Etanercept PSK (Solution) Instructions for Use

Marketing Authorization Holder

PSK Pharma, LLC (Russia)

ATC Code

L04AB01 (Etanercept)

Active Substance

Etanercept (Rec.INN registered by WHO)

Dosage Form

Etanercept PSK

Solution for subcutaneous administration 50 mg/1 ml: syringes 0.5 ml or 1 ml 4, 8, or 24 pcs. in a kit with wipes

Dosage Form, Packaging, and Composition

Solution for subcutaneous administration from colorless to yellowish, transparent or slightly opalescent.

Excipients: glycine – 5.6 mg, sodium citrate dihydrate – 4.5 mg, sodium dihydrogen phosphate dihydrate – 2.6 mg, sucrose – 10 mg, sodium chloride – 3.8 mg, hydrochloric acid solution 6M or sodium hydroxide solution 5M – to pH 6.1-6.5, water for injections – to 1 ml.

0.5 ml – syringes (4) in a kit with alcohol wipes – cardboard packs.
0.5 ml – syringes (8) in a kit with alcohol wipes – cardboard packs.
0.5 ml – syringes (24) in a kit with alcohol wipes – cardboard packs.
1 ml – syringes (4) in a kit with alcohol wipes – cardboard packs.
1 ml – syringes (8) in a kit with alcohol wipes – cardboard packs.
1 ml – syringes (24) in a kit with alcohol wipes – cardboard packs.

Clinical-Pharmacological Group

Drug with anti-inflammatory action. Tumor necrosis factor-alpha (TNF-α) inhibitor

Pharmacotherapeutic Group

TNF-α inhibitor

Pharmacological Action

It is an immunosuppressant, a TNFα inhibitor. It is a hybrid dimeric protein molecule consisting of a TNF receptor with a molecular weight of 75 kD, connected to the Fc fragment (CH2 and CH3 domains) of human IgG1. It is produced using recombinant DNA technology in Chinese hamster ovary cells.

Etanercept is a competitive inhibitor of TNF binding to its receptors on the cell surface, and thus inhibits the biological activity of TNF. TNF and lymphotoxin are pro-inflammatory cytokines that bind to two distinct TNF receptors on the cell surface: 55-kilodalton (p55) and 75-kilodalton (p75). Both TNF receptors are present in the body in membrane-bound and free forms. Soluble TNF receptors regulate the biological activity of TNF.

The dimeric structure of the TNF receptor in the etanercept molecule provides its higher affinity for TNFα, which in turn determines more pronounced competitive inhibition of TNFα activity compared to the monomeric soluble TNF receptor present in biological fluids. Etanercept is also capable of modulating biological responses controlled by other biologically active substances (cytokines, adhesion molecules, or proteinases) that are induced or regulated under the influence of TNF.

It does not cause complement-mediated cytolysis of murine T cells expressing TNF on the cell surface. TNF is an endogenous cytokine involved in normal inflammatory and immune responses. TNF is the dominant cytokine in the inflammatory process in rheumatoid arthritis. Elevated levels of TNF are also found in the synovial fluid and psoriatic plaques of patients with psoriatic arthritis, and in the serum and synovial tissue of patients with ankylosing spondylitis. In psoriasis, infiltration by inflammatory cells, including T cells, leads to increased levels of TNF in psoriatic lesions compared to intact skin.

Pharmacokinetics

After subcutaneous administration, Etanercept is absorbed slowly. C_max is reached 48 hours after administration of a single dose. Absolute bioavailability is 76%. The pharmacokinetic curve is biexponential. The mean V_d is 7.6 L, at steady state V_d is 10.4 L. It is slowly eliminated from the body. T_1/2 is about 70 hours. In patients with rheumatoid arthritis, clearance is 0.066 L/h. The pharmacokinetics of etanercept in patients with rheumatoid arthritis, psoriasis, and ankylosing spondylitis are similar.

Indications

Treatment of moderate or severe active rheumatoid arthritis (in combination with methotrexate or as monotherapy).

Treatment of moderate and severe active juvenile idiopathic polyarthritis in children and adolescents aged 2-17 years (with insufficient efficacy or intolerance to methotrexate).

Treatment of active and progressive psoriatic arthritis in adults (when DMARDs are ineffective).

To reduce symptoms in patients with active ankylosing spondylitis (when standard therapy is ineffective).

Treatment of moderate or severe psoriasis in adults (in the presence of contraindications or intolerance to other systemic therapy, including cyclosporine, methotrexate, or PUVA therapy).

Treatment of children aged 6 years and older with chronic severe psoriasis (with intolerance or insufficient efficacy of other systemic therapy or phototherapy).

ICD codes

Dosage Regimen

Administer subcutaneously.

The standard adult dose is 50 mg once weekly.

Alternatively, for certain conditions, administer 25 mg twice weekly, with doses separated by 72 to 96 hours.

For children and adolescents aged 2 to 17 years, the dose is 800 mcg/kg once weekly, with a maximum single dose of 50 mg.

For pediatric patients weighing over 63 kg, administer the full 50 mg adult dose.

Rotate injection sites with each administration; preferred sites include the thigh, abdomen, and upper arm.

Do not inject into areas where the skin is tender, bruised, red, or hard.

For rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, administer 50 mg weekly or 25 mg twice weekly.

For plaque psoriasis in adults, the initial dose is 50 mg twice weekly for 3 months, followed by a maintenance dose of 50 mg once weekly.

For pediatric plaque psoriasis (ages 6-17), the dose is 800 mcg/kg weekly (max 50 mg).

If a dose is missed, administer it as soon as remembered, then resume the regular weekly schedule.

Always inspect the solution visually for particulate matter and discoloration prior to administration; do not use if cloudy or contains particles.

Allow the prefilled syringe to reach room temperature for 15-30 minutes before injection; do not warm in any other way.

Adverse Reactions

Infections: upper respiratory tract infections, cystitis, skin infections, pneumonia, phlegmon, septic arthritis, sepsis, tuberculosis, opportunistic infections (including invasive fungal, protozoal, bacterial and atypical mycobacterial infections, soft tissue and postoperative wound infections; in children – varicella with symptoms of aseptic meningitis, appendicitis, gastroenteritis, aseptic shock caused by group A streptococci.

Immunological reactions: formation of autoimmune antibodies, autoimmune hepatitis, cutaneous manifestations of subacute lupus erythematosus, discoid lupus erythematosus, lupus-like syndrome, macrophage activation syndrome, antineutrophil cytoplasmic seropositive vasculitis.

Allergic reactions: urticaria, anaphylactic reactions, including angioedema and bronchospasm.

Nervous system disorders: headache, dizziness, cerebral ischemia, depression, seizures, demyelinating phenomena in the CNS, similar to those observed in multiple sclerosis or a state of local demyelination, such as optic neuritis and transverse myelitis; in children – depression/personality disorders.

Hematopoietic system disorders: thrombocytopenia, anemia, leukopenia, neutropenia, pancytopenia, aplastic anemia.

Digestive system disorders: abdominal pain, dyspepsia, vomiting, cholecystitis, pancreatitis, gastrointestinal bleeding, appendicitis, autoimmune hepatitis; in children esophagitis, gastritis.

Musculoskeletal system disorders: bursitis, myositis.

Dermatological reactions: itching, rash, worsening of psoriasis, cutaneous forms of vasculitis (including leukocytoclastic vasculitis), Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme; in children – ulcerative skin lesions.

Cardiovascular system disorders: heart failure, myocardial infarction, myocardial ischemia, arterial hypertension, arterial hypotension, deep vein thrombosis, thrombophlebitis, worsening of congestive heart failure.

Urinary system disorders: membranous glomerulonephropathy, kidney stones.

General reactions: fever, asthenia, peripheral edema, lymphadenopathy; in children – type 1 diabetes mellitus.

Local reactions: pain, swelling, redness.

Malignancy: cases of lymphoma, colon cancer, breast cancer, lung cancer, prostate cancer, non-cutaneous solid cancer, skin cancer (not melanoma), melanoma, Merkel cell carcinoma have been described.

Contraindications

Sepsis or conditions with an increased risk of its development; severe active infections, including chronic or localized infections; pregnancy, lactation (breastfeeding); hypersensitivity to etanercept.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Pediatric Use

In children under 4 years of age, the efficacy and safety of etanercept have not been studied. In children and adolescents under 18 years of age, the efficacy and safety of etanercept for the treatment of psoriasis have not been studied.

Special Precautions

The expected benefit of therapy and the existing risk should be carefully weighed when it is necessary to use etanercept in the following categories of patients: with chronic or recurrent infections; those exposed to tuberculosis infection; living or temporarily staying in areas endemic for tuberculosis, mycosis; with histoplasmosis, coccidioidomycosis or blastomycosis; with diseases and conditions predisposing to the development of infections, for example, progressive or therapy-resistant diabetes mellitus, extensive surgical intervention; with moderate and severe alcoholic hepatitis, hepatitis C; with congestive heart failure; immunodeficiency states; hematological disorders, with multiple sclerosis, optic neuritis, transverse myelitis.

Before starting, during, and after completion of treatment with etanercept, the patient should be examined to assess the risk of occurrence and presence of infections, including opportunistic ones. Etanercept should be discontinued if severe infections (including tuberculosis, mycobacterial infection) or sepsis develop.

If hematological disorders develop during treatment, Etanercept should be discontinued.

In patients with chronic heart failure, because during treatment, the course of this disease may worsen.

In patients who are carriers of the hepatitis B virus, reactivation of the infection is possible during treatment with etanercept; in such cases, it should be discontinued immediately.

When using etanercept in patients with diabetes mellitus, dose adjustment of hypoglycemic drugs may be required.

The frequency of development of various types of non-cutaneous malignant tumors was significantly higher in patients with Wegener’s granulomatosis receiving Etanercept than in the control group. Therefore, Etanercept is not recommended for use in patients with Wegener’s granulomatosis.

Etanercept should not be used in patients with psoriasis simultaneously with immunosuppressants or phototherapy, as an enhancement of the immunosuppressive effect is possible.

Vaccination with live vaccines should not be carried out during treatment with etanercept.

Drug Interactions

Etanercept can be used in combination with methotrexate for the treatment of rheumatoid arthritis. In clinical studies on safety and efficacy, it has been shown that methotrexate does not affect the pharmacokinetics of etanercept. The effect of etanercept on the pharmacokinetics of methotrexate in humans has not been studied. The safety and efficacy of the combination with methotrexate for the treatment of psoriasis have not been studied. Etanercept should be used with caution in combination with methotrexate for the treatment of psoriasis.

When etanercept and anakinra are used concomitantly, the frequency of severe infections increases, while the therapeutic effect is not enhanced (this combination is not advisable).

Concomitant use with abatacept was accompanied by an increase in the frequency of serious adverse reactions. No clinical advantages of this combination were noted, therefore concomitant use is not recommended.

When used concomitantly with sulfasalazine, a more pronounced decrease in the number of leukocytes is observed compared with the use of each of these active substances separately.

Etanercept does not have a significant effect on the bioavailability of digoxin. However, in the presence of digoxin, a decrease in the bioavailability of etanercept was observed, which was characterized by significant individual variability.

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.