Date of report 20 Jun 2019
Reported case interaction between
Rilpivirine and METHADONE

FLS Science

Drugs suspected to be involved in the DDI

Rilpivirine
Daily Dose
25 (mg)
Dose adjustment performed
No
Administration Route
Oral
Start date
Jan. 21, 2014
End date
April 30, 2019
METHADONE
Daily Dose
165 (mg)
Dose adjustment performed
Yes
Administration Route
Oral
Start date
Unknown
End date
Ongoing

Complete list of drugs taken by the patient

Antiretroviral treatment
Rilpivirine
Atazanavir (unboosted)
Raltegravir
Complete list of all comedications taken by the patient, included that involved in the DDI

Methadone, Sofosbuvir/velpatasvir

Clinical case description

Gender
Male
Age
45
eGFR (mL/min)
>60
Liver function impairment
Yes
Child-Pugh
Child-Pugh A
Description

45 year-old HIV/HCV patient. On antiretroviral therapy with raltegravir plus rilpivirine and unboosted atazanavir (GI intolerant to ritonavir and cobicistat; suspected resistance to NRTI -further reviewed and considered to retain activity for TDF/TAF). Concomitat treatment with methadone (165 mg qd). Prolonged QTc in ECG (673 msec). It was considered that rilpivirine, atazanavir and methadone were all potentially contributing to increase QTc. Antiretroviral therapy was changed to Bictegravir/FTC/TAF and methadone dose was decreased to 150 mg qd. A new ECG performed 2 weeks after showed a decrease in QTc to 443 msec.

Clinical Outcome

Toxicity

Drug Interaction Probability Scale (DIPS)

Score
7 - Probable

Editorial Comment

ATV and RIL have only slight effect on methadone plasmatic concentrations. However, considering that the three drugs have all shown to have the potential to increase QT interval, prescription of such association (or other drug combination known for sharing the same potential side effect) should be performed with caution. Currently, unboosted atazanavir is rarely prescribed although it could be eventually chosen to build an active ARV regimen when ritonavir or cobicistat need to be avoided.

University of Liverpool Recommendation

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