isoniazid; isonicotinic acid hydrazide (INH, Nydrazid, Hyzyd, Laniazid, Niazid)
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Introduction
Tradename: Nydrazid, INH. (isonicotinic acid hydrazide).
Indications
- treatment of active & latent tuberculosis[9]
- prophylaxis for tuberculosis exposure
Dosage
Tuberculosis: 10-20 mg/kg up to 300 mg PO QD.
Tabs: 50,100, 300 mg.
Syrup: 50 mg/5 mL.
Injection: 100 mg/mL (10 mL vials)
Dosage adjustment in renal failure
- none, dose after hemodialysis
Pharmacokinetics
- rapid & complete absorption after oral administration
- distributed to most body tissues including CSF
- metabolized by liver
- eliminated in urine
- 1/2 life dependent upon acetylation status of patient
- rapid acetylators 1-1.5 hours
- slow acetylators 2-2.5 hours
- prolonged in liver impairment (8-17 hours ESRD)
- 50-100% removed by hemodialysis
elimination via liver
elimination via kidney
1/2life = 45-80 hours fast acetylators
1/2life = 140-200 hours slow acetylators
protein binding = <5 %
elimination by hemodialysis = +
elimination by peritoneal dialysis = +
Monitor
- liver function tests baseline & monthly if
- Canadian guidelines: LFTS periodically in all patients[12]
Adverse effects
- common (> 10%)
- peripheral neuritis
- give supplemental pyridoxine 25 mg PO QD
- loss of appetite
- nausea/vomiting
- stomach pain
- weakness
- peripheral neuritis
- less common (1-10%)
- hepatotoxicity, hepatitis (1-2.5%), 0.6%[8][10]
- dizziness, slurred speech, lethargy, hyperreflexia
- uncommon (< 1%)
- blood dyscrasias, fever, skin rash, arthralgia, seizures, mental depression, psychosis,
- ocular adverse effects optic neurpathy, blurred vision, loss of vision
- other
- decreases synthesis of GABA, resulting in CNS stimulation
- symptoms include nausea, vomiting, dizziness, slurred speech, coma, seizures & metabolic acidosis
- treatment: GI decontamination followed by activated charcoal. Pyridoxine slowly IV in weight equivalent to ingested isoniazid, or empirically 5 g IV over 30 min as 5-10% solution
Drug interactions
- antacids & aluminum salts may delay & decrease INH absorption; take 2 hours apart
- alcohol increases risk of hepatotoxicity
- INH inhibits metabolism of carbamazepine & phenytoin
- disulfiram in combination may cause altered mental status
- corticosteroids in combination enhance metabolism of INH
- ketoconazole levels are decreased with INH; SHOULD NOT BE TAKEN TOGETHER
- phenobarbital may increase metabolism of INH
- p-aminosalicylate, procainamide, chlorpromazine increase INH t1/2
- INH may enhance metabolism of theophylline
- INH inhibits cyt P450 CYP1A2 & CYP2C9
- may increase levels of drugs metabolized by cyt P450 CYP1A2 & CYP2C9
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) of antibiotics with warfarin
Test interactions
- chemical interferences
- isoniazid may increase plasma ammonia levels
Laboratory
- specimen:
- methods: GLC, HPLC, color, fluorometry
- interferences:
- color method is insensitive & cumbersome
- pyrazinamide & p-aminosalicylic acid (high conc.) can interfere
Mechanism of action
- inhibits synthesis of mycolic acid, a component of mycobacterial cell wall
- bacteriostatic or bactericidal depending upon bacterial replication rate & concentration
More general terms
Additional terms
- cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)
- cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996.
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 133
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ 5.0 5.1 Medical Knowledge Self Assessment Program (MKSAP) 11, 17. American College of Physicians, Philadelphia 1998, 2015
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ 7.0 7.1 Prescriber's Letter 8(8):48, 2001
- ↑ 8.0 8.1 Journal Watch 25(17):137-38, 2005 Fountain FF, Tolley E, Chrisman CR, Self TH. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. Chest. 2005 Jul;128(1):116-23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16002924
- ↑ 9.0 9.1 CDC & American Thoracic Society http://www.thoracic.org/adobe/statements/latenttb1-27.pdf
- ↑ 10.0 10.1 Chalasani N et al. for the Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008 Dec; 135:1924. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18955056
- ↑ 11.0 11.1 deprecated reference
- ↑ 12.0 12.1 12.2 Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com