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Use of Delamanid in Drug resistant TB in India-RNTCP 2018 guideline


Use of Delamanid in Drug resistant TB in India-RNTCP 2018 guideline

The Ministry of Health and Family Welfare, India under the aegis of the Revised National Tuberculosis Control Programme (RNTCP) has developed a guideline for the use of Delamanid (Dlm) in the treatment of drug-resistant tuberculosis (DR-TB) in India. 

The emergence of drug resistance is a major threat to global tuberculosis (TB) care and control. Multidrug-resistant TB (MDR-TB) is defined as TB with resistance at least to isoniazid (H) and rifampicin (R) with or without resistance to other first-line anti-TB drugs. Additional resistance to fluoroquinolones (FQs) and second-line injectables (SLIs), either alone or together i.e extensively drug-resistant TB (XDR-TB), is considered to be advanced forms of MDR-TB. 

The guideline has been developed as the end-product of a series of meetings and deliberations with national experts from the government of India (GoI), WHO country office for India (WHO India) and key technical and developmental partners in 2017.

The emergence of drug resistance is a major threat to global tuberculosis (TB) care and control. Multidrug-resistant TB (MDR-TB) is defined as TB with resistance at least to isoniazid (H) and rifampicin (R) with or without resistance to other first-line anti-TB drugs.

Delamanid is one of two drugs developed specifically for the treatment of TB in the last 40 years. It is the first approved drug in the class of nitro-dihydro-imidazo-oxazoles for the treatment of MDR-TB. It has been developed by Otsuka Pharmaceutical Ltd. for the treatment of MDR-TB.

Seven states have been identified as initial sites for the introduction of DLM under the RNTCP PMDT through conditional access. These include Punjab, Chandigarh, Rajasthan, Karnataka, Odisha, Kerala, Lakshadweep. 

Delamanid has been given approval for use along with the background regimen under conditional access through the RNTCP PMDT services in India. However, Dlm will continue to be available for “compassionate use” in the country till such time that the expanded access programme is rolled out under RNTCP.

Delamanid is indicated for use as part of an appropriate combination regimen for pulmonary MDR-TB in adult and adolescent (6-17 years) patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.

It has the following characteristics 
• Chemical class: nitroimidazole 
• Mechanism of Action: Bactericidal (Half-life: 36 hours) 
– By blocking the synthesis of mycolic acids (i.e., stopping the bacteria from creating building blocks important for their cell walls). 
– By poisoning them with nitric oxide, which the drugs release when metabolized 
• Each film-coated tablet contains 50 mg Delamanid.
• Excipient with known effect: Each film-coated tablet contains 100 mg lactose (as monohydrate).

The guidance recommends that Dlm may be added to a WHO-recommended regimen in adult patients with pulmonary MDR-TB under the following conditions: 

  • When an effective treatment regimen containing four second-line drugs in addition to pyrazinamide (Z) according to WHO recommendations cannot be designed.
  • When there is documented evidence of resistance to any FQ or second-line injectable drug in addition to MDR.
  • When there is a higher risk for poor outcomes (eg. drug intolerance or contraindication, extensive or advanced disease).

Inclusion criteria:
 Adults (≥18 yrs), including people living with HIV (PLHIV), not eligible for a shorter MDR-TB regimen for reasons of resistance, contraindication or tolerability
– MDR/RR-TB with resistance to any/all FQ OR any/all SLI
– Extensively drug-resistant TB-XDR-TB
– Mixed Pattern DR-TB including patients who are failing any DR-TB regimen or have drug intolerance or contraindications or who return after interruption or emergence of any exclusion criteria for shorter MDR-TB regimen or with extensive or advanced disease and others deemed at higher baseline risk for poor outcomes.
 Special caution: HIV+ (in consultation with ART centres), 65yrs+, patients with diabetes, hepatic or severe renal impairment, those with serum albumin <2.8 g/dL or those who use alcohol or substances.

Based on the examination of the data on global clinical trials conducted and approval by European Union (EU) and Japan for this drug, and risk-benefit analysis, the committee recommended for waiver of a local clinical trial as Delamanid is required as an unmet need in an emergency for the treatment of MDR/XDR-TB in adult. Further, the Committee recommended for approval of the drug in the conditional access programme through RNTCP. It was also recommended that the firm shall submit the data of monitoring after 3 years for further review by the office of DCGI.

For further reference follow the link: https://tbcindia.gov.in/showfile.php?lid=3343

Source: With inputs from RNTCP

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