Date of report 28 Jul 2020
Reported case interaction between
Etravirine and Fluconazole

FLS Science

Drugs suspected to be involved in the DDI

Victim
Etravirine
Daily Dose
400 (mg)
Dose adjustment performed
No
Administration Route
Oral
Start date
Unknown
End date
Ongoing
Perpetrator
Fluconazole
Daily Dose
400 (mg)
Dose adjustment performed
No
Administration Route
Intravenous
Start date
April 12, 2020
End date
May 29, 2020

Complete list of drugs taken by the patient

Antiretroviral treatment
Darunavir (with Ritonavir or Cobicistat)
Etravirine
Complete list of all comedications taken by the patient, included that involved in the DDI

Fluconazole, atorvastatin, cloxacillin, enalpril, enoxaparin, metamizol, insulin, paracetamol, omeprazol

Clinical case description

Gender
Male
Age
54
eGFR (mL/min)
60-30
Liver function impairment
No
Description

This is a HIV patients with an acute infection of a hip prothesis caused by a Candida rugosa, that was isolated in surgical cultures and treated with fluconazol. Fluconazol inhibits etravirine metabolism and coadministration may increase etravirine exposures (AUC by 86%, Cmax by 75%, Cmin by 2.09-fold) while it has no significant effect on fluconazole exposure. No dose adjustments were done. The patient presented a multifactorial severe anemia that may be worsened by an increased exposure to etravirine and that improved when fluconazole treatment was stopped.

Clinical Outcome

Toxicity

Drug Interaction Probability Scale (DIPS)

Score
3 - Possible

Editorial Comment

Coadministration significantly increased etravirine exposures (AUC by 86%, Cmax by 75%, Cmin by 2.09-fold) and had no significant effect on fluconazole exposure. Although no dose adjustments are needed, etravirine and fluconazole should be coadministered with caution as there are limited safety data on increased etravirine exposure. Anemia is among common laboratory abnormalities (4%) in etravirine prescribing information, although no clear relationship with etravirine concentrations has been described.

University of Liverpool Recommendation

Potential interaction - may require close monitoring, alteration of drug dosage or timing of administration
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