Rifampin isoniazid pyrazinamide

Rifampin isoniazid pyrazinamide

Error creating thumbnail: File missing
Clinical data
Pregnancy category	C
Routes of administration	oral, intramuscular, intravenous
ATC code	J04AC01 (WHO)
Legal status
Legal status	prescription only (US)
Pharmacokinetic data
Protein binding	Very low (0-10%)
Metabolism	liver; CYP450: 2C19, 3A4 inhibitor
Elimination half-life	0.5-1.6h (fast acetylators), 2-5h (slow acetylators)
Excretion	urine (primarily), feces
Identifiers
IUPAC name pyridine-4-carbohydrazide
CAS Number	54-85-3
PubChem CID	3767
DrugBank	APRD01055
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C6H7N3O
Molar mass	137.139 g/mol

WikiDoc Resources for Rifampin isoniazid pyrazinamide
Articles
Most recent articles on Rifampin isoniazid pyrazinamide Most cited articles on Rifampin isoniazid pyrazinamide Review articles on Rifampin isoniazid pyrazinamide Articles on Rifampin isoniazid pyrazinamide in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Rifampin isoniazid pyrazinamide Images of Rifampin isoniazid pyrazinamide Photos of Rifampin isoniazid pyrazinamide Podcasts & MP3s on Rifampin isoniazid pyrazinamide Videos on Rifampin isoniazid pyrazinamide
Evidence Based Medicine
Cochrane Collaboration on Rifampin isoniazid pyrazinamide Bandolier on Rifampin isoniazid pyrazinamide TRIP on Rifampin isoniazid pyrazinamide
Clinical Trials
Ongoing Trials on Rifampin isoniazid pyrazinamide at Clinical Trials.gov Trial results on Rifampin isoniazid pyrazinamide Clinical Trials on Rifampin isoniazid pyrazinamide at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Rifampin isoniazid pyrazinamide NICE Guidance on Rifampin isoniazid pyrazinamide NHS PRODIGY Guidance FDA on Rifampin isoniazid pyrazinamide CDC on Rifampin isoniazid pyrazinamide
Books
Books on Rifampin isoniazid pyrazinamide
News
Rifampin isoniazid pyrazinamide in the news Be alerted to news on Rifampin isoniazid pyrazinamide News trends on Rifampin isoniazid pyrazinamide
Commentary
Blogs on Rifampin isoniazid pyrazinamide
Definitions
Definitions of Rifampin isoniazid pyrazinamide
Patient Resources / Community
Patient resources on Rifampin isoniazid pyrazinamide Discussion groups on Rifampin isoniazid pyrazinamide Patient Handouts on Rifampin isoniazid pyrazinamide Directions to Hospitals Treating Rifampin isoniazid pyrazinamide Risk calculators and risk factors for Rifampin isoniazid pyrazinamide
Healthcare Provider Resources
Symptoms of Rifampin isoniazid pyrazinamide Causes & Risk Factors for Rifampin isoniazid pyrazinamide Diagnostic studies for Rifampin isoniazid pyrazinamide Treatment of Rifampin isoniazid pyrazinamide
Continuing Medical Education (CME)
CME Programs on Rifampin isoniazid pyrazinamide
International
Rifampin isoniazid pyrazinamide en Espanol Rifampin isoniazid pyrazinamide en Francais
Business
Rifampin isoniazid pyrazinamide in the Marketplace Patents on Rifampin isoniazid pyrazinamide
Experimental / Informatics
List of terms related to Rifampin isoniazid pyrazinamide

Isoniazid is also called isonicotinyl hydrazine or INH. Isoniazid is a first-line antituberculous medication used in the prevention and treatment of tuberculosis. Isoniazid is never used on its own to treat active tuberculosis because resistance quickly develops.

Isoniazid is used in the treatment of mycobacterial infection. It was discovered in 1952, when for the first time, a cure for tuberculosis was considered reasonable. It is available in tablet, syrup, and injectable forms (given intramuscularly or intravenously). Isoniazid is available world-wide, is inexpensive to produce and is generally well tolerated.

Mechanism of action

Isoniazid is a prodrug and must be activated by bacterial catalase. It is activated by catalase-peroxidase enzyme katG to form isonicotinic acyl anion or radical. These forms will then react with a NADH radical or anion to form isonicotinic acyl-NADH complex. This complex will bind tightly to ketoenoylreductase known as InhA and prevents access of the natural enoyl-AcpM substrate. This mechanism inhibits the synthesis of mycolic acid in the mycobacterial cell wall.

Isoniazid reaches therapeutic concentrations in serum, cerebrospinal fluid (CSF), and within caseous granulomas. Isoniazid is metabolized in the liver via acetylation. There are two forms of the enzyme responsible for acetylation, so that some patients metabolize the drug quicker than others. Hence, the half-life is bimodal with peaks at 1 hour and 3 hours in the US population. The metabolites are excreted in the urine. Doses do not usually have to be adjusted in case of renal failure.

Isoniazid is bactericidal to rapidly-dividing mycobacteria, but is bacteriostatic if the mycobacterium is slow-growing.

Dosing

The standard dose of isoniazid is 3-5mg/kg/day (max 300mg daily). When prescribed intermittently (twice or thrice weekly) the dose is 15mg/kg (max 900mg daily).

Side effects

Adverse reactions include rash, abnormal liver function tests, hepatitis, sideroblastic anemia, peripheral neuropathy, mild central nervous system (CNS) effects, and drug interactions resulting in increased phenytoin (Dilantin) or disulfiram (Antabuse) levels.

Peripheral neuropathy and CNS effects are associated with the use of isoniazid and are due to pyridoxine (vitamin B6) depletion, but are uncommon at doses of 5 mg/kg. Persons with conditions in which neuropathy is common (e.g., diabetes, uremia, alcoholism, malnutrition, HIV-infection), as well as pregnant women and persons with a seizure disorder, may be given pyridoxine (vitamin B6) (10-50 mg/day) with isoniazid.

Hepatoxicity can be avoided with close clinical monitoring of the patient, specifically nausea, vomiting, abdominal pain and appetite.

Headache, poor concentration, poor memory and depression have all been associated with isoniazid use. The frequency of these side effects is not known, and the association with isoniazid is not well validated. The presence of these symptoms is not frequently disabling and is certainly not a reason to stop treatment with isoniazid; the patient should be strongly encouraged to continue treatment despite these symptoms. It must be explained to the patient that the harm done from not taking isoniazid far outweighs the problems arising from these symptoms.

INH therapy will decrease the efficacy of hormonal birth control when combined with Rifampin.

Synonyms and abbreviations

• Isonicotinyl hydrazine
• Isonicotinic acid hydrazide
• INH
• H (for "hydrazide", and also the WHO standard abbreviation)

Wikipedia links

• Tuberculosis treatment
• Tuberculosis
• Mycobacterium tuberculosis

References

• Core Curriculum on Tuberculosis (2000) Division of Tuberculosis Elimination, Centers for Disease Control and Prevention

See Chapter 6, Treatment of LTBI Regimens - Isoniazid
See Chapter 7 - Treatment of TB Disease Monitoring - Adverse Reactions to First-Line TB Drugs - Isoniazid
See Table 5 First-Line Anti-TB Medications

• Isoniazid Overdose: Recognition and Management American Family Physician 1998 Feb 15