Usage
Infliximab is prescribed for the treatment of various autoimmune and inflammatory conditions. These include:
- Crohn’s Disease: Moderate to severely active Crohn’s disease in adults and children 6 years and older. It is also used for fistulizing Crohn’s disease.
- Ulcerative Colitis: Moderately to severely active ulcerative colitis in adults and children 6 years and older.
- Rheumatoid Arthritis: Moderately to severely active rheumatoid arthritis in adults, usually in conjunction with methotrexate.
- Ankylosing Spondylitis: Active ankylosing spondylitis in adults.
- Psoriatic Arthritis: Active psoriatic arthritis in adults, with or without methotrexate.
- Plaque Psoriasis: Chronic severe plaque psoriasis in adults.
Pharmacological Classification: Infliximab is a tumor necrosis factor-alpha (TNF-α) inhibitor, classified as a biologic or a disease-modifying antirheumatic drug (DMARD).
Mechanism of Action: Infliximab binds specifically to TNF-α, a key cytokine involved in inflammatory processes. By neutralizing TNF-α, infliximab reduces inflammation and modulates the immune response, thus alleviating symptoms and slowing disease progression in the conditions mentioned above.
Alternate Names
Infliximab is also known internationally by its generic name. Brand names under which infliximab is marketed include Remicade®, Inflectra®, Renflexis®, Ixifi®, and Avsola®.
How It Works
Pharmacodynamics: Infliximab primarily works by neutralizing TNF-α, leading to a decrease in inflammation and a modulation of the immune response. This reduces the infiltration of inflammatory cells into affected tissues and diminishes the production of other pro-inflammatory cytokines.
Pharmacokinetics: Infliximab is administered intravenously. After administration, it distributes mainly within the vascular compartment. The median terminal half-life ranges from 7.7 to 9.5 days. Elimination occurs through systemic clearance mechanisms, including proteolytic degradation.
Mode of Action: Infliximab binds with high affinity to both soluble and transmembrane forms of TNF-α, preventing its interaction with TNF receptors. This blocks the cascade of inflammatory events initiated by TNF-α.
Receptor Binding: Infliximab specifically binds to TNF-α.
Elimination Pathways: Infliximab is primarily eliminated through proteolytic degradation, a process where proteins are broken down into smaller peptides. Hepatic and renal elimination play minor roles.
Dosage
Infliximab dosage is based on the patient’s weight and the condition being treated. It’s crucial to monitor patients during and after infusions for potential infusion reactions.
Standard Dosage
Adults:
- The standard induction regimen is 5 mg/kg administered intravenously at 0, 2, and 6 weeks, followed by maintenance dosing every 8 weeks for most indications. Ankylosing spondylitis requires maintenance dosing every 6 weeks.
- Rheumatoid arthritis: Induction dose is 3 mg/kg at 0, 2 and 6 weeks in combination with methotrexate, followed by 3mg/kg every 8 weeks. The dose may be increased to 10 mg/kg if response is inadequate.
- For some indications, dose escalation to 10 mg/kg or shortening the dosing interval to every 4 weeks may be considered for patients who lose response.
Children (6 years and older):
- Crohn’s Disease and Ulcerative Colitis: 5 mg/kg intravenously at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks.
Special Cases:
- Elderly Patients: Caution should be used as the incidence of serious infections is higher in patients 65 years and older.
- Patients with Renal Impairment: No dose adjustment is typically necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is typically necessary.
- Patients with Comorbid Conditions: Patients with heart failure should not receive doses > 5 mg/kg. Monitor patients with other comorbidities closely.
Clinical Use Cases
Infliximab is not typically used in the contexts of intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Its primary role is in managing chronic inflammatory conditions.
Dosage Adjustments
Dose adjustments may be needed based on therapeutic response and tolerance. Some patients who lose response may benefit from an increased dose (up to 10 mg/kg) or a shorter dosing interval (every 4 weeks).
Side Effects
Common Side Effects:
Upper respiratory infections (sinus infections, sore throat), headache, cough, abdominal pain, infusion reactions (fever, chills, rash, chest pain, itching, changes in blood pressure).
Rare but Serious Side Effects:
Serious infections (including tuberculosis and invasive fungal infections), lymphoma (especially hepatosplenic T-cell lymphoma), heart failure, liver injury, nervous system disorders (seizures, multiple sclerosis), blood disorders (neutropenia, thrombocytopenia), allergic reactions (including anaphylaxis). Malignancies such as melanoma and Merkel cell carcinoma have also been reported.
Long-Term Effects:
Increased risk of infections, development of malignancies (lymphoma, skin cancer), demyelinating disorders, and reactivation of latent infections (e.g., tuberculosis, hepatitis B).
Adverse Drug Reactions (ADR):
Infusion reactions (ranging from mild to severe, including anaphylaxis), infections, heart failure exacerbation, hepatotoxicity, and cytopenias.
Contraindications
- Moderate to severe heart failure (New York Heart Association Class III/IV).
- History of severe hypersensitivity to infliximab, any of its components, or murine proteins.
- Active severe infections (including tuberculosis).
Drug Interactions
Infliximab can interact with various medications:
- Live vaccines: Avoid concurrent use and for at least six months after the last infliximab dose.
- Immunosuppressants (e.g., azathioprine, methotrexate, 6-mercaptopurine): Increased risk of infection and malignancy.
- Therapeutic monoclonal antibodies (e.g. abatacept, anakinra): Avoid concomitant use.
- Kineret®: Avoid concomitant use.
Pregnancy and Breastfeeding
- Pregnancy: Infliximab should be used during pregnancy only if the benefit clearly outweighs the risk. It crosses the placenta, especially during the third trimester. Infants exposed to infliximab in utero may have an increased risk of infection.
- Breastfeeding: Infliximab is present in breast milk at low levels and is considered compatible with breastfeeding by many experts. However, discuss the risks and benefits with the mother.
Drug Profile Summary
- Mechanism of Action: Binds to TNF-α, reducing inflammation.
- Side Effects: Infections, infusion reactions, headache, abdominal pain. Serious side effects include lymphoma, heart failure, and serious infections.
- Contraindications: Moderate to severe heart failure, hypersensitivity to infliximab, active severe infections.
- Drug Interactions: Live vaccines, immunosuppressants, anakinra.
- Pregnancy & Breastfeeding: Use with caution during pregnancy; generally compatible with breastfeeding.
- Dosage: 5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks (or 6 weeks for ankylosing spondylitis) for most indications; adjustments may be necessary.
- Monitoring Parameters: Complete blood counts, liver function tests, signs and symptoms of infection, and heart failure.
Popular Combinations
Infliximab is often used in combination with methotrexate for rheumatoid arthritis and psoriatic arthritis. This combination can enhance efficacy.
Precautions
- Screen for latent tuberculosis and hepatitis B before initiating treatment.
- Monitor closely for infections during treatment.
- Exercise caution in patients with heart failure or a history of malignancy.
- Avoid live vaccines.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Infliximab?
A: The standard adult induction dose is 5 mg/kg IV at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks for most indications (every 6 weeks for ankylosing spondylitis). Pediatric dosing (6 years and older) for Crohn’s disease and ulcerative colitis is the same as the adult dose. Dose adjustments may be required based on individual response and tolerability.
Q2: What are the most common side effects of Infliximab?
A: Upper respiratory infections, headache, cough, and abdominal pain are common side effects. Infusion reactions can also occur.
Q3: What are the serious side effects of Infliximab?
A: Serious infections (including tuberculosis), lymphoma, heart failure, and liver injury are potential serious side effects. Malignancies such as melanoma and Merkel cell carcinoma have also been reported.
Q4: Can Infliximab be used during pregnancy?
A: Infliximab should be used during pregnancy only if clearly needed, as it crosses the placenta and may pose risks to the fetus.
Q5: Can Infliximab be used during breastfeeding?
A: Infliximab is considered generally compatible with breastfeeding, as it is present in breast milk at low levels. However, the decision to breastfeed while on infliximab should be made in consultation with a physician.
Q6: What are the contraindications for Infliximab?
A: Moderate to severe heart failure, a history of severe hypersensitivity to infliximab, and active severe infections are contraindications.
Q7: How is Infliximab administered?
A: Infliximab is administered intravenously as an infusion over at least 2 hours.
Q8: What monitoring is required for patients on Infliximab?
A: Regular monitoring of complete blood counts, liver function tests, and assessment for signs and symptoms of infection and heart failure are necessary.
Q9: Does Infliximab interact with other medications?
A: Yes, Infliximab can interact with medications such as live vaccines, immunosuppressants, and other biologics. It is essential to discuss all concomitant medications with the prescribing physician.
Q10: Can Infliximab be used in children?
A: Yes, Infliximab is approved for use in children 6 years and older for the treatment of Crohn’s disease and ulcerative colitis.
