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Rifapentine


General


Pronunciation

(rif a PEN teen)


Brand Names: U.S.

  • Priftin

Indications


Use: Labeled Indications

Active pulmonary tuberculosis: 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.

Latent tuberculosis 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 and Administration


Dosing: Adult

Active pulmonary tuberculosis: Oral: Rifapentine should not be used alone; initial phase should include a 3- to 4-drug regimen

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

Continuation phase: 600 mg once weekly by DOT for 4 months

Latent tuberculosis infection: Oral: Use once weekly for 3 months; Note: Must be administered under DOT and given in combination with isoniazid (maximum dose: 900 mg).

25.1 to 32 kg: 600 mg

32.1 to 50 kg: 750 mg

>50 kg: 900 mg


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Active pulmonary tuberculosis: Children ≥12 years and Adolescents: Oral: Refer to adult dosing.

Latent tuberculosis infection: Children ≥2 years and Adolescents: Oral: Use once weekly for 3 months; Note: Must be administered under direct observation therapy (DOT) and given in combination with isoniazid (maximum dose: 900 mg):

10 to 14 kg: 300 mg

14.1 to 25 kg: 450 mg

25.1 to 32 kg: 600 mg

32.1 to 50 kg: 750 mg

>50 kg: 900 mg


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied).


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer 's labeling; use with caution. Pharmacokinetics in varying degrees of hepatic impairment were similar to those in healthy volunteers.


Administration

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.


Dosage Forms/Strengths


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]


Drug Interactions

Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate. Management: Avoid whenever possible. If such a combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during concomitant use. Avoid combination

Alfentanil: Rifamycin Derivatives may decrease the serum concentration of Alfentanil. Management: Monitor closely for decreased alfentanil effectiveness. Increased alfentanil doses will likely be needed. Alternatively, changing from alfentanil to a different opioid anesthetic (e.g., sufentanil) may also be considered. 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 (Strong) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination

Apixaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban. Avoid combination

Apremilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast. Avoid combination

Aprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Aprepitant. Avoid combination

ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor response. Reduce oral aripiprazole dose to 10-15 mg/day (for adults) if the inducer is discontinued. Avoid use of CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Consider therapy modification

ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Patients taking the 441 mg dose of aripiprazole lauroxil increase their dose to 662 mg if used with a strong CYP3A4 inducer for more than 14 days. No dose adjustment is necessary for patients using the 662 mg or 882 mg doses of aripiprazole lauroxil. Consider therapy modification

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. Avoid combination

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

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

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

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

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

Beta-Blockers: Rifamycin Derivatives may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Carteolol (Ophthalmic); Levobunolol; Metipranolol; Nadolol. Monitor therapy

Boceprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Boceprevir. Avoid combination

Bortezomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. Avoid combination

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

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. Monitor therapy

Brexpiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brexpiprazole. Management: If brexpiprazole is used together with a strong CYP3A4 inducer, the brexpiprazole dose should gradually be doubled over the course of 1 to 2 weeks. Consider therapy modification

Buprenorphine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Buprenorphine. Monitor therapy

BusPIRone: Rifamycin Derivatives may decrease the serum concentration of BusPIRone. Management: The degree to which rifampin alters buspirone concentrations warrants the consideration of an alternative to buspirone that is not metabolized by CYP3A4. If these agents are used together, buspirone dose adjustments may be needed. Consider therapy modification

Cabozantinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. Consider therapy modification

Calcifediol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcifediol. 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 contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Exceptions: Clevidipine. Consider therapy modification

Cannabidiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol. Monitor therapy

Cannabis: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Monitor therapy

Cariprazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cariprazine. Avoid combination

Ceritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib. Avoid combination

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. 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 may impair clarithromycin efficacy. Consider therapy modification

Clopidogrel: Rifamycin Derivatives may enhance the adverse/toxic effect of Clopidogrel. Specifically,clopidogrel antiplatelet effects may be enhanced. Monitor therapy

CloZAPine: CYP3A4 Inducers (Strong) may decrease the serum concentration of CloZAPine. Avoid combination

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

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

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

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

Corticosteroids (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Corticosteroids (Systemic). Exceptions: Hydrocortisone (Systemic); PrednisoLONE (Systemic); PredniSONE. Monitor therapy

Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. Avoid combination

CycloSPORINE (Systemic): Rifamycin Derivatives may increase the metabolism of CycloSPORINE (Systemic). Consider therapy modification

CYP2C8 Substrates: CYP2C8 Inducers (Strong) may increase the metabolism of CYP2C8 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP2C9 Substrates: CYP2C9 Inducers (Strong) may increase the metabolism of CYP2C9 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Substrates: CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Exceptions: Buprenorphine; Etizolam; HYDROcodone. Consider therapy modification

Dabrafenib: CYP2C8 Inducers (Strong) may decrease the serum concentration of Dabrafenib. Avoid combination

Dabrafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dabrafenib. Avoid combination

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): Rifamycin Derivatives may increase the metabolism of Dapsone (Systemic). Consider therapy modification

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

Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Consider therapy modification

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 (Strong) may decrease the serum concentration of Dexamethasone (Systemic). Management: Consider dexamethasone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Consider therapy modification

Diclofenac (Systemic): CYP2C9 Inducers (Strong) may decrease the serum concentration of Diclofenac (Systemic). Monitor therapy

Dienogest: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest. Management: Avoid use of dienogest for contraception when using medications that induce CYP3A4 and for at least 28 days after discontinuation of a CYP3A4 inducer. An alternative form of contraception should be used during this time. Avoid combination

Doxercalciferol: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy

DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inducers in patients treated with doxorubicin. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Dronabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronabinol. Monitor therapy

Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Avoid combination

Eliglustat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat. Avoid combination

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

Enzalutamide: CYP2C8 Inducers (Strong) may decrease the serum concentration of Enzalutamide. Avoid combination

Enzalutamide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Enzalutamide. Management: Consider using an alternative agent that has no or minimal CYP3A4 induction potential when possible. If this combination cannot be avoided, increase the dose of enzalutamide from 160 mg daily to 240 mg daily. Avoid combination

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

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

Etizolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etizolam. Monitor therapy

Etoposide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide. If these combinations cannot be avoided, monitor patients closely for diminished etoposide response. Consider therapy modification

Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response. Consider therapy modification

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

Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers, but if strong CYP3A4 inducers cannot be avoided, consider gradually (in 5 mg increments) increasing the everolimus dose from 10 mg/day to 20 mg/day (adult doses). Avoid combination

Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Exemestane U.S. product labeling recommends using an increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers. The Canadian product labeling does not recommend a dose adjustment with concurrent use of strong CYP3A4 inducers. Consider therapy modification

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

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

Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Consider therapy modification

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

GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating concomitant therapy with strong CYP3A4 inducers. Increase guanfacine dose gradually over 1-2 weeks if strong CYP3A4 inducer therapy is just beginning. Consider therapy modification

HMG-CoA Reductase Inhibitors: Rifamycin Derivatives may decrease the serum concentration of HMG-CoA Reductase Inhibitors. 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. Exceptions: Pitavastatin; Rosuvastatin. Consider therapy modification

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

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

Ibrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib. Avoid combination

Idelalisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib. Avoid combination

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. 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 patients clinical response closely. Consider therapy modification

Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with strong CYP3A4 inducers 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

Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan Products. Avoid combination

Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Avoid combination

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

Itraconazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole. Avoid combination

Ivabradine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine. Avoid combination

Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor. Avoid combination

Ixabepilone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m2 to 60 mg/m2 (given as a 4-hour infusion), as tolerated, should be considered. Consider therapy modification

Ixazomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixazomib. Avoid combination

Lapatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Avoid combination

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

Linagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Linagliptin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Consider therapy modification

Lumefantrine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumefantrine. Avoid combination

Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Avoid combination

Macitentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan. Avoid combination

Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with CrCl less than 30 mL/min. Consider therapy modification

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 (Strong) may decrease the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Consider therapy modification

MiFEPRIStone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MiFEPRIStone. Avoid combination

Mirodenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mirodenafil. Management: Consider avoiding the concomitant use of mirodenafil and strong CYP3A4 inducers. If combined, monitor for decreased mirodenafil effects. Mirodenafil dose increases may be required to achieve desired effects. Consider therapy modification

Morphine (Systemic): Rifamycin Derivatives may decrease the serum concentration of Morphine (Systemic). 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

Naloxegol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol. Avoid combination

Netupitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant. Avoid combination

NIFEdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine. Avoid combination

Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Avoid combination

NiMODipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NiMODipine. Avoid combination

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

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

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: CYP2C8 Inducers (Strong) may decrease the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the serum concentrations of dasabuvir may decrease significantly. Avoid combination

Osimertinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Osimertinib. Avoid combination

Palbociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib. Avoid combination

Panobinostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat. Avoid combination

PAZOPanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PAZOPanib. Avoid combination

Perampanel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Perampanel. Management: Avoid use of perampanel with strong CYP3A inducers other than enzyme-inducing antiepileptic drugs (EIAEDs). Increase perampanel starting dose to 4 mg/day when used with EIAEDs such as phenytoin, carbamazepine, or oxcarbazepine. Avoid combination

Pimavanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pimavanserin. Monitor therapy

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

PONATinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PONATinib. Avoid combination

Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Management: Avoid concomitant use of praziquantel with strong CYP3A4 inducers. Discontinue rifampin 4 weeks prior to initiation of praziquantel therapy. Rifampin may be resumed the day following praziquantel completion. Avoid combination

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

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

Propafenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Propafenone. Monitor therapy

QUEtiapine: CYP3A4 Inducers (Strong) may decrease the serum concentration of QUEtiapine. Management: Quetiapine dose increases to as much as 5 times the regular dose may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7-14 days of discontinuing the inducer. 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

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

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

Reboxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Reboxetine. Monitor therapy

Regorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib. Avoid combination

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

Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban. Avoid combination

Roflumilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast. Management: Roflumilast U.S. prescribing information recommends against combining strong CYP3A4 inducers with roflumilast. The Canadian product monograph makes no such recommendation but notes that such agents may reduce roflumilast therapeutic effects. Avoid combination

Rolapitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rolapitant. Management: Avoid rolapitant use in patients requiring chronic administration of strong CYP3A4 inducers. Monitor for reduced rolapitant response and the need for alternative or additional antiemetic therapy even with shorter-term use of such inducers. Consider therapy modification

RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. Avoid combination

SAXagliptin: CYP3A4 Inducers may decrease the serum concentration of SAXagliptin. Monitor therapy

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

Sirolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sirolimus. Management: Avoid concomitant use of strong CYP3A4 inducers and sirolimus if possible. If combined, monitor for reduced serum sirolimus concentrations. Sirolimus dose increases will likely be necessary to prevent subtherapeutic sirolimus levels. Consider therapy modification

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

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

SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. Avoid combination

SUNItinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing sunitinib dose and monitor clinical response and toxicity closely. Consider therapy modification

Suvorexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Suvorexant. Avoid combination

Tacrolimus (Systemic): Rifamycin Derivatives may decrease the serum concentration of Tacrolimus (Systemic). Management: Consider alternatives when possible. If these combination are used, monitor for reduced tacrolimus concentrations/effects following rifamycin initiation/dose increase, or increased concentrations/effects following rifamycin discontinuation/dose decrease. Consider therapy modification

Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Consider therapy modification

Tamoxifen: Rifamycin Derivatives may increase the metabolism of Tamoxifen. Consider therapy modification

Tasimelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon. Avoid combination

Telaprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Telaprevir. 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

Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol. Monitor therapy

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. Avoid combination

Tofacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib. Avoid combination

Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: If concurrent use is necessary, increased doses of tolvaptan (with close monitoring for toxicity and clinical response) may be needed. Avoid combination

Toremifene: CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene. Avoid combination

Trabectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin. Avoid combination

Treprostinil: CYP2C8 Inducers (Strong) may decrease the serum concentration of Treprostinil. Monitor therapy

Tropisetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tropisetron. Monitor therapy

Udenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Udenafil. Monitor therapy

Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Avoid combination

Vandetanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Avoid combination

Velpatasvir: CYP2C8 Inducers (Strong) may decrease the serum concentration of Velpatasvir. Avoid combination

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

Vemurafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Avoid combination

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

Vilazodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vilazodone. Management: Consider increasing vilazodone dose by as much as 2-fold (do not exceed 80 mg/day), based on response, in patients receiving strong CYP3A4 inducers for > 14 days. Reduce to the original vilazodone dose over 1-2 weeks after inducer discontinuation. Consider therapy modification

VinCRIStine (Liposomal): CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vinflunine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinflunine. Avoid combination

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

Voriconazole: May increase the serum concentration of Rifamycin Derivatives. Rifamycin Derivatives may decrease the serum concentration of Voriconazole. Avoid combination

Vortioxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vortioxetine. Management: Consider increasing the vortioxetine dose to no more than 3 times the original dose when used with a strong drug metabolism inducer for more than 14 days. The vortioxetine dose should be returned to normal within 14 days of stopping the strong inducer. Consider therapy modification

Zaleplon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zaleplon. Management: Consider the use of an alternative hypnotic that is not metabolized by CYP3A4 in patients receiving strong CYP3A4 inducers. If zalephon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Consider therapy modification

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

Zolpidem: Rifamycin Derivatives may decrease the serum concentration of Zolpidem. Management: Seek alternatives. If used together, monitor for decreased therapeutic effects of zolpidem if a rifamycin derivative is initiated/dose increased, or increased effects if a rifamycin derivative is discontinued/dose decreased. Consider therapy modification

Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. Monitor therapy


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).


Lab Test Interferences


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


Frequency may vary based on treatment phase; adverse reaction data is based on rifapentine combination therapy.

>10%:

Endocrine & metabolic: Hyperuricemia ( ≤32%; most likely due to pyrazinamide from initiation phase)

Genitourinary: Pyuria (11% to 22%), hematuria (10% to 18%), urinary tract infection (7% to 13%)

Hematologic & oncologic: Neutropenia (6% to 13%), lymphocytopenia (3% to 13%), anemia (2% to 11%)

1% to 10%:

Cardiovascular: Chest pain (3% to 6%), edema (1%)

Central nervous system: Pain (3% to 6%), headache ( ≤3%), dizziness ( ≤1%), fatigue ( ≤1%)

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

Endocrine & metabolic: Hypoglycemia (5% to 10%), hyperglycemia (1% to 4%), increased nonprotein nitrogen (1% to 3%), gout (1%), hyperphosphatemia (1%)

Gastrointestinal: Anorexia (3% to 4%), nausea ( ≤3%), constipation (1% to 2%), dyspepsia (1% to 2%), abdominal pain ( ≤2%), diarrhea ( ≤2%), vomiting ( ≤2%), hemorrhoids (1%)

Genitourinary: Casts in urine (4% to 8%), cystitis (1%)

Hematologic & oncologic: Leukopenia (4% to 7%), thrombocytosis ( ≤6%), leukocytosis (2% to 3%), neutrophilia (1% to 3%), thrombocythemia (1% to 3%), polycythemia ( ≤2%), lymphadenopathy ( ≤1%)

Hepatic: Increased serum ALT (2% to 7%), increased serum AST (2% to 6%), hepatotoxicity ( ≤2%)

Hypersensitivity: Hypersensitivity reaction ( ≤4%; children & adolescents 1%)

Infection: Influenza (3% to 8%), herpes zoster (1%), infection (1%)

Neuromuscular & skeletal: Back pain (4% to 7%), arthralgia ( ≤4%), osteoarthrosis (1%), tremor (1%)

Ophthalmic: Conjunctivitis ( ≤3%)

Respiratory: Hemoptysis (2% to 8%), cough (3% to 6%), bronchitis (3%), pharyngitis (1% to 2%), epistaxis (1%), pleurisy (1%)

Miscellaneous: Accidental injury (1% to 5%), fever ( ≤1%)

<1% (Limited to important or life-threatening): Ageusia, allergic skin reaction, alopecia, anaphylaxis, asthma, azotemia, confusion, convulsions, depression, diabetes mellitus, disorientation, dysuria, enlargement of salivary glands, erythematous rash, esophagitis, fungal infection, gastritis, hematoma, hepatitis, hepatomegaly, hyperbilirubinemia, hypercalcemia, hyperhidrosis, hyperkalemia, hyperlipidemia, increased blood urea nitrogen, increased serum alkaline phosphatase, jitteriness, laryngeal edema, laryngitis, leukorrhea, lymphocytosis, myalgia, myasthenia, myositis, oropharyngeal pain, orthostatic hypotension, palpitations, pancreatitis, paresthesia, pericarditis, peripheral neuropathy, pneumonitis, pulmonary fibrosis, pulmonary tuberculosis (exacerbation), purpura, pyelonephritis, rhabdomyolysis, seizure, skin discoloration, suicidal ideation, syncope, tachycardia, thrombosis, urinary incontinence, vaginal hemorrhage, vaginitis, viral infection, voice disorder, vulvovaginal candidiasis, weight gain, weight loss


Warnings/Precautions


Concerns related to adverse effects:

- 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.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

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.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Information related to the use of rifapentine in pregnant women is limited. Postnatal hemorrhages have been reported in the infant and mother with rifampin (another rifamycin) administration during the last few weeks of pregnancy. Due to the risk of tuberculosis to the fetus, treatment is recommended when the probability of maternal disease is moderate to high. The CDC does not recommend rifapentine as part of the treatment regimen due to insufficient data in pregnant women (CDC, 2003).


Actions


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%.


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)


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%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience diarrhea, lack of appetite, joint pain, nausea, vomiting, body tissue or body fluid discoloration, or denture discoloration. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), arrhythmia, severe loss of strength and energy, bruising, bleeding, angina, tachycardia, severe dizziness, passing out, flu-like symptoms, muscle pain, eye irritation, eye redness, shortness of breath, enlarged lymph nodes, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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