Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, doravirine should not be administered with products containing another NNRTI (i.e. rilpivirine).

Coadministration has not been studied but based on the results of the interaction study with rifampicin, rifapentine is expected to substantially decrease doravirine exposure. Coadministration is contraindicated as it may result in loss of therapeutic effect and development of resistance. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration has not been studied and is contraindicated. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Doravirine is metabolized by CYP3A4. Doravirine is unlikely to affect phenytoin metabolism. However, phenytoin is a strong inducer of CYP3A4 and is expected to substantially decrease doravirine exposure which may result in loss of therapeutic effect and development of resistance. Alternative anticonvulsants should be considered. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration is contraindicated. Oxcarbazepine is an inducer of CYP3A4 and is expected to decrease doravirine exposure which may result in loss of therapeutic effect and development of resistance. An alternative anticonvulsant should be considered. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Doravirine should not be administered with another NNRTI. Furthermore, coadministration is expected to decrease doravirine exposure. Note: switching from efavirenz to doravirine resulted in a transient decrease in doravirine exposure (doravirine AUC, Cmax and Cmin decreased by 52%, 35% and 85%, respectively, one day after stopping efavirenz and by 32%, 14% and 50%, respectively, 14 days after stopping efavirenz). Dose adjustment may not be necessary to maintain therapeutic concentrations of at least one drug during switching in a virologically suppressed individual.

Doravirine should not be administered with another NNRTI. Furthermore, coadministration is expected to decrease doravirine exposure.

Doravirine should not be administered with another NNRTI. Furthermore, coadministration is expected to decrease doravirine exposure.

Doravirine should not be administered with another NNRTI.

Coadministration has not been studied and is not recommended. Eslicarbazepine is partly eliminated unchanged renally and partly glucuronidated by UGT2B4. Eslicarbazepine is a weak/moderate inducer of CYP3A4. Eslicarbazepine was shown to reduce simvastatin (CYP3A4 substrate) exposure by 50%. A similar effect is expected on doravirine, leading to loss of therapeutic effect and possible development of resistance. An alternative anticonvulsant should be considered. At least a 4-week cessation period is recommended prior to initiation of doravirine due to a persistent inducing effect after discontinuation of a moderate/strong inducer.

Coadministration has not been studied and is contraindicated. Primidone is metabolised by CYP3A4 to the active metabolite phenobarbital. Phenobarbital induces CYP3A4 and is expected to significantly decrease doravirine exposure, leading to loss of therapeutic effect and possible development of resistance. Alternative anticonvulsants should be considered. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Odefsey (rilpivirine, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with another NNRTI.

Coadministration is contraindicated. Phenobarbital is a strong inducer of CYP3A4 and is expected to substantially decrease doravirine exposure which may result in loss of therapeutic effect and development of resistance. An alternative anticonvulsant should be considered. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration is contraindicated in the product labels for doravirine as a significant decrease in doravirine exposure may occur. At least a 4 week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer. 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.

Coadministration decreased doravirine exposure by 82% and is contraindicated as this may result in loss of therapeutic effect and development of resistance. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer. Coadministration of doravirine (100 mg single dose) and rifampicin (600 mg once daily) decreased doravirine AUC, Cmax and C24 by 88%, 57% and 97%, respectively (n=10).

Coadministration has not been studied. Ifosfamide is predominantly metabolized by CYP3A4 and CYP2B6 but doravirine does not inhibit or induce CYP enzymes. However, in vitro studies have demonstrated the ability of ifosfamide to both inhibit and induce CYP3A4. Clinical data with sunitinib suggests that ifosfamide can decrease sunitinib levels via CYP3A4 induction. Therefore there is potential for ifosfamide to alter levels of doravirine via modulation of CYP3A4 activity. Use with caution.

Coadministration has not been studied. Limited data are available on the effect of malabar nut tree on drug metabolism. In vitro data with leaf extracts suggest it could act as an inducer of phase I and phase II metabolic enzymes although the clinical relevance has not been evaluated. In the absence of data, caution is recommended. 

Coadministration has not been studied. Tamoxifen metabolism occurs mostly via two pathways: the formation of N-desmethyltamoxifen (via mainly CYP3A4 and CYP3A5) is the main route (92%) and the formation of 4-hydroxytamoxifen (via CYP2D6 > 2C9/19, CYP3A4 and CYP2B6) is a minor route (7%). Further metabolism of both metabolites results in the formation of endoxifen which is thought to be the most important metabolite contributing to the pharmacologic activity of tamoxifen. No effect on tamoxifen is expected as doravirine does not inhibit or induce CYP enzymes. However, tamoxifen has been shown to have some inducing effects on CYP3A4 in vivo and in vitro and could potentially decrease doravirine exposure and thereby efficacy. Use with caution. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration has not been studied. Coadministration of doravirine and the sensitive CYP3A4 substrate midazolam decreased midazolam exposure by 18%. Sirolimus is metabolized by CYP3A4 and a decrease in sirolimus exposure cannot be excluded. Monitoring of sirolimus blood concentrations is recommended as the dose may need to be adjusted. No effect on doravirine concentrations is expected.

Coadministration has not been studied and should be avoided. Doravirine is metabolized by CYP3A4 and griseofulvin is an enzyme inducer and therefore could potentially reduce doravirine exposure and efficacy. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration has not been studied. Betamethasone is metabolized by CYP3A4 and is a moderate inducer of CYP3A4 and therefore could decrease doravirine exposure and efficacy particularly when administered at high doses or for a long duration. If coadministration cannot be avoided, doravirine should be administered 100 mg twice daily (based on the interaction study with rifabutin, another moderate inducer) and maintained at this dose for at least another two weeks following cessation of betamethasone. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer. However, the inducing effect is expected to be modest when using lower doses of betamethasone in which case a dose adjustment may not be needed.

Coadministration has not been studied. In vitro data suggest that paclitaxel induces CYP3A4 via PXR mediated activation which could reduce doravirine exposure and efficacy. If coadministration cannot be avoided, doravirine should be administered 100 mg twice daily (based on the interaction study with rifabutin, another moderate inducer) and maintained at this dose for at least another two weeks following cessation of paclitaxel. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

When doravirine/lamivudine/tenofovir-DF (Delstrigo) is coadministered with rifabutin, an additional tablet of doravirine alone (Pifeltro) should be taken approximately 12 hours after the dose of Delstrigo. Doravirine should be kept at 100 mg twice daily for at least another 2 weeks following cessation of rifabutin due to the persisting inducing effect upon discontinuation.

Coadministration has not been studied. Coadministration of doravirine and the sensitive CYP3A4 substrate midazolam decreased midazolam exposure by 18%. Tacrolimus is metabolized by CYP3A4 and a decrease in tacrolimus exposure cannot be excluded. Monitoring of tacrolimus blood concentrations is recommended as the dose may need to be adjusted. No effect on doravirine concentrations is expected.

Coadministration has not been studied. Bosentan is a moderate inducer of CYP3A4 and could decrease doravirine exposure and efficacy. If coadministration cannot be avoided, doravirine should be administered 100 mg twice daily (based on the interaction study with rifabutin, another moderate inducer) and maintained at this dose for at least another two weeks following cessation of bosentan. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration has not been studied. Thioridazine is a moderate inducer of CYP3A4 and could decrease doravirine exposure and efficacy. If coadministration cannot be avoided, doravirine should be administered 100 mg twice daily (based on the interaction study with rifabutin, another moderate inducer) and maintained at this dose for at least another two weeks following cessation of thioridazine. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration of doravirine and multiple doses of the moderate CYP3A4 inducer rifabutin (300 mg once daily) decreased doravirine AUC, and Cmin by 50% and 68%, respectively. The product label for doravirine recommends to increase doravirine dosage to 100 mg twice daily when co-administered with rifabutin. Doravirine should be kept at 100 mg twice daily for at least another 2 weeks following cessation of rifabutin due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration has not been studied. Garlic supplements have been shown to decrease unboosted saquinavir AUC by 50% in a clinical trial and there is a case report of treatment failure due to garlic cloves (six garlic cloves three times weekly) decreasing ritonavir-boosted atazanavir trough concentrations by ~70%. This effect has been attributed to the induction of intestinal CYP3A4 and/or P-gp by garlic. Garlic could decrease the exposure of doravirine as it is metabolized by CYP3A4. Patients should be advised against the use of garlic supplements. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration has not been studied. Vinblastine is metabolized by CYP3A4. No effect on vinblastine is expected as doravirine does not inhibit or induce CYP enzymes; However, in vitro data suggest that vinblastine induces CYP3A4 partly via PXR mediated activation and therefore could potentially decrease doravirine exposure and thereby efficacy. Use with caution. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration has not been studied. Modafinil is largely metabolized by hydrolysis (esterase-mediated) and to a lesser extent by CYP3A4-mediated oxidative metabolism. Doravirine does not inhibit or induce CYP450 enzymes. Modafinil is a moderate inducer of CYP3A4 and could decrease doravirine exposure and efficacy. If coadministration cannot be avoided, doravirine should be administered 100 mg twice daily (based on the interaction study with rifabutin, another moderate inducer) and maintained at this dose for at least another two weeks following cessation of modafinil. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Coadministration has not been studied. Coadministration with ritonavir increased doravirine AUC by 3.5 fold and Cmin by 2.9 fold. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration with ritonavir increased doravirine AUC by ~3.5 fold and Cmin by ~2.9 fold. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure. Coadministration of doravirine (50 mg single dose; half the recommended approved dose) with ritonavir (100 mg twice daily) increased doravirine AUC, Cmax and C24 by 254%, 31% and 191%, respectively (n=8).

Coadministration has not been studied. Fluconazole is a moderate inhibitor of CYP3A4 and therefore is predicted to increase doravirine exposure although to a limited extent. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Diltiazem is a strong inhibitor of CYP3A4 and is predicted to increase doravirine exposure by ~3-fold based on drug-drug interaction studies with ritonavir and ketoconazole. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Dihydroergotamine is a substrate and inhibitor of CYP3A4 and is expected to increase doravirine concentrations although to a limited extent. No dosage adjustment is needed for doravirine. 

Coadministration has not been studied. Doravirine is metabolized by CYP3A4 and coadministration may increase doravirine concentrations due to inhibition of CYP3A4 by atazanavir. Coadministration with ritonavir (a strong inhibitor of CYP3A4) increased doravirine exposure by ~3.5-fold. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Coadministration with ritonavir increased doravirine AUC by 3.5-fold and Cmin by 2.9-fold. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Doravirine is metabolized by CYP3A4. Cobicistat is a strong inhibitor of CYP3A4 and is expected to increase doravirine exposure by a~ 3.5-fold based on the drug interaction study with ritonavir. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as strontium is predominantly eliminated unchanged by the kidneys. However, food and milk can affect strontium absorption and administration should be separated by at least 2 hours. [Note: this interaction is not specific for doravirine, but for any medication taken with strontium ranelate.] 

Coadministration has not been studied. Gingerols moderately inhibit CYP3A4 and therefore could increase doravirine exposure although to a limited extent. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure. 

Coadministration has not been studied. Doravirine is metabolized by CYP3A4. Ginkgo biloba may decrease doravirine concentrations through induction of CYP3A4 but the magnitude and clinical relevance of this potential interaction is difficult to predict as inconsistent findings have been reported from clinical drug interaction studies with CYP3A4 substrates. 

Coadministration has not been studied. Nicardipine is a moderate inhibitor of CYP3A4 and is expected to increase doravirine exposure although to a limited extent. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied but may increase doravirine concentrations through inhibition of CYP3A4. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. In vitro data indicate that extracts of hops activate PXR and induce expression of CYP3A4, CYP2B6 and MDR1 genes to a degree similar to that of St John's wort. However, a pharmacokinetic study with a standardised hop extract showed no clinically relevant effect on CYPs 2C9, 1A2, and 2D6 and suggested only minor induction of CYP3A4/5 (AUC of alprazolam, a CYP3A4/5 substrate, decreased by ~8%). Based on these results, hop extracts are unlikely to have a clinically significant effect on doravirine.

Coadministration has not been studied. Alantolactone, a component of Inula racemosa, moderately inhibits CYP3A4 in vitro and therefore could potentially increase the exposure of doravirine although to a limited extent. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Ergotamine is a substrate and inhibitor of CYP3A4 and is expected to increase doravirine concentrations although to a limited extent. No dosage adjustment is needed for doravirine. 

Coadministration has not been studied. Glycyrrhizin, the main active component of Glycyrrhiza glabra, is a modest inducer of CYP3A4 and could potentially decrease the exposure of doravirine although to a modest extent.

Coadministration has not been studied. Piperaquine is a modest inhibitor of CYP3A4 and may increase doravirine concentrations, although to a limited extent. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Menthol is a moderate inhibitor of CYP3A4 and therefore could potentially increase the exposure of doravirine although to a limited extent. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

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 doravirine would be possible from a pharmacokinetic standpoint. Doravirine is metabolized by CYP3A4. Coadministration of dolutegravir (50 mg once daily) and doravirine (200 mg once daily) did not significantly alter doravirine exposure. Dolutegravir AUC, Cmax and Cmin were increased by 36%, 43% and 27%, respectively (n=11). These changes are not considered as clinically significant No interaction is expected with lamivudine.

Triumeq (dolutegravir, abacavir, 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 doravirine would be possible from a pharmacokinetic standpoint. Coadministration of dolutegravir (50 mg once daily) and doravirine (200 mg once daily) did not significantly alter doravirine exposure. Dolutegravir AUC, Cmax and Cmin were increased by 36%, 43% and 27%, respectively (n=11). These changes are not considered as clinically significant No interaction is expected with abacavir or lamivudine.

Coadministration has not been studied. Verapamil is a moderate inhibitor of CYP3A4 and therefore is expected to increase doravirine exposure although to a limited extent. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Itraconazole is a strong inhibitor of CYP3A4 and is predicted to increase doravirine exposure by~3-fold based on drug-drug interaction studies with ketoconazole. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Imatinib is primarily metabolized by CYP3A4 and to a lesser extent by CYPs 1A2, 2D6, 2C9 and 2C19. Doravirine does not inhibit or induce CYP enzymes. In vitro data indicate that imatinib inhibits CYPs 3A4, 2D6, 2C9 and 2C19 and therefore could potentially increase doravirine exposure although to a limited extent. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Quercetin inhibits CYP3A4 and therefore could increase doravirine exposure. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Artemisinins undergo rapid metabolism via several CYP450 (CYPs 3A4, 2A6, 2B6) and the active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolized via UGTs 1A9 and 2B7. A clinically significant effect of doravirine on artemisins is unlikely. However, artemisinins induce CYP3A4 and/or CYP2C19 and could potentially decrease doravirine concentrations, but this is unlikely to be clinically relevant due to the short treatment duration for artemisinins.

Ketoconazole is a strong inhibitor of CYP3A4 and was shown to increase doravirine exposure by ~3-fold. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure. Coadministration of doravirine (100 mg single dose) and ketoconazole (400 mg once daily) increased doravirine AUC, Cmax and C24 by 206%, 25% and 175%, respectively (n=10). 

Coadministration has not been studied. Doravirine is metabolized by CYP3A4. Miconazole inhibits CYP2C9 and CYP3A4 and therefore is expected to increase doravirine concentrations although to a limited extent. No dosage adjustment is needed for doravirine. 

Coadministration has not been studied but may increase doravirine concentrations through inhibition of intestinal CYP3A4. The increase in doravirine exposure does not require any dose adjustment based on phase I trials showing a good tolerability of doravirine up to 3-4 fold increase in exposure.

Coadministration has not been studied. Doravirine is metabolized by CYP3A4. Telithromycin is a strong inhibitor of CYP3A4 and is predicted to increase doravirine exposure by ~3-fold based on drug-drug interaction studies with ritonavir and ketoconazole. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Posaconazole is a strong inhibitor of CYP3A4 and is predicted to increase doravirine exposure by ~3-fold based on drug-drug interaction studies with ritonavir and ketoconazole. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Flibanserin is primarily metabolized by CYP3A4 and has been shown to moderately increase the exposure of simvastatin, a CYP3A4 substrate. Doravirine does not inhibit or induce CYP enzymes, however, flibanserin could potentially increase doravirine exposure as doravirine is a substrate of CYP3A4. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Voriconazole is a strong inhibitor of CYP3A4 and is predicted to increase doravirine exposure by ~3-fold based on drug-drug interaction studies with ritonavir and ketoconazole. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Nilotinib is a moderate inhibitor of CYP3A4 and therefore could potentially increase doravirine exposure although to a limited extent. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Doravirine is metabolized by CYP3A4 and therefore the moderate CYP3A4 inhibitor erythromycin is expected to increase doravirine exposure although to a limited extent. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Coadministration with ritonavir alone increased doravirine AUC by 3.5 fold and Cmin by 2.9 fold. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Coadministration with ritonavir alone increased doravirine AUC by 3.5 fold and Cmin by 2.9 fold. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) 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, the coadministration with doravirine would be possible from a pharmacokinetic standpoint. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is metabolized by CYP3A4. Bictegravir is equally metabolized by CYP3A4 and UGT1A1. None of these antiretroviral drugs has any inhibitory or inducing effects on P450 or UGT enzymes therefore no significant interactions are expected between doravirine, bictegravir, emtricitabine, and tenofovir alafenamide. 

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) 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 doravirine would be possible from a pharmacokinetic standpoint. Doravirine is metabolized by CYP3A4. Cobicistat is a strong inhibitor of CYP3A4 and is expected to increase doravirine exposure by ~3.5-fold based on the drug interaction study with ritonavir. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3- to 4-fold increase in exposure. Emtricitabine and tenofovir alafenamide do not interact with doravirine.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) 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 doravirine would be possible from a pharmacokinetic standpoint. Doravirine is metabolized by CYP3A4. Cobicistat is a strong inhibitor of CYP3A4 and is expected to increase doravirine exposure by ~ 3.5-fold based on the drug interaction study with ritonavir. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3- to 4-fold increase in exposure. Emtricitabine and tenofovir-DF do not interact with doravirine.

Coadministration has not been studied. Nefazodone is metabolized mainly by CYP3A4. Nefazodone is a strong inhibitor of CYP3A4 and is predicted to increase doravirine exposure by ~3-fold based on drug-drug interaction studies with ritonavir and ketoconazole. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Orlistat reduces dietary fat absorption and may affect the absorption of antiretrovirals (especially if lipophilic). [Note: this interaction is not specific for doravirine but for any medication taken with orlistat.]

Coadministration has not been studied. Flucloxacillin is mainly eliminated renally, partly by glomerular filtration and partly by active secretion via OAT1. Flucloxacillin is thought to be a weak inducer of CYP3A4 particularly at higher doses (>2-3 g daily). A modest reduction in doravirine concentrations may be observed but this is unlikely to be clinically relevant unless flucloxacillin is prescribed at higher doses for a prolonged course (> 10-14 days).

Coadministration has not been studied. Several constituents of Piper cubeba were shown to inhibit CYP3A4 and therefore could increase doravirine exposure. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied. Echinacea has a selective effect on CYP3A4 activity (inhibition of intestinal CYP3A4 and induction of hepatic CYP3A4) and its effect on the net exposure of a CYP3A4 substrate will depend on the extraction of the drug at the intestinal and hepatic sites. Echinacea could potentially cause a modest reduction in doravirine plasma concentrations. 

Coadministration has not been studied. Doravirine is metabolized by CYP3A4. Cobicistat is a strong inhibitor of CYP3A4 and is expected to increase doravirine exposure by a~ 3.5-fold based on the drug interaction study with ritonavir. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure. 

Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) 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 doravirine would be possible from a pharmacokinetic standpoint. Doravirine is metabolized by CYP3A4. Cobicistat (a component of Symtuza) is a strong inhibitor of CYP3A4 and is expected to increase doravirine exposure by a~ 3.5-fold based on the drug interaction study with ritonavir. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-to 4-fold increase in exposure. No interaction is expected with doravirine and emtricitabine or tenofovir alafenamide.

Coadministration has not been studied. Coadministration with ritonavir increased doravirine AUC by 3.5 fold and Cmin by 2.9 fold. No dose adjustment of doravirine is required as phase I trials showed a good tolerability of doravirine with up to a 3-4 fold increase in exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Meropenem is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporters OAT3>OAT1. Doravirine does not inhibit renal transporters to a significant level.

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. Moxifloxacin is predominantly glucuronidated by UGT1A1. Doravirine does not inhibit or induce UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrofurantoin is partly metabolized in the liver via glucuronidation and N-acetylation and partly eliminated in the urine as unchanged drug (30-40%). Doravirine does not inhibit or induce UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ofloxacin is eliminated unchanged renally by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Doravirine does not inhibit significantly renal transporters. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Para-aminosalicylic acid and its acetylated metabolite are mainly excreted in the urine by glomerular filtration and tubular secretion. Doravirine does not interfere with para-aminosalicylic acid elimination. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Penicillins are mainly eliminated in the urine (20% by glomerular filtration and 80% by tubular secretion via OAT). Doravirine does not interfere with penicillins elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyrazinamide is mainly metabolized by xanthine oxidase. 

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Rifaximin is mainly excreted in faeces, almost entirely as unchanged drug. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Spectinomycin is predominantly eliminated unchanged by the kidneys via glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as streptomycin is excreted rapidly in the urine by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest a role of CYP2C9 in sulfadiazine metabolism. Doravirine does not inhibit or induce CYP enzymes. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetracyclines are eliminated unchanged primarily by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimethoprim is primarily eliminated by the kidneys through glomerular filtration and tubular secretion. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vancomycin is eliminated unchanged predominantly via glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is metabolized by CYP3A4 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid which is further glucuronidated by several UGTs (major UGT1A6). Doravirine does not interfere with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. Doravirine does not inhibit or induce P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dabigatran is not metabolized by CYP450 enzymes and is mainly cleared by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged by the kidneys. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Doravirine does not inhibit or induce UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is eliminated primarily as unchanged drug in urine and is minimally metabolised by hydrolysis (mediated by carboxylesterase 1), conjugation, or oxidation by CYP3A4/5 (<10%).

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1, UGT1A3) and oxidation (via CYP1A2 and CYP2C8). Doravirine does not inhibit or induce UGT or CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enoxaparin does not undergo cytochrome metabolism but is desulphated and depolymerised in the liver, and is excreted predominantly renally. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is eliminated predominantly renally. 

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Heparin is thought to be eliminated via the reticuloendothelial system.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Phenprocoumon is metabolized by CYP2C9 and CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Rivaroxaban is partly metabolized in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine (by P-gp and BCRP). Doravirine does not inhibit or induce CYP enzymes or drug transporters.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Like other proteins, streptokinase is metabolised proteolytically in the liver and eliminated via the kidneys.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Ticagrelor undergoes extensive CYP3A4 metabolism. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Warfarin is a mixture of enantiomers which are metabolised by different cytochromes. R-warfarin is primarily metabolised by CYP1A2 and CYP3A4. S-warfarin (more potent) is metabolised by CYP2C9. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethosuximide is mainly oxidized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gabapentin is cleared mainly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lacosamide is metabolized to O-desmethyl-lacosamide mainly by CYP2C19 (~30% of the dose) and is eliminated unchanged through the kidneys (~40% of the dose). 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lamotrigine is mainly glucuronidated by UGT1A4. Doravirine does not inhibit or induce UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levetiracetam undergoes enzymatic hydrolysis (non-CYP) and is eliminated unchanged in the urine by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as pregabalin is cleared mainly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Topiramate is mainly eliminated by renal elimination in unchanged form (up to 60% of the dose) and partly by oxidation. Weak induction of CYP isozymes has been observed with higher doses of topiramate but this is unlikely to be of clinical relevance with doravirine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as vigabatrin is cleared mainly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zonisamide is metabolized partly by CYP3A4 and also by N-acetyl-transferases and conjugation. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amitriptyline is metabolized predominantly by CYP2D6 and CYP2C19. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bupropion is primarily metabolized by CYP2B6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as desipramine is metabolized by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolized mainly by CYP2C19 to nordoxepin, an active metabolite. In addition, doxepin and nordoxepin are metabolized by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolized by CYP2D6 and CYP1A2. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is metabolized by CYPs 2D6 and 2C9 and to a lesser extent by CYPs 2C19 and 3A4 to form norfluoxetine. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvoxamine is metabolized mainly by CYP2D6 and to a lesser extent by CYP1A2. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipramine is metabolized by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolized by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Lithium is mainly eliminated unchanged through the kidneys and is freely filtered at a rate that is dependent upon the glomerular filtration rate

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Maprotiline is mainly metabolized by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolized by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Milnacipran is mainly eliminated unchanged (50%), and as glucuronides (30%) and oxidative metabolites (20%). 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as nortriptyline is metabolized mainly by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paroxetine is mainly metabolized by CYP2D6 and CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenelzine is primarily metabolized by oxidation via monoamine oxidase and to a lesser extent by acetylation. Doravirine does not interfere with phenelzine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as reboxetine is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertraline is mainly metabolized by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as tranylcypromine is hydroxylated and acetylated. Doravirine does not interact with tranylcypromine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trazodone is primarily metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimipramine is metabolized mainly by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Venlafaxine is mainly metabolized by CYP2D6 and to a lesser extent by CYPs 3A4, 2C19 and 2C9. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of canagliflozin is primarily mediated by UGT1A9 and UGT2B4 which are not affected by doravirine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of dapagliflozin is primarily mediated by UGT1A9 which is not affected by doravirine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dulaglutide is presumed to be degraded by general protein catabolism pathways. Dulaglutide delays gastric emptying and, thus, has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. However, interaction studies did not result in any clinically relevant effects and no dose adjustment of co-medications is recommended.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Empagliflozin is mainly glucuronidated by UGTs 1A3, 1A8, 1A9 and 2B7. It is a substrate of P-gp and BCRP, and also a substrate of the renal transporter OAT3 and the hepatic transporters OATP1B1 and OATP1B3. Doravirine does not inhibit or induce UGT enzymes or drug transporters. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as exenatide is primarily eliminated by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glibenclamide is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C9. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely as gliclazide is metabolised by CYP2C9. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as glimepiride is metabolised by CYP2C9. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely as glipizide is mainly metabolized by CYP2C9. Doravirine does not inhibit or induce CYP enzymes.

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 as linagliptin is mainly eliminated as parent compound in faeces. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as liraglutide is degraded by endogenous endopeptidases. 

Metformin is primarily eliminated by the kidney via OCT2 and MATE1. Coadministration of doravirine and metformin did not have a clinically meaningful effect on metformin pharmacokinetics.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nateglinide is metabolized mainly by CYP2C9 (70%) and to a lesser extent by CYP3A4 (30%). Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pioglitazone is metabolized by mainly CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Repaglinide is metabolized by CYP2C8 and CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Rosiglitazone is metabolized mainly by CYP2C8 and to a lesser extent by CYP2C9. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Saxagliptin is mainly metabolized by CYP3A4/5. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sitagliptin is primarily eliminated in urine as unchanged drug (active secretion by OAT3, OATP4C1, P-gp) and metabolism by CYP3A4 represents a minor elimination pathway. Doravirine is unlikely to interfere with the renal transporters involved in sitagliptin active secretion.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as tolbutamide is mainly metabolized by CYP2C9. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as vildagliptin is inactivated via non-CYP mediated hydrolysis. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amphotericin is not appreciably metabolized and is eliminated to a large extent in the bile.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anidulafungin is not metabolised hepatically but undergoes chemical degradation at physiological temperature. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flucytosine is metabolised to 5-flurouracil which is further metabolised by dihydropyrimidine dehydrogenase.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Systemic absorption of nystatin from oral or topical dosage forms is not significant, therefore no drug interactions are expected. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Terbinafine is metabolized by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYPs 2C8 and 2C19. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Astemizole is metabolized by CYPs 2D6, 2J2 and 3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolized by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fexofenadine undergoes negligible metabolism and is mainly eliminated unchanged in the faeces. Doravirine does not interact with fexofenadine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as less than 14% of a dose of levocetirizine is metabolised. Levocetirizine is mainly eliminated unchanged in the urine through both glomerular filtration and tubular secretion. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loratadine is metabolized mainly by CYP3A4 and to a lesser extent by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Promethazine is metabolized mainly by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terfenadine undergoes extensive metabolism mainly by CYP3A4 to form azacyclonol and terfenadine alcohol. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Almotriptan is partly eliminated unchanged in the urine and partly metabolized (mainly via monoamine oxidase-A and to a lesser extent by CYP3A4, CYP2D6 and flavin monooxygenase). Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rizatriptan is metabolized by oxidative deamination by monoamine oxidase-A (MAO-A). 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sumatriptan is eliminated primarily by metabolism mediated by monoamine oxidase A. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amodiaquine is mainly metabolized by CYP2C8 to N-desethylamodiaquine, an active metabolite but less potent than the parent compound. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atovaquone is mainly eliminated unchanged in the faeces. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benznidazole undergoes non-CYP mediated metabolism and partly CYP mediated metabolism. Renal elimination of unchanged benznidazole appears to be minimal and there is little potential for an interaction via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diloxanide furoate is largely hydrolysed under the combined action of bacterial and gut esterases and subsequently glucuronidated. No clinically significant drug interactions are known, and significant interactions with doravirine are unlikely. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as approximately 80% of oral/intravenous doses of eflornithine are excreted unchanged via the kidneys. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Halofantrine is extensively metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lumefantrine is metabolized predominantly by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mefloquine is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as the predominant route of elimination of meglumine antimoniate is renal glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely, although due to the lack of available data, vigilance is required if administering melarsoprol with antiretrovirals. It is unknown whether urinary metabolites of melarsoprol, such as arsenic, are excreted via active renal mechanisms. However a clinical study has reported that urinary pharmacokinetic parameters are not predictive of toxicity or therapeutic efficacy.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is metabolized by CYP3A4 and in vitro studies have shown that interactions between miltefosine and drugs which are metabolized by cytochrome P450 are unlikely. 

Coadministration has not been studied. Based on limited data concerning metabolism, elimination and toxicity of nifurtimox, a clinically significant interaction is unlikely. Nifurtimox appears to be biotransformed partially at a cytochrome P450 level but mostly by NADPH P450 reductase therefore no interaction is expected with doravirine. 

Coadministration has not been studied but based on metabolism and elimination, a clinically significant interaction is unlikely. Paromomycin is not metabolized and is eliminated unchanged by renal glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pentamidine is metabolized by CYP1A2 and CYP2D6. Doravirine does not inhibit or induce CYP enzymes. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Primaquine is metabolised mainly through a non-CYP mediated mechanism and only a small fraction of the drug is believed to be metabolised through CYP450. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Proguanil is partly excreted unchanged and partly metabolized to its more active metabolite cycloguanil by CYP2C19 and to a lesser extent by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

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. Quinine is extensively metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elimination of sodium stibogluconate is predominantly via renal glomerular filtration. 

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. Amisulpride is weakly metabolized and is primarily eliminated renally (possibly via OCT). Doravirine is unlikely to significantly impair amisulpride elimination. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (mainly CYP1A2, with minor contributions from CYP3A4 and CYP2D6). Doravirine does not inhibit or induce UGT or CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluphenazine is predominantly metabolised via CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Haloperidol undergoes glucuronidation (UGT2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4, 2D6). Doravirine does not inhibit or induce CYP or UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iloperidone is metabolised by CYP3A4 and CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Levomepromazine is metabolised by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olanzapine is metabolized mainly by CYP1A2, but also by glucuronidation (UGT1A4). Doravirine does not inhibit or induce CYP or UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily eliminated renally (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Doravirine is unlikely to significantly impair paliperidone’s elimination or metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perazine is demethylated by CYP3A4 and to a lesser extent by CYP2C9, and oxidated by FMO3. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of periciazine has not been well characterized but is likely to involve CYP2D6. Doravirine does not inhibit or induce CYP enzymes. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perphenazine is metabolized by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quetiapine is primarily metabolised by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Risperidone is metabolized by CYP2D6 and to a lesser extent by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sulpiride is mainly excreted in the urine and faeces as unchanged drug. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as tiapride is excreted largely unchanged in the urine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately two thirds of ziprasidone metabolic clearance is by reduction, with less than one third by CYP enzymes (mainly CYP3A4). Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zotepine is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zuclopenthixol is metabolized by sulphoxidation, N-dealkylation (by CYP2D6 and CYP3A4) and glucuronidation. Doravirine does not inhibit or induce CYP or UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amantadine is mainly eliminated in the kidney by glomerular filtration and active secretion via OCT2. Doravirine does not inhibit renal transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as daclatasvir is partly metabolized by CYP3A4 and mainly eliminated unchanged in bile.

Coadministration of doravirine (100 mg once daily) and elbasvir/grazoprevir (50/200 mg once daily) increased doravirine AUC, Cmax and Cmin by 56%, 41%, 61%, respectively (n=12). The increase in doravirine exposure is not considered to be clinically relevant. Elbasvir/grazoprevir exposure was not significantly altered by doravirine (elbasvir AUC, Cmax and C24 all decreased by 4%; grazoprevir AUC and Cmax increased by 7% and 22%, C24 decreased by 10%).

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Entecavir is eliminated renally via glomerular filtration and active renal secretion by both organic anions and cations transporters. Doravirine does not inhibit renal transporters.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Famciclovir is converted to penciclovir by aldehyde oxidase. Penciclovir is secreted in the urine possibly by OAT1. Doravirine does not interfere with famciclovir elimination.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely as foscarnet is cleared mainly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ganciclovir is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OAT1. Doravirine does not inhibit renal transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is metabolized by CYP3A4. Glecaprevir/pibrentasvir is only a weak inhibitor of CYP3A4 therefore is unlikely to affect the exposure of doravirine to any clinically significant extent. 

Coadministration of doravirine (100 mg once daily) and ledipasvir/sofosbuvir (90/400 mg once daily) increased doravirine AUC, Cmax and Cmin by 15%, 11% and 24%, respectively (n=14). This small increase is not considered clinically meaningful. Doravirine did not significantly alter ledipasvir or sofosbuvir exposures (ledipasvir AUC and Cmax decreased by 8% and 9%; sofosbuvir AUC increased by 4%, Cmax decreased by 11%; AUC and Cmax of GS-331007 both increased by 3%).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oseltamivir is converted to oseltamivir carboxylate by esterases which is then excreted in the urine by glomerular filtration and tubular secretion by OAT1. Doravirine is unlikely to interact significantly with oseltamivir.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Ribavirin is partly metabolized (non-CYP mediated) and partly excreted in the urine. Doravirine is unlikely to interact significantly with ribavirin.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Rimantadine is both hydroxylated and glucuronidated. Doravirine does not inhibit or induce CYP and UGT enzymes.

Coadministration with sofosbuvir alone has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Coadministration of doravirine (100 mg once daily) and ledipasvir/sofosbuvir (90/400 mg once daily) increased doravirine AUC, Cmax and Cmin by 15%, 11% and 24%, respectively. This small increase is not considered clinically meaningful. Doravirine did not significantly alter sofosbuvir exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir/velpatasvir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir/velpatasvir/voxilaprevir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telbivudine is eliminated primarily by urinary excretion as unchanged drug. The renal clearance of telbivudine approaches normal glomerular filtration rate, suggesting that filtration is the main mechanism of excretion. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valaciclovir is converted to aciclovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1. Doravirine does not interfere with valaciclovir elimination. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. A small amount of the orally inhaled zanamivir is systemically absorbed. Absorbed zanamivir is excreted unchanged in the urine whereas unabsorbed zanamivir is excreted in the faeces. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is metabolized mainly by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromazepam undergoes oxidative biotransformation. Drug-drug interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may play a role. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolized to nordiazepam (by CYP3A4 and 2C19) and to temazepam (mainly by CYP3A4). Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Estazolam is metabolized to its major metabolite 4-hydroxyestazolam via CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolized mainly via CYP3A4 and CYP2C19. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of flurazepam is most likely CYP-mediated. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyzine is partly metabolized by alcohol dehydrogenase and partly by CYP3A4. Doravirine does not interact with hydroxyzine’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Lorazepam is mainly glucuronidated. Doravirine does not inhibit or induce UGT enzymes.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Lormetazepam is mainly glucuronidated. Doravirine does not inhibit or induce UGT enzymes.

Coadministration of midazolam (2 mg single dose administered orally) and doravirine (120 mg once daily) did not significantly alter midazolam exposure. Midazolam AUC decreased by 18%, whereas Cmax increased by 2%.

Coadministration with PARENTERALLY administered midazolam has not been studied. Coadministration of ORAL midazolam (2 mg single dose) and doravirine (120 mg once daily) did not significantly alter midazolam exposure (midazolam AUC decreased by 18%, Cmax increased by 2%).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxazepam is mainly glucuronidated by UGTs 2B15, 1A9 and 2B7. Doravirine does not inhibit or induce UGT enzymes.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Temazepam is mainly glucuronidated. Doravirine does not inhibit or induce UGT enzymes.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Triazolam is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zaleplon is mainly metabolized by aldehyde oxidase and to a lesser extent CYP3A4. Doravirine does not interact with zaleplon’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Zolpidem is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C9 and CYP1A2. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Zopiclone is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C8. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pimozide is metabolized mainly by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atenolol is mainly eliminated unchanged by the kidney both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nebivolol metabolism involves CYP2D6. Doravirine does not inhibit or induce CYP enzymes. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxprenolol is largely metabolised by glucuronidation. Doravirine does not inhibit or induce UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pindolol is partly metabolized to hydroxymetabolites (possibly by CYP2D6) and partly eliminated unchanged in the urine. Doravirine does not significantly interfere with pindolol elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propranolol is metabolized by 3 routes (aromatic hydroxylation by CYP2D6, N-dealkylation followed by side chain hydroxylation via CYPs 1A2, 2C19, 2D6, and direct glucuronidation). Doravirine does not inhibit or induce CYP or UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Timolol is predominantly metabolised in the liver by CYP2D6. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aminophylline is a complex of theophylline and ethylenediamine and is given for its theophylline activity. Theophylline is mainly metabolized by CYP1A2. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation being another pathway. Doravirine does not inhibit or induce CYP or UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glycopyrronium bromide is mainly eliminated renally (active secretion via organic cation transporter) and is also partly hydroxylated via multiple CYPs. Doravirine is unlikely to significantly impact glycopyrronium bromide exposure. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indacaterol is eliminated partly unchanged (33%) and partly metabolized by CYP3A4 and UGT1A1, and is a weak substrate of P-gp. Doravirine does not inhibit or induce CYP or UGT enzymes or P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A small proportion of an inhaled ipratropium dose is systemically absorbed (6.9%). Metabolism is via ester hydrolysis and conjugation. Doravirine does not interfere with ipratropium bromide’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Montelukast is mainly metabolized by CYP2C8 and to a lesser extent by CYPs 3A4 and 2C9. Doravirine does not inhibit or induce CYP enzymes. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olodaterol is metabolized by CYP2C8, CYP2C9, is glucuronidated via several UGTs, and is a substrate of P-gp. Doravirine does not inhibit or induce CYP or UGT enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Roflumilast is metabolized by CYP3A4 and CYP1A2 to form roflumilast N-oxide, with both roflumilast and roflumilast N-oxide having PDE4 inhibitory activity. Roflumilast N-oxide is subsequently dealkylated by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salbutamol is metabolized to the inactive salbutamol-4’-O-sulphate. Doravirine does not interfere with salbutamol’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salmeterol is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Theophylline is mainly metabolized by CYP1A2. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tiotropium bromide is predominantly excreted unchanged in the urine. Metabolism by CYP2D6 and CYP3A4 is only a minor role in its elimination. Doravirine does not interfere with tiotropium bromide elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Umeclidinium bromide is mainly metabolized by CYP2D6 and is a substrate of P-gp. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vilanterol is metabolized by CYP3A4 and is a substrate of P-gp. Doravirine does not inhibit or induce CYP enzymes or P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amlodipine is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Felodipine is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nifedipine is metabolised mainly by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nisoldipine is metabolised mainly by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrendipine is extensively metabolized mainly by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Doravirine had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/levonorgestrel. 

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Doravirine does not inhibit or induce CYP enzymes. Doravirine had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/levonorgestrel.

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Doravirine does not inhibit or induce CYP enzymes. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Doravirine does not inhibit or induce CYP enzymes. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration with estradiol as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4, CYP1A2 and is glucuronidated. Doravirine does not inhibit or induce CYP or UGT enzymes.

Coadministration of doravirine (100 mg once daily) and ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgrestrel and doravirine exposures. Ethinylestradiol AUC and Cmax decreased by 2% and 17%; levonorgestrel AUC increased by 21% and Cmax decreased 4% (n=20). Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

Coadministration with an etonogestrel-containing progestogen-only implant and doravirine alone has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes and no effect is expected on etonogestrel exposure. This was confirmed in a pharmacokinetic study comparing etonogestrel Cmin of an etonogestrel implant when coadministered with doravirine, lamivudine, tenofovir-DF or a dolutegravir-containing regimen and which showed no significant differences in the GM Cmin of etonogestrel between the two ARV treatment groups.

Coadministration with etonogestrel as a combined vaginal ring (CVR) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes.

Coadministration with a gestodene-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Ethinylestradiol is mainly metabolized by hydroxylation. Doravirine does not inhibit or induce CYP enzymes. Doravirine had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/levonorgestrel. 

Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Ethinylestradiol is mainly metabolized by hydroxylation. Doravirine had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily). Ethinylestradiol AUC and Cmax decreased by 2% and 17%; levonorgestrel AUC increased by 21% and Cmax decreased 4% (n=20).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Doravirine had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily).

Coadministration with levonorgestrel as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Doravirine had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily). In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration with a levonorgestrel progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Doravirine had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily).

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 progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Doravirine had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily).

Coadministration with doravirine alone has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes and no effect is expected on medroxyprogesterone exposure. This was confirmed in a pharmacokinetic study comparing the Cmin of IM medroxyprogesterone when coadministered with doravirine, lamivudine, tenofovir-DF or a dolutegravir-containing regimen and which showed no significant differences in the GM Cmin of medroxyprogesterone between the two ARV treatment groups.

Coadministration with medroxyprogesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration with transdermally delivered norelgestromin/ethinylestradiol has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norelgestromin is metabolized to norgestrel (possibly by CYP3A4). Ethinylestradiol is mainly metabolized by hydroxylation. Doravirine does not inhibit or induce CYP enzymes. In addition, doravirine had no clinically significant effects on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/levonorgestrel.