March/April 2009
Common Name: efavirenz (EFV)
Brand Name: Sustiva
Class: non-nucleoside analog (also called non-nucleoside reverse transcriptase inhibitor, NNRTI or non-nuke)
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, but do not double up on next dose.
AWP: $627.06 / month for thirty 600 mg tablets
Manufacturer contact: Bristol-Myers Squibb,
www.sustiva.com; 1 (800) 321-1335
AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov
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, or ergot medications (Wigraine, Methergine, and Cafergot), or Vfend, St. John's wort, and 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 should also be boosted with Norvir (Reyataz 300 mg/Norvir 100 mg once daily) when taken with Sustiva. HIV-treatment-experienced people should not use Reyataz with Sustiva. Sustiva and Invirase should not be used in combination. With once-daily Lexiva, boost with 300 mg Norvir. Rifampin decreases Sustiva concentrations, so it should be avoided. 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 Sporanox 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 when taken with Sporanox.
Tips: Sustiva taken at bedtime helps reduce CNS symptoms, but it can be taken at any time. Avoid driving or operating heavy machinery for a few hours after dose. High-fat food and alcohol could up the risk of side effects; this is why taking it on an empty stomach is recommended. Some people adjust to Sustiva when taking Ativan or Ambien to sleep for the first few weeks, but either may make you even more groggy the next morning. Women who can become pregnant need to use appropriate birth control, as Sustiva can affect the effectiveness of the Pill (see Interactions above) and increase the risk of birth defects. 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. Please see package insert for more complete potential side effects and interactions.
Doctor
Sustiva (efavirenz) dosed once daily was approved for HIV infection in 1998. This antiretroviral in combination with Truvada and in the fixed dose combination Atripla (tenofovir/emtricitibine/efavirenz) is preferred by patients and the health care workers who treat HIV infection. CNS side effects (dizziness, headache, vivid dreams, concentration difficulty, worsening depression, etc.) are a prominent issue with its use. We see them in about 30% of our patients. I always tell my patients that means 70% have no or minimal side effects. We do not give this drug to someone who has or has had significant depression. We learned the hard way that suicidal ideation can be part of the depression. Rarely, I have seen seizures increase (in patients with a seizure disorder) with use of efavirenz. In general, the most prominent side effects (dizziness, vivid dreams) do truly decrease within 3-4 weeks. Difficulty concentrating is the major reason for discontinuation of the drug in my patients. 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. This does not mean it cannot be taken with food. I do have patients who take it with food and have no adverse effects. 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. Women of child-bearing potential should consider contraception if they are taking efavirenz (remember Atripla contains efavirenz). -- Frank M. Graziano, M.D., Ph.D.
Activist
Sustiva is the "preferred" DHHS Guidelines NNRTI. It is conveniently dosed once a day in both the 600 mg tablet and as the non-nuke component in Atripla. Sustiva has a long half-life, it stays in the body longer (more so in African-Americans and Hispanics); it is potent and it works. But Sustiva can cause birth defects and should not be used by pregnant women, particularly during the first trimester, and should be avoided by women wanting to have children. Because side effects can affect the central nervous system, Sustiva is probably not the drug of choice for those with a history of depression or other mental health conditions. Heed the warning "Do not drive or operate heavy machinery when taking this drug." Sustiva should be taken at bedtime as it can cause "wooziness." The enhanced dream states that you've all heard about don't last forever, usually going away within time -- a blessing or disappointment. Personally, I thoroughly enjoyed mine. -- Morris Jackson