Usage
Vedolizumab is prescribed for the treatment of moderately to severely active ulcerative colitis and Crohn’s disease in adults when other treatments have been ineffective or are not suitable. It belongs to the pharmacological classification of integrin receptor antagonists, specifically a gut-selective immunosuppressant. It works by inhibiting the migration of gut-homing lymphocytes to the gastrointestinal tract, thereby reducing inflammation.
Alternate Names
Vedolizumab is also marketed under the brand name Entyvio®.
How It Works
Pharmacodynamics: Vedolizumab exerts its therapeutic effect by selectively targeting the α4β7 integrin, a protein found on the surface of certain white blood cells (a subset of memory T lymphocytes). These lymphocytes play a critical role in inflammation within the gastrointestinal tract. By binding to α4β7 integrin, vedolizumab prevents these cells from interacting with mucosal addressin cell adhesion molecule-1 (MAdCAM-1), a protein primarily expressed on gut endothelial cells. This interaction is crucial for the migration (homing) of these lymphocytes into the gut tissue. By disrupting this process, vedolizumab reduces inflammation in the intestinal lining, leading to improvement in symptoms of ulcerative colitis and Crohn’s disease.
Pharmacokinetics: Vedolizumab is administered intravenously or subcutaneously. Following intravenous infusion, the drug exhibits dose-proportional pharmacokinetics. Vedolizumab has a long elimination half-life, allowing for infrequent dosing (every 8 weeks for IV, every 2 weeks for subcutaneous). The drug is primarily eliminated through proteolytic degradation (breakdown of proteins), a process that occurs throughout the body. There is minimal hepatic (liver) metabolism.
Dosage
Standard Dosage
Adults:
- Intravenous (IV) Infusion: 300 mg administered over 30 minutes at weeks 0, 2, and 6, followed by 300 mg every 8 weeks thereafter.
- Subcutaneous (SC) Injection: Following at least 2 IV infusions, 108 mg administered subcutaneously every 2 weeks.
Children:
Vedolizumab is not approved for use in children. Pediatric dosing guidelines are not established.
Special Cases:
- Elderly Patients: No dose adjustment is generally required.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary.
- Patients with Comorbid Conditions: Use with caution in patients with active infections.
Clinical Use Cases
Vedolizumab’s usage is primarily limited to the outpatient setting for maintenance therapy of ulcerative colitis and Crohn’s disease. It is not typically used in situations such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments are not routinely required based on renal or hepatic function, metabolic disorders, or genetic polymorphisms. However, patients showing no evidence of therapeutic benefit by week 14 (for ulcerative colitis) or week 10 (for intravenous treatment) should discontinue therapy.
Side Effects
Common Side Effects:
Common cold symptoms (nasopharyngitis), headache, joint pain, nausea, fever.
Rare but Serious Side Effects:
Allergic reactions (rash, hives, swelling), infections (including progressive multifocal leukoencephalopathy - PML), liver injury (hepatitis).
Long-Term Effects:
The long-term effects of vedolizumab are still being studied. However, the potential for infections, including PML, remains a concern.
Adverse Drug Reactions (ADR):
Severe allergic reactions (anaphylaxis), infusion reactions (chest pain, shortness of breath), signs of liver injury (jaundice, abdominal pain).
Contraindications
- Hypersensitivity to vedolizumab.
- Active severe infections (e.g., tuberculosis, sepsis).
Drug Interactions
- Live vaccines (use with caution; should only be administered if the benefits clearly outweigh the risks).
- Natalizumab (avoid concomitant use).
- Immunosuppressants (e.g., azathioprine, 6-mercaptopurine, methotrexate): Concomitant use may increase the risk of infections.
- TNF-alpha inhibitors (e.g., infliximab, adalimumab): Limited data are available.
Pregnancy and Breastfeeding
Vedolizumab is categorized as Pregnancy Category B. Limited data suggest no increased risk of miscarriage or birth defects. While it is likely low risk during pregnancy, the decision to continue or discontinue treatment should be made in consultation with the patient and her healthcare provider, weighing the benefits against potential risks. Vedolizumab is present in breast milk at low concentrations, and data suggest it poses minimal risk to nursing infants. It is generally considered acceptable during breastfeeding, particularly after the newborn period.
Drug Profile Summary
- Mechanism of Action: α4β7 integrin antagonist, preventing lymphocyte migration to the gut.
- Side Effects: Common cold, headache, joint pain, nausea; rarely allergic reactions, infections (including PML), liver injury.
- Contraindications: Hypersensitivity, active severe infections.
- Drug Interactions: Live vaccines, natalizumab.
- Pregnancy & Breastfeeding: Generally considered safe, but careful evaluation of risks and benefits is essential.
- Dosage: IV: 300 mg at 0, 2, 6 weeks, then every 8 weeks; SC: 108 mg every 2 weeks after at least 2 IV doses.
- Monitoring Parameters: Complete blood count (CBC), liver function tests (LFTs) every 4 months; monitor for signs of infection.
Popular Combinations
Vedolizumab may be used in combination with corticosteroids (e.g., prednisone) for the initial management of active disease. In some instances, other immunosuppressants like azathioprine or 6-mercaptopurine might be added for enhanced efficacy or to maintain remission.
Precautions
Screen for infections (TB, hepatitis B) before starting treatment. Monitor for signs and symptoms of infection during treatment. Exercise caution in patients with a history of infections. Advise patients about the risk of PML. Live vaccines should be avoided or used with caution.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Vedolizumab?
A: Adults: IV: 300 mg at 0, 2, and 6 weeks then every 8 weeks. SC: 108 mg every 2 weeks after at least 2 IV infusions.
Q2: How does Vedolizumab work?
A: It blocks the α4β7 integrin, preventing specific white blood cells from entering the gut lining and causing inflammation.
Q3: What are the common side effects?
A: Common cold, headache, joint pain, nausea.
Q4: What are the serious side effects?
A: Allergic reactions, infections (including PML), and liver damage.
Q5: Can Vedolizumab be used during pregnancy?
A: It’s generally considered low risk, but the decision should be made individually, weighing benefits against potential risks.
Q6: Can Vedolizumab be used during breastfeeding?
A: It is generally considered safe, but caution is advised, especially with newborns or preterm infants.
Q7: What are the contraindications for Vedolizumab?
A: Hypersensitivity to vedolizumab and active severe infections.
Q8: How is Vedolizumab administered?
A: Intravenous infusion over 30 minutes or subcutaneous injection.
Q9: What are the drug interactions with Vedolizumab?
A: Avoid or use with caution: live vaccines and natalizumab. Concomitant use with immunosuppressants may increase the risk of infection.
Q10: How long does it take for Vedolizumab to work?
A: Some patients may experience improvement within a few weeks, but it may take up to 14 weeks to see a significant benefit.
