PREZCOBIX

Indications and Usage ( 1 ) 02/2026 Dosage and Administration ( 2.1 , 2.2 , 2.3 ) 02/2026

1 INDICATIONS AND USAGE PREZCOBIX and PREZCOBIX PED are indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) in treatment-naïve and treatment-experienced adults and pediatric patients 3 years of age and older weighing at least 15 kg with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V) [see Use in Specific Populations (8.4) and Clinical Studies (14) ] . PREZCOBIX and PREZCOBIX PED are a two-drug combination of darunavir, a human immunodeficiency virus (HIV-1) protease inhibitor, and cobicistat, a CYP3A inhibitor, and are indicated for the treatment of HIV-1 in treatment-naïve and treatment-experienced adults and pediatric patients 3 years of age and older weighing at least 15 kg with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V). ( 1 )

2 DOSAGE AND ADMINISTRATION Recommended dosage: Adults and pediatric patients weighing at least 40 kg: One 800 mg/150 mg tablet taken once daily with food. ( 2.1 , 2.2 ) Pediatric patients weighing at least 25 kg to less than 40 kg: One 675 mg/150 mg tablet taken once daily with food. ( 2.1 , 2.2 ) Pediatric patients 3 years of age and older weighing at least 15 kg to less than 25 kg: One 600 mg/90 mg tablet for oral suspension taken once daily with food. PREZCOBIX PED must be dispersed in drinking water and taken immediately with food. ( 2.2 , 2.3 ) Testing Prior to Initiation: HIV genotypic testing is recommended for antiretroviral treatment experienced patients. Assess estimated creatinine clearance in all patients prior to starting PREZCOBIX or PREZCOBIX PED. When used with tenofovir disoproxil fumarate (TDF): Assess urine glucose and urine protein at baseline and monitor creatinine clearance, urine glucose, and urine protein. Monitor serum phosphorus in patients with or at risk for renal impairment. ( 2.5 ) 2.1 Overview of Different Dosage Forms Two different dosage forms are available: PREZCOBIX Tablets: 800 mg/150 mg film-coated tablets for adults and pediatric patients weighing at least 40 kg. 675 mg/150 mg film-coated tablets for pediatric patients weighing at least 25 kg to less than 40 kg. PREZCOBIX PED Tablets for Oral Suspension: 600 mg/90 mg film-coated tablet for oral suspension for pediatric patients aged 3 years and older weighing at least 15 kg to less than 25 kg [see Dosage and Administration (2.2 , 2.3) ] . 2.2 Recommended Dosage in Adults and Pediatrics 3 Years of Age and Older Weighing at Least 15 kg The recommended dosages for adults and pediatric patients weighing at least 15 kg are shown in Table 1. The pediatric dose is based on weight. PREZCOBIX and PREZCOBIX PED are taken orally with food once daily in conjunction with other antiretroviral agents. Table 1: Recommended Dosages of PREZCOBIX and PREZCOBIX PED in Adults and Pediatric Patients Weighing at Least 15 kg, who are Treatment-Naïve or Treatment-Experienced Without DRV RAMs DRV-resistance-associated mutations (RAMs): V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V, L89V. Patient Population Total Daily Dose Adults and pediatric patients weighing at least 40 kg One PREZCOBIX 800 mg darunavir/150 mg cobicistat tablet Pediatric Patients weighing at least 25 kg to less than 40 kg One PREZCOBIX 675 mg darunavir/150 mg cobicistat tablet Pediatric Patients aged 3 years and older weighing at least 15 kg to less than 25 kg One PREZCOBIX PED 600 mg darunavir/90 mg cobicistat tablet for oral suspension Before prescribing PREZCOBIX 675 mg/150 mg tablets, children should be assessed for the ability to swallow tablets. For patients unable to swallow the 675 mg/150 mg tablet whole, the scored tablet may be split by hand into two pieces. Each piece should be consumed immediately after splitting to ensure the entire dose is administered. The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses. 2.3 Preparation and Administration Instructions for PREZCOBIX PED Advise patients or caregivers of patients taking PREZCOBIX PED to refer to the Instructions for Use to properly prepare and take the medication. PREZCOBIX PED must be dispersed in drinking water and taken immediately as described below. If not taken immediately, then the oral suspension should be discarded, and a new dose of medicine should be prepared. The patient should not crush, chew or swallow the PREZCOBIX PED tablet for oral suspension. The following instructions should be followed: Place the tablet for oral suspension in a cup, add 30 mL (2 tablespoons) of non-carbonated room temperature drinking water. Stir well with a spoon until the tablet is completely dispersed. The prepared medicine will appear reddish purple. Take all the prepared medicine immediately or to aid in administration, the prepared medicine can be further diluted with 10 mL ( …

3 DOSAGE FORMS AND STRENGTHS PREZCOBIX Tablets: 800 mg/150 mg as pink, oval-shaped, film-coated tablet debossed with "800" on one side and "TG" on the other side containing 800 mg of darunavir and 150 mg of cobicistat. 675 mg/150 mg as green to dark green, oval-shaped, scored film-coated tablet debossed with "675" on one side and "TG" on the other side containing 675 mg of darunavir and 150 mg of cobicistat. PREZCOBIX PED Tablets for Oral Suspension: 600 mg/90 mg as reddish purple, oval-shaped, film-coated tablet debossed with "690" on one side and "TG" on the other side containing 600 mg of darunavir and 90 mg of cobicistat. Tablets: 800 mg of darunavir and 150 mg of cobicistat. ( 3 ) Tablets: 675 mg of darunavir and 150 mg of cobicistat. ( 3 ) Tablets for oral suspension: 600 mg of darunavir and 90 mg of cobicistat. ( 3 )

4 CONTRAINDICATIONS Darunavir and cobicistat are both inhibitors of the cytochrome P450 3A (CYP3A) isoform. PREZCOBIX should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which increased plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). Darunavir and cobicistat are both substrates of the cytochrome P450 3A (CYP3A) isoform. Co-administration of PREZCOBIX or PREZCOBIX PED with CYP3A inducers may lead to lower exposures of darunavir and cobicistat and potential loss of efficacy of darunavir and possible resistance. Examples of drugs that are contraindicated for co-administration with PREZCOBIX or PREZCOBIX PED [see Drug Interactions (7.3 ) and Clinical Pharmacology (12.3) ] are listed below. Alpha 1-adrenoreceptor antagonist: alfuzosin Anticonvulsants: carbamazepine, phenobarbital, phenytoin Anti-gout: colchicine, in patients with renal and/or hepatic impairment Antimycobacterial: rifampin Antipsychotics: lurasidone, pimozide Cardiac Disorders: dronedarone, ivabradine, ranolazine Ergot derivatives, e.g. dihydroergotamine, ergotamine, methylergonovine Herbal product: St. John's wort ( Hypericum perforatum ) Hepatitis C direct acting antiviral: elbasvir/grazoprevir Lipid modifying agents: lomitapide, lovastatin, simvastatin Opioid Antagonist: naloxegol PDE-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension Sedatives/hypnotics: orally administered midazolam, triazolam PREZCOBIX or PREZCOBIX PED is contraindicated in patients receiving certain co-administered drugs for which altered plasma concentrations are associated with serious and/or life-threatening events or loss of therapeutic effect. ( 4 , 7.2 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ] Severe skin reactions [see Warnings and Precautions (5.2) ] Effects on serum creatinine [see Warnings and Precautions (5.3) ] New onset or worsening renal impairment when used with tenofovir DF [see Warnings and Precautions (5.4) ] Immune Reconstitution Syndrome [see Warnings and Precautions (5.10) ] The most common adverse reactions to darunavir, a component of PREZCOBIX or PREZCOBIX PED (incidence greater than or equal to 5%) of at least moderate severity (greater than or equal to Grade 2) were diarrhea, nausea, rash, headache, abdominal pain, and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Products, LP at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Clinical Trials in Adults During the darunavir clinical development program, where darunavir was co-administered with ritonavir 100 mg once or twice daily, the most common clinical adverse reactions (incidence greater than or equal to 5%) of at least moderate intensity (greater than or equal to Grade 2) were diarrhea, nausea, rash, headache, abdominal pain, and vomiting. See the darunavir full prescribing information for additional information on adverse reactions reported with darunavir co-administered with ritonavir. See cobicistat full prescribing information for clinical trial information on adverse reactions reported with cobicistat. One single arm clinical trial was conducted with darunavir and cobicistat administered as single entities in 313 participants with HIV-1. Adverse reactions evaluated through Week 24 did not differ substantially from those reported in clinical trials with darunavir co-administered with ritonavir. Clinical Trials in Pediatrics No clinical trials with PREZCOBIX and PREZCOBIX PED were performed in pediatric participants. However, the safety of the components of PREZCOBIX, darunavir and cobicistat, co-administered with two nucleoside reverse transcriptase inhibitors, was evaluated through clinical trial GS-US-216-0128 in virologically-suppressed pediatric participants of 12 to less than 18 years of age with weight ≥40 kg (Cohort 1, N=7), pediatric participants 6 to less than 12 years of age with weight ≥25 kg to <40 kg (Cohort 2, N=8) and pediatric participants aged ≥3 years with weight ≥15 kg to <25 kg (Cohort 3, N=11) through Week 48. Safety analyses of this trial in these pediatric participants did not identify new safety concerns compared to the known safety profile of PREZCOBIX in adult participants [see Clinical Studies (14.2) ] . 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of darunavir. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Metabolism and Nutrition Disorders Redistribution of body fat Musculoskeletal and Connective Tissue Disorders Rhabdomyolysis (associated with co-administration with HMG-CoA reductase inhibitors) Renal and Urinary Disorders Crystal nephropathy, crystalluria Skin and Subcutaneous Tissue Disorders Toxic epidermal necrolysis, acute generalized exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms [see Warnings and Precautions (5.2) ] .

7 DRUG INTERACTIONS Co-administration of PREZCOBIX with other drugs can alter the concentration of other drugs and other drugs may alter the concentrations of darunavir or cobicistat. Consult the full prescribing information prior to and during treatment for potential drug interactions. ( 4 , 5.6 , 7 , 12.3 ) 7.1 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 ). 7.2 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 ). 7.3 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 examples of potentially significant interactions but is not all inclusive , and therefore the label of each drug that is co-administered with PREZCOBIX should be consulted for information related to the route of metabolism, interaction pathways, potential risks, and specific actions to be taken with regard to co-administration. For the list of examples of contraindicated drugs, [see Contraindications (4) ] . Table 1: Established and Other Potentially Significant this table is not all inclusive Drug Interactions: Alterations in Dose or Regimen May Be Recommended Concomitant Drug Class: Drug Name Examples Effect on Concentration of Darunavir, Cobicistat, or Concomitant Drug Clinical Comment HIV-1 antiviral agents: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) didanosine ↔ darunavir ↔ cobicistat ↔ didanosine Didanosine should be administered one hour before or two hours after PREZCOBIX (administered with food). HIV-1 antiviral agents: Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) efavirenz ↓ cobicistat ↓ darunavir Co-administration with efavirenz is not recommended because it may result in loss of therapeutic effect and development of resistance to darunavir. etravirine ↓ cobicistat darunavir: effect unknown Co-administration with etravirine is not recommended because it may result in loss of therapeutic effect and development of resistance to darunavir. nevirapine ↓ cobicistat darunavir: effect unknown Co-administration with nevirapine is not recommended because it may result in loss of therapeutic effect and development of resistance to darunavir. HIV-1 antiviral agents: CCR5 co-receptor antagonists maraviroc ↑ maraviroc Maraviroc is a substrate of CYP3A. When co-administered with PREZCOBIX, patients should receive maraviroc 150 mg twice daily. Other agents Alpha 1-adrenoreceptor antagonist: alfuzosin ↑ alfuzosin Co-ad …

8 USE IN SPECIFIC POPULATIONS Pregnancy: PREZCOBIX or PREZCOBIX PED is not recommended during pregnancy due to substantially lower exposures of darunavir and cobicistat during pregnancy. ( 8.1 , 12.3 ) Lactation: Breastfeeding is not recommended. ( 8.2 ) Pediatrics: Not recommended for pediatric patients younger than 3 years or weighing less than 15 kg. ( 8.4 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PREZCOBIX or PREZCOBIX PED during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) 1-800-258-4263. Risk Summary PREZCOBIX or PREZCOBIX PED is not recommended during pregnancy because of substantially lower exposures of darunavir and cobicistat during the second and third trimesters [see Dosage and Administration (2.7) ] . A study evaluating the pharmacokinetics of antiretrovirals during pregnancy demonstrated substantially lower exposures of darunavir and cobicistat in the second and third trimesters compared to the post-partum period (see Data ) and [see Clinical Pharmacology (12.3) ]. Prospective pregnancy data from the APR are not sufficient to adequately assess the risk of birth defects or miscarriage. However, available data from the APR show no statistically significant difference in the overall risk of major birth defects for darunavir and cobicistat compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data ) . The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15–20%. The background risk of major birth defects and miscarriage for the indicated population is unknown. In animal reproduction studies, no adverse developmental effects were observed when the components of PREZCOBIX were administered separately at darunavir exposures less than 1 (mice and rabbits) and 3-times (rats), and at cobicistat exposures 1.6 (rats) and 3.8 (rabbits) times human exposures at the recommended daily dose of these components in PREZCOBIX (see Data ) . No adverse developmental effects were seen when cobicistat was administered to rats through lactation at cobicistat exposures up to 1.2 times the human exposure at the recommended therapeutic dose. Clinical Considerations Not Recommended During Pregnancy PREZCOBIX or PREZCOBIX PED is not recommended for use during pregnancy because of substantially lower exposures of darunavir and cobicistat during pregnancy (see Data ) and [see Clinical Pharmacology (12.3) ] . PREZCOBIX or PREZCOBIX PED should not be initiated in pregnant individuals. An alternative regimen is recommended for individuals who become pregnant during therapy with PREZCOBIX or PREZCOBIX PED. Data Human Data PREZCOBIX in combination with a background regimen was evaluated in a clinical trial of 7 pregnant participants taking PREZCOBIX (800 mg/150 mg) prior to enrollment and who were willing to remain on PREZCOBIX throughout the study. The study period included the second and third trimesters, and through 12 weeks postpartum. Six pregnant participants completed the trial. Exposure to darunavir and cobicistat as part of an antiretroviral regimen was substantially lower during the second and third trimesters of pregnancy compared with postpartum [see Clinical Pharmacology (12.3) ] . One out of 6 pregnant participants who completed the study experienced virologic failure with HIV-1 RNA >1,000 copies/mL from the third trimester visit through the postpartum period. Five pregnant participants had sustained virologic response (HIV-1 RNA <50 copies/mL) throughout the study period. There are no clinical data on the virologic response when PREZCOBIX is initiated during pregnancy. Prospective reports from the APR of overall major birth defects in preg …

12.1 Mechanism of Action PREZCOBIX and PREZCOBIX PED are fixed-dose combinations of an HIV-1 antiviral drug, darunavir and a CYP3A inhibitor, cobicistat [see Microbiology (12.4) ].

11 DESCRIPTION PREZCOBIX and PREZCOBIX PED are fixed-dose combination products containing darunavir and cobicistat. Darunavir is an inhibitor of the human immunodeficiency virus (HIV-1) protease. Cobicistat is a mechanism-based inhibitor of cytochrome P450 (CYP) enzymes of the CYP3A family. Darunavir : Darunavir, in the form of darunavir ethanolate, has the following chemical name: [(1 S ,2 R )-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamic acid (3 R ,3a S ,6a R )-hexahydrofuro[2,3- b ]furan-3-yl ester monoethanolate. Its molecular formula is C 27 H 37 N 3 O 7 S ∙ C 2 H 5 OH and its molecular weight is 593.73. Darunavir ethanolate has the following structural formula: Cobicistat : Cobicistat is adsorbed onto silicon dioxide. The chemical name for cobicistat is 1,3-thiazol-5-ylmethyl[(2 R ,5 R )-5-{[(2 S )2-[(methyl{[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl]amino}-1,6-diphenylhexan-2-yl]carbamate. It has a molecular formula of C 40 H 53 N 7 O 5 S 2 and a molecular weight of 776.0. It has the following structural formula: PREZCOBIX ® 800 mg darunavir/150 mg cobicistat tablets are for oral administration. Each tablet contains darunavir ethanolate equivalent to 800 mg of darunavir and 150 mg of cobicistat. The tablets include the following inactive ingredients: colloidal silicon dioxide, crospovidone, hypromellose, magnesium stearate, and silicified microcrystalline cellulose. The tablets are film-coated with a coating material containing iron oxide black, iron oxide red, polyethylene glycol, polyvinyl alcohol (partially hydrolyzed), talc, and titanium dioxide. PREZCOBIX ® 675 mg darunavir/150 mg cobicistat tablets are for oral administration. Each tablet contains darunavir ethanolate equivalent to 675 mg of darunavir and 150 mg of cobicistat. The tablets include the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The tablets are film-coated with a coating material containing iron oxide black, iron oxide yellow, polyethylene glycol, polyvinyl alcohol (partially hydrolyzed), talc, and titanium dioxide. PREZCOBIX ® PED 600 mg darunavir/90 mg cobicistat tablets for oral suspension are for oral administration. Each tablet for oral suspension contains darunavir ethanolate equivalent to 600 mg of darunavir and 90 mg of cobicistat. The tablets include the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, silicified microcrystalline cellulose, strawberry flavor, and sucralose. The tablets are film-coated with a coating material containing glycerol monocaprylocaprate type 1, iron oxide red, iron oxide black, macrogol polyvinyl alcohol graft copolymer, polyvinyl alcohol (partially hydrolyzed), talc, and titanium dioxide. Chemical Structure Chemical Structure

10 OVERDOSAGE Human experience of acute overdose with PREZCOBIX or PREZCOBIX PED is limited. No specific antidote is available for overdose with PREZCOBIX or PREZCOBIX PED. Treatment of overdose with PREZCOBIX or PREZCOBIX PED consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. Since both darunavir and cobicistat are highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.

16 HOW SUPPLIED/STORAGE AND HANDLING PREZCOBIX Tablets PREZCOBIX ® (darunavir and cobicistat) tablets, 800/150 mg, are supplied as pink, oval-shaped, film-coated tablets debossed with "800" on one side and "TG" on the other side. Bottle of 30 tablets with child-resistant closure (NDC 59676-575-30). PREZCOBIX ® (darunavir and cobicistat) tablets, 675/150 mg, are supplied as green to dark green, oval-shaped, scored film-coated tablet debossed with "675" on one side and "TG" on the other side. Bottle of 30 tablets with child-resistant closure (NDC 59676-578-30). Storage of PREZCOBIX tablets: Store at 20 °C to 25 °C (between 68 °F to 77 °F); with excursions permitted to 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature]. PREZCOBIX PED Tablets for Oral Suspension PREZCOBIX ® PED (darunavir and cobicistat) tablets for oral suspension, 600/90 mg, are supplied as reddish purple, oval-shaped, film-coated tablets debossed with "690" on one side and "TG" on the other side. Bottle of 30 tablets with child-resistant closure (NDC 59676-577-30). Storage of PREZCOBIX PED tablets for oral suspension: Store in the original container in order to protect from light. Keep the container tightly closed. Store at 20 °C to 25 °C (between 68 °F to 77 °F); with excursions permitted to 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature]. Keep PREZCOBIX, PREZCOBIX PED, and all medicines out of reach of children.