infliximab

Infliximab is a medication used in the treatment of autoimmune inflammatory diseases that affect the skin, joints, and gastrointestinal tract.

Infliximab is a human monoclonal immunoglobulin G1 (IgG1) antibody produced in the laboratory using recombinant technology. Infliximab controls inflammation by blocking tumor necrosis factor-alpha (TNF-A), a key protein (cytokine) that is hyperactive in chronic autoimmune diseases.

TNF-A has many biological functions in the promotion of inflammation including induction of pro-inflammatory cytokines such as interleukins 1 and 6, enhancement of leukocyte immune cell migration to the inflammation site, activation of neutrophil and eosinophil immune cells and secretion of liver proteins and enzymes that break down tissue at the inflammation site. Infliximab binds to TNF-A molecules and prevents them from binding to receptors on immune and other cells and activating inflammation.

The uses of infliximab include:

FDA-approved

Adult:

• Rheumatoid arthritis
• Psoriatic arthritis
• Plaque psoriasis
• Ankylosing spondylitis

Adult and Pediatric:

• Crohn’s disease
• Ulcerative colitis

Off-label (Adult)

• Pustular psoriasis
• Pyoderma gangrenosum
• Refractory sarcoidosis

Orphan designation

• Idiopathic pulmonary fibrosis (Adult)
• Juvenile rheumatoid arthritis (Pediatric)

• Do not administer infliximab to patients who have previously had severe hypersensitivity reactions to infliximab, murine proteins or any of the components in the formulation.
• Do not administer doses higher than 5 mg/kg to patients with moderate or severe heart failure (New York Heart Association [NYHA] class III/IV), it can increase the risk of hospitalization and death. Monitor closely and discontinue infliximab if a patient develops new or worsening symptoms of heart failure.
• Infliximab treatment increases the risk for developing serious infections:
• Opportunistic infections reported include bacterial, mycobacterial, invasive fungal, viral, or parasitic infections such as aspergillosis, blastomycosis, candidiasis, listeriosis, coccidioidomycosis, histoplasmosis, legionellosis, pneumocystosis and tuberculosis.
• The risk of infection is higher in patients:
  • Older than 65 years old
  • With comorbidities
  • Receiving other immunosuppressant drugs such as methotrexate or corticosteroids
• Do not initiate infliximab therapy in patients with active serious infections. Discontinue if a patient develops serious infection or sepsis.
  • Consider the risk and benefits of infliximab treatment before initiating in patients with:
  • Chronic or recurrent infection
  • History of opportunistic infection
  • Underlying conditions that predispose them to infection
  • Exposure to tuberculosis; screen patients for latent tuberculosis and if found positive, treat tuberculosis before initiating infliximab. Do not initiate in patients with active tuberculosis.
• Exposure to mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; if a patient develops serious systemic illness, consider appropriate treatment for invasive fungal infection in consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections
• Monitor patients for signs of infection during and after infliximab treatment, including for possible development of tuberculosis in patients who tested negative for latent tuberculosis before starting treatment. Tests for latent tuberculosis infection may also be falsely negative while on infliximab therapy.
• Use of infliximab has been associated with reactivation of hepatitis B virus (HBV). Screen patients for HBV before initiating infliximab, monitor closely during treatment and if a patient develops HBV reactivation, discontinue infliximab and institute HBV treatment in consultation with a physician with expertise in treating HBV.
• There have been reports of malignancies with infliximab, sometimes fatal, including Hodgkin’s and non-Hodgkin’s lymphoma, skin cancers, hepatosplenic T-cell lymphoma (HSTCL), an aggressive, rare type of T-cell lymphoma, and other malignancies. Monitor patients for signs and symptoms and use with caution in patients with a history of malignancy.
• Use infliximab with caution in patients with chronic obstructive pulmonary disease (COPD), who were either current or ex-smokers. Some patients treated with infliximab have developed malignancies.
• There have been rare reports of liver injury, hepatitis, jaundice and liver failure. Monitor patients for signs of liver injury and discontinue infliximab and investigate if liver enzymes are elevated.
• There have been instances of blood disorders such as leukopenia, thrombocytopenia and pancytopenia with infliximab treatment. Administer with caution in patients with pre-existing blood disorders, monitor patients for blood abnormalities and infections, and discontinue if a patient develops such symptoms.
• Infliximab therapy has been associated with hypersensitivity reactions such as hives, hypotension, shortness of breath and anaphylaxis that have occurred during or within 2 hours after infusion. Monitor patients and treat appropriately if such reactions occur.
• There have been rare cases of new onset or exacerbation of neurological disorders. Use infliximab with caution in patients with neurological disorders and discontinue if neurological symptoms occur.
• Infliximab therapy can result in autoantibody formation and rarely, lupus-like syndrome. Discontinue infliximab if a patient develops signs of lupus-like syndrome.
• Use infliximab with caution in patients with a history of seizures. Discontinue treatment if significant adverse reactions develop.
• Update vaccinations in accordance with current vaccination guidelines before initiating infliximab in pediatric and adult patients. Do not administer live vaccines concurrently.
• Do not administer concurrently with other biological products or other immunomodulating drugs including anakinra and abatacept, it may increase the risk for infections.

Common side effects of infliximab include:

• Infusion-related reactions including:
  • Rash
  • Headache
  • Flushing
  • Shortness of breath (dyspnea)
• Development of antinuclear antibodies (ANA)
• Development of antibodies to double-stranded DNA
• Infection
• Abscess
• Upper respiratory tract infection
• Cough
• Sinus inflammation (sinusitis)
• Throat inflammation (pharyngitis)
• Bronchial inflammation (bronchitis)
• Nasal inflammation (rhinitis)
• Lower respiratory tract infection
• Inflammation of the membrane around the lung (pleurisy)
• Pneumonia
• Fluid in lungs (pulmonary edema)
• Nausea
• Abdominal pain
• Diarrhea
• Indigestion (dyspepsia)
• Constipation
• Intestinal obstruction
• Elevation of liver enzyme alanine aminotransferase (ALT)
• Liver inflammation (hepatitis)
• Urinary tract infection
• Rash
• Itching (pruritus)
• Excessive sweating (diaphoresis)
• Dehydration
• Fatigue
• Dizziness
• Pain
• Fever
• Headache
• Back pain
• Joint pain (arthralgia)
• Bone fracture
• Candida yeast infection (candidiasis)
• Viral infection
• Bacterial infection
• Cellulitis
• Sepsis
• Lupus-like symptoms
• Respiratory tract allergic reaction
• High or low blood pressure (hypertension/hypotension)
• Slow heart rate (bradycardia)
• Swelling (edema)
• Flushing
• Blood clot with inflammation in vein (thrombophlebitis)
• Low red blood cell count (anemia)
• Anemia from rapid destruction of red blood cells (hemolytic anemia)
• Low count of leukocyte immune cells (leukopenia)
• Low count of neutrophil immune cells (neutropenia)
• Low platelet count (thrombocytopenia)
• Low count of all types of blood cells (pancytopenia)
• Swelling of lymph nodes (lymphadenopathy)
• Malignant lymphoma
• Hypersensitivity reaction
• Immune-mediated allergic reaction (serum sickness)
• Sarcoidosis, a disease caused by growth of tiny collections of inflammatory cells (granulomas)

Less common side effects of infliximab include:

• Severe allergic reaction (anaphylaxis)
• Fungal lung infection (Pneumocystis pneumonia)
• Tuberculosis
• Infections that can include:
  • Coccidioidomycosis
  • Cytomegalovirus disease
  • Herpes zoster infection
  • Histoplasmosis
  • Nocardiosis
  • Aspergillosis
  • Atypical mycobacterial infection
  • Blastomycosis
  • Fungal infection
  • Listeriosis
  • Parasitic infection
  • Reactivation of HBV
• Opportunistic infections
• Seizure
• Skin reactions including:
  • Skin ulcer
  • Acneiform eruption
  • Acute generalized exanthematous pustulosis
  • Eczematous rash
  • Maculopapular rash
  • Pustular rash
  • Erythema multiforme
  • Lichenoid eruption
  • Psoriasis
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
• Skin cancers including:
  • Malignant melanoma
  • Merkel cell carcinoma
• Chest discomfort
• Fluid buildup around the heart (pericardial effusion)
• New onset or worsening of heart failure symptoms
• Impaired blood flow to the heart (ischemic heart disease)
• Heart attack (myocardial infarction)
• Irregular heart rhythm (cardiac arrhythmia)
• Inflammation of blood vessel (vasculitis)
• Impaired bile flow (cholestasis)
• Toxicity to the liver
• Cholestatic hepatitis
• Autoimmune hepatitis
• Jaundice
• Liver failure
• Malignant growth in colon or rectum
• Malignant growth in cervix
• Malignant growth in breast
• Blood and lymphatic cancers including:
  • Hepatosplenic T-cell lymphoma (HSTCL)
  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma
  • Leukemia
• Severely low count of granulocyte immune cells (agranulocytosis)
• Immune thrombocytopenia
• Blood clots in small vessels due to thrombocytopenia (thrombotic thrombocytopenic purpura)
• Bacterial pneumonia
• Bronchospasm
• Shortness of breath (dyspnea)
• Swelling of throat and voice box (pharyngeal and laryngeal edema)
• Interstitial lung diseases such as
  • Interstitial pneumonitis
  • Pulmonary fibrosis
• Cerebrovascular accident
• Diseases that damage myelin, the protective sheathe over nerve fibers (demyelinating diseases), including:
  • Multiple sclerosis
  • Chronic inflammatory demyelinating polyneuropathy
  • Guillain-Barre syndrome
  • Multifocal motor neuropathy
• Inflammation of the spinal cord (transverse myelitis)
• Nerve damage (neuropathy)
• Optic nerve inflammation (optic neuritis)
• Temporary vision loss
• Lupus-like syndrome

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injection, lyophilized powder for reconstitution

• 100 mg/vial (Remicade, Inflectra, Renflexis, Ixifi, Avsola)

Biosimilars to Remicade

• Inflectra (infliximab-dyyb)
• Renflexis (infliximab-abda)
• Ixifi (infliximab-qbtx)
• Avsola (infliximab-axxq)

Rheumatoid Arthritis

Remicade, Inflectra, Renflexis, Ixifi, Avsola

• Indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately-to-severely active rheumatoid arthritis in combination with methotrexate
• 3 mg/kg intravenous (IV) at 0, 2, and 6 weeks, THEN every 8 weeks thereafter  
• If incomplete response is noted, dose may be increased to 10 mg/kg OR increasing the dosing frequency to every 4 weeks

Psoriatic Arthritis

Remicade, Inflectra, Renflexis, Ixifi, Avsola

• Indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis
• 5 mg/kg IV at 0, 2, and 6 weeks, THEN every 8 weeks thereafter  
• May be used with methotrexate

Plaque Psoriasis

Remicade, Inflectra, Renflexis, Ixifi, Avsola

• Indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate
• Should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician
• 5 mg/kg IV at 0, 2, and 6 weeks, THEN every 8 weeks thereafter  
• Can be used with or without methotrexate

Crohn’s Disease

Remicade, Inflectra, Renflexis, Ixifi, Avsola

• Indicated for moderately-to-severely active Crohn’s disease in patients who have had inadequate response to conventional therapy
• Also, indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease
• 5 mg/kg IV at 0, 2, and 6 weeks, THEN every 8 weeks thereafter  
• For adult patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg
• Patients who do not respond by week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue

Ulcerative Colitis

Remicade, Inflectra, Renflexis, Ixifi, Avsola

• Indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adults with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy
• 5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks  

Ankylosing Spondylitis

Remicade, Inflectra, Renflexis, Ixifi, Avsola

• Indicated for reducing signs and symptoms in patients with active ankylosing spondylitis
• 5 mg/kg IV at 0, 2, and 6 weeks, THEN every 6 weeks thereafter  

Dosage Modifications

• Moderate-to-severe (New York Heart Association [NYHA] class III or IV) heart failure: Not to exceed 5 mg/kg/dose

Dosing Considerations

• Prior to initiating treatment and periodically during therapy, patients should be evaluated for active tuberculosis and tested for latent infection
• Higher incidence of serious infections in infliximab-treated patients 65 years or older; use with caution

Pediatric:

Crohn’s Disease

Remicade, Inflectra, Renflexis, Ixifi, Avsola

• Reduction of signs and symptoms and induction and maintenance of clinical remission in pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease who have had inadequate response to conventional therapy
• Children below 6 years: Not studied
• Children 6 to 17 years: 5 mg/kg IV at 0, 2, and 6 weeks, THEN every 8 weeks thereafter  

Ulcerative Colitis

Remicade, Inflectra, Renflexis, Ixifi, Avsola

• Treatment of moderately to severely active ulcerative colitis in children aged 6 years and above who have had inadequate response to conventional therapy
• Children below 6 years: Not studied
• Children 6 years and above: 5 mg/kg IV at 0, 2, and 6 weeks, THEN every 8 weeks thereafter  

Dosing considerations

• Due to risk of hepatosplenic T-cell lymphoma, a careful risk-benefit assessment should be made when drug is used in combination with other immunosuppressants in pediatric ulcerative colitis patients
• Children should be current with immunizations before starting infliximab
• Do not administer live vaccines while patient is taking infliximab

Overdose

• The potential for toxicity of infliximab in humans is not fully established.
• Single doses of up to 20 mg/kg have been administered without any toxic effect.
• In the event of overdose, patients should be monitored and treated with symptomatic and supportive care.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of infliximab include:
  • upadacitinib
• Infliximab has serious interactions with at least 76 different drugs.
• Infliximab has moderate interactions with at least 30 different drugs.
• Mild interactions of infliximab include:
  • cat's claw

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• It is not known whether infliximab can affect reproductive capacity, or cause fetal harm if administered to a pregnant woman. Infliximab should be used in pregnancy only if clearly needed.
• Infliximab crosses the placenta and has been detected up to 6 months in the infant’s serum after maternal treatment during pregnancy. Live vaccines should not be administered to these infants, because they may be at an increased risk for infection.
• It is not known if infliximab is present in breast milk, but many drugs and immunoglobulins are excreted in breast milk. Decision should be made to discontinue infliximab or breastfeeding, based on the importance of the treatment to the mother, because of the potential for serious adverse reactions in the breastfed infant.

• Notify your physician immediately if you:
  • Experience hypersensitivity reactions such as hives, itching, shortness of breath, drop in blood pressure and severe allergic reactions (anaphylaxis)
  • Develop symptoms such as fever, rash, headache, sore throat, muscle and joint pain, swallowing difficulties, and swelling of hands and face
  • Develop signs of infection
• You will need periodic checkups while you are on infliximab treatment. Follow up with your physician and do not miss your appointments.
• Do not take live, attenuated vaccines while receiving infliximab therapy.