Table 3.
Summary of doravirine drug–drug interactions: the effect of doravirine on the pharmacokinetics of concomitant drugs
| Concomitant medication dosing | Doravirine dosing | Concomitant medication GMR (90% CI) [(doravirine + concomitant medication)/concomitant medication alone] | Reference | |||
|---|---|---|---|---|---|---|
| AUC0–∞ | AUC0–24 | Cmax | C24 | |||
| TDF 300 mg SD + lamivudine 300 mg SD | Doravirine 100 mg SD | Tenofovir: | ||||
| 1.11 (0.97–1.28) | – | 1.17 (0.96–1.42) | – | [31] | ||
| Lamivudine: | ||||||
| 0.94 (0.88–1.00) | – | 0.92 (0.81–1.05) | – | [31] | ||
| Midazolam 2 mg SD | Doravirine 120 mg once daily | 0.82 (0.70–0.97) | – | 1.02 (0.81–1.28) | – | [11] |
| Dolutegravir 50 mg once daily | Doravirine 200 mg once daily | – | 1.36 (1.15–1.62) | 1.43 (1.20–1.71) | 1.27 (1.06–1.53) | [20] |
| Elbasvir 50 mg once daily + grazoprevir 200 mg once daily | Doravirine 100 mg once daily | Elbasvir: | ||||
| – | 0.96 (0.90–1.02) | 0.96 (0.91–1.01) | 0.96 (0.89–1.04) | [27] | ||
| Grazoprevir: | ||||||
| – | 1.07 (0.94–1.23) | 1.22 (1.01–1.47) | 0.90 (0.83–0.96) | [27] | ||
| Ledipasvir 90 mg/sofosbuvir 400 mg SD | Doravirine 100 mg SD | Ledipasvir: | ||||
| 0.92 (0.80–1.06) | – | 0.91 (0.80–1.02) | – | [27] | ||
| Sofosbuvir: | ||||||
| 1.04 (0.91–1.18) | – | 0.89 (0.79–1.00) | – | [27] | ||
| GS-331007: | ||||||
| 1.03 (0.98–1.09) | – | 1.03 (0.97–1.09) | – | [27] | ||
| Metformin 1000 mg SD | Doravirine 100 mg once daily | 0.94 (0.88–1.00) | – | 0.94 (0.86–1.03) | – | [29] |
| Atorvastatin 20 mg SD | Doravirine 100 mg once daily | 0.98 (0.90–1.06) | – | 0.67 (0.52–0.85) | – | [21] |
| Maintenance methadone 20–200 mg once daily | Doravirine 100 mg once daily | (R)-methadone: | ||||
| – | 0.95 (0.90–1.01) | 0.98 (0.93–1.03) | 0.95 (0.88–1.03) | [30] | ||
| (S)-methadone: | ||||||
| – | 0.98 (0.90–1.06) | 0.97 (0.91–1.04) | 0.97 (0.86–1.10) | [30] | ||
| Total methadone: | ||||||
| – | 0.96 (0.90–1.03) | 0.98 (0.92–1.03) | 0.96 (0.87–1.05) | [30] | ||
| Ethinyl estradiol 0.03 mg/levonorgestrel 0.15 mg SD | Doravirine 100 mg once daily | Ethinyl estradiol: | ||||
| 0.98 (0.94–1.03) | – | 0.83 (0.80–0.87) | – | [26] | ||
| Levonorgestrel: | ||||||
| 1.21 (1.14–1.28) | – | 0.96 (0.88–1.05) | – | [26] | ||
AUC0–24 area under the concentration–time curve from time zero to 24 h, AUC0–∞ area under the concentration–time curve from time zero to infinity, C24 plasma concentration 24 h post-dose, CI confidence interval, Cmax maximum plasma concentration, GMR geometric mean ratio, SD single dose, TDF tenofovir disoproxil fumarate