Infliximab

Remicade

The most common side effects of infliximab include:

• upper respiratory tract infections,
• urinary tract infections,
• cough,
• rash,
• back pain,
• nausea,
• vomiting,
• abdominal pain,
• headache,
• weakness and
• fever.

Other important side effects include:

• low or high blood pressure,
• chest pain,
• difficulty breathing,
• rash,
• itching,
• fever and
• chills

Reactions listed above could indicate an allergy to the infliximab. They are more common among patients who develop antibodies to infliximab and are less likely to occur in patients who are taking drugs that suppress the immune system, such as methotrexate.

Infliximab should be discontinued if serious reactions occur. Serious infections have been reported with other drugs that block TNF- alpha, and infections have been reported during treatment with infliximab. Therefore, infliximab should not be used in patients with serious infections. Moreover, infliximab should be discontinued if a serious infection develops during treatment. Testing for tuberculosis (PPD tests for TB) should be doneprior to treatment with infliximab because of reports of reactivation of tuberculosis in patients taking infliximab. Such patients should be treated for tuberculosis.

Decreased white and red blood cell and decreased platelet counts have been reported with infliximab. Vasculitis (inflammation of the arteries) also has been reported.

Patients with Crohn's disease or rheumatoid arthritis, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of malignant lymphoma. More malignancies have been observed in open-label, uncontrolled clinical studies at a rate several-fold higher than expected in the general population. In controlled studies of TNF-alpha blocking agents, including infliximab, more cases of lymphoma and other malignancies have been observed among patients receiving the agents than among control group patients.

Use of infliximab in pregnant women has not been adequately evaluated.

It is not known if infliximab is secreted in breast milk, and, therefore, if there are effects on the nursing infant.

Infliximab, the active ingredient in REMICADE, is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions) specific for human tumor necrosis factor-alpha (TNFα). It has a molecular weight of approximately 149.1 kilodaltons. Infliximab is produced by a recombinant cell line cultured by continuous perfusion and is purified by a series of steps that includes measures to inactivate and remove viruses.

REMICADE is supplied as a sterile, white, lyophilized powder for intravenous infusion. Following reconstitution with 10 mL of Sterile Water for Injection, USP, the resulting pH is approximately 7.2. Each single-dose vial contains 100 mg infliximab, dibasic sodium phosphate, dihydrate (6.1 mg), monobasic sodium phosphate, monohydrate (2.2 mg), polysorbate 80 (0.5 mg), and sucrose (500 mg). No preservatives are present.

REFERENCES

1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221- S247.

2. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.

Single doses up to 20 mg/kg have been administered without any direct toxic effect. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.

Infliximab is a prescription medication used to treat several types of autoimmune disorders including:

• rheumatoid arthritis
• Crohn’s disease
• ulcerative colitis
• ankylosing spondylitis
• psoriasis
• psoriatic arthritis

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with infliximab including the following:

• serious infections, including fungal infections. Do not administer infliximab during an active infection. If an infection develops, monitor carefully and stop infliximab if infection becomes serious.
• increased risk of malignancies. The incidence of malignancies including lymphoma is greater in patients treated with infliximab.
• hepatitis B virus (HBV) reactivation. Patients should be tested for HBV infection before starting infliximab. Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop infliximab and begin anti-viral therapy.
• hepatotoxicity (liver damage). Rare severe liver reactions, some fatal or necessitating liver transplantation, have occurred in patients receiving infliximab. Tell your doctor if you notice yellowing of the skin or eyes while receiving infliximab.
• heart failure. New onset or worsening symptoms of heart failure may occur.
• hypersensitivity. Serious infusion reactions including anaphylaxis or serum sickness-like reactions may occur. Tell your doctor or get medical help right away if you get any of these symptoms during or after an infusion this medication:
  • hives (red itchy welts) or rash
  • itching
  • swelling of your lips, tongue, throat or face
  • sudden cough
  • shortness of breath, difficulty breathing, or wheezing
  • weakness
  • dizziness or feel faint
  • palpitations (feel like your heart is racing or fluttering)
  • chest pain

Do not take infliximab if you are allergic to infliximab or to any of its ingredients.

Do not use high doses of infliximab if you have moderate or severe heart failure.

You should not use this medication if you are allergic to infliximab, or if you are also being treated with anakinra (Kineret) or abatacept (Orencia).

Some people using infliximab have developed a rare fast-growing type of lymphoma (cancer). This condition affects the liver, spleen, and bone marrow, and it can be fatal. This has occurred mainly in teenagers and young adults using infliximab or similar medicines to treat Crohn's disease or ulcerative colitis.

Call your doctor at once if you have any of the following symptoms: fever, night sweats, itching, loss of appetite, weight loss, tiredness, feeling full after eating only a small amount, pain in your upper stomach that may spread to your shoulder, nausea, easy bruising or bleeding, pale skin, feeling light-headed or short of breath, rapid heart rate, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

Infliximab can lower blood cells that help your body fight infections. Your blood may need to be tested often. Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding injury. Serious and sometimes fatal infections may occur during treatment with infliximab. Contact your doctor right away if you have signs of infection such as: fever, chills, flu symptoms, or pain, warmth, or redness of your skin.

Before you receive infliximab, tell your doctor if you have heart failure or other heart problems, an active or recent infection, diabetes, liver disease, seizures, chronic obstructive pulmonary disease (COPD), a history of cancer, a weak immune system, numbness or tingling, a nerve or muscle disorder, or if you have recently received a vaccine.

Before you start treatment with infliximab, your doctor may perform tests to make sure you do not have tuberculosis or other infections.

Some infections are more likely to occur in certain areas of the world. Tell your doctor where you live and where you have recently traveled or plan to travel to during treatment.

Do not receive a "live" vaccine while you are being treated with infliximab.

Do not receive a "live" vaccine while using infliximab. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), Bacillus Calmette-Guérin (BCG), oral polio, rotavirus, smallpox, typhoid, yellow fever, varicella (chickenpox), H1N1 influenza, and nasal flu vaccine.

Make sure your child is current on all vaccines before he or she starts treatment with infliximab.

Avoid activities that may increase your risk of bleeding injury.

Do not receive a "live" vaccine while using infliximab, or you could develop a serious infection. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

• Inflectra
• Remicade
• Renflexis

Juvenile idiopathic arthritis

Data from randomized, placebo-controlled trials support the use of infliximab in the treatment of juvenile idiopathic arthritis (JIA) [Ruperto 2007], [Ruperto 2010], [ Visvanathan 2010]. Additional trials may be necessary to further define the role of infliximab in this condition.

Based on the American College of Rheumatology guidelines for the treatment of JIA, infliximab is effective and is recommended in the management of patients with systemic JIA who require additional therapy due to continued disease activity following initial therapy.

Behçet syndrome uveitis

Initial data from 3 case series suggest that IV infliximab may play a beneficial role in the management of uveitis associated with Behçet syndrome. Additional controlled trials are needed to verify these results.

Pustular psoriasis

Data from noncontrolled studies and case series/reports in a limited number of patients support the use of infliximab in the treatment of pustular psoriasis. Additional trials may be necessary to further define the role of infliximab in this condition.

Based on the National Psoriasis Foundation (NPF) Medical Board consensus statement, infliximab is recommended as a first-line treatment option for some adults with pustular psoriasis, particularly those with severe, acute generalized forms of disease.

Pyoderma gangrenosum

Initial data suggest that infliximab may be beneficial in the treatment of refractory pyoderma gangrenosum. Larger, controlled trials are needed to fully assess the efficacy of infliximab for the treatment of pyoderma gangrenosum.

Note: Premedication with antihistamines (H1-antagonist +/- H2-antagonist), acetaminophen, and/or corticosteroids may be considered to prevent and/or manage infusion-related reactions. Renflexis, Inflectra, and Remsima [Canadian product] are approved as biosimilar to Remicade. Approved uses for biosimilar agents may vary (consult product labeling).

Ankylosing spondylitis: IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 6 weeks thereafter

Crohn disease: IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter; dose may be increased to 10 mg/kg in patients who respond but then lose their response. If no response by week 14, consider discontinuing therapy.

Plaque psoriasis: IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter.

Psoriatic arthritis (with or without methotrexate): IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter.

Rheumatoid arthritis (in combination with methotrexate therapy): IV 3 mg/kg at 0, 2, and 6 weeks, followed by 3 mg/kg every 8 weeks thereafter; Remicade doses have ranged from 3 to 10 mg/kg repeated at 4- to 8-week intervals

Ulcerative colitis: IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter. Doses up to 10 mg/kg were studied in clinical trials with similar efficacy observed with both doses (Rutgeerts 2005).

Pustular psoriasis (off-label use): IV: 5 mg/kg at week 0, 2, and 6, followed by 5 mg/kg every 8 weeks for up to 46 weeks (Suguira 2014; Torii 2011)

Dosage adjustment with heart failure (HF): Weigh risk versus benefits for individual patient:

Mild HF (NYHA Class I/II): No dosage adjustment necessary; use with caution and monitor closely for worsening of HF

Moderate to severe (NYHA Class III or IV): ≤5 mg/kg