Standard DoseOne tablet (800 mg of the PI darunavir boosted by 150 mg cobicistat) once daily with food, in people with no darunavir-associated drug resistance, including both treatment-experienced individuals and those who are treatment-naïve (taking HIV therapy for the first time). Must be taken in combination with another antiretroviral(s) which does not contain the medications in this drug or medication from the same drug classes. Use with non-nucleosides or other protease inhibitors is not recommended.
Prezcobix is only available for people taking darunavir once daily, not those who require darunavir twice daily. It is not recommended to co-administer Prezcobix with tenofovir disoproxil fumarate (brand name Viread, found in Truvada), with creatinine clearance (CrCl) less than 70 mL/min (a measure of kidney function).
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. Prezcobix is not recommended during pregnancy due to substantially lower exposures of darunavir and cobicistat during pregnancy. Cobicistat has not been studied in individuals under 18 years of age, thus Prezcobix should not be used in pediatric patients. Do not use in people with severe liver impairment.
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Potential Side Effects and Toxicity
- See the individual drugs contained in Prezcobix: Prezista and Tybost.
- See package insert for more complete information on potential side effects and interactions.
As darunavir (contained in Prezcobix) contains a sulfa component, patients with a known sulfonamide allergy should be monitored for rash after starting it. The most common side effects reported in at least moderate intensity in 5% or more of study participants were diarrhea, nausea, rash, headache, abdominal pain, and vomiting. 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. Kidney impairment, including cases of acute kidney failure and Fanconi syndrome, has been reported in patients taking both cobicistat and Viread (tenofovir DF or TDF, also found in Truvada). When used with TDF, a baseline CrCl, urine glucose, and urine protein is needed; CrCl, urine glucose, and urine protein should be monitored regularly while taking Tybost-containing regimens. While very rare, severe rash (in 0.4% of those taking it), 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) and an increased risk of cardiovascular (CV) events. 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. With PIs, there can be increased bleeding in hemophiliacs.
Potential Drug Interactions
Cobicistat interacts with many drugs because, as a booster, it inhibits liver enzymes involved in drug metabolism. Do not take with betamethasone, budesonide, carbamazepine, ciclesonide, dexamethasone, dronedarone, ergot derivatives, eslicarbazepine, fluticasone, triazolam, oral midazolam, lomitapide, lurasidone, methylprednisolone, mometasone, oxcarbazepine, phenobarbital, phenytoin, pimozide, rivaroxaban, Revatio, simvastatin, lovastatin, St. John’s wort, triamcinolone, alfuzosin, ranolazine, or rifampin. Not recommended to be taken with avanafil, everolimus, rifapentine, salmeterol, ticagrelor, or voriconazole. Apixaban dose may need to be adjusted. Beclomethasone, prednisolone, 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. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not.
Since Prezista (darunavir) must be used with a PK enhancer such as cobicistat or ritonavir, this formulation makes for greater convenience, one less pill, and one less co-pay. The resulting co-formulation, however, is rather large in size, but the tablets are designed as an immediate-release formulation, so no potential problem with absorption is anticipated if the tablets are chewed, split, or crushed. A single-tablet, once-daily regimen containing darunavir/COBI/FTC/TAF is now available (see Symtuza). Darunavir is recommended as part of an initial regimen “in certain clinical situations” in DHHS guidelines. DHHS wrote this is “in part because of greater tolerability” with the integrase inhibitor medications compared to Prezista + Norvir or Prezcobix. According to the guidelines, “An example of a situation in which a darunavir-based regimen may still be preferred is when a high genetic barrier to resistance is particularly important, such as when there is substantial concern regarding a person’s adherence or when antiretroviral therapy (ART) should be initiated before resistance test results are available [go to aidsinfo.nih.gov].” Examples of people needing to start treatment immediately before resistance test results are available include newly infected individuals, pregnant women, and those who are experiencing certain opportunistic infections (an indication of advanced disease).
Dr. David Hardy says:
Approved in early 2015, this two-drug tablet consolidated Prezista and the booster Tybost into one tablet. It assures that Prezista will always be taken with its necessary booster. It has the “distinction” of being the largest antiretroviral tablet, which may be a problem for some PLWH to swallow. It was developed not only to ensure boosting and reduce pill number, but also as part of the run-up to the development of Symtuza. Its side effects are identical to those mentioned in Prezista.
Activist Moisés Agosto-Rosario says:
This is a protease inhibitor (PI) combined in one tablet with the booster known as cobicistat (COBI). Because of COBI, this PI can be taken once a day and should be used in combination with other HIV medicines. This protease inhibitor is superior in efficacy and tolerability when compared to Kaletra (lopinavir/ritonavir), another boosted PI. Darunavir is lipid-friendly and less likely to cause metabolic complications. If prescribed with Truvada, it is important to then monitor kidney functions and bone density. As with the other protease inhibitors, darunavir is metabolized by the liver; many drug-drug interactions can occur, either increasing or decreasing drug levels, causing serious problems. Your doctor must be aware of all the medications you take, even
if they are over-the-counter or supplements.