title: Drug-drug interaction profile of the all-oral anti-hepatitis C virus regimen of paritaprevir/ritonavir, ombitasvir, and dasabuvir.
abstract: OBJECTIVE
  Paritaprevir (administered with ritonavir, PTV/r), ombitasvir (OBV), and dasabuvir (DSV) are direct-acting antiviral agents (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection. Thirteen studies were conducted to characterize drug-drug interactions for the 3D regimen of OBV, PTV/r, and DSV and various medications in healthy volunteers to inform dosing recommendations in HCV-infected patients.
  
  
  METHODS
  Mechanism-based drug-drug interactions were evaluated for gemfibrozil, ketoconazole, carbamazepine, warfarin, omeprazole, digoxin, pravastatin, and rosuvastatin. Drug-drug interactions with medications commonly used in HCV-infected patients were evaluated for amlodipine, furosemide, alprazolam, zolpidem, duloxetine, escitalopram, methadone, buprenorphine/naloxone, and oral contraceptives. Ratios of geometric means with 90% confidence intervals for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were used to determine the magnitude of interaction.
  
  
  RESULTS
  Coadministration with the 3D regimen of OBV, PTV/r, and DSV resulted in a <2-fold change in mean Cmax and AUC for most medications and the DAAs, indicating minimal to modest interactions. Carbamazepine decreased PTV, ritonavir, and DSV exposures substantially, while gemfibrozil increased DSV exposures substantially. Although coadministration with ethinyl estradiol-containing contraceptives resulted in elevated alanine aminotransferase levels, coadministration with a progestin-only contraceptive did not.
  
  
  CONCLUSIONS
  The majority of medications can be coadministered with the 3D regimen of OBV, PTV/r, and DSV without dose adjustment, or with clinical monitoring or dose adjustment. Although no dose adjustment is necessary for the 3D regimen when coadministered with 17 of the 20 medications, coadministration with gemfibrozil, carbamazepine, or ethinyl estradiol-containing contraceptives is contraindicated.
authors: AbbVie Inc., North Chicago, IL, USA. Electronic address: Rajeev.menon@abbvie.com.
authors: Rajeev M
authors: RM
authors: Menon
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Prajakta S
authors: PS
authors: Badri
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Tianli
authors: T
authors: Wang
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Akshanth R
authors: AR
authors: Polepally
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Jiuhong
authors: J
authors: Zha
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Amit
authors: A
authors: Khatri
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Haoyu
authors: H
authors: Wang
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Beibei
authors: B
authors: Hu
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Eoin P
authors: EP
authors: Coakley
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Thomas J
authors: TJ
authors: Podsadecki
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Walid M
authors: WM
authors: Awni
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Sandeep
authors: S
authors: Dutta
mesh_terms: D015081:2-Naphthylamine; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000813:Anilides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002219:Carbamates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003521:Cyclopropanes; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014633:Valine; D055815:Young Adult
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D018937:Hepatitis C Antibodies; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir
keywords: Dasabuvir; Drug-drug interactions; Hepatitis C virus; Ombitasvir; Paritaprevir; Ritonavir