Pretomanid

Pretomanid is a nitroimidazooxazine antimycobacterial drug [see Microbiology (12.4) ] .

• Limited Population: Pretomanid Tablet is indicated, as part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary tuberculosis (TB) resistant to isoniazid, rifamycins, a fluoroquinolone and a second line injectable antibacterial drug OR adults with pulmonary TB resistant to isoniazid and rifampin, who are treatment-intolerant or nonresponsive to standard therapy. Approval of this indication is based on limited clinical safety and efficacy data.ICD-10: A15.9

• 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.contraindicated

Important Administration Instructions: ( 2.1 ) • Pretomanid Tablets must be administered only in combination with bedaquiline and linezolid as part of the recommended dosage regimen. • Administer the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid by directly observed therapy (DOT). • Pretomanid Tablets must be administered in combination with bedaquiline and linezolid with food. • Doses of the combination regimen missed for safety reasons can be made up at the end of treatment; doses of linezolid alone missed due to linezolid adverse reactions should not be made up. • Administer Pretomanid Tablets in combination with bedaquiline and linezolid as follows: ( 2.2 ) • Pretomanid Tablets: • Pretomanid Tablet 200 mg orally once daily for 26 weeks. Administer Pretomanid Tablets whole with water. • For patients with swallowing difficulties see the full prescribing information for crushing or soaking followed by crushing instructions of the Pretomanid Tablets. • Bedaquiline : • Bedaquiline 400 mg orally once daily for 2 weeks followed by 200 mg 3 times per week, with at least 48 hours between doses, for 24 weeks for a total of 26 weeks. • Bedaquiline 200 mg orally once daily for 8 weeks followed by 100 mg once daily for 18 weeks, for a total of 26 weeks. • Linezolid : • Linezolid Preferred: 600 mg orally once daily for 26 weeks. Alternative: 1,200 mg orally once daily for 26 weeks. • If myelosuppression, peripheral neuropathy, or optic neuropathy occurs, reduce or interrupt linezolid dosing as necessary.

• 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 myelosuppression develops or worsens. ( 5.3 ) • Peripheral and optic neuropathy were reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor visual function. Obtain an ophthalmologic evaluation if there are symptoms of visual impairment. Decrease or interrupt linezolid dosing if neuropathy develops or worsens. ( 5.4 ) • QT prolongation was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Use with drugs that prolong the QT interval may cause additive QT prolongation. Monitor ECGs. Discontinue the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid if significant ventricular arrhythmia or if QTcF interval prolongation of greater than 500 ms develops. ( 5.5 ) • Reproductive effects: Pretomanid caused testicular atrophy and impaired fertility in male rats. Advise patients of reproductive toxicities seen in animal studies and that the potential effects on human male fertility have not been adequately evaluated.

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 neuropathy, anemia, nausea, acne, vomiting, increased transaminases, headache, musculoskeletal pain, dyspepsia, rash, pruritus, decreased appetite, abdominal pain, pleuritic pain, increased gamma-glutamyltransferase, hemoptysis and hyperamylasemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. When Pretomanid Tablets are administered in combination with bedaquiline and linezolid, refer to the prescribing information for the respective drugs for a description of the adverse reactions associated with their use. Approximately 3100 subjects have been exposed to Pretomanid Tablets, either alone or as part of a combination therapy in clinical trials.

• Lactation: Breastfeeding is not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary There are no studies or available data on pretomanid use in pregnant women to inform any drug-associated risks. There are risks associated with active tuberculosis during pregnancy (see Clinical Considerations ). When Pretomanid Tablets are administered in combination with bedaquiline and linezolid, the pregnancy information for bedaquiline and linezolid also applies to this combination regimen. Refer to the bedaquiline and linezolid prescribing information for more information on bedaquiline and linezolid associated risks of use during pregnancy. In animal reproduction studies, there was increased post-implantation loss in the presence of maternal toxicity (reduced bodyweight and feed consumption) with oral administration of pretomanid during organogenesis in rats at doses about 4 times the exposure at the recommended dose in humans. There were no adverse embryo fetal effects in rats or rabbits dosed with oral pretomanid during organogenesis at doses up to approximately 2 times the exposure in humans. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

Metabolism

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 accumulation ratio was approximately 2.

There is no experience with the treatment of acute overdose with pretomanid. Take general measures to support basic vital functions including monitoring of vital signs and ECG (QT interval) in case of deliberate or accidental overdose.

• Aug 14, 2019NDANDA212862Mylan Ireland Ltd

1. 1Death11418%
2. 2Anaemia7211%
3. 3Neuropathy Peripheral649.9%
4. 4Off Label Use477.3%
5. 5Nausea406.2%
6. 6Electrocardiogram Qt Prolonged345.3%
7. 7Acute Kidney Injury253.9%
8. 8Toxicity To Various Agents243.7%
9. 9Alanine Aminotransferase Increased223.4%
10. 10Hepatotoxicity223.4%
11. 11Aspartate Aminotransferase Increased203.1%
12. 12Decreased Appetite172.6%
13. 13Optic Neuritis162.5%
14. 14Drug Ineffective152.3%
15. 15Drug Level Increased142.2%

The 10 most recently updated of 46 ClinicalTrials.gov registrations naming Pretomanid as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Bactericidal Activity of TBD09 in Combination With Other Drugs in Pulmonary Tuberculosis
  Recruiting · Phase 2 · Interventional · 150 enrolled · Gates Medical Research Institute
  NCT07525427updated 2026-06-03
• Bactericidal Activity and Safety of Nicotinamide in Combination With Bedaquiline, Pretomanid, and Linezolid in Drug-susceptible Pulmonary Tuberculosis
  Recruiting · Phase 2 · Interventional · 165 enrolled · Gates Medical Research Institute
  NCT07517445updated 2026-05-22
• Efficacy and Safety Evaluation of Two to Four Months of Treatment With the Combination Regimens of DBOS and PBOS in Adults With Pulmonary Tuberculosis
  Terminated · Phase 2 · Interventional · 93 enrolled · Gates Medical Research Institute
  NCT05971602updated 2026-05-20
• Study of a Single Dose of Pretomanid Added to an Optimized Background Regimen in Children With Rifampicin-Resistant Tuberculosis
  Completed · Phase 1 · Interventional · 32 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT05586230updated 2026-05-20
• Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis
  Recruiting · Phase 2 · Interventional · 315 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT06192160updated 2026-05-19
• A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis
  Recruiting · Phase 3 · Interventional · 532 enrolled · Otsuka Pharmaceutical Development & Commercialization, Inc.
  NCT07209761updated 2026-05-06
• B-PaLMZ for TB Meningitis
  Not yet recruiting · Phase 2 · Interventional · 240 enrolled · University of Minnesota
  NCT07227779updated 2026-04-14
• Program for Rifampicin-Resistant Disease With Stratified Medicine for Tuberculosis
  Recruiting · Phase 2 · Phase 3 · Interventional · 400 enrolled · University of California, San Francisco
  NCT06441006updated 2026-01-20
• Biodistribution and Pharmacokinetics of Pretomanid in Tuberculosis Patients Using 18F-Pretomanid PET
  Completed · Observational · 10 enrolled · Johns Hopkins University
  NCT05609552updated 2025-12-12
• Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy
  Completed · Observational · 1,578 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT00042289updated 2025-12-02

Frequently asked questions

How does Pretomanid work?

Pretomanid is a nitroimidazooxazine antimycobacterial drug [see Microbiology (12.4) ] .

What is Pretomanid used for?

According to FDA labeling, Pretomanid carries indications including: Limited Population: Pretomanid Tablet is indicated, as part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary tuberculosis (TB) resistant to isoniazid, rifamycins, a fluoroquinolone and a second line injectable antibacterial drug OR adults with pulmonary TB resistant to isoniazid and rifampin, who are treatment-intolerant or nonresponsive to standard therapy. Approval of this indication is based on limited clinical safety and efficacy data.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Pretomanid?

Pretomanid is classified as Other drugs for treatment of tuberculosis, Antimycobacterial, Organic Anion Transporter 3 Inhibitors, Decreased Cell Wall Synthesis & Repair.

What are the contraindications for Pretomanid?

Pretomanid labeling lists contraindications including: 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.. Always consult the full prescribing information and a clinician.