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. Author manuscript; available in PMC: 2019 Jun 1.
Published in final edited form as: Infect Dis Clin North Am. 2018 Jun;32(2):347–370. doi: 10.1016/j.idc.2018.02.001

Table 2.

Drug interactions between methadone or buprenorphine and DAAs

DAA Methadone Buprenorphine
(/naloxone)		 Symptoms of
withdrawal		 Treatment
Recommendation		 Reference
Telaprevir
  • R-methadone
    • Cmax: 0.71 (0.66–0.76)
    • AUC: 0.71 (0.66–0.76)
  • S-methadone
    • Cmax: 0.65 (0.60–0.71)
    • AUC: 0.64 (0.58–0.70)
  • Buprenorphine
    • Cmax: 0.80 (0.69, 0.93)
    • AUC: 0.96 (0.84, 1.10)
  • Norbuprenorphine
    • Cmax: 0.85 (0.66, 1.09)
    • AUC: 0.91 (0.71, 1.16)
 No difference in symptoms between opioid alone or opioid with telaprevir as measured by SOWS No dose adjustment Luo et al., Van Heeswijk et al.98,99
Boceprevir
  • R-methadone
    • Cmax: 0.90 (0.71–1.13)
    • AUC: 0.85 (0.74–0.96)
  • S-methadone
    • Cmax: 0.83 (0.64–1.09)
    • AUC: 0.78 (0.66–0.93)
  • Buprenorphine
    • Cmax: 1.18 (0.93–1.50)
    • AUC: 1.19 (0.91–1.57)
  • Norbuprenorphine
    • Cmax: 0.54 (0.36–0.83)
    • AUC: 0.55 (0.36–0.86)
 No evidence of opioid withdrawal or opioid excess, measured by SOWS No dose adjustment Hulskotte et al.100
Simeprevir
  • R-methadone
    • Cmax: 1.03 (0.97–1.09)
    • AUC: 0.99 (0.91–1.09)
  • S-methadone
    • Cmax, AUC: unchanged, data not reported
 No Data No Data Ouwerkerk-Mahadevan et al.101
Sofosbuvir
  • R-Methadone
    • Cmax: 0.99 (0.85–1.16)
    • AUC: 1.01 (0.85–1.22)
  • S-Methadone
    • Cmax: 0.95 (0.79–1.13)
    • AUC: 0.95 (0.77–1.17)
 No Data None as measured by DDQ, SOWS or pupil diameter No dose adjustment Denning et al.102
Sofosbuvir/Ledipasvir No PK Data No PK Data No difference in pooled Phase 2/3 data for CNS adverse events for patients on methadone versus not on methadone No dose adjustment German et al.103
Ombitasvir/paritaprevir/ritonavir and Dasabuvir
  • R-Methadone
    • Cmax: 1.04 (0.98–1.11)
    • AUC: 1.05 (0.98–1.11)
  • S-Methadone
    • Cmax: 0.99 (0.91–1.08)
    • AUC: 0.99 (0.89–1.09)
  • Buprenorphine
    • Cmax: 2.18 (1.78, 2.68)
    • AUC: 2.07 (1.78, 2.40)
  • Norbuprenorphine
    • Cmax: 2.07 (1.42, 3.01)
    • AUC: 1.84 (1.30, 2.60)
 No difference in pupil diameter, SOWS, or DDQ score between opioid alone or opioid with HCV regimen No dose adjustment. Monitor for increased sedation for patients on Buprenorphine given increase in Cmax, AUC Menon et al.104
Daclatasvir
  • R-Methadone
    • Cmax: 1.07(0.97–1.18)
    • AUC: 1.08 (0.94–1.24)
  • S-Methadone
    • Cmax: 0.95 (0.79–1.13)
    • AUC: 0.95 (0.77–1.17)
  • Buprenorphine
    • Cmax: 1.30 (1.03–1.64)
    • AUC: 1.37 (1.24–1.52)
  • Norbuprenorphine
    • Cmax: 1.65 (1.38–1.99)
    • AUC: 1.62 (1.30–2.02)
 No effect on opioid withdrawal or toxicity scores measured by COW and OOA No dose adjustment Garimella et al.105
Grazoprevir
  • R-Methadone
    • Cmax: 1.03 (0.96–1.11)
    • AUC: 1.09 (1.02–1.17)
  • S-Methadone
    • Cmax: 1.15 (1.07, 1.25)
    • AUC: 1.23 (1.12– 1.35)
  • Buprenorphine
    • Cmax: 0.90 (0.76–1.07)
    • AUC: 0.98 (0.81–1.19)
  • Norbuprenorphine
    • Cmax: 1.10 (0.97–1.25)
    • AUC: 1.13 (0.97–1.32)
 No symptoms or signs of toxicity or withdrawal in clinical trials No dose adjustment Fraser et al.106
Elbasvir
  • R-Methadone
    • Cmax: 1.07 (0.95–1.20)
    • AUC: 1.03 (0.92–1.15)
  • S-Methadone
    • Cmax: 1.09 (0.95– 1.25)
    • AUC: 1.09 (0.94– 1.26)
  • Buprenorphine
    • Cmax: 0.94 (0.82–1.08)
    • AUC: 0.98 (0.89–1.08)
  • Norbuprenorphine
    • No Data
 No symptoms or signs of toxicity or withdrawal in clinical trials No dose adjustment Marshall et al.107,108
Velpatasvir No PK Data No PK Data No symptoms or signs of toxicity or withdrawal in clinical trials No dose adjustment Grebely et al.51,109

AUC, area under the curve; COWS, SOWS, subjective opiate withdrawal scale clinical opiate withdrawal scale; DDQ, desire for drugs questionnaire; OOA, opioid overdose assessment; NA, not available; PK, pharmacokinetic