PRIFTIN Film-coated tablet Ref.[11132] Active ingredients: Rifapentine

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 to 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 Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome have been reported in association with the use of rifapentine (PRIFTIN) treatment regimens in patients with active and latent tuberculosis. Discontinue PRIFTIN at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity [see Patient Counseling Information (17)].

5.4 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 [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)].

5.5 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, 7.4) and Clinical Pharmacology (12.3)].

5.6 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.

5.7 Clostridioides Difficile–Associated Diarrhea

Clostridioides 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.

5.8 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.

The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:

• Hepatotoxicity [see Warnings and Precautions (5.1)]
• Hypersensitivity [see Contraindications (4.1) and Warnings and Precautions (5.2)]
• Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.3)]
• Discoloration of Body Fluids [see Warnings and Precautions (5.6)]
• Clostridioides Difficile–Associated Diarrhea [see Warnings and Precautions (5.7)]
• Porphyria [see Warnings and Precautions (5.8)]

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 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.

Table 2. Selected Treatment Emergent Adverse Reactions during Treatment of Active Pulmonary Tuberculosis and through Three Months Follow-up:

^* Initial phase consisted of therapy with either PRIFTIN twice weekly or rifampin daily combined with daily isoniazid, pyrazinamide, and ethambutol for 60 days.
^† Continuation phase consisted of therapy with either PRIFTIN once weekly or rifampin twice weekly combined with daily isoniazid for 120 days.

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: 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. Five hundred and two non–HIV-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 Dosage 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 to 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 to 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. One hundred and sixty-one (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. One hundred and thirteen (3%) 9INH subjects and 24 (0.6%) 3RPT/INH subjects developed hepatotoxicity.

One hundred and ninety-six 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%.

Table 3. Select Adverse Reactions Occurring in 0.5% or Greater of Patients* in the Latent Tuberculosis Infection Main Study:

Pediatric substudy

Six hundred and ninety children 2 to 17 years of age received at least one dose of study drugs in the main study. An additional 342 children 2 to 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 to 11 years of age and 12 to 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 than 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, 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.

The following adverse reactions have been identified from postmarketing surveillance of rifapentine. Because these reactions are reported from a population of unknown size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

Skin and subcutaneous tissue disorders: Severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome [see Warnings and Precautions (5.3)].

7.1 Protease Inhibitors and Reverse Transcriptase Inhibitors

Rifapentine is an inducer of CYP450 enzymes. Concomitant use of PRIFTIN with other drugs metabolized by these enzymes, such as protease inhibitors and certain reverse transcriptase inhibitors, may cause a significant decrease in plasma concentrations and loss of therapeutic effect of the protease inhibitor or reverse transcriptase inhibitor [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)].

7.2 Fixed-Dose Combination of Efavirenz, Emtricitabine, and Tenofovir

Once-weekly coadministration of 900 mg PRIFTIN with the antiretroviral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in HIV-infected patients did not result in any substantial change in steady state exposures of efavirenz, emtricitabine, and tenofovir. No clinically significant change in CD4 cell counts or viral loads were noted [see Clinical Pharmacology (12.3)].

7.3 Hormonal Contraceptives

PRIFTIN may reduce the effectiveness of hormonal contraceptives. Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method or add a barrier method of contraception during treatment with PRIFTIN [see Use in Specific Populations (8.3) and Clinical Pharmacology (12.3)].

7.4 Cytochrome P450 3A4 and 2C8/9

Rifapentine is an inducer of cytochromes P450 3A4 and P450 2C8/9. Therefore, PRIFTIN may increase the metabolism of other coadministered drugs that are metabolized by these enzymes. Induction of enzyme activities by PRIFTIN occurred within 4 days after the first dose. Enzyme activities returned to baseline levels 14 days after discontinuing PRIFTIN.

Rifampin has been reported to accelerate the metabolism and may reduce the activity of the following drugs; hence, PRIFTIN may also increase the metabolism and decrease the activity of these drugs. Dosage adjustments of the drugs in Table 4 or of other drugs metabolized by cytochrome P450 3A4 or P450 2C8/9 may be necessary if they are given concurrently with PRIFTIN.

Table 4. Drug Interactions with PRIFTIN: Dosage Adjustment May be Necessary:

7.5 Other Interactions

The conversion of PRIFTIN to 25-desacetyl rifapentine is mediated by an esterase enzyme. There is minimal potential for PRIFTIN metabolism to be inhibited or induced by another drug, based upon the characteristics of the esterase enzymes.

Since PRIFTIN is highly bound to albumin, drug displacement interactions may also occur [see Clinical Pharmacology (12.3)].

7.6 Interactions with Laboratory Tests

Therapeutic concentrations of rifampin have been shown to inhibit standard microbiological assays for serum folate and Vitamin B₁₂. Similar drug-laboratory interactions should be considered for PRIFTIN; thus, alternative assay methods should be considered.

Risk Summary

Based on animal data, PRIFTIN may cause fetal harm when administered to a pregnant woman. Available data from clinical trials, case reports, epidemiology studies and postmarketing experience with PRIFTIN use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, adverse maternal or fetal outcomes. In two clinical trials, a total of 59 patients who were treated with rifapentine in combination with other anti-tuberculosis drugs became pregnant. Overall, the reported rate of miscarriage following rifapentine exposure in these two clinical trials did not represent an increase over the background rate of miscarriage reported in the general population (see Data). There are risks associated with active tuberculosis during pregnancy. When administered during the last few weeks of pregnancy, PRIFTIN may be associated with maternal postpartum hemorrhage and bleeding in the exposed neonates (see Clinical Considerations). In animal reproduction and developmental toxicity studies, adverse developmental outcomes (including cleft palate or mal-positioned aortic arches) were observed following administration of rifapentine to pregnant rats and rabbits at doses approximately 0.6 and 0.3 to 1.3 times, respectively, of the recommended human dose based on body surface area comparisons (see Data). Based on animal data, advise pregnant women of the risk for fetal harm. As rifapentine is always used in combination with other antituberculosis drugs such as isoniazid, ethambutol, and pyrazinamide, refer to the prescribing information of the other drug(s) for more information on their associated risks of use during pregnancy.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo-fetal risk

Active tuberculosis in pregnancy is associated with adverse maternal and neonatal outcomes including maternal anemia, cesarean delivery, preterm birth, low birth weight, birth asphyxia, and perinatal infant death.

Labor or delivery

When administered during the last few weeks of pregnancy, PRIFTIN may increase the risk for maternal postpartum hemorrhage and bleeding in the exposed neonate. Monitor prothrombin time of pregnant women and neonates who are exposed to PRIFTIN during the last few weeks of pregnancy. Treatment with Vitamin K may be indicated.

Data

Human data

Fourteen patients with active tuberculosis treated with multiple antituberculosis drugs including PRIFTIN became pregnant during clinical studies. Six delivered normal infants, four had first trimester spontaneous abortions (of these, one patient abused ethanol and another patient was HIV-infected), one had an elective abortion, and outcome was unknown in three patients. These data are, however, limited by the quality of reporting and confounded by comorbid medical conditions and multiple antituberculosis drug exposures.

In the trial that compared the safety and effectiveness of PRIFTIN in combination with isoniazid to isoniazid alone for the treatment of latent tuberculosis infection, a total of 45 (2.5%) women in the PRIFTIN/isoniazid arm and 71 (4.1%) women in the isoniazid arm became pregnant. Among the 46 total pregnancies in the PRIFTIN/isoniazid arm, there were 31 live births, 6 elective abortions, 7 spontaneous abortions, and 2 unknown outcomes. Of the 31 live infants, 21 were reported healthy while in the other ten cases no further details were available. The rate of spontaneous abortion in the PRIFTIN/isoniazid arm (15%) and the rate of spontaneous abortion in the isoniazid arm (19%) did not represent an increase over the background rate of 15 to 20 percent reported in the general population. Further interpretation of these results is limited by the quality of adverse event reporting.

Animal data

Animal studies in rats and rabbits revealed malformations and other adverse developmental outcomes in both species. Pregnant rats given oral rifapentine during organogenesis (gestational days 5 through 15) at 40 mg/kg/day (0.6 times the human dose of 600 mg based on body surface area comparisons) produced pups with cleft palates and mal-positioned aortic arches, delayed ossification, increased number of ribs, a decrease in litter size and mean litter weight, an increase in number of stillbirths, and an increase in mortality during lactation.

When rifapentine was administered orally to mated female rats late in gestation, at 20 mg/kg/day (0.3 times the human dose based on body surface area), pup weights and gestational survival (live pups born/pups born) were reduced compared to controls. Increased resorptions and postimplantation loss, decreased mean fetal weights, increased numbers of stillborn pups, and slightly increased pup mortality during lactation were also noted. When pregnant rabbits received oral rifapentine at 10 mg/kg to 40 mg/kg (0.3 times to 1.3 times the human dose based on body surface area) during organogenesis (GD6 to GD18), major fetal malformations occurred including: ovarian agenesis, pes varus, arhinia, microphthalmia, and irregularities of the ossified facial tissues. At 40 mg/kg/day, there were increases in postimplantation loss and the incidence of stillborn pups.

Risk Summary

There are no data on the presence of rifapentine or its metabolite in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Since PRIFTIN 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 (see Clinical Considerations). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for PRIFTIN and any potential adverse effects on the breastfed infant from PRIFTIN or from the underlying maternal condition.

Clinical Considerations

Monitor infants exposed to rifapentine through breast milk for signs of hepatotoxicity to include irritability, prolonged unexplained crying, yellowing of the eyes, loss of appetite, vomiting, and changes in color of the urine (darkening) or stool (lightening, pale or light brown).

Contraception

Use of PRIFTIN may reduce the efficacy of hormonal contraceptives. Advise patients using hormonal contraceptives to use an alternative non-hormonal contraceptive method or add a barrier method of contraception during treatment with PRIFTIN [see Warnings and Precautions (5.5) and Drug Interactions (7.3)].

The safety and effectiveness of PRIFTIN in the treatment of active pulmonary tuberculosis have not been established in pediatric patients under the age of 12.

The safety and effectiveness of PRIFTIN in combination with isoniazid once-weekly regimen has been evaluated in pediatric patients (2 to 17 years of age) for the treatment of latent tuberculosis infection. In clinical studies, the safety profile in children was similar to that observed in adult patients [see Adverse Reactions (6.1) and Clinical Studies (14.2)].

In a pharmacokinetic study conducted in 2 to 11-year-old pediatric patients with latent tuberculosis infection, PRIFTIN was administered once weekly based on weight (15 mg/kg to 30 mg/kg, up to a maximum of 900 mg). Exposures (AUC) in children 2 to 11 years old with latent tuberculosis infection were higher (average 31%) than those observed in adults receiving PRIFTIN 900 mg once weekly [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

Clinical studies with PRIFTIN did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. In a pharmacokinetic study with PRIFTIN, no substantial differences in the pharmacokinetics of rifapentine and 25-desacetyl metabolite were observed in the elderly compared to younger adults [see Clinical Pharmacology (12.3)].