Infliximab (Lyophilisate) Instructions for Use

ATC Code

L04AB02 (Infliximab)

Active Substance

Infliximab (Rec.INN registered by WHO)

Clinical-Pharmacological Group

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

Pharmacotherapeutic Group

Immunosuppressants; tumor necrosis factor-alpha (TNF-alpha) inhibitors

Pharmacological Action

Infliximab is a TNFα inhibitor. Infliximab is a chimeric murine-human monoclonal antibody. It has a high affinity for TNFα, which is a cytokine with a wide spectrum of biological activity, is also a mediator of the inflammatory response and is involved in immune system modulation processes. It is evident that TNFα plays a role in the development of autoimmune and inflammatory diseases.

Infliximab rapidly binds and forms a stable complex with both forms (soluble and transmembrane) of human TNFα, thereby reducing the functional activity of TNFα. The specificity of infliximab for TNFα is confirmed by its inability to neutralize the cytotoxic effect of lymphotoxin alpha (LTα or TNFβ), a cytokine that interacts with the same receptors as TNFα.

Elevated concentrations of TNFα were detected in the joints of patients with rheumatoid arthritis and correlated with disease activity. In patients with rheumatoid arthritis, therapy with infliximab led to a reduction in the infiltration of inflammatory cells into inflamed joint areas, as well as a decrease in the expression of molecules mediating cellular adhesion, chemotaxis, and tissue destruction.

After therapy with infliximab, a decrease in serum concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP), as well as an increase in hemoglobin concentration in patients with rheumatoid arthritis who had a reduced baseline hemoglobin concentration, were noted. No significant reduction in the number of lymphocytes in peripheral blood or their proliferative response to mitogenic stimulation compared to the response of cells from untreated patients in vitro was detected.

In patients with psoriasis, therapy with infliximab led to a reduction in inflammation in the epidermal layer and normalization of keratinocyte differentiation in psoriatic plaques. In patients with psoriatic arthritis, short-term therapy with infliximab was accompanied by a reduction in the number of T-cells and blood vessels in the synovial membrane and skin areas affected by the psoriatic process.

Histological examination of colon biopsies taken before and 4 weeks after infliximab administration revealed a significant decrease in TNFα concentration. Therapy with infliximab in patients with Crohn’s disease was accompanied by a significant decrease in the concentration of the nonspecific serum marker of inflammation, CRP. The total number of peripheral blood leukocytes changed minimally during infliximab therapy, although a trend towards normalization of the numbers of lymphocytes, monocytes, and neutrophils was observed.

In patients treated with Infliximab, the proliferative response of peripheral blood mononuclear cells to stimulation was not reduced compared to that in untreated patients. No significant changes in cytokine secretion by stimulated peripheral blood mononuclear cells after infliximab therapy were detected. Examination of mononuclear cells from lamina propria biopsies of the intestinal mucosa showed that infliximab therapy causes a decrease in the number of cells expressing TNFα and interferon gamma. Additional histological studies confirmed that Infliximab reduces the infiltration of inflammatory cells and the content of inflammatory markers in affected areas of the intestine. Endoscopic studies demonstrated healing of the intestinal mucosa in patients treated with Infliximab.

Indications

Active rheumatoid arthritis in patients 18 years and older (in combination with methotrexate) when previous therapy, including treatment with methotrexate, has been ineffective.

Severe active Crohn’s disease (including with fistula formation) in patients 18 years and older, not responding to standard therapy, including corticosteroids and/or immunosuppressants.

Active Crohn’s disease of moderate or severe degree in children and adolescents aged 6 to 17 years inclusive – in case of inefficacy, intolerance, or contraindications to standard therapy, including corticosteroids and/or immunosuppressants.

Ulcerative colitis in adults when standard therapy is ineffective.

Ulcerative colitis of moderate or severe degree in children and adolescents aged 6 to 17 years – with insufficient efficacy of standard therapy with corticosteroids, 6-mercaptopurine, or azathioprine, or in case of intolerance or contraindications to standard therapy.

Ankylosing spondylitis.

Psoriatic arthritis.

Psoriasis.

ICD codes

Dosage Regimen

Administer as an intravenous infusion over a period of not less than 2 hours. Do not administer as an intravenous push or bolus.

Reconstitute each 100 mg vial with 10 mL of Sterile Water for Injections. Direct the stream of water to the side of the vial to minimize foaming. Swirl the vial gently to dissolve. Do not shake. Allow the reconstituted solution to stand for 5 minutes.

The resulting concentration is 10 mg/mL. Further dilute the total dose of the reconstituted infliximab solution in 250 mL of 0.9% Sodium Chloride infusion solution. The final concentration should be within 0.4 mg/mL to 4 mg/mL.

Initiate therapy with a starting dose based on indication and patient weight. For rheumatoid arthritis, administer 3 mg/kg at Weeks 0, 2, and 6, then every 8 weeks thereafter, in combination with methotrexate.

For Crohn’s disease and ulcerative colitis in adults, administer 5 mg/kg at Weeks 0, 2, and 6, then every 8 weeks. For pediatric patients (6-17 years), administer 5 mg/kg at Weeks 0, 2, and 6, then every 8 weeks.

For ankylosing spondylitis and psoriatic arthritis, administer 5 mg/kg at Weeks 0, 2, and 6, then every 6 to 8 weeks.

For plaque psoriasis, administer 5 mg/kg at Weeks 0, 2, and 6, then every 8 weeks.

Monitor patients for at least 1-2 hours post-infusion for acute hypersensitivity reactions. Premedication with an antihistamine, hydrocortisone, and/or paracetamol may be considered to reduce infusion-related reactions.

If a patient does not respond by Week 14, do not continue treatment. For patients who respond, consider increasing the dose up to 10 mg/kg or shortening the dosing interval if a patient later loses response.

Use the diluted solution immediately. If not used immediately, store the infusion solution at 2°C to 8°C for a maximum of 24 hours. Do not freeze.

Adverse Reactions

From the nervous system common – headache, dizziness, feeling tired; rare – depression, psychosis, anxiety, amnesia, apathy, nervousness, drowsiness.

From the digestive system common – nausea, diarrhea, abdominal pain, dyspepsia; rare – constipation, gastroesophageal reflux, cheilitis, diverticulitis, impaired liver function, cholecystitis.

From the hematopoietic system rare – anemia, leukopenia, lymphadenopathy, lymphocytosis, lymphopenia, neutropenia, thrombocytopenia.

From the cardiovascular system common – flushing, chest pain; rare – arterial hypertension, arterial hypotension, syncope, thrombophlebitis, bradycardia, palpitations, vasospasm, cyanosis, peripheral circulatory disorder, arrhythmia, edema.

From the respiratory system common – dyspnea, viral infection (influenza, herpes), fever, upper respiratory tract infections, bronchitis, pneumonia; rare – bronchospasm, pleurisy, pulmonary edema.

From the organ of vision rare – conjunctivitis, keratoconjunctivitis, endophthalmitis.

From the urinary system rare – urinary tract infections, pyelonephritis.

From the blood coagulation system rare – ecchymosis/hematoma, petechiae, epistaxis.

Dermatological reactions common – rash, skin rash, itching, urticaria, sweating, dry skin; rare – fungal dermatitis (onychomycosis, eczema), seborrhea, erysipelas, warts, furunculosis, periorbital edema, hyperkeratosis, skin pigmentation disorder, alopecia, bullous rash.

Allergic reactions urticaria, itching, swelling of the face, lips, hands, myalgia and/or arthralgia with fever, formation of autoantibodies, lupus-like syndrome.

Other common – fever; rare – abscesses, cellulitis, sepsis, bacterial and fungal infections, myalgia, arthralgia, vaginitis, infusion syndrome, injection site reaction.

Contraindications

Severe infectious process (including abscess, sepsis, tuberculosis, opportunistic infections), hypersensitivity to infliximab and other murine proteins.

Use in Pregnancy and Lactation

Infliximab is not recommended for use during pregnancy, as it may affect the development of the fetal immune system. Women of childbearing potential during treatment and for at least 6 months after its completion should use reliable methods of contraception.

It is not known whether Infliximab is excreted in human breast milk. If use during lactation is necessary, breastfeeding should be discontinued. Resumption of breastfeeding is allowed no earlier than 6 months after the end of treatment.

Use in Hepatic Impairment

The efficacy and safety of infliximab in patients with liver diseases have not been established.

Use in Renal Impairment

The efficacy and safety of infliximab in patients with kidney diseases have not been established.

Pediatric Use

The safety and efficacy of infliximab in children and adolescents under 17 years of age with rheumatoid arthritis or Crohn’s disease have not been studied.

Geriatric Use

The efficacy and safety of infliximab in elderly patients have not been established.

Special Precautions

When using infliximab, the development of acute allergic reactions and delayed-type allergic reactions is possible.

Some patients may develop antibodies to infliximab, which in rare cases cause severe allergic reactions. In the absence of tolerance to methotrexate or to other non-steroidal immunosuppressants (for example, azathioprine, 6-mercaptopurine) and their discontinuation before or during the use of infliximab, the risk of formation of these antibodies increases.

Delayed-type hypersensitivity reactions were observed with high frequency (25%) in Crohn’s disease after re-treatment was administered 2-4 hours after the initial treatment.

Since the elimination of infliximab occurs over 6 months, the patient should be under medical supervision during this period for the timely detection of signs of an infectious process. The use of infliximab should be discontinued in case of a severe infection or sepsis.

If active tuberculosis is suspected, treatment should be discontinued until the diagnosis is established and appropriate treatment is carried out.

Before starting therapy with infliximab, patients should be thoroughly examined for both active and latent tuberculosis. It should be taken into account that in severely ill patients and patients with immunosuppression, a false-negative tuberculin test may be obtained. If latent tuberculosis is detected, measures must be taken to prevent activation of the process, and the ratio of expected benefit and potential risk of using infliximab in this category of patients should be assessed.

If symptoms resembling lupus-like syndrome (persistent rash, fever, joint pain, fatigue) appear during treatment, and antibodies to DNA are detected, Infliximab should be discontinued.

The efficacy and safety of infliximab in elderly patients, as well as in patients with liver and kidney diseases, have not been established.

The safety and efficacy of infliximab in children and adolescents under 17 years of age with rheumatoid arthritis or Crohn’s disease have not been studied. Until relevant data are obtained, use in this category of patients should be avoided.

Drug Interactions

In patients with rheumatoid arthritis, the simultaneous use of methotrexate reduces the formation of antibodies to infliximab and increases its plasma concentration.

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.