Prezcobix (darunavir and cobicistat)

Prezcobix may cause serious side effects, including:

• Diabetes and high blood sugar (hyperglycemia). Some people who take protease inhibitors including Prezcobix can get high blood sugar, develop diabetes, or your diabetes can get worse. Tell your healthcare provider if you notice an increase in thirst or urinate often while taking Prezcobix.
• Changes in body fat can happen in people who take HIV-1 medications. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known.
• Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having new symptoms after starting your HIV-1 medicine.
• Increased bleeding for hemophiliacs. Some people with hemophilia have increased bleeding with protease inhibitors including Prezcobix.

The most common side effects of darunavir, one of the medicines in Prezcobix, include:

• diarrhea
• nausea
• rash
• headache
• stomach-area (abdominal) pain
• vomiting

These are not all of the possible side effects of Prezcobix. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Recommended Dosage

Prezcobix is a fixed-dose combination product containing 800 mg of darunavir and 150 mg of cobicistat. In treatment-naïve and treatment-experienced adults and pediatric patients weighing at least 40 kg with no darunavir resistance-associated substitutions, the recommended dosage of Prezcobix is one tablet taken once daily orally with food. Administer Prezcobix in conjunction with other antiretroviral agents.

Testing Prior To Initiation Of Prezcobix

HIV Genotypic Testing

• HIV genotypic testing is recommended for antiretroviral treatment-experienced patients.
• However, when HIV genotypic testing is not feasible, Prezcobix can be used in protease inhibitor-naïve patients, but is not recommended in protease inhibitor-experienced patients.

Creatinine Clearance

• Prior to starting Prezcobix, assess estimated creatinine clearance because cobicistat decreases estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function.
• When co-administering Prezcobix with tenofovir disoproxil fumarate (tenofovir DF) assess estimated creatinine clearance, urine glucose, and urine protein at baseline.

Not Recommended In Severe Renal Impairment

• Prezcobix co-administered with tenofovir DF is not recommended in patients who have an estimated creatinine clearance below 70 mL per minute.

Not Recommended In Severe Hepatic Impairment

• Prezcobix is not recommended for use in patients with severe hepatic impairment.

Not Recommended During Pregnancy

• Prezcobix is not recommended during pregnancy because of substantially lower exposures of darunavir and cobicistat during the second and third trimesters.
• Prezcobix should not be initiated in pregnant individuals. An alternative regimen is recommended for those who become pregnant during therapy with Prezcobix.

Potential For Prezcobix To Affect Other Drugs

• Darunavir co-administered with cobicistat is an inhibitor of CYP3A and CYP2D6. Cobicistat inhibits the following transporters:
  • P-glycoprotein (P-gp),
  • BCRP, MATE1, OATP1B1 and
  • OATP1B3.
• Therefore, co-administration of Prezcobix with drugs that are primarily metabolized by CYP3A and/or CYP2D6 or are substrates of P-gp, BCRP, MATE1, OATP1B1 or OATP1B3 may result in increased plasma concentrations of such drugs, which could increase or prolong their therapeutic effect and can be associated with adverse events.
• Co-administration of Prezcobix with drugs that have active metabolite(s) formed by CYP3A may result in reduced plasma concentrations of these active metabolite(s), potentially leading to loss of their therapeutic effect (see Table 1).

Potential For Other Drugs To Affect Prezcobix

• Darunavir is metabolized by CYP3A. Cobicistat is metabolized by CYP3A, and to a minor extent, by CYP2D6.
• Co-administration of Prezcobix and drugs that induce CYP3A activity are expected to increase the clearance of darunavir and cobicistat, resulting in lowered plasma concentrations of darunavir and cobicistat which may lead to loss of therapeutic effect and development of resistance.
• Co-administration of Prezcobix and other drugs that inhibit CYP3A may result in increased plasma concentrations of darunavir and cobicistat (see Table 1).

Established And Other Potentially Significant Drug Interactions

• Table 1 provides dosing recommendations for expected clinically relevant interactions with Prezcobix (this table is not all inclusive). These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of therapeutic effect.
• The table includes potentially significant interactions but is not all inclusive. See prescribing information for the list of contraindicated drugs.

Table 1: Established and Other Potentially Significant* Drug Interactions: Alterations in Dose or Regimen May Be Recommended

Drugs Without Clinically Significant Interactions With Prezcobix

• Clinically relevant drug-drug interactions have not been observed or are not anticipated with concomitant use of darunavir and cobicistat with rilpivirine, dolutegravir, raltegravir, abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, tenofovir DF, lamivudine, stavudine, zidovudine, or acid modifying medications (antacids, H₂-receptor antagonists, proton pump inhibitors).

• There are insufficient data with Prezcobix in pregnant individuals from the APR to inform a drug-associated risk of pregnancy outcomes.
• The Centers for Disease Control and Prevention recommend that HIV infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV.
• There are no data on the presence of darunavir or cobicistat in human milk, the effects on the breastfed infant, or the effects on milk production.
• Darunavir and cobicistat are present in the milk of lactating rats (see Data). Because of the potential for (1) HIV transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in breastfed infants, instruct mothers not to breastfeed if they are receiving Prezcobix.