Sustiva
Common Name: efavirenz
Brand Name: Sustiva
Class: non-nucleoside analogs (also called non-nucleoside reverse transcriptase inhibitors, NNRTIs, or non-nukes)
Standard dose: One 600 mg tablet, once a day, typically at bedtime; on an empty stomach or with a light, low-fat snack. Also available in smaller 50 mg and 200 mg capsules. Dose can be split up. Approved for children 3 years and older. Strawberry/mint flavored solution available to children under expanded access program. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.
AWP: $637.50 / month for thirty 600 mg tablets
Manufacturer contact: Bristol-Myers Squibb,
www.sustiva.com; 1 (800) 321-1335
Potential side effects and toxicity: Because Sustiva penetrates so readily into the brain, up to 50% of patients experience some kind of central nervous system (CNS) or psychiatric symptoms (dizziness, headache, memory loss, somnolence or hypnotic trance, confusion, insomnia, hallucinations, vivid or abnormal dreams or nightmares, depression, euphoria or mania, and agitation). These symptoms typically diminish within four weeks. If you can’t sleep (which more commonly develops later), ask about switching the timing of your dose little by little until you’re taking it in the daytime. Some people in recovery from substance use will experience flashbacks. Other side effects may include rash, nausea, vomiting, diarrhea, fever, and increased liver enzymes. These symptoms occur early and generally resolve within two to four weeks. A serious side effect of the NNRTI class is rash, which can be life-threatening. Rash is more common, and more severe, in children, as is diarrhea, fever, and low levels of some blood cells. May raise levels of triglycerides and the good cholesterol (HDL). May lead to false positive tests for use of marijuana. Women taking Sustiva should not become pregnant or breast-feed because of the risk of birth defects. Increases in liver enzymes in people with hepatitis B and/or C can occur and should be monitored.
Potential drug interactions: Do not take with Atripla, since Sustiva is already in Atripla. You cannot take the following medications with Sustiva: midazolam, triazolam, ergot medications (Wigraine, Methergine, and Cafergot), Vfend, St. John’s wort, Gingko biloba, or bepridil. Do not use with Biaxin. May affect Coumadin (warfarin) therapy. Sustiva decreases methadone levels; dosing adjustment may be necessary to avoid withdrawal symptoms. Increase Kaletra to three tablets twice daily with food (recommended) when taken with Sustiva in people who previously took HIV drugs, especially protease inhibitors. Kaletra cannot be taken once daily with Sustiva. Monitor liver enzymes closely if Sustiva and Norvir are used together due to potential risk of liver damage. Reyataz dose should be higher and also boosted with Norvir (Reyataz 400 mg/Norvir 100 mg once daily) when taken with Sustiva, but treatment-experienced people should not use this drug combination at all. With once-daily Lexiva, boost with 300 mg Norvir. Rifampin decreases Sustiva concentrations, so maintain 600 mg once-daily dose and monitor. Rifabutin levels are decreased, so daily dose of rifabutin should be increased by 50%. When taken with anticonvulsants Dilantin (phenytoin), phenobarbital, or Tegretol (carbamazepine), periodic monitoring of blood levels of anticonvulsants and Sustiva should be performed or alternative anti-seizure medications should be considered. Can affect birth control pill levels, so a second barrier contraceptive method is advised. Sustiva can lower the concentrations of Sporanox (itraconazole), Zoloft, Lipitor, pravastatin, simvastatin, and diltiazem. Dose adjustment may be needed when co-administering these drugs with Sustiva. The maintenance dose of Vfend should be increased to 400 mg every 12 hours and the Sustiva dose should be decreased to 300 mg once daily using the capsule formulation. Drug levels of bupropion are lowered; titrate dose based on clinical response.
Tips: According to current U.S. guidelines, when choosing an NNRTI-based regimen, Sustiva is the preferred drug. Avoid driving or operating heavy machinery for a few hours after dose. Some people adjust to Sustiva by taking Ativan or Ambien to sleep for the first few weeks. However, either may make you even more groggy the next morning. Be careful when stopping Sustiva, so that you avoid the rapid development of HIV resistance to it—check with your doctor or pharmacist first. It is usually recommended that you continue your other HIV medications for several days after stopping Sustiva. A reduction in CNS side effects was found last year in a small study using stepped-up dosing in first-time users (200 mg for six days, 400 mg for seven days, then the full dose), and drug resistance was not seen. Please see package insert for more complete potential side effects and interactions.
Doctor
Sustiva (efavirenz) dosed once daily was approved for HIV infection in 2002. This antiretroviral can be used in several combinations, but its main use is when it is taken in combination with Truvada in the fixed dose combination called Atripla (tenofovir/emtricitabine/efavirenz). This combination is currently preferred by DHHS guidelines and is among the most frequently chosen regimens when starting treatment because this three-drug combination is just one tablet, once daily—and the convenience and enthusiasm for this degree of simplicity has been very important for many patients. In addition, studies have consistently shown that these three drugs are at least as potent and successful as any other three-drug regimen—there is no study that has ever shown a superior outcome versus these three drugs. However, there are some side effects associated with Sustiva. CNS side effects (dizziness, headache, vivid dreams, concentration difficulty, worsening depression, etc.) are a common issue for patients when starting this drug. Typically, up to a half of those who start it will report at least one of these side effects in the first few days of taking it. However, the majority of people find that as they stay on it, these side effects fade away leading to a consistent finding that about 1 in 20 who start this drug eventually stop it, at least in clinical trial settings. In addition, there is a risk of a rash when starting this drug, though most patients find that this rash will fade with continued dosing. Since taking the drug with food increases its concentration in the bloodstream (possibly leading to more CNS side effects), efavirenz is generally dosed at night (you are asleep and don’t perceive the problems) and on an empty stomach. Efavirenz is a category D medication in pregnancy. Its potential effects on the fetus are well documented, and it shouldn’t be given to women who are planning pregnancy. If there is incomplete virus suppression, resistance is often observed first to efavirenz in various regimens. Fortunately the most common initial mutation to this drug—K103N—does not lead to cross-resistance to etravirine. —Cal Cohen, MD
Activist
The most popular of the non-nukes, Sustiva does offer convenient once-a-day dosing. The major downsides are the sleep disturbances, vivid dreams, and nightmares that never go away for some patients. Taking the drug at bedtime, and not taking it with high fat foods can lessen those effects for some. Sustiva can also raise blood lipids (cholesterol, etc.), so patients should be sure to get fasting lipid levels, and consider switching if it causes lipid problems. The long half-life that makes Sustiva such a good once-a-day drug also means that if you have to stop it for any reason, you should consult your doctor and stop several days before your other drugs to avoid developing resistance. —Jeff Taylor
