Symfi and Symfi Lo
Single-tablet regimens containing an NNRTI and two NRTIs, efavirenz/lamivudine/tenofovir disoproxil fumarate EFV/3TC/TDF
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 people 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 also similar STR, Atripla.
- 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 include headache, body pain, fever, abdominal pain, back pain, asthenia (physical weakness or lack of energy), diarrhea, nausea, vomiting, arthralgia (joint pain), depression, insomnia, anxiety, pneumonia, and rash. 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 receiving mental health care. See also similar STR, Atripla. See Viread for TDF information. Kidney function should be assessed before initiating treatment and throughout therapy as determined by a provider. Prior to initiation, people should be tested for hepatitis B (HBV). Severe exacerbations of HBV have been reported in people with HBV co-infection and have discontinued emtricitabine and/or tenofovir, both of which treat hepatitis B. Monitor liver enzymes closely in co-infection. Initiation of HBV therapy may be warranted upon discontinuation. Efavirenz has been associated with central nervous system (CNS) birth defects in non-human primates, and cases of neural tube defects have been reported after first trimester exposure in humans. See Atripla. Efavirenz 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 Cimduo/Temixys, Descovy, Emtriva, Epivir-HBV, Hepsera, Truvada, Vemlidy, or Viread, all 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 for torsades de pointes. For people weighing at least 110 pounds (50 kg) and taking rifampin, it is recommended to give a 200 mg efavirenz dose (for total efavirenz dose of 800 mg). 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. May decrease effectiveness of birth control pills; 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). 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. 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 that are not listed here.
Symfi and Symfi Lo are basically alternative versions of Atripla, a medication that’s no longer preferred when starting therapy. The advantage is they may be a cheaper alternative than some first-line medications because their components are all available as generics. 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 efavirenz, 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. Randomized clinical trial data have demonstrated the efficacy of lower dose efavirenz along with fewer side effects. Be careful when stopping these medications, so that you avoid rapid development of HIV resistance to them. Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; go to apregistry.com
Dr. Melanie Thompson:
Atripla revolutionized HIV treatment in 2006 when it became the first once-daily STR, but it has not been recommended for initial therapy for most people in the U.S. for a number of years, largely due its many side effects. Central nervous system side effects include depression, dizziness, sleepiness, abnormal dreams, headache, and most notably, suicidality. Others include rash, elevation of LDL cholesterol, and EKG changes that could be associated with serious heart rhythm abnormalities (QTc prolongation). Efavirenz also has many drug-drug interactions that complicate its use with many drugs. The generics Symfi and Symfi Lo both use 3TC (which is generic) instead of FTC, and Symfi Lo uses a 400 mg dose of efavirenz that has been associated with fewer side effects. It’s unfortunate that HIV generics often only emerge after the usefulness of the drug has passed. This speaks to the complicated and profit-driven game that is drug development in the U.S. but also to the extremely rapid pace of drug advances in HIV treatment.
Activist Michael Broder:
Symfi and Symfi Lo were approved in 2018, and are “branded generic” versions of Atripla. When Atripla was approved, efavirenz and TDF were the “it” drugs (and emtricitabine was virtually a carbon copy of the highly successful lamivudine), and Atripla quickly became the market leader. But efavirenz causes neurologic side effects such as nightmares, depression, and suicidal ideation. As for TDF, it is effective and tolerable with a great resistance profile, but has worrisome bone and kidney side effects, and has been supplanted by its safer chemical cousin, TAF. Given other available options, it’s hard to imagine why any provider today would recommend Symfi for anybody. If your provider recommends Symfi or Symfi Lo, they may have a good reason, but make sure they tell you what it is.