NYDRAZID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NYDRAZID (NYDRAZID).
Inhibits bacterial cell wall synthesis by blocking the incorporation of mycolic acid into the arabinogalactan layer, specific to mycobacteria.
| Metabolism | Hepatic metabolism primarily via N-acetyltransferase 2 (NAT2) to acetylisoniazid, which is further metabolized to hepatotoxic metabolites. |
| Excretion | Renal excretion of unchanged drug and metabolites; 50-70% excreted in urine within 24 hours, mainly as acetylisoniazid and isonicotinic acid. Biliary/fecal: <10%. |
| Half-life | Terminal elimination half-life: 1-4 hours (fast acetylators), 2-8 hours (slow acetylators). Half-life prolonged in hepatic impairment; adjust dose. |
| Protein binding | 10-20% bound primarily to albumin; binding is low and clinically insignificant. |
| Volume of Distribution | Vd: 0.6-0.8 L/kg; distributes into total body water, including CSF, pleural fluid, and caseous granulomas. |
| Bioavailability | Oral: 90-100% (fasting). Food may decrease absorption by 20-50%; take on empty stomach. |
| Onset of Action | Oral: 1-2 hours (peak serum levels). IM: 1-2 hours. Clinical effect (bactericidal activity) begins within hours of achieving therapeutic concentrations. |
| Duration of Action | Duration of bactericidal effect: 24 hours. Daily dosing for active TB; dosing interval may be extended to 2-3 times weekly in continuation phase. |
300 mg orally once daily; alternatively, 5 mg/kg (max 300 mg) orally once daily for 6-9 months for latent tuberculosis; for active tuberculosis, 5 mg/kg (max 300 mg) orally once daily for 2 months followed by 3 times weekly dosing (15 mg/kg, max 900 mg) for 4-7 months.
| Dosage form | TABLET |
| Renal impairment | If GFR < 30 mL/min: administer 200 mg once daily or 300 mg three times weekly. For severe renal impairment (GFR < 10 mL/min) or hemodialysis: 200 mg daily or 300 mg three times weekly, given after dialysis. |
| Liver impairment | Child-Pugh Class A: no adjustment needed. Child-Pugh Class B: reduce dose by 50% (e.g., 150 mg daily). Child-Pugh Class C: reduce dose by 50-75% (e.g., 100-150 mg daily) or consider alternative therapy; monitor liver function closely. |
| Pediatric use | For latent tuberculosis: 10-15 mg/kg (max 300 mg) orally once daily for 6-9 months. For active tuberculosis: 10-15 mg/kg (max 300 mg) orally once daily for 2 months, then 15 mg/kg (max 900 mg) orally three times weekly for 4-7 months. |
| Geriatric use | Start at lower end of dosing range (e.g., 200-300 mg daily) due to potential renal impairment; monitor liver function and signs of hepatotoxicity; adjust dose based on creatinine clearance if GFR < 30 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NYDRAZID (NYDRAZID).
| Breastfeeding | Isoniazid is excreted into breast milk in concentrations similar to maternal plasma. The milk-to-plasma (M/P) ratio is approximately 1.0. The American Academy of Pediatrics considers it compatible with breastfeeding. However, due to the theoretical risk of hepatotoxicity and peripheral neuropathy in the infant, monitoring of the infant for signs of jaundice, hepatitis, or neuropathy is recommended. The dose to the infant is subtherapeutic (about 0.5-2% of the maternal dose) and is unlikely to cause adverse effects. |
| Teratogenic Risk | Isoniazid (INH) is not associated with major congenital malformations in humans. However, in vivo animal studies have shown embryocidal effects at high doses. The drug is considered safe during all trimesters; however, due to the risk of hepatotoxicity, monitoring of liver function is recommended, especially in the third trimester. Perinatal exposure increases the risk of neonatal hemorrhage due to vitamin K deficiency, which can be prevented by prophylactic vitamin K administration to the mother. |
■ FDA Black Box Warning
Severe and sometimes fatal hepatitis has been reported, even after months of treatment. Risk increases with age, daily alcohol use, and pre-existing liver disease. Monitor liver function tests closely.
| Serious Effects |
Severe hepatic disease, acute liver disease, or previous isoniazid-associated hepatitis; hypersensitivity to isoniazid or any component.
| Precautions | Peripheral neuropathy (prevent with pyridoxine), hepatotoxicity, hypersensitivity reactions (e.g., fever, rash), lupus-like syndrome, seizures, optic neuritis, drug interactions (e.g., phenytoin, carbamazepine, disulfiram). |
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| Fetal Monitoring | Monthly liver function tests (AST, ALT) and bilirubin levels. Monitor for signs of hepatitis, peripheral neuropathy, and optic neuritis. In neonates, assess for signs of jaundice and neurological abnormalities. For pregnant patients with tuberculosis, periodic sputum cultures and chest X-rays (with abdominal shielding) are indicated to assess treatment response. |
| Fertility Effects | No known adverse effects on fertility in either males or females. However, untreated tuberculosis can impair maternal and fetal health, and effective treatment is essential to preserve fertility and pregnancy outcomes. |