PRIFTIN^® – Helping to Reduce Progression to TB Disease

PRIFTIN^® Explained

PRIFTIN (rifapentine) is an antimycobacterial approved in the US since 1998, in combination with one or more anti-tuberculosis (TB) drugs, for the treatment of active pulmonary tuberculosis caused by the Mycobacterium tuberculosis bacterium.¹

In 2014, the Food and Drug Administration (FDA) further approved PRIFTIN in combination with the antibiotic isoniazid (INH) as directly observed therapy for the treatment of latent tuberculosis infection (LTBI) in people 2 years of age or older at high risk of progression to TB disease.²

The combination of PRIFTIN-INH treatment is a 12-dose regimen, also known as 3HP, which translates into 3 months of once weekly doses of the two drugs, INH and RPT.³

Indications, Dosage and Administration for LTBI

A Large TB Study on 3HP

The impetus for FDA approval of PRIFTIN^® was the findings of the PREVENT TB study conducted by the CDC-Tuberculosis Trials Consortium (TBTC) and published in the New England Journal of Medicine in 2011.⁴

This multi-center, prospective, open-label, randomized, active-controlled, non-inferiority trial compared the effectiveness of 12 weekly doses of PRIFTIN in combination with isoniazid (3RPT/INH arm) administered by directly observed therapy with 9 months of self-administered daily isoniazid (9INH).¹

The trial enrolled patients 2 years of age or older with a positive tuberculin skin test and at high risk of progression to tuberculosis disease. Enrolled patients included those having close contact with a patient with active tuberculosis disease, recent (within 2 years) conversion to a positive tuberculin skin test, HIV infection, or fibrosis on a 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.

Active tuberculosis developed in 5 of 3074 randomized patients in the 3RPT/INH group (0.16%) versus 10 of 3074 patients in the 9INH group (0.32%), for a difference in cumulative rates of 0.17%, 95% CI (-043, 0.09). There was higher treatment completion with the 12-dose regimen, with 81.2% of participants completing the 3-month course of medication, compared to 68.3% who completed the 9-month course.

In the pediatric sub-study, one child in the 9INH group developed tuberculosis (1/367, cumulative rate 0.32%) versus zero tuberculosis cases in the 3RPT/INH group (0/375) at 33 months post enrollment. The proportion of patients completing treatment in the 3RPT/INH and the 9INH groups was 87.5% and 79.6% respectively for a difference of 7.9%, 95% CI (2.5, 13.2).

In the HIV study, tuberculosis disease developed in 2/206 patients in the 3RPT/INH group (cumulative rate, 1.01%) and in 6/193 patients in the 9INH group (cumulative rate, 3.45%). The proportion of patients completing treatment in the 3RPT/INH and 9INH groups was 88.8% and 63.7%, respectively for a difference of 25.1%, 95% CI (16.8, 32.9).

Select Adverse Reactions Occurring in 0.5% or Greater of Patients in the Latent Tuberculosis Infection Main Study

System Organ Class Preferred Term	3RPT/INH (N=4040) N (%)	9INH (N=3759) N (%)
Immune system disorders
Hypersensitivity	161 (4)	18 (0.5)
Hepatobiliary
Hepatitis	24 (0.6)	113 (3)
Nervous System disorders
Headache	26 (0.6)	17 (0.5)
Skin and subcutaneous tissue disorders
Skin reaction	31 (0.8)	21 (0.6)

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.

Treatment of LTBI - A Public Health Priority

Important Safety Information for PRIFTIN^® (rifapentine)

Priftin is contraindicated in patients with a history of hypersensitivity to rifamycins.

Elevations of liver transaminases may occur in patients receiving Priftin. Patients should be monitored for symptoms of liver injury. Patients with abnormal liver function 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. Discontinue Priftin if evidence of liver injury occurs.

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. There have been reports of anaphylaxis. Monitor patients for signs and/or symptoms of hypersensitivity reactions. If these symptoms occur, administer supportive measures and discontinue Priftin.

Severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome 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.

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 relapse in these patients.

Rifapentine is an inducer of Cytochrome P450 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 of these drugs. Dosage adjustment of the drugs may be necessary.

Priftin may produce a red-orange discoloration of body tissues and/or fluids and may permanently stain contact lenses or dentures red-orange.

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. CDAD must be considered in all patients who present with diarrhea following antibacterial use. If CDAD is suspected or confirmed, discontinue antibacterial use not directed against C. difficile if possible and institute appropriate treatment measures.

Avoid the use of Priftin in patients with porphyria.

In Priftin studies, the most common adverse reactions with the regimen for active pulmonary tuberculosis (≥3%) are anemia, lymphopenia, hemoptyis, neutropenia, cough, thrombocytosis, increased sweating, increased ALT, increased AST, back pain, rash, anorexia, arthralgia, increased blood urea, and headache. The most common adverse reaction (≥3%) with the regimen for latent tuberculosis infection is hypersensitivity reaction.

Indications

Active Pulmonary Tuberculosis

Priftin^® (rifapentine) is indicated in adults and children 12 years and older for the treatment of active pulmonary tuberculosis caused by Mycobacterium tuberculosis. Priftin must always be used in combination with one or more antituberculosis 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-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 INH as a 12-week once-weekly regimen for the treatment of latent tuberculosis infection. Priftin in combination with INH is not recommended for Individuals presumed to be exposed to rifamycin- or - INH resistant M. tuberculosis.

Read Full Prescribing Information for PRIFTIN (rifapentine)
Read Full Important Safety Information for PRIFTIN (rifapentine)

1 Priftin Highlights of Prescribing Information (drug label). Available at: http://products.sanofi.us/priftin/Priftin.pdf 2 Sanofi US News Release. Sanofi Receives FDA Approval of Priftin® Tablets for the Treatment of Latent Tuberculosis Infection. December 2, 2014 3 Centers for Disease Control and Prevention. 3HP FAQs for Health Providers. Available at: https://www.cdc.gov/tb/education/FAQforProviders.htm 4 Sterling et al. NEJM, 2011; 365(23):2155-2166 5 Centers for Disease Control and Prevention, TB in the United States: A Snapshot 2016. Available at: https://www.cdc.gov/nchhstp/newsroom/docs/factsheets/tb-in-the-us-a-snapshot.pdf

Weight Range	PRIFTIN Dose	Number of Tablets
10 – 14 kg	300 mg	2
14.1 – 25 kg	450 mg	3
25.1 – 32 kg	600 mg	4
32.1 – 50 kg	750 mg	5
>50 kg	900 mg	6

PRIFTIN^® – Helping to Reduce Progression to TB Disease

PRIFTIN^® Explained

Indications, Dosage and Administration for LTBI

Dosage for adults and children ≥12 years

Dosage for children 2 to 11 years

A Large TB Study on 3HP

Select Adverse Reactions Occurring in 0.5% or Greater of Patients in the Latent Tuberculosis Infection Main Study

Treatment of LTBI - A Public Health Priority

Why Now?

Important Safety Information for PRIFTIN^® (rifapentine)

PRIFTIN® – Helping to Reduce Progression to TB Disease

PRIFTIN® Explained

Indications, Dosage and Administration for LTBI

A Large TB Study on 3HP

Treatment of LTBI - A Public Health Priority

Important Safety Information for PRIFTIN® (rifapentine)

PRIFTIN^® – Helping to Reduce Progression to TB Disease

PRIFTIN^® Explained

Important Safety Information for PRIFTIN^® (rifapentine)