Intelence

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

INTELENCE 25 mg tablets
INTELENCE 100 mg tablets
INTELENCE 200 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

INTELENCE 25 mg tablets

Each tablet contains 25 mg of etravirine.

Excipient with known effect
Each tablet contains 40 mg lactose (as monohydrate).
Each tablet contains less than 1 mmol sodium (23 mg), and is essentially sodium-free.

INTELENCE 100 mg tablets

Each tablet contains 100 mg of etravirine.

Excipient with known effect
Each tablet contains 160 mg lactose (as monohydrate).
Each tablet contains less than 1 mmol sodium (23 mg), and is essentially sodium-free.

INTELENCE 200 mg tablets

Each tablet contains 200 mg of etravirine.

Excipient with known effect
Each tablet contains less than 1 mmol sodium (23 mg), and is essentially sodium-free.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

INTELENCE 25 mg tablets

Tablet
White to off-white, oval, scored tablet, debossed with “TMC” on one side.
The tablet can be divided into two equal doses.

INTELENCE 100 mg tablets

Tablet
White to off-white, oval tablet debossed with “T125” on one side and “100” on the other side.

INTELENCE 200 mg tablets

Tablet
White to off-white, biconvex, oblong tablet debossed with “T200” on one side.



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4. CLINICAL PARTICULARS

4.1 Therapeutic indications

INTELENCE, in combination with a boosted protease inhibitor and other antiretroviral medicinal 
products, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in 
antiretroviral treatment-experienced adult patients and in antiretroviral treatment-experienced 
paediatric patients from 2 years of age (see sections 4.4, 4.5 and 5.1).

4.2 Posology and method of administration

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.

Adults
The recommended dose of etravirine for adults is 200 mg (one 200 mg tablet or two 100 mg tablets) 
taken orally twice daily following a meal (see section 5.2).

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). INTELENCE tablet(s) should be 
taken orally, following a meal (see section 5.2).

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.

Elderly
There is limited information regarding the use of INTELENCE in patients > 65 years of age (see 
section 5.2), 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 



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impairment. The pharmacokinetics of etravirine have not been studied in patients with severe hepatic 
impairment (Child-Pugh Class C). Therefore, INTELENCE is not recommended in patients with 
severe hepatic impairment (see sections 4.4 and 5.2).

Renal impairment
No dose adjustment is required in patients with renal impairment (see section 5.2).

Paediatric population (less than 2 years of age)
INTELENCE should not be used in children less than 2 years of age. Currently available data for 
children between 1 and 2 years old are described in sections 4.8, 5.1 and 5.2 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. Patients who 
are unable to swallow the tablet(s) whole may disperse the tablet(s) in a glass of water (see 
section 4.4).

For instructions on dispersion of the medicinal product before administration, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Co-administration with elbasvir/grazoprevir (see section 4.5).

4.4 Special warnings and precautions for use

While effective viral suppression with antiretroviral therapy has been proven to substantially reduce 
the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission 
should be taken in accordance with national guidelines.

INTELENCE should optimally be combined with other antiretrovirals that exhibit activity against the 
patient’s virus (see section 5.1).

A decreased virologic response to etravirine was observed in patients with viral strains harbouring 3 or 
more among the following mutations V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V, 
and G190A/S (see section 5.1).

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.

No data other than drug-drug interaction data (see section 4.5) are available when etravirine is 
combined with raltegravir or maraviroc.

Severe cutaneous and hypersensitivity reactions

Severe cutaneous adverse reactions have been reported with etravirine. In clinical trials, 
Stevens-Johnson Syndrome and erythema multiforme have been rarely (< 0.1%) 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.



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Cases of severe hypersensitivity syndromes, including DRESS (Drug Rash with Eosinophilia and
Systemic Symptoms) and TEN (toxic epidermal necrolysis), sometimes fatal, have been reported with 
the use of etravirine (see section 4.8). 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. When prescribing INTELENCE to females, 
prescribers should be aware that the incidence of rash was higher in females (see section 4.8).

Paediatric population

For children who cannot swallow the tablet(s) whole, the tablet(s) may be dispersed in liquid. This 
should only be considered if the child is likely to take the entire dose of the tablet(s) in liquid (see 
sections 4.2 and 6.6). The importance of consuming the entire dose needs to be highlighted to the child 
and his/her caregiver to avoid too low exposure and lack of virologic response. In case of any doubt 
that a child will take the entire dose of the tablet(s) dispersed in liquid, treatment with another 
antiretroviral product needs to be considered.

Elderly

Experience in geriatric patients is limited: in the Phase III trials, 6 patients aged 65 years or older and 
53 patients aged 56-64 years received etravirine. The type and incidence of adverse reactions in 
patients > 55 years of age were similar to the ones in younger patients (see sections 4.2 and 5.2).

Pregnancy

Given the increased etravirine exposure during pregnancy, caution should be applied for those 
pregnant patients that require concomitant medicinal products or have comorbidities that may further 
increase etravirine exposure.

Patients with coexisting conditions

Hepatic impairment
Etravirine is primarily metabolised and eliminated by the liver and highly bound to plasma proteins. 
Effects on unbound exposure could be expected (has not been studied) and therefore caution is advised 
in patients with moderate hepatic impairment. Etravirine has not been studied in patients with severe 
hepatic impairment (Child-Pugh Class C) and its use is therefore not recommended in this group of 
patients (see sections 4.2 and 5.2).



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Co-infection with HBV (hepatitis B virus) or HCV (hepatitis C virus)
Caution should be exercised in patients co-infected with hepatitis B or C virus due to the current 
limited data available. A potential increased risk of liver enzymes increase cannot be excluded.

Weight and metabolic parameters
An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral 
therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in 
some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating 
this to any particular treatment. For monitoring of blood lipids and glucose reference is made to 
established HIV treatment guidelines. Lipid disorders should be managed as clinically appropriate.

Immune reconstitution 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.

Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to 
occur in the setting of immune reactivation; however, the reported time to onset is more variable and 
these events can occur many months after initiation of treatment (see section 4.8).

Osteonecrosis

Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported particularly in patients with advanced HIV disease and/or long-term exposure to CART. 
Patients should be advised to seek medical advice if they experience joint aches and pain, joint 
stiffness or difficulty in movement.

Interactions with medicinal products

It is not recommended to combine etravirine with tipranavir/ritonavir, due to a marked 
pharmacokinetic interaction (76% decrease of etravirine AUC) that could significantly impair the 
virologic response to etravirine.

The combination of etravirine with daclatasvir, atazanavir/cobicistat or darunavir/cobicistat is not 
recommended (see section 4.5).

For further information on interactions with medicinal products see section 4.5.

Lactose intolerance and lactase deficiency

INTELENCE 25 mg tablets
Each tablet contains 40 mg of lactose monohydrate. Patients with rare hereditary problems of 
galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take 
this medicine.

INTELENCE 100 mg tablets
Each tablet contains 160 mg of lactose monohydrate. Patients with rare hereditary problems of 
galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take 
this medicine.



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4.5 Interaction with other medicinal products and other forms of interaction

Medicinal products that affect etravirine exposure

Etravirine is metabolised by CYP3A4, CYP2C9 and CYP2C19 followed by glucuronidation of the 
metabolites by uridine diphosphate glucuronosyl transferase (UDPGT). Medicinal products that 
induce CYP3A4, CYP2C9 or CYP2C19 may increase the clearance of etravirine, resulting in lowered 
plasma concentrations of etravirine.
Co-administration of etravirine and medicinal products that inhibit CYP3A4, CYP2C9 or CYP2C19 
may decrease the clearance of etravirine and may result in increased plasma concentrations of 
etravirine.

Medicinal products that are affected by the use of etravirine

Etravirine is a weak inducer of CYP3A4. Co-administration of etravirine with medicinal products 
primarily metabolised by CYP3A4 may result in decreased plasma concentrations of such medicinal 
products, which could decrease or shorten their therapeutic effects.
Etravirine is a weak inhibitor of CYP2C9 and CYP2C19. Etravirine is also a weak inhibitor of 
P-glycoprotein. Co-administration with medicinal products primarily metabolised by CYP2C9 or 
CYP2C19, or transported by P-glycoprotein, may result in increased plasma concentrations of such 
medicinal products, which could increase or prolong their therapeutic effect or alter their adverse 
events profile.

Known and theoretical interactions with selected antiretrovirals and non-antiretroviral medicinal 
products are listed in table 2. The table is not all-inclusive.

Interaction table

Interactions between etravirine and co-administered medicinal products are listed in table 2 (increase 
is indicated as “↑”, decrease as “↓”, no change as “↔”, not done as “ND”, confidence interval as 
“CI”).

Table 2: Interactions and dose recommendations with other medicinal products
Medicinal products by 
therapeutic areas

Effects on drug levels
Least Squares Mean Ratio
(90% CI; 1.00 = No effect)

Recommendations 
concerning 
co-administration

ANTI-INFECTIVES
Antiretrovirals
NRTIs

Didanosine
400 mg once daily

didanosine
AUC ↔ 0.99 (0.79-1.25)
Cmin ND
Cmax ↔ 0.91 (0.58-1.42)
etravirine
AUC ↔ 1.11 (0.99-1.25)
Cmin ↔ 1.05 (0.93-1.18)
Cmax ↔ 1.16 (1.02-1.32)

No significant effect on 
didanosine and etravirine PK 
parameters is seen. 
INTELENCE and didanosine 
can be used without dose 
adjustments.

Tenofovir disoproxil
245 mg once dailyb

tenofovir
AUC ↔ 1.15 (1.09-1.21)
Cmin ↑ 1.19 (1.13-1.26)
Cmax ↑ 1.15 (1.04-1.27)
etravirine
AUC ↓ 0.81 (0.75-0.88)
Cmin ↓ 0.82 (0.73-0.91)
Cmax ↓ 0.81 (0.75-0.88)

No significant effect on 
tenofovir and etravirine PK 
parameters is seen. 
INTELENCE and tenofovir 
can be used without dose 
adjustments.

Other NRTIs Not studied, but no interaction expected based 
on the primary renal elimination route for other 
NRTIs (e.g., abacavir, emtricitabine, 
lamivudine, stavudine and zidovudine).

INTELENCE can be used 
with these NRTIs without 
dose adjustment.



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NNRTIs
Efavirenz
Nevirapine
Rilpivirine

Combining two NNRTIs has not been shown to 
be beneficial. Concomitant use of etravirine 
with efavirenz or nevirapine may cause a 
significant decrease in the plasma concentration 
of etravirine and loss of therapeutic effect of 
etravirine.
Concomitant use of etravirine with rilpivirine 
may cause a decrease in the plasma 
concentration of rilpivirine and loss of 
therapeutic effect of rilpivirine.

It is not recommended to 
co-administer INTELENCE 
with other NNRTIs.

HIV Protease Inhibitors (PIs) – Unboosted (i.e. without co-administration of low-dose ritonavir)
Indinavir Concomitant use of etravirine with indinavir 

may cause a significant decrease in the plasma 
concentration of indinavir and loss of 
therapeutic effect of indinavir.

It is not recommended to 
co-administer INTELENCE 
with indinavir.

HIV PIs – Boosted with low-dose ritonavir
Atazanavir/ritonavir
300/100 mg once daily

atazanavir
AUC ↓ 0.86 (0.79-0.93)
Cmin ↓ 0.62 (0.55-0.71)
Cmax ↔ 0.97 (0.89-1.05)
etravirine
AUC ↑ 1.30 (1.18-1.44)
Cmin ↑ 1.26 (1.12-1.42)
Cmax ↑ 1.30 (1.17-1.44)

INTELENCE and 
atazanavir/ritonavir can be 
used without dose 
adjustment.

Darunavir/ritonavir
600/100 mg twice daily

darunavir
AUC ↔ 1.15 (1.05-1.26)
Cmin ↔ 1.02 (0.90-1.17)
Cmax ↔ 1.11 (1.01-1.22)
etravirine
AUC ↓ 0.63 (0.54-0.73)
Cmin ↓ 0.51 (0.44-0.61)
Cmax ↓ 0.68 (0.57-0.82)

INTELENCE and 
darunavir/ritonavir can be 
used without dose 
adjustments (see also 
section 5.1).

Fosamprenavir/ritonavir
700/100 mg twice daily

amprenavir
AUC ↑ 1.69 (1.53-1.86)
Cmin ↑ 1.77 (1.39-2.25)
Cmax ↑ 1.62 (1.47-1.79)
etravirine
AUC ↔a

Cmin ↔
a

Cmax ↔
a

Amprenavir/ritonavir and 
fosamprenavir/ritonavir may 
require dose reduction when 
co-administered with 
INTELENCE. Using the oral 
solution may be considered 
for dose reduction.

Lopinavir/ritonavir
(tablet)
400/100 mg twice daily

lopinavir
AUC ↔ 0.87 (0.83-0.92)
Cmin ↓ 0.80 (0.73-0.88)
Cmax ↔ 0.89 (0.82-0.96)
etravirine
AUC ↓ 0.65 (0.59-0.71)
Cmin ↓ 0.55 (0.49-0.62)
Cmax ↓ 0.70 (0.64-0.78)

INTELENCE and 
lopinavir/ritonavir can be 
used without dose 
adjustments.

Saquinavir/ritonavir
1,000/100 mg twice daily

saquinavir
AUC ↔ 0.95 (0.64-1.42)
Cmin ↓ 0.80 (0.46-1.38)
Cmax ↔ 1.00 (0.70-1.42)
etravirine
AUC ↓ 0.67 (0.56-0.80)
Cmin ↓ 0.71 (0.58-0.87)
Cmax ↓ 0.63 (0.53-0.75)

INTELENCE and 
saquinavir/ritonavir can be 
used without dose 
adjustments.



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Tipranavir/ritonavir
500/200 mg twice daily

tipranavir
AUC ↑ 1.18 (1.03-1.36)
Cmin ↑ 1.24 (0.96-1.59)
Cmax ↑ 1.14 (1.02-1.27)
etravirine
AUC ↓ 0.24 (0.18-0.33)
Cmin ↓ 0.18 (0.13-0.25)
Cmax ↓ 0.29 (0.22-0.40)

It is not recommended to 
co-administer 
tipranavir/ritonavir and 
INTELENCE (see 
section 4.4).

HIV PIs – Boosted with cobicistat
Atazanavir/cobicistat
Darunavir/cobicistat

Not studied. Co-administration of etravirine
with atazanavir/cobicistat or 
darunavir/cobicistat may decrease plasma 
concentrations of the PI and/or cobicistat, 
which may result in loss of therapeutic effect 
and development of resistance.

Co-administration of 
INTELENCE with 
atazanavir/cobicistat or 
darunavir/cobicistat is not 
recommended.

CCR5 Antagonists
Maraviroc
300 mg twice daily

Maraviroc/darunavir/
ritonavir
150/600/100 mg twice 
daily

maraviroc
AUC ↓ 0.47 (0.38-0.58)
Cmin ↓ 0.61 (0.53-0.71)
Cmax ↓ 0.40 (0.28-0.57)
etravirine
AUC ↔ 1.06 (0.99-1.14)
Cmin ↔ 1.08 (0.98-1.19)
Cmax ↔ 1.05 (0.95-1.17)
maraviroc*
AUC ↑ 3.10 (2.57-3.74)
Cmin ↑ 5.27 (4.51-6.15)
Cmax ↑ 1.77 (1.20-2.60)
* compared to maraviroc 150 mg twice daily

The recommended dose for 
maraviroc when combined 
with INTELENCE and a PI 
is 150 mg twice daily, except 
for fosamprenavir/ritonavir 
which is not recommended 
with maraviroc. No dose 
adjustment for INTELENCE 
is necessary.
See also section 4.4.

Fusion Inhibitors
Enfuvirtide
90 mg twice daily

etravirine*
AUC ↔a

C0h ↔
a

Enfuvirtide concentrations not studied and no 
effect is expected.
* based on population pharmacokinetic analyses

No interaction is expected for 
either INTELENCE or 
enfuvirtide when 
co-administered.



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Integrase Strand Transfer Inhibitors
Dolutegravir
50 mg once daily

Dolutegravir + 
darunavir/ritonavir
50 mg once daily + 
600/100 mg twice daily

Dolutegravir + 
Lopinavir/ritonavir
50 mg once daily + 
400/100 mg twice daily

dolutegravir
AUC ↓ 0.29 (0.26-0.34)
Cmin ↓ 0.12 (0.09-0.16)
Cmax ↓ 0.48 (0.43-0.54)
etravirine
AUC ↔a

Cmin ↔
a

Cmax ↔
a

dolutegravir
AUC↓ 0.75 (0.69-0.81)
Cmin ↓ 0.63 (0.52-0.77)
Cmax ↓ 0.88 (0.78-1.00)
etravirine
AUC ↔a

Cmin ↔
a

Cmax ↔
a

dolutegravir
AUC↔ 1.11(1.02-1.20)
Cmin ↑ 1.28 (1.13-1.45)
Cmax ↔ 1.07 (1.02-1.13)
etravirine
AUC ↔a

Cmin ↔
a

Cmax ↔
a

Etravirine significantly 
reduced plasma 
concentrations of 
dolutegravir. The effect of 
etravirine on dolutegravir 
plasma concentrations was 
mitigated by 
co-administration of 
darunavir/ritonavir or 
lopinavir/ritonavir, and is
expected to be mitigated by 
atazanavir/ritonavir.

INTELENCE should only be 
used with dolutegravir when 
co-administered with 
atazanavir/ritonavir,
darunavir/ritonavir, or 
lopinavir/ritonavir. This 
combination can be used 
without dose adjustment.

Raltegravir
400 mg twice daily

raltegravir
AUC ↓ 0.90 (0.68-1.18)
Cmin ↓ 0.66 (0.34-1.26)
Cmax ↓ 0.89 (0.68-1.15)
etravirine
AUC ↔ 1.10 (1.03-1.16)
Cmin ↔ 1.17 (1.10-1.26)
Cmax ↔ 1.04 (0.97-1.12)

INTELENCE and raltegravir 
can be used without dose 
adjustments.

ANTIARRHYTHMICS
Digoxin
0.5 mg single dose

digoxin
AUC ↑ 1.18 (0.90-1.56)
Cmin ND
Cmax ↑ 1.19 (0.96-1.49)

INTELENCE and digoxin 
can be used without dose 
adjustments. It is 
recommended that digoxin 
levels be monitored when 
digoxin is combined with 
INTELENCE.

Amiodarone
Bepridil
Disopyramide
Flecainide
Lidocaine (systemic)
Mexiletine
Propafenone
Quinidine

Not studied. INTELENCE is expected to 
decrease plasma concentrations of these 
antiarrhythmics.

Caution is warranted and 
therapeutic concentration 
monitoring, if available, is 
recommended for 
antiarrhythmics when 
co-administered with 
INTELENCE.

ANTIBIOTICS
Azithromycin Not studied. Based on the biliary elimination 

pathway of azithromycin, no drug interactions 
are expected between azithromycin and 
INTELENCE.

INTELENCE and 
azithromycin can be used 
without dose adjustments.



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Clarithromycin
500 mg twice daily

clarithromycin
AUC ↓ 0.61 (0.53-0.69)
Cmin ↓ 0.47 (0.38-0.57)
Cmax ↓ 0.66 (0.57-0.77)
14-OH-clarithromycin
AUC ↑ 1.21 (1.05-1.39)
Cmin ↔ 1.05 (0.90-1.22)
Cmax ↑ 1.33 (1.13-1.56)
etravirine
AUC ↑ 1.42 (1.34-1.50)
Cmin ↑ 1.46 (1.36-1.58)
Cmax ↑ 1.46 (1.38-1.56)

Clarithromycin exposure was 
decreased by etravirine; 
however, concentrations of 
the active metabolite, 
14-OH-clarithromycin, were 
increased. Because 
14-OH-clarithromycin has 
reduced activity against 
Mycobacterium avium
complex (MAC), overall 
activity against this pathogen 
may be altered; therefore 
alternatives to clarithromycin 
should be considered for the 
treatment of MAC.

ANTICOAGULANTS
Warfarin Not studied. Etravirine is expected to increase 

plasma concentrations of warfarin.
It is recommended that the 
international normalised ratio 
(INR) be monitored when 
warfarin is combined with 
INTELENCE.

ANTICONVULSANTS
Carbamazepine
Phenobarbital
Phenytoin

Not studied. Carbazamepine, phenobarbital and 
phenytoin are expected to decrease plasma 
concentrations of etravirine.

Combination not 
recommended.

ANTIFUNGALS
Fluconazole
200 mg once in the 
morning

fluconazole
AUC ↔ 0.94 (0.88-1.01)
Cmin ↔ 0.91 (0.84-0.98)
Cmax ↔ 0.92 (0.85-1.00)
etravirine
AUC ↑ 1.86 (1.73-2.00)
Cmin ↑ 2.09 (1.90-2.31)
Cmax ↑ 1.75 (1.60-1.91)

INTELENCE and 
fluconazole can be used 
without dose adjustments.

Itraconazole
Ketoconazole
Posaconazole

Not studied. Posaconazole, a potent inhibitor of 
CYP3A4, may increase plasma concentrations 
of etravirine. Itraconazole and ketoconazole are 
potent inhibitors as well as substrates of 
CYP3A4. Concomitant systemic use of 
itraconazole or ketoconazole and etravirine may 
increase plasma concentrations of etravirine. 
Simultaneously, plasma concentrations of 
itraconazole or ketoconazole may be decreased 
by etravirine.

INTELENCE and these 
antifungals can be used 
without dose adjustments.

Voriconazole
200 mg twice daily

voriconazole
AUC ↑ 1.14 (0.88-1.47)
Cmin ↑ 1.23 (0.87-1.75)
Cmax ↓ 0.95 (0.75-1.21)
etravirine
AUC ↑ 1.36 (1.25-1.47)
Cmin ↑ 1.52 (1.41-1.64)
Cmax ↑ 1.26 (1.16-1.38)

INTELENCE and 
voriconazole can be used 
without dose adjustments.



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ANTIMALARIALS
Artemether/
Lumefantrine
80/480 mg, 6 doses at 0, 
8, 24, 36, 48, and 
60 hours

artemether
AUC ↓ 0.62 (0.48-0.80)
Cmin ↓ 0.82 (0.67-1.01)
Cmax ↓ 0.72 (0.55-0.94)
dihydroartemisinin
AUC ↓ 0.85 (0.75-0.97)
Cmin ↓ 0.83 (0.71-0.97)
Cmax ↓ 0.84 (0.71-0.99)
lumefantrine
AUC ↓ 0.87 (0.77-0.98)
Cmin ↔ 0.97 (0.83-1.15)
Cmax ↔ 1.07 (0.94-1.23)
etravirine
AUC ↔ 1.10 (1.06-1.15)
Cmin ↔ 1.08 (1.04-1.14)
Cmax ↔ 1.11 (1.06-1.17)

Close monitoring of 
antimalarial response is 
warranted when 
co-administering 
INTELENCE and 
artemether/lumefantrine as a 
significant decrease in 
exposure of artemether and 
its active metabolite, 
dihydroartemisinin, may 
result in decreased 
antimalarial efficacy. No 
dose adjustment is needed for 
INTELENCE.

ANTIMYCOBACTERIALS
Rifampicin
Rifapentine

Not studied. Rifampicin and rifapentine are 
expected to decrease plasma concentrations of 
etravirine.
INTELENCE should be used in combination 
with a boosted PI. Rifampicin is contraindicated 
in combination with boosted Pis.

Combination not 
recommended.

Rifabutin
300 mg once daily

With an associated boosted PI:
No interaction study has been performed. Based 
on historical data, a decrease in etravirine 
exposure may be expected whereas an increase 
in rifabutin exposure and especially in 
25-O-desacetyl-rifabutin may be expected.

With no associated boosted PI (out of the 
recommended indication for etravirine):
rifabutin
AUC ↓ 0.83 (0.75-0.94)
Cmin ↓ 0.76 (0.66-0.87)
Cmax ↓ 0.90 (0.78-1.03)
25-O-desacetyl-rifabutin
AUC ↓ 0.83 (0.74-0.92)
Cmin ↓ 0.78 (0.70-0.87)
Cmax ↓ 0.85 (0.72-1.00)
etravirine
AUC ↓ 0.63 (0.54-0.74)
Cmin ↓ 0.65 (0.56-0.74)
Cmax ↓ 0.63 (0.53-0.74)

The combination of 
INTELENCE with a boosted 
PI and rifabutin should be 
used with caution due to the 
risk of decrease in etravirine 
exposure and the risk of 
increase in rifabutin and 
25-O-desacetyl-rifabutin 
exposures.
Close monitoring for 
virologic response and for 
rifabutin related adverse 
reactions is recommended.
Please refer to the product 
information of the associated 
boosted PI for the dose 
adjustment of rifabutin to be 
used.

BENZODIAZEPINES
Diazepam Not studied. Etravirine is expected to increase 

plasma concentrations of diazepam.
Alternatives to diazepam 
should be considered.

CORTICOSTEROIDS
Dexamethasone 
(systemic)

Not studied. Dexamethasone is expected to 
decrease plasma concentrations of etravirine

Systemic dexamethasone 
should be used with caution 
or alternatives should be 
considered, particularly for 
chronic use.



13

OESTROGEN-BASED CONTRACEPTIVES
Ethinylestradiol
0.035 mg once daily
Norethindrone
1 mg once daily

ethinylestradiol
AUC ↑ 1.22 (1.13-1.31)
Cmin ↔ 1.09 (1.01-1.18)
Cmax ↑ 1.33 (1.21-1.46)
norethindrone
AUC ↔ 0.95 (0.90-0.99)
Cmin ↓ 0.78 (0.68-0.90)
Cmax ↔ 1.05 (0.98-1.12)
etravirine
AUC ↔a

Cmin ↔
a

Cmax ↔
a

The combination of 
oestrogen- and/or 
progesterone-based 
contraceptives and 
INTELENCE can be used 
without dose adjustment.

HEPATITIS C VIRUS (HCV) DIRECT-ACTING ANTIVIRALS
Ribavirin Not studied, but no interaction expected based 

on the renal elimination pathway of ribavirin.
The combination of 
INTELENCE and ribavirin 
can be used without dose 
adjustments.

Daclatasvir Not studied. Co-administration of etravirine
with daclatasvir may decrease daclatasvir 
concentrations. 

Co-administration of 
Intelence and daclatasvir is 
not recommended.

Elbasvir/grazoprevir Not studied. Co-administration of etravirine
with elbasvir/grazoprevir may decrease elbasvir 
and grazoprevir concentrations, leading to 
reduced therapeutic effect of 
elbasvir/grazoprevir.

Co-administration is 
contraindicated (see 
section 4.3).

HERBAL PRODUCTS
St John’s wort 
(Hypericum perforatum)

Not studied. St John’s wort is expected to 
decrease the plasma concentrations of 
etravirine.

Combination not 
recommended.

HMG CO-A REDUCTASE INHIBITORS
Atorvastatin
40 mg once daily

atorvastatin
AUC ↓ 0.63 (0.58-0.68)
Cmin ND
Cmax ↑ 1.04 (0.84-1.30)
2-OH-atorvastatin
AUC ↑ 1.27 (1.19-1.36)
Cmin ND
Cmax ↑ 1.76 (1.60-1.94)
etravirine
AUC ↔ 1.02 (0.97-1.07)
Cmin ↔ 1.10 (1.02-1.19)
Cmax ↔ 0.97 (0.93-1.02)

The combination of 
INTELENCE and 
atorvastatin can be given 
without any dose 
adjustments, however, the 
dose of atorvastatin may 
need to be altered based on 
clinical response.

Fluvastatin
Lovastatin
Pravastatin
Rosuvastatin
Simvastatin

Not studied. No interaction between pravastatin
and etravirine is expected.
Lovastatin, rosuvastatin and simvastatin are 
CYP3A4 substrates and co-administration with 
etravirine may result in lower plasma 
concentrations of the HMG Co-A reductase 
inhibitor. Fluvastatin, and rosuvastatin are 
metabolised by CYP2C9 and co-administration 
with etravirine may result in higher plasma 
concentrations of the HMG Co-A reductase 
inhibitor.

Dose adjustments for these 
HMG Co-A reductase 
inhibitors may be necessary.

H2-RECEPTOR ANTAGONISTS
Ranitidine
150 mg twice daily

etravirine
AUC ↓ 0.86 (0.76-0.97)
Cmin ND
Cmax ↓ 0.94 (0.75-1.17)

INTELENCE can be 
co-administered with 
H2-receptor antagonists 
without dose adjustments.



14

IMMUNOSUPPRESSANTS
Cyclosporin
Sirolimus
Tacrolimus

Not studied. Etravirine is expected to decrease 
plasma concentrations of cyclosporine, 
sirolimus and tacrolimus.

Co-administration with 
systemic 
immunosuppressants should 
be done with caution because 
plasma concentrations of 
cyclosporin, sirolimus and 
tacrolimus may be affected 
when co-administered with 
INTELENCE.

NARCOTIC ANALGESICS
Methadone
individual dose ranging 
from 60 mg to 130 mg 
once daily

R(-) methadone
AUC ↔ 1.06 (0.99-1.13)
Cmin ↔ 1.10 (1.02-1.19)
Cmax ↔ 1.02 (0.96-1.09)
S(+) methadone
AUC ↔ 0.89 (0.82-0.96)
Cmin ↔ 0.89 (0.81-0.98)
Cmax ↔ 0.89 (0.83-0.97)
etravirine
AUC ↔a

Cmin ↔
a

Cmax ↔
a

No changes in methadone 
dosage were required based 
on clinical status during or 
after the period of 
INTELENCE 
co-administration.

PHOSPHODIESTERASE, TYPE 5 (PDE-5) INHIBITORS
Sildenafil 50 mg single 
dose
Tadalafil
Vardenafil

sildenafil
AUC ↓ 0.43 (0.36-0.51)
Cmin ND
Cmax ↓ 0.55 (0.40-0.75)
N-desmethyl-sildenafil
AUC ↓ 0.59 (0.52-0.68)
Cmin ND
Cmax ↓ 0.75 (0.59-0.96)

Concomitant use of PDE-5 
inhibitors with INTELENCE 
may require dose adjustment 
of the PDE-5 inhibitor to 
attain the desired clinical 
effect.

PLATELET AGGREGGATION INHIBITORS
Clopidogrel In vitro data show that etravirine has inhibitory 

properties on CYP2C19. It is therefore possible 
that etravirine may inhibit the metabolism of 
clopidogrel to its active metabolite by such 
inhibition of CYP2C19 in vivo. The clinical 
relevance of this interaction has not been
demonstrated.

As a precaution it is 
recommended that 
concomitant use of etravirine 
and clopidogrel should be 
discouraged.

PROTON PUMP INHIBITORS
Omeprazole
40 mg once daily

etravirine
AUC ↑ 1.41 (1.22-1.62)
Cmin ND
Cmax ↑ 1.17 (0.96-1.43)

INTELENCE can be 
co-administered with proton 
pump inhibitors without dose 
adjustments.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS)
Paroxetine
20 mg once daily

paroxetine
AUC ↔ 1.03 (0.90-1.18)
Cmin ↓ 0.87 (0.75-1.02)
Cmax ↔ 1.06 (0.95-1.20)
etravirine
AUC ↔ 1.01 (0.93-1.10)
Cmin ↔ 1.07 (0.98-1.17)
Cmax ↔ 1.05 (0.96-1.15)

INTELENCE can be 
co-administered with 
paroxetine without dose 
adjustments.

a
Comparison based on historic control.

b
Study was conducted with tenofovir disoproxil fumarate 300 mg once daily

Note: In drug-drug interaction studies, different formulations and/or doses of etravirine were used which led to similar 
exposures and, therefore, interactions relevant for one formulation are relevant for the other.

Paediatric population

Interaction studies have only been performed in adults.



15

4.6 Fertility, pregnancy and lactation

Pregnancy

As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in
pregnant women, and consequently for reducing the risk of HIV vertical transmission to the newborn, 
the animal data as well as the clinical experience in pregnant women should be taken into account in 
order to characterise the safety for the foetus.

Placental transfer has been seen in pregnant rats, but it is not known whether placental transfer of 
etravirine also occurs in pregnant women. Studies in animals do not indicate direct or indirect harmful 
effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development 
(see section 5.3). Based on animal data the malformative risk is unlikely in humans. The clinical data 
do not raise safety concern but are very limited.

Breast-feeding

Etravirine is excreted in human milk.
As a general rule, it is recommended that mothers infected by HIV do not breastfeed their babies under 
any circumstances in order to avoid transmission of HIV.

Fertility

No human data on the effect of etravirine on fertility are available. In rats, there was no effect on 
mating or fertility with etravirine treatment (see section 5.3).

4.7 Effects on ability to drive and use machines

INTELENCE has minor influence on the ability to drive and use machines. No studies on the effects 
of INTELENCE on the ability to drive or operate machines have been performed. Adverse reactions 
such as somnolence and vertigo have been reported in etravirine-treated patients and should be 
considered when assessing a patient’s ability to drive or operate machinery (see section 4.8).

4.8 Undesirable effects

Summary of the safety profile

The most frequent (incidence ≥ 10%) adverse reactions of all intensities reported for etravirine were 
rash, diarrhoea, nausea and headache. In the Phase III studies, the rates of discontinuation due to any 
adverse reaction were 7.2% 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

Blood and lymphatic 
system disorders

common thrombocytopaenia, anaemia, decreased neutrophils
uncommon decreased white blood cell count



16

Immune system 
disorders

common drug hypersensitivity
uncommon immune reconstitution syndrome

Metabolism and 
nutrition disorders

common diabetes mellitus, hyperglycaemia, 
hypercholesterolaemia, increased low density 
lipoprotein (LDL), hypertriglyceridaemia, 
hyperlipidaemia, dyslipidaemia, anorexia

Psychiatric disorders common anxiety, insomnia, sleep disorders
uncommon confusional state, disorientation, nightmares, 

nervousness, abnormal dreams
Nervous system 
disorders

very common headache
common peripheral neuropathy, paraesthesia, hypoaesthesia, 

amnesia, somnolence 
uncommon convulsion, syncope, tremor, hypersomnia, disturbance 

in attention
Eye disorders common blurred vision
Ear and labyrinth 
disorders

uncommon vertigo

Cardiac disorders common myocardial infarction
uncommon atrial fibrillation, angina pectoris 

Vascular disorders common hypertension
rare haemorrhagic strokea

Respiratory, thoracic 
and mediastinal 
disorders

common exertional dyspnoea
uncommon bronchospasm

Gastrointestinal 
disorders

very common diarrhoea, nausea
common gastrooesophageal reflux disease, vomiting, abdominal 

pain, abdominal distension, flatulence, gastritis, 
constipation, dry mouth, stomatitis, lipase increased, 
blood amylase increased

uncommon pancreatitis, haematemesis, retching
Hepatobiliary disorders common increased alanine aminotransferase (ALT), increased 

aspartate aminotransferase (AST)
uncommon hepatitis, hepatic steatosis, cytolytic hepatitis, 

hepatomegaly
Skin and subcutaneous 
tissue disorders

very common rash
common night sweats, dry skin, prurigo
uncommon angioneurotic oedemaa, swelling face, hyperhidrosis 
rare Stevens-Johnson Syndromea, erythema multiformea

very rare toxic epidermal necrolysisa, DRESSb

Renal and urinary 
disorders

common renal failure, blood creatinine increased

Reproductive system 
and breast disorders

uncommon gynaecomastia

General disorders and 
administration site 
conditions

common fatigue
uncommon sluggishness

a
These adverse reactions were observed in other clinical trials than DUET-1 and DUET-2.

b
These adverse reactions have been identified through postmarketing experience with etravirine.

Description of selected adverse reactions

Rash
Rash was most frequently mild to moderate, generally macular to maculopapular or erythematous, 
mostly occurred in the second week of therapy, and was infrequent after week 4. Rash was mostly 
self-limiting, and generally resolved within 1-2 weeks on continued therapy (see section 4.4). The 
incidence of rash was higher in women compared to men in the etravirine arm in the DUET trials 



17

(rash ≥ grade 2 was reported in 9/60 [15.0%] women versus 51/539 [9.5%] men; discontinuations due 
to rash were reported in 3/60 [5.0%] women versus 10/539 [1.9%] men) (see section 4.4). There was 
no gender difference in severity or treatment discontinuation due to rash. The clinical data are limited 
and an increased risk of cutaneous reactions in patients with a history of NNRTI-associated cutaneous 
reaction cannot be excluded (see section 4.4).

Metabolic parameters
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see 
section 4.4)

Immune reconstitution 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. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have 
also been reported; however, the reported time to onset is more variable and these events can occur 
many months after initiation of treatment (see section 4.4).

Osteonecrosis
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk 
factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy. The 
frequency of this is unknown (see section 4.4).

Paediatric population (1 year to less than 18 years of age)

The safety assessment in children and adolescents is based on two single-arm trials. PIANO 
(TMC125-C213) is a Phase II trial in which 101 antiretroviral treatment-experienced HIV-1 infected 
paediatric patients 6 years to less than 18 years of age received INTELENCE in combination with 
other antiretroviral agents. TMC125-C234/IMPAACT P1090 is a Phase I/II trial in which 
26 antiretroviral treatment-experienced HIV-1 infected paediatric patients aged 1 years to less than 
6 years received INTELENCE in combination with other antiretroviral agents (see section 5.1).

In PIANO and TMC125-C234/IMPAACT P1090, the frequency, type and severity of adverse 
reactions in paediatric patients were comparable to those observed in adults. In PIANO, rash was 
reported more frequently in female subjects than in male subjects (rash ≥ grade 2 was reported in 
13/64 [20.3%] females versus 2/37 [5.4%] males; discontinuations due to rash were reported in 4/64 
[6.3%] females versus 0/37 [0%] males) (see section 4.4). Most often, rash was mild to moderate, of 
macular/papular type, and occurred in the second week of therapy. Rash was mostly self-limiting and 
generally resolved within 1 week on continued therapy.

In a postmarketing retrospective cohort study aiming at substantiating the long-term safety profile of 
etravirine in HIV-1-infected children and adolescents receiving etravirine with other HIV-1 
antiretrovirals (N = 182), Stevens-Johnson Syndrome was reported at a higher incidence (1%) than has 
been reported in adult clinical trials (< 0.1%).

Other special populations

Patients co-infected with hepatitis B and/or hepatitis C virus
In the pooled analysis for DUET-1 and DUET-2, the incidence of hepatic events tended to be higher in 
co-infected subjects treated with etravirine compared to co-infected subjects in the placebo group. 
INTELENCE should be used with caution in these patients (see also sections 4.4 and 5.2).

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. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


18

4.9 Overdose

There are no data with regard to symptomatic overdose with etravirine, but it is possible that the most 
frequent adverse reactions of etravirine, i.e. rash, diarrhoea, nausea, and headache would be the most 
common symptoms noted. There is no specific antidote for overdose with etravirine. Treatment of 
overdose with INTELENCE consists of general supportive measures including monitoring of vital 
signs and observation of the clinical status of the patient. Since etravirine is highly protein bound, 
dialysis is unlikely to result in significant removal of the active substance.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antivirals for systemic use, non-nucleoside reverse transcriptase 
inhibitors, ATC code: J05AG04.

Mechanism of action

Etravirine is an NNRTI of human immunodeficiency virus type 1 (HIV-1). Etravirine binds directly to 
reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase 
activities by causing a disruption of the enzyme’s catalytic site.

Antiviral activity in vitro

Etravirine exhibits activity against wild type HIV-1 in T-cell lines and primary cells with median 
EC50 values ranging from 0.9 to 5.5 nM. Etravirine demonstrates activity against HIV-1 group M 
(subtypes A, B, C, D, E, F, and G) and HIV-1 group O primary isolates with EC50 values ranging from 
0.3 to 1.7 nM and from 11.5 to 21.7 nM, respectively. Although etravirine demonstrates in vitro 
activity against wild type HIV-2 with median EC50 values ranging from 5.7 to 7.2 µM, treatment of 
HIV-2 infection with etravirine is not recommended in the absence of clinical data. Etravirine retains 
activity against HIV-1 viral strains resistant to nucleoside reverse transcriptase and/or protease 
inhibitors. In addition, etravirine demonstrates a fold change (FC) in EC50 ≤ 3 against 60% of 
6,171 NNRTI-resistant clinical isolates.

Resistance

Etravirine efficacy in relation to NNRTI resistance at baseline has mainly been analysed with 
etravirine given in combination with darunavir/ritonavir (DUET-1 and DUET-2). Boosted protease
inhibitors, like darunavir/ritonavir, show a higher barrier to resistance compared to other classes of 
antiretrovirals. The breakpoints for reduced efficacy with etravirine (> 2 etravirine-associated 
mutations at baseline, see clinical results section) applies when etravirine is given in combination with 
a boosted protease inhibitor. This breakpoint might be lower in antiretroviral combination therapy not 
including a boosted protease inhibitor.

In the Phase III trials DUET-1 and DUET-2, mutations that developed most commonly in patients 
with virologic failure to the etravirine containing regimen were V108I, V179F, V179I, Y181C and 
Y181I, which usually emerged in a background of multiple other NNRTI resistance-associated 
mutations (RAMs). In all the other trials conducted with etravirine in HIV-1 infected patients, the 
following mutations emerged most commonly: L100I, E138G, V179F, V179I, Y181C and H221Y.

Cross-resistance

Following virologic failure of an etravirine-containing regimen it is not recommended to treat patients 
with efavirenz and/or nevirapine.



19

Clinical efficacy and safety

Treatment-experienced adult patients
Pivotal studies
The evidence of efficacy of etravirine is based on 48-week data from 2 Phase III trials DUET-1 and 
DUET-2. These trials were identical in design and similar efficacy for etravirine was seen in each trial. 
The results below are pooled data from the two trials.

Trial characteristics
- Design: randomised (1:1), double-blinded, placebo-controlled.
- Treatment: Etravirine vs. placebo, in addition to a background regimen (BR) including

darunavir/ritonavir (DRV/rtv), investigator-selected N(t)RTIs and optional enfuvirtide (ENF).
- Main inclusion criteria:

 HIV-1 plasma viral load > 5,000 HIV-1 RNA copies/ml at screening
 1 or more NNRTI resistance-associated mutations (RAMs) at screening or from prior 

genotypic analysis (i.e., archived resistance)
 3 or more primary PI mutations at screening
 on a stable antiretroviral regimen for at least 8 weeks.

- Stratification: Randomisation was stratified by the intended use of ENF in the BR, previous use 
of darunavir and screening viral load.

- Virologic response was defined as achieving a confirmed undetectable viral load 
(< 50 HIV-1 RNA copies/ml).

Summary of efficacy results

Table 4: DUET-1 and DUET-2 pooled 48-week data

Etravirine + BR
N = 599

Placebo + BR
N = 604

Treatment 
difference
(95% CI)

Baseline characteristics
Median plasma HIV-1 RNA 4.8 log10 copies/ml 4.8 log10 copies/ml
Median CD4 cell count 99 x 106 cells/l 109 x 106 cells/l
Outcomes
Confirmed undetectable viral 
load (< 50 HIV-1 RNA 
copies/ml)a

n (%)

Overall 363 (60.6%) 240 (39.7%)
20.9%

(15.3%; 26.4%)d

de novo ENF 109 (71.2%) 93 (58.5%)
12.8%

(2.3%; 23.2%)f

Not de novo ENF 254 (57.0%) 147 (33.0%)
23.9%

(17.6%; 30.3%)f

< 400 HIV-1 RNA copies/mla

n (%)
428 (71.5%) 286 (47.4%)

24.1%
(18.7%; 29.5%)d

HIV-1 RNA log10 mean change 
from baseline (log10 copies/ml)

b -2.25 -1.49
-0.6

(-0.8; -0.5)c

CD4 cell count mean change 
from baseline (x 106/l)b

+98.2 +72.9
24.4

(10.4; 38.5)c

Any AIDS defining illness 
and/or death n (%)

35 (5.8%) 59 (9.8%)
-3.9%

(-6.9%; -0.9%)e



20

a
Imputations according to the TLOVR algorithm (TLOVR = Time to Loss of Virologic Response).

b
Non-completer is failure (NC = F) imputation.

c
Treatment differences are based on Least Square Means from an ANCOVA model including the stratification factors. 
P-value < 0.0001 for mean decrease in HIV-1 RNA; P-value = 0.0006 for mean change in CD4 cell count.

d
Confidence interval around observed difference of response rates; P-value < 0.0001 from logistic regression model, 
including stratification factors.

e
Confidence interval around observed difference of response rates; P-value = 0.0408.

f
Confidence interval around observed difference of response rates; P-value from CMH test controlling for stratification 
factors = 0.0199 for de novo, and < 0.0001 for not de novo.

Since there was a significant interaction effect between treatment and ENF, the primary analysis was 
done for 2 ENF strata (patients reusing or not using ENF versus patients using ENF de novo). The 
week 48 results from the pooled analysis of DUET-1 and DUET-2 demonstrated that the etravirine
arm was superior to the placebo arm irrespective of whether ENF was used de novo (p = 0.0199) or 
not (p < 0.0001). Results of this analysis (week 48 data) by ENF stratum are shown in table 4.

Significantly fewer patients in the etravirine arm reached a clinical endpoint (AIDS-defining illness 
and/or death) as compared to the placebo arm (p = 0.0408).

A subgroup analysis of the virologic response (defined as a viral load < 50 HIV-1 RNA copies/ml) at 
week 48 by baseline viral load and baseline CD4 count (pooled DUET data) is presented in table 5.

Table 5: DUET-1 and DUET-2 pooled data

Subgroups

Proportion of subjects with HIV-1 RNA < 50 copies/ml 
at week 48

Etravirine + BR
N = 599

Placebo + BR
N = 604

Baseline HIV-1 RNA
< 30,000 copies/ml
≥ 30,000 and < 100,000 copies/ml
≥ 100,000 copies/ml

75.8%
61.2%
49.1%

55.7%
38.5%
28.1%

Baseline CD4 count (x 106/l)
< 50
≥ 50 and < 200
≥ 200 and < 350
≥ 350

45.1%
65.4%
73.9%
72.4%

21.5%
47.6%
52.0%
50.8%

Note: Imputations according to the TLOVR algorithm (TLOVR = Time to Loss of Virologic Response)

Baseline genotype or phenotype and virologic outcome analyses
In DUET-1 and DUET-2, the presence at baseline of 3 or more of the following mutations: V90I, 
A98G, L100I, K101E, K101P, V106I, V179D, V179F, Y181C, Y181I, Y181V, G190A and G190S, 
(etravirine RAMs) was associated with a decreased virologic response to etravirine (see table 6).
These individual mutations occurred in the presence of other NNRTI RAMs. V179F was never present 
without Y181C.

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.

Table 6: Proportion of subjects with < 50 HIV-1 RNA copies/ml at week 48 by baseline 
number of etravirine RAMs in the non-viral failure excluded population of pooled 
DUET-1 and DUET-2 trials

Baseline number of 
Etravirine RAMs*

Etravirine arms
N = 549

Reused/not used ENF de novo ENF
All ranges 63.3% (254/401) 78.4% (109/139)

0 74.1% (117/158) 91.3% (42/46)



21

1 61.3% (73/119) 80.4% (41/51)
2 64.1% (41/64) 66.7% (18/27)

≥ 3 38.3% (23/60) 53.3% (8/15)
Placebo arms

N = 569
All ranges 37.1% (147/396) 64.1% (93/145)

* Etravirine RAMs = V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V, G190A/S
Note: all patients in the DUET trials received a background regimen consisting of darunavir/rtv, investigator-selected 
NRTIs and optional enfuvirtide.

The presence of K103N alone, which was the most prevalent NNRTI mutation in DUET-1 and 
DUET-2 at baseline, was not identified as a mutation associated with resistance to etravirine. 
Furthermore, the presence of this mutation alone did not affect the response in the etravirine arm. 
Additional data is required to conclude on the influence of K103N when associated with other 
NNRTIs mutations.

Data from the DUET studies suggest that baseline fold change (FC) in EC50 to etravirine was a 
predictive factor of virologic outcome, with gradually decreasing responses observed above FC 3 and 
FC 13.
FC subgroups are based on the select patient populations in DUET-1 and DUET-2 and are not meant 
to represent definitive clinical susceptibility breakpoints for etravirine.

Exploratory head to head comparison with protease inhibitor in protease inhibitor naïve patients 
(trial TMC125-C227)
TMC125-C227 was an exploratory, randomised, active-controlled open-label trial, which investigated 
the efficacy and safety of etravirine in a treatment regimen, which is not approved under the current 
indication. In the TMC125-C227 study, etravirine (N = 59) was administered with 
2 investigator-selected NRTIs (i.e. without a ritonavir-boosted PI) and compared to an 
investigator-selected combination of a PI with 2 NRTIs (N = 57). The trial population included 
PI-naïve, NNRTI-experienced patients with evidence of NNRTI resistance.

At week 12, virologic response was greater in the control-PI arm (-2.2 log10 copies/ml from baseline; 
n = 53) compared to the etravirine arm (-1.4 log10 copies/ml from baseline; n = 40). This difference 
between treatment arms was statistically significant.

Based on these trial results, etravirine is not recommended for use in combination with N(t)RTIs only 
in patients who have experienced virological failure on an NNRTI- and N(t)RTI-containing regimen.

Paediatric population

Treatment-experienced paediatric patients (6 years to less than 18 years of age)
PIANO is a single-arm, Phase II trial evaluating the pharmacokinetics, safety, tolerability, and efficacy 
of etravirine in 101 antiretroviral treatment-experienced HIV-1 infected paediatric patients 6 years to 
less than 18 years of age and weighing at least 16 kg. The study enrolled patients on a stable but 
virologically failing antiretroviral treatment regimen, with a confirmed HIV-1 RNA plasma viral load 
≥ 500 copies/ml. Sensitivity of the virus to etravirine at screening was required.

The median baseline plasma HIV-1 RNA was 3.9 log10 copies/ml, and the median baseline CD4 cell 
count was 385 x 106 cells/l.



22

Table 7: Virologic responses (ITT – TLOVR), change from baseline in log10 viral load (NC = F), and 
change from baseline in CD4 percentage and cell count (NC = F) at week 24 in the 
TMC125-C213 and pooled DUET studies

Study
Age at screening
Treatment group

TMC125-C213
6 to < 12 years

ETR
N = 41

TMC125-C213
12 to < 18 years

ETR
N = 60

TMC125-C213
6 to < 18 years

ETR
N = 101

Pooled DUET 
Studies

≥ 18 years
ETR

N = 599

Virologic parameters

Viral load < 50 copies/ml at 
week 24, n (%)

24 (58.5) 28 (46.7) 52 (51.5) 363 (60.6)

Viral load < 400 copies/ml at 
week 24, n (%)

28 (68.3) 38 (63.3) 66 (65.3) 445 (74.3)

≥ 1 log10 decrease from 
baseline at week 24, n (%)

26 (63.4) 38 (63.3) 64 (63.4) 475 (79.3)

Change from baseline in log10
viral load (copies/ml) at 
week 24, mean (SE) and 
median (range)

-1.62 (0.21)
-1.68 (-4.3; 0.9)

-1.44 (0.17)
-1.68 (-4.0; 0.7)

-1.51 (0.13)
-1.68 (-4.3; 0.9)

-2.37 (0.05)
-2.78 (-4.6; 1.4)

Immunologic parameters

Change from baseline in CD4 
cell count (x 106 cells/l), mean 
(SE) and median (range)

125 (33.0)
124 (-410; 718)

104 (17.5)
81 (-243; 472)

112 (16.9)
108 (-410; 718)

83.5 (3.64)
77.5 (-331; 517)

Change from baseline in CD4 
percentage, median (range)

4%
(-9; 20)

3%
(-4; 14)

4%
(-9; 20)

3%
(-7; 23)

N = number of subjects with data; n = number of observations.

At week 48, 53.5% of all paediatric patients had a confirmed undetectable viral load < 50 HIV-1 RNA 
copies/ml according to the TLOVR algorithm. The proportion of paediatric patients with 
< 400 HIV-1 RNA copies/ml was 63.4%. The mean change in plasma HIV-1 RNA from baseline to 
week 48 was -1.53 log10 copies/ml, and the mean CD4 cell count increase from baseline was 
156 x 106 cells/l.

Treatment-experienced paediatric patients (1 year to less than 6 years of age)

TMC125-C234/IMPAACT P1090 is a Phase I/II trial evaluating the pharmacokinetics, safety, 
tolerability, and efficacy of INTELENCE in 20 antiretroviral treatment-experienced HIV-1 infected 
pediatric patients 2 years to less than 6 years of age (Cohort I) and 6 antiretroviral treatment-
experienced HIV-1 infected pediatric patients 1 year to less than 2 years of age (Cohort II). No 
patients have been enrolled in Cohort III (≥ 2 months to < 1 year). The study enrolled patients on a 
virologically failing antiretroviral treatment regimen for at least 8 weeks or on a treatment interruption 
of at least 4 weeks with a history of virologic failure while on an antiretroviral regimen, with a 
confirmed HIV-1 RNA plasma viral load greater than 1,000 copies/ml and with no evidence of 
phenotypic resistance to etravirine at screening.

Table 8 summarizes the virologic response results for the TMC125-C234/IMPAACT P1090 study.

Table 8: Virologic responses (ITT-FDA Snapshot*) at week 48 in the TMC125-C234/IMPAACT 
P1090 Study

Cohort I
≥ 2 to < 6 years

(N = 20)

Cohort II
≥ 1 to < 2 years

(N = 6)
Baseline

Plasma HIV-1 RNA 4.4 log10 copies/ml 4.4 log10 copies/ml
Median CD4+ cell count 
Median baseline CD4+ 
percentage

817.5 x 106 cells/l
(27.6%)

1,491.5 x 106 cells/l
(26.9%)



23

Week 48
Virologic Response (plasma 
viral load < 400 HIV-1 RNA 
copies/ml) 

16/20
(80.0%)

1/6
(16.7%)

Median change in plasma 
HIV-1 RNA from baseline to 
Week 48 

-2.31 log10 copies/ml -0.665 log10 copies/ml

Median CD4+ change from 
baseline

298.5 x 106 cells/l
(5.15%)

0 x 106 cells/l
(-2.2%)

N = number of subjects per treatment group.
* Intent-to-treat-FDA Snapshot approach.

Subgroup analyses showed that for subjects aged 2 to less than 6 years virologic response [HIV RNA 
< 400 copies/ml] was 100.0% [6/6] for subjects who swallowed the etravirine tablet whole, 100% 
[4/4] for subjects who took a combination of both etravirine dispersed in liquid and etravirine tablet 
whole and 60% [6/10] for subjects who took etravirine dispersed in liquid. Of the 4 subjects who did 
not show virologic response and took etravirine dispersed in liquid, 3 showed virologic failure and had 
adherence issues, and one discontinued prior to Week 48 for safety reasons.

The European Medicines Agency has deferred the obligation to submit the results of studies with 
INTELENCE in one or more subsets of the paediatric population in human immunodeficiency virus 
infection, as per Paediatric Investigation Plan (PIP) decision in the granted indication (see section 4.2 
for information on paediatric use).

Pregnancy and postpartum

Etravirine (200 mg twice daily), evaluated in combination with other antiretroviral medicinal products 
in a study of 15 pregnant women during the second and third trimesters of pregnancy and postpartum, 
demonstrated that exposure to total etravirine was generally higher during pregnancy compared with 
postpartum, and less so for unbound etravirine exposure (see section 5.2). There were no new 
clinically relevant safety findings in the mothers or in the newborns in this trial.

5.2 Pharmacokinetic properties

The pharmacokinetic properties of etravirine have been evaluated in adult healthy subjects and in adult 
and paediatric treatment-experienced HIV-1 infected patients. Exposure to etravirine was lower 
(35-50%) in HIV-1 infected patients than in healthy subjects.

Table 9: Population pharmacokinetic estimates of etravirine 200 mg twice daily in HIV-1
infected adult subjects (integrated data from Phase III trials at week 48)*

Parameter Etravirine 200 mg twice daily
N = 575

AUC12h (ng•h/ml)
Geometric Mean ± Standard Deviation 4,522 ± 4,710
Median (Range) 4,380 (458 - 59,084)

C0h (ng/ml)
Geometric Mean ± Standard Deviation 297 ± 391
Median (Range) 298 (2 - 4,852)

* All HIV-1 infected subjects enrolled in Phase III clinical trials received darunavir/ritonavir 600/100 mg twice daily as 
part of their background regimen. Therefore, the pharmacokinetic parameter estimates shown in the table account for 
reductions in the pharmacokinetic parameters of etravirine due to co-administration of etravirine with 
darunavir/ritonavir.

Note: The median protein binding adjusted EC50 for MT4 cells infected with HIV-1/IIIB in vitro = 4 ng/ml.

Absorption

An intravenous formulation of etravirine is unavailable, thus, the absolute bioavailability of etravirine 
is unknown. After oral administration with food, the maximum plasma concentration of etravirine is 
generally achieved within 4 hours.



24

In healthy subjects, the absorption of etravirine is not affected by co-administration of oral ranitidine 
or omeprazole, medicinal products that are known to increase gastric pH.

Effect of food on absorption
The systemic exposure (AUC) to etravirine was decreased by about 50% when etravirine was 
administered under fasting conditions, as compared to administration following a meal. Therefore, 
INTELENCE should be taken following a meal.

Distribution

Etravirine is approximately 99.9% bound to plasma proteins, primarily to albumin (99.6%) and α1-acid 
glycoprotein (97.66%-99.02%) in vitro. The distribution of etravirine into compartments other than 
plasma (e.g., cerebrospinal fluid, genital tract secretions) has not been evaluated in humans.

Biotransformation

In vitro experiments with human liver microsomes (HLMs) indicate that etravirine primarily 
undergoes oxidative metabolism by the hepatic cytochrome CYP450 (CYP3A) system and, to a lesser 
extent, by the CYP2C family, followed by glucuronidation.

Elimination

After administration of a radiolabeled 14C-etravirine dose, 93.7% and 1.2% of the administered dose of 
14C-etravirine could be retrieved in faeces and urine, respectively. Unchanged etravirine accounted for 
81.2% to 86.4% of the administered dose in faeces. Unchanged etravirine in faeces is likely to be 
unabsorbed drug. Unchanged etravirine was not detected in urine. The terminal elimination half-life of 
etravirine was approximately 30-40 hours.

Special populations

Paediatric population (1 year to less than 18 years of age)
The pharmacokinetics of etravirine in 122 treatment-experienced HIV-1 infected paediatric patients, 
1 year to less than 18 years of age, showed that the administered weight-based dosages resulted in 
etravirine exposure comparable to that in adults receiving etravirine 200 mg twice daily (see 
sections 4.2 and 5.2). The population pharmacokinetic estimates for etravirine AUC12h and C0h are 
summarised in the table below.

Table 10: Pharmacokinetic parameters for etravirine in treatment-experienced HIV-1 
infected paediatric patients 1 year to less than 18 years of age (TMC125-
C234/IMPAACT P1090 [48 week analysis, intensive PK] and PIANO [48 Weeks 
analysis, population PK])

Age Range (years) ≥ 1 year to < 2 years
(Cohort II)

≥ 2 years to < 6 years
(Cohort I) 

6 years to < 18 years

Parameter Etravirine
N = 6

Etravirine
N = 15

Etravirine
N = 101

AUC12h (ng•h/ml)
Geometric 
Mean ± Standard 
Deviation

3,328 ± 3,138 3,824 ± 3,613 3,729 ± 4,305

Median (Range) 3,390 (1,148 - 9,989) 3,709 (1,221 - 12,999) 4,560 (62 - 28,865)

C0h (ng/ml)
Geometric 
Mean ± Standard 
Deviation

193 ± 186 203 ± 280 205 ± 342

Median (Range) 147 (0a - 503) 180 (54 - 908) 287 (2 - 2,276)
a

One subject in Cohort II had etravirine predose concentrations below the detection limit at the intensive PK visit.



25

Elderly
Population pharmacokinetic analysis in HIV infected patients showed that etravirine pharmacokinetics 
are not considerably different in the age range (18 to 77 years) evaluated, with 6 subjects aged 
65 years or older (see sections 4.2 and 4.4).

Gender
No significant pharmacokinetic differences have been observed between males and females. A limited 
number of females were included in the studies.

Race
Population pharmacokinetic analysis of etravirine in HIV infected patients indicated no apparent 
difference in the exposure to etravirine between Caucasian, Hispanic and Black subjects. The 
pharmacokinetics in other races have not been sufficiently evaluated.

Hepatic impairment
Etravirine is primarily metabolised and eliminated by the liver. In a study comparing 8 patients with 
mild (Child-Pugh Class A) hepatic impairment to 8 matched controls and 8 patients with moderate 
(Child-Pugh Class B) hepatic impairment to 8 matched controls, the multiple dose pharmacokinetic 
disposition of etravirine was not altered in patients with mild to moderate hepatic impairment.
However, unbound concentrations have not been assessed. Increased unbound exposure could be
expected. No dose adjustment is suggested but caution is advised in patients with moderate hepatic 
impairment. INTELENCE has not been studied in patients with severe hepatic impairment 
(Child-Pugh Class C) and is therefore not recommended (see sections 4.2 and 4.4).

Hepatitis B and/or hepatitis C virus co-infection
Population pharmacokinetic analysis of the DUET-1 and DUET-2 trials showed reduced clearance 
(potentially leading to increased exposure and alteration of the safety profile) for etravirine in HIV-1 
infected patients with hepatitis B and/or hepatitis C virus co-infection. In view of the limited data 
available in hepatitis B and/or C co-infected patients, particular caution should be paid when 
INTELENCE is used in these patients (see sections 4.4 and 4.8).

Renal impairment
The pharmacokinetics of etravirine have not been studied in patients with renal insufficiency. Results 
from a mass balance study with radioactive 14C-etravirine showed that < 1.2% of the administered 
dose of etravirine is excreted in the urine. No unchanged drug was detected in urine so the impact of 
renal impairment on etravirine elimination is expected to be minimal. As etravirine is highly bound to 
plasma proteins, it is unlikely that it will be significantly removed by haemodialysis or peritoneal 
dialysis (see section 4.2).

Pregnancy and postpartum
Study TMC114HIV3015 evaluated etravirine 200 mg twice daily in combination with other 
antiretroviral medicinal products in 15 pregnant women during the second and third trimesters of 
pregnancy and postpartum. The total etravirine exposure after intake of etravirine 200 mg twice daily
as part of an antiretroviral regimen was generally higher during pregnancy compared with postpartum 
(see Table 11). The differences were less pronounced for unbound etravirine exposure.
In women receiving etravirine 200 mg twice daily, higher mean values for Cmax, AUC12h and Cmin were 
observed during pregnancy compared to postpartum. During the 2nd and 3rd trimester of pregnancy 
mean values of these parameters were comparable.

Table 11: Pharmacokinetic results of total etravirine after administration of etravirine 
200 mg twice daily as part of an antiretroviral regimen, during the 2nd trimester of 
pregnancy, the 3rd trimester of pregnancy, and postpartum.

Pharmacokinetics of 
etravirine
Mean ± SD (median)

Etravirine 200 mg 
twice daily
postpartum

N = 10

Etravirine 200 mg 
twice daily 2nd

trimester
N = 13

Etravirine 200 mg 
twice daily 3rd

trimester
N = 10a

Cmin, ng/ml 269 ± 182 (284) 383 ± 210 (346) 349 ± 103 (371)



26

Cmax, ng/ml
AUC12h, h*ng /ml

569 ± 261 (528)
5004 ± 2521 (5246)

774 ± 300 (828)
6617 ± 2766 (6836)

785 ± 238 (694)
6846 ± 1482 (6028)

a
n = 9 for AUC12h

Each subject served as her own control, and with an intra-individual comparison, the total etravirine
Cmin, Cmax and AUC12h values were 1.2-, 1.4- and 1.4-fold higher, respectively, during the 2

nd trimester 
of pregnancy as compared to postpartum, and 1.1-, 1.4- and 1.2-fold higher, respectively, based during 
the 3rd trimester of pregnancy as compared to postpartum.

5.3 Preclinical safety data

Animal toxicology studies have been conducted with etravirine in mice, rats, rabbits and dogs. In 
mice, the key target organs identified were the liver and the coagulation system. Haemorrhagic 
cardiomyopathy was only observed in male mice and was considered to be secondary to severe 
coagulopathy mediated via the vitamin K pathway. In the rat, the key target organs identified were the 
liver, the thyroid and the coagulation system. Exposure in mice was equivalent to human exposure 
while in rats it was below the clinical exposure at the recommended dose. In the dog, changes were 
observed in the liver and gall bladder at exposures approximately 8-fold higher than human exposure 
observed at the recommended dose (200 mg twice daily).

In a study conducted in rats, there were no effects on mating or fertility at exposure levels equivalent 
to those in humans at the clinically recommended dose. There was no teratogenicity with etravirine in 
rats and rabbits at exposures equivalent to those observed in humans at the recommended clinical 
dose. Etravirine had no effect on offspring development during lactation or post weaning at maternal 
exposures equivalent to those observed at the recommended clinical dose.

Etravirine was not carcinogenic in rats and in male mice. An increase in the incidences of 
hepatocellular adenomas and carcinomas were observed in female mice. The observed hepatocellular 
findings in female mice are generally considered to be rodent specific, associated with liver enzyme 
induction, and of limited relevance to humans. At the highest tested doses, the systemic exposures 
(based on AUC) to etravirine were 0.6-fold (mice) and between 0.2- and 0.7-fold (rats), relative to 
those observed in humans at the recommended therapeutic dose (200 mg twice daily).
In vitro and in vivo studies with etravirine revealed no evidence of a mutagenic potential.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

INTELENCE 25 mg tablets

Hypromellose
Microcrystalline cellulose
Colloidal anhydrous silica
Croscarmellose sodium
Magnesium stearate
Lactose monohydrate

INTELENCE 100 mg tablets

Hypromellose
Microcrystalline cellulose
Colloidal anhydrous silica
Croscarmellose sodium
Magnesium stearate
Lactose monohydrate



27

INTELENCE 200 mg tablets

Hypromellose
Silicified microcrystalline cellulose
Microcrystalline cellulose
Colloidal anhydrous silica
Croscarmellose sodium
Magnesium stearate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

INTELENCE 25 mg tablets

2 years.
8 weeks after opening the bottle.

INTELENCE 100 mg tablets

2 years.

INTELENCE 200 mg tablets

2 years.
6 weeks after opening the bottle.

6.4 Special precautions for storage

Store in the original bottle and keep the bottle tightly closed in order to protect from moisture. Do not 
remove the desiccant pouches.

6.5 Nature and contents of container

INTELENCE 25 mg tablets

The bottle is a high-density polyethylene (HDPE) plastic bottle containing 120 tablets and 2 desiccant 
pouches, fitted with a polypropylene (PP) child resistant closure.
Each carton contains one bottle.

INTELENCE 100 mg tablets

The bottle is a high-density polyethylene (HDPE) plastic bottle containing 120 tablets and 3 desiccant 
pouches, fitted with a polypropylene (PP) child resistant closure.
Each carton contains one bottle.

INTELENCE 200 mg tablets

The bottle is a high-density polyethylene (HDPE) plastic bottle containing 60 tablets and 3 desiccant 
pouches, fitted with a polypropylene (PP) child resistant closure.
Each carton contains one bottle.



28

6.6 Special precautions for disposal and other handling

Patients who are unable to swallow the tablet(s) whole may disperse the tablet(s) in a glass of water.
The patient should be instructed to do the following:
- place the tablet(s) in 5 ml (1 teaspoon) of water, or at least enough liquid to cover the medicine,
- stir well until the water looks milky,
- if desired, add more water or alternatively orange juice or milk (patients should not place the 

tablets in orange juice or milk without first adding water),
- drink it immediately,
- rinse the glass several times with water, orange juice, or milk and completely swallow the rinse 

each time to make sure the patient takes the entire dose.

INTELENCE tablet(s) dispersed in liquid should be taken before other antiretroviral liquids that may 
need to be taken concomitantly.

The patient and his/her caregiver should be instructed to contact the prescribing physician if unable to 
swallow the entire dose when dispersed in liquid (see section 4.4).

The use of warm (> 40°C) or carbonated beverages should be avoided.

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

25 mg: EU/1/08/468/003
100 mg: EU/1/08/468/001
200 mg: EU/1/08/468/002

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 28 August 2008
Date of latest renewal: 23 August 2018

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicine is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/.

http://www.ema.europa.eu/


29

ANNEX II

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH
RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT



30

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release

Janssen-Cilag SpA
Via C. Janssen
04100 Borgo San Michele
Latina
Italy

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2).

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2. of the marketing
authorisation and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency.
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.



31

ANNEX III

LABELLING AND PACKAGE LEAFLET



32

A. LABELLING



33

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

INTELENCE 25 mg tablets
etravirine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 25 mg etravirine.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate.
See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

120 tablets

5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP
Do not use after 8 weeks of first opening the bottle.

9. SPECIAL STORAGE CONDITIONS

Store in the original bottle and keep the bottle tightly closed in order to protect from moisture. Do not 
remove the desiccant pouches.



34

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER

EU/1/08/468/003

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

intelence 25 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



35

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING

BOTTLE LABEL

1. NAME OF THE MEDICINAL PRODUCT

INTELENCE 25 mg tablets
etravirine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 25 mg etravirine.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate.

4. PHARMACEUTICAL FORM AND CONTENTS

120 tablets

5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original bottle and keep the bottle tightly closed in order to protect from moisture.



36

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER

EU/1/08/468/003

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

17. UNIQUE IDENTIFIER – 2D BARCODE

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA



37

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

INTELENCE 100 mg tablets
etravirine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 100 mg etravirine.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate.
See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

120 tablets

5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original bottle and keep the bottle tightly closed in order to protect from moisture. Do not 
remove the desiccant pouches.



38

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER

EU/1/08/468/001

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

intelence 100 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



39

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING

BOTTLE LABEL

1. NAME OF THE MEDICINAL PRODUCT

INTELENCE 100 mg tablets
etravirine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 100 mg etravirine.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate.

4. PHARMACEUTICAL FORM AND CONTENTS

120 tablets

5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original bottle and keep the bottle tightly closed in order to protect from moisture.



40

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER

EU/1/08/468/001

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

17. UNIQUE IDENTIFIER – 2D BARCODE

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA



41

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

INTELENCE 200 mg tablets
etravirine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 200 mg etravirine.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

60 tablets

5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP
Do not use after 6 weeks of first opening the bottle.

9. SPECIAL STORAGE CONDITIONS

Store in the original bottle and keep the bottle tightly closed in order to protect from moisture. Do not 
remove the desiccant pouches.



42

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER

EU/1/08/468/002

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

intelence 200 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



43

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING

BOTTLE LABEL

1. NAME OF THE MEDICINAL PRODUCT

INTELENCE 200 mg tablets
etravirine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 200 mg etravirine.

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

60 tablets

5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use.
Oral use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original bottle and keep the bottle tightly closed in order to protect from moisture.



44

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER

EU/1/08/468/002

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

17. UNIQUE IDENTIFIER – 2D BARCODE

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA



45

B. PACKAGE LEAFLET



46

Package leaflet: Information for the user

INTELENCE 25 mg tablets
etravirine

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet
1. What INTELENCE is and what it is used for
2. What you need to know before you take INTELENCE
3. How to take INTELENCE
4. Possible side effects
5. How to store INTELENCE
6. Contents of the pack and other information

1. What INTELENCE is and what it is used for

INTELENCE contains the active substance etravirine. INTELENCE belongs to a group of anti-HIV 
medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs).

INTELENCE is a medicine used for the treatment of Human Immunodeficiency Virus (HIV) 
infection. INTELENCE works by reducing the amount of HIV in your body. This will improve your 
immune system and reduces the risk of developing illnesses linked to HIV infection.

INTELENCE is used in combination with other anti-HIV medicines to treat adults and children 
2 years of age and older who are infected by HIV and who have used other anti-HIV medicines before.

Your doctor will discuss with you which combination of medicines is best for you.

2. What you need to know before you take INTELENCE

Do not take INTELENCE
- if you are allergic to etravirine or any of the other ingredients of this medicine (listed in 

section 6)
- if you are taking elbasvir/grazoprevir (a medicine to treat hepatitis C infection).

Warnings and precautions
Talk to your doctor or pharmacist before taking INTELENCE.

INTELENCE is not a cure for HIV infection. It is part of a treatment reducing the amount of virus in 
the blood. You can still pass on HIV when taking this medicine, although the risk is lowered by 
effective antiretroviral therapy. Discuss with your physician the precautions needed to avoid infecting 
other people.

Elderly
INTELENCE has only been used in a limited number of patients of 65 years or older. If you belong to 
this age group, please discuss the use of INTELENCE with your doctor.



47

Weight and increased blood lipids and glucose
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves. Your doctor will test for these changes.

Bone problems
Some patients taking combination antiretroviral therapy may develop a bone disease called 
osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of 
combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe 
immunosuppression, higher body mass index, among others, may be some of the many risk factors for 
developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the 
hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please 
inform your doctor.

Tell your doctor about your situation
Make sure that you check the following points and tell your doctor if any of these apply to you.
- Tell your doctor if you develop a rash. If a rash occurs, it usually appears soon after anti-HIV 

treatment with INTELENCE is started and often disappears within 1 to 2 weeks, even with 
continued use of the medicine. Rarely, during INTELENCE treatment, you can experience 
severe skin rash with blisters or peeling skin, particularly around the mouth or eyes or 
hypersensitivity reaction (allergic reaction including rash and fever but also swelling of the face,
tongue or throat, difficulty in breathing or swallowing) which could be potentially 
life-threatening. Please contact your doctor immediately if you experience these symptoms. 
Your doctor will advise you how to deal with your symptoms and whether INTELENCE must
be stopped. If you have stopped treatment due to a hypersensitivity reaction, you should not 
restart therapy with INTELENCE.

- Tell your doctor if you have or have had problems with your liver, including hepatitis B and/or 
C. Your doctor may evaluate how severe your liver disease is before deciding if you can take 
INTELENCE.

- Tell your doctor immediately if you notice any symptoms of infections. In some patients with 
advanced HIV infection and a history of opportunistic infection, signs and symptoms of 
inflammation from previous infections may occur soon after anti-HIV treatment is started. It is 
believed that these symptoms are due to an improvement in the body’s immune response,
enabling the body to fight infections that may have been present with no obvious symptoms.

- In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when 
the immune system attacks healthy body tissue) may also occur after you start taking medicines 
for the treatment of your HIV infection. Autoimmune disorders may occur many months after 
the start of treatment. If you notice any symptoms of infection or other symptoms such as 
muscle weakness, weakness beginning in the hands and feet and moving up towards the trunk of 
the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek 
necessary treatment.

Children and adolescents

Do not give this medicine to children less than 2 years of age and weighing less than 10 kg because the 
potential benefits and risks have not been established.

Other medicines and INTELENCE
INTELENCE might interact with other medicines. Tell your doctor or pharmacist if you are taking, 
have recently taken, or might take any other medicines.

In most cases, INTELENCE can be combined with anti-HIV medicines belonging to another class.
However, some combinations are not recommended. In other cases, increased monitoring and/or a 
change in the dose of the medicine may be needed. Therefore, always tell your doctor which other 
anti-HIV medicines you take. Furthermore, it is important that you carefully read the package leaflets 
that are provided with these medicines. Follow your doctor’s instruction carefully on which medicines 
can be combined.



48

It is not recommended to combine INTELENCE with any of the following medicines:
- tipranavir/ritonavir, efavirenz, nevirapine, rilpivirine, indinavir, atazanavir/cobicistat, 

darunavir/cobicistat (anti-HIV medicine)
- carbamazepine, phenobarbital, phenytoin (medicines to prevent seizures)
- rifampicin, because it is contraindicated with boosted protease inhibitors, and rifapentine 

(medicines to treat some infections such as tuberculosis)
- products that contain St John’s wort (Hypericum perforatum) (a herbal product used for 

depression)
- daclatasvir (a medicine to treat hepatitis C infection).

If you are taking any of these, ask your doctor for advice.

The effects of INTELENCE or other medicines might be influenced if you take INTELENCE 
together with any of the following medicines. The dosages of some medicines might need to be 
changed since their therapeutic effect or side effects may be influenced when combined with 
INTELENCE. Tell your doctor if you take:
- dolutegravir, maraviroc, amprevanir/ritonavir and fosamprenavir/ritonavir (anti-HIV medicine)
- amiodarone, bepridil, digoxin, disopyramide, flecainide, lidocaine, mexiletine, propafenone and 

quinidine (medicines to treat certain heart disorders, e.g., abnormal heart beat)
- warfarin (a medicine used to reduce clotting of the blood). Your doctor will have to check your

blood
- fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole (medicines to treat fungal

infections)
- clarithromycin, rifabutin (antibiotics)
- artemether/lumefantrine (a medicine to treat malaria)
- diazepam (medicines to treat trouble with sleeping and/or anxiety)
- dexamethasone (a corticosteroid used in a variety of conditions such as inflammation and 

allergic reactions)
- atorvastatin, fluvastatin, lovastatin, rosuvastatin, simvastatin (cholesterol-lowering medicines)
- cyclosporine, sirolimus, tacrolimus (immunosuppressants – medicines used to dampen down 

your immune system)
- sildenafil, vardenafil, tadalafil (medicines to treat erectile dysfunction and/or pulmonary arterial

hypertension)
- clopidogrel (a medicine to prevent blood clots).

Pregnancy and breast-feeding
Tell your doctor immediately if you are pregnant. Pregnant women should not take INTELENCE 
unless specifically directed by the doctor.
HIV infected mothers must not breast-feed, as there is a possibility of infecting the baby with HIV.

Driving and using machines
Do not drive or operate machines if you feel sleepy or dizzy after taking your medicines.

INTELENCE contains lactose
INTELENCE tablets contain lactose. If you have been told by your doctor that you have an 
intolerance to some sugars (lactose), contact your doctor before taking this medicine.

INTELENCE contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium 
free’.

3. How to take INTELENCE

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.



49

Use in adults
Other form(s) of this medicine may be more suitable for adults.

The recommended dose of INTELENCE is 200 mg twice a day.
In the morning, take two 100 milligram INTELENCE tablets, following a meal.
In the evening, take two 100 milligram INTELENCE tablets, following a meal.

Use in children and adolescents 2 years of age and older and weighing at least 10 kg
The doctor will work out the right dose based on the weight of the child.
The doctor will inform you exactly how much INTELENCE the child should take.

Instructions for taking INTELENCE for all patients
It is important that you take INTELENCE following a meal. If you take INTELENCE on an empty 
stomach, only half the amount of INTELENCE is absorbed. Follow your doctor’s advice on the type 
of meal you should be taking with INTELENCE.

Swallow the INTELENCE tablet(s) whole with a glass of water. Do not chew the tablet(s). The tablet 
can be divided into two equal doses.

If you are unable to swallow the INTELENCE tablet(s) whole, you may do the following:
- place the tablet(s) in 5 ml (1 teaspoon) of water, or at least enough liquid to cover the

medicine,
- stir well for about 1 minute until the water looks milky,
- if desired, add up to 30 ml (2 tablespoons) more of water or alternatively orange juice or 

milk (do not place the tablets directly in orange juice or milk),
- drink it immediately,
- rinse the glass several times with water, orange juice, or milk and completely swallow the 

rinse each time to make sure you take the entire dose.

If you mix INTELENCE tablet(s) with a liquid, take this first, before other liquid anti-HIV medicines 
that you need to take at the same time.

Contact your doctor if you are not able to swallow the entire dose when mixed with a liquid.

If your child needs to take INTELENCE tablet(s) mixed with a liquid, it is very important that he/she
takes the entire dose so that the right amount of medicine enters into the body. If the full dose is not
taken, the risk of the virus developing resistance is higher. Contact your doctor if your child is not able 
to swallow the entire dose when mixed with a liquid, as they may consider giving another medicine to 
treat your child.

Do not use warm (40°C and above) or carbonated beverages when taking INTELENCE tablet(s).

Removing the child resistant cap

The plastic bottle comes with a child resistant cap and should be opened as
follows:
- Push the plastic screw cap down while turning it counter clockwise.
- Remove the unscrewed cap.

If you take more INTELENCE than you should
Contact your doctor or pharmacist immediately. The most frequent side effects of INTELENCE are
rash, diarrhoea, nausea, and headache (see section ‘4. Possible side effects’).



50

If you forget to take INTELENCE
If you notice within 6 hours of the time you usually take INTELENCE, you must take the tablet(s)
as soon as possible. Always take the tablet(s) following a meal. Then take the next dose as usual. If 
you notice after 6 hours, then skip the intake and take the next doses as usual. Do not take a double 
dose to make up for a forgotten dose.

If you vomit less than 4 hours after taking INTELENCE, take another dose following a meal. If you 
vomit more than 4 hours after taking INTELENCE, then you do not need to take another dose until 
your regularly scheduled dose.

Contact your doctor if you are uncertain about what to do if you miss a dose or vomit.

Do not stop taking INTELENCE without talking to your doctor first
HIV therapy may increase your sense of well-being. Even if you feel better, do not stop taking 
INTELENCE or your other anti-HIV medicines. Doing so could increase the risk of the virus
developing resistance. Talk to your doctor first.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The frequency rate of the side effects associated with INTELENCE is given below.

Very common side effects (may affect more than 1 in 10 people)
- skin rash. The rash is usually mild to moderate. In rare instances, very serious rash has been 

reported which can be potentially life-threatening. It is therefore important to contact your 
doctor immediately if you develop a rash. Your doctor will advise you how to deal with your 
symptoms and whether INTELENCE must be stopped;

- headache;
- diarrhoea, nausea.

Common side effects (may affect up to 1 in 10 people)
- allergic reactions (hypersensitivity);
- diabetes, decrease of appetite;
- anxiety, sleepiness, sleeplessness, sleep disorders;
- tingling or pain in hands or feet, numbness, loss of skin sensibility, loss of memory tiredness;
- blurred vision;
- kidney failure, high blood pressure, heart attack, shortness of breath when exercising;
- vomiting, heartburn, abdominal pain, distension of the abdomen, inflammation of the stomach,

flatulence, constipation, mouth inflammation, dry mouth;
- night sweats, itching, dry skin;
- Change in some values of your blood cells or chemistry. These can be seen in the results of 

blood and/or urine tests. Your doctor will explain these to you. Examples are: low red blood 
cells.

Uncommon side effects (may affect up to 1 in 100 people)
- decreased number of white blood cells;
- symptoms of infection (for example enlarged lymph nodes and fever);
- abnormal dreams, confusion, disorientation, nervousness, nightmares;
- drowsiness, trembling, fainting, seizures, disturbance in attention;
- dizziness, sluggishness;
- angina, irregular heart rhythm;
- difficulty breathing;
- retching, inflammation of the pancreas, vomiting blood;



51

- liver problems such as hepatitis, enlarged liver;
- excessive sweating, swelling of the face and/or throat;
- swelling of breasts in men.

Rare side effects (may affect up to 1 in 1,000 people)
- stroke;
- severe skin rash with blisters or peeling skin, particularly around the mouth or eyes; this may 

occur in children and adolescents more frequently than in adults.

Very rare side effects (may affect up to 1 in 10,000 people)
- severe hypersensitivity reactions characterised by rash accompanied by fever and organ 

inflammation such as hepatitis.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine.

5. How to store INTELENCE

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the bottle after 
EXP. The expiry date refers to the last day of that month.

Do not use after 8 weeks of first opening the bottle.

INTELENCE tablets should be stored in the original bottle and keep the bottle tightly closed in order 
to protect from moisture. The bottle contains 2 little pouches (desiccants) to keep the tablets dry. 
These pouches should stay in the bottle all the time and are not to be eaten.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What INTELENCE contains
- The active substance is etravirine. Each tablet of INTELENCE contains 25 mg of etravirine.
- The other ingredients are hypromellose, microcrystalline cellulose, colloidal anhydrous silica, 

croscarmellose sodium, magnesium stearate and lactose (as monohydrate).

What INTELENCE looks like and contents of the pack
This medicinal product is presented as white to off-white, oval, scored tablet, with “TMC” on one 
side. The tablet can be divided into two equal doses.
A plastic bottle containing 120 tablets and 2 pouches to keep the tablets dry.

Marketing Authorisation Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

Manufacturer
Janssen-Cilag SpA, Via C. Janssen, 04100 Borgo San Michele, Latina, Italy

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


52

België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: +32 14 64 94 11
janssen@jacbe.jnj.com

Lietuva
UAB "JOHNSON & JOHNSON"
Tel: +370 5 278 68 88
lt@its.jnj.com 

България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00
jjsafety@its.jnj.com

Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: +32 14 64 94 11
janssen@jacbe.jnj.com

Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227

Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858
janssenhu@its.jnj.com

Danmark
Janssen-Cilag A/S
Tlf: +45 4594 8282
jacdk@its.jnj.com

Malta
AM MANGION LTD.
Tel: +356 2397 6000

Deutschland
Janssen-Cilag GmbH
Tel: +49 2137 955 955
jancil@its.jnj.com

Nederland
Janssen-Cilag B.V.
Tel: +31 76 711 1111
janssen@jacnl.jnj.com

Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
Tel: +372 617 7410
ee@its.jnj.com

Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00
jacno@its.jnj.com

Ελλάδα
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00
contacto@its.jnj.com

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00

France
Janssen-Cilag
Tél: 0 800 25 50 75 / +33 1 55 00 40 03
medisource@its.jnj.com

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600

Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700
jjsafety@JNJCR.JNJ.com

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Ireland
Janssen Sciences Ireland UC
Tel: +353 1 800 709 122

Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
Janssen_safety_slo@its.jnj.com



53

Ísland
Janssen-Cilag AB
c/o Vistor hf.
Sími: +354 535 7000
janssen@vistor.is

Slovenská republika
Johnson & Johnson s.r.o.
Tel: +421 232 408 400

Italia
Janssen-Cilag SpA
Tel: 800.688.777 / +39 02 2510 1
janssenita@its.jnj.com

Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300
jacfi@its.jnj.com

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Sverige
Janssen-Cilag AB
Tfn: +46 8 626 50 00
jacse@its.jnj.com

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
lv@its.jnj.com

United Kingdom
Janssen-Cilag Ltd.
Tel: +44 1 494 567 444

This leaflet was last revised in {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/.

http://www.ema.europa.eu/


54

Package leaflet: Information for the user

INTELENCE 100 mg tablets
etravirine

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet
1. What INTELENCE is and what it is used for
2. What you need to know before you take INTELENCE
3. How to take INTELENCE
4. Possible side effects
5. How to store INTELENCE
6. Contents of the pack and other information

1. What INTELENCE is and what it is used for

INTELENCE contains the active substance etravirine. INTELENCE belongs to a group of anti-HIV 
medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs).

INTELENCE is a medicine used for the treatment of Human Immunodeficiency Virus (HIV) 
infection. INTELENCE works by reducing the amount of HIV in your body. This will improve your 
immune system and reduces the risk of developing illnesses linked to HIV infection.

INTELENCE is used in combination with other anti-HIV medicines to treat adults and children 
2 years of age and older who are infected by HIV and who have used other anti-HIV medicines before.

Your doctor will discuss with you which combination of medicines is best for you.

2. What you need to know before you take INTELENCE

Do not take INTELENCE
- if you are allergic to etravirine or any of the other ingredients of this medicine (listed in 

section 6)
- if you are taking elbasvir/grazoprevir (a medicine to treat hepatitis C infection).

Warnings and precautions
Talk to your doctor or pharmacist before taking INTELENCE.

INTELENCE is not a cure for HIV infection. It is part of a treatment reducing the amount of virus in 
the blood. You can still pass on HIV when taking this medicine, although the risk is lowered by 
effective antiretroviral therapy. Discuss with your physician the precautions needed to avoid infecting 
other people.

Elderly
INTELENCE has only been used in a limited number of patients of 65 years or older. If you belong to 
this age group, please discuss the use of INTELENCE with your doctor.



55

Weight and increased blood lipids and glucose
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves. Your doctor will test for these changes.

Bone problems
Some patients taking combination antiretroviral therapy may develop a bone disease called 
osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of 
combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe 
immunosuppression, higher body mass index, among others, may be some of the many risk factors for 
developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the 
hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please 
inform your doctor.

Tell your doctor about your situation
Make sure that you check the following points and tell your doctor if any of these apply to you.
- Tell your doctor if you develop a rash. If a rash occurs, it usually appears soon after anti-HIV 

treatment with INTELENCE is started and often disappears within 1 to 2 weeks, even with 
continued use of the medicine. Rarely, during INTELENCE treatment, you can experience 
severe skin rash with blisters or peeling skin, particularly around the mouth or eyes or 
hypersensitivity reaction (allergic reaction including rash and fever but also swelling of the face, 
tongue or throat, difficulty in breathing or swallowing) which could be potentially 
life-threatening. Please contact your doctor immediately if you experience these symptoms. 
Your doctor will advise you how to deal with your symptoms and whether INTELENCE must 
be stopped. If you have stopped treatment due to a hypersensitivity reaction, you should not 
restart therapy with INTELENCE.

- Tell your doctor if you have or have had problems with your liver, including hepatitis B and/or 
C. Your doctor may evaluate how severe your liver disease is before deciding if you can take 
INTELENCE.

- Tell your doctor immediately if you notice any symptoms of infections. In some patients with 
advanced HIV infection and a history of opportunistic infection, signs and symptoms of 
inflammation from previous infections may occur soon after anti-HIV treatment is started. It is 
believed that these symptoms are due to an improvement in the body’s immune response, 
enabling the body to fight infections that may have been present with no obvious symptoms.

- In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when 
the immune system attacks healthy body tissue) may also occur after you start taking medicines 
for the treatment of your HIV infection. Autoimmune disorders may occur many months after 
the start of treatment. If you notice any symptoms of infection or other symptoms such as 
muscle weakness, weakness beginning in the hands and feet and moving up towards the trunk of 
the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek 
necessary treatment.

Children and adolescents
Do not give this medicine to children less than 2 years of age and weighing less than 10 kg because the 
potential benefits and risks have not been established.

Other medicines and INTELENCE
INTELENCE might interact with other medicines. Tell your doctor or pharmacist if you are taking,
have recently taken, or might take any other medicines.

In most cases, INTELENCE can be combined with anti-HIV medicines belonging to another class.
However, some combinations are not recommended. In other cases, increased monitoring and/or a 
change in the dose of the medicine may be needed. Therefore, always tell your doctor which other 
anti-HIV medicines you take. Furthermore, it is important that you carefully read the package leaflets 
that are provided with these medicines. Follow your doctor’s instruction carefully on which medicines 
can be combined.



56

It is not recommended to combine INTELENCE with any of the following medicines:
- tipranavir/ritonavir, efavirenz, nevirapine, rilpivirine, indinavir, atazanavir/cobicistat, 

darunavir/cobicistat (anti-HIV medicine)
- carbamazepine, phenobarbital, phenytoin (medicines to prevent seizures)
- rifampicin, because it is contraindicated with boosted protease inhibitors, and rifapentine 

(medicines to treat some infections such as tuberculosis)
- products that contain St John’s wort (Hypericum perforatum) (a herbal product used for 

depression)
- daclatasvir (a medicine to treat hepatitis C infection).

If you are taking any of these, ask your doctor for advice.

The effects of INTELENCE or other medicines might be influenced if you take INTELENCE 
together with any of the following medicines. The dosages of some medicines might need to be 
changed since their therapeutic effect or side effects may be influenced when combined with 
INTELENCE. Tell your doctor if you take:
- dolutegravir, maraviroc, amprevanir/ritonavir and fosamprenavir/ritonavir (anti-HIV medicine)
- amiodarone, bepridil, digoxin, disopyramide, flecainide, lidocaine, mexiletine, propafenone and 

quinidine (medicines to treat certain heart disorders, e.g., abnormal heart beat)
- warfarin (a medicine used to reduce clotting of the blood). Your doctor will have to check your 

blood
- fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole (medicines to treat fungal 

infections)
- clarithromycin, rifabutin (antibiotics)
- artemether/lumefantrine (a medicine to treat malaria)
- diazepam (medicines to treat trouble with sleeping and/or anxiety)
- dexamethasone (a corticosteroid used in a variety of conditions such as inflammation and 

allergic reactions)
- atorvastatin, fluvastatin, lovastatin, rosuvastatin, simvastatin (cholesterol-lowering medicines)
- cyclosporine, sirolimus, tacrolimus (immunosuppressants – medicines used to dampen down 

your immune system)
- sildenafil, vardenafil, tadalafil (medicines to treat erectile dysfunction and/or pulmonary arterial

hypertension)
- clopidogrel (a medicine to prevent blood clots).

Pregnancy and breast-feeding
Tell your doctor immediately if you are pregnant. Pregnant women should not take INTELENCE 
unless specifically directed by the doctor.
HIV infected mothers must not breast-feed, as there is a possibility of infecting the baby with HIV.

Driving and using machines
Do not drive or operate machines if you feel sleepy or dizzy after taking your medicines.

INTELENCE contains lactose
INTELENCE tablets contain lactose. If you have been told by your doctor that you have an 
intolerance to some sugars (lactose), contact your doctor before taking this medicine.

INTELENCE contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium 
free’.

3. How to take INTELENCE

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.



57

Use in adults
The recommended dose of INTELENCE is two tablets twice a day.
In the morning, take two 100 milligram INTELENCE tablets, following a meal.
In the evening, take two 100 milligram INTELENCE tablets, following a meal.

Use in children and adolescents 2 years of age and older and weighing at least 10 kg
The doctor will work out the right dose based on the weight of the child.
The doctor will inform you exactly how much INTELENCE the child should take.

Instructions for taking INTELENCE for all patients
It is important that you take INTELENCE following a meal. If you take INTELENCE on an empty 
stomach, only half the amount of INTELENCE is absorbed. Follow your doctor’s advice on the type 
of meal you should be taking with INTELENCE.

Swallow the INTELENCE tablet(s) whole with a glass of water. Do not chew the tablet(s).

If you are unable to swallow the INTELENCE tablet(s) whole, you may do the following:
- place the tablet(s) in 5 ml (1 teaspoon) of water, or at least enough liquid to cover the 

medicine,
- stir well for about 1 minute until the water looks milky,
- if desired, add up to 30 ml (2 tablespoons) more of water or alternatively orange juice or 

milk (do not place the tablets directly in orange juice or milk),
- drink it immediately,
- rinse the glass several times with water, orange juice, or milk and completely swallow the 

rinse each time to make sure you take the entire dose.

If you mix INTELENCE tablet(s) with a liquid, take this first, before other liquid anti-HIV medicines 
that you need to take at the same time.

Contact your doctor if you are not able to swallow the entire dose when mixed with a liquid.

If your child needs to take INTELENCE tablet(s) mixed with a liquid, it is very important that he/she
takes the entire dose so that the right amount of medicine enters into the body. If the full dose is not
taken, the risk of the virus developing resistance is higher. Contact your doctor if your child is not able 
to swallow the entire dose when mixed with a liquid, as they may consider giving another medicine to 
treat your child.

Do not use warm (40°C and above) or carbonated beverages when taking INTELENCE tablet(s).

Removing the child resistant cap

The plastic bottle comes with a child resistant cap and should be opened as 
follows:
- Push the plastic screw cap down while turning it counter clockwise.
- Remove the unscrewed cap.

If you take more INTELENCE than you should
Contact your doctor or pharmacist immediately. The most frequent side effects of INTELENCE are 
rash, diarrhoea, nausea, and headache (see section ‘4. Possible side effects’).

If you forget to take INTELENCE
If you notice within 6 hours of the time you usually take INTELENCE, you must take the tablet(s)
as soon as possible. Always take the tablet(s) following a meal. Then take the next dose as usual. If 
you notice after 6 hours, then skip the intake and take the next doses as usual. Do not take a double 
dose to make up for a forgotten dose.



58

If you vomit less than 4 hours after taking INTELENCE, take another dose following a meal. If you 
vomit more than 4 hours after taking INTELENCE, then you do not need to take another dose until 
your regularly scheduled dose.

Contact your doctor if you are uncertain about what to do if you miss a dose or vomit.

Do not stop taking INTELENCE without talking to your doctor first
HIV therapy may increase your sense of well-being. Even if you feel better, do not stop taking 
INTELENCE or your other anti-HIV medicines. Doing so could increase the risk of the virus 
developing resistance. Talk to your doctor first.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The frequency rate of the side effects associated with INTELENCE is given below.

Very common side effects (may affect more than 1 in 10 people)
- skin rash. The rash is usually mild to moderate. In rare instances, very serious rash has been 

reported which can be potentially life-threatening. It is therefore important to contact your 
doctor immediately if you develop a rash. Your doctor will advise you how to deal with your 
symptoms and whether INTELENCE must be stopped;

- headache;
- diarrhoea, nausea.

Common side effects (may affect up to 1 in 10 people)
- allergic reactions (hypersensitivity);
- diabetes, decrease of appetite;
- anxiety, sleepiness, sleeplessness, sleep disorders;
- tingling or pain in hands or feet, numbness, loss of skin sensibility, loss of memory tiredness;
- blurred vision;
- kidney failure, high blood pressure, heart attack, shortness of breath when exercising;
- vomiting, heartburn, abdominal pain, distension of the abdomen, inflammation of the stomach, 

flatulence, constipation, mouth inflammation, dry mouth;
- night sweats, itching, dry skin;
- Change in some values of your blood cells or chemistry. These can be seen in the results of 

blood and/or urine tests. Your doctor will explain these to you. Examples are: low red blood 
cells.

Uncommon side effects (may affect up to 1 in 100 people)
- decreased number of white blood cells;
- symptoms of infection (for example enlarged lymph nodes and fever);
- abnormal dreams, confusion, disorientation, nervousness, nightmares;
- drowsiness, trembling, fainting, seizures, disturbance in attention;
- dizziness, sluggishness;
- angina, irregular heart rhythm;
- difficulty breathing;
- retching, inflammation of the pancreas, vomiting blood;
- liver problems such as hepatitis, enlarged liver;
- excessive sweating, swelling of the face and/or throat;
- swelling of breasts in men.

Rare side effects (may affect up to 1 in 1,000 people)
- stroke;



59

- severe skin rash with blisters or peeling skin, particularly around the mouth or eyes; this may 
occur in children and adolescents more frequently than in adults.

Very rare side effects (may affect up to 1 in 10,000 people)
- severe hypersensitivity reactions characterised by rash accompanied by fever and organ 

inflammation such as hepatitis.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine.

5. How to store INTELENCE

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the bottle after 
EXP. The expiry date refers to the last day of that month.

INTELENCE tablets should be stored in the original bottle and keep the bottle tightly closed in order 
to protect from moisture. The bottle contains 3 little pouches (desiccants) to keep the tablets dry. 
These pouches should stay in the bottle all the time and are not to be eaten.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What INTELENCE contains
- The active substance is etravirine. Each tablet of INTELENCE contains 100 mg of etravirine.
- The other ingredients are hypromellose, microcrystalline cellulose, colloidal anhydrous silica, 

croscarmellose sodium, magnesium stearate and lactose (as monohydrate).

What INTELENCE looks like and contents of the pack
This medicinal product is presented as white to off-white, oval tablet, with “T125” on one side and 
“100” on the other side.
A plastic bottle containing 120 tablets and 3 pouches to keep the tablets dry.

Marketing Authorisation Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

Manufacturer
Janssen-Cilag SpA, Via C. Janssen, 04100 Borgo San Michele, Latina, Italy

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: +32 14 64 94 11
janssen@jacbe.jnj.com

Lietuva
UAB "JOHNSON & JOHNSON"
Tel: +370 5 278 68 88
lt@its.jnj.com

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


60

България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00
jjsafety@its.jnj.com

Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: +32 14 64 94 11
janssen@jacbe.jnj.com

Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227

Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858
janssenhu@its.jnj.com

Danmark
Janssen-Cilag A/S
Tlf: +45 4594 8282
jacdk@its.jnj.com

Malta
AM MANGION LTD.
Tel: +356 2397 6000

Deutschland
Janssen-Cilag GmbH
Tel: +49 2137 955 955
jancil@its.jnj.com

Nederland
Janssen-Cilag B.V.
Tel: +31 76 711 1111
janssen@jacnl.jnj.com

Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
Tel: +372 617 7410
ee@its.jnj.com

Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00
jacno@its.jnj.com

Ελλάδα
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00
contacto@its.jnj.com

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00

France
Janssen-Cilag
Tél: 0 800 25 50 75 / +33 1 55 00 40 03
medisource@its.jnj.com

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600

Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700
jjsafety@JNJCR.JNJ.com

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Ireland
Janssen Sciences Ireland UC
Tel: +353 1 800 709 122

Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
Janssen_safety_slo@its.jnj.com

Ísland
Janssen-Cilag AB
c/o Vistor hf.
Sími: +354 535 7000
janssen@vistor.is

Slovenská republika
Johnson & Johnson s.r.o.
Tel: +421 232 408 400



61

Italia
Janssen-Cilag SpA
Tel: 800.688.777 / +39 02 2510 1
janssenita@its.jnj.com

Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300
jacfi@its.jnj.com

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Sverige
Janssen-Cilag AB
Tfn: +46 8 626 50 00
jacse@its.jnj.com

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
lv@its.jnj.com

United Kingdom
Janssen-Cilag Ltd.
Tel: +44 1 494 567 444

This leaflet was last revised in {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/.

http://www.ema.europa.eu/


62

Package leaflet: Information for the user

INTELENCE 200 mg tablets
etravirine

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet
1. What INTELENCE is and what it is used for
2. What you need to know before you take INTELENCE
3. How to take INTELENCE
4. Possible side effects
5. How to store INTELENCE
6. Contents of the pack and other information

1. What INTELENCE is and what it is used for

INTELENCE contains the active substance etravirine. INTELENCE belongs to a group of anti-HIV 
medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs).

INTELENCE is a medicine used for the treatment of Human Immunodeficiency Virus (HIV) 
infection. INTELENCE works by reducing the amount of HIV in your body. This will improve your 
immune system and reduces the risk of developing illnesses linked to HIV infection.

INTELENCE is used in combination with other anti-HIV medicines to treat adults and children 
2 years of age and older who are infected by HIV and who have used other anti-HIV medicines before.

Your doctor will discuss with you which combination of medicines is best for you.

2. What you need to know before you take INTELENCE

Do not take INTELENCE
- if you are allergic to etravirine or any of the other ingredients of this medicine (listed in 

section 6)
- if you are taking elbasvir/grazoprevir (a medicine to treat hepatitis C infection).

Warnings and precautions
Talk to your doctor or pharmacist before taking INTELENCE.

INTELENCE is not a cure for HIV infection. It is part of a treatment reducing the amount of virus in 
the blood. You can still pass on HIV when taking this medicine, although the risk is lowered by 
effective antiretroviral therapy. Discuss with your physician the precautions needed to avoid infecting 
other people.

Elderly
INTELENCE has only been used in a limited number of patients of 65 years or older. If you belong to 
this age group, please discuss the use of INTELENCE with your doctor.



63

Weight and increased blood lipids and glucose
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves. Your doctor will test for these changes.

Bone problems
Some patients taking combination antiretroviral therapy may develop a bone disease called 
osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of 
combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe 
immunosuppression, higher body mass index, among others, may be some of the many risk factors for 
developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the 
hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please 
inform your doctor.

Tell your doctor about your situation
Make sure that you check the following points and tell your doctor if any of these apply to you.
- Tell your doctor if you develop a rash. If a rash occurs, it usually appears soon after anti-HIV 

treatment with INTELENCE is started and often disappears within 1 to 2 weeks, even with 
continued use of the medicine. Rarely, during INTELENCE treatment, you can experience 
severe skin rash with blisters or peeling skin, particularly around the mouth or eyes or
hypersensitivity reaction (allergic reaction including rash and fever but also swelling of the face, 
tongue or throat, difficulty in breathing or swallowing) which could be potentially 
life-threatening. Please contact your doctor immediately if you experience these symptoms. 
Your doctor will advise you how to deal with your symptoms and whether INTELENCE must 
be stopped. If you have stopped treatment due to a hypersensitivity reaction, you should not 
restart therapy with INTELENCE.

- Tell your doctor if you have or have had problems with your liver, including hepatitis B and/or 
C. Your doctor may evaluate how severe your liver disease is before deciding if you can take 
INTELENCE.

- Tell your doctor immediately if you notice any symptoms of infections. In some patients with 
advanced HIV infection and a history of opportunistic infection, signs and symptoms of 
inflammation from previous infections may occur soon after anti-HIV treatment is started. It is 
believed that these symptoms are due to an improvement in the body’s immune response, 
enabling the body to fight infections that may have been present with no obvious symptoms.

- In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when 
the immune system attacks healthy body tissue) may also occur after you start taking medicines 
for the treatment of your HIV infection. Autoimmune disorders may occur many months after 
the start of treatment. If you notice any symptoms of infection or other symptoms such as 
muscle weakness, weakness beginning in the hands and feet and moving up towards the trunk of 
the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek 
necessary treatment.

Children and adolescents
Do not give this medicine to children less than 2 years of age and weighing less than 10 kg because the 
potential benefits and risks have not been established.

Other medicines and INTELENCE
INTELENCE might interact with other medicines. Tell your doctor or pharmacist if you are taking,
have recently taken, or might take any other medicines.

In most cases, INTELENCE can be combined with anti-HIV medicines belonging to another class.
However, some combinations are not recommended. In other cases, increased monitoring and/or a 
change in the dose of the medicine may be needed. Therefore, always tell your doctor which other 
anti-HIV medicines you take. Furthermore, it is important that you carefully read the package leaflets 
that are provided with these medicines. Follow your doctor’s instruction carefully on which medicines 
can be combined.



64

It is not recommended to combine INTELENCE with any of the following medicines:
- tipranavir/ritonavir, efavirenz, nevirapine, rilpivirine, indinavir, atazanavir/cobicistat, 

darunavir/cobicistat (anti-HIV medicine)
- carbamazepine, phenobarbital, phenytoin (medicines to prevent seizures)
- rifampicin, because it is contraindicated with boosted protease inhibitors, and rifapentine 

(medicines to treat some infections such as tuberculosis)
- products that contain St John’s wort (Hypericum perforatum) (a herbal product used for 

depression)
- daclatasvir (a medicine to treat hepatitis C infection).

If you are taking any of these, ask your doctor for advice.

The effects of INTELENCE or other medicines might be influenced if you take INTELENCE 
together with any of the following medicines. The dosages of some medicines might need to be 
changed since their therapeutic effect or side effects may be influenced when combined with 
INTELENCE. Tell your doctor if you take:
- dolutegravir, maraviroc, amprevanir/ritonavir and fosamprenavir/ritonavir (anti-HIV medicine)
- amiodarone, bepridil, digoxin, disopyramide, flecainide, lidocaine, mexiletine, propafenone and 

quinidine (medicines to treat certain heart disorders, e.g., abnormal heart beat)
- warfarin (a medicine used to reduce clotting of the blood). Your doctor will have to check your 

blood
- fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole (medicines to treat fungal 

infections)
- clarithromycin, rifabutin (antibiotics)
- artemether/lumefantrine (a medicine to treat malaria)
- diazepam (medicines to treat trouble with sleeping and/or anxiety)
- dexamethasone (a corticosteroid used in a variety of conditions such as inflammation and 

allergic reactions)
- atorvastatin, fluvastatin, lovastatin, rosuvastatin, simvastatin (cholesterol-lowering medicines)
- cyclosporine, sirolimus, tacrolimus (immunosuppressants – medicines used to dampen down 

your immune system)
- sildenafil, vardenafil, tadalafil (medicines to treat erectile dysfunction and/or pulmonary arterial 

hypertension)
- clopidogrel (a medicine to prevent blood clots).

Pregnancy and breast-feeding
Tell your doctor immediately if you are pregnant. Pregnant women should not take INTELENCE 
unless specifically directed by the doctor.
HIV infected mothers must not breast-feed, as there is a possibility of infecting the baby with HIV.

Driving and using machines
Do not drive or operate machines if you feel sleepy or dizzy after taking your medicines.

INTELENCE contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium 
free’.

3. How to take INTELENCE

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

Use in adults
The recommended dose of INTELENCE is one tablet twice a day.
In the morning, take one 200 milligram INTELENCE tablet, following a meal.
In the evening, take one 200 milligram INTELENCE tablet, following a meal.



65

Use in children and adolescents 2 years of age and older and weighing at least 10 kg
The doctor will work out the right dose based on the weight of the child.
The doctor will inform you exactly how much INTELENCE the child should take.

Instructions for taking INTELENCE for all patients
It is important that you take INTELENCE following a meal. If you take INTELENCE on an empty 
stomach, only half the amount of INTELENCE is absorbed. Follow your doctor’s advice on the type 
of meal you should be taking with INTELENCE.

Swallow the INTELENCE tablet(s) whole with a glass of water. Do not chew the tablet(s).

If you are unable to swallow the INTELENCE tablet(s) whole, you may do the following:
- place the tablet(s) in 5 ml (1 teaspoon) of water, or at least enough liquid to cover the 

medicine,
- stir well for about 1 minute until the water looks milky,
- if desired, add up to 30 ml (2 tablespoons) more of water or alternatively orange juice or 

milk (do not place the tablets directly in orange juice or milk),
- drink it immediately,
- rinse the glass several times with water, orange juice, or milk and completely swallow the 

rinse each time to make sure you take the entire dose.

If you mix INTELENCE tablet(s) with a liquid, take this first, before other liquid anti-HIV medicines 
that you need to take at the same time.

Contact your doctor if you are not able to swallow the entire dose when mixed with a liquid.

If your child needs to take INTELENCE tablet(s) mixed with a liquid, it is very important that he/she
takes the entire dose so that the right amount of medicine enters into the body. If the full dose is not
taken, the risk of the virus developing resistance is higher. Contact your doctor if your child is not able 
to swallow the entire dose when mixed with a liquid, as they may consider giving another medicine to 
treat your child.

Do not use warm (40°C and above) or carbonated beverages when taking INTELENCE tablet(s).

Removing the child resistant cap

The plastic bottle comes with a child resistant cap and should be opened as 
follows:
- Push the plastic screw cap down while turning it counter clockwise.
- Remove the unscrewed cap.

If you take more INTELENCE than you should
Contact your doctor or pharmacist immediately. The most frequent side effects of INTELENCE are 
rash, diarrhoea, nausea, and headache (see section ‘4. Possible side effects’).

If you forget to take INTELENCE
If you notice within 6 hours of the time you usually take INTELENCE, you must take the tablet as 
soon as possible. Always take the tablet following a meal. Then take the next dose as usual. If you 
notice after 6 hours, then skip the intake and take the next doses as usual. Do not take a double dose 
to make up for a forgotten dose.

If you vomit less than 4 hours after taking INTELENCE, take another dose following a meal. If you 
vomit more than 4 hours after taking INTELENCE, then you do not need to take another dose until 
your regularly scheduled dose.



66

Contact your doctor if you are uncertain about what to do if you miss a dose or vomit.

Do not stop taking INTELENCE without talking to your doctor first
HIV therapy may increase your sense of well-being. Even if you feel better, do not stop taking 
INTELENCE or your other anti-HIV medicines. Doing so could increase the risk of the virus 
developing resistance. Talk to your doctor first.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The frequency rate of the side effects associated with INTELENCE is given below.

Very common side effects (may affect more than 1 in 10 people)
- skin rash. The rash is usually mild to moderate. In rare instances, very serious rash has been 

reported which can be potentially life-threatening. It is therefore important to contact your 
doctor immediately if you develop a rash. Your doctor will advise you how to deal with your 
symptoms and whether INTELENCE must be stopped;

- headache;
- diarrhoea, nausea.

Common side effects (may affect up to 1 in 10 people)
- allergic reactions (hypersensitivity);
- diabetes, decrease of appetite;
- anxiety, sleepiness, sleeplessness, sleep disorders;
- tingling or pain in hands or feet, numbness, loss of skin sensibility, loss of memory tiredness;
- blurred vision;
- kidney failure, high blood pressure, heart attack, shortness of breath when exercising;
- vomiting, heartburn, abdominal pain, distension of the abdomen, inflammation of the stomach, 

flatulence, constipation, mouth inflammation, dry mouth;
- night sweats, itching, dry skin;
- Change in some values of your blood cells or chemistry. These can be seen in the results of 

blood and/or urine tests. Your doctor will explain these to you. Examples are: low red blood 
cells.

Uncommon side effects (may affect up to 1 in 100 people)
- decreased number of white blood cells;
- symptoms of infection (for example enlarged lymph nodes and fever);
- abnormal dreams, confusion, disorientation, nervousness, nightmares;
- drowsiness, trembling, fainting, seizures, disturbance in attention;
- dizziness, sluggishness;
- angina, irregular heart rhythm;
- difficulty breathing;
- retching, inflammation of the pancreas, vomiting blood;
- liver problems such as hepatitis, enlarged liver;
- excessive sweating, swelling of the face and/or throat;
- swelling of breasts in men.

Rare side effects (may affect up to 1 in 1,000 people)
- stroke;
- severe skin rash with blisters or peeling skin, particularly around the mouth or eyes; this may 

occur in children and adolescents more frequently than in adults.



67

Very rare side effects (may affect up to 1 in 10,000 people)
- severe hypersensitivity reactions characterised by rash accompanied by fever and organ 

inflammation such as hepatitis.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine.

5. How to store INTELENCE

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the bottle after 
EXP. The expiry date refers to the last day of that month.

Do not use after 6 weeks of first opening the bottle.

INTELENCE tablets should be stored in the original bottle and keep the bottle tightly closed in order 
to protect from moisture. The bottle contains 3 little pouches (desiccants) to keep the tablets dry. 
These pouches should stay in the bottle all the time and are not to be eaten.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What INTELENCE contains
- The active substance is etravirine. Each tablet of INTELENCE contains 200 mg of etravirine.
- The other ingredients are hypromellose, silicified microcrystalline cellulose, microcrystalline 

cellulose, colloidal anhydrous silica, croscarmellose sodium and magnesium stearate.

What INTELENCE looks like and contents of the pack
This medicinal product is presented as white to off-white, biconvex, oblong tablet with “T200” on one
side.
A plastic bottle containing 60 tablets and 3 pouches to keep the tablets dry.

Marketing Authorisation Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

Manufacturer
Janssen-Cilag SpA, Via C. Janssen, 04100 Borgo San Michele, Latina, Italy

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: +32 14 64 94 11
janssen@jacbe.jnj.com

Lietuva
UAB "JOHNSON & JOHNSON"
Tel: +370 5 278 68 88
lt@its.jnj.com

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


68

България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00
jjsafety@its.jnj.com

Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: +32 14 64 94 11
janssen@jacbe.jnj.com

Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227

Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858
janssenhu@its.jnj.com

Danmark
Janssen-Cilag A/S
Tlf: +45 4594 8282
jacdk@its.jnj.com

Malta
AM MANGION LTD.
Tel: +356 2397 6000

Deutschland
Janssen-Cilag GmbH
Tel: +49 2137 955 955
jancil@its.jnj.com

Nederland
Janssen-Cilag B.V.
Tel: +31 76 711 1111
janssen@jacnl.jnj.com

Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
Tel: +372 617 7410
ee@its.jnj.com

Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00
jacno@its.jnj.com

Ελλάδα
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00
contacto@its.jnj.com

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00

France
Janssen-Cilag
Tél: 0 800 25 50 75 / +33 1 55 00 40 03
medisource@its.jnj.com

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600

Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700
jjsafety@JNJCR.JNJ.com

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Ireland
Janssen Sciences Ireland UC
Tel: +353 1 800 709 122

Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
Janssen_safety_slo@its.jnj.com

Ísland
Janssen-Cilag AB
c/o Vistor hf.
Sími: +354 535 7000
janssen@vistor.is

Slovenská republika
Johnson & Johnson s.r.o.
Tel: +421 232 408 400



69

Italia
Janssen-Cilag SpA
Tel: 800.688.777 / +39 02 2510 1
janssenita@its.jnj.com

Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300
jacfi@its.jnj.com

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Sverige
Janssen-Cilag AB
Tfn: +46 8 626 50 00
jacse@its.jnj.com

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
lv@its.jnj.com 

United Kingdom
Janssen-Cilag Ltd.
Tel: +44 1 494 567 444

This leaflet was last revised in {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/.

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET