Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
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).

Tabulated list of adverse reactions

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.

Table 1. 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            Common            Oropharyngeal pain, mediastinal disorders                                  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         Common            Rash,
disorders                                              Pruritus,
Eczema,
Erythema,
Night sweats,
Acne
Uncommon          Folliculitis



System organ class               Frequency           Adverse reaction(s) Musculoskeletal and connective   Very common         Arthralgia tissue disorders                 Common              Muscle spasms,
Back pain,
Muscular weakness,
Fatigue,
Pain in the extremity
General disorders and            Common              Pyrexia,
administration site conditions                       Infusion site reaction (including: Infusion site pain and Infusion site irritation),
Infusion related reaction,
Injection site reactions#
Uncommon            Chills,
Feeling cold
#
Subcutaneous administration only.

Description of selected adverse reactions

Injection site reactions
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.

Infections

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.


Malignancy
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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il