isoniazid

Isoniazid is an antitubercular agent used to treat latent and active tuberculosis (TB), caused by susceptible organisms of Mycobacterium genus, particularly Mycobacterium tuberculosis.

Active tuberculosis is the active stage of disease when the bacteria is infectious, growing and multiplying, causing damage and inflammation. Latent tuberculosis is when the bacteria are inactive and noninfectious, and the person is asymptomatic, however, it can turn active. TB can affect any part of the body, but most commonly affects the lungs.

Isoniazid works by inhibiting the synthesis of mycoloic acids, an essential component of the bacterial cell wall. Isoniazid kills (bactericidal) fast-growing bacteria and inhibits the growth (bacteriostatic) of slow-growing bacteria. Isoniazid is a part of a multi-drug regimen in the treatment of active tuberculosis, while it may be used as monotherapy or in combination with other antitubercular agents to treat latent tuberculosis. Treatment of latent TB greatly reduces the risk of the infection progressing to active disease. 

• Risk for developing hepatitis:
  • Isoniazid treatment can lead to severe and sometimes fatal hepatitis, within the first 3 months or even after many months of treatment.
  • The risk factors for developing hepatitis include:
    • Age older than 35 years (risk increases progressively with age)
    • Alcohol consumption
    • Chronic liver disease
    • Injection drug use
  • Use with caution in patients with impaired liver function.
  • Monitor patients for signs and symptoms of hepatotoxicity.
  • Inform patients of the symptoms of liver damage and instruct them to report symptoms immediately.
  • Discontinue isoniazid immediately if the patient develops symptoms of liver damage.
• Do not use isoniazid in patients who:
  • Are hypersensitive to any of the components in isoniazid
  • Develop severe hypersensitive reactions, including drug-induced hepatitis
  • Have previous isoniazid-associated liver injury
  • Have severe adverse reaction to isoniazid, such as drug fever, chills or arthritis
  • Have acute liver disease
  • Have acute pancreatitis
• Stop isoniazid immediately if the patient develops hypersensitivity symptoms.
• Isoniazid use should be monitored and used with caution in the following conditions:
  • Impaired kidney function
  • Chronic liver disease
  • Malnourishment
  • Age older than 35 years
  • Pregnancy
  • Women of minority groups, particularly in the postpartum period
  • Use of other regular medications 
  • History of previous discontinuation of isoniazid
  • Daily alcohol consumption
  • Use of illicit injectable drugs
  • HIV seropositive patients
  • Peripheral neuropathy or predisposition to neuropathy
• Administer vitamin B6 (pyridoxine) concurrently to:
  • Pregnant women
  • Malnourished patients
  • Patients with predisposition to neuropathy
• Active tuberculosis must be treated with multiple concomitant anti-tuberculosis medications to prevent the emergence of drug resistance. Monotherapy with any antitubercular agent, including isoniazid, is inadequate.
• A major cause of drug-resistant tuberculosis is patient noncompliance with treatment. The use of Directly Observed Therapy (DOT), in which a healthcare provider or caregiver ensures that the patient takes the drug as prescribed, can help assure patient compliance with drug therapy.

Common side effects of isoniazid include:

• Signs of liver toxicity (hepatotoxicity) including:
  • Increase in liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
  • High bilirubin levels in blood (hyperbilirubinemia)
  • Bilirubin in the urine (bilirubinuria)
  • Yellowing of skin (jaundice)
  • Liver inflammation (hepatitis)
  • Progressive liver damage (incidence increases with age)
• Nausea
• Vomiting
• Upper abdominal (epigastric) distress
• Inflammation of the pancreas (pancreatitis)
• Nerve damage in the extremities (peripheral neuropathy)
• Convulsions
• Toxic brain damage (encephalopathy)
• Optic nerve damage and wasting (optic neuritis and atrophy)
• Memory impairment
• Toxic psychosis
• Blood disorders including:
  • Severely low count of granulocyte immune cells (agranulocytosis)
  • Low red blood cell count due to destruction of red cells (hemolytic anemia)
  • Anemia due to deficient new red cell production (aplastic anemia)
  • Anemia due to abnormal utilization of iron (sideroblastic anemia)
  • Low platelet levels (thrombocytopenia)
  • High count of eosinophil inflammatory cells (eosinophilia)
• Vitamin B6 (pyridoxine) deficiency
• Pellagra, a condition with vitamin B3 deficiency
• High blood glucose levels (hyperglycemia)
• Excessive acidity of body fluids (metabolic acidosis)
• Abnormal breast tissue growth in males (gynecomastia)
• Hypersensitivity reactions including:
  • Fever
  • Skin reactions and eruptions including:
    • Measles-like rash (morbilliform)
    • Raised and flat lesions (maculopapular)
    • Purplish discolored (purpuric) rash
    • Exfoliative dermatitis
    • Toxic epidermal necrolysis
  • Swollen lymph nodes (lymphadenopathy)
  • Blood vessel inflammation (vasculitis)
  • Drug reaction with eosinophilia syndrome (DRESS)
• Rheumatic syndrome
• Systemic lupus erythematosus-like syndrome

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablets

• 50 mg
• 100 mg
• 300 mg

Oral Syrup

• 50 mg/5 mL

Injectable Solution

• 100 mg/mL

Adult:

Latent Tuberculosis Infection

• Treatment of latent TB infection greatly reduces the risk that TB infection will progress to active disease
• Above 30 kg: 300 mg orally once daily for 9 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 human immunodeficiency virus (HIV) infection who are otherwise healthy and not taking antiretrovirals may also use this regimen
• 900 mg orally once weekly for 3 months (administer with rifapentine 900 mg once weekly)
• Administered as Directly Observed Treatment (DOT)
• Not recommended for children below 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

Active Tuberculosis Disease

• 5 mg/kg oral/intramuscular (IM) once daily, not to exceed 300 mg once daily  
• 15 mg/kg oral/IM up; not to exceed 900 mg 1-3 times/week
• Used in multi-drug regimens containing rifampin (or ribabutin or rifapentin), pyrazinamide, and ethambutol
• Duration of treatment dependent on regimen consisting of an initial phase of treatment and a continuation phase of treatment
• Note: Daily treatment has the best results for HIV-positive individuals

Other Indications and Uses

Newly infected patients

• Household members and close associates of people recently diagnosed with TB
  • Positive TB skin test with positive non-progressive chest x-ray
  • Positive TB skin test with underlying disease or immunosuppression
  • Positive TB skin test, below 35 years old; for patients above 35 years old, weigh use against the risk of hepatitis

Pediatric:

Latent Tuberculosis Infection

• Treatment of latent TB infection greatly reduces the risk that TB infection will progress to active disease
• 10-15 mg/kg orally once daily; 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; the preferred regimen for this age group is daily isoniazid for 9 months
• Not recommended for children below 2 years
• Above 12 years: isoniazid 900 mg oral plus rifapentine 900 mg oral once weekly for 3 months

Active Tuberculosis Disease

• 10-15 mg/kg orally once daily; not to exceed 300 mg/day OR  
• 20-30 mg/kg (up to 900 mg) 2 times/week
• Used in a multi-drug regimen

Overdose

Acute overdose

• Early symptoms of acute isoniazid overdose include nausea, vomiting, dizziness, slurring of speech, blurring of vision, and visual hallucinations (including bright colors and strange designs). Severe overdose can lead to respiratory distress, central nervous system (CNS) depression, progressing rapidly from stupor to profound coma, and severe intractable seizures.
• Symptoms can set in from 30 minutes to 3 hours after ingestion. Overdose in asymptomatic patients may be treated with gastric emptying and administration of activated charcoal to eliminate undigested drug in the gastrointestinal tract, and supportive treatment including airway management and administration of pyridoxine. 
• Symptomatic patients, in addition, may require respiratory support and other intensive supportive care and seizure management with benzodiazepines.

Chronic overdose

• Chronic overdose can cause peripheral neuropathy with symptoms that include numbness, tingling, and burning sensation in the extremities, and liver toxicity which can cause nausea, loss of appetite (anorexia), abdominal discomfort with right upper quadrant pain, generalized flu-like symptoms, fatigue, dark urine, and jaundice.
• Chronic overdose is prevented or managed by monitoring patients for symptoms of toxicity and patient’s liver enzyme levels. The drug should be discontinued in the event of chronic overdose symptoms and appropriate treatment instituted.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of isoniazid include:
  • cobimetinib
  • conivaptan
  • dihydroergotamine
  • dihydroergotamine intranasal
  • eliglustat
  • flibanserin
  • infigratinib
  • ivabradine
  • ketoconazole
  • levoketoconazole
  • lomitapide
  • lonafarnib
  • lovastatin
  • lurasidone
  • mavacamten
  • naloxegol
  • pacritinib
  • regorafenib
  • venetoclax
  • voclosporin
• Isoniazid has serious interactions with at least 99 different drugs.
• Isoniazid has moderate interactions with at least 264 different drugs.
• Isoniazid has mild interactions with at least 81 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• There are no adequate and well-controlled studies on isoniazid use in pregnant women, however, animal reproductive studies show isoniazid can cause fetal harm.
• Isoniazid should be used to treat active tuberculosis in pregnant women because the benefits of the treatment justify the potential risk to the fetus.
• Preventive treatment should preferably be initiated after delivery to prevent the risk of drug exposure to the fetus. If preventive treatment is necessary during pregnancy, the benefit of treatment should be weighed against the potential risk to the fetus.
• Breastfeeding is compatible with isoniazid treatment, because the low concentration of the drug in the breastmilk does not pose a hazard to the breastfeeding infant. The low level of drug in the breastmilk cannot either be relied on for prophylaxis therapy in the nursing infant.

• Take isoniazid exactly as instructed, do not skip doses, and complete the full prescribed course even if you feel better because interrupting the course can reduce the treatment efficacy and lead to the development of multidrug-resistant bacteria.
• Avoid alcohol consumption while you are on antitubercular treatment, it can increase the risk for liver damage.
• Inform your physician immediately if you experience:
  • Symptoms of liver damage, which may include unexplained appetite loss, nausea, vomiting, dark urine, jaundice, rash, persistent numbness and tingling of hands and feet, persistent fatigue, weakness or fever of greater than 3 days duration, and/or abdominal tenderness, especially right upper quadrant discomfort
  • Hypersensitivity reactions including skin eruptions, fever, and lymph node swelling
• You will need regular tests while you are on isoniazid therapy. Do not miss your appointments.
• Store isoniazid safely out of reach of children.
• In case of overdose, seek medical help immediately or contact Poison Control.