EFV/3TC/TDF efavirenz/lamivudine/tenofovir disoproxil fumarate
Standard DoseOne tablet once daily on an empty stomach, preferably at bedtime (food increases the risk of central nervous system, or CNS, side effects). The Symfi tablet contains 600 mg of the NNRTI efavirenz plus 300 mg lamivudine and 300 mg tenofovir DF (TDF). The Symfi Lo tablet contains a lower dose of efavirenz, 400 mg, plus 300 mg lamivudine and 300 mg tenofovir DF (TDF).
For adults and pediatric patients weighing at least 77 pounds (35 kg) for Symfi Lo and 88 pounds (40 kg) for Symfi.
Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Do not split or crush the tablet. Dose cannot be adjusted for people with kidney problems. Symfi and Symfi Lo are not recommended for patients with CrCl less than 50 mL/min or individuals requiring dialysis. Symfi or Symfi Lo should not be used in people with moderate or severe kidney or liver impairment.
See the individual drugs contained in SymFi and symfi lo: Sustiva, Epivir, and Viread.
See package insert for more complete information on potential side effects and interactions.
Symfi Lo: $1,961.33/month
Potential Side Effects and Toxicity
The most common side effects occurring in 5% or more of studied individuals include headache (14%), body pain (13%), fever (8%), abdominal pain (7%), back pain (9%), asthenia (6%), diarrhea (11%), nausea (8%), vomiting (5%), arthralgia (joint pain, 5%), depression (11%), insomnia (5%), anxiety (6%), pneumonia (5%), and rash (18%). These side effects are most common at the start of treatment and usually diminish in two to four weeks. Bedtime dosing on an empty stomach can help reduce symptoms. Use with caution in individuals with depression or other psychiatric issues who are not under a psychiatrist’s care. Prior to initiation, people should be tested for hepatitis B (HBV) infection. Severe exacerbations of hepatitis B have been reported in people who are co-infected with hepatitis B and have discontinued the lamivudine and/or tenofovir components. Monitor liver enzymes closely in people co-infected with hepatitis B and, if appropriate, initiation of anti-hepatitis B therapy may be warranted. The efavirenz component in these medications can cause a false positive result for marijuana on certain drug tests. A more specific confirmatory test can be done.
Potential Drug Interactions
Do not take with Epivir-HBV, Hepsera, or Vemlidy (TAF), all three used for treatment of hepatitis B. Do not take with another nephrotoxic (harmful to the kidneys) medication, such as high-dose or multiple NSAIDs (non-steroidal anti-inflammatory drugs; these include aspirin, ibuprofen – Motrin, Advil, and others, and naproxen sodium—Aleve and others). Should not be taken with voriconazole, ergot derivatives, midazolam, pimozide, triazolam, bepridil, or St. John’s wort. Efavirenz should also not be taken with other medications that prolong QTc interval (a heart problem) or medications with a known risk of torsades de pointes. May affect warfarin levels. Can decrease levels of buprenorphine and methadone—monitor for withdrawal. When taken with carbamazepine, phenobarbital, or phenytoin, periodic monitoring of anticonvulsant and efavirenz levels should be done or alternative anti-seizure drugs, such as levetiracetam, should be considered. Effectiveness of birth control pills may be decreased; consider the use of other contraceptive methods. Closer monitoring and dose adjustments may be required with posaconazole (avoid unless benefit outweighs potential risk) and itraconazole. Monitor effectiveness of clarithromycin or consider using azithromycin instead. Levels of immunosuppressants should be monitored when starting or stopping Symfi or Symfi Lo. Cardizem, Lipitor, Pravachol, and Zocor doses may need to be adjusted. Titrate dose of bupropion and sertraline based on clinical response. Avoid use of sorbitol-containing medicines with lamivudine; there are many, such as acetaminophen liquid (Tylenol liquid and others). No dose adjustment of Symfi or Symfi Lo needed with Sovaldi. Use caution when administering with Harvoni and monitor renal function closely due to possible increased tenofovir levels. Should not be taken with Epclusa or Zepatier. Not intended to be taken with other HIV medications, unless prescribed that way. See Atripla page for more potential side effects. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions which are not listed here.
Symfi and Symfi Lo are basically alternative versions of Atripla, a well-established HIV medication that’s no longer preferred when starting therapy. If you can’t sleep, ask your doctor about gradually adjusting the timing of your dose until it’s taken during the day. A genetic trait affecting drug metabolism of Sustiva, leading to a higher rate of side effects, occurs more in African Americans. For individuals with HIV-2, commonly found in some other countries, an NNRTI would not be recommended as HIV-2 is inherently resistant to NNRTIs. Go to aidsinfo.nih.gov.
Randomized clinical trial data have demonstrated the efficacy of lower dose (400 mg) efavirenz found in Symfi Lo along with fewer side effects. Symfi Lo is now approved in the U.S. for initial treatment of HIV infection (although guidelines no longer list it as a preferred option for someone starting medication). There is a discussion of the data on page G-31 of the guidelines.
Symfi and Symfi Lo are listed as a “Recommended Regimen in Certain Clinical Situations” in the DHHS guidelines, just as Atripla is, due to their association with a high rate of central nervous system side effects and possible association with suicidality. Be careful when stopping these medications, so that you avoid the rapid development of HIV resistance to them—check with your provider or pharmacist first.
Dr. Ross Slotten says:
I had not heard of either of these medications until I received a notice from United Health Care in 2018 that they were among the first-tier preferences in its formulary. By switching to one of these two drugs, policyholders living with HIV would have a lower co-pay—the incentive for the switch. Not a bad idea in 2010, but not today. Symfi contains efavirenz (600 mg), lamivudine (Epivir/3TC) and tenofovir disoproxil (TDF); Symfi Lo contains a lower dose of efavirenz (400 mg), which may have fewer side effects than the higher dose, with the same nucleoside backbone as Symfi. These medications are a false choice, unless one disagrees with DHHS guidelines. If we have to switch, why not switch to Biktarvy or Triumeq? There is no longer a role for drugs like Symfi and Symfi Lo as first-line agents because we’re gradually moving away from efavirenz and TDF-containing regimens in favor of agents with fewer adverse side effects.
Activist Bridgette Picou says:
Both Symfi and Symfi Lo are single-tablet regimens with the difference being that Symfi Lo has a lower dose of efavirenz at 400 mg vs. 600 mg in Symfi. The primary benefit of that is fewer neurologic effects like depression or insomnia. Discuss these and any history of mental concerns or upset with your doctor, as these medicines can make you feel angry or agitated under these circumstances. Rash is a common side effect that will usually go away on its own. On the plus side both Symfi and Symfi Lo cost less than comparable regimens available today.