Emisifera^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Petrovax Pharm NPO, LLC (Russia)

ATC Code

A16AX08 (Teduglutide)

Active Substance

Teduglutide (Rec.INN registered by WHO)

Dosage Form

Emisifera®

Lyophilizate for the preparation of solution for subcutaneous administration 5 mg

Dosage Form, Packaging, and Composition

Lyophilizate for the preparation of solution for subcutaneous administration

5 mg – vials (28 pcs.) – carton packs – By prescription

Pharmacotherapeutic Group

Other agents for the treatment of gastrointestinal diseases and metabolic disorders

Pharmacological Action

Teduglutide is an analog of glucagon-like peptide-2 (GLP-2) produced in Escherichia coli cells using recombinant DNA technology.

Natural human GLP-2, secreted by intestinal L cells, enhances intestinal and portal blood flow, suppresses gastric acid secretion, and reduces intestinal motility. Preclinical studies have shown that Teduglutide preserves mucosal integrity by stimulating repair and normal growth of the intestine through increasing intestinal villus size and crypt depth.

Similar to GLP-2, Teduglutide is a 33-amino acid polypeptide chain in which alanine is replaced by glycine at the second position from the N-terminus. This single amino acid substitution compared to naturally produced GLP-2 results in resistance to in vivo degradation by the enzyme dipeptidyl peptidase-4 (DPP-4), thereby prolonging the half-life of Teduglutide. Teduglutide increases villus size and crypt depth of the intestinal epithelium.

Based on preclinical data and the proposed mechanism of action, along with trophic effects on the intestinal mucosa, there is a risk of stimulating the growth of neoplasms in the small and/or large intestine. Conducted clinical studies could neither exclude nor confirm the presence of this increased risk. Several cases of benign colorectal polyp formation were noted during clinical studies, but their frequency did not increase compared to patients receiving placebo. In addition to the need for colonoscopy with polyp removal prior to initiating therapy, each patient should be continuously monitored taking into account their characteristics (e.g., age, underlying disease, history of polyps).

Pharmacokinetics

Teduglutide is rapidly absorbed from the site of subcutaneous injection. The maximum plasma concentration (C_max) is reached approximately 3-5 hours after administration at all doses. The absolute bioavailability of Teduglutide for subcutaneous administration is high – 88%. No accumulation of Teduglutide was observed after repeated subcutaneous administration. The apparent volume of distribution (V_d) of Teduglutide is 26 L in patients with short bowel syndrome. The metabolism of Teduglutide has not been fully studied. Teduglutide is a peptide, so its metabolism likely follows the primary mechanism of peptide metabolism. The terminal half-life of Teduglutide is approximately 2 hours. After intravenous administration, the plasma clearance of Teduglutide was approximately 127 mL/h/kg, which is equivalent to the glomerular filtration rate (GFR). A pharmacokinetic study confirmed the renal excretion of Teduglutide in patients with renal impairment. The rate and extent of absorption of Teduglutide are dose-proportional after single and repeated subcutaneous administration in doses up to 20 mg.

Indications

For the treatment of patients aged 1 year and older with short bowel syndrome (SBS). Patients should be in a stable condition after a period of intestinal adaptation following surgery.

ICD codes

Dosage Regimen

Administer Emisifera^®subcutaneously once daily.

The recommended dose is 50 mcg/kg of body weight.

Calculate the exact dose based on the patient’s current body weight.

For patients with moderate renal impairment (creatinine clearance 30-50 mL/min), reduce the dose to 25 mcg/kg once daily.

For patients with severe renal impairment (creatinine clearance less than 30 mL/min), reduce the dose to 10 mcg/kg once daily.

No dosage adjustment is required for patients with mild renal impairment or for elderly patients over 65 years of age.

Reconstitute the lyophilizate with the provided solvent immediately before administration.

Rotate injection sites (e.g., thighs, abdomen, upper arms) to minimize local reactions.

Monitor fluid and electrolyte balance closely, especially during the initial weeks of therapy and when adjusting parenteral support.

Discontinue therapy if a malignant neoplasm is diagnosed.

Adverse Reactions

Infections and infestations: Very common – respiratory tract infections; Common – influenza-like illness.

Immune system disorders: Frequency unknown – hypersensitivity.

Metabolism and nutrition disorders: Common – decreased appetite, hypervolemia.

Psychiatric disorders: Common – anxiety, insomnia.

Nervous system disorders: Very common – headache.

Cardiac disorders: Common – chronic heart failure; Uncommon – syncope.

Respiratory, thoracic and mediastinal disorders: Common – cough, dyspnea.

Gastrointestinal disorders: Very common – abdominal distension, abdominal pain, nausea, vomiting, gastrointestinal stoma complications (if present); Common – colorectal polyp, colon stenosis, flatulence, intestinal obstruction, pancreatic duct stenosis, pancreatitis, small intestinal stenosis; Uncommon – duodenal polyp; Frequency unknown – gastric polyp.

Hepatobiliary disorders: Common – cholecystitis, acute cholecystitis.

General disorders and administration site conditions: Common – peripheral edema; Frequency unknown – fluid retention.

Administration site reactions: Very common – injection site hematoma, injection site erythema, injection site pain, injection site swelling, and injection site hemorrhage.

Contraindications

Hypersensitivity to Teduglutide; diagnosed or suspected malignancy; patients with a history (within the last 5 years) of malignant neoplasms of the gastrointestinal tract, including the hepatobiliary system and pancreas; children under 1 year of age.

With caution

Cardiovascular diseases (including heart failure, arterial hypertension); severe clinically unstable comorbidities (including diseases of the heart and blood vessels, lungs, kidneys, liver, central nervous system, endocrine system, infectious diseases); concomitant use with drugs requiring dose titration or having a narrow therapeutic index.

Use in Pregnancy and Lactation

There are no data on the use of Teduglutide in pregnant women. Animal studies have not shown direct or indirect reproductive toxicity of Teduglutide. As a precautionary measure, it is recommended to avoid the use of Teduglutide during pregnancy.

It is not known whether Teduglutide is excreted in human breast milk. In lactating rats, the mean concentration of Teduglutide in milk was less than 3% of their plasma concentration after a single subcutaneous administration of 25 mg/kg. A risk to breastfed newborns/infants cannot be excluded. As a precautionary measure, it is recommended to avoid the use of Teduglutide during breastfeeding.

Use in Hepatic Impairment

Studies of Teduglutide in patients with severe hepatic impairment have not been conducted. According to available data, no dose adjustment is required in patients with moderate hepatic impairment.

Use in Renal Impairment

Dosage regimen adjustment is required in patients with moderate and severe renal impairment (creatinine clearance <50 mL/min).

Pediatric Use

Contraindicated in children under 1 year of age.

Geriatric Use

No dose adjustment is required in elderly patients over 65 years of age.

Special Precautions

Before initiating therapy with Teduglutide, a colonoscopy with polyp removal must be performed. During the first 2 years of Teduglutide therapy, an annual colonoscopy (or alternative imaging method) is recommended. Thereafter, colonoscopy is recommended at least once every 5 years. The need for increased frequency of monitoring is determined based on individual patient assessment (e.g., age, underlying disease). If a polyp is detected, current guidelines for polyp surveillance should be followed. If a malignant tumor develops, Teduglutide therapy should be discontinued.

In a carcinogenicity study of Teduglutide in rats, benign tumors were found in the small intestine and extrahepatic bile ducts. These findings were not confirmed in clinical studies lasting more than one year. If neoplasia is detected, it should be removed. If a malignant tumor develops, Teduglutide therapy should be discontinued.

If symptoms of gallbladder or biliary tract disease, adverse reactions from the pancreas, recurrence of intestinal obstruction, or significant worsening of cardiovascular disease occur, the necessity of continuing Teduglutide therapy should be re-evaluated.

To avoid hypervolemia or dehydration, careful adjustment of parenteral support is required in patients receiving Teduglutide therapy. Electrolyte and fluid balance should be carefully monitored throughout treatment, especially during the initial therapeutic response and treatment discontinuation.

Hypervolemia most frequently developed within the first 4 weeks of therapy and decreased over time.

Due to increased fluid absorption, patients with cardiovascular diseases such as heart failure and hypertension should be monitored for the development of hypervolemia, especially at the start of therapy. Patients should inform their doctor of sudden weight gain, swelling of the face and ankles, and/or shortness of breath. In general, hypervolemia can be prevented by timely appropriate assessment of the need for parenteral nutrition. This assessment should be performed more frequently in the first months of therapy.

Patients receiving Teduglutide should cautiously reduce parenteral nutrition and not discontinue it abruptly. After reducing parenteral nutrition, the patient’s fluid status should be assessed and, if necessary, appropriate correction should be made.

Patients receiving concomitant therapy with oral medications requiring dose titration or with a narrow therapeutic index should be carefully monitored due to possible increased absorption.

Due to the risk of dehydration, Teduglutide therapy should be discontinued with caution.

Use in pediatrics

Before initiating Teduglutide, all children and adolescents should undergo a fecal occult blood test. If blood of unclear etiology is present in the stool, colonoscopy/sigmoidoscopy should be performed. Subsequent fecal occult blood testing should be performed annually in all children and adolescents during Teduglutide use.

Colonoscopy/sigmoidoscopy is recommended for all children and adolescents after 1 year of treatment, and then at least once every 5 years as Teduglutide therapy continues, as well as in case of new or unexplained gastrointestinal bleeding.

Effect on ability to drive and use machines

Teduglutide may cause syncope, which should be considered when used in patients engaged in potentially hazardous activities requiring high concentration and speed of psychomotor reactions.

Drug Interactions

Given the pharmacodynamic effect of Teduglutide, there is a possibility of increased absorption of concomitantly administered medicinal products.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.