General Information

Priftin (rifapentine) is a rifamycin antimycobacterial drug.

Priftin is specifically 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 antituberculosis (anti-TB) drugs to which the isolate is susceptible.
• 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.

Priftin is supplied as a tablet for oral administration. Take with food. Tablets may be crushed and added to semi-solid food. The recommended dosing is as follows:

Active pulmonary tuberculosis:

Priftin should be used in regimens consisting of an initial 2 month phase followed by a 4 month continuation phase.

• 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 antituberculosis drugs.
• Continuation phase (4 Months): 600 mg once weekly for 4 months as directly observed therapy with isoniazid or another appropriate antituberculosis agent.

Latent tuberculosis infection:

Prifitn should be administered in combination with isoniazid once weekly for 12 weeks as directly observed therapy.

Adults and children ≥12 years and Children 2 to 11 years: based on weight

For Latent Tuberculosis Infection, the maximum recommended dose of Priftin 900 mg once weekly for 12 weeks.

Mechanism of Action

Priftin (rifapentine) is a rifamycin antimycobacterial drug. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis but does not affect mammalian cells at concentrations that are active against these bacteria. At therapeutic levels, rifapentine inhibits RNA transcription by preventing the initiation of RNA chain formation. It forms a stable complex with bacterial DNA-dependent RNA polymerase, leading to repression of RNA synthesis and cell death. Rifapentine and its 25-desacetyl metabolite accumulate in human monocyte-derived macrophages and are bactericidal to both intracellular and extracellular M. tuberculosis bacilli.

Side Effects

The most common adverse events related to treatment with Priftin combination therapy include:

• hyperuricemia
• increased liver function tests
• neutropenia
• pyuria
• proteinuria
• lymphopenia

Clinical Trial Results

Active Pulmonary Tuberculosis

PRIFTIN was studied in two randomized, open-label controlled clinical trials in the treatment of active pulmonary tuberculosis. The first trial was an open-label, prospective, parallel group, active-controlled trial in HIV-negative patients with active pulmonary tuberculosis. The population mostly comprised Black (approximately 60%) or multiracial (approximately 31%) patients. 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 600 mg in combination with isoniazid, pyrazinamide and ethambutol all administered daily. During the 4 -month continuation phase, 317 patients in the PRIFTIN group continued to receive PRIFTIN 600 mg dosed once weekly with isoniazid 300 mg and 304 patients in the rifampin group received twice weekly rifampin and isoniazid 900 mg. For patients weighing less than 50 kg, the doses of rifampin (450 mg) and isoniazid (600 mg) were reduced. Both treatment groups received pyridoxine (Vitamin B6) over the 6 -month treatment period. Treatment was directly observed. 

Assessments of sputum conversion at end of treatment (6 months) and relapse rates at the end of follow-up (24 months):

Status at End of 6 months of Treatment:

Converted: Priftin 87% (248/286) and Rifampin Combination Treatment 80% (226/283)

Status Through 24 Month Follow-up:

Relapsed: Priftin 12% (29/248) and Rifampin Combination Treatment  7% (15/226)

Sputum Negative: Priftin 57% (142/248) and Rifampin Combination Treatment 64% (145/226)

Latent Tuberculosis Infection

A multicenter, prospective, open-label, randomized, active-controlled trial compared the effectiveness of 12 weekly doses of PRIFTIN in combination with isoniazid (3RPT/INH arm) administered by directly observed therapy to 9 months of self-administered daily isoniazid (9INH arm). The trial enrolled patients two years of age or older with positive tuberculin skin test and at high risk for progression to tuberculosis disease. Enrolled patients included those having close contact with a patient with active tuberculosis disease, recent (within two years) conversion to a positive tuberculin skin test, HIV-infection, or fibrosis on chest radiograph. PRIFTIN was dosed by weight, for a maximum of 900 mg weekly. Isoniazid mg/kg dose was determined by age, for a maximum of 900 mg weekly in the 3RPT/INH arm and 300 mg daily in the 9INH arm. The outcome measure was the development of active tuberculosis disease, defined as culture confirmed tuberculosis in adults and culture-confirmed or clinical tuberculosis in children less than 18 years of age, at 33 months after trial enrollment. Active tuberculosis disease developed in 5 of 3074 randomized patients in the 3RPT/INH group (0.16%) versus 10 of 3074 patients in 9INH group (0.32%), for a difference in cumulative rates of 0.17%.