Medicinal Products

ENTYVIO 300 mg

Generic drug of the therapeutic class: Immunology
active ingredients: Vedolizumab
laboratory: Takeda

Powder for concentrate for solution for infusion IV
Box of 1 vial of 300 mg of powder
All forms

Indication

Hemorrhagic rectocolitis
Treatment of moderate to severe active ulcerative colitis in adult patients with insufficient response or loss of response or intolerance to conventional therapy or anti-TNF (tumor necrosis factor alpha antagonist).

Crohn's disease
Treatment of moderate to severe active Crohn's disease in adult patients with insufficient response or loss of response or intolerance to conventional therapy or anti-TNF (tumor necrosis factor alpha antagonist).

Dosage ENTYVIO 300 mg Powder for concentrate for solution for infusion IV Box of 1 vial of 300 mg powder

Treatment with Entyvio should be initiated and supervised by health professionals experienced in the diagnosis and treatment of ulcerative colitis and Crohn's disease. The package leaflet and patient alert card must be provided to patients.

Dosage

Hemorrhagic rectocolitis

300 mg administered by intravenous infusion followed by additional infusions at two and six weeks, then every eight weeks.

The continuation of the treatment will have to be carefully reconsidered if no therapeutic benefit is observed at the 10th week (see section Pharmacodynamic properties).

Patients who escape treatment may benefit from an increase in the frequency of administration to 300 mg Entyvio every four weeks.

In patients who have responded to treatment with Entyvio, corticosteroids can be reduced and / or discontinued, according to standard care standards.

Re-administration of treatment

After treatment interruption, if re-treatment is necessary, administration every four weeks may be considered (see section 5.1). In clinical trials, treatment interruption lasted up to one year. Efficacy was achieved with the re-administration of vedolizumab, with no apparent increase in adverse events or infusion-related reactions (see section 4.8).

Crohn's disease

300 mg administered by intravenous infusion followed by additional infusions at two, six and eight weeks thereafter.

Patients in whom no response has been observed may receive an administration of Entyvio at the 10th week (see Warnings and precautions for use). From the 14th week, treatment will be continued every eight weeks in responder patients. Treatment should be discontinued if no therapeutic benefit is observed by week 14 (see section 5.1).

Some patients who have escaped treatment may benefit from an increase in the frequency of administration to 300 mg of Entyvio every four weeks.

In patients who have responded to treatment with Entyvio, corticosteroids can be reduced and / or discontinued, according to standard care standards.

Re-administration of treatment

If re-administration of Entyvio is necessary after treatment interruption, once every four weeks it may be considered (see section 5.1). In clinical trials the interruption of treatment lasted up to one year. Efficacy has been achieved with the repeated administration of vedolizumab with no apparent increase in adverse events or infusion-related reactions (see section 4.8).

Pediatric population

The safety and effectiveness of vedolizumab in children aged 0 to 17 years have not been established. No data available.

Elderly patients

No dose adjustment is required in elderly patients. Population pharmacokinetic analyzes showed no effect of age (see section Pharmacokinetic properties).

Patients with renal or hepatic impairment

Entyvio has not been studied in these patients. No recommendation on dosage can be given.

Administration mode

Entyvio is administered intravenously only. It must be reconstituted and then diluted before intravenous administration; for instructions see section Instructions for use, handling and disposal.

Entyvio is administered as an intravenous infusion for 30 minutes. Patient monitoring is required during and after the infusion (see Warnings and Precautions).

Against indications

Hypersensitivity to the active substance or to any of the excipients listed under List of excipients.

Severe active infections such as tuberculosis, septicemia, cytomegalovirus infection and listiosis, and opportunistic infections such as progressive multifocal leukoencephalopathy (PML) (see section 4.4). of employment).

Adverse effects Entyvio

Summary of the Tolerance Profile

Vedolizumab has been studied in three placebo-controlled clinical trials in patients with ulcerative colitis (GEMINI I) or Crohn's disease (GEMINI II and III). In two controlled studies (GEMINI I and II) in which 1, 434 patients received 300 mg vedolizumab at Week 0, Week 2, then every eight weeks or every four weeks for 52 weeks In 297 patients receiving placebo for 52 weeks, adverse events were reported in 84% of vedolizumab-treated patients and in 78% of placebo-treated patients. In 52 weeks, 19% of vedolizumab-treated patients experienced serious adverse events compared with 13% of placebo-treated patients. Similar percentages of adverse events were observed in the groups treated every eight weeks or every four weeks in phase 3 clinical trials. The proportion of patients who stopped treatment was similar. Treatment due to adverse events was 9% for vedolizumab-treated patients and 10% for placebo-treated patients. In the combined studies of GEMINI I and II, adverse events in ≥ 5% of patients were nausea, rhino-pharyngitis, upper airway infection., arthralgia, pyrexia, fatigue, cephalgia, coughing. Infusion-related reactions were reported in 4% of patients receiving vedolizumab.

In the shorter placebo - controlled induction trial (10 weeks), GEMINI III, the types of adverse effects reported were similar but occurred at a frequency lower than that of 52 weeks longer trials.

Two hundred and seventy-nine (279) other patients were treated with vedolizumab at Week 0 and Week 2, followed by placebo for 52 weeks. Of these patients, 84% had adverse events and 15% had serious adverse events.

Patients (n = 1822) previously enrolled in either vedolizumab phase 2 or 3 studies could be enrolled in an ongoing open label study and received 300 mg vedolizumab every four weeks. weeks.

Table re fl ecting the undesirable effects

The following list of adverse effects is based on experience in clinical trials; the actions are presented by classes of organ systems. In the organ system classes, adverse effects are grouped according to the following frequency categories: very common (≥ 1/10), common (≥ 1/100 to <1/10) and not very frequent (≥ 1/1000 to <1/100). Within each frequency group, the undesirable effects are presented in a decreasing order of gravity.

Table 1. Adverse effects

Class of organ systems

Frequency

Side effects)

Infections and infestations

Very common

nasopharyngitis

Frequently

Bronchitis, gastro-enteritis, upper airways infection, influenza, sinusitis, pharyngitis

Rare

Airway infection, vulvovaginal candidiasis, oral candidiasis

Nervous system disorders

Very common

Cephal

Frequently

Paresthetic

Vascular disorders

Frequently

Hypertension

Respiratory, thoracic and metabolic disorders

Frequently

Oropharyngeal pain, nasal congestion, coughing

Gastrointestinal disorders

Frequently

Anal abscess, anal fissure, nausea, dyspepsia, constipation, abdominal distension, flatulence, haemorrhoids

Skin and subcutaneous tissue disorders

Frequently

Skin rash, pruritus, eczema, rhythm, night sweats, acne

Rare

folliculitis

Musculoskeletal and systemic disorders

Very common

arthralgia

Frequently

Muscle spasms, backache, muscle weakness, fatigue

General disorders and abnormalities

Frequently

pyrexia

administration site

Rare

Reaction at the point of infusion (including pain and irritation at the point of infusion), perfusion-related reaction, chills, cold sensation

Description of certain undesirable effects

Reactions related to infusion

In the GEMINI I and II controlled studies, 4% of vedolizumab-treated patients and 3% of placebo-treated patients presented an undesirable event defined by the investigator as an action related to infusion (see section 4.4). None of the effects reported as an infusion related reaction occurred at a rate greater than 1%. The majority of infusion - related reactions were mild to moderate and less than 1% led to discontinuation of treatment; they have usually resolved with minimal or spontaneous intervention after the infusion. Most of the reactions related to the infusion occurred during the first 2 hours. Among patients with infusion-related reactions, infusion-related responses during the first two hours were more frequent in treated patients. by vedolizumab than among those who received the placebo. Most of the infusion-related reactions were non-severe and occurred during the infusion or within the first hour after the end of the infusion.

A serious adverse event related to perfusion was reported in one patient with Crohn's disease during the second infusion (the reported symptoms were dyspnea e, bronchospasm, urticaria, flushing, skin rash and increased arterial pressure and heart rate) and was treated by interruption of infusion and treatment. with an antihistamine and intravenous hydrocortisone. In patients who received vedolizumab at Weeks 0 and 2 before receiving placebo, no increase in the rate of infusion-related reactions was observed during the re-administration of the drug. vedolizumab after a loss of response.

infections

In the GEMINI I and II controlled studies, the rate of infection was 0.85 per patient-year in vedolizumab-treated patients and 0.70 per patient-year. in patients who received placebo. The most common infections were nasopharyngitis, upper airway infection, sinusitis, and urinary tract infections. Most patients continued to take vedolizumab once the infection was stopped.

In the GEMINI I and II controlled studies, the rate of serious infections was 0.07 per patient-year in patients treated with vedolizumab and 0.06 per patient-year. e in patients who received placebo. No significant increase in the rate of serious infections has been observed over time.

In controlled and open-label studies in adults treated with vedolizumab, serious infections have been reported including, tuberculosis, septicemia (some fatal), septicemia to salmonella, listeria meningitis and cytomegalovirus colitis.

Immunogenicity

The controlled studies GEMINI I and II showed an immunogenicity rate of 4% for vedolizumab (56 of the 1434 patients who received continuous treatment with vedolizumab presented anti-vedolizumab antibodies at one time or another of the treatment). The presence of antibodies was persistent in 9 out of 56 patients (presence of anti-vedolizumab antibodies in two or more study visits) and neutralizing anti-vedolizumab antibodies occurred in 33 patients. .

The frequency of detection of anti-vedolizumab antibodies in patients 16 weeks after the last dose of vedolizumab (approximately five half-lives after the last dose) was approximately 10% in GEMINI studies I and II.

In the GEMINI I and II controlled studies, the presence of anti-vedolizumab antibodies was persistent in 5% (3 of 61) of patients who had presented a ven- undesirable considered by the investigator to be a perfusion related reaction.

Overall, there was no apparent correlation between the appearance of anti - vedolizumab antibodies and the clinical response or adverse events. However, the number of patients in whom anti-vedolizumab antibodies were present was too limited to allow a definitive assessment.

Malignant tumor

Overall, the results of clinical trials do not suggest, to date, increased risk of malignancy during vedolizumab therapy; however, the number of malignancies has been low and the long-term exposure limited. Long-term tolerance assessments are underway.

Reporting of suspected adverse reactions
The reporting of suspected side effects after approval of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system - see Annex V.

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