Which Antitubercular Drug Causes Peripheral Neuritis?: A Guide to Isoniazid and Neuropathy

October 8, 2025 •

3 min read

Peripheral neuropathy is a potential adverse effect associated with certain antitubercular medications, with an estimated incidence that varies depending on dosage and patient risk factors. Understanding which antitubercular drug causes peripheral neuritis is crucial for proper patient management, and the primary culprit is isoniazid (INH).

Quick Summary

Isoniazid (INH) is the main antitubercular drug that causes peripheral neuritis. The condition arises from a functional vitamin B6 deficiency induced by INH, preventable with pyridoxine supplementation.

Key Points

Isoniazid (INH) is the Primary Cause: Isoniazid is the antitubercular drug most commonly associated with causing peripheral neuritis.
Mechanism is Vitamin B6 Deficiency: INH causes a functional pyridoxine (vitamin B6) deficiency by interfering with its metabolism, which is toxic to the peripheral nerves.
Pyridoxine Prevents Neuropathy: Co-administration of pyridoxine supplements is the standard practice for preventing INH-induced peripheral neuritis.
Risk Factors Increase Susceptibility: Drug dosage, malnutrition, alcoholism, and a 'slow acetylator' genetic status are key risk factors.
Symptoms Start with Tingling: Patients typically experience tingling and numbness in their hands and feet, which can progress to muscle weakness if untreated.
Prompt Management is Crucial: Immediate reporting of symptoms and adjusting pyridoxine is essential to prevent permanent nerve damage.

The Primary Culprit: Isoniazid

Isoniazid (INH) is a key medication in treating tuberculosis (TB). However, it is known to cause peripheral neuritis, a condition involving damage to peripheral nerves that results in symptoms such as numbness, tingling, and weakness. Monitoring patients for this side effect and implementing preventative measures is particularly important for those at higher risk.

The Mechanism Behind INH-Induced Neuropathy

Isoniazid's link to peripheral neuritis is due to its interference with vitamin B6 (pyridoxine). INH and its breakdown products bind with pyridoxine, forming a complex that is then eliminated from the body, thus reducing the amount of active vitamin B6. Additionally, INH inhibits an enzyme required to convert pyridoxine into its active form, pyridoxal 5'-phosphate (PLP), which is essential for proper nervous system function. This leads to a functional vitamin B6 deficiency, potentially causing neuropathy.

Risk Factors for Developing Isoniazid Peripheral Neuritis

While anyone taking isoniazid is potentially at risk, certain factors increase the likelihood of developing peripheral neuritis:

Dosage: The amount of INH taken is associated with increased risk.
Genetics: Individuals who metabolize INH slowly ("slow acetylators") may have higher drug levels and a greater risk.
Nutritional Status: Malnourished or underweight patients are more susceptible.
Underlying Health Conditions: Conditions such as diabetes, alcoholism, renal failure, and HIV infection increase risk.
Demographics: Advanced age, pregnancy, and lactation are also associated with increased susceptibility.

Common Symptoms and Presentation

Isoniazid-induced peripheral neuritis usually appears after taking the medication for some time, typically starting with changes in sensation in the extremities. Common symptoms include:

Paresthesia: A feeling of tingling, prickling, or burning, often beginning in the feet.
Numbness: Reduced sensation, typically affecting the hands and feet in a characteristic pattern.
Pain: Sharp or shooting sensations in the affected areas.
Muscle Weakness: In more severe cases, muscles may become weak.
Ataxia: Difficulty with coordination and balance.

Reporting these symptoms to a healthcare provider promptly is important for preventing potential long-term damage.

Prevention and Treatment with Pyridoxine (Vitamin B6)

Preventing isoniazid peripheral neuritis is primarily achieved by giving pyridoxine concurrently with INH.

Prevention: Healthcare providers often recommend pyridoxine for patients on INH, especially those with risk factors.
Treatment: If neuropathy develops, a doctor may recommend adjusting the pyridoxine regimen. Pyridoxine is also used in cases of INH overdose.

Comparison of Antitubercular Drugs and Neuropathic Risk

While isoniazid is the most frequent cause of drug-related peripheral neuritis in TB treatment, other medications, particularly in drug-resistant regimens, can also pose a risk. The table below compares the risk of neuropathy with various antitubercular drugs:


Antitubercular Drug	Primary Side Effects	Neuropathy Risk	Prevention/Management
Isoniazid (INH)	Hepatotoxicity, rash, gastrointestinal upset	High (due to B6 deficiency)	Routine pyridoxine supplementation
Rifampicin	Hepatotoxicity, reddish-orange body fluids, rash	Low	No standard prevention for neuropathy
Pyrazinamide	Hepatotoxicity, hyperuricemia (gout), arthralgia	Low	Monitor uric acid levels
Ethambutol	Optic neuritis, gastrointestinal upset	Very Low (rarely)	Monitor vision and color perception
Streptomycin	Ototoxicity (hearing loss, balance issues)	Low	Monitor auditory function
Linezolid	Peripheral and optic neuropathy (with long-term use)	Medium to High (duration-dependent)	Monitor for symptoms, risk increases with other neurotoxic drugs

Conclusion

Isoniazid is the primary antitubercular drug known to cause peripheral neuritis, largely due to its interference with vitamin B6 metabolism. The risk of developing this side effect is elevated in patients with certain risk factors like dosage, malnutrition, or pre-existing conditions. Prophylactic pyridoxine supplementation is a standard and effective measure to prevent this complication. Patients taking INH should be aware of the symptoms of peripheral neuropathy and report them promptly to ensure timely management and prevent permanent nerve damage. The routine use of pyridoxine with isoniazid is a critical step in maintaining patient safety and treatment success.

For additional information on tuberculosis treatment guidelines, consult the CDC's resources.

Frequently Asked Questions

Isoniazid (INH) is the primary antitubercular drug that can cause peripheral neuritis. This common side effect is a result of the drug's interference with vitamin B6 metabolism.

Isoniazid causes nerve damage by creating a functional deficiency of vitamin B6 (pyridoxine). It binds to pyridoxine and also inhibits the enzyme needed to activate it, disrupting nervous system function.

The symptoms typically begin with a tingling or numbness sensation (paresthesia) in the hands and feet. In severe cases, it can progress to pain, muscle weakness, and ataxia (uncoordinated movements).

Risk factors for INH-induced neuropathy include the amount of drug taken, malnutrition, alcoholism, diabetes, renal failure, HIV infection, and having a slow acetylator genetic status.

Yes, it can be largely prevented. Healthcare providers routinely prescribe pyridoxine (vitamin B6) supplements alongside isoniazid, especially for patients with higher risk factors.

Treatment typically involves adjusting the pyridoxine regimen under medical supervision. In some cases, the isoniazid may be adjusted or the drug discontinued if symptoms are severe and do not improve.

While isoniazid is the main culprit, other antitubercular drugs can also have neurotoxic effects. For example, linezolid can cause neuropathy with prolonged use, and ethambutol is known for causing optic neuritis.