Nitrosamine Impurities in Rifampin – What Does it Mean for Your Drug-Drug Interaction (DDI) Study?

N-Nitrosamine impurity findings in marketed formulations of rifampin have disrupted drug development. As a strong cytochrome P450 3A4 (CYP3A4) inducer, rifampin was regularly co-administered with investigational products during pharmacokinetic drug-drug interaction studies. However, due to recent impurity issues, its application in these studies has been suspended in both the US and EU. This webinar will examine the root cause of rifampin impurity and describe the industry and regulatory response to this issue. In addition, the featured speakers will address alternative approaches and CYP3A inducers to encourage the continuation of drug-drug interaction studies and drug development.

N-Nitrosamines are a class of chemicals recognized as a “cohort of concern” due to their mutagenic and carcinogenic potential. Typically, levels above an acceptable intake limit may lead to a probable or possible risk of cancer in humans. Rifampin capsules were found to contain 1-methyl-4-nitrosopiperazine (MNP) above the acceptable intake limit of 0.16 ppm. However, it’s important to note that nitrosamines are not limited to drug products, and low levels can be found in drinking water, processed meats and tobacco exposure. Therefore, in theory, a diet low in nitrosamines could offset any potential exposure during rifampin drug-drug interaction studies.

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