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PRIFTIN® (rifapentine) is indicated in adults and children 12 years and older for the treatment of active pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis. PRIFTIN must always be used in combination with one or more antituberculosis (anti-TB) drugs to which the isolate is susceptible.
Limitations of Use
Do not use PRIFTIN monotherapy in either the initial or the continuation phases of active antituberculous treatment.
PRIFTIN should not be used once-weekly in the continuation phase regimen in combination with isoniazid (INH) in HIV-infected patients with active pulmonary tuberculosis because of a higher rate of failure and/or relapse with rifampin (RIF)-resistant organisms.
PRIFTIN has not been studied as part of the initial phase treatment regimen in HIV- infected patients with active pulmonary tuberculosis.
Latent Tuberculosis Infection
PRIFTIN is indicated in adults and children 2 years and older for the treatment of latent tuberculosis infection caused by Mycobacterium tuberculosis in patients at high risk of progression to tuberculosis disease (including those in close contact with active tuberculosis patients, recent conversion to a positive tuberculin skin test, HIV-infected patients, or those with pulmonary fibrosis on radiograph).
Limitations of Use
Active tuberculosis disease should be ruled out before initiating treatment for latent tuberculosis infection.
PRIFTIN must always be used in combination with isoniazid as a 12-week once-weekly regimen for the treatment of latent tuberculosis infection.
PRIFTIN in combination with isoniazid is not recommended for Individuals presumed to be exposed to rifamycin- or - isoniazid resistant M. tuberculosis.
Dosage
Dosage in Active Pulmonary Tuberculosis
PRIFTIN is only recommended for the treatment of active pulmonary tuberculosis caused by drug-susceptible organisms as part of regimens consisting of a 2 month initial phase followed by a 4 month continuation phase.
PRIFTIN should not be used in the treatment of active pulmonary tuberculosis caused by rifampin-resistant strains.
Initial phase (2 Months): PRIFTIN should be administered at a dose of 600 mg twice weekly for two months as directly observed therapy (DOT), with an interval of no less than 3 consecutive days (72 hours) between doses, in combination with other anti- tuberculosis drugs as part of an appropriate regimen which includes daily companion drugs such as isoniazid (INH), ethambutol (EMB) and pyrazinamide (PZA).
Continuation phase (4 Months): Following the initial phase (2 months), continuation phase (4 months) treatment consists of PRIFTIN 600 mg once-weekly for 4 months in combination with isoniazid or another appropriate anti- tuberculosis agent for susceptible organisms administered as directly observed therapy.
Dosage in Latent Tuberculosis Infection
PRIFTIN should be administered once-weekly in combination with isoniazid for 12 weeks as directly observed therapy.
Adults and children 12 years and older: The recommended dose of PRIFTIN should be determined based on weight of the patient up to a maximum of 900 mg once-weekly (see TABLE 1). The recommended dose of isoniazid is 15 mg/kg (rounded to the nearest 50 mg or 100mg) up to a maximum of 900 mg once-weekly for 12 weeks.
Children 2–11 years: The recommended dose of PRIFTIN should be determined based on weight of the patient up to a maximum of 900 mg once- weekly (see TABLE 1). The recommended dose of isoniazid is 25 mg/kg (rounded to the nearest 50 mg or 100mg) up to a maximum of 900 mg once-weekly for 12 weeks.
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DOSAGE FORMS AND STRENGTHS
PRIFTIN is supplied as 150 mg round normal convex dark-pink film-coated tablets debossed "Priftin" on top and "150" on the bottom.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Rifapentin in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Rifapentin in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Rifapentin in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Rifapentin in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Rifapentin in pediatric patients.
Contraindications
Hypersensitivity
PRIFTIN is contraindicated in patients with a history of hypersensitivity to rifamycins.
Warnings
Hepatotoxicity
Elevations of liver transaminases may occur in patients receiving PRIFTIN. Patients on PRIFTIN should be monitored for symptoms of liver injury.
Patients with abnormal liver tests and/or liver disease or patients initiating treatment for active pulmonary tuberculosis should only be given PRIFTIN in cases of necessity and under strict medical supervision. In such patients, obtain serum transaminase levels prior to therapy and every 2–4 weeks while on therapy. Discontinue PRIFTIN if evidence of liver injury occurs.
Hypersensitivity and Related Reactions
Hypersensitivity reactions may occur in patients receiving PRIFTIN. Signs and symptoms of these reactions may include hypotension, urticaria, angioedema, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, fever, chills, aches, rash, itching, sweats, dizziness, shortness of breath, chest pain, cough, syncope, palpitations). There have been reports of anaphylaxis.
Monitor patients receiving PRIFTIN therapy for signs and/or symptoms of hypersensitivity reactions. If these symptoms occur, administer supportive measures and discontinue PRIFTIN.
Relapse in the Treatment of Active Pulmonary Tuberculosis
PRIFTIN has not been evaluated as part of the initial phase treatment regimen in HIV-infected patients with active pulmonary TB.
Do not use PRIFTIN as a once-weekly continuation phase regimen in HIV-infected patients with active pulmonary tuberculosis because of a higher rate of failure and/or relapse with rifampin-resistant organisms.
Higher relapse rates may occur in patients with cavitary pulmonary lesions and/or positive sputum cultures after the initial phase of active tuberculosis treatment and in patients with evidence of bilateral pulmonary disease. Monitor for signs and symptoms of TB relapse in these patients.
Poor adherence to therapy is associated with high relapse rate. Emphasize the importance of compliance with therapy [see PATIENT COUNSELING INFORMATION (17)]
Drug Interactions
Rifapentine is an inducer of CYP450 enzymes. Concomitant use of rifapentine with other drugs metabolized by these enzymes, such as protease inhibitors, certain reverse transcriptase inhibitors, and hormonal contraception may cause a significant decrease in plasma concentrations and loss of therapeutic effect.
Discoloration of Body Fluids
PRIFTIN may produce a red-orange discoloration of body tissues and/or fluids (e.g., skin, teeth, tongue, urine, feces, saliva, sputum, tears, sweat, and cerebrospinal fluid). Contact lenses or dentures may become permanently stained.
Clostridium difficile-Associated Diarrhea
Clostridium difficile-associated diarrhea (CDAD) has been reported with the use of nearly all systemic antibacterial agents, including PRIFTIN, with severity ranging from mild diarrhea to fatal colitis. Treatment with antibacterial agents can alter the normal flora of the colon and may permit overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, discontinue antibacterial use not directed against C. difficile if possible. Institute appropriate measures such as fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation as clinically indicated.
Porphyria
Porphyria has been reported in patients receiving rifampin, attributed to induction of delta amino levulinic acid synthetase. Because PRIFTIN may have similar enzyme induction properties, avoid the use of PRIFTIN in patients with porphyria.
Adverse Reactions
Clinical Trials Experience
The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
Hepatotoxicity
Hypersensitivity [see CONTRAINDICATIONS
Discoloration of Body Fluids
Clostridium difficile-Associated Diarrhea
Porphyria
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Active Pulmonary Tuberculosis
PRIFTIN was studied in a randomized, open label, active-controlled trial of HIV-negative patients with active pulmonary tuberculosis. The population consisted of primarily of male subjects with a mean age of 37 ± 11 years. In the initial 2 month phase of treatment, 361 patients received PRIFTIN 600 mg twice a week in combination with daily isoniazid, pyrazinamide, and ethambutol and 361 subjects received rifampin in combination with isoniazid, pyrazinamide and ethambutol all administered daily. Ethambutol was discontinued when drug susceptibly testing was known. During the 4 month continuation phase, 317 patients in the PRIFTIN group continued to receive PRIFTIN 600 mg dosed once-weekly with isoniazid and 304 patients in the rifampin group received twice weekly rifampin and isoniazid. Both treatment groups received pyridoxine (Vitamin B6) over the 6 month treatment period.
Because PRIFTIN was administered as part of a combination regimen, the adverse reaction profile reflects the entire regimen.
Twenty-two deaths occurred in the study, eleven in the rifampin combination therapy group and eleven in the PRIFTIN combination therapy group. 18/361 (5%) rifampin combination therapy patients discontinued the study due to an adverse reaction compared to 11/361 (3%) PRIFTIN combination therapy patients. Three patients (two rifampin combination therapy patients and one PRIFTIN combination therapy patient) were discontinued in the initial phase due to hepatotoxicity. Concomitant medications for all three patients included isoniazid, pyrazinamide, ethambutol, and pyridoxine. All three recovered without sequelae.
Five patients had adverse reactions associated with PRIFTIN overdose. These reactions included hematuria, neutropenia, hyperglycemia, ALT increased, hyperuricemia, pruritus, and arthritis.
Table 2 presents selected treatment-emergent adverse reactions associated with the treatment regimens which occurred in at least 1% of patients during treatment and post-treatment through the first three months of follow-up.
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The following selected treatment-emergent adverse reactions were reported in less than 1% of the PRIFTIN combination therapy patients during treatment and post-treatment through the first three months of follow-up.
In another randomized, open-label trial, 1075 HIV non-infected and infected patients with active pulmonary tuberculosis who had completed an initial 2 month phase of treatment with 4 drugs were randomly assigned to receive either PRIFTIN 600 mg and isoniazid once weekly or rifampin and isoniazid twice weekly for the 4 month continuation phase. 502 HIV non-infected and 36 HIV-infected patients were randomized to receive the PRIFTIN regimen and 502 HIV-noninfected and 35 HIV-infected patients were randomized to receive the rifampin regimen.
The death rate was 6.5% for the PRIFTIN combination regimen compared to 6.7% for the rifampin combination regimen.
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Rifapentin in the drug label.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Rifapentin in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Rifapentin during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Rifapentin with respect to nursing mothers.
Pediatric Use
There is no FDA guidance on the use of Rifapentin with respect to pediatric patients.
Geriatic Use
There is no FDA guidance on the use of Rifapentin with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Rifapentin with respect to specific gender populations.
Race
There is no FDA guidance on the use of Rifapentin with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Rifapentin in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Rifapentin in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Rifapentin in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Rifapentin in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral
Take PRIFTIN with meals. Administration of PRIFTIN with a meal increases oral bioavailability and may reduce the incidence of gastrointestinal upset, nausea, and/or vomiting.
For patients who cannot swallow tablets, the tablets may be crushed and added to a small amount of semi-solid food, all of which should be consumed immediately.
Monitoring
There is limited information regarding Monitoring of Rifapentin in the drug label
IV Compatibility
There is limited information regarding IV Compatibility of Rifapentin in the drug label.
Overdosage
Acute Overdose
Signs and Symptoms
Description
Management
Description
Chronic Overdose
There is limited information regarding Chronic Overdose of Rifapentin in the drug label.
Pharmacology
There is limited information regarding Rifapentin Pharmacology in the drug label.
