Etravirine

Etravirine is an antiviral medication used as part of combination HIV therapy for people who have already been treated with other HIV drugs.

• Intelence tablets are FDA-approved to treat HIV-1 infection in antiretroviral treatment-experienced adults and in children ages 2 to under 18 who weigh at least 10 kg, always used with other HIV medications
• Etravirine tablets (generic) carry the same indication — treatment of HIV-1 infection in antiretroviral treatment-experienced adults and children ages 2 to under 18 weighing at least 10 kg, in combination with other antiretroviral agents
• Neither Intelence nor etravirine tablets are approved for use in children under 2 years of age or those weighing less than 10 kg
• Neither product is approved for use as a single agent — combination with other HIV medications is always required

Etravirine belongs to the NNRTI class — non-nucleoside reverse transcriptase inhibitors. HIV needs an enzyme called reverse transcriptase to convert its genetic material into a form that can replicate inside human cells. Etravirine binds directly to this enzyme and blocks it, preventing the virus from copying itself and slowing the spread of infection throughout the body.

Because etravirine is specifically designed for treatment-experienced patients, it retains activity against some HIV strains that have become resistant to other NNRTIs — though resistance to etravirine itself can still develop, which is why it is always paired with other active antiretroviral drugs.

Etravirine tablets are taken twice daily by mouth, always with a meal — food is essential because taking it without food cuts absorption by roughly half. The type of meal does not affect how much drug you absorb. Tablets may be swallowed whole with water, or dissolved in water and mixed with orange juice or milk if swallowing is difficult; avoid warm or carbonated liquids for dissolving.

• Adults and children weighing 30 kg or more follow the standard adult twice-daily schedule
• Children ages 2 to under 18 receive a dose based on body weight, twice daily with a meal, not exceeding the adult dose
• Always follow your prescriber's specific instructions — do not adjust your dose on your own

The most common side effects with etravirine are rash and peripheral neuropathy (tingling or numbness in the hands or feet) in adults, and rash and diarrhea in children.

• Rash — usually mild to moderate, most often appears in the first two weeks, and typically clears up within one to two weeks even with continued treatment; it occurs more frequently in women and girls
• Peripheral neuropathy — tingling, numbness, or pain in the hands or feet
• Diarrhea — particularly common in younger children
• Elevated cholesterol, blood fats (triglycerides), or blood sugar levels detected on lab work
• Nausea, stomach discomfort, or flatulence
• Headache, fatigue, or sleep disturbances

Stop taking etravirine and call your doctor or go to an emergency room immediately if you develop a severe rash with blistering, peeling, mouth sores, eye redness, fever, or feel very unwell — these could be signs of a life-threatening skin reaction.

• Severe skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and DRESS have all been reported — some fatal. Stop etravirine immediately at the first sign of a severe or worsening rash, especially if accompanied by fever, blisters, mouth sores, or organ symptoms. Waiting to stop can be life-threatening.
• Drug interactions causing loss of effectiveness or harm: Many common HIV and non-HIV medications can significantly raise or lower etravirine levels, or vice versa. Your full medication list must be reviewed before and during etravirine therapy.
• Immune reconstitution syndrome: As your immune system recovers, it may overreact to hidden infections (such as TB, cytomegalovirus, or pneumonia), causing new or worsening symptoms. Autoimmune conditions like Graves' disease can also emerge, sometimes months after starting treatment.
• Fat redistribution: Changes in body fat — including buildup around the belly or back of the neck, or loss of fat in the face or limbs — have been seen with antiretroviral therapy. The cause is not fully understood.
• Liver enzyme elevations: Liver abnormalities can occur, especially in people co-infected with hepatitis B or C. Liver tests should be monitored closely.

Etravirine is processed by liver enzymes (CYP3A, CYP2C9, CYP2C19) and also affects those same pathways, meaning it can raise or lower blood levels of many other drugs — and other drugs can raise or lower etravirine levels.

• Other NNRTIs (efavirenz, nevirapine, rilpivirine, delavirdine): Combining two NNRTIs is not recommended and can significantly reduce etravirine's effectiveness
• Tipranavir/ritonavir and full-dose ritonavir: Can sharply lower etravirine levels — avoid this combination
• Anticonvulsants (carbamazepine, phenobarbital, phenytoin): These enzyme inducers can drastically lower etravirine concentrations — do not combine
• Warfarin: Etravirine may increase warfarin levels, raising bleeding risk — INR monitoring required
• Digoxin: Etravirine can raise digoxin levels — monitor digoxin blood levels carefully
• Antiarrhythmics (amiodarone, flecainide, quinidine, others): Etravirine may reduce their levels — use with caution, monitor drug concentrations when possible
• Dolutegravir: Etravirine reduces dolutegravir levels; only combine if a boosted protease inhibitor (atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir) is also part of the regimen
• Certain HIV protease inhibitors without a booster: Combinations such as atazanavir alone, fosamprenavir alone, indinavir alone, or nelfinavir alone are not recommended due to unpredictable drug level changes

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• All current medications: Share your complete medication list with your prescriber — many drugs interact significantly with etravirine
• HIV treatment history: Etravirine is only for people who have already been on HIV treatment; it is not a first-line therapy
• Pregnancy: If you are pregnant or planning to become pregnant, talk to your doctor; a pregnancy exposure registry exists to track outcomes (1-800-258-4263). Etravirine has been used in pregnancy but data are limited.
• Breastfeeding: Do not breastfeed while taking etravirine — HIV can be transmitted through breast milk, and etravirine passes into breast milk
• Children under 2: Etravirine is not recommended for children younger than 2 years — dosing has not been established and virologic failure was more common in that age group in studies
• Older adults: Use with care; age-related declines in liver, kidney, or heart function can affect how drugs are processed
• Liver problems: Mild or moderate liver impairment does not require a dose change; severe liver impairment has not been studied — discuss with your prescriber
• Hepatitis B or C co-infection: Liver enzyme levels can rise more in co-infected patients — closer monitoring is needed
• Kidney problems: No dose adjustment is needed for kidney impairment, as etravirine is mostly eliminated through the digestive tract rather than the kidneys

There is no specific antidote if someone takes too much etravirine. The highest dose studied in healthy volunteers was 400 mg once daily, and experience with overdose in patients is very limited. If an overdose is suspected, medical care should focus on supportive measures — monitoring vital signs and general observation. Because etravirine binds so strongly to proteins in the blood, dialysis is not expected to remove a meaningful amount of the drug.

In a careful study of heart rhythm (QT/QTc interval) in healthy volunteers, etravirine did not cause any concerning changes to the electrical activity of the heart at the doses studied. This means etravirine is not expected to cause the type of heart rhythm disturbance (QT prolongation) associated with some other medications.

After a tablet is taken with food, etravirine reaches peak blood levels in about 2.5 to 4 hours. Taking it without food reduces the amount absorbed by roughly half, which is why food is required. Etravirine is almost entirely bound to proteins in the blood (about 99.9%) and is broken down mainly by liver enzymes (CYP3A, CYP2C9, and CYP2C19). It has a long half-life of about 41 hours, meaning it stays in the body for an extended period. The drug is eliminated primarily through the digestive tract (over 93% in stool), with less than 2% leaving via the kidneys — so kidney disease does not meaningfully affect how the body clears it.

Store Etravirine tablets at 25°C (77°F); with excursions permitted to 15° to 30°C (59° to 86°F) . Store in the original bottle. protect from moisture.