Quinliro (Solution) Instructions for Use

Marketing Authorization Holder

Biokhimik, JSC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

Or

Medsintez Plant, LLC (Russia)

ATC Code

A10BJ02 (Liraglutide)

Active Substance

Liraglutide (Rec.INN registered by WHO)

Dosage Form

Quinliro

Solution for subcutaneous administration 6 mg/ml: cartridges 3 ml in pen-injectors 1, 2, 3, 4, 5 or 6 pcs.

Dosage Form, Packaging, and Composition

Solution for subcutaneous administration as a clear, colorless or brownish liquid.

Excipients: disodium phosphate dihydrate, phenol, propylene glycol, sodium hydroxide 2 M solution or hydrochloric acid 1 M (for pH adjustment), water for injection.

3 ml – cartridges of colorless glass (1) – pen-injectors (1, 2, 3, 4, 5, 6 pcs.) – cardboard packs.

Clinical-Pharmacological Group

Hypoglycemic agent. Glucagon-like peptide receptor agonist

Pharmacotherapeutic Group

Hypoglycemic agent – glucagon-like peptide-1 (GLP-1) analog

Pharmacological Action

Hypoglycemic agent. Liraglutide is an acylated analog of human GLP-1, produced by recombinant DNA biotechnology using a strain of Saccharomyces cerevisiae, with 97% homology to human GLP-1, which binds to and activates the GLP-1 receptor (GLP-1R) in humans.

The long plasma half-life of the drug is ensured by three mechanisms: self-association, which results in delayed absorption of the drug, binding to albumin, and a higher level of enzymatic stability against dipeptidyl peptidase-4 (DPP-4) and neutral endopeptidase (NEP).

GLP-1 is a physiological regulator of appetite and caloric intake, and GLP-1 receptors are located in several areas of the brain involved in the regulation of appetite.

In animal studies, peripheral administration of liraglutide led to the uptake of the drug in specific areas of the brain, including the hypothalamus, where liraglutide, through specific activation of GLP-1 receptors, enhanced satiety signals and attenuated hunger signals, thereby leading to a reduction in body weight.

GLP-1 receptors are also present in specific areas of the heart, blood vessels, immune system, and kidneys. Animal studies have shown that liraglutide prevented the further development of aortic plaques and reduced inflammation in them. Furthermore, liraglutide had a beneficial effect on plasma lipids. However, liraglutide did not reduce the size of existing plaques.

Liraglutide stimulates insulin secretion and reduces inappropriately high glucagon secretion in a glucose-dependent manner, and also improves the function of pancreatic beta-cells, leading to a decrease in fasting and postprandial blood glucose concentrations. The mechanism of blood glucose reduction also includes a slight delay in gastric emptying.

Liraglutide reduces body weight in humans primarily by reducing adipose tissue mass. Weight loss occurs due to reduced food intake. Liraglutide does not increase 24-hour energy expenditure. Liraglutide regulates appetite by enhancing feelings of stomach fullness and satiety, while simultaneously attenuating feelings of hunger and reducing prospective food consumption.

In long-term clinical studies involving patients with overweight and obesity, the use of liraglutide in combination with a low-calorie diet and increased physical activity led to significant weight loss.

Pharmacokinetics

Absorption of liraglutide after subcutaneous administration is slow, with a T_max in plasma of 8-12 hours. The C_max of liraglutide in plasma after a single subcutaneous injection of a 600 mcg dose is 9.4 nmol/L. When liraglutide is administered at a dose of 1.8 mg, its average C_ss in plasma reaches approximately 34 nmol/L. The exposure of liraglutide increases proportionally to the administered dose. After a single dose of liraglutide, the intrapopulation coefficient of variation for AUC is 11%. The absolute bioavailability of liraglutide after subcutaneous administration is approximately 55%.

Liraglutide is highly bound to plasma proteins (>98%).

Throughout 24 hours after administration of a single dose of radioactively labeled [³H]-liraglutide to healthy volunteers, the main component in plasma was unchanged liraglutide. Two metabolites were detected in plasma (≤ 9% and ≤ 5% of the total plasma radioactivity level).

Liraglutide is metabolized endogenously without the involvement of any specific organ as the primary route of elimination. After administration of a dose of [³H]-liraglutide, unchanged liraglutide was not detected in urine or feces. Only a small portion of the administered radioactivity in the form of liraglutide-related metabolites (6% and 5%, respectively) was excreted by the kidneys or through the intestines. Radioactive substances are excreted by the kidneys or through the intestines mainly within the first 6-8 days after dose administration and represent three metabolites. The average body clearance after a single subcutaneous dose of liraglutide is approximately 1.2 L/h with an elimination T_1/2 of approximately 13 hours.

Indications

Type 2 diabetes mellitus – to achieve adequate glycemic control in addition to diet therapy and physical exercise as: monotherapy – in adults, adolescents, and children aged 10 years and older; combination therapy with one or more oral hypoglycemic drugs (metformin, a sulfonylurea derivative, a sodium-glucose cotransporter-2 inhibitor [SGLT2 inhibitor] or a drug from the thiazolidinedione group) – in adult patients (18 years and older) who have not achieved adequate glycemic control on prior therapy; combination therapy with metformin – in adolescents and children aged 10 years and older who have not achieved adequate glycemic control during metformin therapy; combination therapy with insulin – in adult patients, adolescents, and children aged 10 years and older who have not achieved adequate glycemic control during therapy with liraglutide and metformin.

To reduce the risk of developing major adverse cardiovascular events in patients with type 2 diabetes mellitus and diagnosed cardiovascular disease as an addition to standard treatment of cardiovascular diseases (based on the analysis of the time to the first major adverse cardiovascular event, which includes death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke).

For weight management in adult patients with a BMI > 30 kg/m² (obesity) or >27 kg/m² to < 30 kg/m² (overweight) in the presence of at least one weight-related comorbidity, such as prediabetes, type 2 diabetes mellitus, arterial hypertension, dyslipidemia, or obstructive sleep apnea syndrome.

For weight management (as an adjunct to a healthy diet and increased physical activity) in adolescents aged 12 years and older with a body weight > 60 kg and obesity (BMI corresponding to >30 kg/m² for adults according to international cut-off points).

ICD codes

Dosage Regimen

Administer subcutaneously once daily at any time of day, independent of meals.

Inject into the abdomen, thigh, or upper arm. Rotate injection sites with each administration to reduce the risk of lipodystrophy.

Do not administer intravenously or intramuscularly.

The initial dose is 0.6 mg per day for one week. This starting dose is not effective for glycemic control or weight management and is intended to reduce gastrointestinal symptoms.

Increase the dose in increments of 0.6 mg at weekly intervals until the recommended maintenance dose is achieved.

For type 2 diabetes mellitus, the recommended maintenance dose is 1.2 mg or 1.8 mg once daily. The dose may be increased to 1.8 mg if the 1.2 mg dose does not provide adequate glycemic control.

For weight management in adults and adolescents, the recommended maintenance dose is 3.0 mg once daily.

Do not use a daily dose of more than 3.0 mg.

If a dose is missed, resume the once-daily regimen with the next scheduled dose. Do not administer an extra dose or increase the next dose to make up for the missed one.

When used in combination with a sulfonylurea, consider reducing the sulfonylurea dose to lower the risk of hypoglycemia.

Instruct patients on proper injection technique using the prefilled pen, including priming a new needle and inspecting the solution for particles or discoloration before each use.

Adverse Reactions

Immune system disorders: rarely – anaphylactic reactions.

Metabolism and nutrition disorders: often – hypoglycemia; infrequently – dehydration.

Psychiatric disorders: often – insomnia.

Nervous system disorders: often – dizziness, dysgeusia.

Cardiac disorders: infrequently – tachycardia.

Gastrointestinal disorders: very often – nausea, vomiting, diarrhea, constipation; often – dry mouth, dyspepsia, gastritis, gastroesophageal reflux, upper abdominal pain, flatulence, belching, abdominal distension; infrequently – pancreatitis, delayed gastric emptying.

Hepatobiliary disorders: often – cholelithiasis; infrequently – cholecystitis.

Skin and subcutaneous tissue disorders: infrequently – urticaria.

Renal and urinary disorders: rarely – acute renal failure, renal impairment.

General disorders and administration site conditions: often – injection site reactions, asthenia, fatigue; infrequently – malaise.

Investigations: often – increased lipase activity, increased amylase activity.

Contraindications

Hypersensitivity to liraglutide; type 1 diabetes mellitus; diabetic ketoacidosis; history of medullary thyroid carcinoma (including family history); multiple endocrine neoplasia type 2; severe renal failure (creatinine clearance less than 30 ml/min); severe hepatic impairment; chronic heart failure NYHA class IV; severe depression, suicidal thoughts or behavior (including history); inflammatory bowel disease; diabetic gastroparesis; pregnancy; breastfeeding period; children under 10 years of age; children under 12 years of age (depending on the indication and the drug used); adolescents aged 12 to 18 years with a body weight ≤60 kg; in patients aged ≥75 years; concomitant use of other drugs for weight management; use in combination with other GLP-1 receptor agonists; secondary obesity due to endocrine disorders or eating disorders, or due to the use of medications that may lead to weight gain.

With caution

In patients with mild to moderate hepatic impairment, thyroid diseases, and a history of acute pancreatitis.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment.

Use in Renal Impairment

Contraindicated in severe renal failure (creatinine clearance less than 30 ml/min).

Pediatric Use

Contraindications: children under 10 years of age; children under 12 years of age (depending on the indication and the drug used); adolescents aged 12 to 18 years with a body weight ≤60 kg.

Geriatric Use

Contraindicated in patients aged ≥75 years.

Special Precautions

In patients with diabetes mellitus, liraglutide should not be used as a substitute for insulin.

Diabetic ketoacidosis has been reported in patients receiving insulin therapy after rapid discontinuation or reduction of the insulin dose.

The use of GLP-1 receptor agonists has been associated with the development of acute pancreatitis. Patients should be informed about the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, liraglutide should be discontinued; if acute pancreatitis is confirmed, therapy with liraglutide should not be restarted.

Cholelithiasis and cholecystitis may lead to hospitalization and cholecystectomy. Patients should be informed about the characteristic symptoms of cholelithiasis and cholecystitis.

Patients should be informed about the risk of medullary thyroid carcinoma and about the symptoms of thyroid tumors (lumps in the neck, dysphagia, dyspnea, persistent hoarseness).

Heart rate should be monitored during treatment at intervals corresponding to usual clinical practice. Patients should be informed about the symptoms of tachycardia (palpitations or feeling of a rapid heartbeat at rest). In patients with clinically significant persistent resting tachycardia, liraglutide therapy should be discontinued.

Patients receiving liraglutide should be informed about the potential risk of dehydration associated with gastrointestinal side effects and the need for hypovolemia prevention.

The risk of hypoglycemia may be higher in patients with type 2 diabetes mellitus receiving liraglutide in combination with sulfonylurea derivatives. This risk can be reduced by lowering the dose of the sulfonylurea derivative.

Patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unexpected changes in mood or behavior. In patients with suicidal thoughts or behavior, liraglutide should be discontinued.

Effect on ability to drive and operate machinery

Liraglutide has no or negligible influence on the ability to drive and operate machines. Due to the risk of hypoglycemia when using the drug, especially when used in combination with sulfonylurea drugs in patients with type 2 diabetes mellitus, caution should be exercised when driving and operating machinery.

Drug Interactions

In vitro, liraglutide has shown a very low potential for pharmacokinetic drug interactions due to metabolism in the cytochrome P450 system, as well as plasma protein binding.

Diarrhea, which sometimes occurs with liraglutide use, may affect the absorption of concomitantly used oral medications.

At the start of liraglutide treatment in patients receiving warfarin, more frequent monitoring of INR is recommended.

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.