Symtuza
For adults and children weighing at least 88 pounds (40 kg). Take missed dose as soon as possible, as long as it is at least 12 hours before 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 by people with an estimated creatinine clearance of at least 30 mL/min. It should not be used by people who have severe kidney or liver impairment. Symtuza is not recommended during pregnancy due to substantially lower exposures of darunavir and cobicistat components during pregnancy.
For people who took Apretude (CAB-LA) for PrEP, HHS recommended as a component for rapid ART for someone newly diagnosed or entering care with minimal or no labs available.
- See the individual drugs contained in Symtuza: Prezista, Tybost, and Descovy.
- See package insert for more complete information on potential side effects and interactions.
800) JANSSEN (526-7736)
janssen.com; symtuza.com
JO-ANN JOSE, MD, MPH:
Symtuza is a large pill with four drug components—cobicistat, which boosts the protease inhibitor (PI) darunavir, as well as two NRTIs, emtricitabine and tenofovir alafenamide (TAF). TAF poses less of a concern for kidney and bone side effects than TDF, the older version of tenofovir. There is greater potential for drug interactions because cobicistat is a booster that can raise levels of other drugs in the blood. Symtuza makes a PI-based regimen into a convenient once-daily pill. There are some side effects and long-term problems associated with protease inhibitors. Newer protease inhibitors, like darunavir, are less likely to cause this, but they are thought to have an impact on lipid levels, so it would be important to keep an eye on them. For people who were on Apretude for PrEP before acquiring HIV, Symtuza is a preferred Rapid Start regimen because we would not want to use an integrase inhibitor (INSTI) regimen until we know that there are no mutations that are resistant to INSTI drugs. Symtuza is quite an expensive drug, so we don’t use this unless there’s a pretty clear indication that you need it.
Many drug interactions are possible due to cobicistat; see package insert. Do not take with alfuzosin, carbamazepine, dexamethasone, dronedarone, ergot derivatives, ivabradine, triazolam, oral midazolam, lomitapide, lurasidone, naloxegol, phenobarbital, phenytoin, pimozide, Revatio, sildenafil (Viagra, Revatio and generics), simvastatin, lovastatin, St. John’s wort, ranolazine or rifampin. Monitor for lack of virologic response when eslicarbazepine or oxcarbazepine is necessary. Not recommended to be taken with avanafil, ciclesonide, dabigatran etexilate (in renal impairment), everolimus, Intelence, irinotecan, mometasone, rifabutin, rifapentine, rivaroxaban, salmeterol, ticagrelor, triamcinolone or voriconazole. Beclomethasone, prednisolone and prednisone as alternative corticosteroids 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. Apixaban (Eliquis) dose may need to be adjusted. Do not take with colchicine if there is kidney or liver impairment. The dose of colchicine will need to be adjusted. Initiation or dose adjustments of insulin or oral hypoglycemic medications may be required for some individuals. Cannot be taken with Zepatier. Based on its mechanism of action, drug interactions with other hepatitis C medications are probably similar to the interactions with Prezcobix + 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 that are not listed here.
Darunavir contains a sulfa component, so use with caution in people with severe sulfa allergies. Side effects most commonly reported in studies include diarrhea (9%), rash (8%), nausea (6%), fatigue (4%), headache (3%), abdominal discomfort (2%) and flatulence (2%). While very rare (in less than 0.4%), severe rash, accompanied in some cases by fever and/or elevations of AST/ALT (liver enzymes), can be life-threatening. Seek medical attention immediately. Data associate TAF with weight gain. Observational cohort studies reported an association between some PIs (including darunavir taken with ritonavir) and an increased risk of cardiovascular (CV) events. Data on darunavir + cobicistat are too limited to make these conclusions. With PIs, there can be increased bleeding in hemophiliacs. Cobicistat can cause a small, reversible increase in serum creatinine (SCr, which decreases estimated creatinine clearance) within the first few weeks of treatment without affecting glomerular filtration (the process by which the kidneys filter the blood; see Tybost for more information). While cobicistat does not affect actual kidney function, its effect on SCr can make monitoring of impaired kidney function more difficult or less accurate. However, people 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 people with or at risk for kidney impairment should also be monitored. Prior to initiation, people should be tested for hepatitis B virus (HBV). Severe exacerbations of hepatitis B have been reported in people with HIV-HBV co-infection who have discontinued Symtuza (due to elimination of the emtricitabine and TAF components, which also treat hepatitis B). Monitor liver enzymes closely in people co-infected with HBV and, if appropriate, initiation of anti-hepatitis B therapy may be warranted upon Symtuza discontinuation. Call your health care provider right away if you develop any of the following signs or symptoms of hepatitis: yellowing of the skin or whites of the eyes; dark or tea-colored urine; pale-colored bowel movements; nausea or vomiting; loss of appetite or pain, aching or tenderness on the right side below the ribs.
A darunavir-based regimen is the only initiation treatment recommended by HHS for people who have used Apretude (CAB-LA for PrEP) when resistance data have yet to come back (rapid ART). That’s because viral mutations conferring drug resistance to INSTIs like long-acting cabotegravir (found in Apretude and in Cabenuva) have been observed. CAB-LA stays in the body a very long time; drug levels may be too low to prevent infection and therefore may select for resistant virus. The other “clinical situations” mentioned in the HHS recommendation refers to people with adherence problems on their current HIV treatment. Symtuza is not the same as Prezcobix + Descovy, because Symtuza contains a lower dose of TAF than Descovy. A benefit of the PIs is their high genetic barrier to developing 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 it 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.” Darunavir-containing regimens had stronger evidence supporting their use than do regimens containing atazanavir (another PI on the market). Not HHS recommended in pregnancy due to lower blood levels of darunavir and cobicistat seen in second and third trimesters. Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; GO TO apregistry.com.
JUAN MICHAEL PORTER II:
Call me biased, but whenever I see that an HIV medication has a booster, I immediately feel wary. Symtuza has a booster, but it also has the highest genetic barrier protease inhibitor (PI) available, which makes it useful to people who need a boosted PI because they’ve developed resistance to other classes of drugs. That said, it is very expensive.