Dosing and uses of Isoniazid
Adult dosage forms and strengths
tablets
- 50mg
- 100mg
- 300mg
oral syrup
- 50mg/5mL
injectable solution
- 100mg/mL
Latent Tuberculosis Infection
Treatment of latent TB infection greatly reduces the risk that TB infection will progress to acitve disease
>30 kg: 300 mg PO qDay x9 months
3-month regimen
- Recommended for patients aged 12 years and older who are at high risk for developing TB disease including anyone who has had recent exposure to contagious TB, conversion from negative to positive on a test for TB infection, or a chest X-ray indicating prior TB disease
- Persons with HIV who are otherwise healthy and not taking antiretrovirals may also use this regimen
- 900 mg PO once weekly x3 months (administer with rifapentine 900 mg once weekly)
- Administered as DOT
- Not recommended for children <2 years, pregnant women or women planning to become pregnant, HIV-infected persons taking antiretrovirals, and patients whose TB infection is presumed to be the result of exposure to a person with TB disease that is resistant to 1 of the 2 drugs
- References: CDC MMWR 2011;60:1650-3 and NEJM 2011;365:2155-2166
Active Tuberculosis Disease
5 mg/kg PO/IM qDay, not to exceed 300 mg qDay
15 mg/kg PO/IM up; not to exceed 900 mg 1-3 times/week
Used in multi-drug regimen containing rifampin (or ribabutin or rifapentin), pyrazinamide, and ethambutoL
Duration of treatment dependent on regimen consisting of an initial phase of treatment and a continutation phase of treatment
Note: Daily treatment has best results for HIV positive individuals
See Also Combos
With rifampin (Rifamate)
With rifampin and pyrizinamide (Rifater)
Other Indications & Uses
Newly infected patients
Household members and close associates of people recently diagnosed wtih TB
+ve TB skin test with +ve non-progressive chest x-ray
+ve TB skin test with underlying disease or immunosuppression
+ve TB skin test, <35 years old; >35 years old weigh use against risk of hepatitis
Pediatric dosage forms and strengths
tablets
- 50mg
- 100mg
- 300mg
oral syrup
- 50mg/5mL
injectable solution
- 100mg/mL
Latent Tuberculosis Infection
Treatment of latent TB infection greatly reduces the risk that TB infection will progress to acitve disease
10-15 mg/kg PO qDay; not to exceed 300 mg/day
3-month regimen
- Recommended for patients aged 12 years and older who are at high risk for developing TB disease including anyone who has had recent exposure to contagious TB, conversion from negative to positive on a test for TB infection, or a chest X-ray indicating prior TB disease
- Use for children aged 2-11 years and patients with underlying conditions associated with TB should be considered on a case-by-case basis; preferred regimen for this age group is daily isoniazid for 9 months
- Not recommended for children <2 years
- >12 years: isoniazid 900 mg PO plus rifapentine 900 mg PO once weekly for 3 months
- References: CDC MMWR 2011;60:1650-3 and NEJM 2011;365:2155-2166
Active Tuberculosis Disease
10-15 mg/kg PO qDay; not to exceed 300 mg/day Or
20-30 mg/kg (up to 900 mg) 2 times/week
Used in multi-drug regimen
Isoniazid adverse (side) effects
>10%
Mild incr LFTs (10-20%)
Peripheral neuropathy (dose-related incidence, 10-20% incidence with 10 mg/kg/d)
Loss of appetite
Nausea
Vomiting
Stomach pain
Weakness
1-10%
Dizziness
Slurred speech
Lethargy
Progressive liver damage (increases with age; 2.3% in pts > 50 yo)
Hyperreflexia
<1%
Agranulocytosis
Anemia
Megaloblastic anemia
Thrombocytopenia
Systemic lupus erythematosus
Seizure
- other adverse reactions reported: pancreatitis; toxic epidermal necrolysis, and drug reaction with eosinophilia syndrome(DRESS)
Warnings
Black box warnings
Severe and sometimes fatal hepatitis may occur within the first 3 months of treatment and many months after treatment. Risk is related to age and increased with daily alcohol consumption.
Patients should be instructed about signs and symptoms of hepatitis.
Contraindications
Prev INH hepatic injury or reaction; acute liver dz; pancreatitis
Hypersensitivity
• Isoniazid is contraindicated in patients who develop severe hypersensitivity reactions, including drug-induced hepatitis; previous isoniazid-associated hepatic injury; severe adverse reactions to isoniazid such as drug fever, chills, arthritis; and acute liver disease of any etiology
Cautions
Alcohol or illicit injectable drug use, predisposition to neuropathy, malnourished, severe renal impairment, chronic liver dz
Use w/ other anti-TB agents
Give pyridoxine (B6) concurrently for pregnant women, malnourished pts. or those with neuropathic diathesis
Alcohol use, renal or hepatic dysfunction will affect serum levels
Pregnancy and lactation
Pregnancy category: C
Lactation: distributed into milk but safe for nursing infants
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Isoniazid
Mechanism of action
Unknown: prob. inhibits cell-wall biosynthesis by interfering with lipid and DNA synthesis (bactericidal)
Absorption
Rapid and complete; rate can be slowed with food Peak Plasma Time: 1-2 hr
Distribution
All body tissues and fluids including CSF; crosses placenta; enters breast milk
Protein Bound: 10-15%
Metabolism
Hepatic with decay rate determined genetically by acetylation phenotype
Elimination
Half-life elimination: fast acetylators: 30-100 min; slow acetylators: 2-5 hr; may be prolonged with hepatic or severe renal impairment
Excretion: Urine (75-95%); feces
Administration
IM Preparation
At low temperatures, isoniazid in solution tends to crystallize; warm injection to room temperature to redissolve crystals prior to use
IM Administration
May be given by IM injection when oral therapy is not possible
Storage
Protect from light
Store at <40°C, preferably between 15-30°C
Protect from freezing