https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=18984
https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=18984
No pharmaceutical opinion available for this interaction.
Rifampicin may induce the metabolism (UGT 1A1 and CYP3A) and decrease the plasma concentration of Bictegravir.
Possible decrease of clinical efficacy and risk of possible development of resistance to antiretroviral class.
Not recommended association. If used, monitor for clinical efficacy.
According to a PBPK study, co-administration may be possible if administered with a strong CYP 3A4 inhibitor. See comments.
Based on data from a phase 2b study, the combination of bictegravir/ emtricitabine/ tenofovir-alafenamide twice daily may be effective. See comments.
In patients without resistance to integrase inhibitors, dolutegravir 50 mg BID or raltegravir 800 mg BID : see dolutegravir + rifampicin or raltegravir + rifampicin.
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Rifabutin : see dolutegravir + rifabutin or raltegravir + rifabutin.
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Bictegravir plasma level
Viral load HIV
CD4+
| Reference number |
|---|
| # patients |
| HIV |
| Dose |
| Frequency |
| AUC |
| Cmax |
| 3337 | 3440 |
|---|---|
| 15 | 26 |
| - | - |
| 75 mg * | 50 mg † |
| x 1 | BID |
| - 75% | - 61% |
| - 28% | - 47% |
| 3337 | 3440 |
|---|---|
| 15 | 26 |
| - | - |
| 600 mg | 600 mg |
| QD | QD |
Ref #3337 : * Fed.
Association with a potent CYP 3A4 inhibitor
Ref #3639 : This study used Physiologically-Based Pharmacokinetic (PBPK) modeling to predict a mean decrease in bictegravir AUC of 70% when co-administered with a strong CYP 3A4 inducer such as rifampicin. The authors conclude that co-administration should be avoided. On the other hand, they add that the co-administration of bictegravir and a strong CYP 3A4 inducer could be possible if they are administered with a strong CYP 3A4 inhibitor (protease inhibitors, ritonavir, cobicistat). According to the PBPK model, co-administration of bictegravir with a strong CYP 3A4 inducer, and ritonavir, a strong CYP 3A4 inhibitor, would produce a mean increase in bictegravir AUC of 1.2-fold. However, it should be taken into account that bictegravir is co-formulated with tenofovir alafenamide and emtricitabine and possible effects on these drugs. It is also unclear whether the addition of ritonavir would be appropriate from a tolerability perspective.
Bictegravir/emtricitabine/tenofovir alafenamide combination administered twice daily
Ref #3440 : † Administered as a fixed-dose tablet also containing emtricitabine 200mg and tenofovir alafenamide 25mg.
° Compared to standard once daily administration.
Despite the increased frequency of administration, the pharmacokinetic interaction is not counteracted and the increase does not make it possible to achieve the through concentrations reached in phase 3 clinical studies. The authors note that trough concentrations in all subjects were above the protein adjusted EC95 of 162 ng/ml.
Ref #3712 : In an open-label, non-comparative, phase-2b randomised controlled trial in ART-naïve or non-naïve adults with HIV and TB, taking a rifampicin-based TB regimen, 122 participants were randomised 2:1 to the BIC arm [bictegravir/emtricitabine/tenofovir alafenamide] (n=80) or a standard of care DTG arm [tenofovir, lamivudine, dolutegravir] (n=42), with BIC/FTC/TAF or DTG dosed twice daily, until 2 weeks post-TB treatment and once daily thereafter, until 48 weeks. Geometric mean trough concentrations for twice daily BIC during TB treatment and once daily BIC after TB treatment were 73.4% and 45.1%. No serious adverse events were related to study treatment. Viral suppression at week 24 was high and similar (97%) in the BIC and DTG arms. These data suggest that twice daily bictegravir/emtricitabine/tenofovir-alafenamide is effective in PWH with TB taking rifampicin-based treatment. Safety, PK, and virologic response data support the use of this regimen in PWH and TB.