NYDRAZID
Clinical safety rating
cautionComprehensive clinical and safety monograph for NYDRAZID (NYDRAZID).
Comprehensive clinical and safety monograph for NYDRAZID (NYDRAZID).
Treatment of active tuberculosis (in combination with other antituberculous agents)Prophylaxis of tuberculosis in high-risk individuals
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. |
| Molecular Weight | 137.14 |
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 | Isoniazid (NYDRAZID) is associated with an increased risk of neural tube defects if used during the first trimester. Use only if clearly needed and benefit outweighs risk. |
| 2nd trimester | Use with caution; may be associated with maternal hepatitis. Monitor liver function closely. |
| 3rd trimester | Use with caution; risk of maternal hepatitis and possible neonatal hemorrhage (due to vitamin K deficiency). Administer vitamin K to neonate. |
Clinical note
Comprehensive clinical and safety monograph for NYDRAZID (NYDRAZID).
| Placental transfer | Isoniazid crosses the placenta readily; fetal plasma concentrations approximate maternal levels. |
| Breastfeeding | Isoniazid is excreted into human breast milk in small amounts. The American Academy of Pediatrics considers it compatible with breastfeeding. However, monitor the infant for signs of hepatotoxicity or peripheral neuropathy. The concentration in milk is insufficient for tuberculosis prophylaxis in the infant. |
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |
■ 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 |
Acute liver diseaseHistory of isoniazid-associated hepatotoxicitySevere hypersensitivity to isoniazid
| 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). |
| Food/Dietary | Isoniazid inhibits monoamine oxidase (MAO) and reduces metabolism of tyramine, leading to hypertensive crisis. Avoid tyramine-rich foods: aged cheeses (cheddar, blue cheese), cured or fermented meats (salami, pepperoni, pickled herring), soy products (tofu, miso, tempeh), sauerkraut, fava beans, tap beers, and red wines. Also avoid foods containing histamine (tuna, mackerel, sauerkraut). Concomitant alcohol consumption increases risk of hepatotoxicity and should be strictly avoided. High-protein meals or dairy may interfere with absorption; maintain consistent timing relative to meals. There is no restriction on carbohydrates or fats. |
| Clinical Pearls | NYDRAZID (isoniazid) is a first-line antitubercular agent. Always prescribe pyridoxine (vitamin B6) 25-50 mg daily to prevent peripheral neuropathy, especially in patients with risk factors like diabetes, alcoholism, malnutrition, or HIV. Monitor liver function tests closely; hepatotoxicity risk increases with age >35, concurrent use of acetaminophen or other hepatotoxic drugs, and pre-existing liver disease. Slow acetylators (genetic) have higher risk of toxicity. Isoniazid can cause bilateral optic neuritis; monitor for visual symptoms. Drug interactions: increases levels of phenytoin, carbamazepine, and theophylline; reduce doses accordingly. Administer on empty stomach (1 hour before or 2 hours after meals) for optimal absorption. In case of overdose, high-dose pyridoxine is antidote (1 g per gram of isoniazid ingested). |
| Patient Advice | Take isoniazid on an empty stomach with a full glass of water, at least 1 hour before or 2 hours after meals. · Do not drink alcohol while taking this medication; combined with alcohol increases risk of severe liver damage. · Take vitamin B6 (pyridoxine) exactly as prescribed to prevent nerve damage. · Report immediately: dark urine, pale stools, yellowing of skin or eyes, nausea/vomiting, abdominal pain, unusual fatigue (liver toxicity signs). · Report numbness, tingling, or burning in hands/feet; vision changes; rash; or fever. · Avoid foods high in tyramine (aged cheese, cured meats, soy products, tap beer) while taking isoniazid; may cause hypertensive crisis. · Take all doses on schedule; do not skip or stop without consulting provider. · Keep all follow-up appointments for blood tests to monitor liver function. |
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