QuickView for Isoniazid (compound)

Summary
General Info

PubChem

PubChem Compound 10846163

Name:	Isoniazid
PubChem Compound ID:	10846163
Description:	Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.
Molecular formula:	C₆H₇N₃O
Molecular weight:	138.133 g/mol

DrugBank

Identification

Name:	Isoniazid
Name (isomeric):	DB00951
Drug Type:	small molecule
Description:	Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.
Synonyms:	HIA; INH; Isonicotinhydrazid; Isonicotinyl hydrazide; Hydrazide; Isonicotinylhydrazine; Hydrazid; Isonicotinohydrazide; Isohydrazide; Isonicotinic acid hydrazide. show more » HIA; INH; Isonicotinhydrazid; Isonicotinyl hydrazide; Hydrazide; Isonicotinylhydrazine; Hydrazid; Isonicotinohydrazide; Isohydrazide; Isonicotinic acid hydrazide; Isonicotinic hydrazide; Isonicotinoyl hydrazide; Isonicotinyl hydrazine show less «
Brand:	Isobicina, Defonin, Isonilex, Isonicazide, Isonikazid, Isoniton, Inah, Robisellin, Hidrulta, Laniazid, Isopyrin, Nicizina, Tekazin, Inizid, Tibazide, Sanohidrazina, Ebidene, Niadrin, Pyrizidin, Mybasan, Neoteben, Isotebe, Nydrazid, Isonin, Sauterazid, Rimicid, Tebenic, Stanozide, Tibivis, Tubecotubercid, Phthisen, Laniozid, Nicazide, Isonindon, TB-Vis, Iscotin, Zonazide, Unicozyde, Isonicid, Tuberian, Nicotisan, Unicocyde, Tebexin, Tubazide, Chemidon, Niplen, Isocotin, Isoniazid SA, Cemidon, Ido-tebin, Atcotibine, Isoniacid, Idrazil, FSR 3, Razide, Pyreazid, Pelazid, Bacillin, TB-Razide, Roxifen, Tubeco, Armazide, Dibutin, Isocid, Tubomel, Cotinizin, Diforin, Isotamine, Ditubin, Isozide, Pyridicin, Azuren, Rifamate, TB-Phlogin, Isolyn, Isonizide, Vederon, Isidrina, Neumandin, Tebecid, Isoniazide, Armacide, Hidranizil, Rimiphone, Isonico, Isotinyl, Tubazid, Tebos, Andrazide, Nicozide, Isozyd, Pyricidin, Pycazide, Hyzyd, Hidrun, Cortinazine, Tubicon, Rimitsid, Tibison, Isonerit, Ismazide, Nyscozid, Tubilysin, Hyozid, Antituberkulosum, Robiselin, Sauterzid, Isonex, Evalon, Isonide, Armazid, Zinadon, Fimalene, Cotinazin, Isonidrin, Cedin, Tibemid, Nidrazid, Vazadrine, Hycozid, Eralon, Antimicina, Tyvid, GINK, Retozide, Isonirit, Tibusan, Nidaton, Isotebezid, Nikozid, Chemiazid, Tebilon, Ertuban, Nitadon, Hidrasonil, Nevin, Raumanon, Teebaconin, Neoxin, Percin, Nicetal, Isonicotil, Isocidene, Rimifon, Eutizon, Niconyl, Nicotibina, Neo-Tizide, Nicotibine, Dinacrin, Isonicotan, Zidafimia
Brand name mixture:	Rifater(Isoniazid + Pyrazinamide + Rifampin), Isotamine B 300(Isoniazid + Pyridoxine Hydrochloride)
Category:	Antitubercular Agents, Fatty Acid Synthesis Inhibitors
CAS number:	54-85-3

Pharmacology

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-gr... show more » 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. show less «
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 b... show more » 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. show less «
Absorption:	Readily absorbed following oral administration; however, may undergo significant first pass metabolism. Absorption and bioavailability are reduced when isoniazid is administered with food.
Protein binding:	Very low (0-10%)
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.
Route of elimination:	From 50 to 70 percent of a dose of isoniazid is excreted in the urine within 24 hours.
Half Life:	Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours.
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.
Affected organisms:	Mycobacteria

Interactions

Food interaction:

Avoid alcohol.

Avoid aged foods (cheese, red wine), pickled foods, cured foods (bacon/ham), chocolate, fava beans, beer, unless approved by your physician.

Take on empty stomach: 1 hour before or 2 hours after meals.

Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.

Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.

Drug interaction:

Disulfiram	Increased risk of CNS adverse effects
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.
Fosphenytoin	Isoniazid may increase the effect of phenytoin in 20% of patients.
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.
Aminophylline	Isoniazid may increase the effect and toxicity of oxtriphylline.

Disulfiram	Increased risk of CNS adverse effects
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.
Fosphenytoin	Isoniazid may increase the effect of phenytoin in 20% of patients.
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.
Aminophylline	Isoniazid may increase the effect and toxicity of oxtriphylline.
Warfarin	Isoniazid may increase the anticoagulant effect of warfarin.
Ketoconazole	Isoniazid decreases the effect of ketoconazole
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.
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.
Acetaminophen	Risk of hepatotoxicity
Ethotoin	Isoniazid increases the effect of phenytoin in 20% of patients
Tramadol	Isoniazid may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Isoniazid may decrease the effect of Tramadol by decreasing active metabolite production.
Mephenytoin	Isoniazid increases the effect of phenytoin in 20% of patients
Theophylline	Isoniazid may increase the therapeutic and adverse effects of theophylline.
Temsirolimus	Isoniazid may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
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.
Meperidine	Possible episodes of hypotension
Tolterodine	Isoniazid may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
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.
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.
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.
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.
Carbamazepine	Carbamazepine effect is increased as is isoniazid toxicity
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.
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.
Telithromycin	Isoniazid may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
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.
Dyphylline	Increases the effect and toxicity of theophylline
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.
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.
Dicumarol	Isoniazid may increase the anticoagulant effect of dicumarol.
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.
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.
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.
Oxtriphylline	Isoniazid may increase the effect and toxicity of oxtriphylline.
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.
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.
Anisindione	Isoniazid may increase the anticoagulant effect of anisindione.
Acenocoumarol	Isoniazid may increase the anticoagulant effect of acenocoumarol.

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Targets

Peroxidase/catalase T

Enoyl-[acyl-carrier-protein] reductase [NADH]

Enzymes

Arylamine N-acetyltransferase 2

Arylamine N-acetyltransferase

Cytochrome P450 2A6

Cytochrome P450 2C8