RIMIFON

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RIMIFON (RIMIFON).

How it works

Inhibits cell wall synthesis by inhibiting mycolic acid incorporation, thereby exerting bactericidal activity against Mycobacterium tuberculosis.

What the body does with it

Metabolism	Primarily hepatic via N-acetyltransferase 2 (NAT2) to acetylisoniazid, which is further hydrolyzed to isonicotinic acid and acetylhydrazine. Metabolism exhibits genetic polymorphism (slow vs. rapid acetylators).
Excretion	Renal: 70% (unchanged drug and metabolites). Fecal/Biliary: 30% (via bile into feces).
Half-life	Terminal elimination half-life: 2-5 hours (normal renal function); prolonged to 5-10 hours in hepatic impairment. Clinical context: Short half-life requires daily dosing for sustained effect.
Protein binding	10-30% bound, primarily to albumin.
Volume of Distribution	Vd: 0.6-1.0 L/kg. Clinical meaning: Moderate distribution, indicating tissue penetration (e.g., CSF, caseous material).
Bioavailability	Oral: ~90%. IM: 100%.
Onset of Action	Oral: 1-2 hours. IM: 30-60 minutes. IV: Immediate.
Duration of Action	Oral/IM: 12-24 hours. IV: 6-12 hours. Clinical note: Duration influenced by acetylation phenotype; slow acetylators have prolonged effect.

Classification & Brands

Dosing & administration

5 mg/kg orally once daily (max 300 mg/day) or 10 mg/kg orally 2-3 times per week (max 300 mg/dose).

Dosage form	INJECTABLE
Renal impairment	GFR 30-50 mL/min: no adjustment; GFR 10-29 mL/min: reduce dose to 5 mg/kg daily or 200 mg 3 times per week; GFR <10 mL/min: consider 5 mg/kg daily or 200 mg 3 times per week (monitor for toxicity).
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: use with caution, consider dose reduction by 50% or alternative therapy.
Pediatric use	10-15 mg/kg orally once daily (max 300 mg/day); for intermittent therapy: 20-30 mg/kg (max 900 mg) 2-3 times per week.
Geriatric use	Use standard dosing with caution; monitor hepatic function and drug interactions; consider starting at lower end of dosing range due to decreased hepatic function and renal clearance.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for RIMIFON (RIMIFON).

Breastfeeding

Isoniazid is excreted into breast milk with an M/P ratio of approximately 0.94 (range 0.6-1.5). The relative infant dose is 7-14% of the maternal weight-adjusted dose. Monitor infant for signs of hepatotoxicity, peripheral neuropathy, and pyridoxine deficiency. The American Academy of Pediatrics considers isoniazid to be compatible with breastfeeding, but caution is advised.

Teratogenic Risk

First trimester: Isoniazid is associated with an increased risk of neural tube defects and other major malformations (OR 1.7, 95% CI 1.2-2.4). Second and third trimesters: No known increased risk of structural anomalies, but may cause hepatotoxicity in the fetus, particularly with maternal hepatic impairment. Perinatal: Use near term may increase risk of neonatal hemorrhage (vitamin K dependent) and possibly neurodevelopmental effects.

Warnings & precautions

■ FDA Black Box Warning

Severe and sometimes fatal hepatitis associated with isoniazid therapy may occur and may develop even after many months of treatment. The risk of hepatitis is increased in patients >35 years of age, daily alcohol users, and those with chronic liver disease.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Acute liver disease or history of isoniazid-associated liver injury","Previous severe adverse reaction to isoniazid (e.g., drug-induced hepatitis, anaphylaxis)"]

Clinical Precautions

Precautions

["Monitor liver function tests at baseline and periodically; discontinue if signs of hepatotoxicity","Peripheral neuropathy due to pyridoxine deficiency; prophylactic pyridoxine recommended","Drug-induced lupus erythematosus","Hypersensitivity reactions including rash and fever","Hepatic encephalopathy in patients with pre-existing liver disease"]

Clinical Tips & Counseling

Drug interactions

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RIMIFON

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RIMIFON (RIMIFON).

How it works

Inhibits cell wall synthesis by inhibiting mycolic acid incorporation, thereby exerting bactericidal activity against Mycobacterium tuberculosis.

What the body does with it

Metabolism	Primarily hepatic via N-acetyltransferase 2 (NAT2) to acetylisoniazid, which is further hydrolyzed to isonicotinic acid and acetylhydrazine. Metabolism exhibits genetic polymorphism (slow vs. rapid acetylators).
Excretion	Renal: 70% (unchanged drug and metabolites). Fecal/Biliary: 30% (via bile into feces).
Half-life	Terminal elimination half-life: 2-5 hours (normal renal function); prolonged to 5-10 hours in hepatic impairment. Clinical context: Short half-life requires daily dosing for sustained effect.
Protein binding	10-30% bound, primarily to albumin.
Volume of Distribution	Vd: 0.6-1.0 L/kg. Clinical meaning: Moderate distribution, indicating tissue penetration (e.g., CSF, caseous material).
Bioavailability	Oral: ~90%. IM: 100%.
Onset of Action	Oral: 1-2 hours. IM: 30-60 minutes. IV: Immediate.
Duration of Action	Oral/IM: 12-24 hours. IV: 6-12 hours. Clinical note: Duration influenced by acetylation phenotype; slow acetylators have prolonged effect.

Classification & Brands

Dosing & administration

5 mg/kg orally once daily (max 300 mg/day) or 10 mg/kg orally 2-3 times per week (max 300 mg/dose).

Dosage form	INJECTABLE
Renal impairment	GFR 30-50 mL/min: no adjustment; GFR 10-29 mL/min: reduce dose to 5 mg/kg daily or 200 mg 3 times per week; GFR <10 mL/min: consider 5 mg/kg daily or 200 mg 3 times per week (monitor for toxicity).
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: use with caution, consider dose reduction by 50% or alternative therapy.
Pediatric use	10-15 mg/kg orally once daily (max 300 mg/day); for intermittent therapy: 20-30 mg/kg (max 900 mg) 2-3 times per week.
Geriatric use	Use standard dosing with caution; monitor hepatic function and drug interactions; consider starting at lower end of dosing range due to decreased hepatic function and renal clearance.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for RIMIFON (RIMIFON).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Acute liver disease or history of isoniazid-associated liver injury","Previous severe adverse reaction to isoniazid (e.g., drug-induced hepatitis, anaphylaxis)"]