Vedolizumab

Registered South African indications:

• Ulcerative colitis
• Crohn's disease

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Active severe infections such as tuberculosis (TB), sepsis, cytomegalovirus, listeriosis
• Opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML)

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Controlled chronic severe infection
• History of recurring severe infections
• Inflammatory bowel disease
• Patients previously treated with natalizumab or rituximab
• Coadministration with immunomodulatory medicinal agents
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Ulcerative colitis
- Moderately to severely active ulcerative colitis where inadequate response, loss of response or intolerance to either conventional therapy or tumour necrosis factor-alpha (TNFα) antagonists exists
Crohn's disease
- Moderately to severely active Crohn's disease where inadequate response, loss of response or intolerance to either conventional therapy or tumour necrosis factor-alpha (TNFα) antagonists exists 

• IV: 300mg, as an infusion over 30min; Administration schedule: 0, 2 and 6 weeks; Then: 8 weekly thereafter

Treatment should be initiated and supervised by specialist healthcare professionals experienced in the diagnosis and treatment of ulcerative colitis and/or Crohn's disease respectively

Ulcerative colitis: Therapy should be discontinued if no evidence of therapeutic benefit is observed by week 10

Crohn's disease: Patients who have not shown a response may benefit from a dose of intravenous vedolizumab at week 10

Crohn's disease: Therapy should be continued every 8 weeks from week 14 in responding patients. Therapy should be discontinued if no evidence of therapeutic benefit is observed by week 14

Some patients who have experienced a decrease in their response may benefit from an increase in dosing frequency to intravenous vedolizumab 300 mg every 4 weeks

In patients who have responded to treatment with vedolizumab, corticosteroids may be reduced and/or discontinued in accordance with standard of care

Retreatment: See additional prescribing points

Infusion-related reactions and hypersensitivity reactions: See additional prescribing points

Not established for use in children below 18 years

Pregnancy

• Caution
• There are limited amount of data from the use of vedolizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity
• As a precautionary measure, it is preferable to avoid the use of vedolizumab during pregnancy unless the benefits clearly outweigh any potential risk to both the mother and foetus
• Women of childbearing potential should use adequate contraception to prevent pregnancy and to continue its use for at least 18 weeks after the last treatment

Breastfeeding

• Caution
• Vedolizumab has been detected in human milk. The effect of vedolizumab on infants is unknown. The use of vedolizumab in breastfeeding women should take into account the benefit of therapy to the mother and potential risks to the infant

Fertility

• There are no data on the effects of vedolizumab on human fertility. Effects on male and female fertility have not been formally evaluated in animal studies

Renal Impairment

• Caution; no information available

Hepatic Impairment 

• Caution; no information available 
  If jaundice or hepatic injury is observed, discontinue use

Elderly 

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)
  Nausea and vomiting are common adverse reactions that can occur during vedolizumab use, these may be potentially porphyrinogenic if they lead to a decrease in carbohydrate intake. Vigilance in monitoring signs and symptoms of infection is recommended, as infections are common during use of immunosuppressant agents

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Paraesthesia
• Fatigue

Cardiovascular Disorders

• Hypertension

Respiratory Disorders

• Nasal congestion
• Cough
• Nasopharyngitis
• Bronchitis
• Upper respiratory tract infection
• Influenza
• Sinusitis
• Pharyngitis
• Respiratory tract infection
• Pneumonia
• Tuberculosis

Gastrointestinal Disorders

• Anal abscess
• Anal fissure
• Nausea
• Dyspepsia
• Constipation
• Abdominal distension
• Flatulence
• Haemorrhoids
• Oropharyngeal pain
• Gastroenteritis
• Oral candidiasis

Genitourinary Disorders

• Vulvovaginal candidiasis
• Urinary tract infections

Musculoskeletal Disorders

• Arthralgia
• Muscle spasms
• Back pain
• Muscular weakness
• Pain in the extremity

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Eczema
• Erythema
• Night sweats
• Acne
• Folliculitis
• Infusion site reaction
  - Pain
  - Irritation
  - Chills
  - Feeling cold

Immune, Blood and Lymphatic System Disorders

• Herpes zoster
• Anaphylactic reaction
• Anaphylactic shock
• Sepsis (some fatal)
• Salmonella sepsis
• Listeria meningitis
• Cytomegaloviral colitis
• Infusion-related reactions
  - Dyspnoea
  - Bronchospasm
  - Urticaria
  - Flushing
  - Rash
  - Increased blood pressure
  - Increased heart rate
  - Infusion site pain
  - Infusion site irritation
  - Chills
• Fever

Sensory Disorders

• Blurred vision

• Live vaccines (particularly oral)
  See additional prescribing points

• Hepatic function
• Tuberculosis screening

Additional observations

• Hypersensitivity reactions
• Signs and symptoms of infection
• New-onset or worsening neurological signs and symptoms

Ulcerative colitis - Retreatment

• If therapy is interrupted and there is a need to restart treatment with intravenous vedolizumab, dosing at every 4 weeks may be considered
• The treatment interruption period in clinical trials extended up to 1 year
• Efficacy was regained with no evident increase in adverse reactions or infusion-related reactions during retreatment with vedolizumab

Crohn's disease - Retreatment

• If therapy is interrupted and there is a need to restart treatment with intravenous vedolizumab, dosing at every 4 weeks may be considered
• The treatment interruption period in clinical trials extended up to 1 year
• Efficacy was regained with no evident increase in adverse reactions or infusion-related reactions during retreatment with vedolizumab

Infusion-related reactions (IRR) and hypersensitivity reactions

• If a mild to moderate IRR occurs, the infusion rate can be slowed or interrupted and appropriate treatment initiated. Once the mild or moderate IRR subsides, continue the infusion. Physicians should consider pre-treatment (e.g., with antihistamine, hydrocortisone and/or paracetamol) prior to the next infusion for patients with a history of mild to moderate IRR to vedolizumab, in order to minimize their risks 
• If a severe IRR, anaphylactic reaction, or other severe reaction occurs, administration of vedolizumab must be discontinued immediately and appropriate treatment initiated (e.g., epinephrine and antihistamines) 

Administration precautions

• Intravenous vedolizumab should be administered in a healthcare setting equipped to allow management of acute hypersensitivity reactions including anaphylaxis, if they occur
• Appropriate monitoring and medical support measures should be available for immediate use when administering intravenous vedolizumab
• All patients should be observed continuously during each infusion
• For the first 2 infusions, they should also be observed for approximately 2 hours following completion of the infusion for signs and symptoms of acute hypersensitivity reactions
• For all subsequent infusions, patients should be observed for approximately 1 hour following completion of the infusion

Live and oral vaccines

• In a placebo-controlled study of healthy volunteers, a single 750 mg dose of vedolizumab did not lower rates of protective immunity to hepatitis B virus in subjects who were vaccinated intramuscularly with 3 doses of recombinant hepatitis B surface antigen
• Vedolizumab-exposed subjects had lower seroconversion rates after receiving a killed, oral cholera vaccine
• The impact on other oral and nasal vaccines is unknown. It is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating vedolizumab therapy
• Patients receiving vedolizumab treatment may continue to receive non-live vaccines
• There are no data on the secondary transmission of infection by live vaccines in patients receiving vedolizumab
• Administration of the influenza vaccine should be by injection in line with routine clinical practice
• Other live vaccines may be administered concurrently with vedolizumab only if the benefits clearly outweigh the risks

Traceability

• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Vedolizumab is a gut-selective immunosuppressive biologic. It is a humanised monoclonal antibody that binds specifically to the αβ integrin, which is preferentially expressed on gut homing T helper lymphocytes. By binding to αβ on certain lymphocytes, vedolizumab inhibits adhesion of these cells to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), but not to vascular cell adhesion molecule-1 (VCAM-1). MAdCAM-1 is mainly expressed on gut endothelial cells and plays a critical role in the homing of T lymphocytes to tissues within the gastrointestinal tract. Vedolizumab does not bind to, nor inhibit function of, the αβ and αβ integrins.

The αβ integrin is expressed on a discrete subset of memory T helper lymphocytes which preferentially migrate into the gastrointestinal (GI) tract and cause inflammation that is characteristic of ulcerative colitis and Crohn's disease, both of which are chronic inflammatory immunologically mediated conditions of the GI tract. Vedolizumab reduces gastrointestinal inflammation in ulcerative colitis and Crohn's disease patients. Inhibiting the interaction of αβ with MAdCAM-1 with vedolizumab prevents transmigration of gut-homing memory T helper lymphocytes across the vascular endothelium into parenchymal tissue in nonhuman primates and induced a reversible 3-fold elevation of these cells in peripheral blood. The murine precursor of vedolizumab alleviated gastrointestinal inflammation in colitic cotton-top tamarins, a model of ulcerative colitis. Vedolizumab inhibited immune response to a gastrointestinal antigenic challenge in healthy human volunteers. In healthy subjects, ulcerative colitis patients, or Crohn's disease patients, vedolizumab does not elevate neutrophils, basophils, eosinophils, B-helper and cytotoxic T lymphocytes, total memory T helper lymphocytes, monocytes or natural killer cells, in the peripheral blood with no leukocytosis observed.

Injection (per ml) 300mg

• Entyvio (Takeda) originator