rifapentine
Brand: Priftin
Prototype: rifampin
Drug Class: rifamycin antibiotic
Drug Family: antibiotic
Subclass: long-acting rifamycin for TB
Organ Systems: infectious-disease
Mechanism of Action
Inhibits bacterial RNA polymerase; long half-life enables once-weekly dosing; potent CYP3A4 and CYP2C9 inducer comparable to rifampin.
bacterial DNA-dependent RNA polymerase (beta subunit)
Indications
- active tuberculosis (intensive and continuation phases)
- latent TB infection (LTBI) — 3HP regimen: weekly rifapentine + isoniazid for 12 weeks
Contraindications
- rifamycin hypersensitivity
- concurrent use of drugs with narrow therapeutic windows that are significantly affected by CYP induction
Adverse Effects
Common
- orange-brown secretion discoloration
- GI upset
- hyperuricemia
Serious
- hepatotoxicity
- hypersensitivity reactions (including flu-like syndrome)
- drug interactions via potent CYP3A4 induction
Pharmacokinetics (ADME)
| Absorption | 70% oral bioavailability; high-fat meal increases absorption by 40–50% |
| Distribution | large Vd; distributes into macrophages; active metabolite 25-desacetylrifapentine |
| Metabolism | hepatic; potent CYP3A4 and CYP2C9 inducer |
| Excretion | primarily biliary/fecal; renal ~17% |
| Half-life | 13–19 hours |
| Onset | 5–6 hours |
| Peak | 5–6 hours |
| Duration | once-weekly (for LTBI regimen) |
| Protein Binding | 98% (desacetyl metabolite ~93%) |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| HIV antiretrovirals | potent CYP3A4 induction reduces ARV levels; generally avoid with PI-based regimens | major |
| warfarin | CYP2C9 induction reduces warfarin levels; monitor INR closely | major |
| oral contraceptives | CYP3A4 induction reduces OCP levels; contraceptive failure risk | major |
Nursing Considerations
- Administer with food (high-fat meal preferred) to enhance absorption during LTBI treatment.
- Counsel patients to avoid rifapentine during pregnancy (not first choice) and to use non-hormonal contraception during therapy due to CYP3A4 induction.
- The 3HP regimen (weekly rifapentine + isoniazid for 12 weeks) is now a preferred regimen for LTBI; adherence is facilitated by directly observed therapy or self-administration.
- Warn about orange-brown discoloration of secretions — permanent contact lens staining is a practical concern.
Clinical Pearls
- The 3HP regimen (3 months of once-weekly rifapentine + isoniazid) for latent TB infection has become the preferred CDC regimen for most adults, offering superior completion rates compared to 9 months of daily isoniazid monotherapy.
- Rifapentine is a potent CYP3A4 and CYP2C9 inducer like rifampin; all the same drug interaction considerations apply, particularly for antiretrovirals, anticoagulants, and hormonal contraceptives.
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.