Artlegia (Solution) Instructions for Use

Marketing Authorization Holder

R-Pharm JSC (Russia)

Manufactured By

R-Pharm JSC (Russia)

Or

Ajinomoto Althea, Inc. (USA)

Labeled By

R-PHARM, JSC (Russia)

Or

ORTAT, JSC (Russia)

Quality Control Release

R-PHARM, JSC (Russia)

ATC Code

L04AC (Interleukin inhibitors)

Active Substance

Olokizumab (Rec.INN registered with WHO)

Dosage Form

Artlegia

Subcutaneous administration solution 160 mg/1 ml: fl. 0.4 ml, syringe 0.4 ml

Dosage Form, Packaging, and Composition

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

Excipients: sodium chloride, polysorbate 80, L-histidine hydrochloride monohydrate, sorbitol, water for injections.

0.4 ml – vials with a capacity of 2 ml (1) – cardboard packs.
0.4 ml – vials with a capacity of 2 ml (1) in a kit with 1 sterile syringe with a capacity of 1 ml, 2 needles (size G18 and G27) and 2 sterile alcohol wipes – cardboard packs.
0.4 ml – syringes with a capacity of 1 ml (1) – cardboard inserts (1) in a kit with 1 sterile alcohol wipe – cardboard packs.

Clinical-Pharmacological Group

Immunosuppressive drug – monoclonal antibodies

Pharmacotherapeutic Group

Monoclonal antibodies

Pharmacological Action

Humanized (with an attached hypervariable region) monoclonal antibody belonging to the immunoglobulin G4/kappa isotype. Olokizumab selectively binds to human IL-6 and effectively neutralizes the effects of IL-6 in vivo and in vitro. The obtained data indicate that Olokizumab does not bind significantly to other molecules of the IL-6 family and does not affect their functioning, and also does not activate the IL-6 signaling pathway.

In patients with moderate or severe rheumatoid arthritis, insufficiently controlled by methotrexate therapy, subcutaneous administration of olokizumab at a dose of 64 mg every 2 weeks or 64 mg every 4 weeks caused a sharp decrease in the average level of C-reactive protein in plasma by the 2nd week of treatment. Low CRP levels persisted for 24 weeks throughout the entire treatment period.

In patients receiving Olokizumab, improvement in quality of life, reduction in pain and the number of tender and swollen joints were also more frequently noted. The effect of olokizumab was noticeable as early as 4 weeks of treatment, a pronounced effect developed approximately 12 weeks after the start of the drug administration and persisted for at least 24 weeks.

Pharmacokinetics

After a single subcutaneous administration of olokizumab to patients with mild or moderate rheumatoid arthritis in doses from 0.3 to 6 mg/kg, C_max in the blood increased in a dose-dependent manner. The time to reach C_max was from 4 to 12 days, with determinable concentrations of olokizumab persisting for up to 16 weeks. With repeated administration, C_ss of olokizumab in the blood increased during the initial period of therapy and reached a steady state after 16 and 14 weeks from the start of treatment. With subcutaneous administration, the bioavailability is 63%. In an in vitro study on cryopreserved human hepatocytes, Olokizumab reversed the inhibitory effect of IL-6 on the activity of CYP1A1/2, CYP2B6, CYP2C9, CYP3A4/5 and CYP2C19, as well as on the activity of NTCP. The clearance of olokizumab in patients with mild or moderate rheumatoid arthritis was 0.17 L/day with low or medium individual variability.

Indications

Treatment of patients over 18 years of age with rheumatoid arthritis of moderate or high activity in combination with methotrexate, in case of insufficient effectiveness of methotrexate monotherapy.

ICD codes

Dosage Regimen

Administer subcutaneously into the thigh or anterior abdominal wall.

Rotate injection sites with each administration. Do not inject into areas that are tender, bruised, red, or hardened.

The recommended dose is 64 mg administered once every two weeks or once every four weeks.

Use the 0.4 ml pre-filled syringe or vial to deliver the full 64 mg dose. Do not administer more than 64 mg per injection.

Inspect the solution visually for particulate matter and discoloration prior to administration. The solution should be clear or slightly opalescent and colorless to light yellow. Do not use if the solution is cloudy, discolored, or contains visible particles.

Allow the pre-filled syringe to reach room temperature for approximately 30 minutes before injection. Do not warm the solution in any other way.

Follow aseptic technique during preparation and administration. Clean the injection site with an alcohol wipe.

If a dose is missed, administer the dose as soon as possible. Thereafter, resume the regular dosing schedule.

This medication is intended for use under the guidance of a healthcare professional experienced in the treatment of rheumatoid arthritis.

Continue concomitant methotrexate therapy as prescribed.

Adverse Reactions

Infections and parasitic diseases common – bronchitis; uncommon – pulmonary tuberculosis, skin candidiasis, vulvovaginal candidiasis, pityriasis versicolor, subcutaneous abscess, erysipelas, sepsis caused by staphylococcal infection, toxic shock syndrome.

Metabolism and nutrition disorders very common – leukopenia, neutropenia; uncommon – hypercholesterolemia.

Hepatobiliary disorders very common – increased AST activity, increased ALT activity; common – increased GGT activity.

Skin and subcutaneous tissue disorders common – pruritus, rash; uncommon – sweat discoloration, dermatitis, ecchymosis, pruritic rash.

General disorders and administration site conditions uncommon – injection site pain, erythema.

Investigations common – positive test for Mycobacterium tuberculosis.

Contraindications

Hypersensitivity to olokizumab, active infectious diseases (including tuberculosis); children under 18 years of age; pregnancy, breastfeeding period.

With caution

In patients with a history of serious or opportunistic infections; with concomitant diseases and conditions that are risk factors for the development of infections (including diabetes mellitus, renal failure, use of immunosuppressive drugs, elderly age); in patients who have been in contact with tuberculosis patients; with a history of diverticulitis or intestinal perforations and other risk factors for intestinal perforation; with impaired liver function and liver failure.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function and liver failure.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

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

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Prescribing treatment with olokizumab and monitoring the course of treatment is permitted for physicians with experience in the diagnosis and treatment of rheumatoid arthritis.

Anaphylactic or anaphylactoid reactions: administration of drugs containing proteins may be associated with the occurrence of immunological/allergic or non-immunological drug hypersensitivity reactions, which can be severe. These reactions may occur as an acute infusion reaction, an allergic reaction, or a delayed hypersensitivity reaction.

Infections: patients receiving immunosuppressive drugs, including IL-6 signaling pathway blockers, have an increased frequency of infections. The use of olokizumab is associated with an increased risk of developing or activating infections. Therapy with olokizumab should not be initiated in patients with active infections. If serious infections develop, olokizumab therapy should be discontinued. Patients should be instructed about possible signs and symptoms of infection development that require immediate medical attention.

Tuberculosis infection: before starting therapy with olokizumab, the patient should be examined for the presence of latent tuberculosis infection. Patients with identified latent tuberculosis infection should undergo a standard course of anti-tuberculosis therapy before starting therapy with olokizumab.

Olokizumab should be used with caution in patients who are in close contact (cohabitation or being in other confined spaces, for example, at the workplace, at public gatherings, or in a building for long periods during the day) with a person suffering from active tuberculosis. Before using olokizumab in such patients, the risk-benefit ratio of therapy should be carefully assessed.

Risk of gastrointestinal perforation: cases of gastrointestinal perforation have been known with the use of IL-6 signaling pathway inhibitors, mainly against the background of diverticulitis. Caution should be exercised when using olokizumab in patients with a history of diverticulitis or intestinal perforation and other risk factors for intestinal perforation. If gastrointestinal symptoms, such as abdominal pain, appear during treatment with olokizumab, the patient should be examined immediately.

Renal failure: patients with renal failure were not included in the clinical study of olokizumab. Due to the lack of data, caution should be exercised when using olokizumab in patients with impaired renal function.

Vaccination: the safety of immunization with live vaccines while using IL-6 inhibitors, including olokizumab, has not been established. Patients requiring vaccination with live vaccines were not included in the clinical study.

Effect on ability to drive vehicles and machinery

Studies on the effect of the drug on the ability to drive vehicles and machinery have not been conducted. Although adverse reactions associated with dizziness have not been noted so far during therapy with olokizumab, dizziness was often observed during therapy with other IL-6 inhibitors. Patients experiencing dizziness during therapy with Artlegia should be advised not to drive vehicles or operate machinery until the dizziness subsides.

Drug Interactions

Concomitant use with methotrexate did not affect the exposure of olokizumab. No effect of olokizumab on the exposure of methotrexate is expected with their concomitant use, clinical data are lacking. In all clinical studies in patients with rheumatoid arthritis, Olokizumab was used in combination with methotrexate.

Special clinical studies of drug interactions of olokizumab have not been conducted. According to the results of the clinical study CKE001, no cases of clinically significant drug interactions of olokizumab with other drugs were reported.

In an in vitro study on cryopreserved human hepatocytes, Olokizumab reversed the inhibitory effect of IL-6 on the activity of CYP1A1/2, CYP2B6, CYP2C9, CYP3A4/5 and CYP2C19, as well as on the activity of NTCP. Therefore, it should be taken into account that in patients with active rheumatoid arthritis, dose adjustment of drugs metabolized by these isoenzymes may be required after starting the drug.

The concentration of the following drugs may decrease when used concomitantly with olokizumab (the list is not exhaustive): statins (simvastatin, lovastatin, atorvastatin); oral contraceptives; calcium channel blockers; corticosteroids (dexamethasone, methylprednisolone); warfarin; quinidine; theophylline; tizanidine; phenytoin; pimozide; cyclosporine; sirolimus; tacrolimus; benzodiazepines (e.g., diazepam, alprazolam, triazolam, midazolam, bromazepam).

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.