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Monograph for Isoniazid (isonicotinyl hydrazine or INH)

Introduction

Tuberculosis is an infection caused by M tuberculosis which affects millions of people worldwide. The first reasonable cure for tuberculosis was considered at the discovery of isoniazid 1952 by Roche who trademarked it as Rimifon®. Currently INH is used as the first-line antituberculous medication for prophylaxix and treatment of tubercule infection. However isoniazid is not used alone for treatment of active tuberculosis due to the fact that resistance quickly develops and is thus commonly accompanied by Rifampicin1.

Isoniazid is available world wide due to inexpensive production and good tollereance. The drug is available in tablet, syrup, and injectable forms (delivered IM or IV) and kills 90% of viable bacilli within the first 2 months of treatment, rendering the patient non-infectious and reducing of drug resistance.

Summary

Since its discovery in the early 1950's, isoniazid has remained the cornerstone drug in treating tuberculosis. Although INH is used in conjunction with other anti-tuberculosis drugs, resistance to this drug is reduced due to the fact that it kills 90% of viable bacilli within the first 2 months of treatment, which also renders the patient non-infectious. The widespread use of INH can be attributed to its relatively low toxicity and excellent pharmacokinetics. Because of its high early bactericidal activity, INH is also often the first agent against which M tuberculosis develops resistance. With few contraindications, inexpensive production and suitability for adults and children, this has been used world wide.

INH relies on affecting the mycobacterial cell wall production by inhibiting its sysnthesis inhibiting production of mycolic acids. The fact that INH is immediately present in the CSF and serum; there is a high risk of toxicity in the host. Newer drugs are being developed which target the bacterial cell in alternative locations, however until their development is complete, INH will continue to be used in conjunction with other anti-tuberculosis drugs as the primary line of prophylaxix and treatment.

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