What to Know About Complera (Emtricitabine, Rilpivirine, Tenofovir DF)

3-in-1 Antiretroviral Tablet Used to Treat HIV

By
James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.
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James Myhre & Dennis Sifris, MD
Medically reviewed by
Medically reviewed by Latesha Elopre, MD, MSPH on May 23, 2021

Latesha Elopre, MD, is a board-certified internist specializing in HIV and an assistant professor of infectious diseases at the University of Alabama at Birmingham.

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Latesha Elopre, MD, MSPH
on May 23, 2021
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Complera is a fixed-dose combination drug used to treat HIV in adults and older children. Approved for use by the Food and Drug Administration (FDA) in 2011, Complera is comprised of three different antiretroviral drugs:

  • Emtricitabine (FTC), a nucleoside reverse transcriptase inhibitor (NRTI), also sold as a single-drug capsule called Emtriva
  • Rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), also sold as a single-drug pill called Edurant
  • Tenofovir disoproxil fumarate (TDF), another NRTI also sold in a single-drug tablet called Edurant

Complera does not cure HIV. Rather, it prevents the progression of the disease by blocking an enzyme called reverse transcriptase that the virus needs to replicate. By blocking HIV replication, the virus population can be suppressed to undetectable levels where it can do little harm.

There are no generic versions of Complera.

In 2016, an "improved" version of Complera, called Odefsey, was approved by the FDA. This new version replaced TDF with tenofovir alafenamide (TAF), a form that exposes the body to a lower dose of tenofovir and reduces the risk of kidney impairment sometimes seen in TDF users.

Uses

Complera is used to treat HIV infection in adults and children over 12 who weigh at least 77 pounds (35 kilograms). The FDA has issued two indications for use:

  • Newly treated people: Complera can be used in first-line therapy in people who have an HIV viral load of 100,000 or less.
  • Treatment-experienced people: Complera can replace a current therapy if the individual has had an undetectable viral load.

Before Taking

Before starting treatment, your doctor will order tests to "profile" your virus. The tests provide your doctor with information that helps them select the drugs that you are most sensitive to. This include:

  • Genetic resistance testing, a blood test that detects the number and types of drug-resistant mutations your virus has
  • Phenotypic testing, a blood test that isolates the virus and exposes it to all available antiretroviral drugs to see which work best

Genetic resistance testing is crucial even if you are newly infected with HIV as it is possible to pick up a drug-resistant virus through sex, shared needles, and other modes of transmission.

Phenotypic testing is used alongside genetic resistance testing but is generally reserved for people who have had a treatment failure.

Precautions and Contraindications

Complera is contraindicated for use in people who have had a prior hypersensitive reaction to emtricitabine, rilpivirine, or tenofovir.

There are other conditions in which Complera is avoided or used with caution:

  • Hepatitis B: Complera is typically avoided in people coinfected with HIV and hepatitis B as emtricitabine and tenofovir can cause the exacerbation of acute hepatitis B symptoms. Hepatitis B testing is recommended prior to starting treatment in the event of an undiagnosed infection.
  • Kidney disease: Complera is used with caution in people with kidney disease as it can further impair kidney function. Complera should never be used in people with a creatinine clearance of less than 50 milliliters per minute (mL/min), an indication of kidney dysfunction.
  • Liver diseases: Rilpivirine may cause liver toxicity, typically in people with underlying liver diseases (like hepatitis B and hepatitis C) but also in people with no prior history of liver disease. If used, baseline liver function tests should be performed along with routine follow-ups.
  • Osteoporosis: Tenofovir may cause bone mineral loss. Although this is generally not a problem for most people, those with severe osteoporosis or a history of pathologic fractures may benefit from bone mineral density (BMD) testing to assess their risk of harm.

Other Combination Antiretroviral Drugs

In addition to Complera, there are 12 other combination antiretroviral drugs that can be taken on their own with a once-daily dose:

In January 2021, the FDA approved a once-monthly antiretroviral therapy known as Cabenuva, involving one injection of rilpivirine and another of an integrase inhibitor called cabotegravir.

Dosage

Complera is a co-formulated tablet comprised of 25 milligrams (mg) of rilpivirine, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate. The pink, oblong, film-coated tablet is embossed with "GSI" on one side and is plain on the other.

The recommended dose of Complera for adults and children is one tablet daily taken with food. To maintain the optimal therapeutic concentration of the drug in the bloodstream, Complera must be taken daily, ideally at the same time every day.

Modification

The anti-tuberculosis drug rifampin (marketed under the brand names Rifadin, Rifamate, and others) can reduce the concentration of rilpivirine in the blood. If used together, Complera will need to be supplemented with an additional 25 mg dose of rilpivirine in the form of Edurant for the duration of tuberculosis treatment.

How to Take and Store

Taking Complera with a meal increases the absorption of rilpivirine and tenofovir in the gut by 16% and 38%, respectively. Do not chew, split, or crush the tablet as this can also affect drug absorption.

Complera can be stored safely at room temperature, ideally around 77°F (25°C). Do not store the pills on a sunny windowsill or in your glove compartment. Discard any pills that have expired.

If you miss a dose, take it as soon as you remember. If it is near the time of your next dose, skip the original dose and continue as normal. Do not double up doses.

Side Effects

Complera causes few side effects, most of which are mild and transient and tend to resolve within a week or two as your body adapts to treatment. With that said, some people may experience severe side effects or complications that require an immediate change of treatment.

Common

Common side effects of Complera include (by order of frequency):

  • Headache (2%)
  • Insomnia (2%)
  • Depression (2%)
  • Dizziness (1%)
  • Nausea (1%)
  • Abnormal dreams (1%)
  • Rash (1%)

Severe

In rare instances, the drugs in Complera have been known to trigger severe and even life-threatening side effects. Complications include:

  • Hepatitis B exacerbation: Symptoms include fatigue, nausea, vomiting, abdominal swelling, dark urine, and jaundice (yellowing of the eyes and/or skin). Severe cases have been known to cause irreversible liver damage, including decompensated cirrhosis and liver failure.
  • Kidney failure: Tenofovir can cause kidney impairment, which can lead to acute kidney failure in some people (typically those with pre-existing kidney dysfunction). Once treatment is stopped, kidney function is usually restored.
  • Lactic acidosis: NRTIs like tenofovir and emtricitabine can cause the potentially life-threatening build-up of lactic acid in the bloodstream. Symptoms include stomach pain, loss of appetite, diarrhea, muscle pain or cramps, unusual sleepiness, and rapid shallow breathing.
  • Severe rash: Rilpivirine can cause a rare allergy known as drug reaction with eosinophilia and systemic symptoms (DRESS). DRESS tends to develop two to eight weeks after the start of treatment and differs from anaphylaxis in that it generally does not lead to acute respiratory distress. Even so, rare cases can cause acute inflammation and injury to the lungs, kidneys, or liver.

Warning and Interactions

Complera carries a black box warning advising consumers and healthcare professionals of the risk of the acute exacerbation of hepatitis B. A black box warning is the FDA's highest level of advisement about the serious harms a drug may cause.

Complera is generally considered safe during pregnancy. Although well-controlled studies in humans are lacking, the Antiretroviral Pregnancy Registry (APR)—which monitors adverse events in the United States—has reported no increase in the overall risk of birth defects from emtricitabine, rilpivirine, or tenofovir.

It is important to speak with your doctor if you are pregnant or planning to get pregnant before starting Complera to fully understand the benefits and risks of treatment.

Drug Interactions

Complera can interact with many drugs. While some interactions can be overcome by separating the doses by several hours, others may require a drug substitution.

Advise your doctor if you take any of the following drugs or supplements:

Always tell your doctor about any medications you take prior to starting treatment, including prescription, over-the-counter, nutritional, herbal, or recreational drugs.

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Article Sources
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  1. Gilead Sciences. Package insert - Complera. Updated November 2018.

  2. Gilead Science. Package label - Odefsey. Updated October 2018.

  3. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Laboratory testing for initial assessment and monitoring of patients with HIV receiving antiretroviral therapy. Updated December 18, 2019.

  4. Panichsillapakit T, Smith DM, Wertheim JO, Richman DD, Little SJ, Mehta SR. Prevalence of transmitted HIV drug resistance among recently infected [ersons in San Diego, CA 1996-2013. J Acquir Immune Defic Syndr. 2016;71(2):228-36. doi:10.1097/QAI.0000000000000831

  5. U.S. Department of Health and Human Services. FDA-approved HIV medications. Updated September 28, 2020.

  6. U.S. Food and Drug Administration. FDA approves Cabenuva and Vocabria for the treatment of HIV-1 infection. January 27, 2021.

  7. Tourret J, Deray G, Isnard-Bagnis G. Tenofovir effect on the kidneys of HIV-infected patients: A double-edged sword?. J Am Soc Nephrol. 2013 Oct;24(10):1519-27. doi:10.1681/ASN.2012080857

  8. Choudhary S, McLeod M, Torchia D, Romanelli P. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. J Clin Aesthet Dermatol. 2013 Jun; 6(6):31-7.

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