Descovy contains tenofovir alafenamide and therefore should not be administered with tenofovir-DF.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. Dovato contains lamivudine and should not be taken with medicinal products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues, such as lamivudine and emtricitabine.

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied. No interaction is expected with lamivudine. Dolutegravir binds to divalent cations such as magnesium, iron or calcium and forms a complex at the level of the gastro-intestinal tract which results in less dolutegravir being absorbed. Divalent cations can be found in multivitamins. The simultaneous coadministration of a multivitamin preparation decreased dolutegravir AUC by 33%. When taken with food, Dovato and multivitamins can be taken at the same time. Under fasting conditions, Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Coadministration with Dovato (dolutegravir/lamivudine) has not been studied but is expected to decreased dolutegravir exposure. The US Prescribing Information for Dovato advises to avoid coadministration due to insufficient data to make dosing recommendations. However, the European product label for Dovato recommends an additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato, should be taken. This dose adjustment should be maintained for approximately 2 weeks after stopping St John’s wort as the inducing effect may persist after discontinuation of a strong inducer. Considering the limited experience when coadministering inducers with dual antiretroviral regimens, close monitoring of HIV infection is recommended. No significant interaction is expected with lamivudine. A recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (<1 mg/day) of St John’s Wort (hyperforin is the constituent responsible for induction of CYPs and P-gp).

Coadministration has not been studied and is not recommended in the product labels for Descovy. St John’s wort, a P-gp inducer, may decrease tenofovir alafenamide plasma concentrations. However, a recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (<1 mg/day) of St John’s Wort (hyperforin is the constituent responsible for induction of CYPs and P-gp). Coadministration may be considered with St John’s Wort formulations that clearly state the hyperforin content and which have a total daily hyperforin dose of 1 mg or less. In addition, data from a study with rifampicin suggest that use of tenofovir alafenamide 25 mg once daily with primidone may be acceptable. Coadministration of emtricitabine/tenofovir alafenamide (200/25 mg once daily) and the strong inducer rifampicin (600 mg once daily) decreased plasma exposure of tenofovir alafenamide and tenofovir by ~55%. Intracellular tenofovir-DP AUC decreased by 36%, however, intracellular tenofovir-DP exposure was 4.2-fold higher than that achieved with standard dose tenofovir-DF alone (300 mg once daily). No interaction is expected with emtricitabine.

The dolutegravir dose (50 mg) in Dovato is insufficient when coadministered with some medications that may decrease dolutegravir concentrations. An additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato (dolutegravir/lamivudine), is recommended with these medications.

Coadministration has not been studied but is expected to decrease dolutegravir exposure due to induction of UGT1A1 and CYP3A by St John's wort. Interaction studies with dolutegravir and rifampicin (a strong inducer) showed that the effect of induction on dolutegravir concentrations can be overcome by administering an additional 50 mg dose of dolutegravir. The US Prescribing Information for dolutegravir advises to avoid coadministration with St John's wort due to insufficient data to make dosing recommendations. However, the European SPC recommends that dolutegravir be dosed at 50 mg twice daily, but that alternative combinations should be used where possible in INSTI-resistant patients. This dose adjustment should be maintained for approximately 2 weeks after stopping St John’s wort as the inducing effect may persist after discontinuation of a strong inducer. A recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (<1 mg/day) of St John’s Wort (hyperforin is the constituent responsible for induction of CYPs and P-gp).

Dolutegravir binds to divalent cations such as magnesium, iron or calcium and forms a complex at the level of the gastro-intestinal tract which results in less dolutegravir being absorbed. Divalent cations can be found in multivitamins. The simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations. Medicinal products that reduce dolutegravir exposure (e.g. multivitamins) should be avoided in the presence of integrase class resistance.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with tenofovir-DF would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with tenofovir. No clinically significant pharmacokinetic interaction was observed between tenofovir-DF and dolutegravir or lamivudine. Coadministration of tenofovir-DF (300 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax and Ctrough by 3% and 8%, and increased AUC by 1%. Tenofovir Cmax, AUC and Ctrough increased by 9%, 12% and 19%, respectively. Coadministration of tenofovir-DF (300 mg once daily) and lamivudine (150 mg twice daily for 7 days) had no effect on AUC, Cmax or Cmin of tenofovir. Lamivudine AUC and Cmin were unaltered, and there was a 24% decrease in Cmax.

Coadministration with a levonorgestrel intra-uterine device (IUD) has not been studied but there is little potential for an interaction given the local mechanism of action of levonorgestrel.

Coadministration with a levonorgestrel intra-uterine device (IUD) has not been studied but there is little potential for an interaction given the local mechanism of action of levonorgestrel.

Coadministration with a levonorgestrel intra-uterine device (IUD) has not been studied but there is little potential for an interaction given the local mechanism of action of levonorgestrel.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Coadministration with dolutegravir/lamivudine has not been studied. Omeprazole is mainly metabolized by CYP2C19 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Coadministration of omeprazole (40 mg once daily) and dolutegravir (50 mg single dose) had no clinically significant effect on the pharmacokinetics of dolutegravir (Cmax, AUC and Ctrough decreased by 8%, 3% and 5%, respectively). No interaction is expected with lamivudine.

Coadministration has not been studied. St John’s Wort, an inducer of P-gp, could reduce the absorption of tenofovir-DF. However, based on the results of the interaction study between tenofovir-DF and rifampicin (another inducer of P-gp), St John’s Wort would be expected to cause only a small decrease in tenofovir-DF.  

Omeprazole has no clinically significant effect on the pharmacokinetics of dolutegravir. Coadministration of omeprazole (40 mg once daily) and dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC and Ctrough by 8%, 3% and 5%, respectively.

No clinically significant pharmacokinetic interaction was observed between tenofovir-DF and dolutegravir. Coadministration of tenofovir-DF (300 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax and Ctrough by 3% and 8%, and increased AUC by 1%. Tenofovir Cmax, AUC and Ctrough increased by 9%, 12% and 19%, respectively. No dosage adjustment is necessary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as omeprazole is mainly metabolized by CYP2C19 (major) and CYP3A4 (minor). Dose Descovy according to the concomitant antiretroviral.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolized by CYP3A4. Emtricitabine and tenofovir alafenamide are unlikely to interact with fluticasone. Dose Descovy according to the concomitant antiretroviral.

Coadministration of dolutegravir (50 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg, once daily) increased tenofovir AUC and Cmax by 25% and 10% (n=10). No significant effects were observed on dolutegravir pharmacokinetics relative to historical controls. Coadministration of dolutegravir (50 mg once daily) and tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (10/200/150/150 mg) had no significant effect on the pharmacokinetics of dolutegravir and tenofovir alafenamide. The recommended dose of Descovy for HIV-1 treatment is 200/25 mg once daily.