Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Coadministration is predicted to increase dydrogesterone exposure due to inhibition of CYP3A4. The clinical significance of this increase in terms of overall risk of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction in postmenopausal women receiving substitution hormones is unknown. In addition, exposure of estrogens/estradiol administered as part of HRT may also increase. The use of estradiol/estrogens alone or in combination with a progestogen should be at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for individual women. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary.

Coadministration has not been studied. Riociguat is metabolized by CYP1A1, CYP3A4, CYP2C8, CYP2J2 and is also eliminated unchanged in the bile and renally. Riociguat is a substrate of P-gp and BCRP. Elvitegravir/cobicistat is expected to increase riociguat exposure. The European SPC for riociguat does not recommend its use in presence of strong inhibitors of CYPs, P-gp and BCRP such as cobicistat whereas the US Prescribing Information recommends to start riociguat at a dose of 0.5 mg three times daily and to monitor for signs and symptoms of hypotension. Emtricitabine and tenofovir-DF do not interfere with riociguat metabolism.

Coadministration has not been studied. Ayahuasca preparations contain N,N-dimethyltryptamine (DMT, a psychedelic substance along with monoamine oxidase inhibitors (MAOI) which attenuates the breakdown of DMT. MAOI are substrate of MRP2 which is inhibited by elvitegravir/cobicistat thereby potentially increasing DMT toxicity by slowing its breakdown. Given the narrow therapeutic index of DMT, caution is advised. Harma alkaloids found in ayahuasca preparations may cause weak/moderate inhibition of CYP3A4 which is unlikely to alter exposure of elvitegravir/cobicistat. No interaction is expected with emtricitabine or tenofovir-DF.

Coadministration has not been studied. Fluoxetine is metabolized by CYP2D6 and 2C9 and to a lesser extent by 2C19 and 3A4 to form norfluoxetine. Elvitegravir/cobicistat could potentially increase fluoxetine concentrations although to a moderate extent. No a priori dosage adjustment is recommended. Emtricitabine and tenofovir-DF do not interact with this metabolic pathway.

Coadministration has not been studied. Terbinafine is metabolized by CYPs 1A2, 2C9, 3A4 and to a lesser extent CYPs 2C8 and 2C19. Elvitegravir/cobicistat could potentially increase terbinafine concentrations although to a moderate extent as several CYPs are involved in terbinafine metabolism. Emtricitabine and tenofovir-DF do not interact with this metabolic pathway. No a priori dosage adjustment is recommended.

Coadministration has not been studied but is not expected to alter elvitegravir concentrations. No dose adjustment is needed when Stribild is combined with H2 receptor antagonists. Administration of famotidine 12 h apart from elvitegravir/cobicistat had no effect on the AUC and Cmax of elvitegravir or cobicistat. Emtricitabine and tenofovir-DF do not interact with ranitidine.

Coadministration has not been studied but is not expected to alter elvitegravir concentrations. No dose adjustment is needed when Stribild is combined with proton pump inhibitors. When omeprazole was administered 2 h prior to elvitegravir/cobicistat, elvitegravir AUC and Cmax increased by 10% and 16% but those of cobicistat decreased by 8% and 10%. Separating omeprazole and elvitegravir/cobicistat by 12 h had no effect (<10% change) on the AUC or Cmax of elvitegravir or cobicistat. Emtricitabine and tenofovir-DF do not interact with lansoprazole.