Latent tuberculosis infection (LTBI)

INH: Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms.
RPT: Inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis (MTB) (but not in mammalian cells). Rifapentine is bactericidal against both intracellular and extracellular MTB organisms.

INH:
Absorption: Oral, IM: Rapid and complete; food reduces rate and extent of absorptionDistribution: All body tissues and fluids including CSFProtein binding: 10% to 15%Metabolism: Hepatic to acetylisoniazid with decay rate determined genetically by acetylation phenotype; undergoes further hydrolysis to isonicotinic acid and acetylhydrazineHalf-life: May be prolonged in patients with impaired hepatic function or severe renal impairmentFast acetylators: 30 to 100 minutesSlow acetylators: 2 to 5 hoursTime to peak, serum: 1 to 2 hoursExcretion: Urine (75% to 95% as unchanged drug and metabolites); small amounts excreted in feces and saliva.
RPT:
Absorption: High-fat meals increase AUC and Cmax by 40% to 50% In pediatric patients, crushing the tablet results in 26% lower exposure than whole tablets.
Distribution: Vd: ~70 L
Protein binding: Rifapentine: ~98%, primarily to albumin; 25-desacetyl rifapentine: ~93%
Metabolism: Hepatic; hydrolyzed by an esterase enzyme to form the active metabolite 25-desacetyl rifapentine
Bioavailability: 70%
Half-life elimination: Rifapentine: ~17 hours; 25-desacetyl rifapentine: ~24 hours
Time to peak, serum: 3 to 10 hours
Excretion: Feces (70%); urine (17%, primarily as metabolites)
In pediatric patients 2 to 18 years of age, clearance decreases with increasing age.

INH:
Hypersensitivity to isoniazid or any component of the formulation, including drug-induced hepatitis; acute liver disease; previous history of hepatic injury during isoniazid therapy; previous severe adverse reaction (drug fever, chills, arthritis) to isoniazid.
RPT:
Hypersensitivity to rifapentine, other rifamycins, or any component of the formulation

not recommended

Hepatic: Increased serum transaminases (mild and transient 10% to 20%)
Endocrine & metabolic: Hyperuricemia (≥ 32%)
Genitourinary: Pyuria (11% to 22%), hematuria (10% to 18%), urinary tract infection (7% to 13%)
Hematologic & oncologic: Neutropenia (6% to 13%), lymphocytopenia (3% to 13%), anemia (2% to 11%)

INH: QW for 3 months (Total: 12 doses)
2-11 years old: 25 mg/kg, 900 mg maximum.≥ 12 years old: 15 mg/kg, rounded up to the nearest 50 or 100 mg.
RPT: QW for 3 months (Total: 12 doses)
10.0-14.0 kg: 300 mg
14.1-25.0 kg: 450 mg
25.1-32.0 kg: 600 mg
32.1-49.9 kg: 750 mg
≥ 50.0 kg: 900 mg maximum.

INH:
CrCl <30 mL/minute: Treatment of drug-susceptible TB: 300 mg once daily or 900 mg administered 3 times weekly.
ESRD receiving intermittent hemodialysis (IHD):Administer dose postdialysis;Dialyzable (50% to 100%)RPT:
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

INH:
There are no dosage adjustments provided in the manufacturer's labeling; however, use with caution, may accumulate and additional liver damage may occur in patients with preexisting liver disease.RPT:
There are no dosage adjustments provided in the manufacturer’s labeling.