HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use PRIFTIN ® safely and effectively. See full prescribing information for PRIFTIN.
Priftin (rifapentine) Tablets
Initial U.S. Approval: 1998
RECENT MAJOR CHANGES
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Indications and Usage (1.2)
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Dosage and Administration (2.2, 2.3)
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Warnings and Precautions (5)
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11/2014
11/2014
11/2014 |
INDICATIONS AND USAGE
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PRIFTIN is a rifamycin antimycobacterial drug indicated in patients 12 years of age and older for the treatment of active pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis in combination with one or more anti-tuberculosis (anti-TB) drugs to which the isolate is susceptible. (1.1)
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PRIFTIN is indicated for the treatment of latent tuberculosis infection (LTBI) caused by M. tuberculosis in combination with isoniazid in patients 2 years of age and older at high risk of progression to TB disease. (1.2)
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See Limitations of Use. (1.1, 1.2)
DOSAGE AND ADMINISTRATION
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Active pulmonary tuberculosis: PRIFTIN should be used in regimens consisting of an initial 2 month phase followed by a 4 month continuation phase. (2.1)
Initial phase (2 Months): 600 mg twice weekly for two months as directly observed therapy (DOT), with no less than 72 hours between doses, in combination with other anti- tuberculosis drugs. (2.1)
Continuation phase (4 Months): 600 mg once-weekly for 4 months as directly observed therapy with isoniazid or another appropriate anti- tuberculosis agent. (2.1)
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Latent tuberculosis infection: PRIFTIN should be administered in combination with isoniazid once-weekly for 12 weeks as directly observed therapy.
Adults and children ≥ 12 years: PRIFTIN (based on weight, see table below) and isoniazid 15 mg/kg (900 mg maximum)
Children 2–11 years: PRIFTIN (based on weight, see table below) and isoniazid 25 mg/kg (900 mg maximum)
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Weight range |
PRIFTIN dose |
Number of PRIFTIN tablets |
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10–14 kg |
300 mg |
2 |
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14.1–25 kg |
450 mg |
3 |
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25.1– 32 kg |
600 mg |
4 |
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32.1–50 kg |
750 mg |
5 |
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> 50 kg |
900 mg |
6 |
For Latent Tuberculosis Infection, the maximum recommended dose of PRIFTIN is 900 mg once-weekly for 12 weeks.
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Take with food. Tablets may be crushed and added to semi-solid food.(2.3)
DOSAGE FORMS AND STRENGTHS
Known hypersensitivity to any rifamycin (4.1)
WARNINGS AND PRECAUTIONS
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Hepatotoxicity: Monitor for symptoms of liver injury and discontinue PRIFTIN if signs or symptoms or liver injury occur (5.1)
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Hypersensitivity: Discontinue PRIFTIN if signs or symptoms of hypersensitivity reaction occur. (5.2).
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Relapse in the treatment of active pulmonary tuberculosis: Do not use as a once-weekly continuation phase regimen with isoniazid in HIV-infected patients. Monitor for signs or symptoms of relapse in patients with cavitary lesions or bilateral disease. (5.3, 14.1)
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Drug Interactions: May interact with drugs metabolized by CYP450. (5.4, 7.1, 7.4)
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Discoloration of body fluids: May permanently stain contact lenses or dentures red-orange. (5.5)
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Clostridium difficile-associated colitis: eva luate if diarrhea occurs. (5.6)
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Porphyria: Avoid use in patients with porphyria. (5.7)
ADVERSE REACTIONS
The most common adverse reactions with regimen for active pulmonary tuberculosis (1% and greater) are anemia, lymphopenia, neutropenia, increased ALT, arthralgia, conjunctivitis, headache, vomiting, nausea, diarrhea, rash, pruritus, anorexia and lymphadenopathy. The most common adverse reaction (1% and greater) with the regimen for latent tuberculosis infection is hypersensitivity reaction. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
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Protease Inhibitors and Reverse Transcriptase Inhibitors. (5.2, 7.1)
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Hormonal Contraceptives: Use another means of birth control. (7.3)
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May increase metabolism and decrease the activity of drugs metabolized by cytochrome P450 3A4 and 2C8/9. Dosage adjustments may be necessary if given concomitantly. (7.4)
USE IN SPECIFIC POPULATIONS
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Pregnancy: Based on animal data, may cause fetal harm. (8.1)
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Nursing Mothers: Discontinue drug or nursing taking into consideration importance of drug to mother. (8.3)
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Pediatrics: Safety and effectiveness in treating active pulmonary tuberculosis in children under the age of 12 years have not been established. (8.4)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 12/2014
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Active Pulmonary Tuberculosis
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 [see Dosage and Administration (2.1) and Clinical Studies (14.1)].
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 [see Warnings and Precautions (5.3) and Clinical Studies (14.1)].
PRIFTIN has not been studied as part of the initial phase treatment regimen in HIV- infected patients with active pulmonary tuberculosis.
1.2 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) [see Clinical Studies (14.2)].
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. [see Dosage and Administration (2.2) and Clinical Studies (14.2)]
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PRIFTIN in combination with isoniazid is not recommended for Individuals presumed to be exposed to rifamycin- or - isoniazid resistant M. tuberculosis.
2 DOSAGE AND ADMINISTRATION
2.1 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.
2.2 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.
2.3 Administration
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. [see Clinical Pharmacology (12.3)].
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 [see Clinical Pharmacology (12.3)].
3 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.
4 CONTRAINDICATIONS
4.1 Hypersensitivity
PRIFTIN is contraindicated in patients with a history of hypersensitivity to rifamycins.
5 WARNINGS AND PRECAUTIONS
5.1 Hepatotoxicity
Elevations of liver transaminases may occur in patients receiving PRIFTIN [see Adverse Reactions 6.1]. 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.
5.2 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 [see Patient Counseling Information (17)].
Monitor patients receiving PRIFTIN therapy for signs and/or symptoms of hypersensitivity reactions. If these symptoms occur, administer supportive measures and discontinue PRIFTIN.
5.3 Relapse in the Treatment of Active Pulmonary Tuberculosis
PRIFTIN has not been eva luated 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 [see Clinical Studies (14.1)].
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 [see Clinical Studies (14.1)].
Poor adherence to therapy is associated with high relapse rate. Emphasize the importance of compliance with therapy [see Patient Counseling Information (17)]
5.4 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 [see Drug Interactions (7.1, 7.2, 7.3 and 7.4) and Clinical Pharmacology (12.3)].
5.5 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.
5.6 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 eva luation as clinically indicated.
5.7 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.
6 ADVERSE REACTIONS
The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
6.1 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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