Skip directly to site content Skip directly to page options Skip directly to A-Z link


Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, Protecting People
															Search

		Submit


Tuberculosis (TB)


Facebook
        Twitter
        LinkedIn
        Syndicate





Dear Colleague Letters										Related Pages
										Return to Main Menu
**Reported Rifapentine Impurity**
June 18, 2020
Dear Colleague:
Rifapentine (supplied as Priftin® 150 mg film-coated tablets manufactured by Sanofi) is part of a 3-month regimen with isoniazid (3HP) for treating latent tuberculosis infection (LTBI) and preventing TB disease.  It has also been used in several recent and ongoing CDC-funded clinical trials.  Priftin® is the only rifapentine product approved by the U.S. Food and Drug Administration (FDA).  In June 2020 Sanofi alerted the Division of Tuberculosis Elimination, other health agencies, and stakeholders worldwide about a newly detected impurity in Priftin®. The impurity, 1-cyclopentyl-4-nitrosopiperazine, is a nitrosamine and a potential carcinogen.  It was detected through testing based upon recently adopted regulatory standards to assay all medications for nitrosamines. (1,2)  Low levels of the impurity have been detected in some rifapentine drug substance and in some market-ready Priftin® drug product batches at production facilities in Italy. The company is investigating the source of this impurity and any safety implications, and has communicated with FDA. A follow-up submission of the results of Sanofi’s investigation for discussion with FDA (including a benefit-risk evaluation) is anticipated in July.  More background information about nitrosamine impurities in drug products is available on the FDA website. (3)
As a precautionary measure, Sanofi has paused the release of Priftin® from its production sites. This is expected to affect availability of the drug in the United States. This pause is in addition to the ongoing shortage that has affected the U.S. supplies of Priftin® since late 2019, and which was attributed to increased global demand. The investigation underway is the result of chemical testing of drug product and drug substance, and not a consequence of any observed safety signal in the pharmacovigilance databases. At this time, neither FDA nor Sanofi has requested a recall of the Priftin® supply that has already been distributed. FDA has not issued any new advisory about Priftin®.Neither FDA nor Sanofi has recommended that patients presently taking Priftin® as part of 3HP for treating LTBI discontinue this regimen. If a clinician or a patient prefers to discontinue 3HP, treatment for LTBI can be restarted with a complete alternative regimen, or it can be completed with a proportionate duration of an alternative regimen.
The 3HP treatment regimen should not be started for new patients until shipments of Priftin® resume and local supplies are reestablished. Other short-course regimens for treating LTBI — 4 months of daily rifampin or 3 months of daily isoniazid and rifampin — are recommended for their effectiveness and tolerability, per CDC’s updated guidelines on treating LTBI. (4)  When directly observed therapy (DOT) is preferred, regimens of 6 or 9 months of isoniazid administered twice weekly can be considered because the intermittent dosing schedule is useful for DOT. However, these twice-weekly regimens have long durations and unconfirmed tolerability and efficacy.
Please share this notice with your partners in TB prevention such as clinicians at community health centers or correctional facilities. We will send updates about Priftin® when Sanofi and FDA share new information. Please coordinate your efforts with jurisdictional TB control authorities, https://www.cdc.gov/tb/links/default.htm. Send questions by e-mail to RPTqueries@cdc.gov. We will monitor this mailbox daily including weekends.

Sincerely,
Terry Chorba
Terence Chorba, MD, DSc
Chief, Field Services Branch, Division of Tuberculosis Elimination
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Centers for Disease Control and Prevention
1600 Clifton Road NE (US 12-4), Atlanta, GA 30329Referenceshttps://www.fda.gov/regulatory-information/search-fda-guidance-documents/m7r1-assessment-and-control-dna-reactive-mutagenic-impurities-pharmaceuticals-limit-potentialexternal icon
https://database.ich.org/sites/default/files/Q3A%28R2%29%20Guideline.pdfpdf iconexternal icon and https://database.ich.org/sites/default/files/Q3B%28R2%29%20Guideline.pdfpdf iconexternal icon
https://www.fda.gov/drugs/drug-safety-and-availability/information-about-nitrosamine-impurities-medicationsexternal icon
https://www.cdc.gov/mmwr/volumes/69/rr/rr6901a1.htm.
							
					
						Page last reviewed:  June 22, 2020					Content source: 	Division of Tuberculosis Elimination, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention homeTuberculosisBasic TB Factsplus iconHow TB SpreadsLatent TB Infection and TB DiseaseSigns & SymptomsTB Risk FactorsExposure to TBTB PreventionVaccinesTB & HIV CoinfectionTB and DiabetesTB TermsPersonal StoriesTesting & Diagnosisplus iconWho Should be TestedTesting for TB InfectionTesting in BCG-Vaccinated PersonsTB Screening and Testing of Health Care PersonnelTesting During PregnancyDiagnosing latent TB infection and TB diseaseTreatmentplus iconDeciding When to Treat Latent TB InfectionTreatment Regimens for Latent TB Infection (LTBI)Treatment for TB DiseaseAdverse EventsTB Treatment of Persons Living with HIVTB Treatment and PregnancyTB Treatment for ChildrenFrequently Asked QuestionsDrug-Resistant TBResearchplus iconTB Epidemiologic Studies Consortiumplus iconResearch ProjectsPublicationsTB Trials Consortiumplus iconStudy DescriptionsBackgroundBehavioral & Social Science ResearchHealth Care Settingsplus iconTB Infection Control in Health Care SettingsResources for TB Screening and Testing of Health Care Personnelplus iconFrequently Asked QuestionsTB in Specific Populationsplus iconHealth DisparitiesAsian PersonsBlack or African American PersonsHispanic or Latino PersonsChildrenPregnancyCorrectional FacilitiesPeople Experiencing HomelessnessInternational TravelersLaboratory Informationplus iconDrug Susceptibility TestingFalse-Positive Investigation ToolkitInterim Laboratory Biosafety Guidance for XDR  tuberculosis strainsModel Performance Evaluation Program (MPEP)Rapid Molecular Testing to Detect Drug-Resistant TB in the USplus iconExecutive SummaryIntroductionBackground on Tests for Molecular Detection of DRGeneral Considerations and Principles for a Molecular DR Testing ServicePossible Scenarios and Scope of Testing for a Molecular DR Testing ServiceResearch NeedsGeneral Recommendations of the Expert PanelCommunication Plan for the ReportRecommendationsReferencesPanel Members and CDC ParticipantsAppendix 1Appendix 2Appendix 3The Uses of Nucleic Acid Amplification Tests for the Diagnosis of TBplus iconGeneral ConsiderationsGeneral Recommendations of the Expert PanelRecommendations to ACET, CDC, DTBEData & Statisticsplus iconTB Incidence in the United StatesReported TB in the US, 2022 Surveillance Reportplus iconNational DataReporting Area DataRisk FactorsDemographicsTB Treatment and Case OutcomesDrug-Resistant TBMolecular SurveillanceTuberculosis in the United States, 2022 (Slide Set)Archived Surveillance Reports and Slide Sets2021 State and City ReportArchived State and City ReportsProfessional Resources & Toolsplus iconTools for Healthcare ProvidersResources for TB Programsplus iconStrengthening Civil Surgeons’ Capacity to Improve LTBI Surveillance and Outcomes Among Status AdjustersNotice of Funding Opportunity (NOFO)Program EvaluationTB Centers of ExcellenceTB Elimination AllianceTB Genotypingplus iconConventional TB GenotypingWhole Genome SequencingTB GIMSAnalytic ToolsLatent Tuberculosis Infection ResourcesPublications & Productsplus iconPatient and Public MaterialsFact SheetsGuidelinesplus iconControl & EliminationDrug-Resistant TBInfection Control & PreventionLaboratory & GenotypingTB & HIVTB in Specific PopulationsTesting & DiagnosisTreatmentVaccines & ImmunizationsArchived TB GuidelinesGuides & Toolkitsplus iconAggregate ReportsCDC TB Surveillance TrainingCore CurriculumEffective TB Interviewing for Contact InvestigationEthnographic GuidesFalse-Positive Investigation ToolkitForging Partnerships to Eliminate TuberculosisGuide to Application of GenotypingLTBI: A Guide for Primary Health Care ProvidersMantoux Tuberculin Skin Testing ProductsReport of Verified Case of Tuberculosis (RVCT)Self-Study ModulesTB Contact Investigation Interviewing Skills CourseTB eDOT ToolkitUnderstanding the TB Cohort Review ProcessNewslettersplus iconTB Notes, No. 4, 2023TB Notes, No. 3, 2023TB Notes. No. 2, 2023TB Notes. No. 1, 2023TB Notes, No. 4, 2022TB Notes, No. 3, 2022TB Notes, No. 2, 2022TB Notes, No. 1, 2022TB Notes, No. 4, 2021TB Notes, No. 3, 2021TB Notes, No. 2, 2021TB Notes, No. 1, 2021Pamphlets, Brochures, Bookletsplus iconQuestions and AnswersPatient Education SeriesTuberculosis - Get the FactsTuberculosis - The Connection between TB and HIV12-Dose Regimen for Latent TB Infection-Patient Education BrochurePostersplus iconMantoux Tuberculin Skin Test Wall ChartWorld TB DayThink TBStop TBTake on TBReports & Articlesplus iconDTBE Authored Journal ArticlesTuberculosis Laboratory Aggregate ReportsSlide Setsplus iconIntroduction to TuberculosisEpidemiology of Tuberculosis Among Non-U.S.​–Born Persons in the United States, 1993–2016Self-Study Modules on Tuberculosis, 1-5 Slide SetsThe Tuberculosis (TB) in Correctional Settingsplus iconFacilitator GuideIntroduction to TB GenotypingEpidemiology of Tuberculosis in Correctional Facilities, United States, 1993-2017Prevention and Control of Tuberculosis in Correctional and Detention FacilitiesGuidelines for Preventing the Transmission of M. TB in Health care SettingsInvestigation of Contacts of Persons with Infectious TBEpidemiology of Pediatric Tuberculosis in the United StatesTargeted Tuberculosis Testing and Treatment of Latent Tuberculosis InfectionElectronic Tools & ResourcesWeb-Based Courses & Webinarsplus iconTB 101 for Health Care WorkersContent SyndicationInfographicsplus iconSocial Media GraphicsCustomizable Take on TB Infographic with InstructionsEventsWorld TB Dayplus iconU.S. TB ChampionsHistoryFeaturesplus iconTB Risk FactorsTreating Latent TB Infection with Short-Course RegimensWorld Tuberculosis (TB) Day 2021World Tuberculosis (TB) Day 2020Linksplus iconState TB Control OfficesAbout Usplus iconMission Statement and Activitiesplus iconDTBE Strategic PlanNational TB Program ObjectivesOrganization ChartAdvisory Groupsplus iconFederal TB Task Force To receive email updates about this page, enter your email address: Email Address			What's this?				Submit


About CDC
					Contact Us
					800-232-4636
 Facebook Twitter Instagram LinkedIn Youtube Pinterest Snapchat
 CONTACT CDC
				Contact Us
							Call 800-232-4636
							Email Us
			ABOUT CDC
				About CDC
							Jobs
							Funding
			POLICIES
				Accessibility
							External Links
							Privacy
							Policies
							No Fear Act
							FOIA
							OIG
							Nondiscrimination
							Vulnerability Disclosure Policy
			CONNECT WITH US
				Facebook
								Twitter
								Instagram
								LinkedIn
							Youtube
								Pinterest
								Snapchat
								Email
			LANGUAGES
				Español
							繁體中文
							Tiếng Việt
							한국어
							Tagalog
							Русский
							العربية
							Kreyòl Ayisyen
							Français
							Polski
							Português
							Italiano
							Deutsch
							日本語
							فارسی
							English


U.S. Department of Health & Human Services
			Accessibility
			External Links
			Privacy
			Policies
			No Fear Act
			FOIA
			Nondiscrimination
			OIG
			Vulnerability Disclosure Policy
			USA.gov


Exit Notification / Disclaimer Policy Close
 Links with this icon  indicate that you are leaving the CDC website. The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
				Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
				You will be subject to the destination website's privacy policy when you follow the link.
				CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. Website Disclaimers
 Cancel Continue