Vedolizumab

Vedolizumab is a Monoclonal antibody belonging to gut specific immunosuppressant class.

Vedolizumab is an integrin blocker and anti-inflammatory agent used to manage ulcerative colitis and Crohn's disease in adults with inadequate clinical response to immunomodulators.

The intended route of administration is intravenous, therefore there is no absorption data and bioavailability are expected to be 100%. Serum apparent volume of distribution at steady state has been found to be moderately greater than the serum volume. It is therefore expected to be confined to the systemic circulation, as expected for a high molecular weight protein. The expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance. Vedolizumab has a long terminal elimination half-life of 336 to 362 hours. Vedolizumab has a low clearance of 0.180 to 0.266 ml/hr/kg.

Vedolizumab shows side effects like Headache, nausea, joint or back pain, pain in your arms and legs.

Vedolizumab is available in the form of Powder for injection.

Vedolizumab is available in India, US, Canada, Spain, China, Japan, France, Italy, Malaysia, and Australia.

Vedolizumab belongs to the gut specific immunosuppressant class acts as a Monoclonal antibody.

Vedolizumab binds to α4β7 integrin, a key mediator of gastrointestinal inflammation expressed on the surfaces of T and B lymphocytes. By selectively inhibiting the α4β7 integrin, vedolizumab inhibits adhesion of lymphocytes to its natural ligand, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), thereby preventing lymphocytic cells from entering the gut lamina propria and gut-associated lymphoid tissue (GALT). Specifically inhibiting this pathway alleviates GI inflammation without impairing systemic immune responses.

The onset and duration of action of Vedolizumab is not clinically established.

Vedolizumab is an integrin blocker and anti-inflammatory agent used to manage ulcerative colitis and Crohn's disease in adults with inadequate clinical response to immunomodulators.

Vedolizumab is approved for use in the following clinical indications

• Ulcerative Colitis
• Crohn's Disease

• Ulcerative Colitis

IV: 300 mg at 0, 2, and 6 weeks and then every 8 weeks thereafter. Discontinue therapy in patients who show no evidence of therapeutic benefit by week 14.

Subcutaneously: Maintenance: 108 mg once every 2 weeks beginning after at least 2 IV infusions; administer in place of next scheduled IV dose and then every 2 weeks thereafter.

• Crohn's Disease

IV: 300 mg at 0, 2, and 6 weeks and then every 8 weeks thereafter. Discontinue therapy in patients who show no evidence of therapeutic benefit by week 14.

Subcutaneously: Maintenance: 108 mg once every 2 weeks beginning after at least 2 IV infusions; administer in place of next scheduled IV dose and then every 2 weeks thereafter.

Vedolizumab is available in the form of Powder for injection.

Vedolizumab is contraindicated in patients with

• Vedolizumab is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to Vedolizumab or any of its excipients (such as dyspnea, bronchospasm, urticaria, flushing, rash and increased heart rate).

• Infusion-Related Reactions and Hypersensitivity Reactions

In UC Trials I and II and CD Trials I and III, hypersensitivity reactions occurred including a case of anaphylaxis (one out of 1434 patients [0.07%]). Allergic reactions including dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate have also been observed. The majority were mild to moderate in severity as assessed by the investigator. Experience with other biologic medications suggests that hypersensitivity reactions and anaphylaxis to Vedolizumab may vary in their time of onset from during infusion or immediately post-infusion to occurring up to several hours post infusion. If anaphylaxis or other serious allergic reactions occur, discontinue administration of Vedolizumab immediately and initiate appropriate treatment (e.g., epinephrine and antihistamines).

• Infections

Patients treated with Vedolizumab are at increased risk for developing infections. The most commonly reported infections in clinical trials occurring at a rate greater on Vedolizumab than placebo involved the upper respiratory and nasal mucosa (e.g., nasopharyngitis, upper respiratory tract infection). Serious infections have also been reported in patients treated with Vedolizumab, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis and cytomegaloviral colitis. Vedolizumab is not recommended in patients with active, severe infections until the infections are controlled. Consider withholding treatment in patients who develop a severe infection while on treatment with Vedolizumab. Exercise caution when considering the use of Vedolizumab in patients with a history of recurring severe infections. Consider screening for tuberculosis (TB) according to the local practice. For progressive multifocal leukoencephalopathy (PML).

• Progressive Multifocal Leukoencephalopathy

Another integrin receptor antagonist has been associated with progressive multifocal leukoencephalopathy (PML), a rare and often fatal opportunistic infection of the central nervous system (CNS). PML is caused by the John Cunningham (JC) virus and typically only occurs in patients who are immunocompromised. In Vedolizumab clinical trials, patients were actively monitored for PML with frequent and regular screenings, and evaluations of any new, unexplained neurological symptoms, as necessary. While zero cases of PML were identified among patients with at least 24 months of exposure, a risk of PML cannot be ruled out. No claims of comparative safety to other integrin receptor antagonists can be made based on this data. Monitor patients on Vedolizumab for any new onset, or worsening, of neurological signs and symptoms. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. The progression of deficits usually leads to death or severe disability over weeks or months. If PML is suspected, withhold dosing with Vedolizumab and refer to a neurologist; if confirmed, discontinue dosing permanently.

• Liver Injury

There have been reports of elevations of transaminase and/or bilirubin in patients receiving Vedolizumab. In general, the combination of transaminase elevations and elevated bilirubin without evidence of obstruction is generally recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients. Vedolizumab should be discontinued in patients with jaundice or other evidence of significant liver injury.

It is unknown whether vedolizumab is present in human milk. Vedolizumab was detected in the milk of lactating monkeys. Exercise caution when administering vedolizumab to a nursing woman.

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Common

● Antibody development, Headache, Arthralgia, Nasopharyngitis, Pruritus, skin rash, Nausea, Increased serum alanine aminotransferase, increased serum aspartate aminotransferase, Influenza, Fatigue, Back pain, limb pain, Bronchitis, cough, oropharyngeal pain, sinusitis, upper respiratory tract infection, Fever, infusion related reaction.

Rare

● Malignant neoplasm (excluding dysplasia and basal cell carcinoma), Hepatitis, increased serum bilirubin, increased serum transaminases, Anaphylaxis, bronchospasm, hypersensitivity reaction, Infection (including anal abscess, sepsis, tuberculosis, salmonella sepsis, meningitis due to Listeria monocytogenes, giardiasis, cytomegalovirus disease), Progressive multifocal leukoencephalopathy (in a patient with multiple risk factors [ie, HIV, CD4 count 300 cells/mm³, prolonged prior and concurrent immunosuppression]).

• Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents).
• Anti-TNF Agents: May enhance the adverse/toxic effect of Vedolizumab.
• Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib.
• BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products.
• Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir.
• Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine.
• Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results.
• Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections.
• Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents).
• Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents.
• Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents).
• Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab.
• Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored.
• Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents.
• Natalizumab: Vedolizumab may enhance the adverse/toxic effect of Natalizumab.
• Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab.
• Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab.
• Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod.
• Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration.
• Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical).
• Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy.
• Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical).
• Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased.
• Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide.
• Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials.
• Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine.
• Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib.

The common side effects of Vedolizumab include the following

Common side effects

● Headache, nausea, joint or back pain, pain in your arms and legs.

Rare side effects

● Fever, Cough, Runny nose, Sore throat, Chills, Aches and other signs of infection, Red or painful skin or sores on your body, Pain during urination, Confusion or memory problems, Loss of balance, Changes in walking or speech, Decreased strength or weakness on one side of your body, blurred vision or loss of vision, extreme tiredness, loss of appetite, pain in the upper right part of the stomach, unusual bruising or bleeding, dark urine, yellowing of the skin or eyes.

• Pregnancy

Pregnancy Category B

There are no studies with Vedolizumab in pregnant women. No fetal harm was observed in animal reproduction studies with intravenous administration of vedolizumab to rabbits and monkeys at dose levels 20 times the recommended human dosage. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the benefits to the mother outweigh the risk to the unborn child.

• Nursing Mothers

It is unknown whether vedolizumab is present in human milk. Vedolizumab was detected in the milk of lactating monkeys. Exercise caution when administering vedolizumab to a nursing woman.

• Pediatric Use

Safety and effectiveness of Vedolizumab in pediatric patients have not been established.

• Geriatric Use

Clinical trials of Vedolizumab did not include sufficient numbers of subjects aged 65 and over (46 Crohn’s and ulcerative colitis patients aged 65 and over were treated with Vedolizumab during controlled Phase 3 trials) to determine whether they respond differently from younger subjects. However, no overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Pharmacodynamic

Non-clinical studies have shown that the pharmacodynamic effects of vedolizumab are reversible upon removal of the antibody: pharmacologic activity of cells inhibited by vedolizumab could be partially restored within 24 hours after removal, with near complete restoration within 4 days. There are no known drug interactions as vedolizumab is a humanized antibody and does not modulate production of cytokines, which is known to affect drug metabolism.

Pharmacokinetics

• Absorption

The intended route of administration is intravenous, therefore there is no absorption data and bioavailability are expected to be 100%.

• Distribution

Serum apparent volume of distribution at steady state has been found to be moderately greater than the serum volume. It is therefore expected to be confined to the systemic circulation, as expected for a high molecular weight protein.

• Metabolism and Excretion

The expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance. Vedolizumab has a long terminal elimination half-life of 336 to 362 hours. Vedolizumab has a low clearance of 0.180 to 0.266 ml/hr/kg.

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