Isoniazid

Agent: isoniazid

Isoniazid is active only against M. tuberculosis and the related M. kansasii, but it is one of the two most important drugs in tuberculosis pharmacotherapy  (the other being rifampin). It works by preventing the synthesis of mycolic acids in the cell wall, and it is effective against both actively growing and dormant mycobacteria. It is used in the treatment of both active and latent tuberculosis.

Spectrum

Active only against M. tuberculosis and M. kansasii.

Adverse Effects

Isoniazid’s classic adverse reaction is peripheral neuropathy. This can be prevented by administering pyridoxine (vitamin B6), which is recommended for patients at risk for developing neuropathy (e.g., diabetics, pregnant women, alcohol abusers). Other neurotoxicities that are less common include optic neuritis and, rarely, seizures. Drug-induced lupus can also occur; this abates with the cessation of therapy. Like other tuberculosis medications, hepatotoxicity is also possible. Hypersensitivity can be seen, most commonly as rash or drug fever.

Important Facts

• Isoniazid is the drug of choice for the treatment of latent tuberculosis. It can be given as monotherapy for latent disease because the burden of organisms is much lower than in active tuberculosis, where resistance can develop to monotherapy.

• Isoniazid is a classic example of a drug with variable pharmacogenomic metabolism. “Rapid acetylators” of isoniazid metabolize it more quickly than “slow acetylators,” but the clinical significance of this is unknown. Genetic testing is not routinely performed before starting isoniazid.

• Isoniazid is bactericidal against growing mycobacteria, but bacteriostatic against dormant mycobacteria.

• Patients should be advised not to drink alcohol while taking isoniazid. This has nothing to do with the common myth that alcohol decreases antibiotic effectiveness; it is to prevent an additive risk of hepatotoxicity.

What It’s Good For

Isoniazid is the drug of choice for both active and latent tuberculosis. For treatment of active tuberculosis, it must be combined with other medications. The combination of isoniazid and rifampin is common for the consolidation phase of non-multidrug-resistant tuberculosis.

Don’t Forget!

Although guidelines require adding pyridoxine for  preventing neuropathy only in high-risk patients,  there’s no downside in recommending it to all your patients receiving isoniazid. Don’t confuse pyridoxine with pyrazinamide  and assume that your patient is receiving both drugs when he or she is not. Most patients with tuberculosis should be taking both pyridoxine and pyrazinamide.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.