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Information about FDA HIV product approvals, safety warnings, medical product labeling changes, notices of upcoming public meetings, and notices about proposed regulatory guidances.
FDA recently approved changes to the Prezcobix (darunavir and cobicistat) tablet label. The following changes were made:
- To update DRUG INTERACTIONS section with MATE1 transporter information and Potentially Significant Drug Interactions Table 2 with corticosteroid information. A new subsection (section 7.4) was created to include drugs without clinically significant interaction with Prezcobix – see below.
- To update USE IN SPECIFIC POPULATIONS sections 8.1 through 8.4 to be compliant with the “Pregnancy and Lactation Labeling Rule” (PLLR), and to revise relevant parts of Section 13, NONCLINCAL TOXICOLOGY accordingly.
- To abridge CLINICAL PHARMACOLOGY sub-section on Darunavir Cardiac Electrophysiology and to update Drug Interactions sub-section with MATE1 transporter information.
Specifically Section 7: DRUG INTERACTIONS was updated to include MATE1 transporter information and the Potentially Significant Drug Interactions Table 2 was also updated with corticosteroid information as follows:
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 (see Table 2).
Table 2:Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction Trials or Predicted Interaction(see Contraindications (4) for a complete list of contraindicated drugs)
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Concomitant Drug Class:
Drug Name
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Effect on Concentration of Darunavir, Cobicistat, or Concomitant Drug
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Clinical Comment
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Systemic/Inhaled/ Nasal/Ophthalmic Corticosteroids:
e.g.
betamethasone
budesonide
ciclesonide
dexamethasone
fluticasone methylprednisolone
mometasone
prednisone
triamcinolone
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↓ darunavir
↓ cobicistat
↑corticosteroids
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Co-administration with systemic dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to PREZCOBIX. Consider alternative corticosteroids.
Co-administration with corticosteroids of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression.
Alternative corticosteroids including beclomethasone and prednisolone (for which PK and/or PD are less affected by strong CYP3A inhibitors relative to other steroids) should be considered, particularly for long term use.
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The updated labels will soon be available drugs@fda or DailyMed
Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration
Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration
Kimberly Struble
Division of Antiviral Products
Food and Drug Administration
For more information about the HIV Liaison Program visit the FDA Patient Network
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