FDA Works to Mitigate Shortages of Rifampin, Rifapentine Due to Nitrosamine Impurities

The U.S. Food and Drug Administration (FDA) recently became aware of nitrosamine impurities in certain samples of rifampin and rifapentine. These are antibacterial drugs used to treat tuberculosis; rifampin is also used to treat other serious infections. Patients taking rifampin or rifapentine should continue taking their current medicine and consult with their health care professional about any concerns.

To mitigate or avoid shortages and to help ensure patients have access to these necessary medicines, FDA will not object to certain manufacturers temporarily distributing rifampin containing 1-methyl-4-nitrosopiperazine (MNP) or rifapentine containing 1-cyclopentyl-4-nitrosopiperazine (CPNP) above the acceptable intake limits until they can reduce or eliminate the impurities.

The acceptable intake limits are 0.16 parts per million (ppm) for MNP in rifampin and 0.1 ppm for CPNP in rifapentine. The agency will not object to certain manufacturers temporarily distributing rifampin containing MNP below 5 parts per million (ppm). The agency also will not object to certain manufacturers temporarily distributing rifapentine containing CPNP below 14 ppm. FDA will not object to these higher exposures to maintain patient access to these life-saving medications.

Manufacturers should contact the Center for Drug Evaluation and Research’s Drug Shortages Staff when their testing of rifampin or rifapentine shows levels of nitrosamines that exceed the acceptable intake limits of 0.16 ppm for MNP and 0.1 ppm for CPNP. FDA will determine on a case-by-case basis whether those drugs should be released for distribution.

FDA and manufacturers are investigating the origin of these impurities in rifampin and rifapentine, and the agency is developing testing methods for regulators and industry to detect MNP and CPNP in these medicines. FDA continues its ongoing review, surveillance, compliance and pharmaceutical quality efforts across every.