Rifapentine

Synonyms :
3-(((4-Cyclopentyl-1-piperazinyl)imino)methyl)rifamycin, Cyclopentylrifampicin, Priftin (tn)

Status : approved

Category

Leprostatic Agents

Therapeutic Classification

DRUGS FOR TREATMENT OF TUBERCULOSIS

ANTIINFECTIVES FOR SYSTEMIC USE
ANTIMYCOBACTERIALS
DRUGS FOR TREATMENT OF TUBERCULOSIS
Antibiotics, Antitubercular

Description

Rifapentine is an antibiotic drug used in the treatment of tuberculosis. It inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme.

Used

For the treatment of pulmonary tuberculosis.

Mechanism Of Action

Rifapentine has shown higher bacteriostatic and bactericidal activities especially against intracellular bacteria growing in human monocyte-derived macrophages. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of M. tuberculosis. Rifapentine acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.

Dosage

Form Route Strength
Tablet, film coated oral 150 mg

Pharmacodynamics

Rifapentine is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.

Metabolism

Hepatic

Absorption

Rapidly and well absorbed from the gastrointestinal tract.

Protein Binding

97.7% (bound to plasma proteins)

Elimination Route

Following a single 600 mg oral dose of radiolabeled rifapentine to healthy volunteers (n=4), 87% of the total 14C rifapentine was recovered in the urine (17%) and feces (70%).

Clearance

* Apparent Oral cl=2.51 +/- 0.14 L/h [Male tuberculosis patients who received 600 mg rifapentine in combination with isoniazid, pyrazinamide and ethambutol] * Apparent Oral cl=1.69 +/- 0.41 L/h [Female tuberculosis patients who received 600 mg rifapentine in combination with isoniazid, pyrazinamide and ethambutol]

Volume of Distribution

* 70.2 ± 9.1 L

Chemical Classification

Chemical Name

3-(((4-Cyclopentyl-1-piperazinyl)imino)methyl)rifamycin

Brands

name Dosage form Country
Priftin tablet, film coated US

Drug Drug Interactions

  •  Abiraterone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate.
  •  Alfentanil  : Rifamycin Derivatives may decrease the serum concentration of Alfentanil.
  •  Amlodipine  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Amrinone  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Apixaban  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban.
  •  Apremilast  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast.
  •  Aripiprazole  : CYP3A4 Inducers may decrease the serum concentration of Aripiprazole.
  •  Artemether  : CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether. Specifically, dihydroartemisinin concentrations may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether.
  •  Atovaquone  : Rifamycin Derivatives may decrease the serum concentration of Atovaquone.
  •  Axitinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Bedaquiline  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline.
  •  Bepridil  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Boceprevir  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Boceprevir.
  •  Bortezomib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib.
  •  Bosutinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib.
  •  Brentuximab vedotin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased.
  •  Brexpiprazole  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Brexpiprazole.
  •  Buspirone  : Rifamycin Derivatives may decrease the serum concentration of Buspirone.
  •  Butabarbital  : Rifamycin Derivatives may increase the metabolism of Barbiturates.
  •  Butethal  : Rifamycin Derivatives may increase the metabolism of Barbiturates.
  •  Cabozantinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib.
  •  Cannabidiol  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol.
  •  Ceritinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib.
  •  Clarithromycin  : CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin.
  •  Clopidogrel  : Rifamycin Derivatives may enhance the adverse/toxic effect of Clopidogrel. Specifically,clopidogrel antiplatelet effects may be enhanced.
  •  Clozapine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Clozapine.
  •  Cobicistat  : Rifapentine may decrease the serum concentration of Cobicistat.
  •  Crizotinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib.
  •  Daclatasvir  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Daclatasvir.
  •  Darunavir  : Rifapentine may decrease the serum concentration of Darunavir.
  •  Dasatinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib.
  •  Delavirdine  : Rifamycin Derivatives may increase the metabolism of Delavirdine. Delavirdine may increase the serum concentration of Rifamycin Derivatives. Specifically, Rifabutin serum concentration may be increased.
  •  Dienogest  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest.
  •  Dronabinol  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronabinol.
  •  Dronabinol  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol.
  •  Dronedarone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone.
  •  Eliglustat  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat.
  •  Elvitegravir  : Rifapentine may decrease the serum concentration of Elvitegravir.
  •  Enzalutamide  : CYP2C8 Inducers (Strong) may decrease the serum concentration of Enzalutamide.
  •  Enzalutamide  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Enzalutamide.
  •  Erlotinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Erlotinib.
  •  Etoposide  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide.
  •  Etoposide  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide Phosphate.
  •  Etravirine  : Rifamycin Derivatives may decrease the serum concentration of Etravirine.
  •  Everolimus  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus.
  •  Exemestane  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane.
  •  Felodipine  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Fentanyl  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Fentanyl.
  •  Flibanserin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Flibanserin.
  •  Flunarizine  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Gabapentin  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Gefitinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib.
  •  Guanfacine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Guanfacine.
  •  Heptabarbital  : Rifamycin Derivatives may increase the metabolism of Barbiturates.
  •  Hexobarbital  : Rifamycin Derivatives may increase the metabolism of Barbiturates.
  •  Hydrocodone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Hydrocodone.
  •  Ibrutinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib.
  •  Idelalisib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib.
  •  Ifosfamide  : CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide.
  •  Imatinib  : Rifamycin Derivatives may decrease the serum concentration of Imatinib.
  •  Imatinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib.
  •  Irinotecan  : CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan.
  •  Isavuconazonium  : CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations.
  •  Isoniazid  : Rifamycin Derivatives may enhance the hepatotoxic effect of Isoniazid. Even so, this is a frequently employed combination regimen.
  •  Isradipine  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Itraconazole  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole.
  •  Ivabradine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine.
  •  Ivacaftor  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor.
  •  Ixabepilone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone.
  •  Lamotrigine  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Lapatinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib.
  •  Ledipasvir  : Rifapentine may decrease the serum concentration of Ledipasvir.
  •  Lercanidipine  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Linagliptin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Linagliptin.
  •  Lumefantrine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumefantrine.
  •  Lurasidone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone.
  •  MACITENTAN  : CYP3A4 Inducers (Strong) may decrease the serum concentration of MACITENTAN.
  •  Magnesium Sulfate  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Maraviroc  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
  •  Methadone  : Rifamycin Derivatives may decrease the serum concentration of Methadone.
  •  Methohexital  : Rifamycin Derivatives may increase the metabolism of Barbiturates.
  •  Methylprednisolone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Methylprednisolone.
  •  Mifepristone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Mifepristone.
  •  Mycophenolic acid  : Rifamycin Derivatives may decrease the serum concentration of Mycophenolate. Specifically, rifamycin derivatives may decrease the concentration of the active metabolite Mycophenolic acid.
  •  Naloxegol  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol.
  •  Netupitant  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant.
  •  Nicardipine  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Nifedipine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Nifedipine.
  •  Nilotinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
  •  Nimodipine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Nimodipine.
  •  Nisoldipine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine.
  •  Nitrendipine  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Olaparib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Olaparib.
  •  Palbociclib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib.
  •  Panobinostat  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat.
  •  Pazopanib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Pazopanib.
  •  Pentobarbital  : Rifamycin Derivatives may increase the metabolism of Barbiturates.
  •  Perampanel  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Perampanel.
  •  Perhexiline  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Pitavastatin  : Rifamycin Derivatives may increase the serum concentration of Pitavastatin.
  •  Ponatinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ponatinib.
  •  Praziquantel  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel.
  •  Prednisone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Prednisone.
  •  Prenylamine  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Primidone  : Rifamycin Derivatives may increase the metabolism of Barbiturates.
  •  Propafenone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Propafenone.
  •  Quetiapine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Quetiapine.
  •  Quinidine  : Rifamycin Derivatives may decrease the serum concentration of Quinidine.
  •  Raltegravir  : Rifapentine may increase the serum concentration of Raltegravir. Rifapentine may decrease the serum concentration of Raltegravir.
  •  Ramelteon  : Rifamycin Derivatives may increase the metabolism of Ramelteon.
  •  Ranolazine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine.
  •  Regorafenib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib.
  •  Rilpivirine  : Rifamycin Derivatives may decrease the serum concentration of Rilpivirine.
  •  Risedronate  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Rivaroxaban  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban.
  •  Roflumilast  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast.
  •  Romidepsin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Romidepsin.
  •  Saxagliptin  : CYP3A4 Inducers may decrease the serum concentration of Saxagliptin.
  •  Secobarbital  : Rifamycin Derivatives may increase the metabolism of Barbiturates.
  •  Simeprevir  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
  •  Sofosbuvir  : Rifapentine may decrease the serum concentration of Sofosbuvir.
  •  Sonidegib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Sonidegib.
  •  Sorafenib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Sorafenib.
  •  Sunitinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Sunitinib.
  •  Suvorexant  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Suvorexant.
  •  Tadalafil  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil.
  •  Tamoxifen  : Rifamycin Derivatives may increase the metabolism of Tamoxifen.
  •  Tasimelteon  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon.
  •  Telaprevir  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Telaprevir.
  •  Temsirolimus  : Rifamycin Derivatives may decrease the serum concentration of Temsirolimus. Rifamycins will likely cause an even greater decrease in the concentration of the active metabolite sirolimus.
  •  Ticagrelor  : CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor.
  •  Tofacitinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib.
  •  Tolvaptan  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan.
  •  Toremifene  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene.
  •  Trabectedin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin.
  •  Treprostinil  : CYP2C8 Inducers (Strong) may decrease the serum concentration of Treprostinil.
  •  Ulipristal  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal.
  •  Vandetanib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib.
  •  Vemurafenib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib.
  •  Verapamil  : Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers.
  •  Vilazodone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Vilazodone.
  •  Vorapaxar  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar.
  •  Voriconazole  : May increase the serum concentration of Rifamycin Derivatives. Rifamycin Derivatives may decrease the serum concentration of Voriconazole.
  •  Vortioxetine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Vortioxetine.
  •  Zaleplon  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Zaleplon.
  •  Zidovudine  : Rifamycin Derivatives may decrease the serum concentration of Zidovudine.
  •  Zolpidem  : Rifamycin Derivatives may decrease the serum concentration of Zolpidem.
  •  Zuclopenthixol  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol.

Calculated Property

kind Value Source
logP 4.83 ALOGPS
logS -4.6 ALOGPS
Water Solubility 2.13e-02 g/l ALOGPS
logP 3.56 ChemAxon
IUPAC Name (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-26-[(1E)-[(4-cyclopentylpiperazin-1-yl)imino]methyl]-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1⁴,⁷.0⁵,²⁸]triaconta-1(28),2,4,9,19,21,25(29),26-octaen-13-yl acetate ChemAxon
Traditional IUPAC Name (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-26-[(1E)-[(4-cyclopentylpiperazin-1-yl)imino]methyl]-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1⁴,⁷.0⁵,²⁸]triaconta-1(28),2,4,9,19,21,25(29),26-octaen-13-yl acetate ChemAxon
Molecular Weight 877.0307 ChemAxon
Monoisotopic Weight 876.452073532 ChemAxon
SMILES CO[C@H]1C=CO[C@@]2(C)OC3=C(C2=O)C2=C(C(O)=C3C)C(O)=C(NC(=O)C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C(C=NN1CCN(CC1)C1CCCC1)=C2O ChemAxon
Molecular Formula C47H64N4O12 ChemAxon
InChI 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 ChemAxon
InChIKey InChIKey=WDZCUPBHRAEYDL-GZAUEHORSA-N ChemAxon
Polar Surface Area (PSA) 220.15 ChemAxon
Refractivity 242 ChemAxon
Polarizability 93.14 ChemAxon
Rotatable Bond Count 6 ChemAxon
H Bond Acceptor Count 14 ChemAxon
H Bond Donor Count 6 ChemAxon
pKa (strongest acidic) 7.01 ChemAxon
pKa (strongest basic) 7.98 ChemAxon
Physiological Charge 1 ChemAxon
Number of Rings 6 ChemAxon
Bioavailability 0 ChemAxon
Rule of Five 0 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 1 ChemAxon

Affected organism

Mycobacterium tuberculosis

Target within organism

  • DNA-directed RNA polymerase subunit beta’ : in Mycobacterium tuberculosis