Table 2.
An overview of DCV DDIs with other common concomitant medications
| Drug/dose | Concomitant medication | Daclatasvir | |||||
|---|---|---|---|---|---|---|---|
| C max GMR (90% CI) | AUC GMR (90% CI) | AUC | C max GMR (90% CI) | AUC GMR (90% CI) | AUC | Dose adjustment | |
| Immunosuppressants | |||||||
| Cyclosporine (400 mg single dose) | 0.96 (0.91, 1.02) | 1.03 (0.97, 1.09) | ↔ | 1.04 (0.94, 1.15) | 1.40 (1.29, 1.53) | ↔ | None |
| Tacrolimus (5 mg single dose) | 1.05 (0.90, 1.23) | 1.00 (0.87, 1.15) | ↔ | 1.07 (1.02, 1.12) | 1.05 (1.03, 1.07) | ↔ | |
| Sirolimus/mycophenolate mofetil | NS | NS | ↔ | NS | NS | ↔ | |
| Narcotic analgesics | |||||||
| Buprenorphine/naloxone (8/2 to 24/6 mg QD)a | 1.30 (1.03, 1.64)/1.65 (1.38, 1.99) | 1.31 (1.15, 1.48)/1.62 (1.33, 1.96) | ↔/↔ | Comparable to historic data | ↔ | None | |
| NS | NS | ↔ | |||||
| Methadone (40–120 mg QD)b | 1.07 (0.97, 1.18) | 1.08 (0.94, 1.24) | ↔ | ||||
| Sedatives | |||||||
| Midazolam (5 mg single dose) | 0.95 (0.88, 1.04) | 0.87 (0.83, 0.92) | ↔ | NS | NS | ↔ | None |
| Triazolam/alprazolam | NS | NS | ↔ | NS | NS | ↔ | |
| Antidepressants | |||||||
| Escitalopram (10 mg QD) | 1.00 (0.92, 1.08) | 1.05 (1.02, 1.08) | ↔ | 1.14 (0.98, 1.32) | 1.12 (1.01, 1.26) | ↔ | None |
| Antibacterials | |||||||
| Azithromycin/ciprofloxacin | NS | NS | ↔ | NS | NS | ↔ |
None None/caution 90 mg |
| Erythromycin | NS | NS | ↔ | NS | NS | ↑ | |
| Clarithromycin/telithromycin | NS | NS | ↔ | NS | NS | ↑ | |
| Antifungals | |||||||
| Fluconazole | NS | NS | ↔ | NS | NS | ↑ |
None 30 mg 30 mg |
| Ketoconazole (400 mg QD)c | NS | NS | ↔ | 1.57 (1.31, 1.88) | 3.00 (2.62, 3.44) | ↑ | |
| Itraconazole/posaconazole/voriconazole | NS | NS | ↔ | NS | NS | ↑ | |
| Antimycobacterials | |||||||
| Rifampicin (600 mg QD) | NS | NS | ↔ | 0.44 (0.40, 0.48) | 0.21 (0.19, 0.23) | ↓ | Contraindicated |
| Hormonal contraceptives | |||||||
| Ethinylestradiol (35 μg QD × 21 days) + norgestimate (0.18/0.215/0.25 mg QD for 7/7/7 days)d | 1.11 (1.02, 1.20) | 1.01 (0.95, 1.07) | ↔ | NS | NS | ↔ | None |
| 1.06 (0.99, 1.14)/1.07 (0.99, 1.16) | 1.12 (1.06, 1.17)/1.12 (1.02, 1.23) | ↔/↔ | NS | NS | ↔ | ||
| Cardiac glycosides | |||||||
| Digoxin (0.125 mg QD) | 1.65 (1.52, 1.80) | 1.27 (1.20, 1.34) | ↑ | NS | NS | ↔ |
None Titrate digoxin |
| HMG-CoA reductase inhibitors | |||||||
| Rosuvastatin (10 mg QD) | 2.04 (1.83, 2.26) | 1.58 (1.44, 1.74) | ↑ | NS | NS | ↔ |
None Caution |
| Anticoagulants | |||||||
| Warfarin | NS | NS | ↔ | NS | NS | ↔ |
None None/monitor safety |
| Dabigatran etexilate | NS | NS | ↑ | NS | NS | ↔ | |
All interaction studies used daclatasvir 60 mg QD, unless otherwise stated (daclatasvir AUC GMR [90% CI] dose normalized to 60 mg QD)
AUC area under curve, CI confidence interval, C max maximal concentration, DCV daclatasvir, DDIs drug–drug interactions, GMR geometric mean ratio, HMG-CoA reductase 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, NS not studied (effects on C max, AUC, and associated dose modifications are predicted), QD once daily, ↓ exposure decreased, ↑ exposure increased, ↔ exposure unchanged (refers to clinically significant change)
aBuprenorphine/naloxone was assessed as buprenorphine/norbuprenorphine
bAssessed as R-methadone
cDaclatasvir 10 mg single dose
dNorgestimate is presented as norelgestromin/norgestrel