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 |
| Molecular Weight | 252.3 |
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 | Contraindicated due to teratogenicity (increased risk of severe birth defects). |
| 2nd trimester | Contraindicated; may cause fetal harm. |
| 3rd trimester | Contraindicated; avoid use near term. |
Clinical note
Comprehensive clinical and safety monograph for REZIRA (REZIRA).
| Placental transfer | Crosses placenta readily with fetal levels approximately 50-80% of maternal levels. |
| Breastfeeding | Concentrates in breast milk; potential for serious adverse reactions in nursing infants. Discontinue drug or bottle-feed. |
| Lactation Rating | L5 (Contraindicated) |
■ 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 |
PregnancyBreastfeedingHypersensitivity to rezira or any componentSevere hepatic impairment
| 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. |
| Food/Dietary | No significant food interactions have been reported. REZIRA can be administered without regard to meals. Maintain adequate hydration during therapy. |
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| 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. |
| 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. |
| Clinical Pearls | REZIRA (ceftolozane/tazobactam) is a cephalosporin/beta-lactamase inhibitor combination approved for complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI), and hospital-acquired/ventilator-associated pneumonia (HABP/VABP) in adults. It has potent activity against multidrug-resistant Pseudomonas aeruginosa, including strains resistant to carbapenems. Dose adjustment is required for creatinine clearance <50 mL/min. Monitor renal function and adjust dose accordingly. For cIAI, use in combination with metronidazole. Infuse over 1 hour. Avoid in patients with severe hypersensitivity to cephalosporins or beta-lactams. |
| Patient Advice | Take this medication exactly as prescribed by your healthcare provider. · If you are on dialysis, inform your doctor before starting treatment. · Report any signs of allergic reaction (rash, hives, difficulty breathing) or severe diarrhea immediately. · You may experience nausea, headache, or injection site reactions; contact your doctor if these persist. · Complete the full course of therapy even if you feel better. |