What are the exclusion criteria for using Rifapentine (Rifapentine) and Moxifloxacin (Moxifloxacin) in a shorter treatment regimen for pulmonary tuberculosis (PTB) in adults?

Exclusion Criteria for 4-Month Rifapentine-Moxifloxacin Regimen in Adults with Pulmonary Tuberculosis

Do not use the 4-month rifapentine-moxifloxacin regimen in patients aged <12 years, body weight <40 kg, or those with known or suspected drug-resistant tuberculosis. 1

Absolute Contraindications

Age and Weight Restrictions

• Age <12 years 1
• Body weight <40 kg 1

Drug Resistance

• Known or suspected resistance to isoniazid, rifamycins (rifampin/rifapentine), fluoroquinolones, or pyrazinamide 1, 2
• Recent exposure to key TB drugs: Patients who received >5 doses of isoniazid, rifampin, rifabutin, rifapentine, pyrazinamide, or any fluoroquinolone in the preceding 30 days (e.g., for urinary tract infection or pneumonia) 1
• Prior TB treatment: Patients who received >14 consecutive days of multidrug TB treatment in the preceding 6 months 1

Pregnancy and Lactation

• Pregnant or breastfeeding women 3

HIV-Related Restrictions

• HIV-positive patients with CD4 counts <100 cells/μL 1
• HIV-positive patients on antiretroviral therapy other than efavirenz-based regimens (unless no other drug-drug interactions exist) 1
• HIV-positive patients not receiving or planning to initiate antiretroviral therapy 1

Situations Requiring Clinical Consultation (Relative Contraindications)

Hepatic Dysfunction

• ALT or AST >3 times the upper limit of normal 1, 3
• Total bilirubin >2.5 times the upper limit of normal 1, 3
• Preexisting advanced liver disease 1

Renal Dysfunction

• Serum creatinine >2 times the upper limit of normal 1
• Renal insufficiency or end-stage renal disease 1, 2

Electrolyte Abnormalities

• Plasma potassium level <3.5 mEq/L 1

Extrapulmonary Tuberculosis

• Paucibacillary extrapulmonary TB (pleural or lymph node TB that does not pose substantial risk for death or disability and does not require prolonged treatment) requires consultation 1, 3
• All other forms of extrapulmonary TB are excluded 3

Microbiological Testing Issues

• Inability to submit a specimen for M. tuberculosis resistance testing before initiating treatment 1

Important Clinical Nuances

Cavitary Disease

The 4-month rifapentine-moxifloxacin regimen can be used in patients with cavitary disease on chest radiograph, as treatment duration is independent of cavitation status. 1, 2 This differs from traditional regimens where cavitation affects continuation phase duration.

Paucibacillary Disease

The regimen was not formally studied in patients with negative sputum culture but clinically suspected paucibacillary pulmonary TB. However, CDC recommends the 4-month regimen may be used in these patients unless they fall into one of the excluded groups listed above. 1

HIV-Positive Patients

Among the 194 HIV-positive participants in the pivotal trial (median CD4+ count 344 cells/μL), the rifapentine-moxifloxacin regimen demonstrated noninferiority to the standard 6-month regimen with fewer adverse events. 4 However, strict criteria must be met: CD4 ≥100 cells/μL and efavirenz-based ART only. 1

Common Pitfalls to Avoid

• Do not assume all smear-negative TB is suitable for this regimen without obtaining cultures and drug susceptibility testing. 3
• Do not use this regimen in patients with recent fluoroquinolone exposure (>5 doses in past 30 days), as this may select for resistance. 1, 2
• Do not skip baseline molecular and phenotypic drug susceptibility testing—testing for at least isoniazid, pyrazinamide, rifampin, and fluoroquinolones is essential before initiating treatment. 1, 2
• Do not use this regimen in HIV-positive patients on non-efavirenz ART regimens without expert consultation on drug-drug interactions. 1