepatide treatment and after dose increase. The risk of delayed action should also be considered for oral medications for which rapid action is important.

After a single dose of tirzepatide 5 mg, the C_max of paracetamol in plasma decreased by 50%, and T_max was delayed by 1 hour. The effect of tirzepatide on the oral absorption of paracetamol is dose- and time-dependent. With low doses (0.5 and 1.5 mg), only a slight change in paracetamol concentration was observed. After administration of four consecutive weekly doses of tirzepatide (5/5/8/10 mg), no effect on the C_max and T_max of paracetamol was observed. There was no effect on AUC. No dose adjustment of paracetamol is required when co-administered with tirzepatide.

Administration of a combined oral contraceptive (0.035 mg ethinylestradiol + 0.25 mg norgestimate, a prodrug of norelgestromin) in the presence of a single dose of tirzepatide (5 mg) led to a reduction in the C_max and AUC of the oral contraceptive. The C_max of ethinylestradiol decreased by 59%, and AUC by 20%, with a delay in T_max of 4 hours. The C_max of norelgestromin decreased by 55%, and AUC by 23%, with a delay in T_max of 4.5 hours. The C_max of norgestimate decreased by 66%, and AUC by 20%, with a delay in T_max of 2.5 hours. This reduction in concentration after a single dose of tirzepatide is not considered clinically significant.

No dose adjustment of oral contraceptives is required.

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.