(Last updated: April 27, 2015; last reviewed: April 27, 2015)
Rilpivirine (RPV, Edurant, TMC 278)For additional information see Drugs@FDA: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
Tablet: 25 mg
Fixed-Dose Combination Tablet:
With emtricitabine and tenofovir disoproxil fumarate (tenofovir):
Antiretroviral-Naive Patients with HIV RNA ≤100,000 copies/mL or Virologically-Suppressed (HIV RNA <50 copies/mL) Patients with No History of Virologic Failure or Resistance to Rilpivirine and Other ARVs and Currently on Their First or Second Regimen:
Selected Adverse Events
Drug Interactions (see also the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents and http://www.hiv-druginteractions.org/)
The International Antiviral Society-USA (IAS-USA) maintains a list of updated resistance mutations (see http://www.iasusa.org/sites/default/files/tam/22-3-642.pdf) and the Stanford University HIV Drug Resistance Database offers a discussion of each mutation (see http://hivdb.stanford.edu/DR/).
Rilpivirine is approved in combination with other antiretroviral (ARV) agents for treatment-naive, HIV-infected adults with viral load ≤100,000 copies/mL. In addition, the combination tablet rilpivirine/emtricitabine/tenofovir (Complera) is approved in virologically-suppressed patients (HIV RNA <50 copies/mL) on their first or second regimen with no history of virologic failure or resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs).
The pharmacokinetics (PK), safety, and efficacy of rilpivirine in pediatric patients have not been established. An international (India, Thailand, Uganda, and South Africa) Phase II trial, Pediatric Study in Adolescents Investigating a New NNRTI TMC278 (PAINT) is investigating a 25-mg dose of rilpivirine in combination with 2 nucleoside reverse transcriptase inhibitors in ARV-naive adolescents aged 12 to <18 years who weigh ≥32 kg and have a viral load ≤100,000 copies/mL.1
In the dose-finding phase of the study 11 youth aged >12 to ≤15 years and 12 youth aged >15 to ≤18 years underwent intensive PK evaluations after an observed dose of rilpivirine taken with a meal. Results and adult comparison data are listed in the table below.2
|PK Parameter, Geometric Mean (Range)||Adolescent PK||Adolescent/Adult Ratio (95% CI)|
|Time to Reach Maximum Concentration
(Median, Range, Hours)
||102 (49–182)||0.88 (0.68–1.14)|
|Cmin (ng/mL)||51 (20–115)a||N/A|
|C24h (ng/mL)||64 (33–162)||1.10 (0.85–1.41)|
||1750 (887–3573)||0.98 (0.78–1.25)|
|a Correction provided by personal communication via email from Herta Crauwels, November 11, 2014.|
|Key to Acronyms: AUC = area under the curve; CI = confidence interval; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; PK = pharmacokinetic|
In a PK study of youth aged 13 to 23 years receiving rilpivirine,3 rilpivirine exposure was slightly higher than results from PAINT in those receiving 25 mg rilpivirine without darunavir/ritonavir (AUC = 2380 ngxh/mL) and substantially higher in those receiving 25 mg rilpivirine with darunavir/ritonavir (AUC = 6740 ngxh/mL). No dose adjustments are currently recommended for adults when rilpivirine is used in combination with darunavir/ritonavir, where a similar 2- to 3-fold increase in rilpivirine exposure has been reported.4
In the PAINT study the observed adverse events were similar to those reported in adults. Eight adverse events were reported in 5 of 25 participants as being at least possibly related to rilpivirine (e.g., somnolence, nausea, upper abdominal pain, fever, dizziness, headache); all were grade 1 in severity.