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Isoniazid Side Effects

For the Consumer

Applies to isoniazid: solution, syrup, tablet

Along with its needed effects, isoniazid may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking isoniazid:

More common
  • Clumsiness or unsteadiness
  • dark urine
  • loss of appetite
  • nausea or vomiting
  • numbness, tingling, burning, or pain in hands and feet
  • unusual tiredness or weakness
  • yellow eyes or skin

Some side effects of isoniazid may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common For injection form
  • Irritation at the place of injection

Dark urine and yellowing of the eyes or skin (signs of liver problems) are more likely to occur in patients over 50 years of age.

For Healthcare Professionals

Applies to isoniazid: intramuscular solution, oral syrup, oral tablet

Nervous system

Overdose of isoniazid has been associated with uncontrollable seizures. Dialysis may be required to decrease isoniazid blood levels, thereby controlling seizures. Seizures, lethargy, and confusion have also been reported in patients with chronic renal failure. Other patients at risk for neurotoxicity include the malnourished and alcoholics. Optic neuritis has also been reported in patients on hemodialysis.[Ref]

Peripheral neuropathy has been observed and occurs frequently, especially at doses greater than 300 mg daily. Neuropathy may be prevented or attenuated by coadministration of pyridoxine 50 to 100 mg daily. Other neurologic reactions, although rare, have included visual disturbances, ataxia, and seizures.[Ref]


Hepatitis has been reported in less than 5% of patients receiving isoniazid alone. Jaundice is usually preceded by a prodromal illness with fatigue, nausea, malaise, abdominal pain, and anorexia. Asymptomatic increases in liver function tests may occur. Isoniazid should be discontinued if hepatotoxicity occurs, usually defined as SGOT greater than four times normal.[Ref]

The mechanism of hepatic injury is unknown but may be related to the acetyl metabolite of isoniazid. Patients exhibiting hepatotoxicity are more likely to be fast acetylators of isoniazid. Eight cases of severe hepatitis resulting in death or transplantation have been evaluated by the Department of Health of New York. Duration of isoniazid use before onset of hepatitis ranged from 21 to 142 days, and seven patients continued use of isoniazid at least 10 days after onset of symptoms. Massive hepatic necrosis was a common finding and cholestasis was present in two of five cases.

The risk is age related with a greater occurrence reported in patients who are 35 years or older. The risk of hepatitis is also increased in patients who consume alcohol daily, in women, and in minorities. In a study of 2651 women beginning isoniazid preventive therapy during pregnancy or postpartum, 5 cases of isoniazid-induced hepatitis were identified, including two fatalities. In another review of deaths due to isoniazid, eight of 21 women between 15 and 44 years old were within one year postpartum. In general, death due to isoniazid hepatotoxicity occurs more frequently in women than men.

Fulminate hepatitis, characterized by jaundice, disorders of consciousness and elevated serum transaminases up to 80 times the upper limit of normal, has occasionally occurred in patients receiving isoniazid with rifampin. Rifampin, by virtue of its enzyme-inducing activity, likely increases the reactive metabolite of isoniazid thought to be responsible for the hepatotoxicity associated with isoniazid.

Monthly monitoring and interviewing of patients should take place. Patients should be fully informed regarding the risk of hepatotoxicity associated with isoniazid, educated about the signs and symptoms of liver damage, and instructed to contact their physician immediately if they develop signs or symptoms.[Ref]


Hematologic abnormalities such as anemia have been reported. Anemia is generally reversible following discontinuation of isoniazid. Agranulocytosis, thrombocytopenia, and eosinophilia have rarely been reported.[Ref]

Several cases have been reported of pure red cell aplasia attributable to isoniazid. Abnormalities resolved following drug discontinuation.[Ref]


Hypersensitivity reactions including drug fever, rash, lymphadenopathy, vasculitis, and urticaria have been reported but are rare. These reactions generally subside following drug discontinuation.[Ref]


Isoniazid-induced lupus-like reactions have been reported with an incidence of approximately 1%. However, as many as 22% of patients on this drug may develop positive antinuclear antibodies. Drug discontinuation is recommended if a lupus-like reaction occurs.[Ref]


Psychosis, depression, and aggression have been rarely reported with isoniazid therapy. Some patients with preexisting schizophrenia have experienced exacerbations when isoniazid was started.[Ref]


Gastrointestinal adverse effects have included nausea, vomiting, and epigastric distress. A few cases of pancreatitis have been reported.[Ref]


Metabolic side effects such as pyridoxine deficiency and pellagra have been reported. Isoniazid induced hypocalcemia and hypophosphatemia has been observed and may be due to altered vitamin D metabolism.[Ref]


Local irritation has been observed at the site of intramuscular injection of isoniazid.[Ref]


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Some side effects of isoniazid may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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