INTELENCE

Therapy should be initiated by a physician experienced in the management of HIV infection. Posology INTELENCE must always be given in combination with other antiretroviral medicinal products. 2). Paediatric population (2 years to less than 18 years of age) The recommended dose of etravirine for paediatric patients (2 years to less than 18 years of age and weighing at least 10 kg) is based on body weight (see table below).

2).

Table 1:

Recommended dose of etravirine for paediatric patients 2 years to less than 18 years of age Body weight Dose Tablets ≥ 10 to < 20 kg 100 mg twice daily four 25 mg tablets twice daily or one 100 mg tablet twice daily ≥ 20 to < 25 kg 125 mg twice daily five 25 mg tablets twice daily or one 100 mg tablet and one 25 mg tablet twice daily ≥ 25 to < 30 kg 150 mg twice daily six 25 mg tablets twice daily or one 100 mg tablet and two 25 mg tablets twice daily ≥ 30 kg 200 mg twice daily eight 25 mg tablets twice daily or two 100 mg tablets twice daily or one 200 mg tablet twice daily Missed dose If the patient misses a dose of INTELENCE within 6 hours of the time it is usually taken, the patient should take it following a meal as soon as possible and then take the next dose at the regularly scheduled time.

If a patient misses a dose by more than 6 hours of the time it is usually taken, the patient should not take the missed dose and simply resume the usual dosing schedule. If a patient vomits within 4 hours of taking the medicine, another dose of INTELENCE should be taken following a meal as soon as possible.

If a patient vomits more than 4 hours after taking the medicine, the patient does not need to take another dose until the next regularly scheduled time. 2), therefore caution should be used in this population. Hepatic impairment No dose adjustment is suggested in patients with mild or moderate hepatic impairment (Child-Pugh Class A or B); INTELENCE should be used with caution in patients with moderate hepatic impairment.

The pharmacokinetics of etravirine have not been studied in patients with severe hepatic impairment (Child-Pugh Class C). 2). 2). Paediatric population (less than 2 years of age) INTELENCE should not be used in children less than 2 years of age.

2 and suggest that the benefits do not outweigh the risks in this age group. No data are available for children less than 1 year of age. Method of administration Oral use. Patients should be instructed to swallow the tablet(s) whole with a liquid such as water.

Summary of the safety profile The most frequent (incidence ≥ 10%) adverse reactions of all intensities reported for etravirine were rash, diarrhoea, nausea and headache. 2% in patients receiving etravirine. The most common adverse reaction leading to discontinuation was rash.

Tabulated list of adverse reactions Adverse reactions reported in patients treated with etravirine are summarised in Table 3. The adverse reactions are listed by system organ class (SOC) and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000).

Table 3:

Adverse reactions observed with etravirine in clinical trials and post-marketing experience System Organ Class (SOC) Frequency category Adverse Reaction common thrombocytopaenia, anaemia, decreased neutrophilsBlood and lymphatic system disorders uncommon decreased white blood cell count common drug hypersensitivityImmune system disorders uncommon immune reconstitution syndrome Metabolism and nutrition disorders common diabetes mellitus, hyperglycaemia, hypercholesterolaemia, increased low density lipoprotein (LDL), hypertriglyceridaemia, hyperlipidaemia, dyslipidaemia, anorexia common anxiety, insomnia, sleep disordersPsychiatric disorders uncommon confusional state, disorientation, nightmares, nervousness, abnormal dreams very common headache common peripheral neuropathy, paraesthesia, hypoaesthesia, amnesia, somnolence Nervous system disorders uncommon convulsion, syncope, tremor, hypersomnia, disturbance in attention Eye disorders common blurred vision Ear and labyrinth disorders uncommon vertigo common myocardial infarctionCardiac disorders uncommon atrial fibrillation, angina pectoris common hypertensionVascular disorders rare haemorrhagic strokea common exertional dyspnoeaRespiratory, thoracic and mediastinal disorders uncommon bronchospasm very common diarrhoea, nausea common gastrooesophageal reflux disease, vomiting, abdominal pain, abdominal distension, flatulence, gastritis, constipation, dry mouth, stomatitis, lipase increased, blood amylase increased Gastrointestinal disorders uncommon pancreatitis, haematemesis, retching common increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST) Hepatobiliary disorders uncommon hepatitis, hepatic steatosis, cytolytic hepatitis, hepatomegaly very common rash common night sweats, dry skin, prurigo uncommon angioneurotic oedemaa, swelling face, hyperhidrosis rare Stevens-Johnson Syndromea, erythema multiformea Skin and subcutaneous tissue disorders very rare toxic epidermal necrolysisa, DRESSb Renal and urinary disorders common renal failure, blood creatinine increased Reproductive system and breast disorders uncommon gynaecomastia common fatigueGeneral disorders and administration site conditions uncommon sluggishness a These adverse reactions were observed in other clinical trials than DUET-1 and DUET-2.

1). 1). Conclusions regarding the relevance of particular mutations or mutational patterns are subject to change with additional data, and it is recommended to always consult current interpretation systems for analysing resistance test results.

5) are available when etravirine is combined with raltegravir or maraviroc. Severe cutaneous and hypersensitivity reactions Severe cutaneous adverse reactions have been reported with etravirine. 1%) reported. Treatment with INTELENCE should be discontinued if a severe cutaneous reaction develops.

The clinical data are limited and an increased risk of cutaneous reactions in patients with a history of NNRTI-associated cutaneous reactions cannot be excluded. Caution should be observed in such patients, especially in case of history of a severe cutaneous drug reaction.

8). The DRESS syndrome is characterised by rash, fever, eosinophilia and systemic involvement (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and eosinophilia).

Time to onset is usually around 3-6 weeks and the outcome in most cases is favourable upon discontinuation and after initiation of corticosteroid therapy. Patients should be informed to seek medical advice if severe rash or hypersensitivity reactions occur.

Patients who are diagnosed with a hypersensitivity reaction whilst on therapy must discontinue INTELENCE immediately. Delay in stopping INTELENCE treatment after the onset of severe rash may result in a life-threatening reaction. Patients who have stopped treatment due to hypersensitivity reactions should not restart therapy with INTELENCE.

Rash Rash has been reported with etravirine. Most frequently, rash was mild to moderate, occurred in the second week of therapy, and was infrequent after week 4. Rash was mostly self-limiting and generally resolved within 1 to 2 weeks on continued therapy.

1. 5).