Sustiva (efavirenz)

July 2006     View PDF     En español
Reprinted from www.aidsmeds.com, US

What is Sustiva?
Sustiva is an anti-HIV medication. It is in a category of HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). Sustiva prevents HIV from entering the nucleus of healthy T-cells. This prevents the cells from producing new virus and decreases the amount of virus in the body.

Sustiva was approved by the U.S. Food and Drug Administration for the treatment of HIV in 1998. It was originally produced by DuPont Pharmaceuticals and is now manufactured by Bristol-Myers Squibb for sale in the United States. In Europe and many other parts of the world, Sustiva has a different brand name: Stocrin®. Stocrin is manufactured by by Merck Sharp and Dohme. Stocrin and Sustiva are the same drug.

Sustiva must be used in combination with other drugs to treat HIV. It is usually combined with two nucleoside reverse transcriptase inhibitors (NRTIs).

Atripla™, a combination tablet containing Sustiva and the NRTIs Viread® (tenofovir) and Emtriva® (emtricitabine), was approved for use in the United States in July 2006. Sustiva can still be purchased separately for use in combination with anti-HIV drugs other than Viread, Emtriva, or Truvada® (tenofovir and emtricitabine combined).

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What is known about Sustiva?
The dose of Sustiva for adults is one 600mg tablet taken once a day.

Because Sustiva can cause sleepiness, dizziness, and trouble concentrating, it's probably best to take it at bedtime.

It is recommended that Sustiva be taken on an empty stomach.

Children who are able to swallow capsules can take Sustiva. Capsules containing lower doses of Sustiva are available. Your child's doctor will determine the right dose based on your child's age and body weight. To learn more about Sustiva dosing for children, click here. For children who aren't able to swallow capsules, a liquid formulation of Sustiva is being developed by the manufacturer. It is currently available through an "expanded access" program. If you are caring for a child requiring Sustiva who cannot swallow capsules, a healthcare provider can enroll the child in the expanded access program by calling this number: (877) 372-7097.

For HIV-positive adults beginning anti-HIV drug therapy for the first time, Sustiva is listed as the "preferred" NNRTI option by the United States Department of Health and Human Services (DHHS) in its treatment guidelines. The NNRTI Viramune® (nevirapine) is listed as an "alternative" option.

The DHHS recommends that Sustiva not be used during the first trimester (first three months) of pregnancy. HIV-positive women who are trying to get pregnant, or are not correctly or consistently using birth control during sexual intercourse, should not use Sustiva.

If your viral load becomes detectable while taking a drug regimen that contains Sustiva, your doctor can order a drug-resistance test to see which drugs your virus are becoming less sensitive to.

All of the currently available NNRTIs are affected by cross-resistance. This means that, if you've tried and failed a drug regimen in the past that contained either Viramune® (nevirapine) or Rescriptor® (delavirdine), your virus might be resistant to Sustiva. Similarly, if you take an anti-HIV drug regimen that contains Sustiva and your virus becomes resistant to the drug, your virus will most likely be resistant to the other NNRTIs. This is why it is very important to use drug-resistance testing to determine which drugs your virus is no longer responding to if you experience a rebound in your viral load while taking an anti-HIV drug regimen. Fortunately, new NNRTIs that are active against HIV strains resistant to current NNRTIs are being developed.

If you decide to stop taking a drug regimen that contains Sustiva and do not immediately switch to another drug regimen, careful planning is needed. It can take two to three weeks for Sustiva to be completely eliminated from the body, whereas it only takes other anti-HIV drugs a few days to be completely eliminated. If you stop taking a drug regimen that contains Sustiva – for example, Sustiva and Combivir – and do not immediately switch to another regimen, this would be like taking Sustiva without any other medications, which can quickly lead to drug resistance. In turn, if you plan to stop a drug regimen that contains Sustiva and do not plan on immediately switching to a new regimen, it is best to stop the Sustiva first, several days before you stop the other anti-HIV drugs (for example, the Combivir). You should plan this out, with your healthcare provider, before stopping your drug regimen.

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What about drug interactions?
Sustiva is broken down (metabolized) by the liver, like many medications used to treat HIV and AIDS. This means that Sustiva can interact with other medications. Sustiva can lower or raise the levels of other medications in the body. Similarly, other medications can lower or raise the levels of Sustiva 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 Sustiva:

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

All of the available nucleoside reverse transcriptase inhibitors can be combined safely with Sustiva.

Sustiva can reduce the amount of various protease inhibitors in the bloodstream, including Reyataz® (atazanavir), Invirase® (saquinavir), Crixivan® (indinavir), Kaletra® (lopinavir/ritonavir), and Agenerase® and and Lexiva® (amprenavir/fosamprenavir). Sustiva can increase the amount of Viracept® (nelfinavir) and Norvir® (ritonavir) in the bloodstream. And when Sustiva and Norvir are combined, Sustiva levels also increase in the bloodstream. If Sustiva is taken with Reyataz, Invirase, 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.

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

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

If you take methadone, Sustiva 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 Sustiva. 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. These feeling may be less noticeable if you take Sustiva 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 Sustiva is used with alcohol or mood-altering (recreational) drugs. You should also avoid driving or operating machinery if you are having these side effects. Check out our lesson on Tips & Tricks on Taking Sustiva to learn more.

A small number of patients have had severe depression, strange thoughts, or angry behavior while taking Sustiva. 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.

Rash is another common side effect of Sustiva. 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.

Other possible side effects include tiredness, upset stomach, vomiting, and diarrhea.

Sustiva 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 Sustiva. This way, the laboratory conducting the test will know to use a more sensitive test to prevent false-positive results.

Rash may be a serious problem in some children. Tell your child's doctor right away if you notice rash or any other side effects while your child is taking Sustiva.

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Can pregnant women take Sustiva?
Sustiva is classified by the FDA as a pregnancy category D drug. When it 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 Sustiva while pregnant, especially during the first trimester (first three months) of the pregnancy, or practice birth control to prevent pregnancy while taking the drug.

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

It is not known if Sustiva can pass from a mother to her baby through breast milk. It is also not known what effect this 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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What should I tell my doctor before taking Sustiva?
Before taking this medication, tell your doctor if you have liver disease.

If you are pregnant, planning on becoming pregnant, or not consistently using birth control, be sure to tell your doctor. Women taking Sustiva should not become pregnant.

Have ever had mental illness or are using drugs or alcohol.

Tell your doctors and pharmacists about all medicines you take. This includes prescription medications, over-the-counter products, or herbal/natural remedies. Also be sure to tell your doctor if you've ever had seizures or are taking medications to control seizures.

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Where can I learn more about clinical trials of Sustiva?
Even though Sustiva is approved for the treatment of HIV, it is still used in clinical trials, either to learn more about its safety and effectiveness or to determine how well it works in combination with experimental treatments.

If you would like to find out if you are eligible for any clinical trials that include Sustiva, there is an interactive website 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 U.S. 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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