Isoniazid

Question 1

Isoniazid

Answer 1

Active only against M. tuberculosis and the related M. kansasii

Effective against both actively growing and dormant mycobacteria

Used in treatment of active and latent TB

Question 2

Isoniazid MOA

Answer 2

Prevents synthesis of mycolic acids in the cell wall by inhibiting enzymes that catalyze their production

Question 3

Isoniazid Spectrum

Answer 3

Active only against M. tuberculosis and M. kansasii

Question 4

Isoniazid Adverse Effects

Answer 4

Hepatotoxicity is a concern
Asymptomatic elevations in liver transaminases early in therapy
Will usually resolve on its own and patient can complete treatment
If enzyme levels many times higher than ULN and/or patient experiences symptoms of hepatitis (nausea, abdominal pain, jaundice)- drug needs to be stopped to prevent severe liver damage

Other characteristic adverse reaction is peripheral neuropathy
Can be prevented by administering pyridoxine (vitamin B6)- given to patients at risk for developing neuropathy (diabetic, pregnancy, alcohol abusers)
No downside to recommend it in all patients receiving isoniazid
Don’t confuse with pyrazinamide
Most patients with TB should be on both p’s during the initial phase of therapy

Other less common neurotoxicities (optic neuritis; rarely seizures)
Drug induced lupus can occur- abates with cessation of therapy

Hypersensitivity can be seen (most commonly as rash or drug fever)

Question 5

Isoniazid Important Facts

Answer 5

Drug of choice for treatment of latent TB
Can be given as monotherapy for latent disease (burden of organisms is much lower than in active TB- resistance can develop to monotherapy in active TB)

Has variable pharmacogenomic metabolism
Rapid acetylators metabolize faster than slow acetylators
Clinical significance unknown
Genetic testing not routinely performed

Cidal against growing mycobacteria
Static against dormant mycobacteria

Don’t drink alcohol to prevent an additive risk of hepatotoxicity (myth is that alcohol decrease effectiveness)

Question 6

Isoniazid Good For

Answer 6

Drug of choice for active and latent TB
For active, must be combined with other drugs
Combo of isoniazid and rifampin is recommended for consolidation phase of non-MDR-TB