FEXINIDAZOLE

The pharmacokinetics (PK) of fexinidazole and its two pharmacologically active M1 (sulfoxide) and M2 (sulfone) metabolites following administration of the recommended adult dosage regimen of Fexinidazole Tablets in 12 healthy adult male subjects under fed conditions are presented in Table 5.

Table 5Pharmacokinetics of Fexinidazole and its Active M1 and M2 Metabolites following Administration of Fexinidazole Tablets 1,800 mg Once Daily for 4 Days, Then 1,200 mg Once Daily for 6 Days to Healthy ...

Trial 1The efficacy and safety of Fexinidazole Tablets were evaluated in a randomized, comparative open-label trial (

Trial 1NCT01685827) conducted in adult patients with late second-stage HAT due to T. brucei gambiense . Patients had evidence of parasites in blood, lymph and/or cerebrospinal fluid (CSF) at trial enrollment. If testing for parasites in CSF was negative, a CSF WBC >20 cells/μL was required to confirm late second-stage HAT. Patients (n=394) were randomized in a 2:1 ratio to a 10-day treatment regimen of either Fexinidazole Tablets (n=264) or nifurtimox-eflornithine combination...

The following serious and otherwise important adverse reactions are discussed in greater detail in other sections of labeling: Decreased Efficacy in Severe Human African Trypanosomiasis Caused by Trypanosoma brucei gambiense [see Warnings and Precautions (5.1) ] QT Interval Prolongation [see Warnings and Precautions (5.2) ] Neuropsychiatric Adverse Reactions [see Warnings and Precautions (5.3) ] Neutropenia [see Warnings and Precautions (5.4) ] Potential for Hepatotoxicity [see Warnings and Prec...

Fexinidazole Tablets are contraindicated in: Patients with known hypersensitivity to Fexinidazole Tablets and/or any nitroimidazole-class drugs (e.g., metronidazole, tinidazole). Patients with severe hepatic impairment [see Warnings and Precautions (5.5) , Adverse Reactions (6.1) , and Use in Specific Populations (8.7) ] . Patients with Cockayne syndrome. Severe irreversible hepatotoxicity/acute l...

Decreased Efficacy in Severe Human African Trypanosomiasis caused by Trypanosoma brucei gambiense. ( 1 , 5.1 ) QT Interval Prolongation: Prolongation of the QT interval due to Fexinidazole Tablets occurs in a concentration-dependent manner. Avoid use in patients with known prolongation, proarrhythmic conditions, and concomitant use with drugs that prolong the QT interval, those that block cardiac potassium channels, and/or those that induce bradycardia, or are inducers of hepatic CYP450. ( 5.2 ,...

7 DRUG INTERACTIONS Avoid use of herbal medicines and supplements. ( 7.1 ) See full prescribing information for complete list of clinically significant drug interactions. ( 7.2 ) 7.1 Pharmacodynamic Interactions Herbal Medicines and Supplements There is a potential for pharmacodynamic interactions and/or toxicities between fexinidazole and herbal medicines and supplements. Avoid concomitant use of...