Infliximab is a medication that belongs to a class of drugs called tumor necrosis factor (TNF) inhibitors. It is primarily used to treat certain autoimmune diseases, particularly inflammatory bowel disease (Crohn's disease and ulcerative colitis) and rheumatic conditions such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

TNF is a protein produced by the immune system that plays a role in inflammation. Infliximab works by binding to TNF and inhibiting its activity. By doing so, it helps reduce the inflammation and symptoms associated with autoimmune diseases.

Infliximab Uses (Indications):

• Ankylosing spondylitis:
  •  Adults with active Ankylosing Spondylitis (to reduce symptoms/signs)
• Crohn disease:
  • Adults and children aged >=6 with Crohn's disease. This treatment is for patients who have not responded to conventional therapy. It is used to relieve signs and to cause or support clinical remission.
• Plaque psoriasis
  • Adults with plaque psoriasis may benefit from it as a therapy for their chronic, severe, and/or disabling plaque psoriasis as a substitute for systemic therapy.
• Psoriatic arthritis
  • Adults with psoriatic arthritis (to reduce symptoms and prevent progression of structural damage, improve physical function, and reduce the signs/symptoms associated with active arthritis).
• Rheumatoid arthritis
  • Methotrexate is used to treat adults suffering from moderately severe rheumatoid arthritis (or other forms of active arthritis). It reduces the symptoms and prevents further structural damage. It also improves physical function.
• Ulcerative colitis
  • Adult and pediatric patients aged >=6 with severe or moderately active ulcerative colitis. This treatment is intended to reduce symptoms, induce and maintain clinical remission, and aid in mucosal healing.
• Notice:
  • Renflexis (infliximab–abda), and Inflectra, (infliximab–dyyb), are biosimilars to Remicade.
  • Remsima (infliximab) is also a biosimilar in Canada.
• Off-Label Use Infliximab for Adults:
  • Crohn's disease (management following surgical resection).
  • Pustular psoriasis
  • Pyoderma Gangrenosum

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Infliximab dose in Adults:

• Note:
  • Infliximab is a medication used to treat certain autoimmune diseases.
  • It works by reducing inflammation in the body.
  • It is given through an IV in a hospital or clinic.
  • Common side effects include fever, rash, headache, and nausea.
  • There is a small risk of serious infections and liver problems.
  • Before starting infliximab, talk to your doctor about the potential risks and benefits.
  • Some similar medications, called biosimilars, are also available.

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Infliximab Dose in the treatment of Crohn's disease:

• In the treatment of Crohn's disease, the recommended dose of infliximab is given through an IV infusion.
• Initially, the dose is 5 mg/kg at weeks 0, 2, and 6.
• After the initial doses, subsequent maintenance doses of 5 mg/kg are administered every 8 weeks.
• In some cases, if a patient initially responds to the treatment but later loses their response, the dose may be increased to 10 mg/kg.
• However, if there is no response to the medication by week 14, discontinuing therapy should be considered.

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Infliximab Dose in the treatment of Crohn's disease management after surgical resection (off-label):

• In the management of Crohn's disease after surgical resection (which is an off-label use), the recommended dose of infliximab is typically the same as in non-surgical cases.
• Initially, it involves an IV infusion of 5 mg/kg at weeks 0, 2, and 6, followed by 5 mg/kg every 8 weeks thereafter.
• It is worth noting that in high-risk patients, the first infusion should be administered within 4 weeks after surgery.

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Infliximab Dose in the treatment of Plaque psoriasis:

• In the treatment of plaque psoriasis, the recommended dose of infliximab is administered through an IV infusion.
• Initially, the dose is 5 mg/kg at weeks 0, 2, and 6.
• After the initial doses, maintenance doses of 5 mg/kg are given every 8 weeks thereafter.

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Infliximab Dose in the treatment of Psoriatic arthritis (with or without methotrexate):

• In the treatment of psoriatic arthritis, with or without concurrent use of methotrexate, the recommended dose of infliximab is administered through an IV infusion.
• Initially, the dose is 5 mg/kg at weeks 0, 2, and 6.
• Following the initial doses, maintenance doses of 5 mg/kg are given every 8 weeks thereafter.

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Infliximab Dose in the treatment of Rheumatoid arthritis (in combination with methotrexate therapy):

• In the treatment of rheumatoid arthritis when used in combination with methotrexate therapy, the recommended dose of infliximab is administered through an IV infusion.
• Initially, the dose is 3 mg/kg at weeks 0, 2, and 6.
• After the initial doses, maintenance doses of 3 mg/kg are given every 8 weeks thereafter.
• The range of doses for Remicade, which is the brand name of infliximab, has been reported as 3 to 10 mg/kg, repeated at 4- to 8-week intervals.

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Infliximab Dose in the treatment of Ulcerative colitis:

• In the treatment of ulcerative colitis, the recommended dose of infliximab is administered through an IV infusion.
• Initially, the dose is 5 mg/kg at weeks 0, 2, and 6.
• After the initial doses, maintenance doses of 5 mg/kg are given every 8 weeks thereafter.
• Clinical trials have also studied doses up to 10 mg/kg, and similar efficacy was observed with both the 5 mg/kg and 10 mg/kg doses.

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Infliximab Dose in the treatment of Pustular psoriasis (off-label):

• In the treatment of pustular psoriasis (which is an off-label use of infliximab), the recommended dose is administered through an IV infusion.
• Initially, the dose is 5 mg/kg at week 0, 2, and 6.
• Following the initial doses, maintenance doses of 5 mg/kg are given every 8 weeks for up to 46 weeks.

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Infliximab Dosage adjustment with heart failure (HF):

When using infliximab in patients with heart failure (HF), dosage adjustment should be considered based on the individual patient's risk versus benefits.

• Mild HF (NYHA Class I/II):
  • For patients with mild HF (New York Heart Association [NYHA] Class I/II), no dosage adjustment is typically necessary.
• Moderate to severe (NYHA Class III or IV):
  • In patients with moderate to severe HF (NYHA Class III or IV), the recommended maximum dosage is typically 5 mg/kg.
  • This lower dose is employed to minimize the potential risk of exacerbating HF symptoms.

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Infliximab Use in Children:

Note:

• Infliximab is a medication used to treat certain autoimmune diseases.
• It works by reducing inflammation in the body.
• It is given through an IV in a hospital or clinic.
• Common side effects include fever, rash, headache, and nausea.
• There is a small risk of serious infections and liver problems.
• Before starting infliximab, talk to your doctor about the potential risks and benefits.
• Some similar medications, called biosimilars, are also available.

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Infliximab Dose in the treatment of Crohn's disease: Remicade/Inflectra/Renflexis:

• In the treatment of Crohn's disease in children aged 6 years and older, as well as adolescents, the recommended dose of infliximab (Remicade/Inflectra/Renflexis) is administered through an IV infusion.
• Initially, the dose is 5 mg/kg/dose at weeks 0, 2, and 6.
• After the initial doses, maintenance doses of 5 mg/kg/dose are given every 8 weeks thereafter.

Note: In adult patients with Crohn's disease, it has been observed that those who do not respond to infliximab treatment by week 14 are unlikely to respond even with continued dosing. Therefore, in such cases, it may be considered to discontinue the therapy.

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Infliximab Dose in the treatment of Juvenile idiopathic arthritis refractory to conventional disease-modifying drugs:

• In the treatment of juvenile idiopathic arthritis (JIA) that is refractory to conventional disease-modifying drugs, the available data for infliximab dosing is limited.
• For children aged 4 years and older, as well as adolescents, the recommended initial dose is 3 mg/kg administered through an IV infusion at weeks 0, 2, and 6.
• Following the initial doses, the maintenance dose is typically in the range of 3 to 6 mg/kg/dose, given every 8 weeks thereafter.
• It is recommended to use infliximab in combination with methotrexate during both the induction and maintenance phases.
• Alternatively, some studies have utilized a different dosing regimen.
• They initiated infliximab at a dose of 6 mg/kg/dose starting at week 14, following a methotrexate induction regimen from weeks 0 to 13.
• This alternate regimen involved repeating the dose (6 mg/kg/dose) at week 16 and 20, and then administering it every 8 weeks thereafter.

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Infliximab Dose in the treatment of Kawasaki disease, refractory to IVIG:

• In the treatment of Kawasaki disease that is refractory to intravenous immunoglobulin (IVIG), the available data for infliximab dosing is limited.
• For infants and children, the recommended dose is 5 mg/kg administered as a single infusion through an IV.

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Infliximab Dose in the treatment of Ulcerative colitis: Remicade:

• In the treatment of ulcerative colitis, specifically using the Remicade brand of infliximab, the recommended dosing for children aged 6 years and older, as well as adolescents, involves an initial dose of 5 mg/kg/dose administered through an IV infusion at weeks 0, 2, and 6.
• Following the initial doses, the maintenance dose is 5 mg/kg/dose every 8 weeks thereafter.

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Infliximab Pregnancy Risk Category: N (Not assigned)

• Infliximab is a medication used to treat certain conditions, but its effects during pregnancy are not fully understood.
• When a pregnant woman takes infliximab, it can cross the placenta and reach the baby.
• Studies have shown that the levels of infliximab in newborns can be higher than in the mother's blood at delivery.
• It takes around 7.3 months for infliximab to be cleared from the baby's body on average.
• There have been reports of some infants experiencing agranulocytosis (a decrease in a type of white blood cell) after being exposed to infliximab in the womb.
• The risk of immunosuppression (reduced immune system function) may be increased if the mother uses infliximab in the third trimester of pregnancy.
• It's important to avoid live vaccines for the first 6 months of a baby's life if the mother was exposed to infliximab in the third trimester.
• Inflammatory bowel disease, the condition infliximab is commonly used for, can have negative effects on pregnancy, so managing the disease before pregnancy is important.
• The decision to use infliximab during pregnancy should be made on an individual basis, considering the risks and benefits.
• Monitoring the health of both the mother and baby is crucial, and healthcare providers can enroll patients in studies to gather more information on pregnancy outcomes after exposure to infliximab.

Infliximab use during breastfeeding:

• Infliximab can be present in breast milk when taken by breastfeeding mothers.
• Several studies have examined the transfer of infliximab into breast milk.
• In some studies, infliximab was detected in breast milk within hours after the maternal dose, with peak concentrations occurring within 1-2 days.
• However, other studies did not find detectable levels of infliximab in breast milk.
• It's important to note that no adverse events were reported in breastfed infants exposed to infliximab through breast milk.
• The decision to breastfeed while receiving infliximab should take into account the potential risk to the infant, the benefits of breastfeeding, and the benefits of treatment for the mother.
• Generally, tumor necrosis factor alpha (TNFα)-blocking agents like infliximab are considered compatible with breastfeeding, according to the American Academy of Dermatology, the American College of Obstetricians and Gynecologists, and the American Association of Dermatology-National Psoriasis Foundation..

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Infliximab Dose in Kidney Disease:

• There are no dosage adjustments provided in the drug manufacturer's labeling.

Infliximab Dose in Liver disease:

• Hepatic impairment prior to treatment initiation:
  • There are no dosage adjustments provided in the drug manufacturer's labeling.
• Hepatotoxicity during treatment:
  • Jaundice and/or marked increase in liver enzymes (≥5 times ULN):
    • Discontinue treatment.

As reported in adults with rheumatoid arthritis, unless otherwise noted.

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Infliximab Adverse effects (Common):

• Central nervous system:
  • Headache
• Gastrointestinal:
  • Abdominal Pain
  • Nausea
• Hematologic & Oncologic:
  • Anemia
• Hepatic:
  • Increased Serum Alanine Aminotransferase
• Immunologic:
  • Antibody Development
  • Increased ANA Titer
  • Antibody Development
• Infection:
  • Infection
  • Serious Infection
  • Abscess
• Respiratory:
  • Upper Respiratory Tract Infection
  • Sinusitis
  • Cough
  • Pharyngitis
• Miscellaneous:
  • Infusion Related Reaction

Infliximab Adverse effects (Less common):

• Cardiovascular:
  • Flushing
  • Hypertension
• Central Nervous System:
  • Fatigue
  • Pain
• Dermatologic:
  • Skin Rash
  • Pruritus
• Gastrointestinal:
  • Dyspepsia
• Genitourinary:
  • Urinary Tract Infection
• Hematologic & Oncologic:
  • Leukopenia
  • Neutropenia
• Hypersensitivity:
  • Hypersensitivity Reaction
  • Type IV Hypersensitivity Reaction
  • Serum Sickness
• Infection:
  • Viral Infection
  • Bacterial Infection
  • Candidiasis
• Neuromuscular & Skeletal:
  • Arthralgia
  • Bone Fracture
• Respiratory:
  • Bronchitis
  • Pneumonia
• Miscellaneous:
  • Fever

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Contraindications to Infliximab:

Infliximab should not be used in individuals who have a hypersensitivity to infliximab, murine proteins, or any ingredient in the formulation. In addition, doses higher than 5 mg/kg should not be given to patients with moderate or severe heart failure (classified as NYHA Class III/IV).

The Canadian labeling for infliximab includes additional contraindications not found in the US labeling, such as severe infections (such as sepsis, abscesses, tuberculosis, and opportunistic infections) and the use in patients with moderate or severe heart failure (NYHA Class III/IV).

Black Box Warning and Precautions for Infliximab

Autoimmune disorder:

• In some patients treated with infliximab, positive antinuclear antibody (ANA) titers have been observed, even in those who initially had negative baseline results.
• Although rare, there have been reported cases of autoimmune disorders, including a lupus-like syndrome, in some individuals.
• It is important to monitor patients closely for any symptoms suggestive of an autoimmune disorder, and if such symptoms develop, discontinuation of infliximab may be necessary.
• Regular monitoring are essential to ensure appropriate management and timely intervention if needed.

During and after infusion, there are both cardiovascular and cerebrovascular reactions

• During and shortly after infliximab infusion, there have been reports of cardiovascular and cerebrovascular reactions.
• These include events such as cerebrovascular accidents (strokes), myocardial infarctions (heart attacks), some of which have been fatal, as well as episodes of low blood pressure, high blood pressure, and irregular heart rhythms.
• Additionally, transient vision loss has been reported either during or within 2 hours of infusion.
• If a serious reaction of this nature occurs, it is important to discontinue infliximab therapy.
• Close monitoring during and after infusion, as well as prompt medical attention, are essential to ensure patient safety and manage any potential adverse events.

Hematologic disorders

• Hematologic disorders, including serious conditions such as leukopenia (low white blood cell count), neutropenia (low neutrophil count), thrombocytopenia (low platelet count), and pancytopenia (low counts of all blood cell types), have been reported in some patients receiving infliximab.
• These hematologic toxicities can be severe and even fatal in rare cases.
• Patients should be informed to promptly seek medical attention if they experience symptoms suggestive of blood disorders, such as persistent fevers.
• If significant abnormalities in blood cell counts are confirmed, it is important to discontinue infliximab treatment.
• Caution is advised when using infliximab in patients with a history of hematologic abnormalities.
• Regular monitoring of blood counts and appropriate management are necessary to ensure patient safety.

Hepatic reactions

• Severe hepatic reactions, such as hepatitis (inflammation of the liver), jaundice (yellowing of the skin and eyes), acute hepatic failure (sudden loss of liver function), and cholestasis (impaired bile flow), have been reported in patients receiving infliximab treatment.
• These reactions can occur within a range of time, from 2 weeks to over 1 year after starting therapy.
• In some cases, these reactions have been fatal or required liver transplantation.
• If a patient develops jaundice (yellowing of the skin and eyes) and/or a significant increase in liver enzymes (at least 5 times the upper limit of normal), it is important to discontinue infliximab treatment.
• Close monitoring of liver function and prompt intervention are crucial to ensure patient safety.

Hepatitis B:

• Reactivation of the hepatitis B virus (HBV) has been observed in individuals who are chronic carriers of the virus, particularly in patients receiving immunosuppressant medications, including infliximab.
• This reactivation can be serious and even fatal.
• Therefore, it is important to assess for HBV infection before starting infliximab treatment in all patients.
• Continuous monitoring is necessary during treatment and for several months after discontinuation, especially in HBV carriers.
• If reactivation occurs, appropriate antiviral therapy should be initiated, and infliximab treatment should be interrupted.
• If the decision is made to resume infliximab therapy, it should be done with caution and close monitoring of the patient.

Hypersensitivity or Infusion reactions

• Acute infusion reactions and hypersensitivity reactions, including anaphylaxis, are possible side effects of infliximab treatment.
• These reactions may occur within 2 hours of infusion.
• It is important to have the necessary medication and equipment on hand to manage hypersensitivity reactions in case they occur.
• In some cases, interruptions or slower infusion rates may be necessary, as guided by specific protocols.
• Pretreatment before infliximab infusion may be considered, especially in patients who have experienced infusion reactions in the past.
• Serum sickness-like reactions have been reported and may be associated with a reduced response to treatment.
• The development of antibodies to infliximab can increase the risk of hypersensitivity and infusion reactions.
• Concurrent use of immunosuppressant medications may reduce the formation of these antibodies.
• The risk of infusion reactions may be higher when re-treating patients after an interruption or discontinuation of previous maintenance therapy.
• In psoriasis patients, re-treatment should be resumed as a scheduled maintenance regimen without induction doses, while caution should be exercised when considering an induction regimen for re-treatment in other patients.

Infections [US Boxed Warning]

• It is important to note that patients receiving infliximab are at an increased risk of developing serious infections, some of which can be severe and life-threatening.
• These infections often occur in patients who are also taking other immunosuppressive medications, such as methotrexate or corticosteroids.
• The infections can be disseminated, meaning they may affect multiple organs or systems in the body rather than being localized.
• Examples of infections that have been reported include tuberculosis, fungal infections (such as aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis), bacterial infections, viral infections, and other opportunistic infections (including legionellosis and listeriosis).
• It is important to closely monitor patients for any signs or symptoms of infection.
• If a serious infection or sepsis occurs, treatment with infliximab should be discontinued.
• Before initiating treatment with infliximab, the risks and benefits should be carefully considered in patients with a history of chronic or recurrent infections.
• In patients who are at risk for invasive fungal infections and develop severe systemic illness, it may be appropriate to consider empiric antifungal therapy.
• Caution should be exercised when considering the use of infliximab in elderly patients or those with conditions that make them more susceptible to infections, such as diabetes, or in patients who reside in or have traveled from areas where certain fungal infections are endemic (such as blastomycosis, coccidioidomycosis, and histoplasmosis), or in patients with latent or localized infections.
• Infliximab should not be initiated in patients with an active infection, including clinically important localized infections.
• Patients who develop a new infection while receiving infliximab treatment should be closely monitored.

Malignancy: [US Boxed Warning]

• Malignancy is a serious concern when using infliximab and other TNF-blocking agents.
• In children and adolescents, there have been reports of lymphomas and other types of cancers, some of which can be fatal.
• There have also been cases of hepatosplenic T-cell lymphoma in patients treated with infliximab, particularly in those who received azathioprine or mercaptopurine alongside the medication.
• These malignancies usually appeared several months after starting TNF blocker therapy, and most patients were also taking immunosuppressants.
• It's important to note that the full impact of infliximab on the development and course of malignancies is not fully understood.
• Certain patient groups, such as those with a history of COPD or those who have undergone phototherapy for psoriasis, may have a higher risk of malignancies.
• Regular skin examinations are recommended for all patients, especially those at increased risk for skin cancer.
• Women with rheumatoid arthritis should continue periodic screening for invasive cervical cancer while receiving infliximab.

Tuberculosis: [US-Boxed Warning]

• Tuberculosis is a serious concern when using infliximab.
• There have been cases of active tuberculosis, including disseminated or extrapulmonary forms, as well as reactivation of latent tuberculosis infections.
• Before starting infliximab treatment, patients should be evaluated for tuberculosis risk factors and tested for latent tuberculosis infection using a tuberculin skin test.
• If latent tuberculosis is detected, it should be treated before starting infliximab.
• Even if the initial test is negative, patients should be closely monitored for tuberculosis throughout the treatment.
• Most cases of reactivation occur within the first few months of treatment.
• It's important to exercise caution when considering infliximab for patients who have been exposed to tuberculosis.

Demyelinating CNS Disease:

• Infliximab should be used cautiously in patients who have preexisting or recently diagnosed demyelinating disorders in the central nervous system (CNS).
• There have been rare cases of optic neuritis and demyelinating diseases such as multiple sclerosis, systemic vasculitis, and Guillain-Barré syndrome reported in patients receiving infliximab.
• If a patient develops significant CNS reactions, it may be necessary to discontinue the therapy.
• Close monitoring and consideration of discontinuation should be done if there are concerns about the patient's CNS health.

Heart failure (HF):

• In patients with heart failure (HF), infliximab should be used cautiously, especially in those with mild HF (NYHA Class I, II) or reduced left ventricular function.
• There have been reports of worsening or new-onset HF in patients receiving infliximab.
• Doses exceeding 5 mg/kg should be avoided in patients with moderate to severe HF (NYHA Class III/IV), and therapy should be discontinued if new or worsening symptoms of HF occur.
• According to a scientific statement from the American Heart Association, TNF blockers like infliximab have the potential to cause direct toxicity to the heart muscle or worsen underlying heart dysfunction.
• Therefore, their use in patients with HF is considered significant and caution should be exercised.

Seizure disorders:

• In patients with a history of seizures, infliximab should be used with caution.
• If significant adverse reactions affecting the central nervous system (CNS) develop, the therapy should be discontinued.
• It is important to monitor patients closely for any signs of CNS adverse effects during treatment with infliximab.

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Infliximab (including biosimilars of infliximab): Drug Interaction

Risk Factor C (Monitor therapy)
AzaTHIOprine	AzaTHIOprine's negative/toxic effects may be amplified by infliximab. Particularly, there may be an increased risk for T-cell non-lymphoma, Hodgkin's which includes hepatosplenic T-cell lymphoma. The active metabolite(s) of azathioprine may have higher serum concentrations when infliximab is administered.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Smallpox and Monkeypox Vaccine (Live)	Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox vaccines (Live).
Tertomotide	Immunosuppressants may reduce Tertomotide's therapeutic efficacy.
Thiopurine Analogs	Thiopurine Analogs may have a more negative or toxic effect when taken with anti-TNF agents. Particularly, there may be an increased risk for T-cell non-lymphoma, Hodgkin's which includes hepatosplenic T-cell lymphoma.
Trastuzumab	May improve the neutropenic impact of Immunosuppressants.
Risk Factor D (Consider therapy modification)
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
Abatacept	Anti-TNF agents may intensify Abatacept's negative/toxic effects. When used concurrently, there has been information about a higher risk of severe infection.
Anakinra	Anti-TNF agents may intensify Anakinra's harmful or hazardous effects. When used concurrently, there has been information about an increased risk of serious infection.
BCG (Intravesical)	Immunosuppressive medications may reduce the therapeutic benefit of BCG (Intravesical).
Belimumab	Biological Disease-Modifying Antirheumatic Drugs may have an enhanced immunosuppressive impact (DMARDs).
Biologic Anti-Psoriasis Agents	The immunosuppressive effects of biologic anti-psoriasis drugs may be strengthened by infliximab.
Biologic Disease-Modifying Antirheumatic Drugs (DMARDs)	may intensify the immunosuppressive effects of further biological disease-modifying antirheumatic medications (DMARDs).
Canakinumab	Anti-TNF agents may intensify Canakinumab's negative or hazardous effects. Particularly, there may be an elevated risk for severe infections and/or neutropenia.
Certolizumab Pegol	Certolizumab Pegol's immunosuppressive impact may be strengthened by anti-TNF agents.
Cladribine	Could make immunosuppressive drugs work more effectively.
Natalizumab	Immunosuppressants may intensify Natalizumab's harmful or hazardous effects. In particular, there may be an elevated risk of concomitant infection.
Pimecrolimus	Immunosuppressants' harmful or toxic effects might be amplified.
Rilonacept	Anti-TNF agents may intensify Rilonacept's negative/toxic effects.
Tacrolimus (Topical)	Immunosuppressants' harmful or toxic effects might be amplified.
Tocilizumab	Could make anti-TNF agents' immunosuppressive effects stronger.
Vaccines (Live)	Immunosuppressive drugs may intensify the negative or harmful effects of vaccines (Live). Immunosuppressive medications may reduce the therapeutic benefit of vaccines (Live). Management: Live attenuated vaccinations shouldn't be administered for at least 3 months following immunosuppressants; avoid using live organism vaccines with immunosuppressants. Smallpox and monkeypox vaccines are exceptions (Live).
Vedolizumab	Anti-TNF agents may intensify Vedolizumab's negative/toxic effects.

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Monitoring parameters:

Symptom and Physical Function Assessment:

• Monitor the improvement of symptoms and physical function during treatment with infliximab.

Vital Signs Monitoring:

• During infusion, closely monitor vital signs every 2 to 10 minutes based on the severity of any observed reaction until they return to normal.

Serious Infusion Reactions:

• If a serious reaction occurs, such as a cardiovascular or cerebrovascular reaction, discontinue the infusion immediately.

Tuberculosis Screening:

• Conduct screening for active and latent tuberculosis prior to starting infliximab therapy and continue monitoring during treatment.

Infection Monitoring:

• Watch for signs and symptoms of infection before, during, and after therapy with infliximab.

Complete Blood Count (CBC):

• Regularly check CBC with differential to monitor for any hematologic abnormalities.

Heart Failure Monitoring:

• Monitor for signs and symptoms of heart failure and worsening heart function.

Hepatitis B Virus (HBV) Screening:

• Screen all patients for HBV prior to initiating infliximab therapy, and continue monitoring in HBV carriers for several months after treatment.

Hypersensitivity Reaction:

• Be vigilant for symptoms of hypersensitivity reactions and discontinue treatment if they occur.

Lupus-Like Syndrome:

• Monitor for symptoms suggestive of a lupus-like syndrome and discontinue therapy if necessary.

Liver Function Tests (LFTs):

• Conduct regular LFTs and discontinue infliximab if liver enzymes increase to more than five times the upper limit of normal (ULN).

Malignancy Monitoring:

• Be alert to signs and symptoms of malignancies, such as splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

Nonmelanoma Skin Cancer:

• Psoriasis patients with a history of phototherapy should be monitored for nonmelanoma skin cancer.

Cervical Cancer Screening:

• Women treated with infliximab should undergo periodic screening for cervical cancer.

Therapeutic Drug Monitoring:

• The American Gastroenterological Association suggests using reactive therapeutic drug monitoring to guide treatment changes in adult patients with active inflammatory bowel disease treated with infliximab.

These monitoring and safety considerations aim to ensure the appropriate use of infliximab and to promptly detect any potential adverse effects or complications during the course of treatment.

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How to administer Infliximab?

Timing:

• Begin the infusion within 3 hours of reconstitution and dilution.

Infusion Duration:

• Infuse over at least 2 hours, although a shorter duration (e.g., 1 hour) may be used in patients who previously tolerated four 2-hour infusions. Refer to institution-specific protocols for guidance.

Compatibility:

• Do not infuse infliximab with other agents. Use an inline low protein binding filter (≤1.2 microns).

Infusion-Related Reactions:

• Temporarily discontinue or decrease the infusion rate if infusion-related reactions occur. Manage reactions with antihistamines (H1-antagonist +/- H2-antagonist), acetaminophen, and/or corticosteroids. Once mild to moderate symptoms resolve, the infusion may be reinitiated at a lower rate.

Treatment and Prophylaxis of Infusion Reactions:

• The following recommendations are for adult patients with Crohn's disease.
• For mild reactions, decrease the infusion rate and provide symptomatic treatment.
• For moderate reactions, slow or stop the infusion, initiate symptomatic treatment, and gradually resume the infusion.
• For severe reactions, stop the infusion, administer appropriate symptomatic treatment, and closely monitor vital signs.
• Re-treatment after a severe reaction should be considered carefully, and prophylaxis may be necessary.
• Delayed infusion reactions can occur 1 to 7 days later and should be treated symptomatically.
• Prophylaxis with acetaminophen and diphenhydramine prior to infusion and corticosteroid administration in severe reactions are recommended.

Test Dose and Rate Escalation:

• Consider a test dose at a slow rate initially, followed by incremental increases in the infusion rate, as tolerated, until completion.
• Maximum infusion rates differ based on the severity of prior reactions.

Cutaneous Flushing:

• Aspirin may be considered for patients experiencing cutaneous flushing.

Delayed Infusion Reactions:

• Premedicate with acetaminophen and diphenhydramine prior to infusion and gradually increase the infusion rate over 3 hours. Post infusion therapy with acetaminophen for 3 days and an antihistamine for 7 days is recommended for delayed reactions.

These guidelines outline the proper administration and management of infliximab infusions, including precautions for infusion-related reactions and protocols for treatment and prophylaxis. It is important to follow these recommendations to ensure the safe and effective use of infliximab.

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Mechanism of action of Infliximab:

• Infliximab is a type of medication called a chimeric monoclonal antibody.
• It works by binding to a protein in the body called tumor necrosis factor alpha (TNFα), which is involved in inflammation.
• Elevated levels of TNFα are found in conditions such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease, and ulcerative colitis.
• TNFα promotes inflammation by causing the release of other proinflammatory substances and activating certain immune cells.
• Infliximab blocks the activity of TNFα, thereby reducing inflammation and its harmful effects.
• Studies in animals have shown that by inhibiting TNFα, infliximab can prevent and heal joint inflammation.

Notification:

• The pharmacokinetic data of pediatric patients (ages 6-17 years) was similar to adult data.

The onset of action:

• Onset of action refers to the time it takes for a medication to start having an effect.
• For Crohn's disease, it typically takes about 1 to 2 weeks for infliximab to show its therapeutic benefits.
• In the case of rheumatoid arthritis, the onset of action is usually faster, occurring within 3 to 7 days.

Time of action:

• The duration of action refers to how long the medication remains effective in the body.
• For Crohn's disease, the effects of infliximab can last anywhere from 8 to 48 weeks.
• In the case of rheumatoid arthritis, the duration of action is generally shorter, ranging from 6 to 12 weeks.

Distribution:

• In terms of distribution in the body, infliximab is primarily distributed within the vascular compartment, which refers to the blood vessels.
• The volume of distribution (V) for infliximab is estimated to be around 3 to 6 liters.

Half-life elimination:

• The half-life elimination of a medication is the time it takes for the concentration of the drug in the body to decrease by half.
• For infliximab, the half-life elimination is reported to be approximately 7 to 12 days.

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Infliximab Brand Names (International):

• Inflectra
• Remicade
• Renflexis
• Remsima
• Flixabi
• Infimab
• Inflectra
• Reemsima
• Remicade
• Remsima
• Renflexis
• Revellex
• Zessly

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Infliximab Brand Names in Pakistan:

Infliximab Infusion 100 mg
Remicade	Bayer Health Care