Prezista

Prezista contains a sulfa component and should be used with caution by patients with known sulfonamide allergy. Most common side effects may include diarrhea, nausea, headache, rash, vomiting, and abdominal pain. Measure liver function before starting and then monitor, with perhaps closer monitoring for those with underlying liver problems, especially during the first several months. No dose adjustment necessary with mild to moderate liver disease, but Prezista + Norvir is not recommended for people with severe liver impairment.

While very rare, severe rash can be accompanied by fever and/or elevations of liver enzymes, and can be life-threatening. Seek immediate medical attention. When used with Tybost a small increase in serum creatinine (SCr) may be observed that does not translate to a decrease in kidney function. Observational cohort studies reported an association between some PIs (including darunavir taken with ritonavir) and an increased risk of cardiovascular events. Although some older PIs have been associated with liver toxicity, lactic acidosis, diabetes, or fat redistribution, these conditions are only rarely—if at all—observed 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. Protease inhibitors can cause increased risk for bleeding in hemophiliacs.

Drug interactions of Prezista + Norvir may be different from those with Prezista + Tybost. Note: Tybost is not interchangeable with Norvir. Do not take with alfuzosin, cisapride, colchicine (in patients with kidney or liver impairment), dronedarone, ivabradine, lomitapide, lurasidone, naloxegol, ranolazine, pimozide, ergot derivatives, triazolam, oral midazolam, rifampin, Revatio, St. John’s wort, or Zepatier. Not recommended with the blood thinners everolimus, rivaroxaban (Xarelto), or ticagrelor. Not recommended with Mavyret (glecaprevir/pibrentasvir), simeprevir, rifapentine, irinotecan, salmeterol, and avanafil. Tramadol dose decrease may be needed. Monitor therapeutic effects and adverse reactions with use of some analgesics, such as fentanyl and oxycodone. Monitoring of clonazepam, phenytoin, and phenobarbital is recommended. Reducing dose of rifabutin is recommended. Do not use lovastatin or simvastatin, or co-formulations containing these drugs (Advicor and Vytorin).

Cholesterol-lowering alternatives are rosuvastatin, atorvastatin (should not exceed 20 mg per day), pitavastatin, and pravastatin, but should be used with caution and started at the lowest dose possible. Monitor for increased side effects from these medications. Reduce clarithromycin dose by 50 to 75% in kidney impairment. The antifungal drugs isavuconazole, posaconazole, ketoconazole, and itraconazole should be used with caution (maximum dose is 200 mg per day for the last two). Voriconazole should not be used unless the benefits outweigh the risks. Prezista increases levels of nasal and inhaled fluticasone (found in Advair, Flonase, Breo Ellipta, Arnuity Ellipta, and Flovent) and budesonide, as well as systemic corticosteroids ciclesonide, betamethasone, dexamethasone, methylprednisolone, mometasone, and triamcinolone. Use alternative corticosteroid and monitor for signs of Cushing’s syndrome. Beclomethasone, prednisolone, and prednisone as alternative corticosteroids may be considered, particularly for long-term use. Erectile dysfunction drugs should not exceed 10 mg Cialis, or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of oral contraceptives may be decreased; consider using alternative methods of contraception.

Monitoring is recommended for co-administration with drospirenone due to the potential for hyperkalemia (higher than normal potassium levels in the blood). Monitoring is recommended with buprenorphine, buprenorphine/naloxone, and methadone. Titration or decreased dose may be needed for buspirone, diazepam, estazolam, and zolpidem. Therapeutic drug monitoring is recommended for antiarrhythmics amiodarone, bepridil, disopyramide, flecainamide, systemic lidocaine, mexiletine, propafenone, and quinidine. Cannot be taken with Zepatier. Based on its 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, as there are many other drug interactions not listed here.

Prezista 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.” Examples of people needing to start treatment immediately before resistance test results are available include newly diagnosed individuals, pregnant women, and those who are experiencing certain opportunistic infections (an indication of advanced disease). Read about regimens in the online version of this page. Prezista + Norvir is a preferred component in the DHHS perinatal guidelines for use in pregnancy. 

There is growing evidence that a protease inhibitor-based regimen, boosted by ritonavir plus Epivir (lamivudine), can maintain viral suppression in patients who initiated triple-drug therapy, who achieved sustained viral suppression for at least 1 year, and who have no evidence of, or risk of resistance to, either darunavir or lamivudine. Use of Prezista with Norvir and Epivir may be a reasonable option when the continued use of TDF, TAF, or ABC is contraindicated or not desirable. Additionally, another ART switch strategy with some supporting evidence in patients with viral suppression in the DHHS guidelines is to switch patients to a boosted protease inhibitor + integrase inhibitor. In two small observational studies, patients were switched from their current ART regimens to Prezista + Norvir + Tivicay, and viral suppression was maintained in over 97% of participants. For patients on a complicated salvage regimen with current viral suppression and a history of treatment failure, there is evidence to support simplifying the regimen to a combination of Genvoya + Prezista.

Dr. Melanie Thompson:

Darunavir quickly became the “go to” PI because of its tolerability, hardy activity against resistant virus, and once daily dosing (at 800 mg) with a booster when viral resistance is not a concern. It should be taken twice daily at 600 mg with a booster in the setting of resistance. It is available coformulated with cobicistat as Prezcobix, and with cobi, TAF, and FTC as Symtuza.

Darunavir may cause an allergic reaction in some, but not all, people who are allergic to sulfa. Boosted darunavir has many drug interactions due to the booster, but also due to its own pharmacologic properties that raises some drug levels and lowers others. Don’t guess about this—look it up and consult an expert! This is one reason that boosted drugs are no longer considered first choice for therapy. Large cohort studies have associated darunavir, like abacavir, with increased rates of cardiovascular disease.

Activist Bridgette Picou:

Like other boosted regimens, Prezista is metabolized in the liver, which means potential drug-drug reactions. Discuss all supplements and over-the-counter medications with your provider. An advantage could be that it is lipid friendly. Side effects can happen and should be discussed with a clinician to see if there are other more tolerable options.