Pretomanid is an

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

medication used for the treatment of

multi-drug-resistant tuberculosis Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs): isoniazid and rifampin. Some f ...

affecting the

lungs The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of th ...

. It is generally used together with

bedaquiline Bedaquiline, sold under the brand name Sirturo, is a medication used to treat active tuberculosis. Specifically, it is used to treat multi-drug-resistant tuberculosis (MDR-TB) along with other medications for tuberculosis. It is used by mouth. ...

and

linezolid Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, van ...

. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. The most common side effects include

nerve damage Nerve injury is an injury to nervous tissue. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve f ...

acne Acne, also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, black ...

, vomiting, headache,

low blood sugar Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

, diarrhea, and liver inflammation. It is in the

nitroimidazole 5-Nitroimidazole is an organic compound with the formula O2NC3H2N2H. The nitro group at position 5 on the imidazole ring is the most common positional isomer. The term nitroimidazole also refers to a class of antibiotics that share similar chemi ...

class of medications. Pretomanid was approved for medical use in the United States in August 2019, and in the European Union in July 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Pretomanid was developed by

TB Alliance TB Alliance (formallyThe Global Alliance for TB Drug Development) is a not-for-profit product development partnership (PDP) dedicated to the discovery and development of new, faster-acting and affordable tuberculosis (TB) medicines. Since its inc ...

. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a pharmaceutical that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medicat ...

Medical uses

Pretomanid is indicated in combination with bedaquiline and linezolid, in adults, for the treatment of pulmonary extensively drug resistant (XDR), or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB).

History

Pretomanid is the generic, nonproprietary name for the novel anti-bacterial drug compound formerly called PA-824. Pretomanid is referred to as "Pa" in regimen abbreviations, such as BPaL. The "preto" part of the compound's name honors

Pretoria Pretoria () is South Africa's administrative capital, serving as the seat of the Executive (government), executive branch of government, and as the host to all foreign embassies to South Africa. Pretoria straddles the Apies River and extends ...

, South Africa, the home of a TB Alliance clinical development office where much of the drug's development took place, while the "-manid" stem designates compounds with similar chemical structures. This class of drug is variously referred to as

s or nitroimidazooxazines. Development of this compound was initiated because of the urgent need for new antibacterial drugs effective against resistant strains of tuberculosis. Also, current anti-TB drugs are mainly effective against replicating and metabolically active bacteria, creating a need for drugs effective against persisting or latent bacterial infections as often occur in patients with tuberculosis.

Discovery and pre-clinical development

Pretomanid was first identified in 2000, in a series of 100 nitroimidazopyran derivatives synthesized and tested for antitubercular activity, by PathoGenesis (now a subsidiary of Novartis). Importantly, pretomanid has activity against static ''M. tuberculosis'' isolates that survive under anaerobic conditions, with bactericidal activity comparable to that of the existing drug

metronidazole Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It i ...

. Pretomanid requires metabolic activation by ''Mycobacterium'' for antibacterial activity. Pretomanid was not the most potent compound in the series against cultures of ''M. tuberculosis'', but it was the most active in infected mice after oral administration. Oral pretomanid was active against tuberculosis in mice and guinea pigs at safely tolerated dosages for up to 28 days.

Limited FDA approval

The U.S.

(FDA) approved pretomanid only in combination with

and

for treatment of a limited and specific population of adults with extensively drug resistant, treatment-intolerant or nonresponsive multidrug resistant pulmonary tuberculosis. Pretomanid was approved under the Limited Population Pathway (LPAD pathway) for antibacterial and antifungal drugs. The LPAD Pathway was established by Congress under the

21st Century Cures Act The 21st Century Cures Act is a United States law enacted by the 114th United States Congress in December 2016 and then signed into law on December 13, 2016. It authorized $6.3 billion in funding, mostly for the National Institutes of Health. The ...

to expedite development and approval of

antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

and antifungal drugs to treat serious or life-threatening infections in a limited population of patients with unmet need. Pretomanid is only the third tuberculosis drug to receive FDA approval in more than 40 years. The FDA granted Pretomanid

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

and

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

designation. The FDA granted The Global Alliance for TB Drug Development (

) the approval of Pretomanid and a Tropical Disease Priority Review Voucher.

References

External links

* {{Portal bar , Medicine Anti-tuberculosis drugs Orphan drugs Prodrugs Trifluoromethyl ethers