Labeling update for Intelence (etravirine)

On August 20, 2014, the Intelence (etravirine) label was updated to include information regarding coadministration of etravirine with the following drugs:

  • dolutegravir, dolutegravir/darunavir/ritonavir, dolutegravir/lopinavir/ritonavir 
  • atazanavir/ritonavir 
  • boceprevir  


Below are the specific recommendations.

Concomitant Drug

Class:

Drug Name  

Effect on

Concentration of

Etravirine

or

Concomitant Drug

Clinical Comment

HIV-Antiviral Agents: Integrase Strand Inhibitors

dolutegravir*

 

 

 

dolutegravir/darunavir

/ritonavir*

 

 

dolutegravir/lopinavir

/ritonavir*

¯ dolutegravir

« etravirine

 

 

 ¯ dolutegravir

« etravirine

 

 

« dolutegravir

« etravirine

Etravirine significantly reduced plasma concentrations of dolutegravir. Using cross-study comparisons to historical pharmacokinetic data for etravirine, dolutegravir did not appear to affect the pharmacokinetics of etravirine.

 

 

The effect of etravirine on dolutegravir plasma concentrations was mitigated by co‚ÄĎadministration of darunavir/ritonavir or lopinavir/ritonavir, and is expected to be mitigated by atazanavir/ritonavir. Dolutegravir should only be used with INTELENCE® when co‚ÄĎadministered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir.

HIV-Antiviral Agents: Protease Inhibitors (PIs)

atazanavir*

(without ritonavir)

 

 

 

atazanavir/ritonavir*

 

¯ atazanavir

 

 

 

 

¯ atazanavir

« etravirine

 

 

INTELENCE® should not be co-administered with atazanavir without low-dose ritonavir.

 

Concomitant use of INTELENCE® with atazanavir/ritonavir decreased atazanavir Cmin but it is not considered clinically relevant.. The mean systemic exposure (AUC) of etravirine after co-administration of INTELENCE® with atazanavir/ritonavir in HIV-infected patients was similar to the mean systemic exposure of etravirine observed in the Phase 3 trials after co-administration of INTELENCE® and darunavir/ritonavir (as part of the background regimen). INTELENCE® and atazanavir/ritonavir can be co-administered without dose adjustments.

Hepatitis C Virus (HCV) Direct-Acting Antivirals:

boceprevir*

 

 

 

 

¯etravirine

↑ boceprevir

 

 

 

 

The combination of INTELENCE® and boceprevir can be used without dose adjustments.

 

However, co-administration of INTELENCE® and boceprevir is not recommended in the presence of other drugs which may further decrease etravirine exposure. This includes, but is not limited to, darunavir/ritonavir, lopinavir/ritonavir, saquinavir/ritonavir,  tenofovir disoproxil fumarate, or rifabutin.

 

The complete revised label can be viewed at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails

Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration

Kimberly Struble
Division of Antiviral Products
Food and Drug Administration

Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration