EDURANT

Therapy should be initiated by a physician experienced in the management of HIV infection. Posology The recommended dosage of EDURANT in paediatric patients aged 2 to less than 18 years is based on body weight (see Table 1). 5 mg dispersible tablets should only be given to paediatric patients weighing at least 14 kg and less than 25 kg.

2). 5 mg dispersible tablets) Film-Coated tablets EDURANT is also available as EDURANT 25 mg tablets. EDURANT 25 mg film-coated tablets should be given to paediatric and adult patients weighing at least 25 kg. 5 mg dispersible tablets was observed, therefore they are not interchangeable.

Missed dose If the patient misses a dose of EDURANT within 12 hours of the time it is usually taken, the patient must take the medicine with a meal as soon as possible and resume the normal dosing schedule. If a patient misses a dose of EDURANT by more than 12 hours, the patient should not take the missed dose, but resume the usual dosing schedule.

If a patient vomits within 4 hours of taking the medicine, another EDURANT dose should be taken with a meal. If a patient vomits more than 4 hours after taking the medicine, the patient does not need to take another dose of EDURANT until the next regularly scheduled dose.

Special populations Renal impairment EDURANT has mainly been studied in patients with normal renal function. No dose adjustment of rilpivirine is required in patients with mild or moderate renal impairment. In patients with severe renal impairment or end-stage renal disease, rilpivirine should be used with caution.

2). 8). Hepatic impairment There is limited information regarding the use of EDURANT in patients with mild or moderate hepatic impairment (Child-Pugh score A or B). No dose adjustment of EDURANT is required in patients with mild or moderate hepatic impairment.

EDURANT should be used with caution in patients with moderate hepatic impairment. EDURANT has not been studied in patients with severe hepatic impairment (Child-Pugh score C). 2). Paediatric population The safety and efficacy of EDURANT in children less than 2 years or weighing less than 14 kg have not been established.

No data are available. Pregnancy Lower exposures of rilpivirine were observed during pregnancy, therefore viral load should be monitored closely. 2). 2). The patient should not chew or swallow EDURANT dispersible tablets whole. To aid with administration, the dispersed mixture can be further diluted with the following beverages or soft food: water, milk, orange juice or applesauce.

The following instructions should be followed: - Place the tablets in a cup, add 5 ml (1 teaspoon) of water at room temperature. Do not crush the tablets. - Swirl the cup carefully to disperse the tablets. The mixture will start to look cloudy.

- Take all the prepared medicine immediately or add another 5 ml (1 teaspoon) of either water or any of the following to aid in administration: milk, orange juice or applesauce which has acclimated to room temperature before use. Swirl and take all the medicine immediately.

A spoon can be used if needed. - Make sure the entire dose is taken and no medicine is left in the cup, if required add another 5 ml (1 teaspoon) of water or same beverage (milk, orange juice) or applesauce, swirl and drink immediately.

The patient must take the dose of medicine immediately. If not taken immediately, then the mixture should be discarded, and a new dose of medicine should be prepared.

1). 0%). 0%) patients receiving rilpivirine. 1 weeks, respectively. Most ADRs occurred in the first 48 weeks of treatment. 1%). Tabulated summary of adverse reactions ADRs reported in adult patients treated with rilpivirine are summarised in Table 3.

The ADRs are listed by system organ class (SOC) and frequency. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100). Within each frequency grouping, ADRs are presented in order of decreasing frequency.

Table 3:

ADRs reported in antiretroviral treatment-naïve HIV-1 infected adult patients treated with rilpivirine (pooled data from the week 96 analysis of the phase 3 ECHO and THRIVE trials) N=686 System Organ Class (SOC) Frequency Category ADRs (Rilpivirine + BR) Blood and lymphatic system disorders common decreased white blood cell count decreased haemoglobin decreased platelet count Immune system disorders uncommon immune reactivation syndrome very common increased total cholesterol (fasted) increased LDL cholesterol (fasted) Metabolism and nutrition disorders common decreased appetite increased triglycerides (fasted) Psychiatric disorders very common insomnia common abnormal dreams depression sleep disorders depressed mood very common headache dizziness Nervous system disorders common somnolence very common nausea increased pancreatic amylase Gastrointestinal disorders common abdominal pain vomiting increased lipase abdominal discomfort dry mouth very common increased transaminasesHepatobiliary disorders common increased bilirubin Skin and subcutaneous tissue disorders common rash General disorders and administration site conditions common fatigue BR=background regimen N=number of subjects Laboratory abnormalities In the rilpivirine arm in the week 96 analysis of the phase 3 ECHO and THRIVE trials, mean change from baseline in total cholesterol (fasted) was 5 mg/dl, in HDL cholesterol (fasted) 4 mg/dl, in LDL cholesterol (fasted) 1 mg/dl, and in triglycerides (fasted) -7 mg/dl.

Description of selected adverse reactions Immune reactivation syndrome In HIV infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise.

4). 1). 5 weeks. There were no patients who discontinued treatment due to ADRs. No new ADRs were identified compared to those seen in adults. Most ADRs were grade 1 or 2. 1%). No grade 3-4 laboratory abnormalities for AST/ALT or grade 3-4 ADRs of transaminase increased were reported.

There were no new safety concerns identified in the week 240 analysis of the TMC278-C213 Cohort 1 trial in adolescents. 1). 5 (range 35 to 218) weeks. All ADRs were mild or moderate. 1%). There were no patients who discontinued treatment due to ADRs.

No new ADRs were identified compared to those seen in adults. 1). 4 (range […]

Virologic failure and development of resistance EDURANT has not been evaluated in patients with previous virologic failure to any other antiretroviral therapy. 1 should only guide the use of EDURANT in the treatment-naïve population.

6% with efavirenz). 1). Patients with a baseline viral load > 100,000 HIV-1 RNA copies/ml who experienced virologic failure exhibited a higher rate of treatment-emergent resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class.

1). Findings in adolescents and paediatric patients in trial TMC278-C213 were generally in line with these data. 1). Only patients deemed likely to have good adherence to antiretroviral therapy should be treated with rilpivirine, as suboptimal adherence can lead to development of resistance and the loss of future treatment options.

1). 2). EDURANT at the recommended dose of 25 mg once daily is not associated with a clinically relevant effect on QTc. EDURANT should be used with caution when co-administered with medicinal products with a known risk of Torsade de Pointes.

Immune reactivation syndrome In HIV infected patients with severe immune deficiency at the time of initiation of CART, an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions or aggravation of symptoms.

Typically, such reactions have been observed within the first weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections and Pneumocystis jiroveci pneumonia.

Any inflammatory symptoms should be evaluated, and treatment instituted when necessary. 8). Pregnancy EDURANT should be used during pregnancy only if the potential benefit justifies the risk. Lower exposures of rilpivirine were observed when rilpivirine 25 mg once daily was taken during pregnancy.

2). Alternatively, switching to another ART regimen could be considered. Important information about some of the ingredients of EDURANT EDURANT contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

1. 5): - the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin - the antimycobacterials rifampicin, rifapentine - proton pump inhibitors, such as omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole - the systemic glucocorticoid dexamethasone, except as a single dose treatment - St John’s wort (Hypericum perforatum).