Rifapentine

Last updated
Rifapentine
Rifapentine.svg
Clinical data
Trade names Priftin
Other names3{[(4-cyclopentyl-1-piperazinyl)imino]methyl}rifamycin
AHFS/Drugs.com Monograph
MedlinePlus a616011
License data
Routes of
administration 		By mouth
Drug class Macrolactam
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability increases when administered with food
Identifiers
  • (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z,26E)-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[23.3.1.14,7.05,28]triaconta-1(28),2,4,9,19,21,25(29)-heptaen-13-yl acetate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.057.021 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C47H64N4O12
Molar mass 877.045 g·mol−1
3D model (JSmol)
Melting point 179 to 180 °C (354 to 356 °F)
  • 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
  • InChI=1S/C47H64N4O12/c1-24-13-12-14-25(2)46(59)49-37-32(23-48-51-20-18-50(19-21-51)31-15-10-11-16-31)41(56)34-35(42(37)57)40(55)29(6)44-36(34)45(58)47(8,63-44)61-22-17-33(60-9)26(3)43(62-30(7)52)28(5)39(54)27(4)38(24)53/h12-14,17,22-24,26-28,31,33,38-39,43,53-57H,10-11,15-16,18-21H2,1-9H3,(H,49,59)/b13-12+,22-17+,25-14-,48-23+/t24-,26+,27+,28+,33-,38-,39+,43+,47-/m0/s1 Yes check.svgY
  • Key:WDZCUPBHRAEYDL-GZAUEHORSA-N Yes check.svgY
   (verify)

Rifapentine, sold under the brand name Priftin, is an antibiotic used in the treatment of tuberculosis. [1] In active tuberculosis it is used together with other antituberculosis medications. [1] In latent tuberculosis it is typically used with isoniazid. [1] It is taken by mouth. [1]

Contents

Common side effects include low neutrophil counts in the blood, elevated liver enzymes, and white blood cells in the urine. [2] Serious side effects may include liver problems or Clostridioides difficile associated diarrhea. [2] It is unclear if use during pregnancy is safe. [2] Rifapentine is in the rifamycin family of medication and works by blocking DNA-dependent RNA polymerase. [2]

Rifapentine was approved for medical use in the United States in 1998. [1] It is on the World Health Organization's List of Essential Medicines. [3] In many areas of the world it is not easy to get as of 2015. [4]

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. [5]

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. [1]

Adverse effects

Common side effects include allergic reaction, anemia, neutropenia, elevated transaminases, [1] and pyuria. [2] Overdoses have been associated with hematuria and hyperuricemia. [1]

Contraindications

Rifapentine should be avoided in patients with an allergy to the rifamycin class of drugs. [1] This drug class includes rifampicin and rifabutin. [6]

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 inhibitors and birth control pills. [1]

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 ] The drug was approved by the U.S. Food and Drug Administration (FDA) in June 1998. [7] [8] It is made from rifampicin.[ medical citation needed ]

Rifapentine was granted orphan drug designation by the FDA in June 1995, [9] and by the European Commission in June 2010. [10]

Society and culture

Cancer-causing impurities

In August 2020, the U.S. Food and Drug Administration (FDA) became aware of nitrosamine impurities in certain samples of rifapentine. [11] 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). [11] 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. [11] 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. [11]

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. [12]

See also

Related Research Articles

<span class="mw-page-title-main">Isoniazid</span> Antibiotic for treatment of tuberculosis

Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis, it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For latent tuberculosis, it is often used alone. It may also be used for atypical types of mycobacteria, such as M. avium, M. kansasii, and M. xenopi. It is usually taken by mouth, but may be used by injection into muscle.

<span class="mw-page-title-main">Irbesartan</span> Chemical compound

Irbesartan, sold under the brand name Aprovel among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination irbesartan/hydrochlorothiazide.

<span class="mw-page-title-main">Rifamycin</span> Group of antibiotics

The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium Amycolatopsis rifamycinica or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective against mycobacteria, and are therefore used to treat tuberculosis, leprosy, and mycobacterium avium complex (MAC) infections.

<span class="mw-page-title-main">Rifampicin</span> Antibiotic medication

Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), Mycobacterium avium complex, leprosy, and Legionnaires' disease. It is almost always used together with other antibiotics with two notable exceptions: when given as a "preferred treatment that is strongly recommended" for latent TB infection; and when used as post-exposure prophylaxis to prevent Haemophilus influenzae type b and meningococcal disease in people who have been exposed to those bacteria. Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended. Rifampicin may be given either by mouth or intravenously.

<span class="mw-page-title-main">Management of tuberculosis</span> Disease treatment

Management of tuberculosis refers to techniques and procedures utilized for treating tuberculosis (TB), or simply a treatment plan for TB.

<span class="mw-page-title-main">Losartan</span> Blood pressure medication

Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin receptor blocker (ARB) family of medication, and is considered protective of the kidneys. Besides hypertension, it is also used in diabetic kidney disease, heart failure, and left ventricular enlargement. It comes as a tablet that is taken by mouth. It may be used alone or in addition to other blood pressure medication. Up to six weeks may be required for the full effects to occur.

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Pyrazinamide</span> Medication

Pyrazinamide is a medication used to treat tuberculosis. For active tuberculosis, it is often used with rifampicin, isoniazid, and either streptomycin or ethambutol. It is not generally recommended for the treatment of latent tuberculosis. It is taken by mouth.

<span class="mw-page-title-main">4-Aminosalicylic acid</span> Anti-tuberculosis and anti-inflammatory drug

4-Aminosalicylic acid, also known as para-aminosalicylic acid (PAS) and sold under the brand name Paser among others, is an antibiotic primarily used to treat tuberculosis. Specifically it is used to treat active drug resistant tuberculosis together with other antituberculosis medications. It has also been used as a second line agent to sulfasalazine in people with inflammatory bowel disease such as ulcerative colitis and Crohn's disease. It is typically taken by mouth.

<span class="mw-page-title-main">Rifabutin</span> Chemical compound

Rifabutin (Rfb) is an antibiotic used to treat tuberculosis and prevent and treat Mycobacterium avium complex. It is typically only used in those who cannot tolerate rifampin such as people with HIV/AIDS on antiretrovirals. For active tuberculosis it is used with other antimycobacterial medications. For latent tuberculosis it may be used by itself when the exposure was with drug-resistant TB.

Latent tuberculosis (LTB), also called latent tuberculosis infection (LTBI) is when a person is infected with Mycobacterium tuberculosis, but does not have active tuberculosis (TB). Active tuberculosis can be contagious while latent tuberculosis is not, and it is therefore not possible to get TB from someone with latent tuberculosis. The main risk is that approximately 10% of these people will go on to develop active tuberculosis. This is particularly true, and there is added risk, in particular situations such as medication that suppresses the immune system or advancing age.

<span class="mw-page-title-main">Rifampicin/isoniazid/pyrazinamide</span> Combination drug

Rifampicin/isoniazid/pyrazinamide, also known as rifampin/isoniazid/pyrazinamide, and sold under the trade name Rifater, is a medication used to treat tuberculosis. It is a fixed dose combination of rifampicin, isoniazid, and pyrazinamide. It is used either by itself or along with other antituberculosis medication. It is taken by mouth.

<span class="mw-page-title-main">Ethionamide</span> Chemical compound

Ethionamide is an antibiotic used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, to treat active multidrug-resistant tuberculosis. It is no longer recommended for leprosy. It is taken by mouth.

<span class="mw-page-title-main">Multidrug-resistant tuberculosis</span> Medical condition

Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs): isoniazid and rifampicin. Some forms of TB are also resistant to second-line medications, and are called extensively drug-resistant TB (XDR-TB).

<span class="mw-page-title-main">Bedaquiline</span> Medication used to treat tuberculosis

Bedaquiline, sold under the brand name Sirturo, is a medication used for the treatment of active tuberculosis. Specifically, it is used to treat multi-drug-resistant tuberculosis along with other medications for tuberculosis. It is taken by mouth.

<span class="mw-page-title-main">Pretomanid</span> Chemical compound

Pretomanid is an antibiotic medication used for the treatment of multi-drug-resistant tuberculosis affecting the lungs. It is generally used together with bedaquiline and linezolid. It is taken by mouth.

<i>N</i>-Nitrosodimethylamine Chemical compound

N-Nitrosodimethylamine (NDMA), also known as dimethylnitrosamine (DMN), is an organic compound with the formula (CH3)2NNO. It is one of the simplest members of a large class of nitrosamines. It is a volatile yellow oil. NDMA has attracted wide attention as being highly hepatotoxic and a known carcinogen in laboratory animals.

Delamanid is sold under the brand name Deltyba, is a medication used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active multidrug-resistant tuberculosis. It is taken by mouth.

Isoniazid/rifampicin, also known as isoniazid/rifampin, is a medication used to treat tuberculosis. It is a fixed dose combination of isoniazid and rifampicin (rifampin). It is used together with other antituberculosis medication. It is taken by mouth.

Ethambutol/isoniazid/rifampicin, also known as ethambutol/isoniazid/rifampin, is a fixed-dose combination medication used to treat tuberculosis. It contains ethambutol, isoniazid, and rifampicin. It is used either along or with other anti-tuberculosis medication. It is taken by mouth. Side effects are those of the underlying medications. Use may not be suitable in children.

References

  1. 1 2 3 4 5 6 7 8 9 10 "Priftin- rifapentine tablet, film coated". DailyMed. 22 October 2019. Retrieved 6 November 2020.
  2. 1 2 3 4 5 "Rifapentine". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
  3. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  4. ↑ Nieburg P, Dubovi T, Angelo S (2015). Tuberculosis—A Complex Health Threat: A Policy Primer of Global TB Challenges. Rowman & Littlefield. p. 15. ISBN   9781442240957. Archived from the original on 2016-12-20.
  5. ↑ Sharma SK, Sharma A, Kadhiravan T, et al. (July 2013). "Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB". Cochrane Database of Systematic Reviews. 7 (7): CD007545. doi:10.1002/14651858.CD007545.pub2. PMC   6532682 . PMID   23828580.
  6. ↑ CDC. (2013) Core Curriculum on Tuberculosis: What the Clinician Should Know. Retrieved from "CDC - Core Curriculum: What the Clinician Should Know - TB". Archived from the original on 2017-07-11. Retrieved 2017-09-10..
  7. ↑ "Drug Approval Package: Priftin/Rifapentine NDA# 21024". U.S. Food and Drug Administration (FDA). 30 March 2001. Retrieved 16 March 2020.
  8. ↑ "Priftin". U.S. Food and Drug Administration (FDA). Retrieved 16 March 2020.
  9. ↑ "Rifapentine Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 16 March 2020.
  10. ↑ "EU/3/10/750". European Medicines Agency (EMA). 21 June 2010. EMA/COMP/165383/2010. Retrieved 16 March 2020.
  11. 1 2 3 4 "FDA works to mitigate shortages of rifampin and rifapentine". U.S. Food and Drug Administration (FDA). 26 August 2020. Retrieved 28 August 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  12. ↑ "Laboratory analysis of rifampin/rifapentine products". U.S. Food and Drug Administration (FDA). 28 January 2021. Retrieved 28 January 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.