Arcerix^® (Solution) Instructions for Use

Marketing Authorization Holder

R-Pharm JSC (Russia)

ATC Code

L04AC (Interleukin inhibitors)

Active Substance

Goflikicept (Rec.INN registered by WHO)

Dosage Form

Arcerix®

Solution for subcutaneous administration 80 mg/2 ml vial 1 pc.

Dosage Form, Packaging, and Composition

Solution for subcutaneous administration transparent or opalescent, from colorless to light yellow.

Excipients: sucrose, polyethylene glycol 3350, sodium chloride, histidine, water for injections.

Contains less than 1 mmol (23 mg) of sodium per vial, i.e., it is essentially sodium-free.

2 ml – vials of colorless glass (1) – cardboard packs.

Clinical-Pharmacological Group

Drug for the treatment of heart diseases

Pharmacotherapeutic Group

Immunosuppressants, interleukin inhibitors

Pharmacological Action

Goflikicept is a hybrid protein, a heterodimer with a molecular weight of the non-glycosylated form of 126.8 kilodaltons (kDa), which selectively binds and inactivates interleukin-1 beta (IL-1β), with lower affinity Goflikicept binds to interleukin-1 alpha (IL-1α) and the interleukin-1 receptor antagonist (IL-1RA).

Goflikicept is produced by pharmaceutical cultivation of Chinese hamster ovary (CHO) cells in large-scale production.

IL-1 is a cytokine that plays a key role in the development of many inflammatory processes and is considered a cause of recurrent pericarditis. Excessive production of IL-1α, released from damaged pericardial cells, as well as IL-1β, released from inflammatory cells (monocytes, macrophages) through inflammasome activation, triggers an inflammation cascade upon binding of these pro-inflammatory cytokines to the type I IL-1 membrane receptor. Goflikicept, by binding IL-1β and IL-1α, prevents their interaction with the type I IL-1 receptor, thus blocking the inflammatory signal. Inhibition of IL-1 leads to a decrease in the level of inflammatory markers (C-reactive protein), reduction in the severity of chest pain, size of pericardial effusion, and a decrease in the risk of recurrent relapses.

Pharmacokinetics

After a single subcutaneous administration of goflikicept at doses of 80 and 160 mg to healthy volunteers, the mean C_max values in plasma were 5120±1410 and 10300±4470 ng/ml, respectively. C_max was reached within 4-5 days.

After a single subcutaneous administration of goflikicept at doses of 80 to 160 mg to patients with an acute gout attack, the C_max values were 4930±886 and 10200±3350 ng/ml, respectively. A dose-dependent increase in C_max and AUC of goflikicept was observed. The median time to reach C_max was 336 h (14 days). The AUC value with multiple administrations of goflikicept was 18627643.79±6630768.40 ng×h/ml.

The distribution of goflikicept has not been studied.

Goflikicept consists of amino acids and carbohydrates, like a natural immunoglobulin, and therefore its elimination via hepatic metabolic pathways is unlikely. Therefore, it is assumed that the elimination of the drug occurs through standard pathways of immunoglobulin degradation, resulting in breakdown into small peptides and individual amino acids.

T_1/2 in studies in healthy volunteers and patients with an acute gout attack was 10 days.

The results of a pharmacokinetic study of goflikicept after a single subcutaneous administration from 4 to 160 mg (inclusive) in healthy volunteers demonstrated a linear and dose-dependent increase in C_max and AUC_0-t values.

Indications

Pathogenetic therapy of idiopathic recurrent pericarditis in patients 18 years of age and older.

ICD codes

Dosage Regimen

For subcutaneous administration into the anterior abdominal wall area. It is allowed to alternate injection sites with another area suitable for subcutaneous injection: the outer surface of the upper arm, the anterior surface of the thigh, or another area with well-developed subcutaneous fat.

Loading regimen: at a dose of 160 mg (single dose – Day 0) followed by administrations at a dose of 80 mg on Day 7, Day 14.

Maintenance regimen: at a dose of 80 mg once every 2 weeks.

The duration of use is determined individually.

Adverse Reactions

Infections and infestations common – nasopharyngitis, pharyngitis, pneumonia1, urinary tract infection, sepsis.

Blood and lymphatic system disorders common – anemia, neutropenia.

Metabolism and nutrition disorders common – hyperglycemia, dyslipidemia.

Nervous system disorders common – headache.

Gastrointestinal disorders common – nausea, diarrhea, vomiting.

Skin and subcutaneous tissue disorders uncommon – allergic dermatitis.

Musculoskeletal and connective tissue disorders common – arthralgia.

General disorders and administration site conditions: common – injection site reactions, asthenia.

Investigations common – increased ALT, AST, GGT activity, increased creatinine, cholesterol, triglycerides, C-reactive protein concentration.

Contraindications

Hypersensitivity to goflikicept; severe and/or acute infections; pregnancy, breastfeeding period.

With caution

Patients with an increased risk of developing infections, incl. with a history of severe or opportunistic infections; elderly patients; during immunosuppressive therapy; in patients with diabetes mellitus, bronchial asthma, renal failure, chronic alcoholism, HIV infection, immunodeficiency.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

The safety and efficacy of goflikicept in patients with hepatic impairment have not been studied. No data on use are available.

Dosage adjustment is not required

Use in Renal Impairment

Dosage adjustment is not required.

The safety and efficacy of goflikicept in patients with renal impairment have not been studied. No data on use are available.

Pediatric Use

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

Geriatric Use

Dosage adjustment is not required.

Special Precautions

Goflikicept therapy should be discontinued if the patient experiences: increased liver function biochemical parameters (increase in ALT and/or AST activity more than 8 times the ULN, increase in ALT and/or AST activity more than 5 times the ULN for 2 consecutive weeks, increase in ALT and/or AST activity more than 3 times the ULN in combination with an increase in bilirubin level more than 2 times the ULN; increase in ALT and/or AST activity more than 3 times the ULN in combination with jaundice, weakness, nausea, vomiting, pain/heaviness in the hypochondrium, fever, rash, and/or eosinophilia; the patient has any of the following laboratory abnormalities – absolute neutrophil count <500×10⁶/l (<500 /mm³), platelet count <50×10⁹/l (<50000 /mm³ or <50000×10⁶/l), lymphocyte count based on two consecutive tests
<500×10⁶/l (<500 /mm³); confirmed pregnancy during goflikicept therapy; severe or life-threatening infection.

Interleukin-1 (IL-1) blockade may affect the immune response to infections, therefore patients receiving immunosuppressive drugs such as IL-1 inhibitors have a higher frequency of infections.

Patients should be medically monitored for signs of infections developing during treatment with Goflikicept.

Goflikicept treatment should not be initiated in patients with active infections, including localized ones.

The risk of developing tuberculosis infection may increase with the use of IL-1 inhibitors. Before starting therapy and during treatment with goflikicept, the patient should be examined for the presence of tuberculosis infection, including its latent form. If tuberculosis infection is detected, treatment with goflikicept should not be started or continued.

If serious infections develop, goflikicept therapy should be discontinued.

ALT and AST activity should be monitored for 4 weeks after the start of therapy and then every three months during treatment. If necessary, additional examination should be performed to assess liver function.

Blood counts should be assessed before starting therapy, then 8-12 weeks after starting therapy and further as needed based on clinical indications.

Before starting therapy, it is recommended to be vaccinated, in accordance with national recommendations, including pneumococcal vaccine and inactivated influenza vaccine.

Effect on ability to drive vehicles and operate machinery

Patients who experience dizziness during goflikicept therapy should refrain from driving vehicles and operating machinery until the dizziness subsides.

Drug Interactions

The use of goflikicept with TNF inhibitors is not recommended due to an increased risk of serious infections.

It is assumed that by inhibiting IL-1, Goflikicept will suppress IL-6-mediated inhibition of CYP enzyme or transporter protein production, such as CYP1A1/2, 2B6, 2C9, 3A4/5, 2C19 enzymes and the Na-taurocholate cotransporting polypeptide (NTCP).

A decrease in the suppression of CYP enzyme or transporter protein production may lead to decreased concentrations of drugs metabolized by these enzymes. Such a decrease may be clinically significant when using CYP450 substrate drugs with a narrow therapeutic range, the dose of which is adjusted on an individual basis (e.g., warfarin). Thus, the use of goflikicept may lead to changes in systemic concentrations and/or the effect of concomitant drugs that are metabolized with the participation of CYP enzymes and/or NTCP. These drugs include (but are not limited to) certain statins, calcium channel blockers, oral contraceptives, benzodiazepines, as well as theophylline, warfarin, phenytoin, and cyclosporine. Accordingly, during goflikicept therapy, close attention should be paid to the efficacy or toxicity of the patient’s concomitant medications that are known to be metabolized/eliminated with the participation of CYP1A1/2, 2B6, 2C9, 2C19, 3A4/5 and NTCP; furthermore, dose adjustment of concomitant medications may be 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.