Elbasvir / Grazoprevir

Rifampin

Contraindicated.

Available pharmaceutical opinion

Document made available to the pharmacist to communicate a drug interaction to the doctor.

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Mechanism

Rifampin at steady state may induce CYP 3A4 and decrease the plasma concentration of Elbasvir / Grazoprevir.

Rifampin can inhibit OATP1B1 and increase the plasma concentration of Elbasvir / Grazoprevir.

Elbasvir / Grazoprevir

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Possible significant increase of grazoprevir plasma levels.

Risk of increase in ALT levels.

Recommendations

Do not administer with potent CYP3A4 inducers.

Do not administer with OATP1B inhibitors.

Alternative solution(s)

Rifampin

Pharmacodynamic effects

Recommendations

Avoid association. Choose an alternative.

Alternative solution(s)

Monitor

Tests

Pharmacokinetic parameters
Parameters
Reference number
# patients
Dose
Frequency
AUC
Cmax
Cmin
Duration (days)
Elbasvir / Grazoprevir
3030 3222
12 14/12
200 mg ° 50/200* mg †
QD x 1/QD
- 7% ° + 10.7x/+ 1.2x †
+ 16% ° + 1.4x/+ 10.9x †
- 90% ° + 1.3x/+ 1.8x †
   
Rifampin
3030 3222
12 14
600 mg 600 mg IV
QD x 1
   
   
   
14  
Comment

Ref #3030 : ° Only the interaction between grazoprevir and rifampicine at steady state was studied.

Ref #3222 : † Elbasvir and grazoprevir were studied separately.
With a single dose of rifampin 600 mg orally, elbasvir increases were : AUC +1.2x, Cmax +1.3x and Cmin +1.2x; grazoprevir increases : AUC +8.4x, Cmax +6.5x and Cmin +1.6x.

Reference
  • 3030
    Caro L, Talaty J, Guo Z, Butterfield K, Prueksaritanont T et al. Pharmacokinetic Interaction Between the HCV Protease Inhibitor MK-5172 and IV and Oral Rifampin in Healthy Volunteers. 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013). Washington DC USA, November 1-5, 2013. Abstract 495.
  • 3222
    Elbasvir/Grazoprevir (Zepatier), Merck, Québec, Canada, 28 juin 2017.