Tribuvia^® (Concentrate) Instructions for Use

Marketing Authorization Holder

Biocad, JSC (Russia)

ATC Code

L04AG (Monoclonal antibodies)

Active Substance

Seniprutug (Rec.INN registered by WHO)

Dosage Form

Tribuvia®

Concentrate for solution for infusion 25 mg/1 ml: fl. 1 ml, 1.6 ml or 5 ml

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion as a clear or slightly opalescent, colorless to light brown or light yellow liquid.

Excipients: proline, histidine, histidine hydrochloride monohydrate, water for injections.

1 ml (25 mg seniprutug) – colorless glass vials (1) – contour cell packs (1) – cardboard boxes.
1.6 ml (40 mg seniprutug) – colorless glass vials (1) – contour cell packs (1) – cardboard boxes.
1 ml (25 mg seniprutug) – colorless glass vials (1) – cardboard boxes.
1.6 ml (40 mg seniprutug) – colorless glass vials (1) – cardboard boxes.
5 ml (125 mg seniprutug) – colorless glass vials (1) – cardboard boxes.

The application of a first-opening control label on the cardboard box is allowed.

Clinical-Pharmacological Group

Immunosuppressive drug – monoclonal antibodies

Pharmacotherapeutic Group

Immunosuppressants; monoclonal antibodies

Pharmacological Action

Seniprutug is a recombinant monoclonal antibody of the IgG1 class with a fully human constant domain and humanized light and heavy chain variable domains. Seniprutug is produced by genetic engineering in a selected culture of Chinese hamster ovary cells. The target of seniprutug is a segment of the cytotoxic T-lymphocyte receptor – the TRBV9 segment.

Lymphocytes with the TRBV9 segment in their receptor apparatus constitute a small part of all T-lymphocytes in the human body, but they are the main link in immunopathological reactions during the development of axial spondyloarthritis. TRBV9+ T-lymphocytes belong to autoreactive clones and trigger the proliferation and differentiation of immune cells with subsequent synthesis of pro-inflammatory cytokines and tissue damage. In axial spondyloarthritis, TRBV9+ T-lymphocytes accumulate at the site of inflammation. Seniprutug binds to the TRBV9 segment of T-lymphocytes, causing depletion of this specific narrow group of immune cells, which leads to a reduction in inflammation and serves as the basis for reducing the clinical manifestations of axial spondyloarthritis. Seniprutug does not affect other types of T-lymphocytes or B-cells. The ability to recover T-cells, as well as existing cellular and humoral immunity, is preserved.

Pharmacokinetics

When studying the pharmacokinetic properties of a single intravenous administration of seniprutug at doses from 0.03 mg/kg to 7 mg/kg, an increase in the values of pharmacokinetic parameters C_max, AUC_0-2016, AUC_0-∞ was observed with increasing administered dose. Changes in other pharmacokinetic parameters were not dose-dependent.

After the first infusion of seniprutug at a dose of 3.5 mg/kg, which is half the therapeutic dose of 7 mg/kg, the mean C_max value was 94.4 µg/ml, and the mean time to reach it (T_max) was 32.5 h. The mean AUC_0-12w value of seniprutug over three months after the infusion was 34.2 mg×h/ml. When using seniprutug in the recommended dosage regimen, the mean residual concentrations were 2.6 µg/ml before administration at week 12 and 0.6 µg/ml before administration at week 36.

The mean V_d value after the first infusion of seniprutug at a dose of 3.5 mg/kg, which is half the therapeutic dose of 7 mg/kg, is 5.02 ml.

It is known that the metabolism of biological drugs involves proteolytic breakdown into oligopeptides and individual amino acids.

The mean clearance value of seniprutug was 11.7 ml/h. The mean elimination rate constant was 0.00183 and was dose-independent.

The mean T_1/2 value of seniprutug did not have a clear dose dependence in the dose range from 0.03 mg/kg to 7 mg/kg and for the recommended dose of 7 mg/kg was 21.1 days.

Indications

Patients with confirmed carriage of the HLA-B27 antigen and an established diagnosis of active radiographic axial spondyloarthritis (ankylosing spondylitis) who have not responded, had an insufficient response, or have contraindications to NSAIDs, and who have not received biological drugs for the treatment of axial spondyloarthritis.

ICD codes

Dosage Regimen

Treatment of patients with axial spondyloarthritis with seniprutug should be initiated and conducted under the supervision of a specialist experienced in the use of genetically engineered biological drugs.

Seniprutug is intended for administration in both outpatient and inpatient settings. The infusion should be performed under the supervision of qualified and experienced medical personnel. The medical facility where Seniprutug is used must have appropriate medical equipment, including access to emergency medical equipment, as well as drugs such as adrenaline (epinephrine), antihistamines, and corticosteroids, for immediate use in case of adverse reactions, such as severe infusion or allergic reactions.

Before each administration of seniprutug, premedication according to a special scheme should be performed to prevent the development and reduce the severity of infusion reactions, as well as to reduce the emetogenic potential.

The recommended dose of seniprutug is 7 mg/kg as an intravenous infusion and is calculated according to the patient’s body weight.

A stepwise dosing regimen is used to reduce the risk of infusion reactions.

Adverse Reactions

Infections and infestations common – upper respiratory tract infections, lower respiratory tract infections; uncommon – herpes virus infections (nasal herpes and oral herpes), ear infections.

Blood and lymphatic system disorders common – leukocytosis, neutrophilia, anemia, neutropenia, leukopenia, lymphopenia, monocytosis.

Endocrine system disorders common – hyperthyroidism, hypothyroidism.

Cardiac disorders common – bradycardia, tachycardia.

Skin and subcutaneous tissue disorders common – dermatitis; uncommon – pruritus, rash.

General disorders and administration site conditions very common – infusion reactions; common – pyrexia.

Investigations common – increased blood bilirubin level, increased ALT activity, increased AST activity, increased TSH level, decreased thyroxine level, increased blood pressure.

Contraindications

Hypersensitivity to seniprutug; history of life-threatening infusion reactions with the use of monoclonal antibodies; active infectious diseases, including tuberculosis; hepatitis B; severe immunodeficiency of any nature; presence of a malignant neoplasm with a remission duration of less than 5 years, except for cured basal cell carcinoma and cervical cancer in situ; pregnancy, breastfeeding period.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Since Seniprutug is not metabolized in the liver, it is assumed that dose adjustment in patients with impaired liver function is not required.

Use in Renal Impairment

Since Seniprutug is eliminated by catabolic breakdown into peptides and amino acids (the kidneys are not involved in the elimination process), it is assumed that dose adjustment in patients with impaired renal function is not required.

Pediatric Use

The safety and efficacy of seniprutug in children and adolescents under 18 years of age have not been established to date. Data are not available.

Geriatric Use

The efficacy and safety of seniprutug use in patients over 65 years of age have not been studied.

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Special Precautions

Before intravenous infusion of Seniprutug, it is recommended to consume a sufficient amount of water.

Before starting treatment, patients should be informed about the risks and benefits of therapy, as well as the need for follow-up from the start of treatment.

The development of infusion reactions in patients receiving Seniprutug may be associated with the release of cytokines and/or chemical mediators during the depletion of TRBV9+ T-lymphocytes. Infusion reactions may develop during administration and within 24 hours after the infusion.

If life-threatening symptoms of an infusion reaction develop during the infusion, immediate discontinuation of seniprutug administration and appropriate therapy are required. The patient should be monitored until all symptoms of the infusion reaction have completely resolved.

In patients who have developed a life-threatening infusion reaction, continuation of therapy with seniprutug is prohibited.

In case of a severe infusion reaction, the seniprutug infusion should be interrupted immediately. Symptomatic treatment should be provided, after which the patient should be monitored until the symptoms have completely resolved. The decision to continue therapy in case of severe manifestations of an infusion reaction is made individually based on the risk-benefit ratio for the particular patient. If the infusion is resumed, the initial rate should be half the infusion rate at the time the reaction developed. If a hypersensitivity reaction is suspected, the use of seniprutug must be discontinued and not resumed in the future.

If a mild or moderate infusion reaction develops (e.g., headache, nausea, vomiting), the infusion rate should be adjusted.

To monitor the development of immunological reactions, including delayed ones, it is recommended to observe the patient for at least 4 hours after the end of the infusion.

Longer observation and hospitalization may be considered if necessary.

The physician should warn the patient about the possibility of developing an infusion reaction within 24 hours after the infusion and to seek immediate medical attention if any symptoms of an infusion reaction appear.

Infusion reactions may be clinically indistinguishable from type 1 acute hypersensitivity reactions (IgE-mediated).

During therapy with seniprutug, as with other biological drugs, hypersensitivity reactions may develop. For differential diagnosis, it should be taken into account that, unlike infusion reactions, hypersensitivity symptoms more often develop during subsequent administrations, while infusion reactions are most pronounced during the first infusion. If during subsequent infusions previously observed symptoms worsen or new severe symptoms occur, the possibility of a hypersensitivity reaction should be immediately considered. If a hypersensitivity reaction is suspected during the infusion, the infusion must be stopped immediately and not resumed in the future.

Seniprutug is a selective immunosuppressant, and therefore should not be used in patients with active infections (e.g., tuberculosis).

Increased body temperature can be a symptom of both an infusion reaction and an infection. If fever persists for more than 24 hours after seniprutug infusion or is increasing, additional examination of the patient to rule out an infectious disease should be considered. Therapy for an identified infection is carried out according to accepted standards depending on the etiological factor.

Before prescribing seniprutug, all patients should be screened for hepatitis B virus infection according to local guidelines. Seniprutug should not be prescribed to patients with hepatitis B.

Effect on ability to drive and operate machinery

However, after administration of seniprutug, adverse reactions such as dizziness, headache, and decreased blood pressure as part of infusion reactions may occur. In this regard, one should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions shortly after the administration of seniprutug until it is established that these adverse reactions are absent or have ceased.

Drug Interactions

When seniprutug is used concomitantly with immunosuppressive therapy, including corticosteroids in immunosuppressive doses and basic anti-inflammatory drugs (methotrexate, sulfasalazine), an increase in immunosuppression cannot be excluded. Thus, the risk of an additive effect on the immune system must be considered.

The decision on the possibility of using seniprutug in patients receiving immunosuppressive therapy should be made by the attending physician, taking into account the risk-benefit ratio for each individual patient.

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.