Table 1.
Summary of interactions between dolutegravir, selected antiretrovirals, and other drugs, with effects of food on dolutegravir exposure
| Effect on DTG exposure | Comments | |||
|---|---|---|---|---|
| PI | ||||
| ATV | ↑AUC (0,τ) 91% | No dose adjustment for DTG | ||
| ↑Cmax 50%↑Cτ 180% | Increased occurrence of jaundice | |||
| ATV/r | ↑AUC (0,τ) 62% | No dose adjustment for DTG | ||
| ↑Cmax 34%↑Cτ 121% | Increased occurrence of jaundice | |||
| LPV/r | No effect on steady-state DTG pharmacokinetics | No dose adjustment for DTG | ||
| DRV/r | ↓AUC (0,τ) 22%↓Cmax 11%↓Cτ 38% | No dose adjustment for DTG | ||
| TPV/r and FVP/r | Decreased exposure to DTG | No dose adjustment for DTG | ||
| N(d)RTI-NNRTI | ||||
| TDF | No effect on steady-state DTG PK | No dose adjustment for DTG | ||
| ZDV, ABC, 3TC, FTC, DDI, d4T | No interactions expected | No dose adjustment for DTG | ||
| EFV | Decreased exposure to DTG | No dose adjustment for DTG | ||
| ETR | ↓AUC (0,τ) 71%↓C 52%↓Cτ 88% | Avoid ETR alone ETR should be coadministered only with LPV/r or DRV/r | ||
| NVP | Decreased exposure to DTG (similar to ETR) | Avoid the combination: decreased levels of DTG due to enzyme induction | ||
| Other drugs | Effect on DTG levels | Remarks | ||
|
| ||||
| Barbiturates | May cause ↓C of DTG | Caution if coadministered* | ||
| Phenytoin | May cause ↓C of DTG | Caution if coadministered* | ||
| Phenobarbital | May cause ↓C of DTG | Caution if coadministered* | ||
| Carbamazepine | May cause ↓C of DTG | Caution if coadministered* | ||
| Modafinil | May cause ↓C of DTG | Caution if coadministered* | ||
| Pioglitazone | May cause ↓C of DTG | Caution if coadministered* | ||
| Troglitazone | May cause ↓C of DTG | Caution if coadministered* | ||
| Rifampin | May cause ↓C of DTG | Caution if coadministered* | ||
| Rifabutin | May cause ↓C of DTG | Caution if coadministered* | ||
| St John’s wort | May cause ↓C of DTG | Caution if coadministered* | ||
| Multivitamins | ↓AUC (0,τ) 33% | No dose adjustment for DTG | ||
| Antacids | ↓AUC (0,τ) 77% | Administer antacids after 2 hours from DTG | ||
| Proton pump inhibitors | No effects | No dose adjustment for DTG | ||
| Foods | AUC | Cmax | Cτ | |
|
| ||||
| Low fat | 1.33 | 1.46 | 1.33 | No dose adjustments for DTG |
| Moderate fat | 1.41 | 1.52 | 1.67 | No dose adjustments for DTG |
| High fat | 1.66 | 1.67 | 1.73 | No dose adjustments for DTG |
Note: *Interactions may be relevant with other antiretrovirals included in combination antiretroviral therapy.
Abbreviations: C, concentration; DTG, dolutegravir; PI, protease inhibitor; ATV, atazanavir; ATV/r, atazanavir/ritonavir; AUC, area under the concentration-time curve; Cτ, concentration at end of dosing interval at steady state; Cmax, maximum concentration; LPV/r, lopinavir–ritonavir; DRV/r, darunavir–ritonavir; TPV/r, tipranavir–ritonavir; FVP/r, fosamprenavir–ritonavir; N(t)RTI, nucleos(t)ide reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; TDF, tenofovir difumarate; ZDV, zidovudine; ABC, abacavir; 3TC, lamivudine; FTC, emtricitabine; DDI, didanosine; d4T, stavudine; EFV, efavirenz; ETR, etravirine; NVP, nevirapine; PK, pharmacokinetics.