Pretomanid

Moderate CYP3A4 inducer that decreases pretomanid plasma concentrations. Co-administration should be avoided.

Strong CYP3A4 inducer that decreases pretomanid plasma concentrations. Co-administration should be avoided.

OAT3 substrate. Pretomanid inhibits OAT3 transporter, potentially increasing ciprofloxacin concentrations and adverse reactions. Monitor and consider dose reduction.

OAT3 substrate. Pretomanid inhibits OAT3 transporter, potentially increasing indomethacin concentrations and adverse reactions. Monitor and consider dose reduction.

OAT3 substrate. Pretomanid inhibits OAT3 transporter, potentially increasing methotrexate concentrations and adverse reactions. Monitor and consider dose reduction.

P-gp substrate. In vitro studies suggest pretomanid may inhibit P-gp, potentially increasing dabigatran etexilate exposure. Clinical impact unknown; monitor for adverse reactions.

P-gp substrate. In vitro studies suggest pretomanid may inhibit P-gp, potentially increasing digoxin exposure. Clinical impact unknown; monitor for adverse reactions.

BCRP substrate. In vitro studies suggest pretomanid may inhibit BCRP, potentially increasing glyburide exposure. Clinical impact unknown; monitor for adverse reactions.

Lopinavir/Ritonavir Co-administration of pretomanid with lopinavir/ritonavir did not affect the plasma concentrations of pretomanid [see Clinical Pharmacology (12.3) ] . Lopinavir/ritonavir can be co-administered with the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.

7.2 Effect of Pretomanid on Other Drugs Midazolam Co-administration of pretomanid with the CYP3A4 substrate, midazolam, resulted in no clinically significant effect on the pharmacokinetics of midazolam or its major metabolite, 1-hydroxy-midazolam [see Clinical Pharmacology (12.3) ] .

Therefore, it cannot be excluded that co-administration of pretomanid with sensitive OATP1B3 substrates (e.g., valsartan, statins), BCRP substrates (e.g., rosuvastatin, prazosin, glyburide, sulfasalazine) and P-gp substrates (e.g., digoxin, dabigatran etexilate, verapamil) may increase their exposure.

Lopinavir/Ritonavir Co-administration of pretomanid with lopinavir/ritonavir did not affect the plasma concentrations of pretomanid [see Clinical Pharmacology (12.3) ] . Lopinavir/ritonavir can be co-administered with the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.

Therefore, it cannot be excluded that co-administration of pretomanid with sensitive OATP1B3 substrates (e.g., valsartan, statins), BCRP substrates (e.g., rosuvastatin, prazosin, glyburide, sulfasalazine) and P-gp substrates (e.g., digoxin, dabigatran etexilate, verapamil) may increase their exposure.

BCRP substrate. In vitro studies suggest pretomanid may inhibit BCRP, potentially increasing sulfasalazine exposure. Clinical impact unknown; monitor for adverse reactions.

Therefore, it cannot be excluded that co-administration of pretomanid with sensitive OATP1B3 substrates (e.g., valsartan, statins), BCRP substrates (e.g., rosuvastatin, prazosin, glyburide, sulfasalazine) and P-gp substrates (e.g., digoxin, dabigatran etexilate, verapamil) may increase their exposure.

P-gp substrate. In vitro studies suggest pretomanid may inhibit P-gp, potentially increasing verapamil exposure. Clinical impact unknown; monitor for adverse reactions.