Sustiva, Stocrin (outside the U.S.) – brand names

efavirenz – generic name

Sustiva belongs to a class of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), also known as non-nucleoside analogs or “non-nukes.”

The NNRTIs block reverse transcriptase, a protein that HIV needs to make more copies of itself. This may slow down HIV disease.

The Food and Drug Administration (FDA) has approved Sustiva for use in combination with other HIV drugs for the treatment of HIV infection in adults and children over three years old.

The FDA has also granted tentative approval of a generic formulation of Sustiva, although this version is not yet available in the U.S.

Sustiva comes in:

• 50 milligram (mg), 100 mg, and 200 mg capsules
• 600 mg tablets
• A liquid formulation is being studied in children under three years old and is available through an expanded access program from the manufacturer

The usual dose for adults is one 600 mg tablet once daily.

Check with your child’s doctor for children’s dosing.

Sustiva must be used with other medications to treat HIV.

You can take Sustiva with food or on an empty stomach, but taking it on an empty stomach at bedtime reduces side effects. Sustiva should not be taken with a high fat meal because this increases the chances of side effects.

Speak to your doctor if you have liver problems or mental health issues (such as depression), or are using street drugs or alcohol.

It can take two to three weeks for Sustiva to be eliminated from your body after you stop taking it. Careful planning with your doctor is needed if you stop taking a drug regimen that contains Sustiva, especially if you do not immediately switch to another drug regimen.

Sustiva is one of the easiest HIV drugs to take—you take one pill, once a day. Once-daily drugs are convenient but more demanding, because good adherence is crucial. Missing or skipping doses can cause your blood levels of the drug to fall too low and resistance can develop. When your virus becomes resistant to an HIV medication, that drug may stop working.

Sustiva can be used if you’re just starting HIV treatment.

• Studies have shown that Sustiva can be as effective, or more effective than protease inhibitor (PI) regimens in people being treated for the first time (including those with high viral loads).

Sustiva is one of the options to consider if you need a “protease-sparing” drug regimen (a regimen that does not include a PI).

Sustiva can be used if you’ve been on treatment before, however, it will not work well for people whose virus is already resistant to the other NNRTIs: Rescriptor (delavirdine) and Viramune (nevirapine).

Your doctor can run a resistance test to help determine whether Sustiva is likely to work for you.

Sustiva seems to cross the blood-brain barrier (which protects the brain and spinal cord), so it may be able to fight HIV in the brain.

If your virus develops resistance to Sustiva then it may stop working or not work as well for you. You are also not likely to benefit from the other NNRTIs.

Sometimes taking more than one medication can cause drug interactions. Taking certain drugs (such as cholesterol-lowering drugs) with Sustiva can change the amount of one or both drugs in your blood. Your doctor may need to adjust the doses of your drugs to avoid under- or overdosing.

• Sustiva lowers blood levels of most PIs. Your doctor will need to increase your dosage of Crixivan (indinavir), Agenerase (amprenavir), Reyataz (atazanavir), Kaletra (lopinavir/ritonavir), and Lexiva (fosamprenavir)
• Sustiva and Fortovase (saquinavir) or Invirase (saquinavir) should not be used together
• Methadone doses may need to be increased if you are taking Sustiva

Sustiva decreases the effectiveness of birth control pills, so alternative birth control methods should be used.

Certain medications, including some sedatives, antihistamines, antibiotics, antifungals, migraine headache, acid reflux, and TB medications, should not be taken with Sustiva. Also, you should not take St. John's wort, an over-the-counter herbal supplement.

Sustiva plus Videx EC (ddI or didanosine) plus Viread (tenofovir) should not be used in patients new to HIV therapy.

Be sure your doctor knows about all the medications you are taking (including over-the-counter, prescription, street drugs, and herbs), even if you only use them occasionally.

For more information and additional resources to check interactions between the particular drugs you are taking, see our info sheet on drug interactions.

The Sustiva (efavirenz) package insert has been recently updated by the Federal Drug Administration (FDA) to include drug-drug interaction information to state Sustiva should not be administered at the same time with bepridil (which is a calcium channel blocker), pimozide (which is for seizures and some mood disorders) and standard doses of voriconazole (which is a very popular anti-fungal treatment). The FDA stresses that SUSTIVA tablets should not be broken.

Sustiva side effects usually occur in the first two to four weeks of treatment and generally improve as your body adjusts to the medication. In some cases, side effects may continue for longer than the first month.

Many of the side effects associated with Sustiva affect the central nervous system (CNS):

• Dizziness
• Insomnia (trouble sleeping)
• Drowsiness
• Trouble concentrating
• Vivid dreams
• Changes in mood
• Depression

Other side effects include:

• Skin rash (rash may be a serious problem in some children)
• Headaches
• Nausea
• Diarrhea
• Fatigue (unusual tiredness)

Many people find that they can handle the side effects better if they take Sustiva at bedtime. Your doctor can help you manage Sustiva side effects by prescribing medications to treat insomnia and anxiety. If the side effects do not go away or become intolerable, call your doctor for advice. Don’t just stop taking your medication.

More serious side effects:

• Although rare, some people experience clinical depression, paranoia, and thoughts of suicide
• Sustiva is less likely to cause a rash than other NNRTI drugs, but in rare cases it has caused a life-threatening hypersensitivity reaction (Stevens-Johnson syndrome). Symptoms may include a severe rash, blisters, mouth sores, swelling, fever, and weakness
• Liver toxicity: this may be indicated by elevated liver enzymes or yellowing of the skin and eyes (jaundice)

Call your doctor right away if you are experiencing any of the more serious side effects.

Sustiva has been studied in many women. Studies of Sustiva pharmacokinetics (how the drug is processed by the body) showed that the drug behaves similarly in the bodies of women and men, but some research indicates that Sustiva may reach higher levels in women. The drug manufacturer does not recommend any dose adjustments based on weight or sex.

Study DMP266-006 compared Retrovir (zidovudine or AZT) plus Epivir (lamivudine or 3TC) plus Sustiva to Retrovir plus Epivir plus Crixivan to Sustiva plus Crixivan in people who had not taken NNRTIs or protease inhibitors before. This study included 17 percent women, or about 215 women out of 1,266 total participants.

After 48 weeks, more people taking Retrovir plus Epivir plus Sustiva had undetectable viral loads than those taking either Retrovir plus Epivir plus Crixivan or Sustiva plus Crixivan. More people in the Crixivan groups stopped treatment due to side effects (although more people in the Sustiva group developed a rash or nervous system side effects). At 72 weeks, Retrovir plus Epivir plus Sustiva still worked better, but at three years, the rates of treatment failure in the Sustiva and Crixivan groups were similar.

Study ACTG 364 compared Sustiva to Viracept (nelfinavir) to Sustiva plus Viracept in treatment-experienced people who were also taking nucleoside reverse transcriptase inhibitors (NRTIs). This trial included 12 percent women, or about 23 women out of 196 total participants. In this study, people taking Sustiva plus Viracept plus NRTIs or Sustiva plus NRTIs were more likely to achieve undetectable viral loads than those taking Viracept plus NRTIs.

Study DMP-020 found that Sustiva plus Crixivan plus NRTIs worked better than Crixivan plus NRTIs without Sustiva. This trial included about 17 percent women, or 55 women out of 327 total participants.

Study AI424-034 compared Retrovir plus Epivir plus Sustiva to Retrovir plus Epivir plus Reyataz in people who had not used HIV drugs before. This study included 35 percent women, or about 280 women out of 805 total participants. In this study Sustiva and Reyataz worked equally well against HIV, but Reyataz did not increase blood fat levels as much as Sustiva.

ACTG 384, a large study comparing six different drug combinations, found that Retrovir plus Epivir plus Sustiva was one of the best first regimens in terms of effectiveness and side effects.

The 2NN study compared Zerit (stavudine or d4T) plus Epivir plus Sustiva versus Zerit plus Epivir plus Viramune to Zerit plus Epivir plus Sustiva plus Viramune in people who had not taken HIV drugs before. This trial included 37 percent women, or about 449 women out of 1,216 total participants.

In this study, Sustiva and Viramune worked about equally well overall, but Sustiva appeared to work better in people with high viral loads. People who took both Sustiva and Viramune did worse than those who took only one NNRTI, since more stopped treatment due to side effects.

Study ACTG 5095 found that drug regimens containing Sustiva worked better than the all-NRTI combination of Retrovir plus Epivir plus Ziagen (abacavir); these three drugs are in the Trizivir combination pill. This study included 19 percent women, or about 218 women out of 1,147 total participants.

Several studies have looked at people switching from PIs to NNRTIs (for example, study DMP266-049, which included 10 percent women, or about 22 women out of 226 total participants). Overall, these studies have found that people who switch from a PI to Sustiva have a similar or better response to treatment, as well as increased levels of HDL (“good”) cholesterol, lower levels of LDL (“bad”) cholesterol and lower levels of triglycerides, all of which may protect against heart disease.

In terms of side effects, studies show that Sustiva can cause a skin rash or nervous system side effects. In study DMP266-006 (described above), 34 percent of participants taking Sustiva developed a rash, and 58 percent developed nervous system side effects. These side effects were most likely during the first month of treatment. Studies do not seem to indicate that women taking Sustiva experience more or different side effects than men. But we know that in general depression and mood disorders are more common in women, so more research is needed on nervous system side effects in women taking this medication.

Studies have shown that pregnant women who use HIV drugs can greatly reduce the risk of passing HIV on to their babies. There have been no formal studies on the use of Sustiva during pregnancy. However, Sustiva has recently been linked to birth defects in humans causing the FDA to recommend that Sustiva not be used during pregnancy. Because of this, pregnant women should not use Sustiva, and women who are taking the drug should use effective birth control. (Sustiva decreases the effectiveness of birth control pills, so alternative birth control methods should be used.)

Check with your doctor about the best treatment options for you and your baby if you are thinking of getting pregnant.

Click this link for more information on pregnancy.

Sustiva may cause a false positive result if you are given a drug test for marijuana.

People who are starting HIV treatment for the first time may develop Immune Reconstitution Syndrome or IRS (also called Immune Reconstitution Inflammatory Syndrome or IRIS). IRS can happen as a result of the immune system getting stronger and responding to an HIV-related infection such as Mycobacterium avium infection (MAC), cytomegalovirus (CMV), Pneumocystis jirovecii pneumonia (PCP), or tuberculosis (TB). People may have been treated for these infections in the past or not even know they have them. If you notice any unusual symptoms soon after starting HIV drugs for the first time, let your doctor know right away so you can be evaluated and, if necessary, treated.

1		Moyle, G., et. al. (1999). Management of protease inhibitor-associated metabolic changes by substitution with efavirenz in virologically controlled HIV-1 RNA positive patients. 6th Conference on Retroviruses and Opportunistic Infections. Chicago, IL. Abstract 383.
2		Van Leth, F., et. al. (2003). Results of the 2NN study: A randomized comparative trial of first-line antiretroviral therapy with regimens containing either nevirapine alone, efavirenz alone or both drugs combined, together with stavudine and lamivudine. 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA. Abstract 176.
3		Welch, K.J., et. al. (2002). Association between efavirenz and selected psychiatric and neurological conditions. Journal of Infectious Diseases, 185(2). 268-269.