Atripla (efavirenz + tenofovir + emtricitabine)

February 2007     View PDF     En español
Reprinted from www.aidsmeds.com, US

What is Atripla?
Atripla is an anti-HIV medication. It contains two different types of anti-HIV drugs: one non-nucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs).

Atripla is marketed by two companies: Bristol-Myers Squibb and Gilead Sciences. It was approved by the U.S. Food and Drug Administration (FDA) in July 2006.

Atripla is a combination of three drugs: 600 mg of Sustiva® (efavirenz), 300mg of Viread® (tenofovir DF) and 200mg of Emtriva® (FTC). Atripla should be prescribed by a healthcare provider for patients who need all three of these drugs. All three drugs can still be purchased individually for use in combination with other anti-HIV drugs.

Atripla is considered to be a complete one-pill, once-daily anti-HIV treatment regimen, at least for people starting anti-HIV treatment for the first time. It does not need to be combined with other anti-HIV drugs.

Both the Viread and the Emtriva in Atripla are active against the hepatitis B virus (HBV), the virus responsible for causing hepatitis B. See What about side effects? below for more important information regarding Viread, Emtriva, and hepatitis B.

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What is known about Atripla?
Atripla is a tablet taken once a day. It should be taken without food, preferably at bedtime.

Atripla should not be any more or less effective than Sustiva, Viread, and Emtriva taken as separate pills together. However, it is considered to be a much more convenient way of taking these three anti-HIV drugs.

For HIV-positive adults beginning anti-HIV drug therapy for the first time, the three drugs in Atripla are listed as a “preferred” regimen.

See the “What is known about...” sections of Sustiva, Viread and Emtriva for information about possible drug resistance.

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What about drug interactions?
The Sustiva in Atripla is broken down (metabolized) by the liver, like many medications used to treat HIV and AIDS. This means that Atripla can interact with other medications. Atripla can lower or raise the levels of other medications in the body. Similarly, other medications can lower or raise the levels of Sustiva in Atripla in the body. While many interactions are not a problem, some can cause your medications to be less effective or increase the risk of side effects.

Tell your doctors and pharmacists about all medicines you take. This includes those you buy over-the-counter and herbal or natural remedies, such as St. John’s Wort. Bring all your medicines when you see a doctor, or make a list of their names, how much you take, and how often you take them. Your doctor can then tell you if you need to change the dosages of any of your medications.

The following medications should not be taken while you are being treated with Atripla:

Antibiotics: Priftin® (rifapentine)
Antifungals: Vfend® (voriconazole)
Antihistamines: Hismanal® (astemizole)
Antipsychotics: Orap® (pimozide)
Acid reflux/heartburn medications: Propulsid® (cisapride)
Heart medications: Vascor® (bepridil)
Sedatives: Versed® (midazolam) and Halcion® (triazolam)
Antimigraine medications: Wigraine® and Cafergot® (ergot medications)

The Sustiva in Atripla can reduce the amount of various protease inhibitors in the bloodstream, including Reyataz® (atazanavir), Invirase® and Fortovase® (saquinavir), Crixivan® (indinavir), Kaletra® (lopinavir/ritonavir), and Agenerase® and and Lexiva® (amprenavir/fosamprenavir). Atripla can increase the amount of Viracept® (nelfinavir) and Norvir® (ritonavir) in the bloodstream. The Viread in Atripla can also decrease Reyataz and Kaletra levels in the bloodstream. Kaletra can also increase Viread levels in the bloodstream.

If Atripla is taken with Reyataz, Invirase, Fortovase, Kaletra, Crixivan, Agenerase, or Lexiva, their doses may need to be increased or they may need to be combined with a low dose of Norvir (e.g., 100 mg) to help maintain necessary drug levels in the bloodstream. If Kaletra and Atripla are used together, it is important to watch out for potential side effects of Viread (e.g., kidney problems).

Atripla should not be taken at the same time as Epivir® or other combination tablets that contain Epivir (for example, Epzicom™, Combivir®, or Trizivir®). This is because Epivir is very similar to the Emtriva in Atripla, and it is not believed that combining these two anti-HIV drugs will make a regimen any more effective against the virus.

Because of significant drug interactions between the Viread in Atripla and Videx®/Videx EC® (ddI), many experts recommend avoiding the use of Videx in drug regimens that include Viread.

The Sustiva in Atripla can interact with some medications used to treat TB, MAC and other bacterial infections. Rifadin® (rifampin) can decrease Sustiva levels (Sustiva should probably be taken separately at a dose of 800mg a day). Atripla can decrease Mycobutin® (rifabutin) levels (Mycobutin dose should be increased). Atripla can also decrease Biaxin® (clarithromycin) levels; an alternative to clarithromycin is recommended.

The Sustiva in Atripla can interact with some medications used to treat various fungal infections, including candidiasis and cryptococcal meningitis. If Vfend® (voriconazole) must be used, the Sustiva dose must be reduced to 300 mg once daily. This requires stopping Atripla and starting the older 100 mg capsule formulation of Sustiva (three capsules once a day) plus Truvada® (tenofovir plus emtricitabine). The Vfend dose should also be increased to 400 mg every 12 hours.

The Sustiva in Atripla can also decrease levels of Sporanox® (itraconazole); it is recommended that a Sporanox alternative be used instead. Nizoral® (ketoconazole) levels can decrease as well; no dosing recommendations have been made.

The Sustiva in Atripla can decrease blood levels of calcium channel blockers (used to control blood pressure, regulate heartbeats, and manage chest pain). Examples include Cardizem® (diltiazem), Plendil® (felodipine), Cardene® (nicardipine), Procardia® (nifedipine), Calan® (verapamil). Increasing the doses of these medications may be necessary.

The Sustiva in Atripla can interact with oral contraceptives/birth control pills (ethinyl estradiol). Atripla increases the amount of ethinyl estradiol in the bloodstream. No alternative has been recommended.

If you take methadone, the Sustiva in Atripla can decrease the amount of it in your blood. This might cause you to experience withdrawal symptoms and may require that your doctor or your rehabilitation program increase your dose of methadone.

Blood levels of Viagra® (sildenafil) and Levitra® (vardenafil), two drugs used for erectile dysfunction, can decrease if they are combined with Atripla. In turn, it may be necessary to increase the dose of Viagra or Levitra to achieve the desired effect.

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What about side effects?
Many patients have dizziness, trouble sleeping, drowsiness, trouble concentrating, and/or unusual dreams a few hours after starting treatment with Sustiva, one of the drugs in Atripla. These feeling may be less noticeable if you take Atripla at bedtime. They also tend to go away after you’ve taken the medicine for a few weeks. If you have these side effects, such as dizziness, it does not mean that you will also have severe depression, strange thoughts or angry behavior. Tell your doctor promptly if any of these side effects continue or if they bother you. There is the possibility that these symptoms may be more severe if Atripla is used with alcohol or mood-altering (recreational) drugs. You should also avoid driving or operating machinery if you are having these side effects.

A small number of patients have had severe depression, strange thoughts, or angry behavior while taking Sustiva, one of the drugs in Atripla. Some patients have had thoughts of suicide and a few patients have actually committed suicide. These problems tend to occur more often in patients with a history of mental illness. You should contact your doctor immediately if you think you are having these symptoms, so your doctor can decide whether you should continue to take Sustiva.

Lactic acidosis, which can be fatal, and severe liver problems have been reported in people taking nucleoside reverse transcriptase inhibitors (NRTIs). Contact your doctor immediately if you experience nausea, vomiting, or unusual or unexpected stomach discomfort; weakness and tiredness; shortness of breath; weakness in the arms and legs; yellowing of the skin or eyes; or pain in the upper stomach area.

Rash is another common side effect of the Sustiva in Atripla. These rashes usually go away without any change in treatment. In a small number of patients, rash may be serious. If you develop rash, call your doctor as soon as possible.

The Viread in Atripla may cause bone problems. In one clinical trial conducted by the manufacturer involving HIV-positive patients who were new to anti-HIV therapy, Viread [combined with Sustiva® and Epivir®] was more likely to cause decreased bone mineral density (osteopenia)—which can lead to osteoporosis—than Zerit® (d4T) [combined with Sustiva and Epivir]. This can increase the risk of bone breakage, including the hip, spine, and wrist. Researchers are currently looking into the seriousness of this possible side effect. If you have a history of bone fracture or are at risk for osteopenia, your doctor may want to consider ordering bone scans on a regular basis while you are taking Atripla. While it’s not clear if calcium and vitamin D supplementation can help reverse this side effect, it might be a good idea if you have either osteopenia or osteoporosis and are taking Atripla.

The Viread in Atripla can be problematic for HIV-positive people who have a history of kidney problems (renal impairment). If you have a history of kidney problems, your doctor will need to order a simple laboratory test to measure your “creatinine clearance”—the rate your kidneys remove this protein produced by muscles from the bloodstream. Depending on the results of this test, you may not be able to take Atripla. You may need to take the individual Viread tablets, using a lower dose. It is always important to be careful if using Atripla in combination with Vistide® (cidofovir), Cytovene® (ganciclovir), and Valcyte™ (valganciclovir), three treatments for CMV that can also cause kidney problems.

Anti-HIV drug regimens containing Sustiva, Viread, and Emtriva can can cause increased fat levels (cholesterol and triglycerides) in the blood, abnormal body-shape changes (lipodystrophy; including increased fat around the abdomen, breasts, and back of the neck, as well as decreased fat in the face, arms, and legs), and diabetes.

If you have hepatitis B and HIV and plan to stop taking Atripla, your doctor might want to frequently check your liver enzymes after stopping treatment. This is because the Viread and Emtriva in Atripla are also active against the hepatitis B virus (HBV). If Truvada is stopped abruptly, it can cause liver disease to “flare” and damage the liver.

The Sustiva in Atripla can cause someone to test positive for marijuana as a result of testing for elicit drug use. If you are asked to submit urine for a drug test, you may want to tell the person collecting the sample that you take Atripla. This way, the laboratory conducting the test will know to use a more sensitive test to prevent false-positive results.

See the “What about side effects?” sections of Sustiva, Viread and Emtriva for additional possible side effects.

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Can pregnant women take Atripla?
Because Atripla contains Sustiva, it is classified by the FDA as a pregnancy category D drug. When Sustiva was first approved it was classified as a category C drug. This important change is a result of four reports to the FDA of neural tube defects (a birth defect occurring in the brain or spinal cord) in infants born to women who took Sustiva during the first three months of pregnancy. Because of this, it is recommended that HIV-positive women refrain from using Atripla while pregnant, especially during the first trimester (first three months) of the pregnancy, or practice birth control to prevent pregnancy while taking the drug. Using Viread and Emtriva separately (or together as Truvada®) is possible during pregnancy.

The Sustiva in Atripla has caused serious side effects in infant monkeys born to adult female monkeys.

It is not known whether the three drugs in Atripla pass into breast milk and what effect they may have on a nursing baby. To prevent transmission of the virus to uninfected babies, it is recommended that HIV-positive mothers not breast-feed.

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Who should not take Atripla?
Before taking this medication, tell your doctor if you have: kidney disease; liver disease; a history of pancreatitis; decreased activity of your bone marrow (low red blood cells [anemia] or low white blood cells). You may not be able to take Atripla if you have any of these conditions.

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Where can I learn more about clinical trials of Atripla?
If you would like to find out if you are eligible for any clinical trials that include Atripla, there is an interactive web site run by ACRIA, the AIDS Community Research Initiative of America.

Another useful service for finding clinical trials is AIDSinfo.nih.gov, a site run by the US National Institutes of Health. They have "health information specialists" you can talk to at their toll-free number at 1-800-HIV-0440 (1-800-448-0440).

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