|
|
| (15 intermediate revisions by one other user not shown) |
| Line 1: |
Line 1: |
| {{DrugProjectFormSinglePage
| | #REDIRECT[[Rifapentine]] |
| |authorTag={{KS}}
| |
| |genericName=rifapentine
| |
| |aOrAn=an
| |
| |drugClass=antimycobacterial drug
| |
| |indicationType=treatment
| |
| |indication=active [[pulmonary tuberculosis]] and [[latent tuberculosis]]
| |
| |adverseReactions=[[anemia]], [[lymphopenia]], [[neutropenia]], increased ALT, [[arthralgia]], [[conjunctivitis]], [[headache]], [[vomiting]], [[nausea]], [[diarrhea]], [[rash]], [[pruritus]], [[anorexia]] and [[lymphadenopathy]]
| |
| |blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
| |
| |blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
| |
| | |
| * Content
| |
| | |
| <!--Adult Indications and Dosage-->
| |
| | |
| <!--FDA-Labeled Indications and Dosage (Adult)-->
| |
| |fdaLIADAdult===Indications==
| |
| | |
| '''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.
| |
| | |
| '''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.
| |
| | |
| [[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
| |
| | |
| ==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.
| |
| |offLabelAdultGuideSupport=* There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
| |
| |offLabelAdultNoGuideSupport=* There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
| |
| |fdaLIADPed=* There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
| |
| | |
| | |
| <!--Guideline-Supported Use (Pediatric)-->
| |
| |offLabelPedGuideSupport=* There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
| |
| |offLabelPedNoGuideSupport=* There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} 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.
| |
| |clinicalTrials=* The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
| |
| :*Hepatotoxicity
| |
| :*Hypersensitivity
| |
| :*Discoloration of Body Fluids
| |
| :*Clostridium difficile-Associated Diarrhea
| |
| :*Porphyria
| |
| | |
| * 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.
| |
| | |
| [[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
| |
| | |
| * 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.
| |
| | |
| :*'''Blood and Lymphatics''': [[lymphocytosis]], [[hematoma]], [[purpura]], [[thrombosis]].
| |
| | |
| :*'''Cardiovascular''': [[syncope]], [[tachycardia]], [[palpitation]], [[orthostatic hypotension]], [[pericarditis]].
| |
| | |
| :*'''Metabolic & Nutritional''': BUN increased, alkaline phosphatase increased.
| |
| | |
| :*'''Gastrointestinal''': [[gastritis]], [[esophagitis]], [[pancreatitis]], salivary gland enlargement.
| |
| | |
| :*''General'': [[asthenia]], facial [[edema]].
| |
| | |
| :*'''Hepatobiliary''': [[bilirubinemia]], [[hepatomegaly]], [[jaundice]].
| |
| | |
| :*'''Infectious Disease''': infection fungal.
| |
| | |
| :*'''Musculoskeletal''': [[myalgia]], [[myositis]].
| |
| | |
| :*'''Neurologic''': [[somnolence]], [[dysphonia]].
| |
| | |
| :'''Pregnancy, Puerperium and Perinatal conditions''': abortion
| |
| | |
| :*'''Psychiatric''': [[anxiety]], [[confusion]]
| |
| | |
| :*'''Reproductive Disorders''': [[vaginitis]], vaginal hemorrhage, [[leukorrhea]].
| |
| | |
| :*'''Respiratory''': [[dyspnea]], [[pneumonitis]], [[pulmonary fibrosis]], [[asthma]], [[bronchospasm]], laryngeal [[edema]], [[laryngitis]].
| |
| | |
| :*'''Skin''': [[urticaria]], skin discoloration,
| |
| | |
| * 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.
| |
| | |
| '''Latent Tuberculosis Infection'''
| |
| | |
| '''Main Study'''
| |
| | |
| * PRIFTIN in combination with isoniazid given once-weekly for 3 months (3RPT/INH) was compared to isoniazid given once daily for 9 months (9INH) in an open-label, randomized trial in patients with a positive tuberculin skin test, and at high risk for progression from latent tuberculosis infection to active tuberculosis disease. PRIFTIN was dosed by weight, and isoniazid mg/kg dose was determined according to age [see DOSING AND ADMINISTRATION (2.2)] to a maximum of 900 mg each.
| |
| | |
| * A total of 4040 patients received at least one dose of the 3RPT/INH regimen, including 348 children 2–17 years of age and 105 HIV-infected individuals. A total of 3759 received at least one dose of the 9INH regimen, including 342 children 2 years–17 years of age and 95 HIV-infected individuals.
| |
| | |
| * Patients were followed for 33 months from the time of enrollment. Treatment-emergent adverse reactions were defined as those occurring during treatment and 60 days after the last dose of treatment. 161 (4%) 3RPT/INH subjects had a rifamycin hypersensitivity reaction, defined as either: a) one of the following: hypotension, urticaria, angioedema, acute bronchospasm, or conjunctivitis occurring in relation to study drug or b) at least four of the following symptoms occurring in relation to the study drug, with at least one symptom being CTCAE Grade 2 or higher: weakness, fatigue, nausea, vomiting, headache, fever, aches, sweats, dizziness, shortness of breath, flushing or chills. No specific definition was used for isoniazid hypersensitivity; 18 (0.5%) 9INH subjects were classified as having a hypersensitivity reaction. Hepatotoxicity was defined as AST≥3× upper limit of normal in the presence of specific signs and symptoms of hepatitis, or AST>5× upper limit of normal regardless of signs or symptoms. 113 (3%) 9INH subjects and 24 (0.6%) 3RPT/INH subjects developed hepatotoxicity.
| |
| | |
| * 196 subjects (4.9%) in the 3RPT/INH arm discontinued treatment due to a treatment related adverse reaction patients and 142 (3.8%) in the 9INH arm discontinued treatment due to a treatment related adverse reaction. In the 3RPT/INH group, the most frequent treatment related adverse reaction resulting in treatment discontinuation was hypersensitivity reaction, occurring in 120 (3%) patients. In the 9INH group, the most frequent treatment related adverse reaction resulting in treatment discontinuation was hepatotoxicity, occurring in 76 (2%) patients.
| |
| | |
| * Seventy one deaths occurred, 31/4040, 0.77% in the 3RPT/INH group and 40/3759 (1.06%) in the 9INH group) during the 33 month study period. During the treatment emergent period, 11 deaths occurred, 4 in the 3RPT/INH group and 7 in the 9INH group. None of the reported deaths were considered related to treatment with study drugs or were attributed to tuberculosis disease.
| |
| | |
| * Table 3 presents select adverse reactions that occurred during the treatment emergent period in the main study in LTBI patients treated with 3RPT/INH or 9INH at a frequency greater than 0.5%.
| |
| | |
| [[File:XXXXX.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
| |
| | |
| '''Pediatric Substudy'''
| |
| | |
| * Six-hundred and ninety children 2 years–17 years of age received at least one dose of study drugs in the main study. An additional 342 children 2 years–17 years of age received at least one dose in the pediatric extension study (total 1032 children; 539 received 3RPT/INH and 493 received 9INH).
| |
| | |
| * No children in either treatment arm developed hepatotoxicity. Using the same definition for rifamycin hypersensitivity reaction as in the main study, 7 (1.3%) of children in the 3RPT/INH group experienced a rifamycin hypersensitivity reaction. Adverse reactions in children 2 years–11 years of age and 12 years–17 years of age were similar.
| |
| | |
| '''HIV Substudy'''
| |
| | |
| * Two-hundred HIV-infected patients with latent tuberculosis infection received at least one dose of study drugs in the main study and an additional 193 patients received at least one dose in the extension study (total of 393; 207 received 3RPT/INH and 186 received 9INH). Compared to the HIV-negative patients enrolled in the main study, a higher proportion of HIV-infected patients in each treatment arm experienced a treatment emergent adverse reaction, including a higher incidence of hepatotoxicity. Hepatotoxicity occurred in 3/207 (1.5%) patients in the 3RPT/INH arm and in 14/186 (7.5%) in the 9INH arm. Rifamycin hypersensitivity occurred in only one HIV-infected patient.
| |
| | |
| * Eleven deaths occurred during the 33 month follow up period (6/207 in the 3RPT/INH group and 5/186 in the 9INH group) including one death in the 9INH arm during the treatment emergent period. None of the reported deaths were considered related to treatment with study drugs or tuberculosis disease.
| |
| | |
| * Selected treatment-emergent adverse reactions reported during treatment and 60 days post-treatment in less 0.5% of the 3RPT/INH combination-therapy group in the main study are presented below by body system.
| |
| | |
| :*'''Eye Disorders''': [[conjunctivitis]].
| |
| | |
| :*'''Blood and Lymphatic System Disorders''': [[leukopenia]], [[anemia]], [[lymphadenopathy]], [[neutropenia]].
| |
| | |
| :*'''Gastrointestinal Disorders''': [[nausea]], [[diarrhea]], [[vomiting]], [[abdominal pain]], [[constipation]], [[dry mouth]], [[dyspepsia]], esophageal irritation, [[gastritis]], [[pancreatitis]].
| |
| | |
| :*'''General Disorders and Administration Site Conditions''': [[fatigue]], [[pyrexia]], [[asthenia]], [[chest pain]], [[chills]], feeling jittery.
| |
| | |
| :*'''Infections and Infestations''': [[pharyngitis]], [[viral infection]], [[vulvovaginal candidiasis]].
| |
| | |
| :*'''Metabolism and Nutrition Disorders''': [[hyperglycemia]], [[gout]], [[hyperkalemia]], decreased appetite, [[hyperlipidemia]].
| |
| | |
| :*'''Musculoskeletal and Connective Tissue Disorders''': [[arthralgia]], [[myalgia]], [[back pain]], [[rhabdomyolysis]].
| |
| | |
| :*'''Nervous system Disorders''': [[dizziness]], [[convulsion]], [[paresthesia]], [[headache]], [[peripheral neuropathy|neuropathy peripheral]], [[syncope]].
| |
| | |
| :*'''Psychiatric Disorders''': [[depression]], [[anxiety]], disorientation, suicidal ideation.
| |
| | |
| Renal and Urinary Disorders: azotemia.
| |
| | |
| Reproductive System and Breast Disorders: vulvovaginal pruritus.
| |
| | |
| Respiratory, Thoracic and Mediastinal Disorders: cough, dyspnea, oropharyngeal pain, asthma, bronchial hyperactivity, epistaxis.
| |
| | |
| Skin and Subcutaneous Tissue Disorders: rash, hyperhidrosis, pruritus, urticaria.
| |
| |alcohol=Alcohol-Rifapentin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
| |
| }}
| |