Medicinal Products

EDURANT 25 mg

Generic drug of the therapeutic class: Infectiology - Parasitology
Active ingredients: Rilpivirine
laboratory: Janssen Cilag

Coated tablet
box of 1 bottle of 30
All forms

Indication

EDURANT, in combination with other antiretroviral medicinal products, is indicated for the treatment of Human Immunodeficiency Virus (HIV-1) infection in patients aged 12 years or older who are receiving antiretroviral therapy. viral load ≤ 100, 000 copies / ml of HIV-1 RNA.

As with other antiretroviral drugs, a genotypic resistance test should guide the use of EDURANT (see sections Warnings and Precautions and Pharmacodynamic Properties ).

Dosage EDURANT 25 mg film-coated tablet box of 1 vial of 30

EDURANT, in combination with other antiretroviral medicinal products, is indicated for the treatment of Human Immunodeficiency Virus (HIV-1) infection in patients aged 12 years or older who are receiving antiretroviral therapy. viral load ≤ 100, 000 copies / ml of HIV-1 RNA.

As with other antiretroviral drugs, a genotypic resistance test should guide the use of EDURANT (see sections Warnings and Precautions and Pharmacodynamic Properties ).

Against indications

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

EDURANT should not be co-administered with the following drugs, as a significant decrease in plasma concentrations of rilpivirine may occur (by induction of CYP3A enzymes or increased gastric pH), which may result in loss of the therapeutic effect of EDURANT (see section Interactions with other medicinal products and other forms of interaction):

- anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin

- antimycobacterial rifampicin, rifapentine

proton pump inhibitors such as: omeprazole, esomeprazole, lansoprazole pantoprazole, rabeprazole

- the systemic glucocorticoid dexamethasone, except in the case of a single-dose treatment

- St. John's wort ( Hypericum perforatum ).

Edurant side effects

Summary of the job security profile

The safety-of-use assessment is based on 96 weeks of 1, 368 patients in the TMC278-C209 (ECHO) and TMC278-C215 (THRIVE) Phase III controlled studies in adult patients infected with HIV-1 naive antiretroviral therapy, of which 686 received EDURANT (25 mg once daily) (see section Pharmacodynamic properties ). The median duration of exposure was 104.3 weeks for the EDURANT patient group and 104.1 weeks for the efavirenz patient group, respectively. The majority of adverse events occurred during the first 48 weeks of treatment.

Summary table of adverse effects

Adverse reactions reported in adult patients treated with EDURANT are summarized in Table 2. The specific laboratory abnormalities (grade 3 or grade 4) that occurred after initiation of treatment and are considered adverse events are included in the footnote below. Table 2. Adverse reactions are presented by system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to <1/10), and uncommon (≥ 1/1000 to <1/100). In each frequency group, adverse effects are presented in order of decreasing frequency.

Table 2: Adverse Reactions Reported in Adult Patients Infected with HIV-1 Naive

antiretroviral therapy treated with EDURANT

(Compiled data from 96-week analysis of Phase III ECHO and THRIVE studies) N =

686

Class of organ systems

Frequency

Side effects

(EDURANT + TO)

affections

hematologic and lymphatic system

Frequent

decrease in white blood cell count #

decreased hemoglobin #
decrease in platelet count

Immune system disorders

rare

immune restoration syndrome

Disorders of

metabolism and nutrition

very common

increase in total cholesterol (fasting) # increase in LDL cholesterol (fasting) #

Frequent

decreased appetite increased triglycerides (fasting) #

affections

psychiatric

very common

insomnia*

Frequent

abnormal dreams depression *
sleep disorders depressed mood

Nervous system disorders

very common

headache *

dizzying sensations

Frequent

drowsiness

affections

gastrointestinal

very common

nausea

increased pancreatic amylase #

Frequent

abdominal pain*

vomiting

increased lipase #

abdominal discomfort

oral dryness

affections

Hepatobiliary

very common

increased transaminsases #

Frequent

increased bilirubin #

Skin disorders and

subcutaneous tissue

Frequent

skin rash*

General disorders and administration site conditions

Frequent

tired

TO = optimized treatment

N = number of subjects

* In the 96-week Phase III ECHO and THRIVE Controlled Trials, the most commonly reported adverse reactions (AEs) (≥ 2%) of moderate intensity or greater were depression (4.1%), headache (3.5%), insomnia (3.5%), rash (2.3%) and abdominal pain (2.0%).

# Based on 96-week data from ECHO and THRIVE studies, laboratory abnormalities (grade 3 or grade 4) after treatment initiation, considered as AEs, and reported in patients treated with EDURANT were as follows : increase in pancreatic amylase (3.8%), increase in ASAT (2.3%), increase in ALT (1.6%), increase in LDL-cholesterol (fasting, 1.5%), decrease white blood cell counts (1.2%), increased lipase (0.9%), increased bilirubin (0.7%), increased triglycerides (fasting, 0.6%), decreased hemoglobin (0.1%), decreased platelet count (0.1%), and increased total cholesterol (fasting, 0.1%).

No new adverse events were identified in adult patients who participated in the Phase III ECHO and THRIVE studies between weeks 48 and 96, nor in those who participated in the TMC278-C204 phase IIb study for 240 weeks.

Biological abnormalities

The 96-week analysis of the ECHO and THRIVE phase III studies showed that in the EDURANT treatment arm, the mean change from baseline in total (fasting) cholesterol was 5 mg / dL, HDL-cholesterol (fasting) of 4 mg / dL, LDL-cholesterol (fasting) of 1 mg / dL and triglycerides (fasting) of -7 mg / dL.

In the ECHO and THRIVE Phase III compilations, serum creatinine levels increased only minimally during 96 weeks of treatment with EDURANT. This increase occurred mainly during the first four weeks of treatment, with a total average change of 0.1 mg / dl (extreme values: -0.3 mg / dl to 0.6 mg / dl). In subjects who started the studies with mild to moderate renal impairment, the observed serum creatinine increase was similar to that observed in subjects with normal renal function. These variations are not considered clinically significant because they do not reflect a change in glomerular filtration rate and because no subject interrupted treatment because of increases in serum creatinine. Increases in creatinine were comparable regardless of the IN (t) TI of the optimized treatment.

In the compiled Phase III ECHO and THRIVE studies, a baseline change in basal cortisol was observed at Week 96, compared with an initial value of -19.11 (-30.85; 37) nmol / l in the EDURANT arm and -0.6 (-13, 29; 12, 17) nmol / l in the efavirenz arm. At week 96, the mean change in ACTH-stimulated cortisol levels from baseline was lower in the EDURANT group (+18.4 ± 8.36 nmol / l) than in the efavirenz group (+ 54.1 ± 7.24 nmol / l). Mean values ​​of basal cortisol and ACTH-stimulated cortisol at week 96 were within normal range. These variations in adrenal tolerance parameters were not clinically significant. There were no signs or clinical symptoms suggestive of adrenal or gonadal dysfunction in adults.

Description of particular adverse effects

lipodystrophy

Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV-infected patients, including loss of subcutaneous facial and peripheral adipose tissue, increased intra-fat mass abdominal and visceral, breast hypertrophy and accumulation of fat at the cervical level (buffalo hump) (see Warnings and Precautions ).

Immune restoration syndrome

In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy, an inflammatory response to asymptomatic or residual opportunistic infections may occur. Autoimmune diseases (such as Graves' disease) have also been reported; however, the time of onset described is more variable and these events may occur several months after the initiation of treatment (see section Warnings and precautions for use ).

Pediatric population (aged 12 to under 18 years)

The safety assessment is based on a 48-week analysis of the Phase_2 TMC278-C213 study, open and single-arm, in which 36 HIV-1 infected and treatment-naive adolescents were treated. anti-retroviral drugs weighing at least 32 kg received EDURANT (25 mg once daily) in combination with other antiretroviral agents (see section 5.1 ). The median duration of exposure in patients was 63.5 weeks. No patients stopped treatment because of adverse effects. No new adverse effects were identified compared to those seen in adults.

The majority of adverse events were grade 1 or 2. The most common adverse events (all grades, greater than or equal to 10%) were: headache (19.4%), depression (19.4%), drowsiness ( 13.9%), and nausea (11.1%). No biological abnormalities of Grade 3-4 ASAT / ALAT or Grade 3-4 elevation transaminase-like adverse events have been reported.

The safety and effectiveness of EDURANT in children under 12 years of age have not been established. No data available.

Other special populations

Patients co-infected with hepatitis B and / or hepatitis C viruses

In patients co-infected with hepatitis B or C virus who received EDURANT, the incidence of hepatic enzyme elevation was greater than in unco-infected patients receiving EDURANT. The same observation was also made in the patients of the efavirenz group. The pharmacokinetic exposure to rilpivirine in co-infected patients was comparable to that observed in unco-infected patients.

Reporting of suspected adverse reactions

The reporting of suspected adverse reactions after authorization 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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