REZIRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REZIRA (REZIRA).
REZIRA is a fixed-dose combination of rifapentine and isoniazid. Rifapentine inhibits bacterial RNA polymerase, thereby inhibiting RNA synthesis. Isoniazid inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall.
| Metabolism | Rifapentine is metabolized primarily via esterases to 25-desacetylrifapentine and also undergoes deacetylation and hydrolysis. Isoniazid is metabolized by the liver via N-acetyltransferase 2 (NAT2) to acetylisoniazid, which is then hydrolyzed to isonicotinic acid and acetylhydrazine. |
| Excretion | Renal: <1% unchanged; Fecal: >99% as metabolites |
| Half-life | Terminal elimination half-life: 120-150 hours; achieves steady-state by 4 weeks |
| Protein binding | >99.9% bound to plasma proteins (mainly albumin and lipoproteins) |
| Volume of Distribution | 500-800 L/kg; extensive tissue distribution, especially skin and adipose |
| Bioavailability | Oral: 50-60% (with high-fat meal); Topical: negligible systemic absorption |
| Onset of Action | Oral: 2-4 hours; Topical: 2-4 weeks |
| Duration of Action | Dosing interval: every 12 weeks; therapeutic effect persists for 12 weeks after oral dose |
400 mg orally twice daily with food
| Dosage form | SOLUTION |
| Renal impairment | eGFR 30-89 mL/min: 200 mg orally twice daily; eGFR <30 mL/min or dialysis: 200 mg orally once daily |
| Liver impairment | Child-Pugh A: 400 mg orally twice daily; Child-Pugh B or C: 200 mg orally twice daily |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established |
| Geriatric use | No specific dose adjustment; use with caution due to age-related renal function decline |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REZIRA (REZIRA).
| Breastfeeding | Small amounts of rifapentine are excreted into breast milk (M/P ratio not reported). Due to potential for adverse effects in breastfed infants (e.g., hepatic toxicity, discoloration of bodily fluids), caution is advised; use only if clearly needed. |
| Teratogenic Risk | Pregnancy Category D: REZIRA (rifapentine) is associated with an increased risk of fetal harm based on animal studies. In the first trimester, use only if potential benefit justifies risk due to possible teratogenic effects; in second and third trimesters, risk of toxicity including jaundice and bleeding diathesis in neonates. Monitor for hyperbilirubinemia and kernicterus. |
■ FDA Black Box Warning
REZIRA can cause severe and potentially fatal liver injury. This risk is increased in patients with pre-existing liver disease, those who consume alcohol daily, and those taking other hepatotoxic drugs. Discontinue immediately if signs or symptoms of liver injury occur.
| Serious Effects |
Hypersensitivity to rifapentine, isoniazid, or any component; acute liver disease; history of isoniazid-associated liver injury; severe adverse reaction to isoniazid (e.g., drug fever, chills, arthritis); concurrent use of alcohol-containing products.
| Precautions | Hepatotoxicity including fatal hepatitis; peripheral neuropathy (pyridoxine deficiency); hypersensitivity reactions; monitoring for liver function tests; interactions with oral contraceptives, warfarin, and antidiabetic agents; caution in patients with renal impairment; use with pyridoxine to prevent neuropathy. |
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| Fetal Monitoring | Pregnancy test before initiation. Monitor liver function tests, bilirubin, and complete blood count periodically. In third trimester, monitor neonatal jaundice and coagulation status. Fetal ultrasound to assess growth and development. |
| Fertility Effects | Animal studies have shown no significant impact on fertility. However, hormonal contraceptive efficacy may be reduced due to enzyme induction; advise non-hormonal contraception. |