Isoniazid


Thông tin thuốc gốc
Chỉ định và Liều dùng
Intramuscular
Tuberculosis
Adult: 5 mg/kg up to 300 mg daily as a single dose or 15 mg/kg up to 900 mg/day, 2 or 3 times wkly.
Child: 10-15 mg/kg up to 300 mg daily as a single dose or 20-40 mg/kg up to 900 mg/day, 2 or 3 times wkly.

Oral
Tuberculosis
Adult: 5 mg/kg up to 300 mg daily as a single dose or 15 mg/kg up to 900 mg/day, 2 or 3 times wkly.
Child: 10-15 mg/kg up to 300 mg daily as a single dose or 20-40 mg/kg up to 900 mg/day, 2 or 3 times wkly.
Renal Impairment
Severe: Dose reduction may be needed.
Cách dùng
Should be taken on an empty stomach. Best taken on an empty stomach 1 hr before or 2 hr after meals. May be taken w/ meals to reduce GI discomfort.
Chống chỉ định
Hypersensitivity. Patient w/ acute liver disease or a history of isoniazid-associated hepatic injury.
Thận trọng
Patient w/ convulsive disorders, history of psychosis. Patient at risk of neuropathy (e.g. diabetics, alcoholics, malnourished, uraemic, infected w/ HIV) or pyridoxine deficiency. Hepatic and severe renal impairment. Pregnancy and lactation.
Phản ứng phụ
Peripheral neuritis, psychotic reactions, convulsions, optic neuritis, transient increases in liver enzymes; haematological effects (e.g. anaemias, agranulocytosis, thrombocytopenia, eosinophilia); hypersensitivity reactions include skin eruptions (including erythema multiforme), fever, vasculitis; nausea, vomiting, dry mouth, constipation, pellagra, purpura, hyperglycaemia, lupus-like syndrome, vertigo, hyperreflexia, urinary retention, gynaecomastia.
Potentially Fatal: Hepatitis.
IM/Parenteral/PO: C
MonitoringParameters
Monitor baseline and periodic LFTs (ALT and AST), sputum cultures mthly until 2 consecutive negative cultures reported and prodromal signs of hepatitis.
Quá liều
Symptoms: Nausea, vomiting, dizziness, slurred speech, blurred vision, and visual hallucinations (including bright colors and strange designs). Resp distress and CNS depression, progressing rapidly from stupor to coma, severe intractable seizures, metabolic acidosis, acetonuria and hyperglycaemia may occur after marked overdosage. Management: Secure the airway and ensure adequate ventilation. Seizures may be controlled w/ IV diazepam or short-acting barbiturates and a dosage of pyridoxine HCl equal to the amount of isoniazid ingested (generally, 1-4 g IV followed by 1 g IM every 30 min until the entire dose has been given). If seizures are controlled and overdosage is recent (w/in 2-3 hr), empty the stomach by gastric lavage and perform necessary laboratory tests. Give IV Na bicarbonate to control metabolic acidosis, may repeat as needed. Forced osmotic diuresis should be initiated as soon as possible to increase renal clearance. In severe cases, haemodialysis or peritoneal dialysis is used in conjunction w/ forced osmotic diuresis.
Tương tác
Inhibit the hepatic metabolism of antiepileptics (e.g. carbamazepine, ethosuximide, primidone, phenytoin), benzodiazepines (e.g. diazepam, triazolam), chlorzoxazone, theophylline, disulfiram, sometimes leading to increased toxicity. Increased metabolism of enflurane, resulting in potentially nephrotoxic levels of fluoride. Increased concentrations and enhanced effects or toxicity of clofazimine, cycloserine and warfarin. Reduced absorption w/ Al-containing antacids. Increased risk of peripheral neuropathy w/ zalcitabine and stavudine.
Food Interaction
Decreased bioavailability if taken w/ food. Avoid tyramine-containing (e.g. cheese, red wine) and histamine-containing foods (e.g. skipjack, tuna, other tropical fish) as exaggerated response (e.g. headache, sweating, palpitations, flushing, hypotension) may occur. Alcohol may reduce the efficacy of isoniazid and may increase risk of developing peripheral neuropathies and hepatic damage.
Lab Interference
May cause false-positive results w/ cupric sulfate soln (Benedict's reagent and Clinitest®) for urine glucose determinations.
Tác dụng
Description: Isoniazid inhibits the synthesis of mycoloic acids in susceptible bacteria which results in loss of acid-fastness and disruption of bacterial cell wall. At therapeutic levels, it is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms.
Pharmacokinetics:
Absorption: Readily absorbed from the GI tract and after IM inj. Rate and extent of absorption is reduced by food. Time to peak plasma concentration: After 1-2 hr (oral).
Distribution: Distributed into all body tissues and fluids including CSF. Crosses the placenta and enters breast milk.
Metabolism: Undergoes acetylation of isoniazid to acetylisoniazid by N-acetyltransferase found in the liver and small intestine, which is then hydrolysed to isonicotinic acid and monoacetylhydrazine; isonicotinic acid is conjugated w/ glycine to isonicotinyl glycine (isonicotinuric acid) and monoacetylhydrazine is further acetylated to diacetylhydrazine.
Excretion: Via urine (>75%, mainly as metabolites) and faeces (small amounts). Plasma half-life: Approx 1-6 hr.
Đặc tính

Chemical Structure Image
Isoniazid

Source: National Center for Biotechnology Information. PubChem Database. Isoniazid, CID=3767, https://pubchem.ncbi.nlm.nih.gov/compound/Isoniazid (accessed on Jan. 21, 2020)

Bảo quản
Store between 20-25°C. Protect from moisture and light.
Phân loại MIMS
References
Anon. Isoniazid. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 26/08/2014.

Buckingham R (ed). Isoniazid. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/08/2014.

Isoniazid Injection, Solution (Sandoz Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 26/08/2014.

Isoniazid Tablet (Barr Laboratories Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 26/08/2014.

McEvoy GK, Snow EK, Miller J et al (eds). Isoniazid. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 26/08/2014.

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