Emtricitabine, Rilpivirine, and Tenofovir

Emtricitabine, rilpivirine, and tenofovir is used as a complete, once-daily tablet regimen for the treatment of HIV-1 infection. Specific approvals depend on the product:

• Complera and generic emtricitabine/rilpivirine/tenofovir disoproxil fumarate tablets: approved for adults and pediatric patients weighing at least 35 kg — either as a first HIV treatment (with a starting viral load at or below 100,000 copies/mL) or to switch from a stable HIV regimen in patients who are already virologically suppressed (viral load below 50 copies/mL for at least 6 months with no treatment failures or known resistance)
• Odefsey: approved for adults and pediatric patients weighing at least 25 kg — for the same two uses as above
• Not recommended as a first treatment in people with a viral load above 100,000 copies/mL, as virologic failure rates are higher in this group
• Should not be combined with other antiretroviral HIV medications, as it is already a complete regimen

This tablet combines three antiretroviral drugs that all block the same viral enzyme — called HIV-1 reverse transcriptase — but through two different mechanisms. Emtricitabine and tenofovir (NRTIs) work like fake building blocks: they get incorporated into the virus's genetic copying process and cause the chain to stop, so HIV can't make complete copies of itself. Rilpivirine (an NNRTI) takes a different approach — it physically binds to the enzyme and shuts it down directly. Using two attack strategies at once makes it much harder for HIV to develop resistance and continue replicating.

Because all three drugs target the same enzyme, resistance to one component can affect the whole regimen. Your provider will check for pre-existing resistance before starting this therapy.

All formulations are taken as one tablet by mouth once daily. Food is essential — taking this medication with a meal improves absorption of rilpivirine significantly, and taking it on an empty stomach can reduce drug levels enough to affect how well it works.

• Complera and generic tenofovir disoproxil fumarate-containing tablets: once daily with food; not for use if kidney function (creatinine clearance) is below 50 mL/min
• Odefsey: once daily with a meal; specific kidney function thresholds apply — ask your prescriber
• If you are pregnant and already on this medication with good viral suppression, you may be able to continue — but your viral load should be monitored closely because rilpivirine levels are lower during pregnancy
• If coadministered with rifabutin, an extra rilpivirine tablet (Edurant 25 mg) is needed daily for the duration — follow your prescriber's guidance exactly

The most commonly reported side effects are generally mild to moderate:

• Headache
• Sleep disturbances, including trouble falling asleep or vivid dreams
• Depressive mood or mood changes
• Rash (usually mild and most common in the first 4–6 weeks)
• Nausea
• Dizziness

Serious reactions — including severe skin reactions (DRESS syndrome), liver toxicity, lactic acidosis (a dangerous buildup of acid in the blood), significant depression or suicidal thoughts, and kidney problems — require immediate medical attention. Do not wait to contact your doctor if any of these occur.

• Hepatitis B flare after stopping: If you have both HIV and hepatitis B (HBV), stopping this medication can trigger a severe and potentially life-threatening worsening of hepatitis B. Liver function must be monitored for at least several months after stopping.
• Kidney damage: Tenofovir disoproxil fumarate has been linked to acute kidney failure and Fanconi syndrome (damage to the kidney's filtering tubes). Kidney function should be checked before and regularly during treatment. Avoid high-dose or repeated NSAID use.
• Depression and suicidal thinking: Rilpivirine has been associated with serious depressive disorders, including suicidal ideation. Seek immediate care if you experience severe mood changes.
• Lactic acidosis and severe liver enlargement: A rare but potentially fatal buildup of lactic acid in the blood has been reported with nucleoside antivirals. Symptoms include unusual muscle pain, weakness, stomach pain, or difficulty breathing.
• Severe skin reactions: DRESS syndrome and other serious hypersensitivity reactions have been reported. Stop the medication immediately and seek care if you develop a severe or spreading rash, especially with fever or other symptoms.
• Bone density loss: Tenofovir disoproxil fumarate may reduce bone mineral density. Consider bone monitoring if you have a history of fractures or osteoporosis risk factors.
• Heart rhythm (QT prolongation): At doses much higher than recommended, rilpivirine can affect heart rhythm. Avoid combining with other drugs known to prolong the QT interval.

This medication has several important drug interactions — some of which are contraindicated (meaning you must not combine them):

• Proton pump inhibitors (e.g., omeprazole, pantoprazole, esomeprazole) — contraindicated; raise stomach pH and greatly reduce rilpivirine absorption, risking treatment failure
• Certain seizure medications (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) — contraindicated; speed up rilpivirine breakdown and lower its levels
• Rifampin and rifapentine (TB drugs) — contraindicated; severely reduce rilpivirine levels; rifabutin may be used with an added rilpivirine dose
• St. John's Wort — contraindicated; this herbal supplement reduces rilpivirine to ineffective levels
• Systemic dexamethasone (more than a single dose) — contraindicated; reduces rilpivirine effectiveness
• Antacids — take at least 2 hours before or 4 hours after this tablet to avoid blocking rilpivirine absorption
• H2-blockers (e.g., famotidine) — take at least 12 hours before or 4 hours after this tablet
• NSAIDs at high or multiple doses — can increase kidney stress when combined with tenofovir
• Certain macrolide antibiotics (clarithromycin, erythromycin) — may raise rilpivirine levels; consider azithromycin as an alternative when possible
• Hepatitis C medications (ledipasvir/sofosbuvir, sofosbuvir/velpatasvir combinations) — may increase tenofovir levels; monitor for tenofovir-related side effects

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

• Anyone with hepatitis B (HBV) must be identified before starting — stopping treatment without monitoring can cause dangerous liver flares
• People with kidney disease should be evaluated; this medication is not recommended if creatinine clearance falls below 50 mL/min (tenofovir DF products) or below 30 mL/min (Odefsey)
• People with liver disease or elevated liver enzymes should have liver function monitored throughout treatment
• Anyone with a history of depression or psychiatric illness should discuss this with their provider before starting
• Pregnant individuals already on this medication with good viral control may continue, but rilpivirine levels are lower during pregnancy — close viral load monitoring is required
• Breastfeeding is not recommended — HIV can be transmitted through breast milk, and some drug components are present in human milk
• Children weighing less than 35 kg should not use Complera or generic tenofovir disoproxil fumarate-based tablets; Odefsey is not for children weighing less than 25 kg
• Tell your doctor about all medications, vitamins, and herbal supplements — several common drugs interact dangerously with this combination

If an overdose is suspected, the patient should be monitored for signs of toxicity, including heart rhythm changes (ECG/QT interval monitoring) and vital signs. There is no specific antidote for rilpivirine overdose, and because rilpivirine is highly protein-bound, dialysis is unlikely to remove much of it. Emtricitabine and tenofovir can be partially removed by hemodialysis. Contact Poison Control or seek emergency care immediately if an overdose occurs.

At the standard recommended dose, rilpivirine has a minimal effect on the heart's QT interval (the electrical recovery time between heartbeats) — well below the threshold of clinical concern. However, at doses three to twelve times higher than recommended, rilpivirine has been shown to meaningfully prolong the QT interval, which can increase the risk of a serious heart rhythm problem called Torsade de Pointes. This is why combining this medication with other drugs known to prolong QT is a concern, and why the dose should never be increased without medical guidance.

All three components are absorbed after oral dosing, but food significantly improves how much rilpivirine reaches your bloodstream — a standard meal increases rilpivirine exposure by about 16% compared to fasting, while tenofovir absorption also increases with food. Rilpivirine is very highly bound to proteins in the blood (about 99%), which is why dialysis is not an effective way to remove it in overdose. Emtricitabine and tenofovir are primarily cleared by the kidneys, which is why kidney function matters so much for dosing decisions — reduced kidney function can cause these drugs to build up to higher levels. Rilpivirine, by contrast, is not eliminated by the kidneys.

Store at 25 °C (77 °F), excursions permitted to 15 °C–30 °C (59 °F–86 °F) .