Pretomanid

Table of contents

• What is pretomanid?
• How does pretomanid work?
• Which conditions is pretomanid used or studied for?
• How is pretomanid given?
• What do the clinical trials show?
• What side effects are known?

What is pretomanid?

Pretomanid is a chemically synthesised antibiotic substance.^[1] It belongs to the therapeutic area of bacterial infections and respiratory tract diseases.^[1] The substance is authorised as a medicine and is listed under the product name pretomanid.^[1] In the United Kingdom, it is recorded as a virtual therapeutic moiety with a 200 mg tablet formulation.^[4] The World Health Organization has received an application to include pretomanid 200 mg tablets on the Model List of Essential Medicines.^[3]

How does pretomanid work?

Pretomanid is used together with other TB medicines in regimens such as BPaL (bedaquiline, pretomanid, linezolid) and BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin).^[3] These combination regimens are designed to shorten treatment for drug-resistant tuberculosis from the conventional longer courses to around six months.^[3] The European Medicines Agency assessment report describes pretomanid as an active substance for which quality, non-clinical and clinical aspects have been evaluated.^[5]

Which conditions is pretomanid used or studied for?

• Rifampicin-resistant tuberculosis (RR-TB): the EU trial enrols people diagnosed with rifampicin-resistant tuberculosis.^[1]
• Multidrug-resistant tuberculosis (MDR-TB): pretomanid-containing regimens are studied in MDR-TB, as described in the WHO application.^[3]

How is pretomanid given?

Pretomanid is given by mouth as 200 mg tablets.^[1][4] In the EU trial, pretomanid 200 mg is taken orally together with moxifloxacin 400 mg, clofazimine 200 mg, linezolid 600 mg and bedaquiline 400 mg.^[1]

What do the clinical trials show?

One Phase 3 interventional trial is registered in the EU Clinical Trials Information System.^[1] It is authorised and plans to enrol 50 participants in France.^[1] The study, called FAST-MDR, tests whether the six-month BPaLM regimen is non-inferior at 18 months after treatment start compared with conventional longer MDR-TB regimens used in a historical cohort of patients treated in France between 2006 and 2022.^[1] The primary outcome is the proportion of participants achieving sustained treatment success at 18 months according to 2021 WHO definitions.^[1]

What side effects are known?

The WHO application lists adverse events, electrocardiogram monitoring, and liver enzyme changes such as alanine aminotransferase and aspartate aminotransferase among the safety information collected for pretomanid.^[3] The FDA approval letter notes that the prescribing information includes an Adverse Reactions section and a Medication Guide.^[2]