Rifapentine has shown higher bacteriostatic and bactericidal activities especially against intracellular bacteria growing in human monocyte-derived macrophages. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of M. tuberculosis. Rifapentine acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.
A review of alternative regimens for prevention of active tuberculosis in HIV-negative individuals with latent TB found that a weekly, directly observed regimen of rifapentine with isoniazid for three months was as effective as a daily, self -administered regimen of isoniazid for nine months. But the rifapentine-isoniazid regimen had higher rates of treatment completion and lower rates of hepatotoxicity. However, the rate of treatment-limiting adverse events was higher in the rifapentine-isoniazid regimen.
The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
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
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.
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.
Fixed Dose Combination Of Efavirenz, Emtricitabine And Tenofovir
Once-weekly co-administration of 900 mg PRIFTIN with the antiretroviral fixed dose combination of efavirenz 600 mg, emtricitabine 200 mg and tenofovir disoproxyl fumarate 300mg 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 .
PRIFTIN may reduce the effectiveness of hormonal contraceptives. Therefore, patients using oral, transdermal patch, or other systemic hormonal contraceptives should be advised to change to non-hormonal methods of birth control.
Cytochrome P450 3A4 And 2C8/9
Rifapentine is an inducer of cytochromes P4503A4 and P4502C8/9. 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.
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.
Tell your doctor about all the medicines you take, including prescription and over-thecounter medicines, vitamins, and herbal supplements.
Using PRIFTIN with other medicines may affect each other causing serious
side effects. PRIFTIN may affect the way other medicines work, and other
medicines may affect how PRIFTIN works. Especially tell your doctor if you take
medicines to treat HIV infection or oral contraceptives.
Before taking rifapentine, tell your doctor or pharmacist if you are allergic to it; or to other rifamycins (such as rifampin); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: HIV infection, a certain blood disorder (porphyria), liver disease, alcoholise. Alcohol may increase the risk of liver disease. Avoid alcoholic beverages while using this medication. Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Rifapentine may cause live bacterial vaccines (such as typhoid vaccine) not to work as well. Therefore, do not have any immunizations/vaccinations while using this medication without the consent of your doctor. During pregnancy, this medication should be used only when clearly needed. When this drug is taken during the last few weeks of pregnancy, the risk of bleeding in both mother and infant may be increased. Tell your doctor immediately if you notice any bleeding in your new-born. Discuss the risks and benefits with your doctor. It is unknown if rifapentine passes into breast milk. However, similar drugs pass into breast milk. Discuss the risks and benefits with your doctor before breast-feeding.