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Rifapentine

Medically reviewed by Drugs.com. Last updated on Jul 28, 2020.

Pronunciation

(rif a PEN teen)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Priftin: 150 mg [contains disodium edta, fd&c blue #2 aluminum lake]

Brand Names: U.S.

  • Priftin

Pharmacologic Category

  • Antitubercular Agent
  • Rifamycin

Pharmacology

Inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis (MTB) (but not in mammalian cells). Rifapentine is bactericidal against both intracellular and extracellular MTB organisms.

Absorption

High-fat meals increase AUC and Cmax by 40% to 50%

In pediatric patients, crushing the tablet results in 26% lower exposure than whole tablets.

Distribution

Vd: ~70 L

Metabolism

Hepatic; hydrolyzed by an esterase enzyme to form the active metabolite 25-desacetyl rifapentine

Excretion

Feces (70%); urine (17%, primarily as metabolites)

In pediatric patients 2 to 18 years of age, clearance decreases with increasing age.

Time to Peak

Serum: 3 to 10 hours

Half-Life Elimination

Rifapentine: ~17 hours; 25-desacetyl rifapentine: ~24 hours

Protein Binding

Rifapentine: ~98%, primarily to albumin; 25-desacetyl rifapentine: ~93%

Use: Labeled Indications

Tuberculosis, active: Treatment of active pulmonary tuberculosis caused by Mycobacterium tuberculosis in adults and children 12 years and older; must be used in combination with one or more antituberculosis drugs to which the isolate is susceptible.

Limitations of use: Rifapentine should not be used once weekly in the continuation phase regimen in combination with isoniazid in HIV-infected patients with active pulmonary tuberculosis because of a higher rate of failure and/or relapse with rifampin-resistant organisms. Rifapentine has not been studied as part of the initial phase treatment regimen in HIV-infected patients with active pulmonary tuberculosis.

Tuberculosis, latent infection: Treatment of latent tuberculosis infection caused by Mycobacterium tuberculosis, in combination with isoniazid, in adults and children 2 years and older at high risk of progression to tuberculosis disease. To identify candidates for latent tuberculosis infection treatment, refer to Centers for Disease Control and Prevention (CDC) guidelines for current recommendations.

Limitations of use: Rifapentine in combination with isoniazid is not recommended for individuals presumed to be exposed to rifamycin- or isoniazid-resistant M. tuberculosis.

Contraindications

Hypersensitivity to rifapentine, other rifamycins, or any component of the formulation

Dosing: Adult

Tuberculosis, active (drug-susceptible): Oral:

Initial phase: 600 mg twice weekly (with an interval ≥72 hours between doses) by directly observed therapy (DOT) for 2 months as part of multidrug regimen.

Continuation phase: 600 mg once weekly by DOT for 4 months as part of a multidrug regimen. Note: Drug-susceptible TB guidelines recommend against once-weekly therapy; use should only be considered in rare situations in certain HIV-uninfected individuals with no cavitation on chest x-ray (Nahid 2016).

Tuberculosis, latent infection:

Once-weekly regimen: Oral: Administer for 12 weeks in combination with isoniazid. Note: May be administered by DOT or as self-administered therapy. This regimen may only be used in patients who are not pregnant and/or not expecting to become pregnant; if used in HIV-infected patients, it may only be used in those receiving antiretroviral therapy (ART) with acceptable drug-drug interactions with rifapentine (CDC [Borisov 2018]).

25.1 to 32 kg: 600 mg once weekly

32.1 to 50 kg: 750 mg once weekly

>50 kg: 900 mg once weekly

Once-daily regimen (HIV-infected patients): Oral: Administer for 1 month in combination with isoniazid. Note: This regimen has been studied in HIV-infected patients living in regions with high tuberculosis prevalence or with evidence of latent tuberculosis infection (Swindells 2019), but is not yet widely recommended (Menzies 2019).

<35 kg: 300 mg once daily

35 to 45 kg: 450 mg once daily

>45 kg: 600 mg once daily

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Rifapentine must always be used in conjunction with at least one other antituberculosis drug to which the isolate is susceptible.

Tuberculosis, treatment; active pulmonary infection: Children ≥12 years and Adolescents:

Initial phase: Oral: 600 mg twice weekly (with an interval ≥72 hours between doses) by directly observed therapy (DOT) for 2 months. Note: Initial phase should include a 3- to 4-drug regimen.

Continuation phase: Oral: 600 mg once weekly by DOT for 4 months in combination with isoniazid (INH) or another appropriate agent for susceptible organisms. Note: Drug-susceptible TB guidelines recommend against once-weekly therapy; use should only be considered in rare situations in certain HIV-uninfected individuals with no cavitation on chest x-ray (Nahid 2016).

Latent tuberculosis infection (LTBI): Note: For HIV-positive patients, including those with AIDS, rifapentine in combination with isoniazid is recommended if receiving HAART therapy with acceptable drug-drug interactions with rifapentine when guided by experienced clinicians (CDC [Borisov 2018]). Children ≥2 years and Adolescents: Oral: Administer by DOT or self-administered therapy (SAT) at the clinician's discretion based on local practice, patient attributes/preferences, and other factors including risk for TB disease progression (CDC [Borisov 2018]) for 12 weeks (12 doses) in combination with isoniazid:

10 to 14 kg: 300 mg/dose once weekly

>14 to 25 kg: 450 mg/dose once weekly

>25 to 32 kg: 600 mg/dose once weekly

>32 to 50 kg: 750 mg/dose once weekly

>50 kg: 900 mg/dose once weekly

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Oral: Administer with meals. For patients who cannot swallow tablets, the tablets may be crushed and added to a small amount of semi-solid food and consumed immediately.

Dietary Considerations

Take with food.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from excessive heat and humidity.

Drug Interactions

Abemaciclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abemaciclib. Avoid combination

Abiraterone Acetate: Rifapentine may decrease the serum concentration of Abiraterone Acetate. Monitor therapy

Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Acalabrutinib. Monitor therapy

Alfentanil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Alfentanil. Management: If concomitant use of alfentanil and moderate CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Consider therapy modification

Antifungal Agents (Azole Derivatives, Systemic): May increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Rifamycin Derivatives may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Avoid these combinations when possible. Voriconazole and isavuconazonium are considered contraindicated. Consider therapy modification

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination

Apremilast: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Apremilast. Monitor therapy

Aprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Aprepitant. Monitor therapy

ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole. Monitor therapy

ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole Lauroxil. Monitor therapy

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Avoid combination

Atovaquone: Rifamycin Derivatives may decrease the serum concentration of Atovaquone. Avoid combination

Avanafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avanafil. Avoid combination

Avapritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avapritinib. Avoid combination

Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Avoid combination

Barbiturates: Rifamycin Derivatives may increase the metabolism of Barbiturates. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Avoid combination

Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Monitor therapy

Beta-Blockers: Rifamycin Derivatives may decrease the serum concentration of Beta-Blockers. Monitor therapy

Bictegravir: Rifapentine may decrease the serum concentration of Bictegravir. Avoid combination

Bortezomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bortezomib. Monitor therapy

Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Avoid combination

Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brexpiprazole. Monitor therapy

Brigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Consider therapy modification

Cabozantinib: Rifapentine may decrease the serum concentration of Cabozantinib. Monitor therapy

Calcium Channel Blockers: Rifamycin Derivatives may decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers (CCBs) contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. If coadministered, monitor for decreased CCB efficiacy. Consider therapy modification

Capmatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capmatinib. Avoid combination

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

Clarithromycin: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Consider therapy modification

CloZAPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Monitor therapy

Cobicistat: Rifapentine may decrease the serum concentration of Cobicistat. Avoid combination

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Avoid combination

Codeine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Codeine. Monitor therapy

Copanlisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Copanlisib. Monitor therapy

Crizotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Crizotinib. Monitor therapy

CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CycloSPORINE (Systemic). Monitor therapy

CYP2C9 Substrates (High risk with Inducers): Rifapentine may decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Daclatasvir: Rifapentine may decrease the serum concentration of Daclatasvir. Management: US labeling recommends increasing the daclatasvir dose to 90 mg once daily if used with rifapentine. Canadian labeling states that the combination of daclatasvir and rifapentine is contraindicated. Consider therapy modification

Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dapsone (Systemic). Monitor therapy

Darunavir: Rifapentine may decrease the serum concentration of Darunavir. Avoid combination

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dasabuvir. Avoid combination

Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination

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. Avoid combination

DexAMETHasone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of DexAMETHasone (Systemic). Monitor therapy

Doravirine: Rifapentine may decrease the serum concentration of Doravirine. Avoid combination

Elbasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elbasvir. Avoid combination

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Monitor therapy

Elvitegravir: Rifapentine may decrease the serum concentration of Elvitegravir. Avoid combination

Encorafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Encorafenib. Avoid combination

Entrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Entrectinib. Avoid combination

Enzalutamide: Rifapentine may decrease the serum concentration of Enzalutamide. Monitor therapy

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Consider therapy modification

Erlotinib: Rifapentine may decrease the serum concentration of Erlotinib. Management: Avoid combination if possible. If combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Consider therapy modification

Estriol (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Systemic). Monitor therapy

Estriol (Topical): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Topical). Monitor therapy

Estrogen Derivatives (Contraceptive): Rifamycin Derivatives may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification

Etoposide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide. Monitor therapy

Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide Phosphate. Monitor therapy

Etravirine: Rifapentine may decrease the serum concentration of Etravirine. Avoid combination

Everolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Everolimus. Monitor therapy

Fedratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fedratinib. Avoid combination

FentaNYL: CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL. Monitor therapy

Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Avoid combination

Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Monitor therapy

Glasdegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Consider therapy modification

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Grazoprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Grazoprevir. Avoid combination

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Consider therapy modification

HMG-CoA Reductase Inhibitors (Statins): Rifamycin Derivatives may decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Consider use of noninteracting antilipemic agents (note: pitavastatin concentrations may increase with rifamycin treatment). Monitor for altered HMG-CoA reductase inhibitor effects. Rifabutin and fluvastatin, or possibly pravastatin, may pose lower risk. Consider therapy modification

HYDROcodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of HYDROcodone. Monitor therapy

Hydrocortisone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Hydrocortisone (Systemic). Monitor therapy

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Monitor therapy

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Imatinib: Rifamycin Derivatives may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with the rifamycin derivatives when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Consider therapy modification

Indinavir: Rifapentine may decrease the serum concentration of Indinavir. Management: Consider avoiding the combination of indinavir and rifapentine whenever possible due to the risk for decreased indinavir concentrations, reduced efficacy, and development of resistance. If combined, monitor for indinavir treatment failure. Consider therapy modification

Irinotecan Products: Rifapentine may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Rifapentine may decrease the serum concentration of Irinotecan Products. Monitor therapy

Isoniazid: Rifamycin Derivatives may enhance the hepatotoxic effect of Isoniazid. Even so, this is a frequently employed combination regimen. Monitor therapy

Istradefylline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Istradefylline. Monitor therapy

Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivacaftor. Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Lapatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lapatinib. Monitor therapy

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Larotrectinib. Monitor therapy

Ledipasvir: Rifapentine may decrease the serum concentration of Ledipasvir. Avoid combination

Lefamulin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lemborexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lemborexant. Avoid combination

Lorlatinib: CYP3A4 Inducers (Moderate) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, monitor AST, ALT, and bilirubin within 48 hours of starting the combination and at least three times within the first week of combined use. Consider therapy modification

Lumacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumacaftor and Ivacaftor. Monitor therapy

Lumateperone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumateperone. Avoid combination

Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Consider therapy modification

Lurbinectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurbinectedin. Avoid combination

Macitentan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Macitentan. Monitor therapy

Meperidine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Meperidine. Monitor therapy

Methadone: Rifamycin Derivatives may decrease the serum concentration of Methadone. Management: Seek alternatives when possible. If used concomitantly, monitor closely for symptoms of methadone withdrawal upon rifamycin derivative initiation, and for excess sedation upon rifamycin derivative discontinuation. Consider therapy modification

MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of MethylPREDNISolone. Monitor therapy

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil. Monitor therapy

Mycophenolate: Rifamycin Derivatives may decrease the serum concentration of Mycophenolate. Specifically, rifamycin derivatives may decrease the concentration of the active metabolite mycophenolic acid. Avoid combination

Naldemedine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naldemedine. Monitor therapy

Naloxegol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naloxegol. Monitor therapy

Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Avoid combination

Nilotinib: Rifapentine may decrease the serum concentration of Nilotinib. Monitor therapy

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Avoid combination

Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Avoid combination

Oliceridine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Oliceridine. Monitor therapy

Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Monitor therapy

PAZOPanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PAZOPanib. Monitor therapy

Pemigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pemigatinib. Avoid combination

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Monitor perampanel response closely, particularly with changes to CYP3A4 inducer therapy. Consider therapy modification

Pexidartinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pexidartinib. Monitor therapy

Pimavanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pimavanserin. Avoid combination

Pitavastatin: Rifamycin Derivatives may increase the serum concentration of Pitavastatin. Management: Limit pitavastatin dose to a maximum of 2 mg/day with concurrent rifampin. Consider therapy modification

Pitolisant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pitolisant. Monitor therapy

Pralsetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pralsetinib. Monitor therapy

PrednisoLONE (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PrednisoLONE (Systemic). Monitor therapy

PredniSONE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PredniSONE. Monitor therapy

Pretomanid: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pretomanid. Avoid combination

Progestins (Contraceptive): Rifamycin Derivatives may decrease the serum concentration of Progestins (Contraceptive). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Recommendations outside the US recommend doubling the levonorgestrel dose to 3 mg if used for emergency contraception. Consider therapy modification

QuiNIDine: Rifamycin Derivatives may decrease the serum concentration of QuiNIDine. Management: Consider alternatives to combination treatment with quinidine and rifampin due to large potential decreases in quinidine concentrations. Monitor for decreased quinidine concentrations/effects with initiation/dose increase of any rifamycin derivative. Consider therapy modification

Raltegravir: Rifapentine may increase the serum concentration of Raltegravir. Rifapentine may decrease the serum concentration of Raltegravir. Monitor therapy

Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Avoid combination

Rilpivirine: Rifamycin Derivatives may decrease the serum concentration of Rilpivirine. Avoid combination

Rimegepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rimegepant. Avoid combination

Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Monitor therapy

Selpercatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selpercatinib. Avoid combination

Selumetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selumetinib. Avoid combination

Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Avoid combination

Sirolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Sofosbuvir: Rifapentine may decrease the serum concentration of Sofosbuvir. Avoid combination

Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Avoid combination

SUNItinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUNItinib. Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tamoxifen: Rifamycin Derivatives may increase the metabolism of Tamoxifen. Management: Consider alternatives to coadministration of rifampin and tamoxifen. If this combination cannot be avoided, monitor for decrease tamoxifen efficacy. It is unclear if rifapentine or rifabutin would participate in this interaction. Consider therapy modification

Tazemetostat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tazemetostat. Avoid combination

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. Management: Temsirolimus prescribing information recommends against coadministration with strong CYP3A4 inducers such as rifampin; however, if concurrent therapy is necessary, an increase in temsirolimus adult dose to 50 mg/week should be considered. Consider therapy modification

Tenofovir Alafenamide: Rifapentine may decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tezacaftor and Ivacaftor. Monitor therapy

Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ticagrelor. Monitor therapy

Tofacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tofacitinib. Monitor therapy

Tolvaptan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tolvaptan. Monitor therapy

Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Toremifene. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Toremifene. Monitor therapy

Trabectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Trabectedin. Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Consider therapy modification

Ubrogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Consider therapy modification

Upadacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Upadacitinib. Monitor therapy

Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Valbenazine. Monitor therapy

Vandetanib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vandetanib. Monitor therapy

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Vemurafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vemurafenib. Monitor therapy

Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Avoid combination

Vilazodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vilazodone. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Rifamycin Derivatives may decrease the serum concentration of Vitamin K Antagonists. Management: Monitor for reduced anticoagulant effects (ie, decreased INR, thromboembolic events) if a rifamycin derivative is initiated in a vitamin K antagonist treated patient. Vitamin K antagonist dose adjustments will likely be required. Consider therapy modification

Vorapaxar: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vorapaxar. Avoid combination

Vortioxetine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vortioxetine. Monitor therapy

Voxelotor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If concomitant use is unavoidable, increase the voxelotor dose to 2,500 mg once daily. Consider therapy modification

Voxilaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxilaprevir. Avoid combination

Zaleplon: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zaleplon. Monitor therapy

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zanubrutinib. Avoid combination

Zidovudine: Rifamycin Derivatives may decrease the serum concentration of Zidovudine. Monitor therapy

Zolpidem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zolpidem. Monitor therapy

Zopiclone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zopiclone. Monitor therapy

Test Interactions

Rifampin has been shown to inhibit standard microbiological assays for serum folate and vitamin B12; this should be considered for rifapentine; therefore, alternative assay methods should be considered.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency may vary based on treatment phase; adverse reaction data is based on rifapentine combination therapy.

>10%: Hematologic & oncologic: Anemia (≤11%), lymphocytopenia (3% to 11%)

1% to 10%:

Dermatologic: Diaphoresis (2% to 5%), maculopapular rash (2%), pruritus (≤3%), skin rash (3% to 4%)

Gastrointestinal: Abdominal pain (≤1%), anorexia (3% to 4%), diarrhea (≤1%), dyspepsia (≤2%), nausea (≤2%), vomiting (≤2%)

Genitourinary: Uremia (1% to 3%)

Hematologic & oncologic: Leukocytosis (2%), lymphadenopathy (≤1%), neutropenia (≤9%), thrombocythemia (≤6%), thrombocytopenia (1% to 2%)

Hepatic: Increased serum alanine aminotransferase (2% to 5%), increased serum aspartate aminotransferase (2% to 4%)

Hypersensitivity: Hypersensitivity reaction (4%)

Nervous system: Dizziness (≤1%), headache (≤3%)

Neuromuscular & skeletal: Arthralgia (≤4%), back pain (≤4%)

Ophthalmic: Conjunctivitis (≤2%)

Respiratory: Cough (3% to 6%), hemoptysis (2% to 8%)

Miscellaneous: Fever (≤1%)

<1%:

Cardiovascular: Chest pain, facial edema, orthostatic hypotension, palpitations, pericarditis, syncope, tachycardia, thrombosis

Dermatologic: Skin discoloration, urticaria

Endocrine & metabolic: Gout, hyperglycemia, hyperkalemia, hyperlipidemia

Gastrointestinal: Constipation, decreased appetite, enlargement of salivary glands, esophagitis, gastritis, pancreatitis, xerostomia

Genitourinary: Azotemia, leukorrhea, vaginal hemorrhage, vaginitis, vulvovaginal candidiasis, vulvovaginal pruritus

Hematologic & oncologic: Hematoma, leukopenia, lymphocytosis, purpuric disease

Hepatic: Hepatitis, hepatomegaly, hepatotoxicity, hyperbilirubinemia, increased serum alkaline phosphatase, jaundice

Infection: Fungal infection, viral infection

Nervous system: Anxiety, chills, confusion, depression, disorientation, drowsiness, fatigue, jitteriness, paresthesia, peripheral neuropathy, seizure, suicidal ideation, voice disorder

Neuromuscular & skeletal: Asthenia, myalgia, myositis, rhabdomyolysis

Respiratory: Asthma, bronchospasm, dyspnea, epistaxis, laryngeal edema, laryngitis, oropharyngeal pain, pharyngitis, pneumonitis, pulmonary fibrosis

Postmarketing:

Dermatologic: Stevens-Johnson syndrome

Gastrointestinal: Clostridioides difficile associated diarrhea

Hypersensitivity: Anaphylaxis

Immunologic: Drug reaction with eosinophilia and systemic symptoms

Warnings/Precautions

Concerns related to adverse effects:

• Dermatologic reactions: Cases of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms syndrome have been reported. Discontinue treatment immediately and institute appropriate therapy if signs or symptoms of SCAR develop.

• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, may occur. Discontinue therapy and administer supportive measures if hypersensitivity occurs.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Hepatic impairment: Patients with abnormal liver tests and/or liver disease should only be given rifapentine when absolutely necessary and under strict medical supervision. Monitoring of liver function tests (eg, serum transaminases) should be carried out prior to therapy and then every 2 to 4 weeks during therapy. Combination therapy should be discontinued if ALT is ≥5 times the upper limit of normal (ULN) even in the absence of liver dysfunction symptoms or ≥3 times ULN in the presence of symptoms (CDC 2012).

• Porphyria: Use is not recommended in patients with porphyria; exacerbation is possible due to enzyme-inducing properties.

Special populations:

• HIV-seropositive patients: Use of rifapentine during the initial phase of treatment in HIV-seropositive patients has not been evaluated. Rifapentine should not be used during the continuation phase of treatment in HIV-seropositive patients; a higher rate of failure and/or relapse with rifampin-resistant organisms has been reported.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Appropriate use: Use with caution in patients with cavitary pulmonary lesions and/or positive sputum cultures after initial treatment phase and patients with bilateral pulmonary disease; higher relapse rates may occur in these patients.

• Compliance: Compliance with dosing regimen is absolutely necessary for successful drug therapy.

• Contact lenses: Remove soft contact lenses during therapy since permanent staining may occur.

• Red/orange discoloration: Urine, feces, saliva, sweat, tears, skin, teeth, tongue, and CSF may be discolored to red/orange. Advise patients with dentures that permanent staining of dentures may occur.

Monitoring Parameters

Patients with preexisting hepatic problems should have liver function tests monitored (eg, serum transaminases) prior to therapy and then every 2 to 4 weeks during therapy. In treatment of latent infection with rifapentine and isoniazid combination therapy, patients with HIV infection, liver disorders, immediate postpartum (≤ 3 months after delivery), or regular ethanol use should have liver function (at least alanine aminotransferase [ALT]) monitored prior to therapy and then at subsequent clinical visits whose baseline testing is abnormal or for others at risk for liver disease (CDC, 2012).

Reproductive Considerations

Rifapentine may reduce the efficacy of hormonal contraceptives; nonhormonal contraception or the addition of a barrier method of contraception is recommended. Because rifapentine is not currently recommended for use during pregnancy, patients taking rifapentine should notify their healthcare provider if they wish to become pregnant (CDC [Borisov 2018]).

Pregnancy Considerations

Information related to the use of rifapentine during pregnancy is limited (Moro 2018). Rifapentine may increase the risk of maternal postpartum hemorrhage and neonatal bleeding when exposure occurs near delivery. Monitoring of the prothrombin time in the mother and neonate is recommended following exposure late in pregnancy; treatment with vitamin K may be needed.

Active tuberculosis infection is associated with adverse fetal outcomes, including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020), as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020). Because information related to the use of rifapentine in pregnancy is limited, it is not currently recommended for use in pregnant patients (CDC [Borisov 2018]; WHO 2020).

Patient Education

What is this drug used for?

• It is used to treat TB (tuberculosis).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Not hungry

• Joint pain

• Body tissue or body fluid discoloration

• Denture discoloration

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes

• Abnormal heartbeat

• Feeling very tired or weak

• Chills

• Sore throat

• Bruising

• Bleeding

• Chest pain

• Fast heartbeat

• Dizziness

• Passing out

• Flu-like symptoms

• Muscle pain

• Swollen glands

• Cough

• Eye redness

• Shortness of breath

Clostridioides (formerly Clostridium) difficile-associated diarrhea like stomach pain or cramps, severe diarrhea or watery stools, or bloody stools

Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.