Isoniazid Uses, Dosage, Side Effects & FAQ

Introduction

Isoniazid, also known as isonicotinic acid hydrazide or INH, is a widely used antibiotic for the treatment and prevention of tuberculosis (TB) caused by Mycobacterium tuberculosis. It is a key component of the standard multi-drug therapy for active TB and is also used for the treatment of latent TB to prevent the development of active disease. Isoniazid was first synthesized in 1912 but its antibacterial properties were not discovered until 1951, making it one of the earliest drugs used to treat TB [1].

Chemical and Pharmacological Properties

Isoniazid is a small organic molecule with the chemical formula C ₆H ₇N ₃O. It is a white, crystalline powder that is soluble in water. The primary mechanism of action of isoniazid is the inhibition of mycolic acid synthesis, which is essential for the cell wall of M. tuberculosis. Isoniazid is a prodrug that is activated by a bacterial catalase-peroxidase enzyme called KatG. The activated form of isoniazid inhibits the enzyme InhA, which is involved in the synthesis of mycolic acids [2].

Uses

The main use of isoniazid is in the treatment of active tuberculosis as part of a multi-drug regimen. It is always used in combination with other anti-tubercular drugs such as rifampicin, pyrazinamide, and ethambutol to prevent the development of drug resistance. Isoniazid is also used for the treatment of latent TB infection, which is a state of persistent immune response to stimulation by M. tuberculosis antigens without evidence of clinically manifested active TB. The treatment of latent TB with isoniazid can prevent the development of active TB disease [3].

Dosage and Administration

The dosage of isoniazid depends on the indication, age, and weight of the patient. For the treatment of active TB in adults, the recommended dose is 5 mg/kg (maximum 300 mg) orally once daily in combination with other anti-tubercular drugs. For the treatment of latent TB in adults, the recommended dose is 300 mg orally once daily for 9 months. Isoniazid can be administered orally or intramuscularly. The oral dose should be taken on an empty stomach, at least 1 hour before or 2 hours after meals [4].

Side Effects and Adverse Reactions

The most common side effects of isoniazid include nausea, vomiting, loss of appetite, fatigue, and weakness. The most serious adverse effect of isoniazid is hepatotoxicity, which can range from asymptomatic elevation of liver enzymes to hepatitis and liver failure. The risk of hepatotoxicity increases with age, alcohol consumption, and pre-existing liver disease. Other serious adverse effects include peripheral neuropathy, which can cause numbness, tingling, and burning in the hands and feet, and hematologic reactions such as anemia, thrombocytopenia, and agranulocytosis [5].

Drug Interactions

Isoniazid can interact with several drugs, including other anti-tubercular drugs, anticonvulsants, and anticoagulants. It can increase the metabolism of drugs that are substrates of CYP2C19, CYP2D6, and CYP3A4 enzymes, leading to decreased plasma concentrations and reduced efficacy of these drugs. Isoniazid can also increase the risk of hepatotoxicity when used with other hepatotoxic drugs such as acetaminophen, rifampin, and pyrazinamide. The concomitant use of isoniazid with tofacitinib, a Janus kinase inhibitor used for the treatment of rheumatoid arthritis, can increase the risk of hepatotoxicity [6].

Special Precautions

Isoniazid should be used with caution in patients with liver disease, alcoholism, malnutrition, and HIV infection, as these conditions can increase the risk of hepatotoxicity. It should also be used with caution in patients with diabetes, as it can affect blood sugar levels. Isoniazid should be avoided in patients with a history of severe allergic reactions to isoniazid or any of the ingredients in the formulation. It should also be avoided in patients with active liver disease or acute liver failure. Pregnant women should only use isoniazid if the potential benefit justifies the potential risk to the fetus [4].

Warnings and Alerts

Isoniazid has a black box warning for the risk of severe and sometimes fatal hepatitis. Patients should be monitored for signs and symptoms of liver damage, such as fatigue, weakness, loss of appetite, nausea, vomiting, abdominal pain, dark urine, and yellowing of the skin or eyes. Liver function tests should be performed before starting isoniazid therapy and periodically during treatment. Isoniazid should be discontinued if signs or symptoms of liver damage occur [4].

Clinical Studies and Evidence

Isoniazid has been extensively studied for the treatment and prevention of tuberculosis. A meta-analysis of randomized controlled trials found that isoniazid monotherapy for 6 to 12 months reduced the risk of active TB by 60% to 70% in patients with latent TB infection [3]. Another meta-analysis found that isoniazid in combination with rifampicin, pyrazinamide, and ethambutol for 6 months was effective in treating active TB, with a cure rate of 95% [7].

Mechanism of Action

Isoniazid is a prodrug that is activated by the bacterial catalase-peroxidase enzyme KatG. The activated form of isoniazid inhibits the enzyme InhA, which is involved in the synthesis of mycolic acids, a key component of the cell wall of M. tuberculosis. Inhibition of mycolic acid synthesis leads to disruption of the bacterial cell wall and cell death [2].

Patient Counseling Information

Patients should be advised to take isoniazid exactly as prescribed and not to stop taking it without talking to their healthcare provider. They should be advised to take isoniazid on an empty stomach, at least 1 hour before or 2 hours after meals. Patients should be informed about the signs and symptoms of liver damage and advised to contact their healthcare provider immediately if they experience any of these symptoms. They should also be advised to avoid alcohol while taking isoniazid, as it can increase the risk of liver damage [4].

Visual and Descriptive Information

Isoniazid is available as tablets and oral solution for oral administration and as a solution for intramuscular injection. The tablets are available in strengths of 100 mg and 300 mg. The oral solution is available in a strength of 50 mg/5 mL. The solution for intramuscular injection is available in a strength of 100 mg/mL [4].

Regulatory and Approval Information

Isoniazid was approved by the US Food and Drug Administration (FDA) in 1952 for the treatment of tuberculosis. It is included in the World Health Organization‘s List of Essential Medicines, which includes the most effective and safe medicines needed in a health system [8].

FAQs

1. What is isoniazid used for?
   Isoniazid is an antibiotic used for the treatment and prevention of tuberculosis (TB).
2. How does isoniazid work?
   Isoniazid works by inhibiting the synthesis of mycolic acids, which are essential components of the cell wall of the bacteria that cause TB.
3. What are the side effects of isoniazid?
   The most common side effects of isoniazid include nausea, vomiting, loss of appetite, fatigue, and weakness. Serious side effects include hepatotoxicity and peripheral neuropathy.
4. How should isoniazid be taken?
   Isoniazid should be taken orally on an empty stomach, at least 1 hour before or 2 hours after meals. It can also be administered intramuscularly.
5. What should I avoid while taking isoniazid?
   Patients should avoid alcohol while taking isoniazid, as it can increase the risk of liver damage. They should also avoid taking other medications that can affect liver function without talking to their healthcare provider.

References and Further Reading

1. Isoniazid – StatPearls
2. Isoniazid: an overview from 1952 to the present
3. Latent Tuberculosis Infection: A Guide for Primary Health Care Providers
4. Isoniazid: MedlinePlus Drug Information
5. Isoniazid Toxicity
6. Isoniazid: A Review of Characteristics, Properties and Analytical Methods
7. Treatment of Tuberculosis
8. World Health Organization Model List of Essential Medicines