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Home / Drugs / Starting with I / Isoniazid
 
Isoniazid
 

Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [PubChem]
BrandsAndrazide
Antimicina
Antituberkulosum
Armacide
Armazid
Armazide
Atcotibine
Azuren
Bacillin
Cedin
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GINK
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Isidrina
Ismazide
Isobicina
Isocid
Isocidene
Isocotin
Isolyn
Isonerit
Isonex
Isoniacid
Isoniazid SA
Isoniazide
Isonicazide
Isonicid
Isonico
Isonicotan
Isonicotil
Isonide
Isonidrin
Isonikazid
Isonilex
Isonin
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TB-Phlogin
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Tyvid
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Vederon
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CategoriesAntitubercular Agents
Fatty Acid Synthesis Inhibitors
ManufacturersSandoz canada inc
Sandoz inc
Hoffmann la roche inc
Carolina medical products co
Mikart inc
Lannett co inc
Dow pharmaceutical corp sub dow chemical co
Medpointe pharmaceuticals medpointe healthcare inc
Novartis pharmaceuticals corp
Barr laboratories inc
Duramed pharmaceuticals inc sub barr laboratories inc
Halsey drug co inc
Impax laboratories inc
Ivax pharmaceuticals inc sub teva pharmaceuticals usa
Eli lilly and co
Mk laboratories inc
Mutual pharmaceutical co inc
Nexgen pharma inc
Panray corp sub ormont drug and chemical co inc
L perrigo co
Pharmavite pharmaceuticals
Phoenix laboratories inc
Purepac pharmaceutical co
Watson laboratories inc
West ward pharmaceutical corp
Whiteworth towne paulsen inc
Bristol myers squibb co
Everylife
PackagersAdvanced Pharmaceutical Services Inc.
Aidarex Pharmacuticals LLC
Amend
Amneal Pharmaceuticals
Apotheca Inc.
A-S Medication Solutions LLC
Barr Pharmaceuticals
Blenheim Pharmacal
Bristol-Myers Squibb Co.
Bryant Ranch Prepack
Carolina Medical Products Co.
Consolidated Midland Corp.
Dept Health Central Pharmacy
Direct Dispensing Inc.
Dispensing Solutions
E.R. Squibb and Sons LLC
Eon Labs
Golden State Medical Supply Inc.
H.J. Harkins Co. Inc.
Heartland Repack Services LLC
Huffman Laboratories
Liberty Pharmaceuticals
Major Pharmaceuticals
Murfreesboro Pharmaceutical Nursing Supply
Nexgen Pharma Inc.
Nucare Pharmaceuticals Inc.
PCA LLC
PD-Rx Pharmaceuticals Inc.
Pharmpak Inc.
Physicians Total Care Inc.
Preferred Pharmaceuticals Inc.
Prepackage Specialists
Prepak Systems Inc.
Remedy Repack
Sandhills Packaging Inc.
Sandoz
Sanofi-Aventis Inc.
Southwood Pharmaceuticals
UDL Laboratories
Versapharm Inc.
West-Ward Pharmaceuticals
SynonymsHIA
Hydrazid
Hydrazide
INH
Isohydrazide
Isonicotinhydrazid
Isonicotinic acid hydrazide
Isonicotinic hydrazide
Isonicotinohydrazide
Isonicotinoyl hydrazide
Isonicotinyl hydrazide
Isonicotinyl hydrazine
Isonicotinylhydrazine

indication

For the treatment of all forms of tuberculosis in which organisms are susceptible.

pharmacology

Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically M. tuberculosis, M. bovis and M. kansasii. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal to rapidly-dividing mycobacteria, but is bacteriostatic if the mycobacterium is slow-growing.

mechanism of action

Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.

toxicity

LD50 100 mg/kg (Human, oral). Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects. In vivo, Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate; high doses interfere with the coenzyme function of the latter.

biotransformation

Primarily hepatic. Isoniazid is acetylated by N -acetyl transferase to N -acetylisoniazid; it is then biotransformed to isonicotinic acid and monoacetylhydrazine. Monoacetylhydrazine is associated with hepatotoxicity via formation of a reactive intermediate metabolite when N-hydroxylated by the cytochrome P450 mixed oxidase system. The rate of acetylation is genetically determined. Slow acetylators are characterized by a relative lack of hepatic N -acetyltransferase.

absorption

Readily absorbed following oral administration; however, may undergo significant first pass metabolism. Absorption and bioavailability are reduced when isoniazid is administered with food.

half life

Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours.

route of elimination

From 50 to 70 percent of a dose of isoniazid is excreted in the urine within 24 hours.

drug interactions

Acenocoumarol: Isoniazid may increase the anticoagulant effect of acenocoumarol.

Acetaminophen: Risk of hepatotoxicity

Aminophylline: Isoniazid may increase the effect and toxicity of oxtriphylline.

Anisindione: Isoniazid may increase the anticoagulant effect of anisindione.

Bromazepam: Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if isoniazid is initiated, discontinued or dose changed. Dosage adjustments may be required.

Carbamazepine: Carbamazepine effect is increased as is isoniazid toxicity

Carisoprodol: Strong CYP2C19 inhibitors such as isoniazid may decrease the metabolism of CYP2C19 substrates such as carisoprodol. Consider an alternative for one of the interacting drugs in order to avoid toxicity of the substrate. Some combinations are specifically contraindicated by manufacturers. Suggested dosage adjustments are also offered by some manufacturers. Please review applicable package inserts. Monitor for increased effects of the CYP substrate if a CYP inhibitor is initiated/dose increased, and decreased effects if a CYP inhibitor is discontinued/dose decreased.

Dantrolene: Isoniazid may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if isoniazid is initiated, discontinued or dose changed.

Dicumarol: Isoniazid may increase the anticoagulant effect of dicumarol.

Disulfiram: Increased risk of CNS adverse effects

Dyphylline: Increases the effect and toxicity of theophylline

Ethotoin: Isoniazid increases the effect of phenytoin in 20% of patients

Fosphenytoin: Isoniazid may increase the effect of phenytoin in 20% of patients.

Ketoconazole: Isoniazid decreases the effect of ketoconazole

Meperidine: Possible episodes of hypotension

Mephenytoin: Isoniazid increases the effect of phenytoin in 20% of patients

Oxtriphylline: Isoniazid may increase the effect and toxicity of oxtriphylline.

Phenytoin: Isoniazid increases the effect of phenytoin in 20% of patients

Tacrolimus: The strong CYP3A4 inhibitor, Isoniazid, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Isoniazid is initiated, discontinued or dose changed.

Tadalafil: Isoniazid may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.

Tamoxifen: Isoniazid may increase the serum concentration of Tamoxifen by decreasing its metabolism and clearance. Isoniazid may also decrease the therapeutic effect of Tamoxifen by decreasing active metabolite production. Monitor for changes in the therapeutic/adverse effects of Tamoxifen if Isoniazid is initiated, discontinued or dose changed.

Tamsulosin: Isoniazid, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Isoniazid is initiated, discontinued, or dose changed.

Telithromycin: Isoniazid may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.

Temsirolimus: Isoniazid may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.

Teniposide: The strong CYP3A4 inhibitor, Isoniazid, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Isoniazid is initiated, discontinued or dose changed.

Theophylline: Isoniazid may increase the therapeutic and adverse effects of theophylline.

Tiagabine: The strong CYP3A4 inhibitor, Isoniazid, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Isoniazid is initiated, discontinued or dose changed.

Tolterodine: Isoniazid may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.

Tramadol: Isoniazid may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Isoniazid may decrease the effect of Tramadol by decreasing active metabolite production.

Trazodone: The CYP3A4 inhibitor, Isoniazid, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Isoniazid is initiated, discontinued or dose changed.

Trimipramine: The strong CYP3A4/CYP2C19 inhibitor, Isoniazide, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Isoniazid is initiated, discontinued or dose changed.

Vardenafil: Isoniazid, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.

Venlafaxine: Isoniazid, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Isoniazid is initiated, discontinued, or dose changed.

Verapamil: Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Isoniazid is initiated, discontinued or dose changed.

Vinblastine: Isoniazid, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Isoniazid is initiated, discontinued or dose changed.

Vincristine: Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Isoniazid is initiated, discontinued or dose changed.

Vinorelbine: Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Isoniazid is initiated, discontinued or dose changed.

Warfarin: Isoniazid may increase the anticoagulant effect of warfarin.

Zolpidem: Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if isoniazid is initiated, discontinued or dose changed.

Zonisamide: Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if isoniazid is initiated, discontinued or dose changed.

Zopiclone: Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if isoniazid is initiated, discontinued or dose changed.