darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/COBI/FTC/TAF)
Standard DoseOne tablet once daily with food for treatment-naïve people or people with suppressed viral load on a stable HIV regimen for at least 6 months who have no known resistance to the darunavir or tenofovir components of the regimen. Tablet contains 800 mg darunavir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg tenofovir alafenamide.
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. Dose cannot be adjusted for people with kidney or liver problems. Symtuza can be used in people with an estimated creatinine clearance of at least 30 mL/ min. It should not be used in people with severe kidney or liver impairment.
(800) JANSSEN (526-7736)
Potential Side Effects and Toxicity
➤ SEE THE INDIVIDUAL DRUGS CONTAINED IN SYMTUZA: Prezista, Tybost, and Emtriva (TAF is not marketed separately for HIV, but see also Descovy).
➤ SEE PACKAGE INSERT for more complete informa- tion on potential side effects and interactions.
As darunavir contains a sulfa component, use with caution in patients with sulfa allergies. Side effects most commonly reported in studied subjects include diarrhea (9%), rash (8%), nausea (6%), fatigue (4%), headache (3%), abdominal discomfort (2%), and flatulence (2%). While very rare, severe rash, accompanied in some cases by fever and/or elevations of AST/ ALT (liver enzymes), can be life-threatening. Seek medical attention immediately. Observational cohort studies reported an association between some PIs (including darunavir when given with Norvir) and an increased risk of cardiovascular (CV) events, but data with darunavir/cobicistat is too limited to see such a connection. With PIs, there can be increased bleeding in hemophiliacs. Cobicistat can cause a small, reversible increase in serum creatinine (SCr, which indicates the eGFR or estimated CrCl lab values) within the first few weeks of treatment without affecting actual kidney function (see Tybost for more information). Patients experiencing a confirmed increase in serum creatinine of greater than 0.4 mg/dL from baseline should be closely monitored for renal safety. Serum phosphorus in patients with or at risk for kidney impairment should also be monitored. 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 emtricitabine 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. Although some older PIs have been associated with liver toxicity, lactic acidosis, diabetes, or fat redistribution, these conditions are only rarely, or never, seen with darunavir. IRIS (immune reconstitution inflammatory syndrome) may occur as the immune system regains strength; signs and symptoms from previous infections may occur soon after HIV treatment is initiated. Report symptoms of illness, such as shingles or TB, to a health care provider.
Potential Drug Interactions
Do not take with Epivir-HBV, Hepsera, or Vemlidy (TAF), all three used for the treatment of hepatitis B. Use with other protease inhibitors or Intelence, Sustiva, or Viramune is not recommended. Do not take with betamethasone, budesonide, carbamazepine, dexamethasone, dronedarone, eslicarbazepine, ergot derivatives, fluticasone, triazolam, oral midazolam, lurasidone, methylprednisolone, oxcarbazepine, phenobarbital, phenytoin, pimozide, Revatio, simvastatin, lovastatin, St. John’s wort, alfuzosin, ranolazine, or rifampin. Not recommended to be taken with apixaban, avanafil, dabigatran etexilate (in renal impairment), everolimus, rifampentine, salmeterol, ticagrelor, or voriconazole. Beclomethasone and prednisone as alternative corticosteriods may be considered, particularly for long-term use. Atorvastatin and rosuvastatin dose should not exceed 20 mg daily. Clinical monitoring is recommended with drospirenone, due to potential for hyperkalemia. Do not take with colchicine if there is kidney or liver impairment. Can be used with Daklinza. Cannot be taken with Zepatier. Based on the mechanism, drug interactions with other hepatitis C medications are probably similar to the interactions with Prezista + Norvir + Descovy. Not intended to be taken with other HIV medications, unless prescribed that way. 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.
This medication was approved in 2018 and is the first STR containing a protease inhibitor. This formulation is much more convenient and is associated with fewer copays. A benefit of the PIs is their high genetic barrier to the development of drug resistance. While medical providers may hate to say it out loud, this means greater forgiveness of missed doses; missing a dose here and there is never advisable but does happen. As such, a PI-based regimen such as Symtuza suits some people who may have trouble with the near-perfect drug adherence required of HIV treatment. In fact, the FDA allowed Janssen to advertise Symtuza as “help[s] protect against resistance.” Symtuza may be used in rapid initiation, treatment given within 7 days of HIV diagnosis, before resistance test results are available. Treatment-experienced individuals with undetectable viral loads for at least six months may switch to Symtuza. Darunavir is available under the brand name Prezista and is also found in the co-formulated pill Prezcobix (with cobicistat). Compared with tenofovir DF, the tenofovir alafenamide in Symtuza is safer on kidney and bone health. Also as a result of the TAF, Symtuza can be taken by people with more advanced kidney disease, down to a renal function (CrCL) of 30 mL/min.
Dr. David Hardy says:
What makes Symtuza unique among STRs is that it is the first one to contain a boosted protease inhibitor. It will essentially combine two currently available medications, Prezcobix and Descovy, into one tablet which promises to be smaller (more pharmaceutical magic) than the size of a Prezcobix tablet (which is the largest STR tablet to date). For PLWH who are doing well with a boosted protease inhibitor-containing regimen, Symtuza offers these folks the opportunity to experience the benefits of a one-tablet, once-a-day regimen for the first time. It is thought that many HIV-treating healthcare providers now offer this new STR to their patients on protease inhibitor-containing regimens. For those PLWH whose access or adherence to their ART regimens is, or is predicted to be, difficult or unreliable, this new STR offers them an option for a proven “HIV resistance-resistant” ART regimen in one pill. On the other hand, many HIV-treating healthcare providers and PLWH are feeling increasingly confident that an integrase inhibitor-containing regimen (e.g., Triumeq, Biktarvy) is just as resistant-to-resistance as a boosted protease inhibitor regimen and has better tolerability. Clinical trial data with Symtuza and clinical experience with Prezcobix and Descovy show that PLWH tolerate this regimen fairly well, but not as well as they tolerate unboosted integrase inhibitors (Triumeq, Biktarvy, and Isentress). Nausea, queasiness, diarrhea, and rash are most common side effects seen with Symtuza or its components.
Activist Moisés Agosto-Rosario says:
This is the first once-a-day single-tablet regimen containing a protease inhibitor, darunavir. One good thing about darunavir is that it has a high barrier to resistance. This also makes it a good candidate for treatment-naïve individuals as initial therapy. Because of the way darunavir and cobicistat, a booster contained in Symtuza, are metabolized by the liver you will have to monitor for many drug-drug interactions that can cause serious problems. Among them, you will find commonly prescribed drugs such as statins and some benzodiazepines (Halcion, for example).