Drug information of Rifapentine

Mechanism of effect

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.

Pharmacodynamic

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.

Pharmacokinetics

• Peak Plasma Time: 5-6 hr
• Protein Bound: 98%
• Enzymes induced: CYP3A4, CYP2C9/10
• Half-Life: 13 hr
• Excretion: feces (70%); urine

Drug indications

Tuberculosis - Active

Dosage

Adult

Pulmonary Tuberculosis

Initial phase (2 months): 600 mg PO 2x/week for 2 months; interval between doses not <3 d (in combination with other antiTB drugs) THEN

Continuation phase (4 months): 600 mg PO qWeek for 4 months by direct observation therapy with isoniazid or another appropriate antiTB drug

Latent Tuberculosis

Once weekly rifapentine PO (weight based dosing below) plus isoniazid once-weekly for 12 weeks as directly observed therapy (DOT)

≥12 years and >50 kg: 900 mg

≥12 years and 32.1-50 kg: 750 mg

Isoniazid dose: 15 mg/kg (rounded to nearest 50 mg or 100 mg); not to exceed 900 mg once-weekly for 12 weeks

Pediatric

Latent Tuberculosis

2-11 years

Once weekly rifapentine PO (weight based dosing below) plus isoniazid once-weekly for 12 weeks as directly observed therapy (DOT)

10-14 kg: 300 mg

>14-25 kg: 450 mg

>25-32 kg: 600 mg

>32-49.9 kg: 750 mg

≥50 kg: Not to exceed 900 mg

Isoniazid dose: 25 mg/kg (rounded to nearest 50 mg or 100 mg); not to exceed 900 mg once-weekly for 12 weeks

Side effects

anemia , Pain , Diarrhea , Acne , Headache , nausea , dizziness , vomiting , Hypertension , anorexia , Proteinuria , itching , blood in the urine , Leukopenia , Rash

Interactions

Amlodipine/Atorvastatine , Irinotecan , Dapsone , Erythromycin , Everolimus , Trazodone , Dihydroergotamine , Sirolimus , Sildenafil , Hydrocodone , lumefantrine , Praziquantel , Darunavir , BCG vaccine , Ethinyl Estradiol , ritonavir , nelfinavir , Simvastatin , Lovastatin , Daclatasvir , Sofosbuvir , ergotamine , Atazanavir , Ranolazine , Axitinib , saquinavir , Copanlisib , Tipranavir , Simeprevir , lumacaftor and Ivacaftor , Ulipristal , Etravirine , Dabrafenib , Acalabrutinib , cobicistat , Sofosbuvir and velpatasvir , Fostamatinib , Apremilast , Palbociclib , Tasimelteon , Doravirine , raltegravir , Duvelisib , tezacaftor/ivacaftor , Darolutamide , Pitolisant , atovaquone/proguanil , Cabozantinib , ELBASVIR/GRAZOPREVIR , Larotrectinib , gilteritinib , glasdegib , Abemaciclib , Triphasic , Eliglustat , rilpivirine , bedaquiline , Gefitinib , Dasatinib , Cannabidiol , vemurafenib , Typhoid vaccine (live), oral , rolapitant , Bictegravir , voxelotor , stiripentol , Avapritinib , Netupitant , Capmatinib , Dienestrol

Alerts

May increase liver enzymes; initiation in patients with existing abnormal liver tests and/or liver disease only in cases of necessity and under strict medical supervision; monitor LFTs every 2-4 week and discontinue if evidence of liver injury occurs

Hypersensitivity or anaphylaxis reported including hypotension, urticaria, angioedema, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, or flu-like syndrome

Not for use as initial phase treatment in HIV-infected individuals with active pulmonary TB

Higher relapse rate may occur in patients with cavitary pulmonary lesions and/or positive sputum cultures after the initial phase of active TB treatment, and in patients with bilateral pulmonary disease

Induces CYP450 isoenzymes; coadministration with drugs metabolized by these enzymes (eg, protease inhibitors, certain NRTIs, hormonal contraception) may result in significant decreased plasma concentrations and loss of therapeutic effect

May produce a red-orange discoloration of body tissues/fluids (eg, skin, teeth, tongue, urine, feces, saliva, sputum, tears, sweat, CSF); contact lenses or dentures may become permanently stained

As with the use of nearly all systemic antibacterial agents, Clostridium difficile-associated diarrhea (CDAD) reported; discontinue if CDAD confirmed

Porphyria reported in patients receiving rifampin, avoid in patients with history of porphyria

Points of recommendation

This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take rifapentine.

Have blood work checked as you have been told by the doctor. Talk with the doctor.

Do not skip doses. Skipping doses may cause rifapentine to not work as well. Other TB drugs may no longer work as well either.

Take vitamin B6 (pyridoxine) as you were told by your doctor.

This medicine may stain contact lenses.

Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking rifapentine.

This medicine may color breast milk an orange or red color. Talk with the doctor.

Take with food.

If you cannot swallow tablets, the tablet may be crushed and added to a small amount of soft food. Take the mixture right away. Do not store for future use.

Pregnancy level

C

Related drugs

Rifampin , Capreomycin , Pyrazinamide