Action and Spectrum

Actions and Spectrum: 

It inhibits the synthesis of mycobacterial cell wall components. More specifically, delamanid targets the enzyme called mycobacterial ATP synthase, essential for producing energy (ATP) in bacteria. By inhibiting this enzyme, delamanid disrupts the energy production process and ultimately leads to the death of the mycobacterial cells. 

delamanid is primarily active against Mycobacterium tuberculosis, the causative agent of tuberculosis. It is particularly effective against drug-resistant strains of the bacterium, including MDR-TB and extensively drug-resistant tuberculosis (XDR-TB). MDR-TB is tuberculosis resistant to at least two potent first-line anti-TB drugs, isoniazid and rifampicin. XDR-TB is a more severe form of drug-resistant tuberculosis that shows resistance to fluoroquinolones and at least one of three injectable second-line drugs. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Reticulocytosis 

Ear pain 

Haemoptysis 

Tinnitus 

Hypokalaemia 

Headache 

Hypertension 

Dyspnea 

Insomnia 

Dermatitis 

Photophobia 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: delamanid should not be used in individuals with known hypersensitivity or allergic reactions to the drug or its components.  
• Concomitant Use with Terfenadine, Astemizole, or Cisapride: delamanid may interact with these medications, potentially leading to serious cardiac arrhythmias.  
• Severe Hepatic Impairment: delamanid is primarily metabolized in the liver, and individuals with severe hepatic impairment may have difficulty metabolizing the drug properly. Therefore, delamanid is contraindicated in patients with severe liver disease. 

Caution: 

• Hepatic Impairment: Although delamanid is generally well-tolerated, it is primarily metabolized in the liver.  
• Cardiac Effects: delamanid may affect the QT interval (a measure of heart rhythm) on an electrocardiogram (ECG). Therefore, it should be used cautiously in patients with pre-existing heart rhythm disorders or conditions predisposing them to QT interval prolongation.  
• Drug Interactions: delamanid is metabolized by various enzymes in the liver, and it may interact with other drugs metabolized by these enzymes.  
• Peripheral Neuropathy: In clinical studies, peripheral neuropathy was reported as an adverse effect in some delamanid patients.  
• Optic Neuritis: Cases of optic neuritis have been reported during treatment with delamanid. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

delamanid inhibits the synthesis of mycobacterial cell wall components, particularly by targeting the enzyme called mycobacterial ATP synthase. ATP synthase is crucial to produce energy (ATP) in Mycobacterium tuberculosis, the bacterium responsible for tuberculosis. By inhibiting this enzyme, delamanid disrupts the energy production process and leads to the death of the mycobacterial cells, effectively combating the tuberculosis infection. 

Pharmacodynamics:  

• Antimycobacterial activity: It inhibits the synthesis of mycobacterial cell wall components by targeting mycobacterial ATP synthase, an enzyme crucial for energy production in the bacteria. This disruption of ATP synthesis leads to a decrease in cellular energy levels, ultimately resulting in the death of the mycobacterial cells. 
• Concentration-Dependent Bactericidal Activity: The antimycobacterial activity of delamanid is concentration-dependent, meaning that its efficacy is directly related to the drug’s concentration at the site of infection.  
• Activity Against Drug-Resistant Strains: delamanid has demonstrated efficacy against multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). MDR-TB resists at least two potent first-line anti-TB drugs, isoniazid and rifampicin. XDR-TB is a more severe form of drug-resistant tuberculosis, resistant to additional second-line drugs.  
• Synergistic Effect with Other TB Drugs: delamanid is often used with other appropriate drugs to treat MDR-TB effectively. The combination of delamanid with other TB medications has shown a synergistic effect, where the combination is more effective in killing the bacteria than each drug used alone.  
• Time-Dependent Killing: delamanid’s bactericidal activity against Mycobacterium tuberculosis is generally time-dependent, meaning that the drug needs to be present for a particular duration to kill the bacteria effectively. 

Pharmacokinetics: 

Absorption 

delamanid is administered orally as part of a treatment regimen for multidrug-resistant tuberculosis (MDR-TB). It is taken with food to enhance its bioavailability, which means the body can absorb and utilize more of the drug when it is taken with a meal. 

Distribution 

delamanid is widely distributed throughout the body after absorption, allowing it to reach different tissues and target sites to exert its antimicrobial effects. 

Metabolism 

delamanid undergoes metabolism mainly in plasma by albumin, and to a lesser extent, it is metabolized via hydroxylation and oxidation by CYP3A4 enzymes to form an active metabolite called DM-6705. This process is crucial in breaking down the drug into metabolites that can be further eliminated from the body. 

Elimination and Excretion 

delamanid is primarily eliminated from the body through feces. The elimination half-life of delamanid is approximately 30-38 hours. 

Adminstartion

Administration: 

Oral administration 

delamanid is taken orally, usually in the form of tablets or granules. The tablets are swallowed whole with water, and the granules are mixed with a specific amount before administration. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: delamanid 

Why do we use delamanid? 

delamanid is an antimycobacterial drug primarily used to treat multidrug-resistant tuberculosis (MDR-TB). MDR-TB is a form of tuberculosis caused by Mycobacterium tuberculosis strains resistant to at least two of the most potent first-line anti-TB drugs, isoniazid and rifampicin. delamanid is an important treatment option in the management of MDR-TB and is specifically indicated for the following uses: 

• Treatment of Multidrug-Resistant Tuberculosis (MDR-TB): delamanid is part of a combination therapy regimen for treating MDR-TB. It is typically recommended for patients who have failed previous TB treatment, have been deemed intolerant to other medications, or are likely to develop further resistance to conventional anti-TB drugs. 
• Extensively Drug-Resistant Tuberculosis (XDR-TB): In some cases, delamanid may also be considered to treat extensively drug-resistant tuberculosis (XDR-TB). XDR-TB is a more severe form of drug-resistant tuberculosis resistant to multiple first-line and second-line anti-TB drugs, including fluoroquinolones and injectable agents. 
• Combination Therapy: delamanid is not used as a standalone treatment. It is always administered in combination with other appropriate anti-TB medications to improve treatment outcomes and prevent the development of further drug resistance. The choice of the combination regimen depends on the specific drug susceptibility profile of the patient’s MDR-TB strain.