REKAMBYS (Rilpivirine)
Long-Acting Injectable NNRTI for HIV-1 Treatment
Quick Facts About REKAMBYS
Key Takeaways About REKAMBYS
- First long-acting injectable HIV treatment: REKAMBYS, combined with cabotegravir, allows people living with HIV to replace daily pills with injections given once a month or every two months
- Only for virologically suppressed patients: This regimen is for people whose HIV viral load is already undetectable on their current oral antiretroviral therapy – it is not a first-line treatment
- Always used with cabotegravir: REKAMBYS must always be given alongside cabotegravir injection at each clinic visit – neither medicine should be used alone
- Injection site reactions are common: Pain, discomfort, or a lump at the injection site occurs in more than 1 in 10 people, but reactions typically become milder over time
- Appointment adherence is critical: Missing injection appointments can lead to low drug levels, allowing the virus to replicate and potentially develop resistance to multiple medications
What Is REKAMBYS and What Is It Used For?
REKAMBYS (rilpivirine) is a long-acting injectable antiretroviral medicine belonging to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class. It is used in combination with cabotegravir injections to treat HIV-1 infection in adults and adolescents (aged 12 years and older, weighing at least 35 kg) whose viral load is already suppressed on their current oral antiretroviral therapy.
REKAMBYS contains the active substance rilpivirine, which belongs to a group of anti-HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). These medicines work by blocking the activity of the reverse transcriptase enzyme, a key protein that HIV needs to replicate its genetic material inside human cells. By preventing this crucial step in the viral life cycle, rilpivirine stops the virus from making copies of itself and spreading to new cells.
What makes REKAMBYS unique is its long-acting injectable formulation. Unlike traditional antiretroviral tablets that must be taken every day, REKAMBYS is administered as an intramuscular injection into the gluteal muscle (buttock) by a healthcare professional. The medicine is formulated as a depot suspension, meaning it is slowly released from the injection site into the bloodstream over weeks, maintaining therapeutic drug concentrations without the need for daily dosing.
REKAMBYS is always used together with another injectable medicine called cabotegravir (an integrase strand transfer inhibitor). Together, these two injections form a complete two-drug antiretroviral regimen. Both injections are given at the same clinic visit, either once a month or once every two months, depending on the dosing schedule chosen by the patient and their healthcare provider.
It is important to understand that REKAMBYS does not cure HIV infection. Rather, it helps to keep the amount of HIV in the body at very low levels (undetectable viral load), which delays damage to the immune system and prevents the development of opportunistic infections and AIDS-related illnesses. Effective antiretroviral therapy also greatly reduces the risk of transmitting HIV to others. The landmark ATLAS and FLAIR clinical trials demonstrated that monthly or bimonthly injections of rilpivirine plus cabotegravir were non-inferior to daily oral three-drug regimens in maintaining virological suppression, with high rates of patient satisfaction and preference for the injectable regimen.
REKAMBYS was approved by the European Medicines Agency (EMA) in 2020 and by the U.S. FDA (marketed as Cabenuva in combination with cabotegravir) in 2021. It represented a paradigm shift in HIV treatment, offering the first complete long-acting injectable antiretroviral regimen. This is particularly beneficial for people who have difficulty with daily pill adherence, those who want greater privacy in their treatment, or those who simply prefer the convenience of less frequent dosing.
What Should You Know Before Taking REKAMBYS?
Before starting REKAMBYS, inform your doctor about all medical conditions, liver or kidney problems, current medications, and whether you are pregnant or breastfeeding. REKAMBYS must not be used with certain anticonvulsants, rifamycin antibiotics, systemic dexamethasone, or St. John’s wort, as these drugs dramatically reduce rilpivirine levels and can cause treatment failure.
Contraindications
You must not use REKAMBYS if any of the following apply to you:
- Allergy to rilpivirine or any of the other ingredients in REKAMBYS (poloxamer 338, citric acid monohydrate, glucose monohydrate, sodium dihydrogen phosphate monohydrate, sodium hydroxide, and water for injections)
- Carbamazepine, oxcarbazepine, phenobarbital, or phenytoin – these anticonvulsant medicines strongly induce CYP3A4 and can reduce rilpivirine levels by more than 50%, leading to virological failure and resistance
- Rifabutin, rifampicin, or rifapentine – these rifamycin antibiotics (used to treat tuberculosis and other bacterial infections) dramatically decrease rilpivirine concentrations
- Systemic dexamethasone (oral or injectable, except as a single dose) – this corticosteroid induces CYP3A4 metabolism of rilpivirine
- St. John’s wort (Hypericum perforatum) – this herbal remedy significantly reduces rilpivirine levels and must be avoided completely
If you are taking any of the contraindicated medicines listed above, you must speak with your doctor about alternative treatments before starting REKAMBYS. Using these medicines together can cause your HIV viral load to become detectable again and may lead to the development of drug-resistant HIV, which limits future treatment options.
Warnings and Precautions
Talk to your doctor or healthcare provider before using REKAMBYS if you have or have had any of the following conditions:
- Liver problems, including hepatitis B or hepatitis C – your doctor may need to monitor your liver function more closely, as liver damage (including elevated transaminases and jaundice) has been reported with REKAMBYS
- Kidney problems – although no dose adjustment is generally needed, your doctor may monitor your kidney function
- Medicines that can cause abnormal heart rhythm (QT prolongation / torsade de pointes) – rilpivirine has been associated with QT prolongation at supratherapeutic doses in clinical studies
Post-injection reactions: Some people experience symptoms within a few minutes of receiving a REKAMBYS injection. These post-injection reactions may include difficulty breathing, stomach cramps, rash, sweating, numbness of the mouth, feeling anxious, feeling warm, feeling lightheaded or faint, changes in blood pressure, and pain (such as back pain or chest pain). Most symptoms resolve within a few minutes. Tell your healthcare provider immediately if you experience these symptoms after an injection.
Immune reconstitution inflammatory syndrome (IRIS): Shortly after starting HIV treatment, some patients may experience signs and symptoms of inflammation from infections that were previously present but caused no obvious symptoms. This is thought to occur because the improving immune system begins to fight pre-existing infections. Symptoms may include fever, chills, and sweating. In addition, autoimmune disorders (where the immune system mistakenly attacks healthy body tissue) may develop months after starting treatment, potentially causing muscle weakness, palpitations, tremors, or hyperactivity.
Pregnancy and Breastfeeding
If you are pregnant, planning to become pregnant, or think you might be pregnant, tell your doctor immediately. Your doctor will carefully weigh the benefits and risks of using REKAMBYS during pregnancy. Because rilpivirine can remain in the body for up to 4 years after the last injection, this long tail of drug exposure should be discussed with your doctor if you are planning to have a baby, as rilpivirine will still be present in your body for a significant period after stopping REKAMBYS.
Breastfeeding is not recommended for women living with HIV, because HIV infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and Operating Machinery
Some patients may experience tiredness, dizziness, or drowsiness during treatment with REKAMBYS. If you experience any of these side effects, do not drive or operate machinery until the symptoms have resolved. Post-injection reactions, which may include feeling lightheaded or faint, may also impair your ability to drive safely immediately after receiving the injection.
Use in Children and Adolescents
REKAMBYS is approved for use in adolescents aged 12 years and older who weigh at least 35 kg and whose HIV-1 infection is virologically suppressed on a stable antiretroviral regimen. It should not be used in children under 12 years of age or in adolescents weighing less than 35 kg, as the safety and efficacy have not been established in these populations.
How Does REKAMBYS Interact with Other Drugs?
REKAMBYS can interact with several important drug classes, including anticonvulsants, rifamycin antibiotics, certain macrolide antibiotics, systemic corticosteroids, and methadone. Some interactions are absolutely contraindicated, while others require monitoring or dose adjustments. Always inform your healthcare provider about all medicines you are taking.
Rilpivirine is primarily metabolised by the cytochrome P450 3A (CYP3A) enzyme system. Medicines that strongly induce CYP3A can significantly decrease rilpivirine plasma concentrations, potentially leading to loss of virological response and development of resistance. Conversely, medicines that inhibit CYP3A may increase rilpivirine levels, although this is generally less clinically significant for the long-acting injectable formulation. It is crucial to inform your healthcare provider about all prescription medicines, over-the-counter drugs, and herbal supplements you are using.
Contraindicated Interactions
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Carbamazepine, Oxcarbazepine, Phenobarbital, Phenytoin | Anticonvulsants | Strong CYP3A induction significantly reduces rilpivirine levels, risking virological failure | Absolutely contraindicated – use alternative anticonvulsant |
| Rifampicin, Rifabutin, Rifapentine | Rifamycin antibiotics | Potent CYP3A induction dramatically decreases rilpivirine concentrations | Absolutely contraindicated – discuss TB treatment alternatives with your doctor |
| Dexamethasone (systemic, multiple doses) | Corticosteroid | CYP3A induction reduces rilpivirine levels | Contraindicated except single-dose use – use alternative corticosteroids |
| St. John’s wort (Hypericum perforatum) | Herbal supplement | Significant CYP3A induction decreases rilpivirine levels | Absolutely contraindicated – do not use |
Other Interactions Requiring Monitoring
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Clarithromycin | Macrolide antibiotic | CYP3A inhibition may increase rilpivirine levels | Consider azithromycin as an alternative where possible |
| Erythromycin | Macrolide antibiotic | CYP3A inhibition may increase rilpivirine levels | Consider azithromycin as an alternative where possible |
| Methadone | Opioid agonist | Rilpivirine may decrease methadone levels; no clinically significant effect observed in studies, but individual variation is possible | Monitor for withdrawal symptoms; dose adjustment of methadone may be needed |
Because REKAMBYS is a long-acting injectable, rilpivirine remains in your body for weeks to months after each injection and up to 4 years after the last dose. This means that drug interactions can persist long after the injection is given. It is especially important to inform your healthcare provider about REKAMBYS if you need to start any new medication, even months after your last injection.
What Is the Correct Dosage of REKAMBYS?
REKAMBYS is given by a healthcare professional as an intramuscular injection in the buttock. It can be administered once monthly (600 mg maintenance dose) or once every two months (900 mg maintenance dose), always together with cabotegravir injection. The first injection is a higher loading dose to rapidly achieve therapeutic drug levels.
REKAMBYS is always administered by a doctor or nurse as an intramuscular injection into the gluteal muscle. You will never need to inject REKAMBYS yourself. The injection is given at the same time as the cabotegravir injection, at two different sites in the buttock (one injection in each buttock).
Optional Oral Lead-In Period
Before starting injections, you and your doctor may choose to take an oral lead-in period of approximately one month. During this time, you take one rilpivirine 25 mg tablet daily (with a meal) and one cabotegravir 30 mg tablet daily. This lead-in period allows your doctor to check how well you tolerate the medicines before committing to the long-acting injectable formulation. Alternatively, you and your doctor may decide to start directly with injections without the oral lead-in.
Monthly Dosing Schedule
| Visit | REKAMBYS (Rilpivirine) Dose | Cabotegravir Dose | Timing |
|---|---|---|---|
| First injection | 900 mg (loading dose) | 600 mg (loading dose) | Day 1 |
| Second and subsequent injections | 600 mg (maintenance dose) | 400 mg (maintenance dose) | Every month thereafter |
Every-Two-Months Dosing Schedule
| Visit | REKAMBYS (Rilpivirine) Dose | Cabotegravir Dose | Timing |
|---|---|---|---|
| First injection | 900 mg (loading dose) | 600 mg (loading dose) | Day 1 |
| Second injection | 900 mg (loading dose) | 600 mg (loading dose) | Month 2 (one month after first) |
| Third and subsequent injections | 900 mg (maintenance dose) | 600 mg (maintenance dose) | Every 2 months thereafter |
Missed Dose
It is critical that you attend all scheduled injection appointments. If you miss an appointment, contact your doctor immediately to reschedule. Missing injections allows drug levels to drop below the therapeutic threshold, which can cause the HIV virus to replicate and develop resistance to rilpivirine and potentially to other medicines in the NNRTI class.
If you cannot receive your injection at the usual time, your doctor may prescribe oral bridging therapy – daily rilpivirine tablets and cabotegravir tablets – to maintain adequate drug levels until you can receive the next injection. Do not attempt to manage missed doses on your own; always seek guidance from your healthcare provider.
Overdose
REKAMBYS is administered by a healthcare professional in a clinical setting, so overdose is unlikely. If you are concerned that you may have received too much, speak with your doctor or nurse. There is no specific antidote for rilpivirine overdose; treatment would be supportive and symptom-directed.
Stopping Treatment
Do not stop receiving REKAMBYS without consulting your doctor. After the last injection, low levels of rilpivirine can remain in the body for up to 4 years. However, these residual drug levels are not sufficient to suppress the virus, and the virus may become resistant. To keep your HIV-1 infection under control and prevent resistance, you must start an alternative oral antiretroviral regimen at the time your next REKAMBYS injection would have been due.
What Are the Side Effects of REKAMBYS?
The most common side effects of REKAMBYS (affecting more than 1 in 10 people) are injection site reactions (pain, discomfort, hardening or a lump), headache, and a feeling of warmth or fever within a week of the injection. Most side effects are mild to moderate and become less common with continued treatment.
Like all medicines, REKAMBYS can cause side effects, although not everybody gets them. The side effects listed below have been reported when REKAMBYS is used together with cabotegravir injection. It is important to report any new or worsening symptoms to your healthcare provider, as some side effects may require medical attention.
Very Common
- Headache
- Injection site reactions: pain, discomfort, hardening or a lump at the injection site
- Feeling of warmth or fever, which may occur within a week of the injection
- Increased cholesterol levels in the blood
- Increased pancreatic amylase levels in the blood
Common
- Depression
- Anxiety
- Abnormal dreams
- Difficulty sleeping (insomnia)
- Dizziness
- Nausea
- Vomiting
- Abdominal pain
- Flatulence (excess gas)
- Diarrhoea
- Skin rash
- Muscle pain (myalgia)
- Tiredness (fatigue)
- Feeling weak (asthenia)
- General feeling of being unwell (malaise)
- Weight gain
- Injection site reactions: redness, itching, swelling, warmth, or bruising
- Decreased appetite
- Sleep disturbances
- Low mood (depressed mood)
- Stomach discomfort
- Dry mouth
- Low white blood cell count and/or platelet count
- Decreased haemoglobin
- Increased triglycerides and/or lipase in the blood
Uncommon
- Drowsiness (somnolence)
- Feeling lightheaded or faint during or after injection (vasovagal reaction)
- Liver damage – signs may include yellowing of the skin and eyes, loss of appetite, itching, tenderness of the abdomen, light-coloured stools, or unusually dark urine
- Changes in liver tests (elevated transaminases)
- Increased bilirubin in the blood
- Injection site reactions: numbness, minor bleeding, an abscess, or cellulitis
- Signs or symptoms of inflammation or infection (immune reconstitution inflammatory syndrome)
Rare / Other Reported
- Severe abdominal pain caused by inflammation of the pancreas (pancreatitis)
Contact your doctor or seek emergency medical help immediately if you experience signs of liver damage (yellow skin or eyes, dark urine, persistent nausea, abdominal tenderness), signs of a severe allergic reaction (difficulty breathing, severe rash, facial or throat swelling), or signs of a severe post-injection reaction that does not resolve within a few minutes.
Post-injection reactions: Some patients have experienced symptoms within minutes of receiving the rilpivirine injection. These reactions may include difficulty breathing, stomach cramps, rash, sweating, mouth numbness, anxiety, feeling warm, feeling lightheaded, blood pressure changes, and pain (including back and chest pain). Most symptoms resolve within a few minutes of the injection. Tell your healthcare provider if you experience any of these symptoms.
How Should You Store REKAMBYS?
REKAMBYS must be stored in a refrigerator (2°C–8°C) and must not be frozen. It should be kept out of the sight and reach of children. Since it is administered by a healthcare professional, you will not normally need to store it yourself.
REKAMBYS is supplied as a prolonged-release suspension for injection in a glass vial. Because it is given by a doctor or nurse at a healthcare facility, you will not typically need to store REKAMBYS at home. However, if for any reason you are given the medicine to transport, the following storage conditions must be maintained:
- Store in a refrigerator at 2°C to 8°C
- Do not freeze – freezing may damage the depot suspension and affect its release characteristics
- Keep out of the sight and reach of children
- Do not use after the expiry date printed on the carton (the expiry date refers to the last day of that month)
- Dispose of properly – do not dispose of medicines in household waste or sewage; ask your pharmacist for guidance on proper disposal to protect the environment
What Does REKAMBYS Contain?
Each 2 mL vial of REKAMBYS contains 600 mg of rilpivirine as the active substance. It also contains poloxamer 338, citric acid monohydrate, glucose monohydrate, sodium dihydrogen phosphate monohydrate, sodium hydroxide, and water for injections.
Active Ingredient
The active substance is rilpivirine. Each 2 mL glass vial contains 600 mg of rilpivirine formulated as a prolonged-release suspension for intramuscular injection.
Inactive Ingredients (Excipients)
- Poloxamer 338 – a surfactant that helps maintain the suspension
- Citric acid monohydrate (E330) – a buffering agent
- Glucose monohydrate – used for isotonicity
- Sodium dihydrogen phosphate monohydrate – a buffering agent
- Sodium hydroxide (E524) – used for pH adjustment and to ensure isotonicity
- Water for injections – the solvent
This medicine contains less than 1 mmol (23 mg) sodium per 2 mL injection and is essentially sodium-free.
Packaging
REKAMBYS is supplied as a prolonged-release suspension for injection in a glass vial. Each pack also contains 1 syringe, 1 vial adapter, and 1 injection needle. The marketing authorisation holder is Janssen-Cilag International NV, based in Beerse, Belgium.
Frequently Asked Questions About REKAMBYS
REKAMBYS (rilpivirine) is a long-acting injectable antiretroviral medicine used to treat HIV-1 infection. It is always given together with cabotegravir injections as a complete two-drug regimen. This combination replaces daily oral HIV pills in adults and adolescents (aged 12 years and older, weighing at least 35 kg) whose HIV infection is already suppressed (undetectable viral load) on their current antiretroviral therapy.
REKAMBYS can be given either once a month or once every two months, depending on which schedule you and your doctor choose. If you choose monthly injections, you receive a higher loading dose (900 mg) at the first visit, then 600 mg each month thereafter. If you choose bimonthly injections, you receive 900 mg loading doses at the first and second visits (one month apart), then 900 mg every two months. The cabotegravir injection is always given at the same appointment.
The most common side effects (affecting more than 1 in 10 people) are injection site reactions (pain, discomfort, hardening, or a lump at the injection site), headache, and a feeling of warmth or fever within a week of the injection. Injection site reactions are generally mild to moderate and tend to become less frequent with continued treatment.
Yes, you can switch from daily oral antiretroviral therapy to REKAMBYS injections, provided your HIV viral load is already undetectable (virologically suppressed) on your current regimen. Before switching, your doctor may recommend a one-month oral lead-in period with rilpivirine 25 mg and cabotegravir 30 mg tablets to check tolerability. Alternatively, you may start directly with injections without the oral lead-in period.
If you miss a scheduled injection, contact your doctor immediately to reschedule. Missing appointments can cause drug levels to drop, potentially allowing HIV to replicate and develop resistance. Your doctor may prescribe oral rilpivirine and cabotegravir tablets as bridging therapy until your next injection. Never try to manage missed doses on your own.
Low levels of rilpivirine can remain in the body for up to 4 years after the last REKAMBYS injection. These residual levels are not sufficient to suppress HIV on their own, so it is essential to start an alternative oral antiretroviral regimen at the time your next injection would have been due, to prevent the virus from replicating and developing resistance.
References
- European Medicines Agency (EMA). REKAMBYS – Summary of Product Characteristics. Available at: ema.europa.eu/en/medicines/human/EPAR/rekambys. Last updated 2025.
- Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression. N Engl J Med. 2020;382(12):1112–1123. doi:10.1056/NEJMoa1904398 (ATLAS trial).
- Orkin C, Arasteh K, Hernandez-Mora MG, et al. Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection. N Engl J Med. 2020;382(12):1124–1135. doi:10.1056/NEJMoa1909512 (FLAIR trial).
- Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results. Lancet. 2021;396(10267):1994–2005. doi:10.1016/S0140-6736(20)32666-0.
- European AIDS Clinical Society (EACS). EACS Guidelines Version 12.0. October 2023. Available at: eacsociety.org/guidelines.
- Panel on Antiretroviral Guidelines for Adults and Adolescents (DHHS). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. Updated 2024.
- World Health Organization (WHO). Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring. Geneva: WHO; 2024.
- British HIV Association (BHIVA). BHIVA Guidelines for the Treatment of HIV-1-Positive Adults with Antiretroviral Therapy. 2024 update.
Editorial Team
Specialist physicians in infectious diseases, virology, and clinical pharmacology with expertise in HIV/AIDS treatment and long-acting antiretroviral therapy.
Independent panel of medical experts who review all content according to international guidelines from WHO, EACS, DHHS, and BHIVA. All reviewers declare no conflicts of interest.
This article was written and medically reviewed by the iMedic Medical Editorial Team. Our content follows Evidence Level 1A standards, based on systematic reviews, randomised controlled trials (ATLAS, FLAIR, ATLAS-2M), and international clinical guidelines. We have no commercial funding and receive no pharmaceutical company sponsorship.