Delamanid is sold under the brand name Deltyba, is a medication used to treat

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

. Specifically it is used, along with other

antituberculosis medication Management of tuberculosis refers to techniques and procedures utilized for treating tuberculosis (TB), or simply a treatment plan for TB. The medical standard for active TB is a short course treatment involving a combination of isoniazid, rifa ...

s, for active

multidrug-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 rifampicin. S ...

. It is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

. There are common side effects which include headache, dizziness, and nausea. Other side effects include

QT prolongation QT or Qt may refer to: Businesses * The Qt Company, a Finnish software developer * QT Hotels & Resorts, an Australasian hospitality provider * QT Inc., an American bracelet manufacturer * QuikTrip, an American convenience store chain People * ...

. Delamanid works by blocking the manufacture of

mycolic acid Mycolic acids are long fatty acids found in the cell walls of Mycobacteriales taxon, a group of bacteria that includes ''Mycobacterium tuberculosis'', the causative agent of the disease tuberculosis. They form the major component of the cell wall ...

s thus destabilising the bacterial

cell wall A cell wall is a structural layer that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...

. It is in the

nitroimidazole Nitroimidazoles are the group of organic compound, organic compounds consisting of an imidazole ring with at least one nitro group substituent. The term also refers to the class of antibiotics that have nitroimidazole in their structures. These an ...

class of medications. Delamanid was approved for medical use in 2014 in Europe, Japan, and South Korea. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. As of 2016 the

Stop TB Partnership The Stop TB Partnership was established in 2001 to eliminate tuberculosis as a public health problem. Its 2000 partner organizations include international, nongovernmental and governmental organizations and patient groups. The secretariat is base ...

had an agreement to get the medication for US$1,700 per six month for use in more than 100 countries.

Medical uses

Delamanid is used, along with other

s, for active

Adverse effects

Common side effects include headache, dizziness, and nausea. Other side effects include

. Use in pregnancy has not been extensively studied, but there have been reports of success and it is currently recommended as part of the standard treatment regimen for pregnant women with rifampicin-resistant tuberculosis in South Africa.

Interactions

Delamanid is metabolised by the liver enzyme

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

; therefore strong inducers of this enzyme can reduce its effectiveness.

Mechanism of action

Delamanid is activated in the mycobacterium by deazaflavin-dependent nitroreductase (''Ddn''), an enzyme which uses dihydro-F₄₂₀ (reduced form), into

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

and a highly reactive metabolite. This metabolite attacks the synthesis enzyme ''DprE2'', which is important for the synthesis of cell wall

arabinogalactan Arabinogalactan, also known as galactoarabinan, larch arabinogalactan, and larch gum, is a biopolymer consisting of arabinose and galactose monosaccharides. Two classes of arabinogalactans are found in nature: plant arabinogalactan and microbial ...

, to which mycolic acid would be attached. This mechanism is shared with

pretomanid Pretomanid is an antibiotic medication used for the treatment of multi-drug-resistant tuberculosis affecting the lungs. It is generally used together with bedaquiline and linezolid. It is taken by mouth. The most common side effects include ...

. Clinical isolates resistant to this drug tend to have mutations in the biosynthetic pathway for Coenzyme F₄₂₀.

History

In phase II

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s, the drug was used in combination with standard treatments, such as four or five of the drugs

ethambutol Ethambutol (EMB, E) is a medication primarily used to treat tuberculosis. It is usually given in combination with other tuberculosis medications, such as isoniazid, rifampicin and pyrazinamide. It may also be used to treat ''Mycobacterium avi ...

isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis, it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. F ...

pyrazinamide Pyrazinamide is a medication used to treat tuberculosis. For active tuberculosis, it is often used with rifampicin, isoniazid, and either streptomycin or ethambutol. It is not generally recommended for the treatment of latent tuberculosis. It i ...

rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires' disease. It is almost always used tog ...

aminoglycoside antibiotic Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...

s, and

quinolones Quinolone may refer to: * 2-Quinolone * 4-Quinolone * Quinolone antibiotic Quinolone antibiotics constitute a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They ar ...

. Healing rates (measured as sputum

culture conversion Culture conversion is a diagnostic criteria indicating the point at which samples taken from a person infected with a tuberculosis can no longer produce tuberculosis cell culture Cell culture or tissue culture is the process by which cell (b ...

) were significantly better in patients who additionally took delamanid. The

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) recommended conditional marketing authorization for delamanid in adults with multidrug-resistant pulmonary tuberculosis without other treatment options because of resistance or tolerability. The EMA considered the data show that the benefits of delamanid outweigh the risks, but that additional studies were needed on the long-term effectiveness.

Society and culture

The medication was not readily available globally as of 2015. It was believed that pricing will be similar to

bedaquiline Bedaquiline, sold under the brand name Sirturo, is a medication used for the treatment of active tuberculosis. Specifically, it is used to treat multi-drug-resistant tuberculosis along with other medications for tuberculosis. It is taken by mo ...

, which for six months is approximately US$900 in low income countries, US$3,000 in middle income countries, and US$30,000 in high income countries. As of 2016 the

had an agreement to get the medication for US$1,700 per six month.

References

{{Authority control Anti-tuberculosis drugs Trifluoromethyl ethers World Health Organization essential medicines Wikipedia medicine articles ready to translate