INTELENCE

What Is INTELENCE and What Is It Used For?

INTELENCE (etravirine) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination with other antiretroviral medicines to treat HIV-1 infection. It is specifically indicated for treatment-experienced adults and children aged 2 years and older who weigh at least 10 kg, particularly those whose virus has developed resistance to other HIV medications.

INTELENCE contains the active substance etravirine, which belongs to a group of HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). These medications work by directly binding to and blocking the activity of reverse transcriptase, an enzyme that HIV needs to replicate its genetic material. Without functional reverse transcriptase, the virus cannot make copies of itself, which reduces the amount of HIV in the blood (viral load) and allows the immune system to recover.

What distinguishes INTELENCE from first-generation NNRTIs such as efavirenz and nevirapine is its flexible binding mode. HIV frequently develops mutations in the reverse transcriptase enzyme that prevent first-generation NNRTIs from binding effectively, leading to drug resistance. Etravirine was specifically engineered with a flexible molecular structure that allows it to reposition itself within the binding pocket of the enzyme, maintaining its inhibitory activity even in the presence of many common NNRTI resistance mutations. This property is known as conformational flexibility and represents a significant advancement in HIV treatment.

INTELENCE is never used alone. It must always be taken in combination with other antiretroviral medicines as part of a regimen known as combination antiretroviral therapy (cART) or highly active antiretroviral therapy (HAART). Your doctor will determine the most appropriate combination based on your treatment history, resistance test results, and overall health status. The goal of treatment is to achieve and maintain an undetectable viral load, which preserves immune function and prevents progression to AIDS.

According to the European AIDS Clinical Society (EACS) and the U.S. Department of Health and Human Services (DHHS) guidelines, etravirine is recommended as part of an optimised background regimen for treatment-experienced patients with evidence of viral resistance to first-generation NNRTIs. The pivotal DUET clinical trials demonstrated that etravirine, when combined with darunavir/ritonavir and an optimised background regimen, significantly reduced viral load and increased CD4 cell counts in heavily treatment-experienced patients.

What Should You Know Before Taking INTELENCE?

Before starting INTELENCE, inform your doctor about all medical conditions, allergies, and other medications you take. INTELENCE is contraindicated if you are allergic to etravirine or if you are taking elbasvir/grazoprevir for hepatitis C. Special caution is needed for patients with liver disease, and serious skin reactions have been reported.

Contraindications

You should not take INTELENCE if any of the following apply to you:

• Allergy to etravirine or any of the other ingredients in INTELENCE (including hypromellose, microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, magnesium stearate, and lactose monohydrate)
• Concurrent use of elbasvir/grazoprevir (Zepatier), a medicine used to treat hepatitis C infection – the combination leads to significant drug interactions that reduce the effectiveness of both treatments

Warnings and Precautions

Talk to your doctor or pharmacist before taking INTELENCE if you have or have had any of the following conditions:

Skin rash: Rash is the most common side effect of INTELENCE and usually appears within the first few weeks of treatment. Most rashes are mild to moderate and resolve within 1 to 2 weeks even with continued use. However, in rare cases, INTELENCE can cause severe skin reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), characterised by blistering or peeling skin, particularly around the mouth and eyes. These reactions can be life-threatening. Hypersensitivity reactions with rash accompanied by fever, facial swelling, tongue or throat swelling, and difficulty breathing or swallowing have also been reported. Contact your doctor immediately if you develop any severe skin reaction. If treatment was discontinued due to a hypersensitivity reaction, do not restart INTELENCE.

Liver disease: Tell your doctor if you have or have had liver problems, including hepatitis B and/or C. Your doctor will assess the severity of your liver disease before deciding whether you can take INTELENCE. Liver function may need to be monitored during treatment.

Immune reconstitution inflammatory syndrome (IRIS): In patients with advanced HIV infection who have previously had opportunistic infections, signs and symptoms of inflammation from previous infections may occur shortly after starting antiretroviral treatment. These symptoms are believed to result from an improvement in the body’s immune response, enabling the body to fight infections that may have been present without obvious symptoms. Additionally, autoimmune disorders (conditions where the immune system attacks healthy body tissue) may also occur after starting HIV treatment, sometimes several months after treatment initiation. Symptoms may include muscle weakness, weakness starting in the hands or feet and moving towards the trunk, palpitations, tremor, or hyperactivity. Contact your doctor immediately if you notice any of these symptoms.

Bone problems (osteonecrosis): Some patients receiving combination antiretroviral therapy may develop a bone condition called osteonecrosis, where bone tissue dies due to reduced blood supply. Risk factors include the duration of combination therapy, corticosteroid use, alcohol consumption, severe immunosuppression, and higher body mass index (BMI). Signs include joint stiffness, aches, and pain (especially in the hips, knees, and shoulders) and difficulty moving. Tell your doctor if you notice any of these symptoms.

Weight gain and metabolic changes: During HIV treatment, increases in weight and blood levels of lipids (fats) and glucose (sugar) may occur. This is partly related to restored health and lifestyle, and in the case of blood lipids, sometimes to the HIV medicines themselves. Your doctor will monitor these changes through regular blood tests.

Elderly Patients

INTELENCE has been studied in only a limited number of patients aged 65 years or older. If you belong to this age group, discuss with your doctor whether INTELENCE is appropriate for you. Elderly patients may be more susceptible to side effects and may require closer monitoring.

Use in Children and Adolescents

INTELENCE is approved for use in children aged 2 years and older who weigh at least 10 kg. It should not be given to children under 2 years of age or those weighing less than 10 kg, as the potential risks and benefits have not been established in this population. The dose for children is determined by body weight, and your doctor will calculate the appropriate dose for your child.

Pregnancy and Breastfeeding

Tell your doctor immediately if you are pregnant or planning to become pregnant. Pregnant women should not take INTELENCE unless their doctor has specifically prescribed it after careful consideration of the benefits and risks. The safety of etravirine during human pregnancy has not been fully established.

Breastfeeding is not recommended for women taking INTELENCE for two important reasons: first, there is a risk of side effects in the nursing infant from exposure to the drug through breast milk; second, and more critically, HIV infection itself can be transmitted to the infant through breast milk. The World Health Organization (WHO) and all major HIV treatment guidelines recommend that women living with HIV should not breastfeed if safe alternatives (such as formula feeding) are available and affordable.

Driving and Operating Machinery

You should not drive or operate machinery if you feel drowsy or dizzy after taking INTELENCE. These effects may impair your ability to react quickly and safely. If you experience such symptoms, wait until they have resolved before driving or performing tasks that require alertness.

Lactose and Sodium Content

INTELENCE tablets contain lactose (as monohydrate). If you have been told by your doctor that you have an intolerance to certain sugars, contact your doctor before taking this medicine. INTELENCE contains less than 1 mmol (23 mg) sodium per tablet, meaning it is essentially “sodium-free”.

How Does INTELENCE Interact with Other Drugs?

INTELENCE has significant interactions with many medications, including other antiretrovirals, antiepileptics, antibiotics, antifungals, and herbal products. Several combinations are contraindicated or not recommended. Always tell your doctor about every medicine you are taking, including over-the-counter products and herbal supplements.

Etravirine is metabolised by the liver enzymes CYP3A4, CYP2C9, and CYP2C19, and it also acts as an inducer of CYP3A4 and an inhibitor of CYP2C9 and CYP2C19. This means INTELENCE can both be affected by other drugs and affect the levels of other drugs in your body. The following tables summarise the most clinically important interactions. Always inform your doctor and pharmacist about all medicines you take.

Contraindicated and Not Recommended Combinations

Interactions Requiring Dose Adjustment or Monitoring

In most cases, INTELENCE can be safely combined with HIV medicines belonging to other drug classes, including nucleoside reverse transcriptase inhibitors (NRTIs) and certain boosted protease inhibitors (particularly darunavir/ritonavir). However, always follow your doctor’s instructions precisely regarding which medicines can be combined, and read the patient information leaflets of all your HIV medicines carefully.

What Is the Correct Dosage of INTELENCE?

The recommended adult dose of INTELENCE is 200 mg twice daily, taken after a meal. For children aged 2 years and older weighing at least 10 kg, the dose is based on body weight. INTELENCE must always be taken after food to ensure adequate absorption.

Always take INTELENCE exactly as your doctor or pharmacist has told you. Do not change your dose without consulting your doctor. The importance of taking INTELENCE after a meal cannot be overstated – if taken on an empty stomach, only approximately half of the drug is absorbed, which can lead to subtherapeutic blood levels, reduced efficacy, and an increased risk of developing drug resistance.

Adults

Children and Adolescents (2 years and older, weighing at least 10 kg)

How to Take INTELENCE

Swallow the INTELENCE tablet(s) whole with a glass of water. The tablet can be split into two equal halves if needed. For patients who cannot swallow whole tablets, the following alternative method may be used:

1. Place the tablet(s) in at least 5 ml (1 teaspoon) of water, or enough liquid to cover the medicine
2. Stir well for approximately 1 minute until the water appears milky
3. If desired, add up to 30 ml (2 tablespoons) more water, or alternatively orange juice or milk (do not place tablets directly in orange juice or milk)
4. Drink the mixture immediately
5. Rinse the glass several times with water, orange juice, or milk and swallow all the rinsing liquid each time to ensure the full dose is taken

Elderly Patients

Limited data are available on the use of INTELENCE in patients aged 65 years and older. No specific dose adjustment has been established for elderly patients, but they should be monitored closely given the general increase in hepatic, renal, and cardiac dysfunction in this age group, as well as the higher likelihood of concomitant diseases and other drug therapy.

Missed Dose

If you notice a missed dose within 6 hours of the time you usually take INTELENCE, take the tablets as soon as possible. Always take them after a meal, then take the next dose at the regular time. If you notice the missed dose more than 6 hours later, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the one you forgot.

If you vomit within 4 hours of taking INTELENCE, take another dose after a meal. If you vomit more than 4 hours after taking INTELENCE, you do not need to take another dose until your next scheduled dose. Contact your doctor if you are unsure about what to do.

Overdose

Stopping INTELENCE

Do not stop taking INTELENCE without first talking to your doctor. HIV treatment can improve your sense of wellbeing, and even if you feel better, you must not stop taking INTELENCE or your other HIV medicines. Discontinuing treatment can lead to a rapid increase in the amount of virus in your blood (viral rebound), allow the virus to develop further drug resistance, and increase the risk of progression to AIDS-related illnesses. Always discuss any concerns about your treatment with your doctor.

What Are the Side Effects of INTELENCE?

The most common side effects of INTELENCE are skin rash, headache, diarrhoea, and nausea. Rash affects more than 1 in 10 patients and is usually mild to moderate. In rare cases, severe skin reactions including Stevens-Johnson syndrome can occur, requiring immediate medical attention.

Like all medicines, INTELENCE can cause side effects, although not everybody gets them. The frequency and severity of side effects are described below. If you experience any unusual symptoms or if side effects become severe or persistent, contact your doctor immediately.

If you notice any side effects not listed here, or if any side effect becomes severe, contact your doctor or pharmacist. Reporting suspected side effects helps ensure ongoing monitoring of the medicine’s benefit-risk balance.

How Should You Store INTELENCE?

Store INTELENCE tablets in the original container with the lid tightly closed, protected from moisture. Keep out of the reach and sight of children. Do not use after the expiry date or more than 8 weeks after first opening the bottle.

Keep INTELENCE tablets in the original plastic bottle and close the bottle tightly after each use. The medicine is moisture-sensitive, and the bottle contains two small desiccant sachets (silica gel) that help keep the tablets dry. These sachets must remain in the bottle at all times and must not be swallowed.

Check the expiry date printed on the carton and bottle (marked “EXP”). The expiry date refers to the last day of the stated month. Additionally, INTELENCE tablets should not be used for more than 8 weeks after the bottle has been first opened, regardless of the printed expiry date. Consider writing the date you first opened the bottle on the label to help you keep track.

Do not flush unused tablets down the toilet or throw them in household waste. Return any unused or expired medication to your pharmacy for safe disposal, which protects the environment from pharmaceutical contamination.

Child-Resistant Cap

The plastic bottle has a child-resistant cap. To open: push the screw cap down while turning it anticlockwise, then remove the cap. Always replace the cap securely after use to protect both children and the medicine from moisture exposure.

What Does INTELENCE Contain?

Each INTELENCE 25 mg tablet contains 25 mg of etravirine as the active substance, along with inactive ingredients including hypromellose, microcrystalline cellulose, and lactose monohydrate. The 25 mg tablets are white to off-white, oval, with a score line and “TMC” imprinted on one side.

Active Ingredient

The active substance is etravirine. Each 25 mg tablet contains 25 mg of etravirine. INTELENCE is also available in 100 mg and 200 mg tablet strengths.

Inactive Ingredients (Excipients)

The other ingredients are: hypromellose, microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, magnesium stearate, and lactose (as monohydrate). These are standard pharmaceutical excipients that ensure proper tablet formation, stability, disintegration, and absorption.

Tablet Appearance and Packaging

25 mg tablets: White to off-white, oval-shaped tablets with a score line. “TMC” is imprinted on one side. The tablet can be split into two equal halves.

INTELENCE 25 mg is supplied in plastic bottles containing 120 tablets with 2 desiccant sachets.

Marketing Authorisation Holder

Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. The manufacturer is Janssen-Cilag SpA, Via C. Janssen, 04100 Borgo San Michele, Latina, Italy.

How Does INTELENCE Work in the Body?

INTELENCE works by directly binding to HIV-1 reverse transcriptase, blocking the enzyme’s ability to convert viral RNA into DNA. Its flexible molecular structure allows it to maintain activity against many HIV strains that are resistant to first-generation NNRTIs, making it a critical treatment option for experienced patients.

HIV-1 is a retrovirus, meaning it carries its genetic information as RNA rather than DNA. To reproduce inside human cells, the virus must first convert its RNA into DNA using an enzyme called reverse transcriptase. This newly synthesised DNA is then integrated into the host cell’s genome, allowing the virus to hijack the cell’s machinery to produce new viral particles. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as etravirine work by binding directly to a specific site on the reverse transcriptase enzyme (the NNRTI binding pocket), which changes the enzyme’s shape and blocks its ability to function.

First-generation NNRTIs (efavirenz and nevirapine) have a relatively rigid molecular structure. When HIV develops mutations in the reverse transcriptase enzyme – particularly the common K103N mutation – the shape of the NNRTI binding pocket changes enough that these rigid drugs can no longer fit properly, rendering them ineffective. Etravirine was designed to overcome this limitation. Its diarylpyrimidine (DAPY) chemical structure gives it remarkable conformational flexibility, allowing the molecule to twist and rotate within the binding pocket to maintain contact with the enzyme even when mutations are present. This is sometimes described as a “wiggle” and “jiggle” mechanism.

However, etravirine is not impervious to all resistance mutations. Accumulation of multiple mutations in the NNRTI binding pocket – such as Y181C, K101E, G190S, and others – can progressively reduce its effectiveness. This is why resistance testing (genotypic or phenotypic) is essential before starting INTELENCE, to confirm that the patient’s virus is likely to respond to the drug.

Pharmacokinetic Profile

After oral administration with food, etravirine is absorbed with peak plasma concentrations reached in approximately 2.5 to 4 hours. Food is critically important for absorption: taking INTELENCE with a meal increases bioavailability by approximately 50% compared to the fasted state. Etravirine is highly protein-bound (99.9%, primarily to albumin and alpha-1-acid glycoprotein) and is extensively distributed throughout the body.

Etravirine is metabolised primarily by the liver enzymes CYP3A4, CYP2C9, and CYP2C19 through oxidation, followed by glucuronidation. The metabolites are pharmacologically inactive. The terminal elimination half-life is approximately 30 to 40 hours, supporting the twice-daily dosing regimen. Approximately 93.7% of the administered dose is recovered in the faeces (81.2% as unchanged etravirine and 1.2% as metabolites) and 1.2% in the urine. The long half-life and extensive faecal excretion are characteristic of drugs that undergo extensive enterohepatic recirculation.

Frequently Asked Questions About INTELENCE