Usage
- Itolizumab is prescribed for the treatment of moderate to severe chronic plaque psoriasis in adults. It has also been used to manage cytokine release syndrome (CRS) in COVID-19 patients with moderate to severe acute respiratory distress syndrome (ARDS). Its utility in treating other immune-mediated disorders like rheumatoid arthritis and multiple sclerosis is being explored.
- Pharmacological classification: Immunomodulator, monoclonal antibody (specifically, a humanized recombinant IgG1 monoclonal antibody).
- Mechanism of Action: Itolizumab targets the CD6 receptor on T lymphocytes, which plays a crucial role in T-cell activation and proliferation. By binding to the CD6 receptor, itolizumab downregulates the production of pro-inflammatory cytokines (e.g., IFN-γ, TNFα, and IL-6), thus reducing inflammation.
Alternate Names
- Alzumab-L™ (Brand name in India)
How It Works
- Pharmacodynamics: Itolizumab binds to domain 1 of the CD6 receptor on T-cells. This binding inhibits T-cell activation, proliferation, and differentiation, ultimately reducing the release of pro-inflammatory cytokines. This modulation of the immune response leads to decreased inflammation.
- Pharmacokinetics: Administered intravenously, itolizumab reaches peak serum concentration at the end of the infusion. The elimination half-life is approximately 11 days. The precise metabolic pathways have not been fully elucidated.
- Mode of Action: Itolizumab binds with high affinity to the extracellular SRCR distal domain 1 of CD6, a cell surface glycoprotein expressed on T lymphocytes. This binding interferes with the CD6-ALCAM (activated leukocyte cell adhesion molecule) pathway, disrupting the costimulatory signal required for T-cell activation and pro-inflammatory cytokine production.
- Elimination pathways: Primarily through protein catabolism, no specific CYP enzyme involvement has been noted.
Dosage
Standard Dosage
Adults:
- Plaque Psoriasis: 1.6 mg/kg body weight, administered as an intravenous infusion every 2 weeks for 12 weeks, followed by 1.6 mg/kg every 4 weeks for up to 24 weeks. Infuse the dose over 2 hours (approximately 50 mL in the first hour and the remaining 200 mL in the next hour).
- Cytokine Release Syndrome (CRS) in COVID-19: Initial dose of 1.6 mg/kg intravenous infusion, followed by a weekly dose of 0.8 mg/kg if required, based on clinical response and inflammatory markers. The first infusion can be completed over 3-4 hours.
Children: Safety and efficacy have not been established in patients younger than 18 years.
Special Cases:
- Elderly Patients: No specific dose adjustments are indicated.
- Patients with Renal Impairment: No specific dose adjustments are noted; use with caution.
- Patients with Hepatic Dysfunction: No specific dose adjustments are noted; use with caution.
- Patients with Comorbid Conditions: Use cautiously in immunocompromised individuals with HIV, Hepatitis B/C, and chronic infections.
Clinical Use Cases
- Intubation: No specific dosage guidelines.
- Surgical Procedures: No specific dosage guidelines.
- Mechanical Ventilation: No specific dosage guidelines.
- Intensive Care Unit (ICU) Use: As per specific clinical protocols for the condition being treated (e.g., CRS).
- Emergency Situations: As per specific clinical protocols for the condition being treated (e.g., CRS).
Dosage Adjustments: Dose modifications are not well established. Exercise caution in patients with renal/hepatic dysfunction or active infections.
Side Effects
Common Side Effects
- Infusion reactions (chills, fever, nausea, headache, dizziness, rash, urticaria, cough, dyspnea)
- Upper respiratory tract infection
- Diarrhea
- Itching
Rare but Serious Side Effects
- Severe hypersensitivity reactions.
Long-Term Effects
- Data on long-term effects are limited.
Adverse Drug Reactions (ADR)
- Severe infusion reactions require immediate medical attention
Contraindications
- Active infections (including latent infections like tuberculosis)
- Hypersensitivity to itolizumab or murine proteins
Drug Interactions
- Live vaccines
- Limited drug interaction studies available.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not established. Itolizumab can cross the placental barrier. Use only if potential benefit outweighs the potential risk to the fetus.
- Breastfeeding: It is unknown if itolizumab is excreted in human milk. Discontinue breastfeeding or the drug, taking into account the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: Inhibits T-cell activation by targeting the CD6 receptor, reducing the production of pro-inflammatory cytokines.
- Side Effects: Infusion reactions, upper respiratory tract infection, fever, itching, diarrhea, dizziness.
- Contraindications: Active or latent infections, hypersensitivity to itolizumab or murine proteins.
- Drug Interactions: Live vaccines, limited data available.
- Pregnancy & Breastfeeding: Not recommended unless essential.
- Dosage: 1.6 mg/kg IV infusion (see dosage section for details and variations)
- Monitoring Parameters: Monitor vital signs during infusion, and monitor for signs and symptoms of infection.
Popular Combinations
- No established popular drug combinations.
Precautions
- Screen for active and latent infections before initiating therapy.
- Monitor for infusion reactions.
- Use with caution in patients with hepatic/renal impairment.
- Pregnant Women: Avoid unless absolutely necessary.
- Breastfeeding Mothers: Avoid unless absolutely necessary.
- Children & Elderly: Safety not established in children. No specific dose adjustments in elderly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Itolizumab?
A: For plaque psoriasis: 1.6 mg/kg IV infusion every 2 weeks for 12 weeks, then every 4 weeks for up to 24 weeks. For CRS: 1.6 mg/kg IV infusion followed by weekly 0.8mg/kg if needed.
Q2: What is the mechanism of action of Itolizumab?
A: Itolizumab targets the CD6 receptor on T-cells, inhibiting their activation and the subsequent release of pro-inflammatory cytokines.
Q3: What are the common side effects of Itolizumab?
A: Infusion reactions, upper respiratory tract infection, fever, itching, diarrhea, and dizziness.
Q4: Is Itolizumab safe during pregnancy and breastfeeding?
A: Not recommended unless essential. Itolizumab can cross the placental barrier. It’s unknown if it’s excreted in breast milk.
Q5: What are the contraindications for Itolizumab?
A: Active infections (including latent TB), hypersensitivity to itolizumab or murine proteins.
Q6: How is Itolizumab administered?
A: Itolizumab is administered as an intravenous infusion.
Q7: What are the potential drug interactions with Itolizumab?
A: Limited drug interaction studies available. Live vaccines should be avoided.
Q8: What should be monitored in patients receiving Itolizumab?
A: Monitor vital signs during infusion, signs and symptoms of infection, and clinical response.
Q9: Is there a specific dosage adjustment for elderly patients?
A: No specific dosage adjustment for elderly patients has been noted. However, caution is advised.
