PRETOMANID

Pretomanid AUC and C max were approximately dose proportional over a range of single oral doses from 50 mg (0.25 times the approved recommended dosage) to 200 mg (approved recommended dosage); at single doses greater than 200 mg and up to 1,000 mg (5 times the approved recommended dosage), AUC and C max increased in a less than dose proportional manner. Steady-state pretomanid plasma concentrations were achieved approximately 4 to 6 days following multiple dose administration of 200 mg, and the ...

Clinical Studies Efavirenz: Co-administration of 200 mg QD of pretomanid with efavirenz 600 mg QD for 7 days resulted in a decrease of pretomanid mean AUC by 35% and C max by 28%. Mean AUC and C max of efavirenz were not affected when given with pretomanid. Lopinavir/Ritonavir: Co-administration of 200 mg QD pretomanid with lopinavir/ritonavir 400/100 mg BID for 7 days resulted in a decrease of pretomanid mean AUC by 17% and C max by 13%. Mean AUC and C max of lopinavir were decreased by 14% and 17%, respectively, when given with pretomanid. Rifampin: Co-administration of 200 mg QD pretomanid ...

The following serious adverse reactions are discussed here and elsewhere in the labeling:

• Hepatotoxicity [see Warnings and Precautions (5.2) ]
• Myelosuppression [see Warnings and Precautions (5.3) ]
• Peripheral and Optic Neuropathy [see Warnings and Precautions (5.4) ]
• QT Prolongation [see Warnings and Precautions (5.5) ]
• Reproductive Effects [see Warnings and Precautions (5.7) ]
• Lactic Acidosis [see Warnings and Precautions (5.8) ] Most common adverse reactions (≥ 10%) are peripheral ...

Pretomanid Tablets used in the combination regimen with bedaquiline and linezolid are contraindicated in patients for whom bedaquiline and/or linezolid are contraindicated. Refer to the bedaquiline and linezolid prescribing information.

• Pretomanid Tablets used in combination with bedaquiline and linezolid are contraindicated in patients for whom bedaquiline and/or linezolid is contraindicated. (...

• Hepatic adverse reactions were reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor symptoms and signs and liver‑related laboratory tests. Interrupt treatment with the entire regimen if evidence of liver injury occurs. ( 5.2 )
• Myelosuppression was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor complete blood counts. Decrease or interrupt linezolid dosing if significant myelosup...

7 DRUG INTERACTIONS

• Strong or moderate CYP3A4 inducers such as rifampin or efavirenz: Avoid co-administration. ( 5.6 , 7.1 )
• Organic anion transporter-3 (OAT3) substrates: Monitor for OAT3 substrate drug-related adverse reactions and consider dosage reduction for OAT3 substrate drugs, if needed. ( 7.2 ) 7.1 Effect of Other Drugs on Pretomanid CYP3A4 Inducers Co-administration of pretomanid wit...