Inflectra
infliximab
Generic Name
infliximab
Mechanism
- TNF‑α neutralization: Inflectra binds soluble and transmembrane TNF‑α with high affinity, preventing TNF‑α from engaging its p55/p75 receptors on immune cells.
- Downstream effects: Blockade reduces cytokine release (IL‑1, IL‑6), decreases leukocyte migration, and attenuates the chronic inflammatory cascade that drives joint, bowel, and skin pathology.
- Cell‑death modulation: By engaging Fcγ receptors, Inflectra can also mediate antibody‑dependent cellular cytotoxicity (ADCC) against TNF‑α‑expressing cells in inflamed tissue.
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Pharmacokinetics
- Absorption: Intravenous infusions; complete bioavailability.
- Distribution: Large extracellular volume; low penetration into cells, but effective in inflamed tissue.
- Half‑life: 5–10 days (mean ≈ 7 days).
- Elimination: Non‑enzymatic proteolytic catabolism; minimal involvement of hepatic cytochrome P450.
- Steady‑state: Achieved after 2–4 infusions at standard dosing; trough levels correspond to clinical response.
- Immunogenicity: Anti‑drug antibodies (ADAs) develop in up to 20–30 % of patients, potentially reducing efficacy and increasing infusion reactions.
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Indications
- Inflammatory Bowel Disease:
- Crohn disease (moderate‑to‑severe, steroid‑dependent/relapsed)
- Ulcerative colitis (moderate‑to‑severe, steroid‑dependent/relapsed)
- Rheumatologic Conditions:
- Rheumatoid arthritis (inadequate response to methotrexate)
- Ankylosing spondylitis
- Psoriatic arthritis (including psoriatic nail disease)
- Plaque psoriasis (moderate‑to‑severe, inadequate response to topical/systemic therapy)
*Inflectra is a standalone biologic; concomitant disease-modifying antirheumatic drugs (DMARDs) improve outcomes and reduce immunogenicity.*
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Contraindications
- Active, uncontrolled infections (TB, HIV, hepatitis B/C, candidiasis, etc.).
- Known hypersensitivity to infliximab or any excipient.
- Severe heart failure (NYHA III–IV); can precipitate fluid overload.
- Reactivating latent infections: Hepatitis B is a critical risk; screen for surface antigen and core antibody before therapy.
- Known or suspected malignancy: tumors that are TNF‑α dependent; caution in patients with a history of lymphoma or skin cancer.
- Pregnancy & lactation: Category C; use only if benefits outweigh risks.
*Warnings*
• Risk of serious opportunistic infections (e.g., Candida, Mycobacterium tuberculosis).
• Potential for infusion reactions (anaphylaxis, urticaria, angioedema).
• Possible reactivation of hepatitis B; baseline and periodic ALT/AST monitoring.
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Dosing
| Condition | Loading Dose | Maintenance Schedule | Adjustments | |
| Crohn disease | 5‑10 mg/kg (IV) at Weeks 0, 2, 6 | Every 8 weeks (5‑10 mg/kg) | Reach 10‑15 mg/kg if sub‑optimal response or high disease activity | |
| Ulcerative colitis | 5‑10 mg/kg at Weeks 0, 2, 6 | Every 8 weeks | Increase up to 10 mg/kg if needed | |
| Rheumatoid arthritis | 3‑5 mg/kg at Weeks 0, 2, 6 | Every 8 weeks | Use up to 15 mg/kg for inadequate response | |
| Ankylosing spondylitis | 5 mg/kg | Every 8 weeks | ||
| Psoriatic & Plaque psoriasis | 0.5 mg/kg | Every 4 weeks | May dose up to 2 mg/kg |
• Infusion: 2 hr (5‑6 mg/kg), 3 hr (≥ 7 mg/kg); pre‑medicate antiallergic agents if history of reactions.
• Premedication: Acetaminophen, antihistamine, and optionally methylprednisolone 100 mg IV 30 min pre‑infusion.
• Reconstitution: Dilute 10 mL vial in 100 mL 0.9% NaCl; aliquots (10 mL) safely stored up to 2 weeks at 2–8 °C.
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Adverse Effects
Common (≥ 10 %):
• Infusion reactions (rash, pruritus, urticaria, mild fever)
• Nasopharyngitis, upper respiratory infections
• Diarrhea, abdominal pain
• Arthralgia, myalgia
• Incidence of mild elevations in liver enzymes
Serious (≤ 1 %):
• Severe infusion reaction: anaphylaxis, angioedema, hypotension
• Opportunistic infections: tuberculosis, fungal (Candida, Histoplasma), viral (HIV, hepatitis)
• Malignancy risk: lymphomas, skin cancers
• Neutropenia, thrombocytopenia, anemia
• Hepatotoxicity (ALT/AST > 3× ULN)
• Drug-induced lupus (rare)
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Monitoring
- Baseline: CBC, CMP (LFTs), ESR/CRP, hepatitis B/C serology, TB screening (IGRA/PPD).
- During Therapy:
- Liver enzymes every 4–6 weeks; higher frequency if ALT/AST > 3× ULN.
- Complete blood count at least monthly for first 3 mo.
- Clinical response (weight gain, stool calprotectin, CRP, ESR).
- Anti‑drug antibody levels & trough drug levels (therapeutic drug monitoring
- TDM) to guide dose escalation or switch.
- Vaccinations: inactivated hosts – ensure influenza, pneumococcal, HepA, HepB.
- Reactivation surveillance: regular monitoring of hepatitis B surface antigen if prior exposure.
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Clinical Pearls
- Biosimilar equivalence: Inflectra has shown no clinically meaningful differences in safety, efficacy or PK compared with reference infliximab; institutions can switch between them without interruption.
- Infusion reaction mitigation: slowing infusion rates (1 mL min⁻¹ for 5 mg/kg vials) and premedication reduces incidence.
- Immunogenicity control: concomitant MTX (≤ 25 mg weekly) or azathioprine lowers ADA formation; consider cyclophosphamide or belimumab? *for high‑risk or refractory cases.*
- TDM‑driven dosing: Sub‑therapeutic trough levels (< 3 µg/mL) in Crohn disease predict poor response; escalating to 10–15 mg/kg or reducing infusion interval to 4 weeks may rescue disease control.
- Drug‑drug interactions: Minimal CYP interactions; however, concomitant levothyroxine absorption may be reduced if taken simultaneously; space the ingestion by 2 hrs.
- Pregnancy considerations: While data are limited, many clinicians treat pregnancies with continued exposure due to the critical benefit‑risk evaluation; counsel on potential transmission of anti‑TNF agents across placenta in 3rd trimester.
- Serious infection alerts: Check TB status every 6 months in endemic regions; use nucleic acid amplification for rapid TB detection.
- Cost‑efficiency: Biosimilars can reduce healthcare burden by 10–30 % while providing parity in outcomes; pharmacists should ensure proper storage and handling to preserve potency.
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