No, rifapentine is not the same as rifampin—they are distinct rifamycin antibiotics with different pharmacologic properties, dosing schedules, and clinical applications.

Key Structural and Pharmacologic Differences

Rifapentine and rifampin are both rifamycin derivatives but differ significantly in their chemical structure and pharmacokinetic profiles. 1

Chemical structure: Rifapentine is a cyclopentyl rifamycin with molecular formula C47H64N4O12, while rifampin has a different molecular structure 1
Half-life: Rifapentine has a substantially longer half-life (>14 hours) compared to rifampin, allowing for less frequent dosing 2, 3
Protein binding: Rifapentine has much higher protein binding (97%) compared to rifampin, which may affect its efficacy and explain why higher doses are needed 4
MIC against M. tuberculosis: Rifampin has a higher MIC (less potent per dose) against M. tuberculosis than rifapentine, though rifapentine is generally more active 3, 5

The two drugs have different approved indications and cannot be used interchangeably:

Rifampin: Standard first-line agent for all forms of tuberculosis, given daily at 10 mg/kg (maximum 600 mg) 2
Rifapentine: Approved only for specific limited indications—once-weekly dosing (10 mg/kg, maximum 600 mg) with isoniazid during the continuation phase for HIV-negative patients with noncavitary, drug-susceptible pulmonary TB who have negative sputum smears after the initial phase 2

Organisms resistant to rifampin are likely to be resistant to rifapentine due to high cross-resistance:

Cross-resistance occurs because both drugs target the same site (beta subunit of DNA-dependent RNA polymerase) 1, 5
Resistance develops through mutations in the rpoβ gene 1
A high level of cross-resistance between rifampin and rifapentine has been demonstrated with M. tuberculosis strains 1

Both drugs induce hepatic enzymes but with different potencies:

Relative CYP450 induction potency: Rifampin > rifapentine > rifabutin 2, 4
Both cause significant drug interactions with antiretrovirals, oral contraceptives, warfarin, and other medications metabolized by CYP450 2, 6
Drug interaction monitoring requirements are similar for both agents 2

The adverse effects are similar but not identical:

Both cause orange discoloration of body fluids, hepatotoxicity, and gastrointestinal symptoms 2
Rifapentine's adverse effects are described as "similar to those associated with rifampin" but clinical experience is more limited 2
Both drugs can cause flulike syndrome, rash, and hepatotoxicity at comparable frequencies 2

Rifapentine has critical restrictions that rifampin does not:

Contraindicated in HIV-infected patients for once-weekly continuation phase due to unacceptably high relapse rates and acquired rifamycin resistance 2
Not approved for use in children 2
Insufficient data for use in pregnancy 2
No data on CSF penetration, unlike rifampin which achieves 10-20% of serum levels in CSF 2

Clinical trial data show nuanced differences:

In Western studies, rifapentine-based therapy showed slightly higher sputum culture conversion rates at 6 months but higher relapse rates during follow-up, related to poor compliance during the intensive phase 5
In Chinese trials, rifapentine and rifampin produced similar sputum culture conversion rates with low relapse rates 5
Murine models demonstrate rifapentine is approximately 4 times more potent than rifampin in sterilizing activity 7