vedolizumab

VEDOLIZUMAB

Complete information including dosage, side effects, interactions and pregnancy & breast feeding warnings for patient and professional use

Indication (uses)

In adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids. vedolizumab

  • Adult ulcerative colitis
    • Inducing and maintaining clinical response,
    • Inducing and maintaining clinical remission,
    • Improving the endoscopic appearance of the mucosa, and
    • Achieving corticosteroid-free remission
  • Adult crohn’s disease
    • Achieving clinical response,
    • Achieving clinical remission, and
    • Achieving corticosteroid-free remission

Pharmacological classification

Anti-cancer drug used for the treatment of ulcerative colitis and crohn’s disease.

Brand names

ENTYVIO

Dosage form

  • 300 mg of vedolizumab as a lyophilized cake in single dose 20 mL vials for reconstitution.

Mechanism of action

Vedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin and blocks the interaction of α4β7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. Vedolizumab does not bind to or inhibit function of the α4β1 and αEβ7 integrins and does not antagonize the interaction of α4 integrins with vascular cell adhesion molecule-1 (VCAM-1).

The α4β7 integrin is expressed on the surface of a discrete subset of memory T-lymphocytes that preferentially migrate into the gastrointestinal tract. MAdCAM-1 is mainly expressed on gut endothelial cells and plays a critical role in the homing of T-lymphocytes to gut lymph tissue. The interaction of the α4β7 integrin with MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of ulcerative colitis and Crohn’s disease.

Dosage

Dosage in Adults with Ulcerative Colitis or Crohn’s Disease

  • 300 mg administered by intravenous infusion at zero, two and six weeks and then every eight weeks thereafter.
  • Discontinue therapy in patients who show no evidence of therapeutic benefit by Week 14.
  • Prior to initiating treatment with Vedolizumab, all patients should be brought up to date with all immunizations according to current immunization guidelines.
  • Read the manufacturer’s package insert for important administration instructions and reconstitution and dilution instructions.

Renal dose adjustments

  • Data not available. Dose adjustments may be required.

Hepatic dose adjustments

  • Data not available. Dose adjustments may be required.
  • 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.

Geriatric dose adjustments

  • Data not available. Dose adjustments may be required.

Pediatric use

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

Overdosage

  • No specific antidote is known.
  • Seek immediate medical attention.
  • Treatment of overdosage involves
  • General supportive measures.

Side effects or adverse effects

Side effects specific to Vedolizumab for injection

  • Infusion-Related Reactions and Hypersensitivity Reactions
    • Allergic reactions including dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate have also been observed.
    • 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 immune-compromised.
    • 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.

Other side effects

  • Bone marrow depression
    • Bone marrow depression is the most serious side effect/toxicity. It is also a limiting factor for the dose. Infections and bleeding are the common complications.
    • Bone marrow depression results in granulocytopenia, agranulocytosis, thrombocytopenia and aplastic anemia.
    • Consult your doctor as soon as possible if you observe any of the below mentioned symptoms:
      • Sore throat
      • Chills
      • Sudden fever
      • Weakness in limbs
      • Mouth ulcers
      • Bleeding gums
      • Sore mouth
      • Fast heart rate
      • Low blood pressure
      • Sore gums
      • Skin abscesses
      • Rapid breathing
      • Rapid progression of infection of any organ
      • Rapid progression of Septicemia
    • Gastrointestinal side effects
      • Nausea and vomiting are commonly observed with anti-cancer medicines.
      • Mucositis – painful inflammation and ulceration of mucus membrane lining the digestive tract.
      • Diarrhea, shredding of mucosa and haemorrhage due to decreased rate of renewal of gastrointestinal mucosa lining.
    • Skin
      • Alopecia or hair loss.
      • Dermatitis
    • Oral side effects
      • Breaches during chewing.
      • Depression of immunity due to reduction in number of WBCs largely increases the risk of oral infections.
      • Bleeding gums
      • Rapid progression of dental caries.
    • Gonadal side effects
      • Infertility due to Oligozoospermia in males.
      • Impotence in males.
      • Loss or reduces sex drive.
      • Inhibition of ovulation in females
      • Amenorrhea in females.
      • Damage to germinal cells may lead to mutagenesis.
    • Lymphoreticular tissue
      • Lymphocytopenia (reduced number of lymphocytes)
      • Inhibition of lymphocyte function.
      • Suppression of immunity due to bone marrow depression and reduced lymphocyte function highly increases the risk of opportunistic infections like:
        • Candida and other infections causing deep mycosis.
        • Cytomegalo virus
        • Herpes zoster
        • Pneumocystis jiroveci
        • Toxoplasma
      • Fetal side effects
        • Use of anti-cancer medicines in pregnant women may cause fetal damage leading to:
          • Fetal death
          • Abortion
          • Teratogenesis
        • Renal side effects
          • Renal failure, Gout and Urate stones may develop in urinary tract.
        • Hyperuricemia
          • An elevated level of uric acid is common in leukemia and bulky lymphomas.
        • Please note: The side effects mentioned above are from the reported cases. However, side effects are not limited to above mentioned conditions and symptoms. Consult your doctor as soon as possible if you feel or observe any symptoms that you relate to your treatment.

Warnings & Precautions

Live and Oral Vaccines

  • Prior to initiating treatment with Vedolizumab, all patients should be brought up to date with all immunizations according to current immunization guidelines.
  • Patients receiving Vedolizumab may receive non-live vaccines (e.g., influenza vaccine injection) and may receive live vaccines if the benefits outweigh the risks.
  • There are no data on the secondary transmission of infection by live vaccines in patients receiving Vedolizumab.

Contraindications

  • Contraindicated in patients with previous hypersensitivity (dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate) to Vedolizumab.

Pregnancy & breast feeding warnings

Pregnancy

Category B, which means that Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

  • No sufficient human studies have been conducted regarding the use of Vedolizumab in pregnant women.
  • Vedolizumab should be used in pregnancy only if clearly needed or if no other options are available.

Nursing

  • It is not known whether Vedolizumab is excreted in human breast milk or not.
  • Since many drugs are excreted in milk and because of the potential for side effects in nursing infants, a decision should be made whether to discontinue drug or to discontinue nursing.

Interactions

Drug – drug interactions

  • Because of the potential for increased risk of PML and other infections, avoid the concomitant use of Vedolizumab with natalizumab.
  • Because of the potential for increased risk of infections, avoid the concomitant use of Vedolizumab with TNF blockers.
  • Live vaccines may be administered concurrently with Vedolizumab only if the benefits outweigh the risks.
  • Concomitant use of Vedolizumab with following drugs/medicines should be strictly avoided.
    • Leflunomide as it increases the risk of infections.
    • Adalimumab as it increases the risk of infections.
    • Teriflunomide as it increases the risk of infections.
    • Certolizumab as it increases the risk of infections.
    • Influenza virus vaccine (live, trivalent) as it increases the risk of infections.
    • Small pox vaccine as it increases the risk of infections.
    • Measles virus vaccine as it increases the risk of infections.
    • Mumps virus vaccine as it increases the risk of infections.
    • Polio virus vaccine (live, trivalent) as it increases the risk of infections.
    • Varicella virus vaccine as it increases the risk of infections.
    • Typhoid vaccine (live) as it increases the risk of infections.
    • BCG vaccine as it increases the risk of infections.
    • Yellow fever vaccine as it increases the risk of infections.
    • Zoster vaccine (live) as it increases the risk of infections.
    • Tofacitinib as it increases the risk of infections.
    • Etanercept as it increases the risk of infections.
    • Fingolimod as it increases the risk of infections.
    • Golimumab as it increases the risk of infections.
    • Infliximab as it increases the risk of infections.
    • Alefacept as it increases the risk of infections.
    • Alemtuzumab as it increases the risk of infections.
    • Azathioprine as it increases the risk of infections.
    • Canakinumab as it increases the risk of infections.
    • Cladribine as it increases the risk of infections.
    • Denosumab as it increases the risk of infections.
    • Efalizumab as it increases the risk of infections.
    • Ocrelizumab as it increases the risk of infections.
    • Omacetaxine as it increases the risk of infections.
    • Ustekinumab as it increases the risk of infections.

Click here to go to Vedolizumab forums.

Reference

  • Highlights of prescribing information: 1
By |2017-12-20T13:00:10+00:00September 1st, 2017|medicines|1 Comment

About the Author:

B. Pharm (K.L.E. society's S.V.V. Patil College of Pharmacy, Bengaluru) M. Pharm (Maharishi Arvind Institute of Pharmacy, Jaipur)

One Comment

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