Coadministration has not been studied and is not recommended. 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. Phenobarbital induces P-gp and could reduce the absorption of tenofovir-DF, however this effect likely to be small. Lamivudine does not interact with these metabolic pathways.

Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) and Delstrigo (doravirine, lamivudine, tenofovir-DF) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, Symtuza contains emtricitabine and tenofovir alafenamide and must not be administered with products containing lamivudine and tenofovir-DF.

Delstrigo (doravirine, lamivudine, tenofovir-DF) contains tenofovir-DF and must not be administered with products containing tenofovir alafenamide.

Delstrigo (doravirine, lamivudine, tenofovir-DF) and Dovato (dolutegravir, lamivudine) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both Delstrigo and Dovato contain lamivudine and should not be taken with any other medicinal products also containing lamivudine.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products or with additional tenofovir-DF.

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. Lamivudine and tenofovir-DF are predicted to be minimally impacted by phenobarbital. 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 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. Lamivudine and tenofovir-DF are eliminated renally. Doravirine is unlikely to affect phenytoin metabolism. No interaction is expected with lamivudine. Phenytoin is an inducer of P-gp and may reduce the absorption of tenofovir-DF. However, based on the results of the interaction study between tenofovir-DF and rifampicin (another inducer of P-gp), phenytoin would only be expected to cause a small decrease in tenofovir-DF. 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.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products or with additional lamivudine.

Coadministration is contraindicated in the product labels for Delstigo 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. No interaction is expected with lamivudine or tenofovir-DF.

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 not recommended 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. Similarly to rifampicin, rifapentine is unlikely to significantly impact lamivudine and tenofovir-DF exposures. 

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, Delstrigo contains lamivudine and tenofovir-DF and should not be administered products containing emtricitabine or additional tenofovir-DF.

Rifampicin was shown to decrease doravirine exposure by 82% and therefore coadministration is not recommended 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. Previous data have shown no clinically significant effect of rifampicin on lamivudine and tenofovir-DF exposures.

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. Lamivudine and tenofovir-DF are not significantly impacted by eslicarbazepine.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, Delstrigo contains lamivudine and tenofovir-DF and should not be administered products containing emtricitabine or tenofovir alafenamide.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV-1 infection and coadministration with other antiretroviral agents is not recommended in Delstrigo product labels. Atazanavir alone should not be coadministered with Delstrigo as tenofovir-DF may decrease atazanavir concentrations and the atazanavir product labels recommend boosted atazanavir with tenofovir-DF. Coadministration of tenofovir-DF (300 mg once daily; a component of Delstrigo) with atazanavir/ritonavir 300/100 mg once daily) decreased atazanavir AUC, Cmax and Cmin 22%, 16% and 23%, respectively.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, Delstrigo contains lamivudine and should not be administered with emtricitabine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine.

Delstrigo (doravirine, lamivudine, tenofovir-DF) and Odefsey (rilpivirine, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, products containing emtricitabine should not be administered with products containing lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Furthermore, products containing tenofovir-DF should not be coadministered with products containing tenofovir alafenamide.

Delstrigo (doravirine, lamivudine, tenofovir-DF) and Triumeq (dolutegravir, abacavir, lamivudine) are both indicated for use as complete regimens for the treatment of HIV-1 infection should not be administered with other antiretroviral products. In addition, both Delstrigo and Triumeq contain lamivudine and should not be taken with any other medicinal products also containing lamivudine.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, doravirine should not be administered with another NNRTI (i.e., rilpivirine).

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.  Lamivudine and tenofovir-DF are predicted to be minimally impacted by oxcarbazepine. 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.

Delstrigo (doravirine, lamivudine, tenofovir-DF) and Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, products containing emtricitabine should not be administered with products containing lamivudine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Furthermore, products containing tenofovir-DF should not be coadministered with products containing tenofovir alafenamide.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, coadministration is expected to decrease doravirine exposure.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, coadministration is expected to decrease doravirine exposure.

Delstrigo (doravirine, lamivudine, tenofovir-DF) and Juluca (dolutegravir, rilpivirine are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, doravirine should not be administered with another NNRTI (i.e., rilpivirine).

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) and Delstrigo (doravirine, lamivudine, tenofovir-DF) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, Delstrigo contains lamivudine and tenofovir-DF and should not be administered products containing emtricitabine or tenofovir alafenamide.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. 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.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) and Delstrigo (doravirine, lamivudine, tenofovir-DF) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, Delstrigo contains lamivudine and tenofovir-DF and should not be administered products containing emtricitabine or additional tenofovir-DF.

Coadministration has not been studied. Kanamycin is eliminated unchanged predominantly via glomerular filtration. No interaction is expected with doravirine or lamivudine. However, both kanamycin and tenofovir are potentially nephrotoxic and tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amikacin is eliminated renally by glomerular filtration. Doravirine and lamivudine do not interact with amikacin. However tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied. Fuconazole is mainly eliminated renally by glomerular filtration and is an inhibitor of CYP3A4 and P-gp. Fluconazole is unlikely to affect lamivudine concentrations. but may increase plasma concentrations of doravirine (inhibition of CYP3A4) and could potentially increase the absorption of tenofovir-DF (inhibition of P-gp), thereby increasing the systemic concentration of tenofovir. 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. No dose adjustment of tenofovir is required, but monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

Coadministration has not been studied. Flucytosine is metabolised to 5-flurouracil which is further metabolised by dihydropyrimidine dehydrogenase. Doravirine does not interfere with flucytosine metabolism. However, this enzyme is also involved in the catabolic pathway of pyrimidine analogs and competition could potentially increase haematological toxicity. Monitor haematological parameters and consider dose reduction if required. 

Coadministration has not been studied and should be avoided. Doravirine is metabolized by CYP3A4 and griseofulvin is an enzyme inducer and 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. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys therefore no pharmacokinetic interaction is expected with lamvudine and tenofovir-DF.

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. Lamivudine does not interact with itraconazole. However, tenofovir-DF is a substrate of P-gp and inhibitors of P-gp such as itraconazole could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended. 

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. Lamivudine does not interact with ketoconazole. However, tenofovir-DF is a substrate of P-gp and inhibitors of P-gp such as ketoconazole could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended. 

Coadministration has not been studied. Posaconazole is eliminated mainly unchanged in the faeces and only a minimal amount undergoes biotransformation (mainly glucuronidation by UGT1A4). 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. Posaconazole is also an inhibitor of P-gp and could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. No dose adjustment of tenofovir is required, but monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended. Lamivudine is unlikely to be impacted by posaconazole.

Coadministration has not been studied. Voriconazole is metabolised by CYPs 2C19, 2C9 and 3A4. 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. Voriconazole is also an inhibitor of P-gp and could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. No dose adjustment of tenofovir is required, but monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended. Lamivudine is unlikely to be impacted by voriconazole.

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. Lamivudine and tenofovir-DF are unlikely to be impacted by thioridazine.

Coadministration has not been studied. No pharmacokinetic interaction is expected with doravirine and lamivudine, but coadministration could potentially decrease renal elimination of tenofovir (thereby increasing the risk of nephrotoxicity) as diclofenac is a strong inhibitor of MRP4. A retrospective analysis showed that patients treated with diclofenac together with tenofovir-DF containing regimens were at higher risk of developing an acute kidney injury when compared to patients treated with tenofovir-DF-sparing regimens. Since diclofenac can exacerbate tenofovir-DF nephrotoxicity, diclofenac should preferably be avoided or otherwise used with caution and close monitoring of renal function is recommended. Doravirine and lamivudine do not interfere with diclofenac.

Coadministration has not been studied. No pharmacokinetic interaction is expected with doravirine and lamivudine, but coadministration could potentially decrease the renal elimination of tenofovir and thereby increase the risk of nephrotoxicity. The risk is also increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is co-administered with an NSAID, renal function should be monitored adequately. 

Coadministration has not been studied. Capreomycin is predominantly excreted in the urine as unchanged drug. Doravirine does not interact with capreomycin. However, there may be potential competition with lamivudine and tenofovir for renal elimination transport mechanisms resulting in increased drug concentrations. In addition, renal toxicity has been reported during capreomycin treatment. Tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

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. Lamivudine does not interact with verapamil. Tenofovir-DF is a substrate of P-gp and inhibitors of P-gp such as verapamil could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended. 

Coadministration has not been studied. 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. Piperine, a component of Piper cubeba, inhibits intestinal P-gp. No interaction is expected with lamivudine. Tenofovir-DF is a substrate of P-gp and its absorption could potentially increase, thereby increasing tenofovir systemic concentrations. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended. 

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. No interaction is expected between lamivudine or tenofovir-DF and modafinil.

Coadministration has not been assessed in pharmacokinetic or long-term studies. Lithium is mainly eliminated unchanged through the kidneys. Lithium is freely filtered at a rate that is dependent upon the glomerular filtration rate therefore no interaction is expected with doravirine and lamivudine. However, since lithium is nephrotoxic, renal function should be monitored closely and the dosage of tenofovir-DF adjusted accordingly. A randomized control trial of lithium (n=23) versus placebo (n=30) in patients with HIV-associated neurocognitive impairment receiving tenofovir-containing antiretroviral regimens found short-term (24 week) coadministration of lithium and tenofovir-DF did not result in increased nephrotoxicity, however, the results could not rule out nephrotoxicity with longer-term administration.

Coadministration has not been studied. Ifosfamide is predominantly metabolized by CYP3A4 and CYP2B6 but doravirine does not inhibit or induce CYP enzymes. 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. No pharmacokinetic interaction is expected with lamivudine. Ifosfamide has been associated with serious nephrotoxicity including proximal and distal tubular damage, glomerular effects and Fanconi syndrome and therefore renal function should be closely monitored when coadministered with tenofovir-DF due to potential renal additive toxicity. Use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product. If coadministration is unavoidable, renal function should be monitored closely.

Coadministration has not been studied. Clinical studies have reported that the predominant route of elimination of meglumine antimoniate is renal glomerular filtration. No pharmacokinetic interaction with doravirine or lamivudine is expected. An interaction due to competition with tenofovir for active renal transport mechanisms is unlikely. However, renal impairment and sometimes fatal renal failure have been described with meglumine antimoniate treatment. Close monitoring of renal function is warranted. 

Coadministration has not been studied. In vitro studies suggest a role of CYP2C9 in sulfadiazine metabolism. Doravirine does not inhibit or induce CYP enzymes. Sulfadiazine has been associated with crystalluria leading to renal toxicity and in some cases renal failure, with case reports in immunocompromised patients suggesting that AIDS patients may be particularly prone to sulfadiazine-induced renal toxicity. Monitoring of renal function is warranted as sulfadiazine may impair lamivudine renal elimination. Furthermore, use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product. If coadministration is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied. 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. Lamivudine does not interact with topiramate. However, topiramate and tenofovir-DF can cause renal toxicity (i.e., nephrolithiasis with topiramate and Fanconi syndrome with tenofovir-DF), therefore use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product. If coadministration is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied. Methotrexate is predominantly eliminated via the kidneys, including active tubular secretion (OAT1, OAT3 mediate methotrexate transport in the kidney whereas MRP4 and BCRP mediate methotrexate efflux in the urine). Doravirine and lamivudine do not interfere with methotrexate elimination. In theory, there is potential for competition for active renal transport mechanisms if tenofovir-DF and methotrexate are coadministered. However, the results of a clinical study evaluating the co-administration of high-dose of intravenous methotrexate with different NRTI, including tenofovir, showed that methotrexate half-life was not prolonged.  However, since methotrexate and tenofovir may both cause tubular toxicity, the use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product. If coadministration is unavoidable, renal function should be monitored closely. Note, some methotrexate product labels contraindicate its use or advise caution in immunodeficiency and some contraindicate its use in HIV infection. 

Coadministration has not been studied. Oxaliplatin undergoes non-enzymatic biotransformation and is eliminated renally via OCT2 and MATE2-K. Doravirine does not interfere with oxaliplatin elimination. Oxaliplatin and lamivudine could potentially compete for OCT2 which could slow their elimination. Although oxaliplatin is less nephrotoxic than other platinum drugs, renal function should be closely monitored due to a potential risk of additive nephrotoxicity with tenofovir-DF. 

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 dosed at 100 mg twice daily (based on the interaction study with rifabutin, another moderate inducer) by administering one 100 mg tablet of doravirine daily, taken approximately 12 hours after the dose of Delstrigo. This dose should be maintained 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. Lamivudine and tenofovir-DF do not interact with paclitaxel’s metabolic pathway.

Coadministration has not been studied but is unlikely to result in a pharmacokinetic interaction with doravirine, lamivudine or tenofovir-DF. Aspirin is rapidly deacetylated to form salicylic acid which is further glucuronidated by several UGTs (major UGT1A6). However, coadministration could potentially result in increased risk of nephrotoxicity with tenofovir-DF. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is co-administered with an NSAID, renal function should be monitored adequately. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Pentamidine is metabolized by CYP1A2 and CYP2D6. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interfere with pentamidine elimination. However, tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied but based on metabolism and clearance, a pharmacokinetic interaction is unlikely. Sorafenib is metabolized to a moderate extent by CYP3A4 and UGT1A9, UGT1A1. Doravirine does not inhibit or induce CYP or UGT enzymes. Lamivudine and tenofovir-DF do not interact with sorafenib’s metabolic pathway. However, potential additive nephrotoxicity is expected with use of sorafenib and tenofovir-DF. Monitor renal function if coadministered or consider use of an alternate antiretroviral regimen if possible.

Coadministration has not been studied. Vancomycin is eliminated unchanged predominantly via glomerular filtration. No interaction is expected with doravirine or lamivudine. However, both vancomycin and tenofovir-DF are potentially nephrotoxic and tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. A case study described renal failure in 2 patients taking tenofovir-DF and a prolonged course of vancomycin. 

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. Lamivudine and tenofovir-DF do not interact with tamoxifen.

Coadministration has not been studied. No pharmacokinetic interaction is expected with doravirine and lamivudine, but coadministration could potentially result in increased risk of nephrotoxicity with tenofovir-DF. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is co-administered with an NSAID, renal function should be monitored adequately. 

Coadministration has not been studied. Vinblastine is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF are unlikely to impact vinblastine exposure. 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. Vinblastine is unlikely to alter lamivudine or tenofovir-DF exposures.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. However, hydroxyurea is not licensed for use in combination with stavudine and didanosine as toxicities including pancreatitis and hepatitis (in some cases fatal) in HIV patients have been reported via post marketing surveillance. Thus, caution and monitoring for side effects is recommended if coadministered with other NRTIs such as lamivudine or tenofovir-DF.

Coadministration with doravirine/lamivudine/tenofovir-DF has not been studied. Nonpegylated interferon alpha appears to be metabolized principally in the kidney. No pharmacokinetic interaction is expected with doravirine and tenofovir-DF, and no pharmacokinetic interaction was observed with lamivudine. However, hepatic decompensation (some fatal) has occurred in cirrhotic HIV/HCV co-infected patients receiving NRTI-containing HIV therapy and interferon alpha and ribavirin. Patients receiving interferon with ribavirin and NRTIs should be closely monitored for treatment-associated toxicities, especially hepatic decompensation and anaemia.

Coadministration has not been studied. Interleukin-2 is mainly eliminated by glomerular filtration. Doravirine and lamivudine do not interact with interleukin 2. Tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Doravirine is metabolized by CYP3A4. Peginterferon alfa-2a has no effect on CYP3A4. The metabolism of peginterferon alfa-2a is not fully characterized, though studies in rats indicate that the kidney is a major organ for excretion. However, hepatic decompensation (some fatal) has occurred rarely in cirrhotic HIV/HCV co-infected patients receiving NRTI-containing HIV therapy and interferon alpha and ribavirin. Patients receiving interferon with ribavirin and NRTIs should be closely monitored for treatment-associated toxicities, especially hepatic decompensation and anaemia.

Coadministration has not been studied. No pharmacokinetic interaction is expected with doravirine and lamivudine, but coadministration could potentially result in increased risk of nephrotoxicity with tenofovir-DF. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is co-administered with an NSAID, renal function should be monitored adequately.

Coadministration has not been studied. Gentamicin is eliminated unchanged predominantly via glomerular filtration. No interaction is expected with doravirine or lamivudine. However, both gentamicin and tenofovir-DF are potentially nephrotoxic and tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied. Mycophenolate is mainly glucuronidated by UGT1A9 and UGT2B7. Doravirine does not inhibit or induce UGT enzymes. In vitro data suggest that mycophenolic acid (active metabolite) inhibits the renal transporters OAT1/OAT3. No interaction is expected with lamivudine, but concentrations of mycophenolate and tenofovir could be possibly increased due to competition for active tubular secretion. Closely monitor renal function due to the risk of tubular necrosis that may occur with mycophenolate and tenofovir. 

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. No effect on doravirine or lamivudine is expected. Monitoring of sirolimus blood concentrations is recommended as the dose may need to be adjusted. Monitor renal function as appropriate since sirolimus and tenofovir-DF can display tubular toxicity.

Coadministration with Delstrigo 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. No effect on doravirine or lamivudine is expected, and there was no clinically significant pharmacokinetic interaction when tenofovir-DF (300 mg once daily) was coadministered with tacrolimus (0.05 mg/kg twice daily for 7 days). Monitoring of tacrolimus blood concentrations is recommended as the dose may need to be adjusted.

Coadministration has not been studied. No pharmacokinetic interaction is expected with doravirine and lamivudine, but coadministration could potentially result in increased risk of nephrotoxicity with tenofovir-DF. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is co-administered with an NSAID, renal function should be monitored adequately.

Coadministration has not been studied. Quinidine is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes and no interaction is expected with lamivudine. However, tenofovir-DF is a substrate of P-gp and inhibitors of P-gp such as quinidine could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended. 

Coadministration has not been studied. Amphotericin is not appreciably metabolized and is eliminated to a large extent in the bile therefore a pharmacokinetic interaction is unlikely. However, the use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product (such as amphotericin B). If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

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. No interaction is expected with lamivudine. Tenofovir-DF (the prodrug of tenofovir) is a substrate of P-gp however no significant effect is expected on tenofovir-DF based on the drug interaction study with rifampicin (a strong inducer of P-gp). 

Coadministration has not been studied. Although metabolism of penicillamine is not fully elucidated, multiple mechanisms and sites of metabolism are thought to be involved. There is therefore low potential for pharmacokinetic interactions via modulation of, or competition for metabolic and elimination pathways. However penicillamine has nephrotoxic potential and use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product. If coadministration is unavoidable, renal function should be monitored closely.

Coadministration has not been studied. Probenecid is metabolised by CYP enzymes to a limited extent. Doravirine does not inhibit or induce CYP enzymes. In vitro data suggest that probenecid is a substrate and inhibitor of renal transporters and therefore could increase lamivudine and tenofovir exposures. Monitoring of renal function is advised. 

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. Glycyrrhetinic acid, the main active metabolite of glycyrrhizin, was shown to be a strong inhibitor of P-gp in vitro. No interaction is expected with lamivudine. Tenofovir-DF is a substrate of P-gp and its absorption could potentially increase, thereby increasing tenofovir systemic concentrations. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended. 

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 but based on metabolism and clearance a pharmacokinetic interaction is unlikely as zoledronic acid is eliminated unchanged renally. However, zoledronic acid has been associated with reports of renal dysfunction and use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product. If coadministration is unavoidable, renal function should be monitored closely. 

Delstrigo (doravirine, lamivudine, 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 darunavir/cobicistat would be possible from a pharmacokinetic standpoint, but with close monitoring for tenofovir-associated adverse events. Coadministration with ritonavir increased doravirine AUC by 3.5-fold and Cmin by 2.9-fold and a similar increase may occur with cobicistat. 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. Boosted PIs were shown to increase tenofovir-DF and there are currently inadequate data to determine whether tenofovir-DF plus cobicistat is associated with a greater risk of renal adverse reactions than tenofovir-DF without cobicistat. The European SPC for tenofovir-DF advises close renal monitoring of patients receiving tenofovir-DF with a cobicistat-boosted protease inhibitor. The US Prescribing Information for cobicistat does not recommend coadministration of cobicistat and tenofovir-DF in combination with concomitant or recent use of a nephrotoxic agent. Note, cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine and should not be initiated in patients with creatinine clearance less than 70 ml/min if tenofovir-DF requires dose adjustment based on creatinine clearance.

Delstrigo (doravirine, lamivudine, 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 darunavir would be possible from a pharmacokinetic standpoint, but with close monitoring for tenofovir-associated adverse events. 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- to 4-fold increase in exposure. Coadministration of tenofovir-DF (300 mg once daily) and darunavir/ritonavir (300/100 mg twice daily) increased darunavir Cmax (16%), AUC (21%) and Cmin (24%). Tenofovir Cmax, AUC and Cmin increased by 24%, 22% and 37%, respectively. No adjustments to the licensed doses are required. A higher risk of renal impairment has been reported in patients receiving tenofovir-DF and a ritonavir or cobicistat boosted protease inhibitor. Close monitoring of renal function and for tenofovir-associated adverse reactions is required in these patients. 

Delstrigo (doravirine, lamivudine, 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 lopinavir/ritonavir would be possible from a pharmacokinetic standpoint, but with close monitoring for tenofovir-associated adverse events. 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- to 4-fold increase in exposure. Coadministration of tenofovir-DF (300 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) increased tenofovir-DF AUC by 32%, Cmin increased by 51%, and there was no change in Cmax. A higher risk of renal impairment has been reported in patients receiving tenofovir-DF and a ritonavir boosted protease inhibitor. No dose adjustment is recommended, but close monitoring of renal function and for tenofovir-associated adverse reactions is required. 

Coadministration has not been studied. Betamethasone is metabolized by CYP3A4 and 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. Lamivudine and tenofovir-DF are unlikely to be impacted by betamethasone.

Delstrigo (doravirine, lamivudine, 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 a protease inhibitor boosted with ritonavir would be possible from a pharmacokinetic standpoint, but with close monitoring for tenofovir-associated adverse events. 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- to 4-fold increase in exposure. Coadministration of tenofovir-DF and ritonavir (100 mg twice daily with lopinavir, darunavir or saquinavir) had no significant effect on ritonavir concentrations. However, a higher risk of renal impairment has been reported in patients receiving tenofovir-DF in combination with a ritonavir boosted protease inhibitor. Close monitoring of renal function is required in these patients. 

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. Lamivudine and tenofovir-DF are unlikely to be impacted by bosentan.

Coadministration has not been studied. Amiodarone is metabolized by CYPs 3A4 and 2C8. Doravirine does not inhibit or induce CYP enzymes and no interaction is expected with lamivudine. However, tenofovir-DF is a substrate of P-gp and inhibitors of P-gp such as amiodarone could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

Coadministration has not been studied but a pharmacokinetic interaction is unlikely as foscarnet is cleared mainly by glomerular filtration. However, tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied. Ganciclovir is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OAT1. No interaction is expected with doravirine or lamivudine. Since tenofovir is primarily eliminated by the kidneys, coadministration with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir or the coadministered drug. Tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied. No pharmacokinetic interaction is expected with doravirine and lamivudine, but coadministration could potentially result in increased risk of nephrotoxicity with tenofovir-DF. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is co-administered with an NSAID, renal function should be monitored adequately. 

Coadministration with Delstrigo has not been studied. 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 ledipasvir or sofosbuvir exposures. Similarly, coadministration of lamivudine and ledipasvir/sofosbuvir had no significant effect on the pharmacokinetics of lamivudine, ledipasvir and sofosbuvir. However, coadministration of tenofovir-DF with ledipasvir/sofosbuvir has been shown to increase tenofovir concentrations, especially when used with an HIV regimen containing a pharmacokinetic enhancer (ritonavir or cobicistat). Increased tenofovir exposure has also been shown with HIV regimens containing efavirenz and rilpivirine. The safety of increased tenofovir concentrations in these settings has not been established. The potential risks and benefits associated with coadministration should be considered, particularly in patients at increased risk of renal dysfunction. For patients receiving a boosted HIV protease inhibitor, consider an alternative HCV or antiretroviral therapy. If coadministration is necessary, monitor for tenofovir-associated adverse reactions, including frequent renal monitoring. 

Coadministration has not been studied. Hydralazine is metabolised via primary oxidative metabolism and acetylation. No interaction is expected with doravirine and lamivudine. A pharmacokinetic interaction is unlikely with tenofovir-DF as there is little potential for competition of hydralazine and tenofovir for active renal elimination mechanisms. However hydralazine has some nephrotoxic potential and use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product. If coadministration is unavoidable, renal function should be monitored closely.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as streptomycin is excreted rapidly in the urine by glomerular filtration. No interaction is expected with doravirine or lamivudine. However, both streptomycin and tenofovir-DF are potentially nephrotoxic and tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied. Dacarbazine is a substrate of the renal transporter OAT1. Doravirine and lamivudine do not interfere with dacarbazine elimination. Dacarbazine could compete with tenofovir for renal active secretion. No a priori dosage adjustment is recommended but renal function and haematological parameters should be monitored. 

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.

Delstrigo (doravirine, lamivudine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV-1 infection and coadministration with other antiretroviral agents is not recommended in Delstrigo product labels. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir would be possible from a pharmacokinetic standpoint. 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. In a combined analysis of several clinical studies with tenofovir-DF (300 mg) and atazanavir/ritonavir (300/100 mg), tenofovir AUC, Cmax and Cmin increased by 37%, 34% and 29%, respectively. Thus, patients should be closely monitored for tenofovir-associated adverse events, including renal disorders. Atazanavir/r should be dosed at 400/100 mg once daily in presence of tenofovir-DF and an H2-receptor antagonist due to the resulting decrease in atazanavir exposure.

Delstrigo (doravirine, lamivudine, 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 atazanavir/cobicistat would be possible from a pharmacokinetic standpoint, but with close monitoring for tenofovir-associated adverse events. Coadministration with ritonavir increased doravirine AUC by 3.5-fold and Cmin by 2.9-fold and a similar increase may occur with cobicistat. 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. Boosted PIs were shown to increase tenofovir-DF and there are currently inadequate data to determine whether tenofovir-DF plus cobicistat is associated with a greater risk of renal adverse reactions than tenofovir-DF without cobicistat. The European SmPC for tenofovir-DF advises close renal monitoring of patients receiving tenofovir-DF with a cobicistat-boosted protease inhibitor. The US Prescribing Information for cobicistat does not recommend coadministration of cobicistat and tenofovir-DF in combination with concomitant or recent use of a nephrotoxic agent. Note, cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine and should not be initiated in patients with creatinine clearance less than 70 ml/min if tenofovir-DF requires dose adjustment based on creatinine clearance. A similar recommendation is to be observed for atazanavir/cobicistat. It is not recommended to take both tenofovir-DF and an H2-receptor antagonist with atazanavir, due to the resulting decrease in atazanavir exposure.

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 Delstrigo recommends to increase doravirine dosage to 100 mg twice daily when co-administered with rifabutin by taking an additional tablet of doravirine alone approximately 12 hours after the dose of Delstrigo. Lamivudine and tenofovir-DF are not impacted by rifabutin and therefore have to be maintained at the same dose (300 mg once daily). 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. Doravirine and lamivudine are not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir/velpatasvir. However, sofosbuvir/velpatasvir increased tenofovir AUC by ~30-80% when administered with various regimens containing tenofovir-DF. No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 or velpatasvir was observed. Monitor for tenofovir-associated adverse reactions. 

Coadministration has not been studied. Doravirine and lamivudine are not expected to inhibit or induce any relevant metabolic enzymes or transporters of sofosbuvir/velpatasvir/voxilaprevir. However, sofosbuvir/velpatasvir/voxilaprevir has been shown to increase tenofovir exposure due to inhibition of P-gp inhibition by velpatasvir and voxilaprevir. Tenofovir exposure (AUC and Cmax) increased by ~40% during co-treatment with sofosbuvir/velpatasvir/voxilaprevir and tenofovir-DF (with darunavir/ritonavir/emtricitabine). Patients receiving sofosbuvir/velpatasvir/voxilaprevir concomitantly with tenofovir-DF should be monitored for tenofovir associated adverse reactions. 

Coadministration has not been studied. Valaciclovir is converted to aciclovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1. Doravirine and lamivudine do not interfere with valaciclovir elimination. However, tenofovir-DF could compete for active tubular secretion which may increase concentrations of tenofovir or valaciclovir. Furthermore, tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. The metabolism of canagliflozin is primarily mediated by UGT1A9 and UGT2B4 which are not affected by doravirine, lamivudine and tenofovir-DF. However, since an increased risk for bone fractures has been reported with canagliflozin (particularly in patients with a history of, or at high risk of, cardiovascular disease), caution is recommended when coadministering canagliflozin in the long term with tenofovir-DF due to potential additive bone toxicities.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Doravirine is metabolised by CYP3A4 which is not affected by peginterferon alfa-2b. However, hepatic decompensation (some fatal) has occurred rarely in cirrhotic HIV/HCV co-infected patients receiving NRTI-containing HIV therapy and interferon alpha and ribavirin. Patients receiving interferon with ribavirin and NRTIs should be closely monitored for treatment-associated toxicities, especially hepatic decompensation and anaemia.

Coadministration has not been studied. A clinically significant effect on ranolazine is unlikely as it is primarily metabolized by CYP3A4 and doravirine does not inhibit or induce CYP enzymes. No interaction is expected with lamivudine. However, tenofovir-DF is a substrate of P-gp and inhibitors of P-gp such as ranolazine could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended. 

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. Lamivudine and tenofovir-DF are unlikely to be impacted by miconazole.

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). Tenofovir, but not lamivudine, could potentially compete for renal secretion, however, the clinical relevance of this interaction is unknown as OAT1 is only partly involved in flucloxacillin renal secretion.

Coadministration has not been studied. Sulfadoxine is rarely used alone, but is usually given in combination with pyrimethamine. No pharmacokinetic interaction with doravirine or tenofovir-DF is expected. In vitro data suggest that pyrimethamine inhibits the renal transporters OCT2 and MATE1 and may increase lamivudine exposure. No a priori dosage adjustment is recommended in patients with normal renal function. 

Coadministration has not been studied No effect is expected on doravirine as curcumin and/or turmeric extracts had no significant effect on the pharmacokinetics of probe drugs for various CYP enzymes. No effect is expected on lamivudine, however, the effect on tenofovir-DF is unclear as curcumin and/or turmeric extracts appeared to inhibit P-gp in vivo, but a contradictory effect was observed in vivo. No a priori dose adjustment is recommended.

Delstrigo (doravirine, lamivudine, 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 zidovudine would be possible from a pharmacokinetic standpoint. Coadministration of zidovudine with doravirine or tenofovir-DF has not been studied, but a clinically significant interaction is unlikely. Coadministration of zidovudine (200 mg single dose) and lamivudine (300 mg twice daily) to 12 asymptomatic HIV-infected adult patients increased zidovudine Cmax and AUC by 28% and 13%, but had no effect on the pharmacokinetics of lamivudine.

Coadministration has not been studied. Pramipexole is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporter OCT2. Doravirine and tenofovir do not interfere with pramipexole’s elimination. However, pramipexole may compete with lamivudine for renal elimination transport mechanisms which may lead to increased concentrations of either drug. No a priori dosage adjustment is required unless if the patient presents pramipexole related side effects.

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. Lamivudine and tenofovir-DF are unlikely to be impacted by ergotamine.

Coadministration has not been studied. Atenolol is mainly eliminated unchanged by the kidney both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1. No interaction is expected with doravirine or tenofovir. However, lamivudine and atenolol could potentially compete for elimination via renal transport proteins, which may lead to increased concentrations of either drug.

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. Lamivudine and tenofovir-DF do not interact with erythromycin.

Coadministration has not been studied. Mesna is rapidly oxidised to its only metabolite, mesna disulphide via the physiological cysteine system. Doravirine and lamivudine do not interfere with mesna elimination. Tenofovir is predominantly eliminated by active renal transport mechanisms. Co-administration of mesna with other drugs which are predominantly eliminated by active renal transport, such as tenofovir, may lead to competition for renal transporters and may raise exposure to either drug. Administration of probenecid, a renal organic anion transporter inhibitor, to healthy subjects significantly increased combined mesna and dimesna plasma exposure, while decreasing the renal clearance. This may decrease the efficacy of mesna as a chemoprotectant, increasing the risk of ifosfamide- and cisplatin-induced toxicities. 

Coadministration has not been studied. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine possibly via OCT2. Doravirine does not inhibit or induce CYP enzymes. Data from animal studies indicate that disopyramide is a weak inhibitor of the renal transporter OCT2. Since OCT2 may contribute to the renal elimination of disopyramide, there is potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug. No interaction via OCT2 is expected with doravirine or tenofovir as these drugs are not transported by OCT2.

Coadministration has not been studied. Dofetilide is mainly excreted unchanged in urine. Renal elimination involves both glomerular filtration and active tubular secretion (via cation transport system). There is potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug. Tenofovir and doravirine are not eliminated by organic cation transporters and therefore do not interfere with dofetilide’s elimination.

Coadministration has not been studied. Amiloride is eliminated unchanged by the kidney and in vitro data indicate that it is a substrate of OCT2. Doravirine and tenofovir are unlikely to significantly interfere with amiloride elimination. However, amiloride may potentially compete with lamivudine for renal elimination transport mechanisms which may lead to increased concentrations of either drug.

Coadministration has not been studied. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. Nucleoside/nucleotide analogues such as lamivudine or tenofovir-DF may compete for this metabolic pathway. The clinical relevance of this interaction is unknown.

Coadministration has not been studied. Amantadine is mainly eliminated in the kidney by glomerular filtration and active secretion via OCT2. Doravirine and tenofovir do not interfere with amantadine elimination, however, lamivudine may compete with amantadine for renal elimination. 

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. No interaction is expected with lamivudine and tenofovir-DF.

Coadministration has not been studied. No pharmacokinetic interaction with doravirine or tenofovir-DF is expected. In vitro data suggest that pyrimethamine inhibits the renal transporters OCT2 and MATE1 and may increase lamivudine exposure. No a priori dosage adjustment is recommended in patients with normal renal function. 

Coadministration has not been studied. 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. However, both lamivudine and tenofovir can potentially compete for elimination via renal transport proteins, which may lead to increased concentrations of these drugs. In addition, a clinical study performed with the calcium salt of para-aminosalicylic acid showed an unexpected substantial reduction in tenofovir exposure. The mechanism is unclear but could relate to reduced absorption in presence of the calcium salt of para-aminosalicylic acid. Until further data are available on the mechanism on the interaction, caution is needed when coadministering tenofovir with the calcium salt of para-aminosalicylic acid.

Coadministration has not been studied. Penicillins are mainly eliminated in the urine (20% by glomerular filtration and 80% by tubular secretion via OAT). Doravirine and lamivudine do not interfere with penicillins elimination. Tenofovir could potentially increase due to competition for active tubular secretion, however, no a priori dosage adjustment is recommended. 

Coadministration has not been studied. Famciclovir is converted to penciclovir by aldehyde oxidase. Penciclovir is secreted in the urine possibly by OAT1. Doravirine and lamivudine do not interfere with famciclovir elimination. However, tenofovir-DF could compete for active tubular secretion which may increase concentrations of tenofovir or famciclovir. No a priori dosage adjustment is recommended, but renal function should be monitored. 

Coadministration has not been studied. Trimethoprim is primarily eliminated by the kidneys through glomerular filtration and tubular secretion. No interaction is expected with doravirine or tenofovir-DF. In vitro data indicate that trimethoprim inhibits the renal transporters OCT2 and MATE1 and trimethoprim has been shown to increase lamivudine exposure by 43%. No dose adjustment is required in patients with normal renal function. Note, the bioavailability of lamivudine solution has been shown to be significantly reduced in a dose dependent manner by sorbitol which is present in liquid formulations such trimethoprim/sulfamethoxazole paediatric suspension. When possible, avoid use of sorbitol-containing medicines with lamivudine-containing medicines.

Coadministration has not been studied. Approximately 80% of oral/intravenous doses of eflornithine are excreted unchanged via the kidneys. Doravirine does not interfere with eflornithine elimination. As there are no available data determining whether excretion is via active tubular secretion or glomerular filtration, there is potential for competition with lamivudine or tenofovir for active renal transport mechanisms, which may lead to increased levels of either drug. A clinically significant interaction is not expected with topical preparations as less than 1% of topically applied eflornithine is systemically absorbed. 

Coadministration has not been studied. Nilotinib is a moderate inhibitor of CYP3A4 and therefore could potentially increase doravirine exposure although to a limited extent. 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. Lamivudine and tenofovir-DF do not interfere with nilotinib’s metabolic pathway.

Coadministration has not been studied. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally (via OATs). Doravirine does not inhibit or induce UGTs. In vitro data indicate that furosemide is a weak inhibitor of the renal transporters OAT1/OAT3. No interaction is expected with lamivudine and only a limited effect on tenofovir renal elimination is predicted. No a priori dosage adjustment is recommended. 

Coadministration has not been studied but based. 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. 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. Lamivudine and tenofovir-DF do not interact with imatinib.

Coadministration has not been studied. Sacubitril is rapidly converted to LBQ657 (active metabolite) by carboxylesterases and the active metabolite is not further metabolized to a significant extent. Sacubitril inhibits OATP1B1 and LBQ657 is a substrate of OATP1B1/3, OAT1 and OAT3. Doravirine and lamivudine do not interfere with sacubitril’s metabolic pathway. Tenofovir is eliminated via OAT1 and therefore could potentially compete with LBQ657 renal elimination (clinical relevance is unclear). Start with the lowest recommended dose of sacubitril and titrate dosage as tolerated by the patient. 

Coadministration with Delstrigo has not been studied. Coadministration of doravirine 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 lamivudine (in combination with abacavir) and ombitasvir and paritaprevir/r had no effect on the pharmacokinetic parameters of lamivudine, ombitasvir, and paritaprevir/r. Tenofovir-DF can be administered with ombitasvir/paritaprevir/ritonavir and no dose alteration is required. No significant interactions were seen in clinical studies. Coadministration of ombitasvir/paritaprevir/ritonavir with emtricitabine/tenofovir-DF (200/300 mg once daily) decreased tenofovir Cmax by 20% and increased AUC and Cmin by 1% and 13%. Paritaprevir Cmax, AUC and Cmin increased by 2%, 4% and 9%. Similarly, coadministration of lamivudine (in combination with abacavir) and ombitasvir and paritaprevir/r had no effect on the pharmacokinetic parameters of lamivudine, ombitasvir, and paritaprevir/r.

Coadministration has not been studied. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Doravirine does not interfere with these metabolic pathways. However, nucleoside/tide analogues such as lamivudine or tenofovir-DF may compete for these metabolic pathways. The clinical relevance of this interaction is unknown.

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 on artemisins is unlikely as doravirine does not inhibit or induce CYP or UGT enzymes. 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. Lamivudine and tenofovir-DF do not interact with artemisinin’s metabolic pathway.

Delstrigo (doravirine, lamivudine, 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 ibalizumab would be possible from a pharmacokinetic standpoint as no clinically relevant drug-drug interaction is expected. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Doravirine undergoes hepatic metabolism and lamivudine and tenofovir-DF are eliminated renally, whereas ibalizumab, a monoclonal antibody binding to the CD4 receptor, is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies. Dose modifications of ibalizumab are not required when administered with any other antiretroviral.

Coadministration with Delstrigo has not been studied. Coadministration of doravirine 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 lamivudine (in combination with abacavir) and ombitasvir, paritaprevir/r and dasabuvir had no effect on the pharmacokinetic parameters of lamivudine, ombitasvir, paritaprevir/r and dasabuvir. Tenofovir-DF can be administered with ombitasvir/paritaprevir/ritonavir + dasabuvir and no dose alteration is required. No significant interactions were seen in clinical studies. Coadministration with emtricitabine/tenofovir-DF (200/300 mg once daily) increased tenofovir Cmax, AUC and Cmin by 7%, 13% and 24%, respectively. Ombitasvir Cmax, AUC and Cmin decreased by 11%, 1% and 3%, respectively. Paritaprevir Cmax and AUC decreased by 32% and 16%, but Cmin increased by 6%. Dasabuvir Cmax, AUC and Cmin all decreased by 15%. Similarly, coadministration of lamivudine (in combination with abacavir) and ombitasvir, paritaprevir/r and dasabuvir had no effect on the pharmacokinetic parameters of lamivudine, ombitasvir, paritaprevir/r and dasabuvir.

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. Lamivudine and tenofovir-DF are unlikely to be impacted by ginger.

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. Ginkgo does not impact lamivudine or tenofovir-DF.

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, lamivudine or tenofovir-DF, but for any medication taken with orlistat.]

Delstrigo (doravirine, lamivudine, 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 maraviroc (dosed at 300 mg twice daily) would be possible from a pharmacokinetic standpoint. No clinically relevant drug-drug interaction is expected between maraviroc and doravirine. Coadministration of maraviroc (300 mg twice daily) and lamivudine/zidovudine (150/300 mg twice daily) increased lamivudine AUC (14%) and Cmax (16%), but is not considered to be clinically significant. Maraviroc concentrations were not measured, but no effect is expected. Coadministration of maraviroc (300 mg twice daily) and tenofovir-DF (300 mg once daily) had no significant effect on maraviroc AUC or Cmax. Tenofovir concentrations were not measured, but no effect is expected.

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. Lamivudine and tenofovir-DF are unlikely to be impacted by grapefruit juice.

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. Significant interactions are not expected with lamivudine and tenofovir-DF.

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. Lamivudine and tenofovir-DF are not impacted by telithromycin.

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. Lamivudine and tenofovir-DF are unlikely to be impacted by inula racemosa.

Delstrigo (doravirine, lamivudine, 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 raltegravir would be possible from a pharmacokinetic standpoint. Coadministration of raltegravir and doravirine has not been studied, but a clinically significant interaction is unlikely. In drug interaction studies, raltegravir (400 mg twice daily) did not have a clinically meaningful effect on the pharmacokinetics of lamivudine. Coadministration of raltegravir (400 mg twice daily) and tenofovir-DF increased raltegravir AUC (49%) and Cmax (64%), but had no effect on Cmin; tenofovir AUC, Cmax and Cmin decreased by 10%, 23% and 13%, respectively. The increase in raltegravir exposure does not require any dose adjustment.

Coadministration has not been studied. Pyridostigmine is predominantly excreted unchanged via the kidneys, with up to 74% of renal clearance attributed to active tubular secretion. Doravirine does not interfere with pyridostigmine elimination. However, there is potential for competition with pyridostigmine and lamivudine or tenofovir-DF for active renal transport mechanisms, which may lead to increased drug concentrations.

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, lamivudine or tenofovir-DF, but for any medication taken with strontium ranelate.] 

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. No effect is expected on lamivudine and tenofovir-DF.

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. Lamivudine and tenofovir-DF are unlikely to be impacted by dihydroergotamine.

Delstrigo (doravirine, lamivudine, 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 dolutegravir 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. These changes are not considered as clinically significant thereby supporting the coadministration of dolutegravir and doravirine. Similarly, no clinically significant interactions were observed or are anticipated with tenofovir-DF or lamivudine.

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. Lamivudine and tenofovir-DF are unlikely to be impacted by menthol.

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. 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 as doravirine is a substrate of CYP3A4. Lamivudine and tenofovir-DF are unlikely to be impacted by flibanserin.

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. Lamivudine and tenofovir-DF do not interact with nicardipine.

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. Lamivudine and tenofovir-DF do not interact with nefazodone’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with diltiazem’s metabolic pathway.

Coadministration has not been studied. Renal clearance of ampicillin occurs partly by glomerular filtration and tubular secretion. Doravirine is unlikely to cause a clinically relevant drug interaction. As lamivudine and tenofovir are eliminated by renal tubular secretion, there is potential for competition with ampicillin for renal transporters, which could lead to increased drug levels when ampicillin is administered intravenously. There is little potential for a significant interaction with orally administered ampicillin.

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. Lamivudine and tenofovir-DF are unlikely to be impacted by quercetin.

Coadministration has not been studied. Trospium is minimally metabolized and is mainly eliminated unchanged renally, in part by OCT2. No interaction is expected with doravirine or tenofovir-DF. Trospium could potentially compete with lamivudine for active renal transport, but no a priori dosage adjustment is needed. 

Coadministration has not been studied. Ephedrine is predominantly eliminated unchanged via the kidneys possibly via the renal transporter OCT2. There is potential for competition with lamivudine for active renal transport mechanisms which may lead to increased levels of either drug. Doravirine and tenofovir are unlikely to interact as they are neither substrates nor inhibitors of OCT2.

No effect on the pharmacokinetics of medroxyprogesterone was observed with coadministration of doravirine, lamivudine and tenofovir.  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. Lamivudine and tenofovir-DF do not interact with medroxyprogesterone’s metabolic pathway. However, concurrent use of TDF and medroxyprogesterone has been shown to increase bone mineral density loss compared to TDF alone. Further research is needed to evaluate whether this observation translates into an increased risk of fractures. This observation should be considered during contraceptive counselling particularly for people who may already be at higher risk of bone mineral density loss.

Coadministration has not been studied but may increase doravirine concentrations through inhibition of intestinal 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. Lamivudine and tenofovir-DF are unlikely to be impacted by Seville orange juice.

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. Lamivudine and tenofovir-DF do not interact with mefloquine’s metabolic pathway.

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. Only a small proportion of an administered dose of miltefosine is excreted in the unchanged form therefore there is little potential for an interaction with lamivudine or tenofovir-DF.

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. Since <1% of a dose is excreted unchanged via the kidneys, there is little potential for an interaction with lamivudine or tenofovir-DF.

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. Clinical studies suggest that paromomycin is less nephrotoxic than other aminoglycosides. 

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. Lamivudine and tenofovir-DF do not interact with proguanil’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with quinine’s metabolic pathway.

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. Amisulpride is weakly metabolized and is primarily eliminated renally (via glomerular filtration and possibly active secretion by OCT). Doravirine, lamivudine and tenofovir-DF are 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. Lamivudine and tenofovir-DF do not interact with aripiprazole’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with asenapine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with clozapine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with fluphenazine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with haloperidol’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with iloperidone’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with levomepromazine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with olanzapine’s metabolic pathway.

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, lamivudine and tenofovir-DF are 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. Lamivudine and tenofovir-DF do not interact with olanzapine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with olanzapine’s metabolic pathway. 

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. Lamivudine and tenofovir-DF do not interact with perphenazine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with pimozide’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with pipotiazine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with quetiapine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with risperidone’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with ziprasidone’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with zotepine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with zuclopenthixol’s metabolic pathway.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Daclatasvir is partly metabolized by CYP3A4 and mainly eliminated unchanged in bile. No interaction is expected with doravirine or lamivudine. Coadministration of tenofovir-DF (300 mg once daily) and daclatasvir (60 mg once daily) had no clinically relevant effect on daclatasvir AUC, Cmax or Cmin (increases of 10%, 6% and 15%, respectively). There was no clinically relevant effect on tenofovir AUC (10% increase), Cmax (5% decrease) or Cmin (17% increase).

Coadministration with Delstrigo has not been studied. 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. The increase in doravirine exposure is not considered to be clinically relevant. Elbasvir/grazoprevir exposure was not significantly altered by doravirine. No clinically relevant interaction is expected with lamivudine. The interaction between elbasvir/grazoprevir and tenofovir-DF was evaluated in clinical studies, and no dose adjustments are required. There was no clinically significant effect on tenofovir pharmacokinetics when administered with elbasvir (tenofovir AUC, Cmax, Ctrough increased by 34%, 47%, 29%), grazoprevir (tenofovir AUC, Cmax, Ctrough increased by 18%, 14%, 24%) or elbasvir/grazoprevir (tenofovir AUC, Cmax and Ctrough increased by 27%, 14% and ~20%). Tenofovir-DF had no clinically significant effect on elbasvir (AUC, Cmax, C24 decreased by 7%, 12%, 8%) or grazoprevir (AUC, Cmax, C24 decreased by 14%, 22%, 11%). 

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 interfere with entecavir elimination. No pharmacokinetic interaction was observed with lamivudine. No significant pharmacokinetic interactions were observed when tenofovir-DF (300 mg once daily) was coadministered with entecavir (1 mg once daily). There was no change in tenofovir AUC, Cmax or Cmin and no change in entecavir Cmax or Cmin; however, entecavir AUC increased by 13%.

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. No clinically significant interactions were observed when tenofovir-DF (with efavirenz and emtricitabine) and glecaprevir/pibrentasvir were coadministered or when lamivudine was coadministered with glecaprevir/pibrentasvir.

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, lamivudine and tenofovir-DF are unlikely to interact significantly with oseltamivir.

Coadministration has not been studied. Ribavirin is partly metabolized (non-CYP mediated) and partly excreted in the urine. Based on metabolism and clearance a pharmacokinetic interaction is unlikely with doravirine and tenofovir-DF, and no pharmacokinetic interaction was observed with lamivudine.

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. Lamivudine and tenofovir-DF do not interact with this metabolic pathway.

Coadministration with Delstrigo has not been studied. 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. No clinically significant interaction is expected with lamivudine. Coadministration of tenofovir-DF (300 mg once daily with emtricitabine and efavirenz) and sofosbuvir (400 mg single dose) was studied in 16 subjects. Sofosbuvir Cmax and AUC decreased by 19% and 6%, respectively, with GS-331007 Cmax and AUC decreasing by 23% and 16%, respectively. Tenofovir Cmax increased by 25%, but AUC and Cmin decreased by 2% and 1%, respectively. No dose adjustment is required.

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 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. Lamivudine and tenofovir-DF do not interact with alprazolam’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with bromazepam’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with buspirone’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with diazepam’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with estazolam’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with flunitrazepam’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as the metabolism of flurazepam is most likely CYP-mediated. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with flurazepam’s metabolic pathway.

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, lamivudine and tenofovir-DF do 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. Lamivudine and tenofovir-DF do not interact with lorazepam’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with lormetazepam’s metabolic pathway.

Coadministration of midazolam (2 mg administered orally) and doravirine (120 mg) did not significantly alter midazolam exposure (midazolam AUC decreased by 18%, Cmax increased by 2%). Similarly, lamivudine and tenofovir-DF are unlikely to impact midazolam.

Coadministration with PARENTERALLY administered midazolam has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of ORAL midazolam (2 mg) and doravirine (120 mg) did not significantly alter midazolam exposure (midazolam AUC decreased by 18%, Cmax increased by 2%). Similarly, lamivudine and tenofovir-DF are unlikely to impact midazolam.

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. Lamivudine and tenofovir-DF do not interact with oxazepam’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with temazepam’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with triazolam’s metabolic pathway.

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, lamivudine and tenofovir-DF do 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. Lamivudine and tenofovir-DF do not interact with zolpidem’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with zopiclone’s metabolic pathway.

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. Lamivudine is eliminated by OCT2 and in vitro data indicate that bisoprolol inhibits OCT2. However, the clinical relevance of an interaction via OCT is unknown and given the good tolerability of lamivudine, no a priori dose adjustment of lamivudine is needed. There is no evidence that bisoprolol and tenofovir are eliminated by the same renal transporters.

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. Lamivudine and tenofovir-DF do not interact with metoprolol’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with nebivolol’s metabolic pathway. 

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. Lamivudine and tenofovir-DF do not interact with oxprenolol’s metabolic pathway.

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, lamivudine and tenofovir-DF are not expected to 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. Lamivudine and tenofovir-DF do not interact with propanolol’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with timolol’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with aminophylline’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with formoterol’s metabolic pathway.

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, lamivudine and tenofovir-DF are 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. Lamivudine and tenofovir-DF do not interact with indacaterol’s metabolic pathway.

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, lamivudine and tenofovir-DF do 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. Lamivudine and tenofovir-DF do not interact with montelukast’s metabolic pathway. 

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. Lamivudine and tenofovir-DF do not interact with olodaterol’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with roflumilast’s metabolic pathway.

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, lamivudine and tenofovir-DF do 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. Lamivudine and tenofovir-DF do not interact with salmeterol’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with theophylline’s metabolic pathway.

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 inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with tiotropium’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with umeclidinium bromide’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with vilanterol’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with amlodipine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with felodipine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with nisoldipine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with nitrendipine’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with desogestrel’s metabolic pathway. 

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. Lamivudine and tenofovir-DF do not interact with desogestrel’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with drospirenone’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with drospirenone’s metabolic pathway. 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. Lamivudine and tenofovir-DF do not interact with dydrogesterone’s metabolic pathway. 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. Lamivudine and tenofovir-DF do not interact with estradiol’s metabolic pathway. Coadministration of estradiol and spironolactone as feminizing hormone therapy (FHT) with doravirine, lamivudine and tenofovir to trans women with HIV taking FHT (n=6) had no clinically significant effect on exposure of doravirine, tenofovir and estradiol or on total testosterone concentrations.

Coadministration with Delstrigo has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of doravirine (100 mg once daily) and ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with ethinylestradiol’s metabolic pathway. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

No clinically significant effect on etonogestrel was observed with coadministration of doravirine, lamivudine and tenofovir. 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. Lamivudine and tenofovir-DF do not interact with etonogestrel’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with etonogestrel’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with gestodene’s metabolic pathway.

Coadministration with Delstrigo 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. Ethinylestradiol is mainly metabolized by hydroxylation. Coadministration of doravirine (100 mg once daily) and ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with levonorgestrel’s metabolic pathway.

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. Ethinylestradiol is mainly metabolized by hydroxylation. Coadministration of doravirine (100 mg once daily) and a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with levonorgestrel’s metabolic pathway.

Coadministration with levonorgestrel as hormone replacement therapy (HRT) has not been studied but there is little potential for pharmacokinetic interaction. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration of doravirine (100 mg once daily) and a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with levonorgestrel’s metabolic pathway. 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 there is little potential for pharmacokinetic interaction. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration of doravirine (100 mg once daily) and a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with levonorgestrel’s metabolic pathway.

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 there is little potential for pharmacokinetic interaction. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration of doravirine (100 mg once daily) and a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with levonorgestrel’s metabolic pathway.

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. Lamivudine and tenofovir-DF do not interact with medroxyprogesterone’s metabolic pathway. 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. Lamivudine and tenofovir-DF do not interact with norelgestromin’s metabolic pathway.

Coadministration of a combined oral contraceptive (COC) containing norethisterone and mestranol or ethinylestradiol has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Mestranol is rapidly and almost completely converted to ethinylestradiol by CYP2C9; ethinylestradiol is mainly metabolised by hydroxylation. Doravirine does not inhibit or induce CYP enzymes. Coadministration of doravirine (100 mg once daily) and a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with norethisterone’s metabolic pathway.

Coadministration with norethisterone as hormone replacement therapy (HRT) has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with norethisterone’s metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration of a norethisterone IM depot injection has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with norethisterone’s metabolic pathway.

Coadministration of a norethisterone progestogen-only pill (POP) has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with norethisterone’s metabolic pathway.

Coadministration of a combined oral contraceptive (COC) containing norgestimate/ethinylestradiol has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestimate is deacetylated to the active metabolite norelgestromin which is then metabolised to norgestrel, possibly by CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Doravirine does not inhibit or induce CYP enzymes. Coadministration of doravirine (100 mg once daily) and a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with norgestimate’s metabolic pathway.

Coadministration of a combined oral contraceptive (COC) containing norgestrel/ethinylestradiol has not been studied. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Ethinylestradiol is mainly metabolized by hydroxylation. Coadministration of doravirine (100 mg once daily) and a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with norgestrel’s metabolic pathway.

Coadministration with norgestrel as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Coadministration of doravirine (100 mg once daily) and a COC containing ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with norgestrel’s metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ulipristal is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with ulipristal’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anastrozole is mainly oxidized to hydroxyanastrozole by CYP3A4 (major) and glucuronidated by UGT1A4. Doravirine does not inhibit or induce CYP or UGT enzymes. Lamivudine and tenofovir-DF do not interact with anastrozole’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data suggest that asparaginase is likely to be eliminated by the reticuloendothelial system. Less than 0.1% of a total injected dose is recovered in urine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bevacizumab is metabolized via proteolytic catabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bexarotene is mainly metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with bexarotene’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bleomycin is inactivated by a cytosolic enzyme, bleomycin hydrolase, and two thirds of the administered drug is excreted unchanged in urine, probably by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bortezomib is mainly metabolized by CYP3A4 and 2C19 and to a lesser extent by CYPs 1A2, 2D6 and 2C9. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with bortezomib’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclophosphamide is activated (major pathway) to 4-hydroxycyclophosphamide by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with cyclophosphamide’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cytarabine is metabolized by cytidine deaminase. Doravirine, lamivudine and tenofovir-DF do not interfere with cytarabine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dactinomycin is minimally metabolized, is concentrated in nucleated cells and does not penetrate the blood-brain barrier. Doravirine, lamivudine and doravirine do not interfere with dactinomycin elimination.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Dasatinib is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with dasatinib’s metabolic pathway.

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. Docetaxel is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with docetaxel’s metabolic pathway.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Doxorubicin is mainly eliminated in the bile by P-gp and BCRP and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.)

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely, Droloxifene is mainly glucuronidated. Doravirine does not inhibit or induce UGT enzymes. Lamivudine and tenofovir-DF do not interact with droloxifene’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epirubicin is glucuronidated by UGT2B7. Doravirine does not inhibit or induce UGT enzymes. Lamivudine and tenofovir-DF do not interact with epirubicin’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Erlotinib is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with erlotinib’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Estramustine phosphate undergoes rapid dephosphorylation to estramustine which is then oxidized by 17beta-hydroxysteroid dehydrogenases to estromustine. Estramustine and estromustine are subsequently hydrolyzed to estradiol and estrone, respectively. Estradiol is then hydroxylated by CYPs 1A1, 1A2 and 3A4. Doravirine, lamivudine and tenofovir-DF do not interact with estramustine’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etoposide is partly glucuronidated by UGT1A1 and partly metabolized by CYP3A4 to reactive catechol metabolites. Conversion to reactive metabolites can also be mediated by prostaglandin synthase or myeloperoxidase. Doravirine does not inhibit or induce CYP or UGT enzymes. Lamivudine and tenofovir-DF do not interact with etoposide’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Everolimus is metabolized by CYP3A4. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with everolimus’s metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Exemestane is metabolized by CYP3A4 and aldoketoreductase. Doravirine does not inhibit or induce CYP enzymes. Lamivudine and tenofovir-DF do not interact with exemestane’s metabolic pathway.