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, toxicities). 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.
AWPSymfi Lo: $1,961.33/month
Potential Side Effects and Toxicity
• See the individual drugs contained in SymFi: Sustiva, Epivir, and Viread.
• See package insert for more complete information on potential side effects and interactions.
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 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 contraceptives. 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. Increase dose of Daklinza to 90 mg when used with Symfi or Symfi Lo. Should not be taken with Epclusa, Olysio, Viekira Pak, 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 in favor 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 rare 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. Randomized clinical trial data have demonstrated the efficacy of lower dose (400 mg) efavirenz found in Symfi Lo, however this dose has not been studied in a U.S. population, in pregnant women, or in patients with TB and HIV. The U.S. guidelines therefore preferentially recommends Symfi with higher dose efavirenz (600 mg) over the reduced dose of efavirenz found in Symfi Lo (400 mg) at this time.
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 it—check with your provider or pharmacist first.
Dr. David Hardy says:
Symfi and Symfi Lo are the ninth and tenth STRs approved by the FDA, in March 2018, and are the first fully generic STRs. Of note, while almost identical to the branded medication Atripla, the substitution of lamivudine for emtricitabine (Emtriva) makes them slightly different. The FDA approved these two fixed-dose combinations of previously approved antiretrovirals based not upon clinical trial data, but rather pharmacokinetic demonstration of bioequivalence, which means that Mylan, the manufacturer, had to show that the combination tablet of the three medications combined produced similar blood levels of the three drugs when given as three separate tablets. The lower dose of efavirenz in Symfi Lo (400 mg) is based upon supporting data from the ENCORE1 study which demonstrated similar virologic potency but fewer side effects with the lower dose of efavirenz. The uptake of these two new fully generic STRs in clinical practice is still uncertain as both the DHHS and IAS-USA guidelines removed efavirenz-containing regimens from their first-line recommended regimens many years ago, based primarily upon excessive side effects compared to newer STRs. A unique and distinguishing characteristic of these STRs is their lower monthly wholesale acquisition cost (WAC): $1,630 compared to $2,100 for Delstrigo, $2,950 for Biktarvy, $3,500 for Symtuza, $2,800 for Triumeq, and $3,000 for Genvoya and Stribild.
Activist Moisés Agosto-Rosario says:
Symfi and Symfi Lo are once-daily single-tablet regimens that might offer powerful antiretroviral treatment at a much lower price than comparable antiretroviral treatments on the market. The difference between them is that Symfi Lo has a lower dose of efavirenz than Symfi. Research among adults living with HIV shows that treating them with tenofovir and emtricitabine was comparably effective regardless of whether they also received 400 mg or 600 mg of efavirenz. The advantage of the lower 400 mg dose vs. the 600 mg higher is that the exposure to neurotoxicities is less, therefore individuals with the lower dose report less insomnia, depression, and dizziness.