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Full Prescribing Information

Pretomanid and the BPaL Regimen

Pretomanid is a tuberculosis (TB) drug developed by TB Alliance for use in combination with bedaquiline and linezolid that is now approved by the U.S. Food and Drug Administration for treating a limited and specific population of adult patients with extensively drug-resistant, treatment-intolerant or non-responsive multidrug-resistant pulmonary TB.

In July 2020, the Drug Controller General of India (DCGI) also approved pretomanid for conditional access under the National Tuberculosis Elimination Program (NTEP), making India the second country in the world to provide regulatory approval for this product.

In 2021, pretomanid received EU marketing authorisation in a combination regimen with bedaquiline and linezolid to treat highly drug-resistant TB. Additionally, in 2021 it was prequalified by the World Health Organization (WHO).

In 2022, the WHO updated its guidelines for TB treatment to allow for the programmatic implementation of treating almost all forms of drug-resistant TB with pretomanid-containing regimens.

Learn about pretomanid’s development and review the latest updates here.

About Pretomanid

Pretomanid is a new chemical entity and a member of a class of compounds known as nitroimidazooxazines. Novel compounds are important in pursuing new TB treatments because resistance to drugs and drug classes currently used to treat TB is widespread. During early development, pretomanid was referred to as PA-824. Pretomanid was developed by TB Alliance as an oral tablet formulation for the treatment of tuberculosis in combination with other anti-tuberculosis agents.

One such combination is BPaL, which consists of bedaquiline + pretomanid + linezolid. WHO TB treatment guidelines allow for the programmatic implementation of treating almost all forms of drug-resistant TB with pretomanid-containing regimens.

Learn more about pretomanid here.

About the BPaL Regimen

Pretomanid as part of the BPaL regimen is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with pulmonary extensively drug-resistant tuberculosis (XDR-TB) or multidrug-resistant TB (MDR-TB) that is treatment-intolerant or non-responsive.

BPaL was first studied in the Nix-TB trial, which enrolled people with XDR-TB as well as treatment-intolerant or non-responsive MDR-TB. Nix-TB data have demonstrated a successful outcome in 95 of the first 107 patients after six months of treatment with BPaL and six months of post-treatment follow-up. For two patients, treatment was extended to nine months. BPaL has been tested in drug-resistant TB patients co-infected with HIV, including those receiving antiretrovirals (ARVs).

The global treatment success rate has been 59% with 9+ month treatment standards. Now, the WHO has announced guidelines to treat DR-TB using six-month, all-oral, three or four drug regimens with reported success rates of approximately 90% in clinical trials.
 

How Pretomanid Works
 

Dr. Francesca Conradie: Nix-TB
 

Scientific Publications

A full list of peer-reviewed research studying pretomanid and pretomanid-containing regimens is available.

View the publications

INDICATION | LIMITED POPULATION

Pretomanid Tablet is an antimycobacterial indicated, as part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary extensively drug-resistant (XDR), treatment-intolerant or non-responsive multidrug-resistant (MDR) tuberculosis (TB). Approval of this indication is based on limited clinical safety and efficacy data. This drug is indicated for use in a limited and specific population of patients.

Limitations of Use:
  • Pretomanid Tablets are not indicated for patients with:
    • Drug-sensitive (DS) tuberculosis
    • Latent infection due to Mycobacterium tuberculosis
    • Extra-pulmonary infection due to Mycobacterium tuberculosis
    • MDR-TB that is not treatment-intolerant or non-responsive to standard therapy
  • Safety and effectiveness of Pretomanid Tablets have not been established for its use in combination with drugs other than bedaquiline and linezolid as part of the recommended dosing regimen.

IMPORTANT SAFETY INFORMATION

Contraindications

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

Warnings and Precautions
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Lactic acidosis was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Consider interrupting linezolid or the entire combination regimen of Pretomanid Tablets, bedaquiline, and linezolid dosing if significant lactic acidosis develops.

Adverse Reactions

The most common adverse reactions (≥10%) are peripheral neuropathy, acne, anemia, nausea, vomiting, headache, increased transaminases, dyspepsia, decreased appetite, rash, pruritus, abdominal pain, pleuritic pain, increased gamma-glutamyltransferase, lower respiratory tract infection, hyperamylasemia, hemoptysis, back pain, cough, visual impairment, hypoglycemia, abnormal loss of weight, and diarrhea.