Elbasvir / Grazoprevir

Atorvastatin

Dosage adjustment may be necessary.

Available pharmaceutical opinion

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

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Mechanism

Elbasvir / Grazoprevir can inhibit the CYP 3A4 and potentially BCRP and increase the plasma concentration of Atorvastatin.

Elbasvir / Grazoprevir

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Atorvastatin

Pharmacodynamic effects

Possible increased risk of HMG CoA inhibitor toxicity.

Recommendations

Start with a small dosage. Monitor closely for signs and symptoms of toxicity and adjust dosage as a function of efficacy and tolerance.

Maximum dose: 20 mg once daily.

Alternative solution(s)

Monitor

Symptoms of toxicity associated with hypolipidemic agents : gastrointestinal effects, fatigue and muscular weaknesses, myalgias, muscular cramps, myopathies, rhabdomyolysis and myoglobinuria leading to renal insufficiency.

Tests

CK

AST

ALT

Lipidic profile

Pharmacokinetic parameters
Parameters
Reference number
# patients
HCV
Dose
Frequency
AUC
Cmax
Cmin
Elbasvir / Grazoprevir
3029 3222
9 † 16
-  
200 mg * 50/200* mg
QD QD
+ 26%  
+ 26%  
+ 11%  
Atorvastatin
3029 3222
9 16
-  
20 mg 10 mg
x 1 x 1
+ 200% (3x) + 94%
+ 466% (5.6x) + 334% (4.3x)
  - 79%
Comment

* Since grazoprevir in HCV-infected patients demonstrates ~2-fold higher exposure compared to healthy subjects, a 200 mg dose was used in this study to match the exposure of a 100 mg dose (intended clinical dose).

Ref #3029 : † This study was conducted with grazoprevir alone.
Active atorvastatin metabolites (ortho- and para-hydroxyatorvastatin) had similar trends in PK to atorvastatin parent when coadministered with grazoprevir.

Reference
  • 3029
    Caro L, Talaty J, Guo Z, Reitmann C, Fraser I et al. Pharmacokinetic Interaction Between the HCV Protease Inhibitor MK-5172 and Midazolam, Pitavastatin, and Atorvastatin 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 477.
  • 3222
    Elbasvir/Grazoprevir (Zepatier), Merck, Québec, Canada, 28 juin 2017.