.png?width=200&height=94&name=PDR_stacked_purple%20(002).png)
Priftin
Classes
Antibiotics for Tuberculosis
Rifamycin Antibiotics
Administration
Directly observed therapy (DOT) is recommended.[28483] [34362] [61094] [65588]
Administer with food to increase bioavailability and reduce nausea, vomiting, and/or gastrointestinal upset.[28483
Tablets may be crushed and added to semi-solid food for those patients unable to swallow tablets whole; consume immediately.[28483]
Adverse Reactions
hepatotoxicity / Delayed / 0.2-1.5
pancreatitis / Delayed / 0-1.0
thrombosis / Delayed / 0-1.0
pulmonary fibrosis / Delayed / 0-1.0
laryngeal edema / Rapid / 0-1.0
bronchospasm / Rapid / 0-1.0
spontaneous fetal abortion / Delayed / 0-1.0
pericarditis / Delayed / 0-1.0
angioedema / Rapid / 0-1.0
azotemia / Delayed / 0-0.5
hyperkalemia / Delayed / 0-0.5
seizures / Delayed / 0-0.5
suicidal ideation / Delayed / 0-0.5
rhabdomyolysis / Delayed / 0-0.5
C. difficile-associated diarrhea / Delayed / Incidence not known
porphyria / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
anemia / Delayed / 0-11.4
lymphopenia / Delayed / 3.2-10.5
neutropenia / Delayed / 0-8.5
hemoptysis / Delayed / 1.9-7.5
thrombocytosis / Delayed / 0.3-5.5
elevated hepatic enzymes / Delayed / 2.2-5.0
conjunctivitis / Delayed / 0-2.2
thrombocytopenia / Delayed / 1.3-1.7
lymphadenopathy / Delayed / 0-1.1
esophagitis / Delayed / 0-1.0
gastritis / Delayed / 0-1.0
hepatomegaly / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
hyperbilirubinemia / Delayed / 0-1.0
hematoma / Early / 0-1.0
lymphocytosis / Delayed / 0-1.0
pneumonitis / Delayed / 0-1.0
dyspnea / Early / 0-1.0
dysphonia / Delayed / 0-1.0
confusion / Early / 0-1.0
vaginitis / Delayed / 0-1.0
vaginal bleeding / Delayed / 0-1.0
palpitations / Early / 0-1.0
sinus tachycardia / Rapid / 0-1.0
orthostatic hypotension / Delayed / 0-1.0
hepatitis / Delayed / 0.6-0.6
constipation / Delayed / 0-0.5
candidiasis / Delayed / 0-0.5
hyperlipidemia / Delayed / 0-0.5
hyperglycemia / Delayed / 0-0.5
leukopenia / Delayed / 0.5-0.5
chest pain (unspecified) / Early / 0-0.5
peripheral neuropathy / Delayed / 0-0.5
depression / Delayed / 0-0.5
gout / Delayed / 0-0.5
pseudomembranous colitis / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
cough / Delayed / 0-5.8
diaphoresis / Early / 1.6-5.3
back pain / Delayed / 0-4.2
rash / Early / 0-4.2
anorexia / Delayed / 2.5-3.9
arthralgia / Delayed / 0-3.6
headache / Early / 0-3.0
pruritus / Rapid / 0-2.8
nausea / Early / 0-1.9
vomiting / Early / 0-1.7
dyspepsia / Early / 0-1.7
leukocytosis / Delayed / 1.6-1.7
maculopapular rash / Early / 0-1.7
diarrhea / Early / 0-1.4
fever / Early / 0-1.4
dizziness / Early / 0-1.4
abdominal pain / Early / 0-1.3
infection / Delayed / 0-1.0
purpura / Delayed / 0-1.0
asthenia / Delayed / 0-1.0
laryngitis / Delayed / 0-1.0
drowsiness / Early / 0-1.0
anxiety / Delayed / 0-1.0
myalgia / Early / 0-1.0
leukorrhea / Delayed / 0-1.0
syncope / Early / 0-1.0
urticaria / Rapid / 0-1.0
xerostomia / Early / 0-0.5
pharyngitis / Delayed / 0-0.5
chills / Rapid / 0-0.5
fatigue / Early / 0-0.5
epistaxis / Delayed / 0-0.5
paresthesias / Delayed / 0-0.5
hyperhidrosis / Early / 0-0.5
contact lens discoloration / Delayed / Incidence not known
urine discoloration / Early / Incidence not known
skin discoloration / Delayed / Incidence not known
Common Brand Names
Priftin
Dea Class
Rx
Description
Oral cyclopentyl rifamycin antimycobacterial drug
Used for treatment of active pulmonary tuberculosis (TB) in combination with 1 or more anti-TB drugs and treatment of latent TB infection in patients at high risk of progression to TB disease
Hepatotoxicity and drug-drug interactions may limit use
Dosage And Indications
10 to 20 mg/kg/dose PO once weekly. Guidelines recommend against rifapentine use except in rare circumstances where more than once-weekly directly observed therapy is difficult to achieve in persons without HIV or cavitation on chest radiography.[61094] The FDA-approved dose is 600 mg PO twice weekly for 2 months, then 600 mg PO once weekly for 4 months.[28483]
10 to 20 mg/kg/dose PO once weekly. Guidelines recommend against rifapentine use except in rare circumstances where more than once-weekly directly observed therapy is difficult to achieve in persons without HIV or cavitation on chest radiography.[61094] The FDA-approved dose is 600 mg PO twice weekly for 2 months, then 600 mg PO once weekly for 4 months.[28483]
1,200 mg PO once daily for 17 weeks. In persons living with HIV, this regimen can be used in persons who have a CD4 count of 100 cells/mm3 or more and are receiving or planning to initiate efavirenz as part of their antiretroviral therapy in the absence of any other known drug-interactions.
1,200 mg PO once daily for 17 weeks. In persons living with HIV, this regimen can be used in persons who have a CD4 count of 100 cells/mm3 or more and are receiving or planning to initiate efavirenz as part of their antiretroviral therapy in the absence of any other known drug-interactions.
900 mg PO once weekly for 3 months. For persons with HIV, rifapentine is only recommended with efavirenz or raltegravir-based antiretroviral regimens.[28483] [34362] [65588]
750 mg PO once weekly for 3 months. For persons with HIV, rifapentine is only recommended with efavirenz or raltegravir-based antiretroviral regimens.
900 mg PO once weekly for 3 months. For persons with HIV, rifapentine is only recommended with efavirenz or raltegravir-based antiretroviral regimens.[28483] [34362] [65588]
750 mg PO once weekly for 3 months. For persons with HIV, rifapentine is only recommended with efavirenz or raltegravir-based antiretroviral regimens.
600 mg PO once weekly for 3 months. For persons with HIV, rifapentine is only recommended with efavirenz or raltegravir-based antiretroviral regimens.
450 mg PO once weekly for 3 months. For persons with HIV, rifapentine is only recommended with efavirenz or raltegravir-based antiretroviral regimens.
300 mg PO once weekly for 3 months. For persons with HIV, rifapentine is only recommended with efavirenz or raltegravir-based antiretroviral regimens.
Dosing Considerations
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Renal ImpairmentSpecific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
Abacavir; Dolutegravir; Lamivudine: (Major) Do not administer rifapentine and dolutegravir together in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance who are receiving twice daily doses of dolutegravir. Additionally, avoid use of once daily rifapentine in any patient receiving dolutegravir. However, once weekly doses of rifapentine may be administered with caution to treatment-naive or treatment-experienced, but INSTI-naive patients receiving once daily dolutegravir. Monitor for virologic efficacy if these drugs are administered concurrently. In a drug interaction study, administration of rifapentine (900 mg once weekly) decreased the AUC and trough concentration of dolutegravir by 26% and 47%, respectively. Dolutegravir is a CYP3A and UGT1A substrate and rifapentine is a strong CYP3A and UGT1A inducer.
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Rifapentine appears to increase the glucuronidation of zidovudine, ZDV similar to other rifamycins. This may cause a decrease in zidovudine AUC. However, the effectiveness of zidovudine against HIV does not appear to be altered. The activity of zidovudine is dependent on the intracellular concentration of the triphosphate metabolite which is not correlated with plasma concentrations of the parent compound. The CDC currently considers the nucleoside reverse transcriptase inhibitors (NRTIs), including zidovudine, compatible for concomitant use with rifamycins (including rifampin, rifabutin and rifapentine). No dosing adjustments are necessary.
Abemaciclib: (Major) Avoid coadministration of rifapentine with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Abiraterone: (Major) Avoid the concomitant use of abiraterone and rifapentine due to the risk of decreased abiraterone efficacy. If concomitant use is unavoidable, increase the abiraterone dosing frequency to twice daily. Resume the previous dose and frequency when rifapentine is discontinued. Abiraterone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and rifapentine. If coadministration cannot be avoided, increase the acalabrutinib dose to 200 mg PO twice daily. Decreased acalabrutinib exposure occurred in a drug interaction study. Acalabrutinib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. In healthy subjects, the Cmax and AUC values of acalabrutinib were decreased by 68% and 77%, respectively, when acalabrutinib was coadministered with another strong inducer.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with rifapentine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifapentine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifapentine is a strong CYP3A4 inducer.
Acetaminophen; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If rifapentine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone concentration; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of oxycodone as needed. If rifapentine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Adagrasib: (Major) Avoid concurrent use of adagrasib and rifapentine due to the risk of decreased adagrasib exposure which may reduce its efficacy. Adagrasib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced adagrasib exposure by more than 66%.
Alfentanil: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with rifamycins is necessary. If the rifamycin is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of CYP3A4 inducers like rifamycins with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Alpelisib: (Major) Avoid coadministration of alpelisib with rifapentine due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer.
Alprazolam: (Moderate) Monitor for reduced efficacy of alprazolam and signs of benzodiazepine withdrawal if coadministration with rifapentine is necessary. Alprazolam is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease alprazolam concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Amiodarone: (Moderate) Monitor for decreased efficacy of amiodarone if coadministration with rifapentine is necessary. Coadministration may decrease amiodarone plasma concentrations. Amiodarone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Amitriptyline: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Atorvastatin: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Benazepril: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Celecoxib: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Olmesartan: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Valsartan: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of omeprazole and rifapentine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. (Major) Consider alternatives to clarithromycin if treatment with rifapentine is necessary as concurrent use may decrease efficacy of clarithromycin. Clarithromycin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers. There have been spontaneous or published reports of CYP3A-based interactions of clarithromycin with another CYP3A4 inducer.
Apremilast: (Major) Coadministration of apremilast with rifapentine is not recommended due to decreased plasma concentrations of apremilast. Apremilast is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the single-dose apremilast AUC and Cmax by 72% and 43%, respectively.
Aprepitant, Fosaprepitant: (Major) Avoid the concurrent use of rifapentine with aprepitant, fosaprepitant due to substantially decreased exposure of aprepitant. After administration, fosaprepitant is rapidly converted to aprepitant; therefore, a similar interaction may be expected. Aprepitant is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased the AUC of aprepitant by approximately 11-fold and decreased the mean terminal half-life by 3-fold.
Aripiprazole: (Major) Recommendations for managing aripiprazole and rifapentine vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; rifapentine is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and rifapentine vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; rifapentine is a strong CYP3A inducer.
Artemether; Lumefantrine: (Contraindicated) Concomitant use of rifapentine and artemether; lumefantrine is contraindicated. Coadministration may lead to decreased artemether; lumefantrine concentrations and possible reduction in antimalarial activity. Artemether; lumefantrine is a substrate of CYP3A4 and rifapentine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer reduced the AUC of artemether and dihydroartemisinin (metabolite of artemether) by 89% and 85%, respectively. (Contraindicated) Concomitant use of rifapentine and artemether; lumefantrine is contraindicated. Rifapentine is a potent inducer of CYP3A4 and both components of artemether; lumefantrine are substrates of this isoenzyme; therefore, coadministration may lead to decreased artemether; lumefantrine concentrations and possible reduction in antimalarial activity.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with rifapentine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifapentine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifapentine is a strong CYP3A4 inducer.
Aspirin, ASA; Omeprazole: (Major) Avoid concomitant use of omeprazole and rifapentine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of oxycodone as needed. If rifapentine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atazanavir: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Atazanavir; Cobicistat: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended. (Major) Coadministration of cobicistat and rifapentine is not recommended as concurrent use may result in significant decreases in the plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Cobicistat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Atogepant: (Major) Avoid use of atogepant and rifapentine when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with rifapentine. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer resulted in a 60% reduction in atogepant overall exposure and a 30% reduction in atogepant peak concentration.
Atovaquone: (Moderate) The administration of rifampin with atovaquone is not recommended, as rifampin is known to reduce atovaquone levels by 52%. Rifapentine may exert similar effects on atovaquone pharmacokinetics, but data are not available. In a small study of HIV-positive subjects, concomitant administration of oral rifampin with atovaquone suspension lead to a substantial decrease in average steady-state plasma atovaquone concentrations and a simultaneous increase in average steady-state plasma rifampin concentrations. The half-life of atovaquone decreased from 82 hours (without rifampin) to 50 hours during rifampin administration.
Atovaquone; Proguanil: (Moderate) The administration of rifampin with atovaquone is not recommended, as rifampin is known to reduce atovaquone levels by 52%. Rifapentine may exert similar effects on atovaquone pharmacokinetics, but data are not available. In a small study of HIV-positive subjects, concomitant administration of oral rifampin with atovaquone suspension lead to a substantial decrease in average steady-state plasma atovaquone concentrations and a simultaneous increase in average steady-state plasma rifampin concentrations. The half-life of atovaquone decreased from 82 hours (without rifampin) to 50 hours during rifampin administration.
Avacopan: (Major) Avoid concomitant use of avacopan and rifapentine due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use of another strong CYP3A inducer decreased avacopan overall exposure by 93%.
Avanafil: (Major) Coadministration of avanafil with rifapentine is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Avapritinib: (Major) Avoid coadministration of avapritinib with rifapentine due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of avapritinib by 92% and 74%, respectively.
Avatrombopag: (Major) In patients with chronic immune thrombocytopenia (ITP), increase the starting dose of avatrombopag to 40 mg PO once daily when used concomitantly with rifapentine. In patients starting rifapentine while receiving avatrombopag, monitor platelet counts and adjust the avatrombopag dose as necessary. Dosage adjustments are not required for patients with chronic liver disease. Avatrombopag is a CYP2C9 and CYP3A4 substrate, and dual moderate or strong inducers such as rifapentine decrease avatrombopag exposure, which may reduce efficacy.
Axitinib: (Major) Avoid coadministration of axitinib with rifapentine due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is a CYP3A4/5 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with a strong CYP3A4/5 inducer significantly decreased the plasma exposure of axitinib in healthy volunteers.
Bedaquiline: (Major) Avoid concurrent use of bedaquiline with rifamycins (e.g., rifampin, rifapentine, and rifabutin). Rifamycins may induce the CYP3A4 metabolism of bedaquiline, resulting in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect. One study found bedaquiline AUC decreased by 52% when administered concurrently with rifampin 600 mg PO daily for 21 days.
Belumosudil: (Major) Increase the dosage of belumosudil to 200 mg PO twice daily when coadministered with rifapentine. Belumosudil is a CYP3A4 substrate and rifapentine is a strong CYP3A inducer; concomitant use may result in decreased belumosudil exposure and reduced belumosudil efficacy. Coadministration with another strong CYP3A inducer decreased belumosudil exposure by 72% in healthy subjects.
Benzhydrocodone; Acetaminophen: (Moderate) Monitor for reduced efficacy of benzhydrocodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of benzhydrocodone as needed. If rifapentine is discontinued, consider a dose reduction of benzhydrocodone and frequently monitor for signs of respiratory depression and sedation. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of bictegravir and rifapentine as coadministration may result in decreased bictegravir plasma concentrations, which may result in the loss of therapeutic efficacy and development of resistance. Bictegravir is a substrate of CYP3A4; rifapentine is a strong CYP3A4 inducer.
Bortezomib: (Major) Coadministration of rifapentine with bortezomib is not recommended as concurrent use may decrease bortezomib exposure which may lead to decreased efficacy. Bortezomib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer is expected to decrease the exposure of bortezomib by at least 45%.
Bosutinib: (Major) Avoid coadministration of bosutinib with rifapentine as concurrent use may decrease bosutinib exposure which may lead to decreased efficacy. Bosutinib is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased bosutinib exposure by 94%.
Brentuximab vedotin: (Moderate) Monitor for decreased efficacy of brentuximab if coadministration with rifapentine is necessary. Monomethyl auristatin E (MMAE) is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased MMAE exposure by approximately 46%.
Brexpiprazole: (Major) Double the usual dose of brexpiprazole over 1 to 2 weeks if coadministration with rifapentine is necessary. If rifapentine is discontinued, reduce the brexpiprazole dose to the original level over 1 to 2 weeks. Brexpiprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased brexpiprazole exposure by 73%.
Brigatinib: (Major) Avoid coadministration of brigatinib with rifapentine due to decreased plasma exposure to brigatinib which may result in decreased efficacy. Brigatinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of brigatinib by 80% and 60%, respectively.
Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and rifapentine are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; rifapentine is a strong inducer of CYP3A4.
Bupivacaine; Lidocaine: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with rifapentine is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Buprenorphine: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with rifamycins is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If the rifamycin is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and rifamycins are CYP3A4 inducers.
Buprenorphine; Naloxone: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with rifamycins is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If the rifamycin is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and rifamycins are CYP3A4 inducers.
Buspirone: (Moderate) Monitor for decreased efficacy of buspirone if rifapentine is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased buspirone exposure by 89.6%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with rifapentine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifapentine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifapentine is a strong CYP3A4 inducer.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with rifapentine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifapentine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifapentine is a strong CYP3A4 inducer.
Cabotegravir: (Contraindicated) Coadministration of cabotegravir and rifapentine is contraindicated due to the potential for significant decreases in the plasma concentrations of cabotegravir, which may result in potential loss of virologic response and development of resistance. Cabotegravir is a substrate for UGT1A1 and UGT1A9; rifapentine is an inducer of UGT. Coadministration with another UGT inducer decreased cabotegravir exposure by 59%.
Cabotegravir; Rilpivirine: (Contraindicated) Coadministration of cabotegravir and rifapentine is contraindicated due to the potential for significant decreases in the plasma concentrations of cabotegravir, which may result in potential loss of virologic response and development of resistance. Cabotegravir is a substrate for UGT1A1 and UGT1A9; rifapentine is an inducer of UGT. Coadministration with another UGT inducer decreased cabotegravir exposure by 59%. (Contraindicated) Concurrent use of rifapentine and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifapentine is a strong CYP3A4 inducer, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
Cabozantinib: (Major) Avoid coadministration of cabozantinib with rifapentine due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with rifapentine 2 to 3 days after discontinuation of rifapentine. Cabozantinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Capmatinib: (Major) Avoid coadministration of capmatinib and rifapentine due to the risk of decreased capmatinib exposure, which may reduce its efficacy. Capmatinib is a CYP3A substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased capmatinib exposure by 67%.
Capreomycin: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and any of the rifamycins could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
Carbamazepine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of rifapentine; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A4 substrate and rifapentine is a CYP3A4 inducer.
Cariprazine: (Major) Coadministration of cariprazine with rifapentine is not recommended as the net effect of CYP3A4 induction on cariprazine and its metabolites is unclear. Cariprazine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with cariprazine with CYP3A4 inducers has not been evaluated.
Caspofungin: (Moderate) Consider dosing caspofungin as 70 mg IV once daily in adult patients and 70 mg/m2 IV once daily (Max: 70 mg/day) in pediatric patients receiving rifapentine. Coadministration of CYP450 enzyme inducers, such as rifapentine, with caspofungin may reduce the plasma concentrations of caspofungin.
Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of tramadol as needed. If rifapentine is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ceritinib: (Major) Avoid concomitant use of ceritinib with rifapentine as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Chloramphenicol: (Moderate) It may be necessary to adjust the dosage of chloramphenicol if given concurrently with rifapentine. Rifapentine may induce the metabolism of chloramphenicol; coadministration may result in decreased chloramphenicol plasma concentrations.
Chlordiazepoxide; Amitriptyline: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with rifapentine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifapentine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifapentine is a strong CYP3A4 inducer.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with rifamycins is necessary; consider increasing the dose of dihydrocodeine as needed. If the rifamycin is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Rifamycins are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with rifamycins can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If rifapentine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone concentration; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpropamide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
Clarithromycin: (Major) Consider alternatives to clarithromycin if treatment with rifapentine is necessary as concurrent use may decrease efficacy of clarithromycin. Clarithromycin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers. There have been spontaneous or published reports of CYP3A-based interactions of clarithromycin with another CYP3A4 inducer.
Clindamycin: (Moderate) Monitor for loss of clindamycin efficacy with coadministration of rifapentine as concurrent use may decrease clindamycin exposure. Clindamycin is a CYP3A4 substrate; rifapentine is a strong inducer of CYP3A4.
Clomipramine: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Clonazepam: (Moderate) Monitor patients for decreased efficacy and a change in clonazepam dosage requirements when coadministered with rifapentine. Clonazepam is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Clonazepam concentration decreases of approximately 38% have been reported when clonazepam is used with other strong CYP3A4 inducers.
Clozapine: (Major) Coadministration of clozapine with rifapentine is not recommended due to decreased plasma concentrations of clozapine. If concomitant use is unavoidable, the patient should be monitored for loss of efficacy; consider increasing the clozapine dose if necessary. When rifapentine is discontinued, reduce the clozapine dose based on clinical response. Clozapine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Cobicistat: (Major) Coadministration of cobicistat and rifapentine is not recommended as concurrent use may result in significant decreases in the plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Cobicistat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Cobimetinib: (Major) Avoid coadministration of cobimetinib with rifapentine as concurrent use may decrease cobimetinib exposure, which may reduce its efficacy. Cobimetinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Based on simulations, cobimetinib exposure may decrease by 83% when coadministered with a strong CYP3A4 inducer.
Codeine: (Moderate) Concomitant use of codeine with rifapentine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifapentine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifapentine is a strong CYP3A4 inducer.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with rifapentine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifapentine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifapentine is a strong CYP3A4 inducer.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with rifapentine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifapentine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifapentine is a strong CYP3A4 inducer.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with rifapentine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifapentine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifapentine is a strong CYP3A4 inducer.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with rifapentine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If rifapentine is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Rifapentine is a strong CYP3A4 inducer.
Conjugated Estrogens; Medroxyprogesterone: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Copanlisib: (Major) Avoid the concomitant use of copanlisib and rifapentine; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A4 inducer decreased exposure after a single dose of copanlisib by 63%.
Crizotinib: (Major) Avoid coadministration of crizotinib with rifapentine as concurrent use may decrease crizotinib exposure, which may reduce its efficacy. Crizotinib is primarily metabolized by CYP3A4 and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the crizotinib AUC and Cmax at steady state by 84% and 79%, respectively.
Cyclosporine: (Moderate) Closely monitor cyclosporine concentrations and adjust the dose of cyclosporine as appropriate if coadministration with rifamycins is necessary. Concurrent use may decrease cyclosporine exposure resulting in decreased efficacy. Cyclosporine is extensively metabolized by CYP3A4 and has a narrow therapeutic index; rifamycins are CYP3A4 inducers.
Daclatasvir: (Contraindicated) Coadministration of daclatasvir and rifapentine is contraindicated due to decreased daclatasvir exposure resulting in potential loss of virologic control. Daclatasvir is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer reduced the daclatasvir AUC by 79%.
Daprodustat: (Moderate) Monitor for a decrease in daprodustat efficacy during concomitant use of daprodustat and rifapentine. Concomitant use may decrease daprodustat exposure. Daprodustat is a CYP2C8 substrate and rifapentine is a CYP2C8 inducer.
Dapsone: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with rifapentine is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and rifapentine is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Daridorexant: (Major) Avoid concomitant use of daridorexant and rifapentine. Coadministration may decrease daridorexant exposure which may reduce its efficacy. Daridorexant is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use of another strong CYP3A inducer decreased daridorexant overall exposure by over 50%.
Darifenacin: (Moderate) Monitor for decreased efficacy of darifenacin if coadministration with rifamycins is necessary; coadministration may result in decreased plasma concentrations of darifenacin. Rifamycins are CYP3A4 inducers and darifenacin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of darifenacin.
Darunavir: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Darunavir; Cobicistat: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended. (Major) Coadministration of cobicistat and rifapentine is not recommended as concurrent use may result in significant decreases in the plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Cobicistat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended. (Major) Coadministration of cobicistat and rifapentine is not recommended as concurrent use may result in significant decreases in the plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Cobicistat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Dasatinib: (Major) Avoid coadministration of dasatinib and rifapentine due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to rifapentine with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean AUC of dasatinib by 82%.
Deflazacort: (Major) Avoid concomitant use of deflazacort and rifapentine. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; rifapentine is a strong inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
Delavirdine: (Major) Coadministration of delavirdine with rifapentine is not recommended as there is a potential for decreased delavirdine concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Delavirdine is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased delavirdine exposure by 97%.
Desipramine: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Desogestrel; Ethinyl Estradiol: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Dexamethasone: (Moderate) Monitor for decreased efficacy of dexamethasone if coadministration with rifapentine is necessary; consider increasing the dose of dexamethasone if clinically appropriate. Dexamethasone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Dexlansoprazole: (Major) Avoid coadministration of dexlansoprazole with rifapentine due to the risk of decreased dexlansoprazole plasma concentrations which may decrease efficacy. Dexlansoprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Dextromethorphan; Quinidine: (Moderate) Monitor for decreased efficacy of quinidine if coadministration with rifapentine is necessary. Concomitant use may result in decreased plasma concentrations of quinidine. Quinidine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Diazepam: (Moderate) Monitor patients for decreased efficacy of diazepam if coadministration with rifapentine is necessary. Concurrent use may decrease diazepam exposure. Diazepam is a CYP3A4 substrate and rifapentine is a CYP3A4 inducer.
Dienogest; Estradiol valerate: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Diltiazem: (Major) Avoid coadministration of diltiazem and rifapentine due to decreased plasma concentrations of diltiazem. Diltiazem is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered diltiazem plasma concentrations to undetectable levels.
Disopyramide: (Moderate) Monitor disopyramide plasma concentrations and for decreased efficacy if coadministered with rifapentine as concurrent use may decrease disopyramide exposure. Disopyramide is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Docetaxel: (Major) Avoid coadministration of docetaxel with rifapentine due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
Dolutegravir: (Major) Do not administer rifapentine and dolutegravir together in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance who are receiving twice daily doses of dolutegravir. Additionally, avoid use of once daily rifapentine in any patient receiving dolutegravir. However, once weekly doses of rifapentine may be administered with caution to treatment-naive or treatment-experienced, but INSTI-naive patients receiving once daily dolutegravir. Monitor for virologic efficacy if these drugs are administered concurrently. In a drug interaction study, administration of rifapentine (900 mg once weekly) decreased the AUC and trough concentration of dolutegravir by 26% and 47%, respectively. Dolutegravir is a CYP3A and UGT1A substrate and rifapentine is a strong CYP3A and UGT1A inducer.
Dolutegravir; Lamivudine: (Major) Do not administer rifapentine and dolutegravir together in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance who are receiving twice daily doses of dolutegravir. Additionally, avoid use of once daily rifapentine in any patient receiving dolutegravir. However, once weekly doses of rifapentine may be administered with caution to treatment-naive or treatment-experienced, but INSTI-naive patients receiving once daily dolutegravir. Monitor for virologic efficacy if these drugs are administered concurrently. In a drug interaction study, administration of rifapentine (900 mg once weekly) decreased the AUC and trough concentration of dolutegravir by 26% and 47%, respectively. Dolutegravir is a CYP3A and UGT1A substrate and rifapentine is a strong CYP3A and UGT1A inducer.
Dolutegravir; Rilpivirine: (Contraindicated) Concurrent use of rifapentine and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifapentine is a strong CYP3A4 inducer, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine. (Major) Do not administer rifapentine and dolutegravir together in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance who are receiving twice daily doses of dolutegravir. Additionally, avoid use of once daily rifapentine in any patient receiving dolutegravir. However, once weekly doses of rifapentine may be administered with caution to treatment-naive or treatment-experienced, but INSTI-naive patients receiving once daily dolutegravir. Monitor for virologic efficacy if these drugs are administered concurrently. In a drug interaction study, administration of rifapentine (900 mg once weekly) decreased the AUC and trough concentration of dolutegravir by 26% and 47%, respectively. Dolutegravir is a CYP3A and UGT1A substrate and rifapentine is a strong CYP3A and UGT1A inducer.
Donepezil: (Moderate) Monitor for decreased efficacy of donepezil if coadministration with rifapentine is necessary. Donepezil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Inducers of CYP3A4 could increase the rate of elimination of donepezil.
Donepezil; Memantine: (Moderate) Monitor for decreased efficacy of donepezil if coadministration with rifapentine is necessary. Donepezil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Inducers of CYP3A4 could increase the rate of elimination of donepezil.
Doravirine: (Contraindicated) Concurrent administration of doravirine and rifapentine is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Contraindicated) Concurrent administration of doravirine and rifapentine is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer.
Doxepin: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Doxorubicin Liposomal: (Major) Avoid coadministration of doxorubicin with rifapentine due to decreased doxorubicin plasma concentrations. Doxorubicin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy.
Doxorubicin: (Major) Avoid coadministration of doxorubicin with rifapentine due to decreased doxorubicin plasma concentrations. Doxorubicin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy.
Doxycycline: (Moderate) According to the manufacturer, doxycycline dosage adjustments may be required if administered concurrently with rifapentine. Rifapentine is an inducer of hepatic isoenzymes CYP3A4 and CYP2C8/9, and although doxycycline is not appreciably metabolized by the liver, its clearance has been shown to be substantially increased when administered in combination with other enzyme inducers, including rifampin.
Dronabinol: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with rifapentine is necessary. Coadministration may decrease the exposure of dronabinol. Dronabinol is a CYP3A4 and CYP2C9 substrate; rifapentine is a strong CYP3A4 inducer and moderate CYP2C9 inducer.
Dronedarone: (Major) Avoid coadministration of dronedarone with rifapentine due to the potential for decreased dronedarone exposure and efficacy. Dronedarone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly decreased dronedarone exposure.
Drospirenone:
Drospirenone; Estetrol: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Drospirenone; Estradiol: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Drospirenone; Ethinyl Estradiol: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Duvelisib: (Major) Avoid coadministration of duvelisib with rifapentine. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; rifapentine is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for seven days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Efavirenz: (Moderate) Monitor for decreased efficacy of efavirenz if coadministered with rifapentine. Concurrent use may decrease the plasma concentrations of efavirenz leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Efavirenz is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for decreased efficacy of efavirenz if coadministered with rifapentine. Concurrent use may decrease the plasma concentrations of efavirenz leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Efavirenz is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for decreased efficacy of efavirenz if coadministered with rifapentine. Concurrent use may decrease the plasma concentrations of efavirenz leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Efavirenz is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Elacestrant: (Major) Avoid concurrent use of elacestrant and rifapentine due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Elagolix: (Moderate) Monitor for decreased efficacy of elagolix if coadministration with rifapentine is necessary. Concurrent use may decrease elagolix exposure. Elagolix is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer.
Elagolix; Estradiol; Norethindrone acetate: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. (Moderate) Monitor for decreased efficacy of elagolix if coadministration with rifapentine is necessary. Concurrent use may decrease elagolix exposure. Elagolix is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer.
Elbasvir; Grazoprevir: (Contraindicated) Concomitant use of grazoprevir and rifapentine is contraindicated. Use of these drugs together is expected to significantly decrease the plasma concentrations of grazoprevir, which may result in decreased virologic response. Grazoprevir is a substrate of CYP34A and rifapentine is a strong CYP3A4 inducer. (Contraindicated) Concurrent administration of rifapentine with elbasvir is contraindicated. Use of these drugs together is expected to significantly decrease the plasma concentrations of elbasvir and may result in decreased virologic response. Elbasvir is a substrate of CYP3A and rifapentine is a strong CYP3A inducer.
Elexacaftor; tezacaftor; ivacaftor: (Major) Coadministration of elexacaftor; tezacaftor; ivacaftor with rifapentine is not recommended as concurrent use may decrease exposure of elexacaftor; tezacaftor; ivacaftor. Elexacaftor, tezacaftor, and ivacaftor are CYP3A4 substrates (ivacaftor is a sensitive substrate); rifapentine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer significantly decreased ivacaftor exposure by 89%; elexacaftor and tezacaftor exposures are expected to also decrease during coadministration of strong CYP3A4 inducers. (Major) Coadministration of ivacaftor with rifapentine is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly decreased ivacaftor exposure by approximately 9-fold. (Major) Do not administer tezacaftor; ivacaftor and rifapentine together; coadministration may reduce the efficacy of tezacaftor; ivacaftor. Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by the concomitant use of rifapentine, a strong CYP3A inducer; both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate). Coadministration of ivacaftor with a strong CYP3A inducer decreased ivacaftor exposure 89%. Tezacaftor exposures can also be expected to decrease significantly during coadministration with strong CYP3A inducers.
Eliglustat: (Major) Avoid coadministration of eliglustat and rifapentine as concurrent use may decrease eliglustat exposure and lead to reduced efficacy. Eliglustat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. During clinical trials, systemic exposures (Cmax and AUC) of eliglustat decreased by approximately 90% in extensive metabolizers and intermediate metabolizers after coadministration of eliglustat 127 mg PO twice daily with another strong CYP3A inducer. Additionally, systemic exposures decreased by approximately 95% after coadministration of eliglustat 84 mg PO twice daily with another strong CYP3A inducer in poor metabolizers.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of cobicistat and rifapentine is not recommended as concurrent use may result in significant decreases in the plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Cobicistat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. (Major) Coadministration of elvitegravir with rifapentine is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is metabolized by CYP3A4 and rifapentine is a strong CYP3A4 inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of cobicistat and rifapentine is not recommended as concurrent use may result in significant decreases in the plasma concentrations of cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Cobicistat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. (Major) Coadministration of elvitegravir with rifapentine is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is metabolized by CYP3A4 and rifapentine is a strong CYP3A4 inducer.
Empagliflozin; Linagliptin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and rifapentine if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and rifapentine is a strong CYP3A inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and rifapentine if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and rifapentine is a strong CYP3A inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Concurrent use of rifapentine and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifapentine is a strong CYP3A4 inducer, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concurrent use of rifapentine and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifapentine is a strong CYP3A4 inducer, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
Encorafenib: (Major) Avoid coadministration of encorafenib and rifapentine due to decreased encorafenib exposure and potential loss of efficacy. Encorafenib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration with CYP3A4 inducers has not been studied with encorafenib; however, in clinical trials, steady-state encorafenib exposures were lower than encorafenib exposures after the first dose, suggesting CYP3A4 auto-induction.
Entrectinib: (Major) Avoid coadministration of entrectinib with rifapentine due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Enzalutamide: (Major) Avoid coadministration of enzalutamide with rifapentine if possible due to the risk of decreased enzalutamide plasma concentrations. If concomitant use is unavoidable, increase the dose of enzalutamide from 160 mg to 240 mg PO once daily. If rifapentine is discontinued, resume the dose of enzalutamide used prior to initiation of rifapentine. Enzalutamide is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the composite AUC of enzalutamide plus N-desmethyl enzalutamide by 37%.
Eravacycline: (Major) Increase the dose of eravacycline to 1.5 mg/kg IV every 12 hours when coadministered with a strong CYP3A inducer, such as rifapentine. Concomitant use of strong CYP3A inducers decreases the exposure of eravacycline, which may reduce its efficacy. When eravacycline was administered with a strong CYP3A inducer, the eravacycline AUC was decreased by 35% and its clearance was increased by 54%.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and rifapentine due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A4 and CYP2C9 substrate and rifapentine is a strong CYP3A4 inducer and moderate CYP2C9 inducer.
Erlotinib: (Major) Avoid coadministration of erlotinib with rifapentine if possible due to the risk of decreased erlotinib efficacy. If concomitant use is unavoidable, increase the dose of erlotinib in 50 mg increments at 2-week intervals as tolerated (maximum dose, 450 mg). Erlotinib is a CYP3A4 substrate, and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased erlotinib exposure by 58% to 80%.
Estradiol; Levonorgestrel: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Estradiol; Norethindrone: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Estradiol; Norgestimate: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Estradiol; Progesterone: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Estrogens affected by CYP3A inducers: (Major) Women taking both estrogens and rifamycins should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed rifamycins. In some cases, it may be advisable for patients to change to non-hormonal methods of birth control during rifamycin therapy. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of rifamycins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on rifamycins, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and rifamycins are a CYP3A4 inducers. Concurrent administration may increase estrogen elimination.
Eszopiclone: (Moderate) Monitor for decreased efficacy of eszopiclone if coadministration with rifapentine is necessary. Eszopiclone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased racemic zopiclone exposure by 80%; a similar effect would be expected with eszopiclone.
Ethinyl Estradiol; Norelgestromin: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Ethinyl Estradiol; Norgestrel: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Etonogestrel: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Etonogestrel; Ethinyl Estradiol: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Etravirine: (Major) Etravirine should not be coadministered with rifapentine, a potent inducer of CYP450 enzymes, as significant decreases in etravirine plasma concentrations and, thus, loss of therapeutic effect could occur.
Everolimus: (Major) Avoid coadministration of everolimus with rifapentine due to the risk of decreased efficacy of everolimus. If concomitant use is unavoidable, coadministration requires a dose increase for some indications and close monitoring for others. For oncology indications and tuberous sclerosis complex (TSC)-associated renal angiomyolipoma, double the daily dose using increments of 5 mg or less; multiple increments may be required. For patients with TSC-associated subependymal giant cell astrocytoma (SEGA) and TSC-associated partial-onset seizures, assess the everolimus whole blood trough concentration 2 weeks after initiation of rifapentine and adjust the dose as necessary to remain in the recommended therapeutic range. Also closely monitor everolimus whole blood trough concentrations in patients receiving everolimus for either kidney or liver transplant and adjust the dose as necessary to remain in the recommended therapeutic range. Everolimus is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC of everolimus by 63%. For indications where everolimus trough concentrations are monitored, the addition of a second strong CYP3A4 inducer in a patient already receiving treatment with a strong CYP3A4 inducer may not require additional dose modification.
Exemestane: (Major) If coadministration of exemestane with rifapentine is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Fedratinib: (Major) Avoid coadministration of fedratinib with rifapentine as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of fedratinib with another strong CYP3A4 inducer decreased the overall exposure of fedratinib by 81%.
Fenfluramine: (Major) Avoid concurrent use of fenfluramine and rifapentine due to the risk of decreased fenfluramine plasma concentrations, which may reduce its efficacy. If concomitant use is necessary, monitor for decreased efficacy and consider increasing fenfluramine dose as needed. If rifapentine is discontinued during fenfluramine maintenance treatment, consider gradual reduction in the fenfluramine dosage to the dose administered prior to rifapentine initiation. Fenfluramine is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if coadministration with rifapentine is necessary. If rifapentine is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a strong CYP3A4 inducer like rifapentine with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Finasteride; Tadalafil: (Major) Avoid coadministration of tadalafil with rifapentine in patients with pulmonary hypertension due to decreased plasma concentrations of tadalafil. In patients with erectile dysfunction and/or benign prostatic hyperplasia, consider the potential for loss of efficacy of tadalafil during concurrent administration of rifapentine due to reduced tadalafil exposure. Tadalafil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased tadalafil exposure by 88%.
Finerenone: (Major) Avoid concurrent use of finerenone and rifapentine due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased overall exposure to finerenone by 90%.
Flibanserin: (Major) Avoid coadministration of flibanserin with rifapentine as concurrent use may decrease flibanserin exposure. Flibanserin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased flibanserin exposure by 95%.
Flurazepam: (Moderate) Monitor patients for decreased efficacy of flurazepam if coadministration with rifapentine is necessary. Concurrent use may decrease flurazepam exposure. Flurazepam is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Food: (Major) Advise patients to avoid cannabis use during rifapentine treatment. Concomitant use may decrease the concentration of some cannabinoids and alter their effects. The cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP3A substrates and rifapentine is a strong CYP3A inducer. Concomitant use of a cannabinoid product containing THC and CBD at an approximate 1:1 ratio with another strong CYP3A inducer decreased THC, 11-OH-THC, and CBD peak exposures by 36%, 87%, and 52% respectively.
Fosamprenavir: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Fostamatinib: (Major) Avoid the concomitant use of fostamatinib with rifapentine. Concurrent use of fostamatinib with rifapentine may decrease exposure to the major active metabolite, R406. R406 is extensively metabolized by CYP3A4; rifapentine is a strong CYP3A4 inducer. Concomitant use of fostamatinib with another strong CYP3A4 inducer decreased R406 AUC by 75% and Cmax by 59%.
Fostemsavir: (Contraindicated) Concomitant use of fostemsavir and rifapentine is contraindicated. Use of these drugs together may significantly decrease the plasma concentrations of temsavir, the active moiety of fostemsavir, thereby increasing the risk for HIV treatment failure or development of viral resistance. Temsavir is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Ganaxolone: (Major) Avoid concurrent use of ganaxolone and rifapentine due to the risk of decreased ganaxolone efficacy. If concomitant use is unavoidable, consider increasing ganaxolone dose without exceeding the maximum daily dose. Ganaxolone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ganaxolone overall exposure by 68%.
Gefitinib: (Major) Increase the dose of gefitinib to 500 mg PO once daily if coadministration with rifapentine is necessary. If rifapentine is discontinued, gefitinib at a dose of 250 mg once daily may be resumed seven days later. Gefitinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer reduced gefitinib exposure by 83%.
Glasdegib: (Major) Avoid coadministration of glasdegib and rifapentine due to the potential for decreased glasdegib exposure and risk of decreased efficacy. Glasdegib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the glasdegib AUC by 70% in a drug interaction study.
Glecaprevir; Pibrentasvir: (Major) When possible, avoid concurrent administration of glecaprevir and rifapentine; consider use of an alternative hepatitis C treatment. Use of these drugs together may decrease the plasma concentration of glecaprevir. Use of another rifamycin with glecaprevir resulted in an 88% decrease in the plasma concentration of glecaprevir. (Major) When possible, avoid concurrent administration of pibrentasvir and rifapentine; consider use of an alternative hepatitis C treatment. Use of these drugs together may decrease the plasma concentration of pibrentasvir. Use of another rifamycin with pibrentasvir resulted in an 87% decrease in the plasma concentration of pibrentasvir.
Glimepiride: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
Glipizide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
Glipizide; Metformin: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
Glyburide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
Glyburide; Metformin: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
Granisetron: (Moderate) Monitor for decreased efficacy of granisetron if coadministration with rifapentine is necessary. Concurrent use may decrease granisetron exposure. Granisetron is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. In a human pharmacokinetic study, coadministration with another strong CYP3A4 inducer increased the total plasma clearance of granisetron by 25%. The clinical significance of this change is not known.
Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If rifapentine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone concentration; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Guanfacine: (Major) A dose increase of extended-release (ER) guanfacine should be considered if coadministration with rifapentine is necessary. Consider doubling the recommended dose of guanfacine if therapy is added to a patient already taking rifapentine; increase the dose of guanfacine over 1 to 2 weeks if rifapentine therapy is added to a patient already taking guanfacine. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased guanfacine exposure by 70%.
Haloperidol: (Moderate) Monitor for decreased efficacy of haloperidol if coadministration with rifapentine is necessary. Coadministration may decrease the exposure of haloperidol. Haloperidol is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased haloperidol plasma concentrations by a mean of 70% and increased mean scores on the Brief Psychiatric Rating Scale from baseline.
Homatropine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If rifapentine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone concentration; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If rifapentine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone concentration; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Ibuprofen: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If rifapentine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone concentration; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If rifapentine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone concentration; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with rifapentine. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Ibrutinib: (Major) Avoid concurrent use of ibrutinib with rifapentine due to decreased plasma concentrations of ibrutinib. Ibrutinib is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ibrutinib exposure by more than 10-fold.
Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of oxycodone as needed. If rifapentine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Idelalisib: (Major) Avoid coadministration of idelalisib with rifapentine due to the risk of decreased idelalisib exposure and reduced efficacy. Idelalisib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased idelalisib exposure by 75%.
Ifosfamide: (Moderate) Closely monitor for increased ifosfamide-related toxicities (e.g., neurotoxicity, nephrotoxicity) if coadministration with rifapentine is necessary; consider adjusting the dose of ifosfamide as clinically appropriate. Ifosfamide is metabolized to its active alkylating metabolites by CYP3A4; rifapentine is a strong CYP3A4 inducer. Concomitant use may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde.
Imatinib: (Major) Avoid coadministration of imatinib and rifapentine if possible due to decreased plasma concentrations of imatinib. If concomitant use is unavoidable, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Imatinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Imipramine: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Indinavir: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Infigratinib: (Major) Avoid concurrent use of infigratinib and rifapentine. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Infigratinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC of infigratinib by 56%.
Irinotecan Liposomal: (Major) Avoid administration of rifapentine during treatment with irinotecan and for at least two weeks prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers substantially reduced exposure to irinotecan or SN-38 in both adult and pediatric patients. An appropriate starting dose for patients taking irinotecan with strong CYP3A4 inducers has not been defined.
Irinotecan: (Major) Avoid administration of rifapentine during treatment with irinotecan and for at least two weeks prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers substantially reduced exposure to irinotecan or SN-38 in both adult and pediatric patients. An appropriate starting dose for patients taking irinotecan with strong CYP3A4 inducers has not been defined.
Isavuconazonium: (Contraindicated) Concomitant use of isavuconazonium with rifapentine is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; rifapentine is a strong inducer of this enzyme. Coadministration with another strong CYP3A4 inducer decreased isavuconazole serum concentrations by 97%.
Isoniazid, INH: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifapentine and isoniazid, INH. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifapentine and isoniazid, INH. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
Isoniazid, INH; Rifampin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifapentine and isoniazid, INH. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
Isradipine: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with rifapentine is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Istradefylline: (Major) Avoid coadministration of istradefylline with rifapentine as istradefylline exposure and efficacy may be reduced. Istradefylline is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Istradefylline exposure was decreased by 81% when administered with a strong inducer in a drug interaction study.
Itraconazole: (Major) The use of rifapentine within 2 weeks of itraconazole therapy is not recommended. If coadministration cannot be avoided, monitor for decreased efficacy of itraconazole and increase the dose of itraconazole as necessary. Itraconazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Ivabradine: (Major) Avoid coadministration of ivabradine and rifapentine due to decreased plasma concentrations of ivabradine. Ivabradine is a CYP3A4 substrate and rifapentine is a CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ivabradine exposure by approximately half.
Ivacaftor: (Major) Coadministration of ivacaftor with rifapentine is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly decreased ivacaftor exposure by approximately 9-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with rifapentine due to decreased plasma concentrations of ivosidenib. Ivosidenib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer is predicted to decrease ivosidenib exposure at steady-state by 33%.
Ixabepilone: (Major) Avoid concurrent use of ixabepilone and rifapentine due to decreased plasma concentrations of ixabepilone, which may reduce its efficacy. If concomitant use is unavoidable, gradually increase the dose of ixabepilone as tolerated from 40 mg/m2 to 60 mg/m2 and infuse over 4 hours; monitor carefully for ixabepilone-related toxicities. Ixabepilone is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased ixabepilone exposure by 43%.
Ixazomib: (Major) Avoid the concomitant use of ixazomib and rifapentine; ixazomib levels may be significantly decreased and its efficacy reduced. Ixazomib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the ixazomib Cmax and AUC by 54% and 74%, respectively.
Ketoconazole: (Major) Avoid rifapentine for 2 weeks prior to and during treatment with ketoconazole. Concomitant use may decrease exposure of ketoconazole and reduce its efficacy. If coadministration cannot be avoided, monitor for decreased efficacy of ketoconazole; a ketoconazole dose increase may be necessary. Ketoconazole is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Rifapentine appears to increase the glucuronidation of zidovudine, ZDV similar to other rifamycins. This may cause a decrease in zidovudine AUC. However, the effectiveness of zidovudine against HIV does not appear to be altered. The activity of zidovudine is dependent on the intracellular concentration of the triphosphate metabolite which is not correlated with plasma concentrations of the parent compound. The CDC currently considers the nucleoside reverse transcriptase inhibitors (NRTIs), including zidovudine, compatible for concomitant use with rifamycins (including rifampin, rifabutin and rifapentine). No dosing adjustments are necessary.
Lansoprazole: (Major) Avoid concomitant use of lansoprazole and rifapentine as lansoprazole exposure may be decreased, reducing its efficacy. Lansoprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of lansoprazole and rifapentine as lansoprazole exposure may be decreased, reducing its efficacy. Lansoprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. (Major) Consider alternatives to clarithromycin if treatment with rifapentine is necessary as concurrent use may decrease efficacy of clarithromycin. Clarithromycin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers. There have been spontaneous or published reports of CYP3A-based interactions of clarithromycin with another CYP3A4 inducer.
Lapatinib: (Major) Avoid coadministration of lapatinib with rifapentine due to decreased plasma concentrations of lapatinib. If concomitant use is unavoidable, gradually titrate the dose of lapatinib from 1,250 mg per day to 4,500 mg per day in patients receiving concomitant capecitabine (HER2-positive metastatic breast cancer), and from 1,500 mg per day to 5,500 mg per day in patients receiving concomitant aromatase inhibitor therapy (HR-positive, HER2-positive breast cancer) based on tolerability. If rifapentine is discontinued, reduce lapatinib to the indicated dose. Lapatinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased lapatinib exposure by 72%.
Larotrectinib: (Major) Avoid coadministration of rifapentine with larotrectinib due to the risk of decreased larotrectinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the dose of larotrectinib. After rifapentine has been discontinued for 3 to 5 elimination half-lives, resume the larotrectinib dose taken prior to initiating rifapentine. Larotrectinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the larotrectinib AUC by 81%.
Ledipasvir; Sofosbuvir: (Major) Avoid coadministration of sofosbuvir with rifapentine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Lefamulin: (Major) Avoid coadministration of lefamulin with rifapentine unless the benefits outweigh the risks as concurrent use may decrease lefamulin exposure and efficacy. Lefamulin is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the mean AUC of lefamulin oral tablets by 72% and the mean AUC of lefamulin injection by 28%.
Lemborexant: (Major) Avoid coadministration of lemborexant and rifapentine as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer.
Lenacapavir: (Major) Avoid concurrent use of lenacapavir and rifapentine due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance. Lenacapavir is a CYP3A substrate and rifapentine is a CYP3A inducer.
Leniolisib: (Major) Avoid concomitant use of leniolisib and rifapentine. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Leuprolide; Norethindrone: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Levamlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Levoketoconazole: (Major) Avoid rifapentine for 2 weeks prior to and during treatment with ketoconazole. Concomitant use may decrease exposure of ketoconazole and reduce its efficacy. If coadministration cannot be avoided, monitor for decreased efficacy of ketoconazole; a ketoconazole dose increase may be necessary. Ketoconazole is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Levonorgestrel: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Levonorgestrel; Ethinyl Estradiol: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Lidocaine: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with rifapentine is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Lidocaine; Epinephrine: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with rifapentine is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Lidocaine; Prilocaine: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with rifapentine is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Linagliptin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and rifapentine if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and rifapentine is a strong CYP3A inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Linagliptin; Metformin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and rifapentine if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and rifapentine is a strong CYP3A inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and rifapentine is contraindicated; concurrent use may decrease lonafarnib exposure, which may reduce its efficacy. Lonafarnib is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the exposure of lonafarnib by 98%.
Lopinavir; Ritonavir: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an al ternative agent is recommended.
Lorlatinib: (Contraindicated) Coadministration of lorlatinib with rifapentine is contraindicated due to the risk severe hepatotoxicity as well as decreased lorlatinib exposure which may reduce its efficacy. Discontinue rifapentine for 3 plasma half-lives prior to initiating therapy with lorlatinib. Lorlatinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased lorlatinib exposure by 85% and caused severe (grade 3 or 4) hepatotoxicity in 83% of patients.
Lumacaftor; Ivacaftor: (Major) Coadministration of ivacaftor with rifapentine is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly decreased ivacaftor exposure by approximately 9-fold. (Major) Concomitant use of lumacaftor; ivacaftor and rifapentine is not recommended. Rifapentine may decrease the therapeutic effect of lumacaftor; ivacaftor by significantly decreasing the systemic exposure of ivacaftor. Ivacaftor is a substrate of CYP3A4, and rifapentine is a strong CYP3A4 inducer. In a pharmacokinetic study, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inducer decreased ivacaftor exposure by 57%, with minimal effect on the exposure of lumacaftor.
Lumacaftor; Ivacaftor: (Major) Concomitant use of lumacaftor; ivacaftor and rifapentine is not recommended. Rifapentine may decrease the therapeutic effect of lumacaftor; ivacaftor by significantly decreasing the systemic exposure of ivacaftor. Ivacaftor is a substrate of CYP3A4, and rifapentine is a strong CYP3A4 inducer. In a pharmacokinetic study, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inducer decreased ivacaftor exposure by 57%, with minimal effect on the exposure of lumacaftor.
Lumateperone: (Major) Avoid coadministration of lumateperone and rifapentine as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of lumateperone with a strong CYP3A4 inducer decreased lumateperone overall exposure by greater than 30-fold.
Lurasidone: (Contraindicated) Coadministration of lurasidone with rifapentine is contraindicated due to decreased plasma concentrations of lurasidone. Lurasidone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased lurasidone exposure by 83%.
Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and rifapentine due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Macimorelin: (Major) Discontinue rifapentine and allow a sufficient washout period to pass before administering macimorelin. Use of these drugs together can significantly decrease macimorelin plasma concentrations and may result in a false positive test for growth hormone deficiency. No drug-drug interaction studies have been conducted; however, macimorelin is primarily metabolized by CYP3A4 and rifapentine is a strong CYP3A4 inducer.
Macitentan: (Major) Avoid coadministration of macitentan with rifapentine due to the risk of decreased macitentan exposure which may lead to reduced efficacy. Macitentan is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Maraviroc: (Major) The HIV guidelines recommend avoiding coadministration of maraviroc and rifapentine as decreased concentrations of maraviroc are expected. Maraviroc is a substrate of CYP3A and rifapentine is a CYP3A4 inducer. However, if the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected. Monitor for decreased efficacy if coadministration is necessary.
Maribavir: (Major) Avoid concomitant use of maribavir and rifapentine. Coadministration may decrease maribavir exposure resulting in reduced virologic response. Maribavir is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the exposure of maribavir by 60%.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with rifapentine due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and rifapentine is a strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Mebendazole: (Moderate) Mebendazole is metabolized by hepatic cytochrome P450 enzymes and other enzymes. Rifamycins induce hepatic microsomal enzymes and may increase the metabolism of mebendazole if given concomitantly.
Medroxyprogesterone: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Mefloquine: (Moderate) Use mefloquine with caution if coadministration with rifapentine is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased mefloquine exposure by 68%.
Metformin; Repaglinide: (Moderate) A dose increase of repaglinide and increased frequency of blood glucose monitoring may be required if coadministration with rifapentine is necessary. Repaglinide is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Metformin; Rosiglitazone: (Moderate) Monitor for a decrease in rosiglitazone efficacy during concomitant use with rifapentine; adjust the dose of rosiglitazone based on clinical response. Coadministration may decrease the exposure of rosiglitazone. Rosiglitazone is a CYP2C8 substrate and rifapentine is a moderate CYP2C8 inducer.
Methadone: (Moderate) Monitor for reduced efficacy of methadone and signs of opioid withdrawal if coadministration with rifapentine is necessary; these effects may be more pronounced with rifapentine as it can induce multiple CYP enzymes. Consider increasing the dose of methadone as needed. If rifapentine is discontinued, consider a dose reduction of methadone and frequently monitor for signs of respiratory depression and sedation. Methadone is a substrate of CYP3A4 and CYP2C9; rifapentine is a strong CYP3A4 inducer and moderate CYP2C9 inducer. Concomitant use can decrease methadone exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Methylprednisolone: (Moderate) Monitor for decreased corticosteroid efficacy if methylprednisolone is used with rifapentine; a dosage increase may be necessary. Concurrent use may decrease the exposure of methylprednisolone. Methylprednisolone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Midazolam: (Moderate) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8, and 9. Midazolam is metabolized by CYP3A4 and CYP2C8, and 9 and may require dosage adjustments when administered concurrently with rifapentine.
Midostaurin: (Major) Avoid the concomitant use of midostaurin and rifapentine as significantly decreased exposure of midostaurin and its active metabolites may occur resulting in decreased efficacy. Midostaurin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. The AUC values of midostaurin and its metabolites CGP62221 and CGP52421 decreased by 96%, 92%, and 59%, respectively, when midostaurin was administered with another strong CYP3A4 inducer.
Mifepristone: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of rifapentine. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving rifapentine. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
Mirtazapine: (Moderate) Monitor for decreased efficacy of mirtazapine if coadministration with rifapentine is necessary; an increased mirtazapine dose may be necessary. If rifapentine is discontinued, a decrease in mirtazapine dose may be needed. Concomitant use may decrease mirtazapine exposure. Mirtazapine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers increased mirtazapine clearance by approximately 2-fold, decreasing the average mirtazapine plasma concentrations by 45% to 60%.
Mitapivat: (Major) Avoid coadministration of mitapivat with rifapentine due to decreased mitapivat efficacy. Coadministration decreases mitapivat concentrations. Mitapivat is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased mitapivat overall exposure by 91% to 95%.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and rifapentine. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Mobocertinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Use of a strong CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 92%.
Modafinil: (Moderate) Monitor for decreased efficacy of modafinil if coadministration with rifapentine is necessary. Modafinil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. The probability of effect of rifapentine on modafinil exposure is low due to the existence of multiple pathways for modafinil metabolism, as well as the fact that a non-CYP-related pathway is the most rapid in metabolizing modafinil; however, plasma concentrations of modafinil may be impacted by strong CYP3A4 inducers.
Montelukast: (Minor) Monitor for decreased montelukast efficacy if coadministered with rifapentine. The systemic exposure of montelukast may be reduced; however, dosage adjustments are not likely to be needed. Montelukast is metabolized by CYP2C8 (primary), CYP2C9 and CYP3A4; rifapentine is a strong CYP3A4 and moderate CYP2C9 inducer. Coadministration with another strong CYP3A4 and moderate CYP2C9 inducer decreased the exposure of montelukast by approximately 40%.
Naldemedine: (Major) Avoid coadministration of naldemedine with rifapentine due to a significant decrease in naldemedine plasma concentrations which may reduce efficacy. Naldemedine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naldemedine exposure by 83%.
Naloxegol: (Major) Coadministration of naloxegol with rifapentine is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with rifapentine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and rifapentine as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Nateglinide: (Moderate) Rifapentine is expected to reduce the plasma concentrations and possibly the efficacy of nateglinide. If these drugs must be used together, closely monitor blood glucose concentrations and for glycemic control. In some patients, a dosage adjustment of nateglinide may be necessary. Rifapentine is an inducer of CYP2C9. Nateglinide is a CYP2C9 substrate.
Nefazodone: (Moderate) Monitor for decreased efficacy of nefazodone if coadministration with rifapentine is necessary. Concomitant use may decrease nefazodone exposure. Nefazodone is a primary CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased nefazodone and hydroxynefazodone exposure by almost 95%.
Nelfinavir: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Neratinib: (Major) Avoid concomitant use of rifapentine with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased neratinib exposure by 87%, while exposure to active metabolites M6 and M7 were reduced by 37% to 49%. Concomitant use with other strong inducers of CYP3A4 may also decrease neratinib concentrations.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid coadministration of netupitant with chronic use of rifapentine; concurrent use may decrease netupitant exposure and lead to reduced efficacy. Netupitant is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased netupitant exposure by 62%.
Nevirapine: (Major) Avoid coadministration of nevirapine and rifapentine. Concurrent use may decrease the plasma concentrations of nevirapine leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Nevirapine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased nevirapine exposure by greater than 50%.
Nifedipine: (Major) Avoid coadministration of nifedipine with rifapentine and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and rifapentine; significantly decreased nilotinib exposure and reduced nilotinib efficacy may occur. Nilotinib is a CYPA4 substrate and rifapentine is a strong CYP3A4 inducer. In a drug interaction study, coadministration with another strong CYP3A4 inducer decreased nilotinib exposure by approximately 80%.
Nimodipine: (Major) Avoid coadministration of nimodipine and rifapentine due to the risk of decreased nimodipine exposure which may reduce its efficacy. Nimodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Niraparib; Abiraterone: (Major) Avoid the concomitant use of abiraterone and rifapentine due to the risk of decreased abiraterone efficacy. If concomitant use is unavoidable, increase the abiraterone dosing frequency to twice daily. Resume the previous dose and frequency when rifapentine is discontinued. Abiraterone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Nirmatrelvir; Ritonavir: (Contraindicated) Ritonavir-boosted nirmatrelvir is contraindicated for use within 2 weeks of administering rifapentine; consider an alternative COVID-19 therapy. Coadministration may decrease nirmatrelvir exposure resulting in reduced virologic response. The risk for reduced efficacy may persist following rifapentine discontinuation. Nirmatrelvir is a CYP3A substrate and rifapentine is a strong CYP3A inducer. (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with rifapentine due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Norethindrone: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Norethindrone; Ethinyl Estradiol: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Norgestimate; Ethinyl Estradiol: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Norgestrel: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Nortriptyline: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Olanzapine; Samidorphan: (Major) Avoid the concurrent use of samidorphan and rifapentine; decreased samidorphan exposure and loss of efficacy may occur. Samidorphan is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use of another strong CYP3A inducer reduced samidorphan exposure by 73%.
Olaparib: (Major) Avoid coadministration of olaparib with rifapentine due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A4 inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Oliceridine: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of oliceridine as needed. If rifapentine is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Olutasidenib: (Major) Avoid concurrent use of olutasidenib and rifapentine due to the risk of decreased olutasidenib exposure which may reduce its efficacy. Olutasidenib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced olutasidenib exposure by approximately 80%.
Omaveloxolone: (Major) Avoid concurrent use of omaveloxolone and rifapentine. Concurrent use may decrease omaveloxolone exposure which may reduce its efficacy. Omaveloxolone is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Omeprazole: (Major) Avoid concomitant use of omeprazole and rifapentine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid concomitant use of omeprazole and rifapentine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Omeprazole; Sodium Bicarbonate: (Major) Avoid concomitant use of omeprazole and rifapentine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Osilodrostat: (Major) Monitor cortisol concentration and patient's signs and symptoms during coadministration of osilodrostat and rifapentine. Concurrent use may decrease osilodrostat exposure and reduce its efficacy; an increase in osilodrostat dose may be necessary. After discontinuation of rifapentine, monitor cortisol concentration and patient's signs and symptoms; a reduction in osilodrostat dose may be needed. Osilodrostat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Osimertinib: (Major) Avoid coadministration of rifapentine with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If rifapentine is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Ospemifene: (Moderate) Monitor for decreased efficacy of ospemifene if coadministration with rifapentine is necessary. Ospemifene is a CYP3A4 and CYP2C9 substrate; rifapentine is a strong CYP3A4 inducer as well as a moderate inducer of CYP2C9. Coadministration of another dual CYP2C9/CYP3A inhibitor increased ospemifene systemic exposure by 2.7-fold.
Oxcarbazepine: (Moderate) Monitor for decreased plasma levels of MHD, the active metabolite of oxcarbazepine, if coadministered with rifapentine. The oxcarbazepine dose may require adjustment after initiation, dosage modification, or discontinuation of rifapentine. Strong CYP3A4 inducers like rifapentine have been shown to decrease MHD exposure by 25 to 49%.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of oxycodone as needed. If rifapentine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ozanimod: (Major) Coadministration of ozanimod with rifapentine is not recommended. Coadministration may decrease the exposure of the active metabolites of ozanimod, which may reduce its efficacy. Ozanimod is a CYP2C8 substrate and rifapentine is a moderate CYP2C8 inducer. Coadministration with a strong inducer of CYP3A and P-gp, and a moderate inducer of CYP2C8 reduced the exposure for ozanimod, CC112273, and CC1084037 by approximately 24%, 60%, and 55%, respectively. The effect on CC112273 and CC1084037 is primarily caused by induction of CYP2C8.
Paclitaxel: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with rifapentine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Pacritinib: (Contraindicated) Concurrent use of pacritinib with rifapentine is contraindicated due to decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Palbociclib: (Major) Avoid coadministration of palbociclib with rifapentine due to the risk of decreased palbociclib exposure and reduced efficacy. Palbociclib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased the plasma exposure of palbociclib 85%.
Paliperidone: (Major) Avoid using rifapentine if possible during the 1-month injectable dosing interval of Invega Sustenna or the 3-month injectable dosing interval of Invega Trinza. If use of rifapentine is required in patients receiving injectable paliperidone, consider management with oral paliperidone. Oral paliperidone may be used; however, a dosage increase may be necessary. Paliperidone is a P-glycoprotein (P-gp) substrate, with minor contributions in metabolism by CYP3A4. Rifapentine is a strong CYP3A4 inducer.
Palovarotene: (Major) Avoid concomitant use of palovarotene and rifapentine. Concurrent use may decrease palovarotene exposure which may reduce its efficacy. Palovarotene is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced palovarotene overall exposure by 11%.
Panobinostat: (Major) Avoid the concomitant use of panobinostat and rifapentine due to the possibility of significantly decreased plasma concentrations of panobinostat. Rifapentine is a strong CYP3A4 inducer and panobinostat is a CYP3A4 substrate. Using a physiologically-based pharmacokinetic model, the systemic exposure was estimated to be decreased by 70% when a strong CYP3A inducer was co-administered with panobinostat.
Pazopanib: (Major) Avoid coadministration of pazopanib with rifapentine due to the potential for decreased plasma concentrations of pazopanib. Pazopanib should not be used if chronic use of rifapentine cannot be avoided. Pazopanib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and rifapentine due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased pemigatinib exposure by 85%.
Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime if perampanel is added to rifapentine therapy; increase the dose as tolerated in 2 mg increments no more than weekly, based on clinical response. If rifapentine is added or withdrawn from perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Perampanel is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers decreased perampanel exposure by 50% to 67%.
Perindopril; Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Perphenazine; Amitriptyline: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Pexidartinib: (Major) Avoid coadministration of pexidartinib with rifapentine as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Pexidartinib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
Phenothiazines: (Major) Rifamycins can increase the metabolism or reduce the bioavailability of phenothiazines. Dosage increases of phenothiazines may be necessary following the addition of rifampin or another rifamycin.
Pimavanserin: (Major) Avoid coadministration of pimavanserin with rifapentine as concurrent use may decrease pimavanserin exposure which may lead to decreased efficacy. Pimavanserin is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration with another strong inducer decreased pimavanserin exposure by 91%.
Pioglitazone; Glimepiride: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
Pirtobrutinib: (Major) Avoid concurrent use of pirtobrutinib and rifapentine due to the risk of decreased pirtobrutinib exposure which may reduce its efficacy. Pirtobrutinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced pirtobrutinib overall exposure by 71%.
Pitolisant: (Major) Monitor for loss of pitolisant efficacy after initiation of rifapentine. Increase to double the original daily dose of pitolisant over seven days in patients stable on 8.9 mg or 17.8 mg once daily (i.e., 17.8 mg or 35.6 mg, respectively). Decrease the pitolisant dose by one-half if rifapentine is discontinued. Pitolisant is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of strong CYP3A4 inducers decreases pitolisant exposure by 50%.
Ponatinib: (Major) Avoid coadministration of ponatinib with rifapentine due to decreased plasma concentrations of ponatinib. If concomitant use is unavoidable, monitor for reduced efficacy of ponatinib. Ponatinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ponatinib exposure by 62%.
Ponesimod: (Major) Avoid concurrent use of ponesimod and rifapentine and monitor for decreased ponesimod efficacy if use is necessary. Ponesimod is a CYP3A substrate and rifapentine is a strong CYP3A inducer that may decrease ponesimod exposure.
Posaconazole: (Major) The concurrent use of posaconazole and rifapentine should be avoided, if possible, due to the potential for decreased posaconazole efficacy. If used in combination, closely monitor posaconazole drug concentrations and adjust dose as needed. Breakthrough fungal infections may occur if these drugs are used together.
Pralsetinib: (Major) Avoid coadministration of rifapentine with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After rifapentine has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating rifapentine. Pralsetinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Praziquantel: (Contraindicated) Coadministration of praziquantel with rifapentine is contraindicated due to the potential for decreased exposure and efficacy of praziquantel. Praziquantel is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. In a crossover study with a 2-week washout period, administration of praziquantel followed by another strong CYP3A inducer resulted in undetectable plasma concentrations of praziquantel in 7 out of 10 subjects. When praziquantel was administered two weeks after discontinuation of the strong inducer, the mean praziquantel AUC and Cmax were 23% and 35% lower, respectively, than when praziquantel was given alone.
Prednisolone: (Moderate) Monitor for decreased corticosteroid efficacy if prednisolone is used with rifapentine; a dosage increase may be necessary. Concurrent use may decrease the exposure of prednisolone. Prednisolone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Prednisone: (Moderate) Monitor for decreased corticosteroid efficacy if prednisone is used with rifapentine; a dosage increase may be necessary. Concurrent use may decrease the exposure of prednisone. Prednisone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Pretomanid: (Major) Avoid coadministration of pretomanid with rifapentine as concurrent use may decrease pretomanid exposure which may lead to decreased efficacy. Pretomanid is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer decreased pretomanid exposure by 35%.
Progesterone: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Progestins: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Propranolol: (Moderate) Rifamycins are inducers of hepatic enzymes, and may alter the pharmacokinetics of beta-blockers including propranolol. Patients should be monitored for loss of propranolol effects if rifamycins are added.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Rifamycins are inducers of hepatic enzymes, and may alter the pharmacokinetics of beta-blockers including propranolol. Patients should be monitored for loss of propranolol effects if rifamycins are added.
Protease inhibitors: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Protriptyline: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Quazepam: (Moderate) Monitor for withdrawal symptoms or lack of quazepam efficacy if coadministration with rifapentine is necessary. Quazepam is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Quetiapine: (Major) Increase the dose of quetiapine by up to 5-fold if coadministered with rifapentine. Coadministration may significantly decrease quetiapine exposure leading to reduced efficacy. If rifapentine is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Quetiapine is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold.
Quinidine: (Moderate) Monitor for decreased efficacy of quinidine if coadministration with rifapentine is necessary. Concomitant use may result in decreased plasma concentrations of quinidine. Quinidine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Quinine: (Moderate) Monitor for decreased quinine efficacy if coadministration with rifapentine is necessary. Quinine is a CYP3A4 and CYP2C9 substrate; rifapentine is a strong CYP3A4 inducer and moderate CYP2C9 inducer. Coadministration with another strong CYP3A4 inducer that also induces multiple other enzymes decreased the quinine AUC by 75% to 85%.
Quizartinib: (Major) Avoid concomitant use of rifapentine with quizartinib due to the risk of decreased quizartinib exposure which may reduce its efficacy. Quizartinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Ramelteon: (Moderate) Monitor for a decrease in the efficacy of ramelteon if coadministration with rifapentine is necessary. Ramelteon is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased total exposure to ramelteon and metabolite M-II by approximately 80%.
Ranolazine: (Contraindicated) Coadministration of ranolazine with rifapentine is contraindicated due to decreased ranolazine exposure and efficacy. Ranolazine is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased the plasma concentrations of ranolazine by approximately 95%.
Regorafenib: (Major) Avoid coadministration of regorafenib with rifapentine due to decreased plasma concentrations of regorafenib and increased plasma concentrations of the M-5 active metabolite, which may lead to decreased efficacy. Regorafenib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the mean AUC of regorafenib by 50% and increased the mean AUC of M-5 by 264%; no change in the mean AUC of M-2 was observed.
Relugolix; Estradiol; Norethindrone acetate: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Repaglinide: (Moderate) A dose increase of repaglinide and increased frequency of blood glucose monitoring may be required if coadministration with rifapentine is necessary. Repaglinide is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Ribociclib: (Major) Avoid coadministration of ribociclib with rifapentine due to decreased ribociclib exposure resulting in decreased efficacy. Ribociclib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with a strong inducer decreased ribociclib exposure in healthy subjects by 89%.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with rifapentine due to decreased ribociclib exposure resulting in decreased efficacy. Ribociclib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with a strong inducer decreased ribociclib exposure in healthy subjects by 89%.
Rilpivirine: (Contraindicated) Concurrent use of rifapentine and rilpivirine is contraindicated; when these drugs are coadministered, there is a potential for treatment failure and/or the development of rilpivirine or NNRTI resistance. Rifapentine is a strong CYP3A4 inducer, which is primarily responsible for the metabolism of rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine.
Rimegepant: (Major) Avoid coadministration of rimegepant with rifapentine; concurrent use may significantly decrease rimegepant exposure which may result in loss of efficacy. Rimegepant is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration of rimegepant with another strong CYP3A4 inducer decreased rimegepant exposure by 80%.
Riociguat: (Moderate) Coadministration of riociguat with rifapentine may significantly reduce riociguat exposure; however, riociguat dosage adjustment recommendations are not available. Riociguat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Ripretinib: (Major) Avoid coadministration of ripretinib with rifapentine. Coadministration may decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease ripretinib anti-tumor activity. Ripretinib and DP-5439 are metabolized by CYP3A4 and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased ripretinib exposure by 61% and decreased DP-5439 exposure by 57%.
Risperidone: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and rifapentine and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Ritlecitinib: (Moderate) Monitor for a decrease in ritlecitinib efficacy during concomitant use of ritlecitinib and rifapentine. Concomitant use may decrease ritlecitinib exposure. Ritlecitinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced ritlecitinib overall exposure by 0.56-fold.
Ritonavir: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Roflumilast: (Major) Concomitant use of roflumilast and rifapentine is not recommended. Concurrent use may decrease the systemic exposure to roflumilast which may reduce its efficacy. Roflumilast is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased roflumilast exposure by 80%; exposure to roflumilast N-oxide was decreased by 56%.
Rolapitant: (Major) Avoid coadministration of rolapitant with rifapentine due to decreased plasma concentrations of rolapitant. Rolapitant is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased rolapitant exposure by 85%; the mean half-life of rolapitant decreased from 176 hours to 41 hours.
Romidepsin: (Major) Avoid coadministration of romidepsin with rifapentine if possible due to decreased plasma concentrations of romidepsin. Romidepsin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. The effect of strong CYP3A4 inducers on the exposure of romidepsin is unknown.
Rosiglitazone: (Moderate) Monitor for a decrease in rosiglitazone efficacy during concomitant use with rifapentine; adjust the dose of rosiglitazone based on clinical response. Coadministration may decrease the exposure of rosiglitazone. Rosiglitazone is a CYP2C8 substrate and rifapentine is a moderate CYP2C8 inducer.
Ruxolitinib: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with rifapentine; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ruxolitinib exposure by 61%. The relative exposure to ruxolitinib's active metabolites increased approximately 100%.
Saquinavir: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Segesterone Acetate; Ethinyl Estradiol: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer.
Selegiline: (Moderate) Use caution if selegiline and rifapentine are used concomitantly. Although rifapentine is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and rifapentine due to the risk of decreased selpercatinib exposure which may reduce its efficacy. Selpercatinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased selpercatinib exposure by 87%.
Selumetinib: (Major) Avoid coadministration of selumetinib and rifapentine due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased selumetinib exposure by 51%.
Sildenafil: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with rifapentine is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant administration of strong CYP3A4 inducers is expected to substantially decrease plasma concentrations of sildenafil. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
Siponimod: (Major) Concomitant use of siponimod and rifapentine is not recommended due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; rifapentine is a moderate CYP2C9/strong CYP3A4 dual inducer. Coadministration with another moderate CYP2C9/strong CYP3A4 dual inducer decreased siponimod exposure by 57%.
Sirolimus: (Major) Avoid concomitant use of sirolimus and rifapentine as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Sofosbuvir: (Major) Avoid coadministration of sofosbuvir with rifapentine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of sofosbuvir with rifapentine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Concomitant use of velpatasvir with rifapentine is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A4 and CYP2C8 substrate and rifapentine is a strong CYP3A4 inducer and moderate CYP2C8 inducer.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of sofosbuvir with rifapentine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Concomitant use of velpatasvir with rifapentine is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A4 and CYP2C8 substrate and rifapentine is a strong CYP3A4 inducer and moderate CYP2C8 inducer. (Major) Concomitant use of voxilaprevir with rifapentine is not recommended due to the risk of decreased plasma concentrations of voxilaprevir, which may result in loss of antiviral efficacy. Voxilaprevir is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Solifenacin: (Moderate) Monitor for decreased efficacy of solifenacin if coadministration with rifapentine is necessary. Solifenacin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Studies have not been conducted to evaluate the effect of CYP3A4 inducers on solifenacin, but inducers of CYP3A4 may decrease solifenacin plasma concentrations.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and rifapentine; sonidegib exposure may be significantly decreased and its efficacy reduced. Sonidegib is a CYP3A substrate and rifapentine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the geometric mean Cmax and AUC of sonidegib by 54% and 72%, respectively.
Sorafenib: (Major) Avoid coadministration of sorafenib with rifapentine due to decreased plasma concentrations of sorafenib. Sorafenib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased sorafenib exposure by 37%.
Sotorasib: (Major) Avoid concurrent use of sotorasib and rifapentine. Coadministration may decrease sotorasib exposure resulting in decreased efficacy. Sotorasib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC of sotorasib by 51%.
Sparsentan: (Major) Avoid concomitant use of sparsentan and rifapentine due to the risk for decreased sparsentan exposure which may reduce its efficacy. Sparsentan is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer is predicted to decrease sparsentan overall exposure by 47%.
Stiripentol: (Major) Avoid coadministration of stiripentol with rifapentine. If concurrent use is necessary, consider a dose increase of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if rifapentine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of sufentanil injection as needed. If rifapentine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Sulfonylureas: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
Sunitinib: (Major) Avoid coadministration of rifapentine with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
Suvorexant: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with rifapentine is necessary. Suvorexant is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%.
Tacrolimus: (Major) Increase tacrolimus dose and monitor tacrolimus serum concentrations if coadministration with rifapentine is necessary. Concurrent use may decrease tacrolimus serum concentrations and increase the risk of rejection. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range; rifapentine is a strong CYP3A4 inducer.
Tadalafil: (Major) Avoid coadministration of tadalafil with rifapentine in patients with pulmonary hypertension due to decreased plasma concentrations of tadalafil. In patients with erectile dysfunction and/or benign prostatic hyperplasia, consider the potential for loss of efficacy of tadalafil during concurrent administration of rifapentine due to reduced tadalafil exposure. Tadalafil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased tadalafil exposure by 88%.
Tamoxifen: (Major) Avoid coadministration of rifapentine with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Tasimelteon: (Major) Avoid coadministration of tasimelteon with rifapentine due to the potential for a large decrease in tasimelteon exposure resulting in reduced efficacy. Tasimelteon is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased tasimelteon exposure by about 90%.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with rifapentine as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Telmisartan; Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with rifapentine is necessary. Amlodipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Temsirolimus: (Major) Avoid coadministration of temsirolimus and rifapentine due to the risk of decreased temsirolimus exposure which may reduce its efficacy. If concomitant use is unavoidable, consider increasing the dose of temsirolimus from 25 mg per week up to 50 mg per week. If rifapentine is discontinued, resume the original temsirolimus dose. Temsirolimus is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Co administration with another strong CYP3A4 inducer did not have a significant effect on temsirolimus exposure but decreased the exposure of sirolimus (the primary and active metabolite) by 56%.
Teniposide: (Moderate) Monitor patients for reduced efficacy of teniposide if coadministration with rifapentine is necessary. Teniposide is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers reduced plasma concentrations of teniposide.
Tenofovir Alafenamide: (Major) Avoid coadministration of tenofovir alafenamide and rifapentine as concurrent use may decrease tenofovir alafenamide exposure leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Tezacaftor; Ivacaftor: (Major) Coadministration of ivacaftor with rifapentine is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly decreased ivacaftor exposure by approximately 9-fold. (Major) Do not administer tezacaftor; ivacaftor and rifapentine together; coadministration may reduce the efficacy of tezacaftor; ivacaftor. Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by the concomitant use of rifapentine, a strong CYP3A inducer; both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate). Coadministration of ivacaftor with a strong CYP3A inducer decreased ivacaftor exposure 89%. Tezacaftor exposures can also be expected to decrease significantly during coadministration with strong CYP3A inducers.
Thiothixene: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
Tiagabine: (Moderate) Monitor for decreased efficacy of tiagabine if coadministration with rifapentine is necessary. Tiagabine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Population pharmacokinetic analyses indicate that tiagabine clearance is 60% greater in patients taking another strong CYP3A4 inducer.
Ticagrelor: (Major) Avoid coadministration of ticagrelor with rifapentine due to decreased plasma concentrations of ticagrelor. Ticagrelor is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ticagrelor exposure by 86%.
Tinidazole: (Moderate) Monitor for decreased efficacy of tinidazole if coadministration with rifapentine is necessary. Concomitant use may accelerate the elimination of tinidazole, decreasing plasma concentrations. Tinidazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Tipranavir: (Major) Avoid coadministration of protease inhibitors and rifapentine as concurrent use may result in significant decreases in the plasma concentrations of the antiretroviral agents, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Protease inhibitors are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. Additionally, HIV patients treated with rifapentine have a higher rate of TB relapse than those treated with other rifamycin-based regimens; an alternative agent is recommended.
Tivozanib: (Major) Avoid concomitant use of tivozanib with rifapentine due to decreased plasma concentrations of tivozanib, which may reduce its efficacy. Tivozanib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the overall exposure of tivozanib by 52%.
Tofacitinib: (Major) Coadministration of tofacitinib and rifapentine is not recommended due to the potential for a loss of response or reduced clinical response to tofacitinib. Tofacitinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the mean AUC and Cmax of tofacitinib by 84% and 74%, respectively.
Tolazamide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
Tolbutamide: (Moderate) Monitor for decreased efficacy of sulfonylureas during coadministration of rifamycins as plasma concentrations of sulfonylureas may be decreased; dosage adjustments made be necessary. Sulfonylureas are CYP2C9 substrates and rifamycins are CYP2C9 inducers.
Tolvaptan: (Major) Avoid concurrent use of tolvaptan and rifapentine due to the risk for decreased tolvaptan plasma concentrations and reduced efficacy. Tolvaptan is a sensitive CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased tolvaptan exposure by 85%.
Toremifene: (Major) Avoid coadministration of rifapentine with toremifene due to decreased plasma concentrations of toremifene which may result in decreased efficacy. Toremifene is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with strong CYP3A4 inducers lowers steady-state serum concentrations of toremifene.
Trabectedin: (Major) Avoid the concomitant use of trabectedin with rifapentine due to the risk of decreased trabectedin exposure. Trabectedin is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the systemic exposure of a single dose of trabectedin by 31% compared to a single dose of trabectedin given alone.
Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of tramadol as needed. If rifapentine is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with rifapentine is necessary; consider increasing the dose of tramadol as needed. If rifapentine is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Trandolapril; Verapamil: (Moderate) Monitor blood pressure and heart rate if coadministration of verapamil with rifapentine is necessary. Concomitant use may decrease plasma concentrations of verapamil. Verapamil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Trazodone: (Moderate) Consider increasing the trazodone dose based on therapeutic response when coadministered with rifapentine. Concurrent use may decrease trazodone exposure. Trazodone is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers decreased the exposure of trazodone compared to the use of trazodone alone.
Tretinoin, ATRA: (Moderate) Rifapentine may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. No specific studies have been done with oral tretinoin and rifapentine, however, patients should be closely monitored for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
Triazolam: (Moderate) Monitor for withdrawal symptoms or lack of triazolam efficacy if coadministration with rifapentine is necessary. Consider appropriate dose adjustment of triazolam if clinically indicated. Triazolam is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Tricyclic antidepressants: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Trimipramine: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Tricyclic antidepressants are metabolized by CYP3A4 and CYP2C8/9 and may require dosage adjustments when administered concurrently with rifapentine.
Tucatinib: (Major) Avoid coadministration of tucatinib and rifapentine due to the risk of decreased tucatinib exposure which may reduce its efficacy. Tucatinib is a CYP3A4 and CYP2C8 substrate and rifapentine is a strong CYP3A4 inducer and moderate CYP2C8 inducer. Coadministration with another strong CYP3A4/moderate CYP2C8 inducer decreased tucatinib exposure by 50%.
Ubrogepant: (Major) Avoid the coadministration of ubrogepant and rifapentine as concurrent use may decrease ubrogepant exposure and reduce the efficacy. Ubrogepant is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer resulted in an 80% reduction in ubrogepant exposure.
Ulipristal: (Major) Avoid concurrent use of ulipristal and rifapentine. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal. Ulipristal is a substrate of CYP3A4 and rifapentine is a strong CYP3A4 inducer. Another strong CYP3A4 inducer reduced ulipristal exposure by 93% and exposure of its active metabolite by 90%.
Upadacitinib: (Major) Coadministration of upadacitinib with rifapentine is not recommended as upadacitinib exposure may be decreased leading to reduced therapeutic effect. Upadacitinib is CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Concurrent use of a strong CYP3A4 inducer decreased upadacitinib exposure by 61%.
Valbenazine: (Major) Coadministration of valbenazine with rifapentine is not recommended as plasma concentrations of valbenazine and its active metabolite may be decreased. Reduced exposure of valbenazine and its active metabolite may reduce efficacy. Valbenazine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to valbenazine and NBI-98782 by 70% and 80%, respectively.
Vandetanib: (Major) Avoid coadministration of vandetanib with rifapentine due to the risk of decreased vandetanib exposure and reduced efficacy. Vandetanib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the AUC of vandetanib by 40%.
Vemurafenib: (Major) Avoid coadministration of vemurafenib with rifapentine due to the potential for decreased vemurafenib exposure and reduced efficacy. Consider the use of an alternative agent. If use with rifapentine cannot be avoided, increase the vemurafenib dose by 240 mg (as tolerated). The original dose of vemurafenib may be resumed 2 weeks after rifapentine is discontinued. Vemurafenib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the exposure of vemurafenib by 40%.
Venetoclax: (Major) Avoid coadministration of venetoclax with rifapentine as concurrent use may decrease venetoclax exposure and lead to reduced efficacy. Venetoclax is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased venetoclax exposure by 71%.
Verapamil: (Moderate) Monitor blood pressure and heart rate if coadministration of verapamil with rifapentine is necessary. Concomitant use may decrease plasma concentrations of verapamil. Verapamil is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Vilazodone: (Moderate) Consider increasing the dose of vilazodone up to 2-fold over 1 to 2 weeks (maximum, 80 mg per day) based on clinical response if coadministration with rifapentine is necessary for more than 14 days. After discontinuation of rifapentine, resume the previous vilazodone dose over 1 to 2 weeks. Vilazodone is primarily metabolized by CYP3A4 and rifapentine is a strong CYP3A4 inducer. Decreased plasma concentrations of vilazodone are expected if vilazodone is used concomitantly with strong CYP3A4 inducers.
Vincristine Liposomal: (Major) Avoid coadministration of vincristine and rifapentine due to the risk of decreased vincristine exposure which may reduce its efficacy. Vincristine is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Vincristine: (Major) Avoid coadministration of vincristine and rifapentine due to the risk of decreased vincristine exposure which may reduce its efficacy. Vincristine is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Voclosporin: (Major) Avoid coadministration of voclosporin with rifapentine. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of vonoprazan and rifapentine due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Vonoprazan exposures are predicted to be 80% lower when coadministered with a strong CYP3A4 inducer.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of vonoprazan and rifapentine due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Vonoprazan exposures are predicted to be 80% lower when coadministered with a strong CYP3A4 inducer. (Major) Consider alternatives to clarithromycin if treatment with rifapentine is necessary as concurrent use may decrease efficacy of clarithromycin. Clarithromycin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers. There have been spontaneous or published reports of CYP3A-based interactions of clarithromycin with another CYP3A4 inducer.
Vorapaxar: (Major) Avoid coadministration of vorapaxar and rifapentine due to decreased serum concentrations of vorapaxar. Vorapaxar is a CYP3A4 substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A4 inducer decreased vorapaxar exposure by 55%; the impact on efficacy for a change in exposure of this magnitude is not known.
Voriconazole: (Major) Avoid coadministration of voriconazole with rifapentine as concurrent use may decrease voriconazole exposure. Although specific recommendations are unavailable for use with rifapentine, coadministration with other strong CYP3A4 inducers is either contraindicated or requires an increased dose of voriconazole. Voriconazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voriconazole exposure by 96%.
Vortioxetine: (Major) Consider increasing the dose of vortioxetine (maximum, 3 times the original dose) if coadministration with rifapentine for longer than 14 days is necessary. Reduce the dose of vortioxetine to the original level within 14 days when rifapentine is discontinued. Vortioxetine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly reduced the exposure of vortioxetine.
Voxelotor: (Major) Avoid coadministration of voxelotor and rifapentine as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,500 mg PO once daily in patients 12 years and older. In patients 4 to 11 years old, weight-based dosage adjustments are recommended; consult product labeling for specific recommendations. Voxelotor is a substrate of CYP3A; rifapentine is a strong CYP3A inducer. Coadministration of voxelotor with a strong CYP3A inducer is predicted to decrease voxelotor exposure by up to 40%.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with rifamycins is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Rifamycins may induce the hepatic metabolism of warfarin through induction of CYP3A4, CYP2C9, and CYP1A2. A 2- to 3-fold increase in the daily dose of warfarin may be needed within a week of starting rifamycins to maintain appropriate anticoagulation. Once the rifamycin is discontinued, the dose of warfarin will need to be decreased.
Zaleplon: (Moderate) Monitor for decreased efficacy when zaleplon is coadministered with rifapentine due to decreased zaleplon exposure. Zaleplon is partially metabolized by CYP3A4; rifapentine is a strong CYP3A4 inducer. Consider using an alternative non-CYP3A4 substrate hypnotic in patients taking strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer reduced zaleplon exposure by approximately 80%.
Zanubrutinib: (Major) Avoid the concomitant use of zanubrutinib and rifapentine. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Zidovudine, ZDV: (Minor) Rifapentine appears to increase the glucuronidation of zidovudine, ZDV similar to other rifamycins. This may cause a decrease in zidovudine AUC. However, the effectiveness of zidovudine against HIV does not appear to be altered. The activity of zidovudine is dependent on the intracellular concentration of the triphosphate metabolite which is not correlated with plasma concentrations of the parent compound. The CDC currently considers the nucleoside reverse transcriptase inhibitors (NRTIs), including zidovudine, compatible for concomitant use with rifamycins (including rifampin, rifabutin and rifapentine). No dosing adjustments are necessary.
Ziprasidone: (Moderate) Monitor for decreased efficacy of ziprasidone when coadministered with rifapentine. Coadministration may decrease ziprasidone exposure. Ziprasidone is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the exposure of ziprasidone by approximately 35%.
Zolpidem: (Major) Coadministration of zolpidem with rifapentine is not recommended as concurrent use may decrease plasma concentrations of zolpidem. Zolpidem is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased zolpidem exposure by 73% and significantly reduced the pharmacodynamic effects of zolpidem.
Zonisamide: (Moderate) Monitor for decreased efficacy of zonisamide when coadministered with rifapentine; adjust the dose of zonisamide as clinically appropriate. Zonisamide is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers decreased the zonisamide half-life by 8 to 19 hours. These effects are unlikely to be of clinical significance when zonisamide is added to rifapentine therapy; however, changes in zonisamide concentrations may occur if rifapentine is added, dose adjusted, or withdrawn from zonisamide therapy.
How Supplied
Priftin/Rifapentine Oral Tab: 150mg
Maximum Dosage
600 mg PO twice weekly is the FDA-approved maximum dosage for active tuberculosis infection treatment. Maximum dosages are delineated by weight for latent tuberculosis infection.
Weighing 50 kg or more: 900 mg/dose PO.
Weighing 32.1 to 49.9 kg: 750 mg/dose PO.
600 mg PO twice weekly is the FDA-approved maximum dosage for active tuberculosis infection treatment. Maximum dosages are delineated by weight for latent tuberculosis infection.
Weighing 50 kg or more: 900 mg/dose PO.
Weighing 32.1 to 49.9 kg: 750 mg/dose PO.
600 mg PO twice weekly is the FDA-approved maximum dosage for active tuberculosis infection treatment. Maximum dosages are delineated by weight for latent tuberculosis infection.
Weighing 50 kg or more: 900 mg/dose PO.
Weighing 32.1 to 49.9 kg: 750 mg/dose PO.
Weighing 25.1 to 32 kg: 600 mg/dose PO.
Maximum dosages are delineated by weight for latent tuberculosis infection.
2 to 12 years weighing 50 kg or more: 900 mg/dose PO.
2 to 12 years weighing 32.1 to 49.9 kg: 750 mg/dose PO.
2 to 12 years weighing 25.1 to 32 kg: 600 mg/dose PO.
2 to 12 years weighing 14.1 to 25 kg: 450 mg/dose PO.
2 to 12 years weighing 10 to 14 kg: 300 mg/dose PO.
2 to 12 years weighing less than 10 kg: Safety and efficacy have not been established.
1 year: Safety and efficacy have not been established.
Safety and efficacy have not been established.
NeonatesSafety and efficacy have not been established.
Mechanism Of Action
Rifapentine is a cyclopentyl rifamycin antimycobacterial agent. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of M. tuberculosis. It inhibits RNA transcription by preventing the initiation of RNA chain formation. Rifapentine forms a stable complex with bacterial DNA-dependent RNA polymerase, leading to repression of RNA synthesis and cell death. Rifapentine and its active metabolite, 25-desacetyl rifapentine, accumulate in human monocyte-derived macrophages and exhibit bactericidal activity against both intracellular and extracellular M. tuberculosis. Based upon relative in vitro activities and AUC values, rifapentine and 25-desacetyl rifapentine potentially contribute 62% and 38% to the clinical activities against M. tuberculosis, respectively.[28483]
The mechanism of resistance of rifapentine appears to be similar to that of rifampin. Bacterial resistance is caused by an alteration in the target site, the beta subunit of the DNA-dependent RNA polymerase, caused by a single-step mutation of the rpo-beta gene. The incidence of rifapentine resistant mutants in an otherwise susceptible population of M. tuberculosis strains is approximately 1 in 107 to 108 bacilli. Rifapentine resistance appears to be associated with monotherapy. A high level of cross-resistance between other rifamycins and rifapentine has been demonstrated with M. tuberculosis strains. Cross-resistance between rifapentine and non-rifamycin antimycobacterial agents has not been identified in clinical isolates.[28483]
Pharmacokinetics
Rifapentine is administered orally. In healthy volunteers, rifapentine and 25-desacetyl rifapentine are 97.7% and 93.2% bound to plasma proteins, respectively. Rifapentine is mainly bound to albumin. The apparent volume of distribution is 70.2 +/- 9.1 L. After a single 600 mg oral dose of radiolabeled rifapentine, 70% of the dose was recovered in the feces and 17% in the urine. More than 80% of the dose was excreted from the body within 7 days. Rifapentine is hydrolyzed by an esterase enzyme to the active metabolite 25-desacetyl rifapentine. The elimination half-life for both rifapentine and 25-desacetyl rifapentine is about 13 hours. There is no significant auto-induction effect on the steady-state pharmacokinetics of rifapentine.[28483]
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C8/9, CYP3A4
Rifapentine is a potent inducer of CYP3A4.[34362] [46638] [65685] It is also an inducer of CYP2C8/9.[28483]
After oral administration of a single rifapentine 600 mg dose to healthy adult volunteers, the relative bioavailability (using an oral solution as a reference) was 70%; the absolute bioavailability of rifapentine has not been determined. Peak plasma concentrations were achieved 5 to 6 hours after administration of the rifapentine 600 mg dose. On day 10 after administration of rifapentine 600 mg PO every 72 hours, the mean Cmax of rifapentine was 15.05 mcg/mL, and the mean Cmax of 25-desacetyl rifapentine was 6.26 mcg/mL. The mean AUC of rifapentine was 319.54 mcg x hour/mL, and the mean AUC of 25-desacetyl rifapentine was 215.88 mcg x hour/mL.[28483]
The administration of rifapentine with a high-fat meal increased the rifapentine AUC and Cmax by 50% and 40%, respectively, compared to fasting conditions. Administration with a low-fat, high-carbohydrate meal increased the rifapentine AUC and Cmax by 51% and 47%, respectively. Food increased the mean AUC and Cmax of rifapentine observed under fasting conditions in asymptomatic persons with HIV by about 51% and 53%, respectively.[28483]
Pregnancy And Lactation
There are no data on the presence of rifapentine or its metabolite in human or animal milk, the effects on the breast-fed infant, or the effects on milk production. Since rifapentine may produce a red-orange discoloration of body fluids, there is a potential for discoloration of breast milk. Monitor infants exposed to rifapentine through breast milk for signs of hepatotoxicity, such as irritability, prolonged unexplained crying, yellowing of the eyes, loss of appetite, vomiting, and changes in the color of urine (darkening) or stool (lightening, pale or light brown). Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for rifapentine and any potential adverse effects on the breast-fed infant from rifapentine or the underlying maternal condition.[28483] Guidelines encourage breast-feeding for women who are noninfectious and taking first-line tuberculosis agents, such as rifapentine, as the small concentrations of these drugs measured in breast milk have not been reported to produce toxic effects in the nursing infant.[61094] Previous American Academy of Pediatrics (AAP) recommendations considered another rifamycin, rifampin, as usually compatible with breast-feeding.[27500]