indication

For the treatment of pulmonary tuberculosis.

pharmacology

Rifapentine is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.

mechanism of action

Rifapentine has shown higher bacteriostatic and bactericidal activities especially against intracellular bacteria growing in human monocyte-derived macrophages. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of M. tuberculosis. Rifapentine acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.

biotransformation

Hepatic

absorption

Rapidly and well absorbed from the gastrointestinal tract.

route of elimination

Following a single 600 mg oral dose of radiolabeled rifapentine to healthy volunteers (n=4), 87% of the total 14C rifapentine was recovered in the urine (17%) and feces (70%).

drug interactions

Bromazepam: Rifapentine may decrease the serum concentration of bromazepam by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bromazepam if rifapentine is initiated, discontinued or dose changed.

Erlotinib: Decreased levels/effect of erlotinib

Ethinyl Estradiol: This product may cause a slight decrease of contraceptive effect

Methadone: The rifamycin decreases the effect of methadone

Norethindrone: This product may cause a slight decrease of contraceptive effect

Telithromycin: Rifapentine may decrease the plasma concentration of Telithromycin. Consider alternate therapy.

Temsirolimus: Rifapentine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.

Terbinafine: Rifapentine may increase the metabolism and clearance of Terbinafine. To avoid Terbinafine treatment failure, co-administration should be avoided.

Tipranavir: Concomitant therapy may cause decreased Tipranavir and increased Rifapentine plasma concentrations.

Tramadol: Rifapentine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.

Trazodone: The CYP3A4 inducer, Rifapentine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Rifapentine is initiated, discontinued or dose changed.

Tretinoin: The strong CYP2C8 inducer, Rifapentine, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Rifapentine is initiated, discontinued or dose changed.

Verapamil: Rifapentine, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifapentine is initiated, discontinued or dose changed.

Voriconazole: Rifapentine may decrease the serum concentration of voriconazole likely by increasing its metabolism via CYP3A enzymes. Voriconazole may increase the serum concentration of rifapentin likely by inhibiting its metabolism via CYP3A. Concomitant therapy is contraindicated.

Zidovudine: Rifapentin may decrease the serum concentration of zidovudine by increasing its metabolism. Monitor for changes in the serum concentration and therapeutic and adverse effects of zidovudine if rifapentin is initiated, discontinued or dose changed.