Tremfya (Solution) Instructions for Use

Marketing Authorization Holder

Johnson & Johnson, LLC (Russia)

Manufactured By

Cilag, AG (Switzerland)

ATC Code

L04AC16 (Guselkumab)

Active Substance

Guselkumab (Rec.INN registered by WHO)

Dosage Form

Tremfya

Solution for subcutaneous administration 100 mg/1 ml: pen-injector 1 ml

Dosage Form, Packaging, and Composition

Solution for subcutaneous administration colorless or with a brownish, or brownish-yellow, or yellowish tint, transparent or slightly opalescent; may contain a small amount of small transparent or white protein particles.

Excipients: sucrose – 79 mg, L-histidine – 0.6 mg, L-histidine hydrochloride monohydrate – 1.5 mg, polysorbate 80 – 0.5 mg, water for injections – up to 1 ml.

1 ml – disposable pen-injectors (1) – cardboard packs.

Clinical-Pharmacological Group

Myotropic antispasmodic

Pharmacotherapeutic Group

Immunosuppressants, interleukin inhibitors

Pharmacological Action

A human monoclonal antibody of the IgG1λ type, which selectively binds to the interleukin-23 (IL-23) protein with high specificity and affinity. IL-23 is a regulatory cytokine that influences the differentiation, proliferation, and viability of T-cell subpopulations (e.g., Th17 and Tc17) and immature subpopulations of immune cells that are a source of effector cytokines, including IL-17A, IL-17F, and IL-22, which contribute to the development of inflammatory diseases.

In human studies, selective blockade of IL-23 has been shown to normalize the production of these cytokines. The concentration of IL-23 is elevated in the skin of patients with plaque psoriasis. In vitro studies have shown that Guselkumab inhibits the biological activity of IL-23 by blocking its interaction with the IL-23 receptor on the cell surface, thereby disrupting IL-23-mediated signaling, activation, and cytokine cascades.

The clinical effects of guselkumab in plaque psoriasis are associated with the blockade of the IL-23 cytokine pathway.

Guselkumab therapy has been shown to lead to a reduction in the expression of IL-23/Th17 pathway genes and a change in the expression profile of genes associated with psoriasis. Guselkumab therapy led to an improvement in histological parameters, including a reduction in epidermal layer thickness and a decrease in the specific number of T-cells.

Furthermore, patients treated with guselkumab showed a reduction in plasma concentrations of IL-17A, IL-17F, and IL-22 compared to the placebo group. These findings correlate with the positive clinical effect observed with the use of guselkumab in patients with plaque psoriasis.

Guselkumab has the potential for immunogenicity. Among patients in whom antibody formation to the drug was detected, approximately 7% of antibodies were classified as neutralizing, which represents 0.4% of the total number of patients treated with Guselkumab. The formation of antibodies to guselkumab was not associated with lower efficacy or the development of injection site reactions.

Pharmacokinetics

In healthy volunteers after a single subcutaneous injection of 100 mg, the mean C_max of guselkumab in plasma was 8.09±3.68 µg/ml and was reached approximately 5.5 days after administration. The steady-state plasma concentration (C_ss) of guselkumab was reached by week 20 after subcutaneous administration of guselkumab at a dose of 100 mg at weeks 0 and 4, followed by administrations every 8 weeks.

The absolute bioavailability of guselkumab after a single subcutaneous injection of 100 mg in healthy volunteers was about 49%. In various studies, the mean volume of distribution (V_d) in the terminal phase after a single intravenous administration to healthy volunteers ranged from 7 to 10 L. The exact metabolic pathway of guselkumab has not been determined.

It is assumed that Guselkumab, as a human monoclonal IgG antibody, should be broken down into small peptides and amino acids via various catabolic pathways, similar to other endogenous IgG antibodies. The mean systemic clearance after a single intravenous administration in healthy volunteers ranged from 0.288 to 0.479 L/day in various studies. The mean half-life (T_1/2) of guselkumab was about 17 days in healthy volunteers and ranged from 15 to 18 days in patients with plaque psoriasis in various studies.

Systemic exposure to guselkumab (C_max and AUC) after a single subcutaneous administration in doses from 10 mg to 300 mg to healthy volunteers and patients with plaque psoriasis increased approximately proportionally to the dose.

Indications

Treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy.

ICD codes

Dosage Regimen

Intended for use under the supervision and monitoring of a physician.

For subcutaneous injection.

The recommended dose is 100 mg as a subcutaneous injection. The second injection is administered 4 weeks after the first, followed by administrations once every 8 weeks.

Discontinuation of therapy should be considered in patients who show no response to therapy after 16 weeks of use.

Adverse Reactions

Infections and infestations very common – upper respiratory tract infections; common – gastroenteritis, fungal skin infections, infections caused by herpes simplex virus.

Immune system disorders uncommon – hypersensitivity.

Nervous system disorders common – headache.

Gastrointestinal disorders common – diarrhea.

Allergic reactions common – urticaria.

Musculoskeletal and connective tissue disorders common – arthralgia.

Local reactions pain and redness at the injection site.

Contraindications

Severe hypersensitivity to guselkumab;
Clinically significant active infections (e.g., active tuberculosis); children under 18 years of age.

Use in Pregnancy and Lactation

There are no data on the use of guselkumab in pregnant women. In animal studies, no direct or indirect adverse effects of guselkumab on pregnancy, embryonic/fetal development, childbirth, or postnatal development were observed. As a precautionary measure, it is advisable to avoid the use of guselkumab during pregnancy.

Women of childbearing potential should use effective methods of contraception during treatment and for at least 12 weeks after its discontinuation.

It is currently unknown whether Guselkumab is excreted in human breast milk. The decision to discontinue breastfeeding during treatment with guselkumab and for 12 weeks after the last dose, or to discontinue therapy, should be made taking into account the benefits of breastfeeding for the infant and the benefits of therapy for the mother.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

Therapy with guselkumab should not be initiated in patients with any clinically significant active infection until the infection has resolved or until adequate therapy for the infection has been initiated.

If a patient develops a clinically significant or serious infection, or if there is no response to standard therapy for an infection, the patient should be closely monitored and guselkumab therapy should be discontinued until the infection resolves.

Guselkumab should not be used in patients with active tuberculosis. The appropriateness of anti-tuberculosis therapy should be considered before initiating treatment with guselkumab in patients with a history of latent or active tuberculosis for whom there is no confirmation of an adequate course of tuberculosis therapy.

If severe hypersensitivity reactions occur, the use of guselkumab should be discontinued immediately and appropriate therapy initiated.

Overdose

The need for all age-appropriate vaccinations according to the immunization schedule should be considered before starting therapy with guselkumab. Live vaccines should not be administered to patients receiving guselkumab therapy (there are no data on the response to the administration of live or inactivated vaccines).

If administration of a live viral or bacterial vaccine is necessary, the use of guselkumab should be suspended for at least 12 weeks after the last dose and may be resumed no earlier than 2 weeks after vaccination.

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.