Dosing and uses of Priftin (rifapentine)
Adult dosage forms and strengths
tablet
- 150mg
Pulmonary Tuberculosis
Indicated for treatment of pulmonary TB caused by Mycobacterium tuberculosis in combination with 1 or more antituberculosis drugs
Initial phase (2 months): 600 mg PO 2x/week for 2 months; interval between doses not <3 d (in combination with other antiTB drugs) THEn
Continuation phase (4 months): 600 mg PO qWeek for 4 months by direct observation therapy with isoniazid or another appropriate antiTB drug
Administration: take with meaL
Latent Tuberculosis
Indicated for treatment of latent TB infection caused by M. tuberculosis in adults and children aged ≥2 yr at high risk of progression to TB disease (including those in close contact with active TB patients, recent conversion to a positive tuberculin skin test, HIV-infected patients, or those with pulmonary fibrosis on radiograph)
Once weekly rifapentine PO (weight based dosing below) plus isoniazid once-weekly for 12 weeks as directly observed therapy (DOT)
≥12 years and >50 kg: 900 mg
≥12 years and 32.1-50 kg: 750 mg
Isoniazid dose: 15 mg/kg (rounded to nearest 50 mg or 100 mg); not to exceed 900 mg once-weekly for 12 weeks
References: CDC MMWR 2011;60:1650-3 and NEJM 2011;365:2155-2166
Limitations of use
- Active TB disease should be ruled out before initiating
- Must always be used in combination with isoniazid as a 12-wk once-weekly regimen
- Rifapentine in combination with isoniazid is not recommended for rifamycin or isoniazid resistant M tuberculosis
MAC Prophylaxis (Orphan)
Prophylactic treatment of Mycobacterium avium complex (MAC) in patients with AIDS and a CD4+ count less than or equal to 75/cu.mm
Orphan indication sponsor
- Hoechst Marion Roussel, Inc; P.O. Box 9627, Mail Station: H3-M2516; Kansas City, MO 64134-0627
MAC Treatment (Orphan)
Treatment of Mycobacterium avium complex (MAC) in patients with AIDs
Orphan indication sponsor
- Hoechst Marion Roussel, Inc; P.O. Box 9627, Mail Station: H3-M2516; Kansas City, MO 64134-0627
Pediatric dosage forms and strengths
tablet
- 150mg
Latent Tuberculosis
Indicated for treatment of latent TB infection caused by M. tuberculosis in adults and children aged ≥2 yr at high risk of progression to TB disease (including those in close contact with active TB patients, recent conversion to a positive tuberculin skin test, HIV-infected patients, or those with pulmonary fibrosis on radiograph)
<2 years: Safety and efficacy not established
2-11 years
- Once weekly rifapentine PO (weight based dosing below) plus isoniazid once-weekly for 12 weeks as directly observed therapy (DOT)
- 10-14 kg: 300 mg
- >14-25 kg: 450 mg
- >25-32 kg: 600 mg
- >32-49.9 kg: 750 mg
- ≥50 kg: Not to exceed 900 mg
- Isoniazid dose: 25 mg/kg (rounded to nearest 50 mg or 100 mg); not to exceed 900 mg once-weekly for 12 weeks
- References: CDC MMWR 2011;60:1650-3 and NEJM 2011;365:2155-2166
Limitations of use
- Active TB disease should be ruled out before initiating
- Must always be used in combination with isoniazid as a 12-wk once-weekly regimen
- Rifapentine in combination with isoniazid is not recommended for rifamycin or isoniazid resistant M tuberculosis
Priftin (rifapentine) adverse (side) effects
>10%
Hyperuricemia (most likely d/t pyrazinamide from initial phase combo Tx)
1-10%
Hypertension
Headache
Dizziness
Rash
Pruritus
Acne
Anorexia
Nausea/vomiting
Dyspepsia
Diarrhea
Neutropenia
Lymphopenia
Anemia
Leukopenia
Thrombocytosis
Increased ALT/ASt
Arthralgia
Pain
Pyuria
Proteinuria
Hematuria
Urinary casts
Hemoptysis
Warnings
Contraindications
Hypersensitivity to rifamycins
Cautions
May increase liver enzymes; initiation in patients with existing abnormal liver tests and/or liver disease only in cases of necessity and under strict medical supervision; monitor LFTs every 2-4 week and discontinue if evidence of liver injury occurs
Hypersensitivity or anaphylaxis reported including hypotension, urticaria, angioedema, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, or flu-like syndrome
Not for use as initial phase treatment in HIV-infected individuals with active pulmonary TB
Higher relapse rate may occur in patients with cavitary pulmonary lesions and/or positive sputum cultures after the initial phase of active TB treatment, and in patients with bilateral pulmonary disease
Induces CYP450 isoenzymes; coadministration with drugs metabolized by these enzymes (eg, protease inhibitors, certain NRTIs, hormonal contraception) may result in significant decreased plasma concentrations and loss of therapeutic effect
May produce a red-orange discoloration of body tissues/fluids (eg, skin, teeth, tongue, urine, feces, saliva, sputum, tears, sweat, CSF); contact lenses or dentures may become permanently stained
As with the use of nearly all systemic antibacterial agents, Clostridium difficile-associated diarrhea (CDAD) reported; discontinue if CDAD confirmed
Porphyria reported in patients receiving rifampin, attributed to induction of delta amino levulinic acid synthetase; rifapentine may have similar enzyme induction properties; avoid in patients with history of porphyria
Pregnancy and lactation
Pregnancy category: C
Lactation: unknown
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Priftin (rifapentine)
Mechanism of action
Inhibits RNA polymerase in M. tuberculosis
Absorption
Peak Plasma Time: 5-6 hr
Distribution
Protein Bound: 98%
Metabolism
Enzymes induced: CYP3A4, CYP2C9/10
Elimination
Half-Life: 13 hr
Excretion: feces (70%); urine
