Interim Advice on the use of Rifampicin for post-exposure prophylaxis (PEP)

Issued by the ILEP Technical Commission, February 2021. This is a non-technical version of the advice. The full version is available here.

 

Various problems have affected the supply of MDT this year. The most recent has been the discovery of impurities, known as nitrosamines, in rifampicin. The discovery came through a new drug screening process recommended by WHO. Nitrosamines appear to be a by-product in the production of rifampicin and have probably been present for many years.

Nitrosamines are assumed to pose a health risk if a high enough cumulative amount is consumed over a person’s lifetime. For this reason, they are not considered a serious issue when used for treatment with MDT (normally one dose a month for up to 12 months) or for leprosy prevention as SDR-PEP (one single dose). The US Food & Drug Administration (FDA) and the European Medicines Agency (EMA) have both indicated that rifampicin should continue to be used to treat TB (where it is given daily) and leprosy, while the manufacturing process is revised to minimise the impurities. However, no statements have been made about rifampicin use for SDR-PEP.

In line with the statements from FDA and EMA about MDT, the ITC considers the potential health risk of a single dose of rifampicin to be extremely small. However, since SDR-PEP is given to healthy individuals, we have an obligation to minimise all known risks to health. Since another drug with similar nitrosamine impurities is used for chemoprophylaxis in TB, ITC has consulted with the WHO Global Leprosy Programme, WHO Global TB Programme and WHO Pre-qualification Team – Medicines (WHO PQT/MED), a global quality assurance programme for medicines. WHO-PQT/MED is tackling this issue for TB and leprosy jointly and will give guidance on rifampicin when it has completed its investigation.

In view of the above, the ITC will withhold recommendations regarding SDR-PEP distribution until the various ongoing investigations and the conversation with the Global TB and PQ programmes have concluded and their position has become clear. In the meantime, the ITC makes four recommendations:

  1. Where ILEP is involved in the distribution of MDT or rifampicin, batches should only be purchased or used that have maximum nitrosamine levels below 5ppm per day as recommended by the US FDA.
  2. When there is an acute shortage of MDT, any available rifampicin may need to be used for treatment of leprosy patients, rather than for chemoprophylaxis among contacts.
  3. Whenever active case-finding efforts are undertaken, including contact examinations, the availability of treatment for any new cases identified must be ensured (preferably MDT). MDT, with impurity levels below the safety level mentioned above, is essential and safe for treatment of leprosy patients.
  4. ILEP offices should do everything in their power to facilitate nitrosamine testing of rifampicin already available in their country, that is designated for SDR-PEP. Ideally, such testing should be done by each company producing rifampicin and by the national authority in charge of monitoring the quality of drugs. Recent random samples from currently available batches of MDT have found levels of nitrosamine to be under this limit, so if testing is not possible at present, current stocks of MDT are deemed to be safe.