Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Rifapentine: Difference between pages

{{Short description|Chemical compound}}

{{Infobox drug

| verifiedrevid = 464382415

| drug_name =

| INN =

| type = <!-- empty -->

| alt =

| caption =

<!-- Clinical data -->

| pronounce =

| tradename = Priftin

| MedlinePlus = a616011

| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->

| licence_EU = <!-- EMA uses INN (or special INN_EMA) -->

| DailyMedID = Rifapentine

| licence_US = Rifapentine

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

| pregnancy_AU_comment =

| pregnancy_US = C

| pregnancy_US_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Rifapentine (Priftin) Use During Pregnancy | website=Drugs.com | date=2 December 2019 | url=https://www.drugs.com/pregnancy/rifapentine.html | access-date=16 March 2020}}</ref>

| pregnancy_category =

| dependency_liability =

| addiction_liability =

| routes_of_administration = [[By mouth]]

| class = [[Macrolactam]]

| ATCvet =

| ATC_prefix = J04

| ATC_suffix = AB05

| ATC_supplemental =

<!-- Legal status -->

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled-->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment =

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->

| legal_UN_comment =

| legal_status = <!--For countries not listed above-->

<!-- Pharmacokinetic data -->

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life =

| duration_of_action =

| excretion =

<!-- Identifiers -->

| CAS_supplemental =

| PubChem = 6323497

| PubChem2 = 135403821

| IUPHAR_ligand =

| UNII_Ref = {{fdacite|correct|FDA}}

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG2_Ref = {{keggcite|correct|kegg}}

| KEGG2 = C08059

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| NIAID_ChemDB = 007686

| PDB_ligand = RPT

| synonyms = 3{[(4-cyclopentyl-1-piperazinyl)imino]methyl}rifamycin

<!-- Chemical and physical data -->

| IUPAC_name = (7''S'',9''E'',11''S'',12''R'',13''S'',14''R'',15''R'',16''R'',17''S'',18''S'',19''E'',21''Z'',26''E'')-26-{[(4-cyclopentylpiperazin-1-yl)amino]methylidene}-2,15,17,29-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,27-trioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1^4,7.0^5,28]triaconta-1(28),2,4,9,19,21,25(29)-heptaen-13-yl acetate

| chemical_formula =

| SMILES = CC(=O)O[C@H]3[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(\C)C(=O)Nc6c(/C=N/N1CCN(CC1)C2CCCC2)c(O)c5c4C(=O)[C@@](C)(O/C=C/[C@H](OC)[C@H]3C)Oc4c(C)c(O)c5c6O

| Jmol =

| StdInChI_comment =

| density =

| density_notes =

| melting_point = 179

| melting_high = 180

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

<!-- Definition and medical uses -->

'''Rifapentine''', sold under the brand name '''Priftin''', is an [[antibiotic]] used in the treatment of [[tuberculosis]].<ref name="Priftin FDA label">{{cite web | title=Priftin- rifapentine tablet, film coated | website=DailyMed | date=22 October 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f768e337-a948-420a-9fbe-9be359c7a170 | access-date=6 November 2020}}</ref> In active tuberculosis it is used together with other [[antituberculosis medication]]s.<ref name="Priftin FDA label"/> In latent tuberculosis it is typically used with [[isoniazid]].<ref name="Priftin FDA label"/> It is taken by mouth.<ref name="Priftin FDA label"/>

<!-- Side effects and mechanism -->

Common side effects include [[neutropenia|low neutrophil counts in the blood]], [[elevated transaminases|elevated liver enzymes]], and [[pyuria|white blood cells in the urine]].<ref name=AHFS2016>{{cite web|title=Rifapentine|url= https://www.drugs.com/monograph/rifapentine.html| publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url= https://web.archive.org/web/20161220231103/https://www.drugs.com/monograph/rifapentine.html|archive-date=20 December 2016}}</ref> Serious side effects may include [[liver problems]] or [[Clostridium difficile diarrhea|''Clostridium difficile'' associated diarrhea]].<ref name=AHFS2016/> It is unclear if use during [[pregnancy]] is safe.<ref name=AHFS2016/> Rifapentine is in the [[rifamycin]] family of medication and works by blocking [[DNA-dependent RNA polymerase]].<ref name=AHFS2016/>

<!-- History and culture -->

Rifapentine was approved for medical use in the United States in 1998.<ref name="Priftin FDA label"/> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> In many areas of the world it is not easy to get {{as of|2015|lc=yes}}.<ref>{{cite book| vauthors = Nieburg P, Dubovi T, Angelo S |title=Tuberculosis—A Complex Health Threat: A Policy Primer of Global TB Challenges|date=2015|publisher=Rowman & Littlefield|isbn=9781442240957|page=15|url=https://books.google.com/books?id=cueYCgAAQBAJ&pg=PA15|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220090019/https://books.google.com/books?id=cueYCgAAQBAJ&pg=PA15|archive-date=2016-12-20|name-list-style=vanc}}</ref>

==Medical uses==

A systematic review of regimens for prevention of active tuberculosis in HIV-negative individuals with latent TB found that a weekly, directly observed regimen of rifapentine with isoniazid for three months was as effective as a daily, self-administered regimen of isoniazid for nine months. The three-month rifapentine-isoniazid regimen had higher rates of treatment completion and lower rates of hepatotoxicity. However, the rate of treatment-limiting adverse events was higher in the rifapentine-isoniazid regimen compared to the nine-month isoniazid regimen.<ref>{{cite journal | vauthors=Sharma SK, Sharma A, Kadhiravan T, Tharyan P | display-authors=3 | title=Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB. | journal=Cochrane Database of Systematic Reviews | date=July 2013 | pmid=23828580 | volume=7 | issue=7 | doi= 10.1002/14651858.CD007545.pub2 | pages=CD007545| pmc=6532682 }}</ref>

===Pregnancy===

Rifapentine has been assigned a [[pregnancy category]] C by the U.S. [[Food and Drug Administration]] (FDA). Rifapentine in pregnant women has not been studied, but animal reproduction studies have resulted in fetal harm and were teratogenic. If rifapentine or rifampin are used in late pregnancy, coagulation should be monitored due to a possible increased risk of maternal postpartum hemorrhage and infant bleeding.<ref name="Priftin FDA label"/>

==Adverse effects==

Common side effects include [[allergic reaction]], [[anemia]], [[neutropenia]], [[elevated transaminases]],<ref name="Priftin FDA label" /> and [[pyuria]].<ref name=AHFS2016/> Overdoses have been associated with [[hematuria]] and [[hyperuricemia]].<ref name="Priftin FDA label" />

==Contraindications==

Rifapentine should be avoided in patients with an allergy to the [[rifamycin]] class of drugs.<ref name="Priftin FDA label" /> This drug class includes [[rifampicin]] and [[rifabutin]].<ref>CDC. (2013) ''Core Curriculum on Tuberculosis: What the Clinician Should Know''. Retrieved from {{cite web |url=https://www.cdc.gov/TB/education/corecurr/default.htm |title=CDC - Core Curriculum: What the Clinician Should Know - TB |access-date=2017-09-10 |url-status=live |archive-url=https://web.archive.org/web/20170711215933/https://www.cdc.gov/tb/education/corecurr/default.htm |archive-date=2017-07-11 }}.</ref>

==Interactions==

Rifapentine induces metabolism by CYP3A4, CYP2C8 and CYP2C9 enzymes. It may be necessary to adjust the dosage of drugs metabolized by these enzymes if they are taken with rifapentine. Examples of drugs that may be affected by rifapentine include [[warfarin]], [[propranolol]], [[digoxin]], [[Protease inhibitor (biology)|protease inhibitor]]s and [[Oral contraceptive pill|birth control pill]]s.<ref name="Priftin FDA label" />

== Chemical structure ==

The chemical structure of rifapentine is similar to that of [[rifamycin]], with the notable substitution of a methyl group for a [[cyclopentane]] (C₅H₉) group.

==History==

Rifapentine was first synthesized in 1965, by the same company that produced [[rifampicin]].{{citation needed|date=March 2020}} The drug was approved by the U.S. [[Food and Drug Administration]] (FDA) in June 1998.<ref>{{cite web | title=Drug Approval Package: Priftin/Rifapentine NDA# 21024 | website=U.S. [[Food and Drug Administration]] (FDA) | date=30 March 2001 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/21024.cfm | access-date=16 March 2020}}</ref><ref>{{cite web | title=Priftin | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=021024 | access-date=16 March 2020}}</ref> It is made from rifampicin.{{medcn|date=March 2020}}

Rifapentine was granted [[orphan drug]] designation by the FDA in June 1995,<ref>{{cite web | title=Rifapentine Orphan Drug Designation and Approval | website=U.S. [[Food and Drug Administration]] (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=89495 | access-date=16 March 2020}}</ref> and by the European Commission in June 2010.<ref>{{cite web | title=EU/3/10/750 | website=[[European Medicines Agency]] (EMA) | date=21 June 2010 | url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu310750 | access-date=16 March 2020 | id=EMA/COMP/165383/2010 }}</ref>

== Society and culture ==

===Cancer-causing impurities===

{{Anchor|impurities}}

{{See also|Ranitidine#impurities}}

In August 2020, the U.S. [[Food and Drug Administration]] (FDA) became aware of nitrosamine impurities in certain samples of rifapentine.<ref name="FDA 20200826">{{cite web | title=FDA works to mitigate shortages of rifampin and rifapentine | website=U.S. [[Food and Drug Administration]] (FDA) | date=26 August 2020 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-works-mitigate-shortages-rifampin-and-rifapentine-after-manufacturers-find-nitrosamine | access-date=28 August 2020}} {{PD-notice}}</ref> The FDA and manufacturers are investigating the origin of these impurities in rifapentine, and the agency is developing testing methods for regulators and industry to detect the 1-cyclopentyl-4-nitrosopiperazine (CPNP).<ref name="FDA 20200826" /> CPNP belongs to the nitrosamine class of compounds, some of which are classified as probable or possible human carcinogens (substances that could cause cancer), based on laboratory tests such as rodent carcinogenicity studies.<ref name="FDA 20200826" /> Although there are no data available to directly evaluate the carcinogenic potential of CPNP, information available on closely related nitrosamine compounds was used to calculate lifetime exposure limits for CPNP.<ref name="FDA 20200826" />

As of January 2021, the FDA continues to investigate the presence of 1-methyl-4-nitrosopiperazine (MNP) in rifampin or 1-cyclopentyl-4-nitrosopiperazine (CPNP) in rifapentine approved for sale in the US.<ref>{{cite web | title=Laboratory analysis of rifampin/rifapentine products | website=U.S. [[Food and Drug Administration]] (FDA) | date=28 January 2021 | url=https://www.fda.gov/drugs/drug-safety-and-availability/laboratory-analysis-rifampinrifapentine-products | access-date=28 January 2021}} {{PD-notice}}</ref>

==See also==

* [[Rifampicin]]

* [[Isoniazid]]

* [[Rifamycin]]

* [[Rifabutin]]

==References==

{{reflist}}

==External links==

* {{cite web | title=Nitrosamine impurities in medications: Guidance | website=Health Canada | date=4 April 2022 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/medications-guidance.html }}

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