HYZYD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYZYD (HYZYD).
Inhibits mycobacterial cell wall synthesis by blocking the enzyme InhA and the synthesis of mycolic acids.
| Metabolism | Primarily hepatic via acetylation by N-acetyltransferase 2 (NAT2); major metabolite is acetylisoniazid. |
| Excretion | Renal: 50-70% unchanged drug; hepatic metabolism: 25-50%; fecal: <5% |
| Half-life | Isoniazid (HYZYD): 1-4 hours (fast acetylators), 2-5 hours (slow acetylators); clinically, half-life determines dosing interval and risk of toxicity |
| Protein binding | 0-10% bound to albumin |
| Volume of Distribution | 0.6-1.2 L/kg; distributes widely into all body fluids and tissues including CSF |
| Bioavailability | Oral: ~90% |
| Onset of Action | Oral: 1-2 hours; IM: 30-60 minutes; IV: Immediate |
| Duration of Action | Bactericidal effect persists 12-24 hours; clinical duration 12-24 hours based on acetylator phenotype |
300 mg orally once daily; or 5 mg/kg orally once daily (max 300 mg/day) as monotherapy or in combination for tuberculosis. For latent TB, 300 mg orally once daily for 6-9 months.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: reduce dose to 200 mg daily or 5 mg/kg thrice weekly. GFR <30 mL/min or on hemodialysis: 200 mg daily or 5 mg/kg thrice weekly (administer after dialysis). |
| Liver impairment | Child-Pugh A: no adjustment needed. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated or use with extreme caution (prefer alternative). |
| Pediatric use | 10-15 mg/kg orally once daily (max 300 mg/day) for active TB; for latent TB, 10-15 mg/kg orally once daily (max 300 mg/day) for 9 months. |
| Geriatric use | Use lower dose (e.g., 200 mg daily) due to age-related renal impairment; monitor hepatic function and serum drug levels if available. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HYZYD (HYZYD).
| Breastfeeding | Isoniazid is excreted into breast milk; M/P ratio approximately 1.0. Infant serum levels are low but may reach therapeutic range. Risk of peripheral neuropathy and hepatotoxicity in infant; monitor infant for jaundice, lethargy, poor feeding. Use caution, benefit outweighs risk for TB treatment. |
| Teratogenic Risk | HYZYD (isoniazid) is categorized as FDA Pregnancy Category C. First trimester: Data limited; no major malformations reported in small studies, but hepatic toxicity risk? Second and third trimesters: Increased risk of maternal hepatitis, which may affect fetus; no direct teratogenicity established. |
■ FDA Black Box Warning
Severe and sometimes fatal hepatitis has been reported; discontinue drug at first signs of hepatitis. Monitor liver function tests closely.
| Serious Effects |
Acute liver disease, previous isoniazid-induced liver injury, hypersensitivity to isoniazid.
| Precautions | Hepatotoxicity (age >35, alcohol use, pre-existing liver disease), peripheral neuropathy (pyridoxine supplementation recommended), hypersensitivity reactions, lupus-like syndrome, drug interactions (e.g., phenytoin, carbamazepine). |
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| Fetal Monitoring | Baseline and monthly LFTs (AST, ALT, bilirubin) during pregnancy; clinical monitoring for maternal hepatitis symptoms (nausea, fatigue, jaundice). Fetal growth ultrasound in third trimester. Monitor infant for neonatal hepatitis if maternal isoniazid used near term. |
| Fertility Effects | No documented adverse effects on fertility in males or females. Tuberculosis itself may impair fertility; treatment restores health. |