PREZCOBIX

PREZCOBIX- darunavir ethanolate and cobicistat tablet, film coated
Janssen Products LP

1 INDICATIONS AND USAGE

PREZCOBIX is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in treatment-naïve and treatment-experienced adults and pediatric patients weighing at least 40 kg with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).

2 DOSAGE AND ADMINISTRATION

2.1 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.

2.2 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 [see Warnings and Precautions (5.3)]. When co-administering PREZCOBIX with tenofovir disoproxil fumarate (tenofovir DF) assess estimated creatinine clearance, urine glucose, and urine protein at baseline [see Warnings and Precautions (5.4)].

2.3 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 [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].

2.4 Not Recommended in Severe Hepatic Impairment

PREZCOBIX is not recommended for use in patients with severe hepatic impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.5 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 [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.3)].

PREZCOBIX should not be initiated in pregnant individuals. An alternative regimen is recommended for those who become pregnant during therapy with PREZCOBIX.

3 DOSAGE FORMS AND STRENGTHS

PREZCOBIX is supplied as pink, oval-shaped, film-coated tablets containing darunavir ethanolate equivalent to 800 mg of darunavir and 150 mg cobicistat. Each tablet is debossed with “800” on one side and “TG” on the other side.

4 CONTRAINDICATIONS

PREZCOBIX is contraindicated in patients receiving the following co-administered drugs [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)].

  • 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

5 WARNINGS AND PRECAUTIONS

5.1 Hepatotoxicity

During the darunavir clinical development program (N=3063), where darunavir was co-administered with ritonavir 100 mg once or twice daily, drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) was reported in 0.5% of subjects. Patients with pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities including severe hepatic adverse reactions.

Post-marketing cases of liver injury, including some fatalities, have also been reported with darunavir co-administered with ritonavir. These have generally occurred in patients with advanced HIV-1 disease taking multiple concomitant medications, having co-morbidities including hepatitis B or C co-infection, and/or developing immune reconstitution syndrome. A causal relationship with darunavir co-administered with ritonavir has not been established.

Appropriate laboratory testing should be conducted prior to initiating therapy with PREZCOBIX and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases, especially during the first several months of PREZCOBIX treatment.

Evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on PREZCOBIX should prompt consideration of interruption or discontinuation of treatment.

5.2 Severe Skin Reactions

During the darunavir clinical development program (n=3063), where darunavir was co-administered with ritonavir 100 mg once or twice daily, severe skin reactions, accompanied by fever and/or elevations of transaminases in some cases, was reported in 0.4% of subjects. Stevens-Johnson Syndrome was rarely (less than 0.1%) reported during the clinical development program. During post-marketing experience toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis have been reported. Discontinue PREZCOBIX immediately if signs or symptoms of severe skin reactions develop. These can include but are not limited to severe rash or rash accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.

Mild-to-moderate rash was also reported and often occurred within the first four weeks of treatment and resolved with continued dosing.

5.3 Effects on Serum Creatinine

Cobicistat decreases estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. This effect should be considered when interpreting changes in estimated creatinine clearance in patients initiating PREZCOBIX, particularly in patients with medical conditions or receiving drugs needing monitoring with estimated creatinine clearance.

Prior to initiating therapy with PREZCOBIX, assess estimated creatinine clearance [see Dosage and Administration (2.2)]. Dosage recommendations are not available for drugs that require dosage adjustments in PREZCOBIX-treated patients with renal impairment [see Drug Interactions (7.3) and Clinical Pharmacology (12.2)]. Consider alternative medications that do not require dosage adjustments in patients with renal impairment.

Although cobicistat may cause modest increases in serum creatinine and modest declines in estimated creatinine clearance without affecting renal glomerular function, patients who experience a confirmed increase in serum creatinine of greater than 0.4 mg/dL from baseline should be closely monitored for renal safety.

5.4 New Onset or Worsening Renal Impairment When Used With Tenofovir Disoproxil Fumarate

Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported when cobicistat, a component of PREZCOBIX, was used in an antiretroviral regimen that contained tenofovir DF. Co-administration of PREZCOBIX and tenofovir DF is not recommended in patients who have an estimated creatinine clearance below 70 mL/min [see Dosage and Administration (2.3)].

  • Document urine glucose and urine protein at baseline [see Dosage and Administration (2.2)] and perform routine monitoring of estimated creatinine clearance, urine glucose, and urine protein during treatment when PREZCOBIX is used with tenofovir DF. Measure serum phosphorus in patients with or at risk for renal impairment when used with tenofovir DF.
  • Co-administration of PREZCOBIX and tenofovir DF in combination with concomitant or recent use of a nephrotoxic agent is not recommended.

See cobicistat full prescribing information for additional information regarding cobicistat.

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