Vedolizumab interacts in the following cases:
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.
Vedolizumab has not been studied in these patient populations. No dose recommendations can be made.
No vedolizumab clinical trial data are available for patients previously treated with natalizumab or rituximab. Caution should be exercised when considering the use of vedolizumab in these patients.
Patients previously exposed to natalizumab should normally wait a minimum of 12 weeks prior to initiating therapy with vedolizumab, unless otherwise indicated by the patient’s clinical condition.
No clinical trial data for concomitant use of vedolizumab with biologic immunosuppressants are available. Therefore, the use of vedolizumab in such patients is not recommended.
There are limited amount of data from the use of vedolizumab in pregnant women.
In a small prospective observational study the rate of major birth defects was 7.4% in 99 women with ulcerative colitis or Crohn’s disease treated with vedolizumab and 5.6% in 76 women with ulcerative colitis or Crohn’s disease treated with other biologic agents (adjusted relative risk (RR) 1.07, 95% Confidence Interval (CI): 0.33, 3.52).
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.
Vedolizumab has been detected in human milk. The effect of vedolizumab on breast-fed infants, and the effects on milk production are unknown. In a milk-only lactation study assessing the concentration of vedolizumab in breast milk of lactating women with active ulcerative colitis or Crohn’s disease receiving vedolizumab, the concentration of vedolizumab in human breast milk was approximately 0.4% to 2.2% of the maternal serum concentration obtained from historical studies of vedolizumab. The estimated average daily dose of vedolizumab ingested by the infant was 0.02 mg/kg/day, which is approximately 21% of the body weight-adjusted average maternal daily dose.
The use of vedolizumab in lactating women should take into account the benefit of therapy to the mother and potential risks to the infant.
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.
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.
Vedolizumab has minor influence on the ability to drive and use machines, as dizziness has been reported in a small number of patients.
The most commonly reported adverse reactions are infections (such as nasopharyngitis, upper respiratory tract infection, bronchitis, influenza and sinusitis), headache, nausea, pyrexia, fatigue, cough, arthralgia.
No clinically relevant differences in the overall safety profile and adverse reactions were observed in patients who received subcutaneous vedolizumab compared to the safety profile observed in clinical studies with intravenous vedolizumab with the exception of injection site reactions (with subcutaneous administration).
The following listing of adverse reactions is based on clinical trial and post marketing experience and is displayed by system organ class. Within the system organ classes, adverse reactions are listed under headings of the following frequency categories: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), very rare (<1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse reactions:
| System organ class | Frequency | Adverse reaction(s) |
|---|---|---|
| Infections and infestations | Very common | Nasopharyngitis |
| Common | Pneumonia, Clostridium difficile infection, Bronchitis, Gastroenteritis, Upper respiratory tract infection, Influenza, Sinusitis, Pharyngitis, Herpes zoster | |
| Uncommon | Respiratory tract infection, Vulvovaginal candidiasis, Oral candidiasis | |
| Immune system disorders | Very rare | Anaphylactic reaction, Anaphylactic shock |
| Nervous system disorders | Very common | Headache |
| Common | Paraesthesia | |
| Eye disorders | Uncommon | Blurred vision |
| Vascular disorders | Common | Hypertension |
| Respiratory, thoracic and mediastinal disorders | Common | Oropharyngeal pain, Nasal congestion, Cough |
| Not known | Interstitial lung disease | |
| Gastrointestinal disorders | Common | Anal Abscess, Anal fissure, Nausea, Dyspepsia, Constipation, Abdominal distension, Flatulence, Haemorrhoids |
| Skin and subcutaneous tissue disorders | Common | Rash, Pruritus, Eczema, Erythema, Night sweats, Acne |
| Uncommon | Folliculitis | |
| Musculoskeletal and connective tissue disorders | Very common | Arthralgia |
| Common | Muscle spasms, Back pain, Muscular weakness, Fatigue, Pain in the extremity | |
| General disorders and administration site conditions | Common | Pyrexia, Infusion site reaction (including: Infusion site pain and Infusion site irritation), Infusion related reaction, Injection site reactions# |
| Uncommon | Chills, Feeling cold |
# Subcutaneous administration only.
Injection site reactions (including pain, oedema, erythema or pruritus) were reported in 5.1% of patients receiving subcutaneous vedolizumab (pooled safety analysis). None resulted in discontinuation of study treatment or changes to the dosing schedule. The majority of injection site reactions resolved within 1-4 days. There were no reports of anaphylaxis following subcutaneous vedolizumab administration.
In GEMINI 1 and 2 controlled studies with intravenous vedolizumab, the rate of infections was 0.85 per patient-year in the vedolizumab-treated patients and 0.70 per patient-year in the placebo-treated patients. The infections consisted primarily of nasopharyngitis, upper respiratory tract infection, sinusitis, and urinary tract infections. Most patients continued on vedolizumab after the infection resolved.
In GEMINI 1 and 2 controlled studies with intravenous vedolizumab, the rate of serious infections was 0.07 per patient year in vedolizumab-treated patients and 0.06 per patient year in placebo-treated patients. Over time, there was no significant increase in the rate of serious infections.
In controlled and open-label studies in adults with intravenous vedolizumab, serious infections have been reported, which include tuberculosis, sepsis (some fatal), salmonella sepsis, listeria meningitis, and cytomegaloviral colitis.
In clinical studies with subcutaneous vedolizumab, the rate of infections was 0.26 per patient year in vedolizumab-treated patients. The most frequent infections were nasopharyngitis, upper respiratory tract infection, bronchitis and influenza.
In clinical studies with subcutaneous vedolizumab, the rate of serious infections was 0.02 per patient year in subcutaneous vedolizumab-treated patients.
In clinical studies with intravenous and subcutaneous vedolizumab, the rate of infections in vedolizumab-treated patients with BMI of 30 kg/m² and above was higher than for those with BMI less than 30 kg/m².
In clinical studies with intravenous and subcutaneous vedolizumab, a slightly higher incidence of serious infections was reported in vedolizumab-treated patients who had prior exposure to TNFα antagonist therapy compared to patients who were naïve to previous TNFα antagonist therapy.
Overall, results from the clinical program to date do not suggest an increased risk for malignancy with vedolizumab treatment; however, the number of malignancies was small and long-term exposure was limited. Long-term safety evaluations are ongoing.
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