Pdf isoniazid inh is highly effective for the management of tuberculosis. American thoracic society documents 937 has not been rigorously tested. Druginduced liver injury dili is a problem of increasing signifi cance, but has been. Druginduced liver injury guidelines caused by inh appears to be due to metabolic idiosyncratic reactions. Therefore a better understanding in hu man origin cells that avoid species difference was required to demonstrate whether ntcp was the factor that contributes to the development of inhinduced hepatotoxicity. The incidences of hepatotoxicity are ranged as the following from high to low. An observational study from 1996 to 2003 of isoniazid hepatotoxicity during ltbi treatment in 3,377 patients from memphis, tennessee, found ast elevations at least five times the uln in 0.
Hepatotoxicity of rifampinpyrazinamide and isoniazid preventive. Case report successful diagnosis of hyperpyrexia induced by isoniazid in a child with suspected extrapulmonary tuberculosis caihong qu 1, xiaoyan li, zhenda zheng2, jieming zhu2 departments of 1clinical pharmacy, 2internal medicine, the third affiliated hospital of sun yatsen university, guangzhou, guangdong province, china. Hepatoprotective effect of rutin against oxidative stress of isoniazid in albino rats 1osama abdelghaffar, 2salwa thabet mahmoud, 3azza ali said and 2fatma abdelazeem youssef sanad 1division of physiology, department of zoology, faculty of science, cairo university, giza, egypt. Patients receiving both rifampicin and isoniazid should be monitored closely for hepatotoxicity. Druginduced liver injury dili in hivtuberculosis tb coinfected patients is a common.
Effects of jetepar glucometamine, glucodiamine and nicotinamide ascorbate on isoniazid induced hepatotoxicity in rabbits. In this case, the patient was receiving antitubercular drugs from 3 months and developed hepatitis which is a severe adverse drug reaction. Concurrent use of alcohol, palclcetamol and other hepatotoxic medication may increase the incidence ol rifampicininduced hepatotoxicity. Canthium dicoccum whole plant exhibited hepatoprotective activity against isoniazid and rifampicin induced hepatotoxicity. Acute inh toxicity leads to central nervous system cns toxicity, including seizures, whereas chronic inh toxicity results in hepatotoxicity. Isoniazid hepatotoxicity associated with treatment of. Inh metabolism has been thought to be associated with inhinduced liver injury. The incidence of isoniazid inh and rifampicin rifinduced abnormal liver enzyme activity is 27% but only 19% with inh alone. Disadvantagesoflaboratory monitoring include questionable costef. While the occurrence of druginduced hepatitis is difficult to predict, it has been observed that certain patients are at higher risk of developing druginduced hepatitis during the course of antitb chemotherapy. Mild isoniazidinduced liver injury in humans is associated with an. Background and aims isoniazid inh is part of the firstlinetherapy for. Nacetyl transferase 2 and cytochrome p450 2e1 genes and isoniazidinduced hepatotoxicity in.
Hepatoprotective activity, canthium dicoccum, silymarin, isoniazid, rifampicin introduction canthium dicoccum the ceylon boxwood also known as nalla balusu in telugu, belongs to the family rubiaceae1. Risk factors for sideeffects of isoniazid, rifampin and. Vitamin b6 is used to prevent isoniazidinduced b6 deficiency and neuropathy in people with a risk factor, such as pregnancy, lactation, hiv infection, alcoholism, diabetes, kidney failure, or malnutrition. Although inh related hepatotoxicity is well recognized, progression to severe liver dysfunction requiring care at a transplant center remains unpredictable. Santos np, callegarijacques sm, ribeiro dos santos ak, et al. Isoniazid 50 mgkg was administered to all the animals for 28 days orally. Mild inh hepatotoxicity refers to hepatic injury that is typically subclinical and evidenced only by mildly elevated serum aminotransferases usually isoniazid. Increased age, injection substance abuse, and alcohol consumption have been associated with a higher risk of developing isoniazidinduced hepatotoxicity. Case report successful diagnosis of hyperpyrexia induced.
Use isoniazid with caution in patients with chronic hepatic disease e. Main outcome measures the rate of developing symptoms and signs of hepatotoxicity among all persons starting isoniazid preventive. Hepatotoxicity associated with isoniazid preventive therapy ipt and antiretroviral therapy art has not been well studied in severely immunosuppressed people with hiv. Isoniazid metabolism and hepatotoxicity sciencedirect. Pdf isoniazid metabolism and hepatotoxicity researchgate. Association and clinical utility of nat2 in the prediction of isoniazid. Histologic effects of isoniazid induced hepatotoxicity in male albino mice how to cite. However, it can cause liver injury and even liver failure. Firstline antitb drugs associated with hepatotoxicity are isoniazid inh, rifampicin rif and pyrazinamide pza. Hepatotoxicity of antituberculosis therapy american thoracic society. Concurrent use with carbamazepineqcarbamazepine blood levels and risk of hepatotoxicity.
Although practically nonexistent among individuals under 20 years of age, it occurs in 0. Antituberculosis druginduced hepatitis has also been. However, 4 matches were made to compensate for those patients with missing or incomplete files. Cyp2e1 genotype and isoniazidinduced hepatotoxicity in patients treated for latent tuberculosis.
Isoniazid therapy is often associated with minor, transient and asymptomatic elevations in serum aminotransferase levels but, more importantly, isoniazid is a well known cause of acute clinically apparent liver injury which can be severe and is sometimes fatal. The use of isoniazid is contraindicated in patients with acute liver disease or a history of hepatic injury due to isoniazid. Multicenter study in resourcelimited settings with. Selected pharmaceutical excipient prevent isoniazid and. Caution is advised when using the drug in patients with chronic liver disease or a history of alcoholism. Isoniazid inh is highly effective for the management of tuberculosis. People with liver dysfunction are at a higher risk for hepatitis caused by inh, and may need a lower dose. A model of isoniazid induced hepatotoxicity in rabbits.
The mechanism of inhinduced liver injury remains controversial. One possible mechanism for the additive or synergistic hepatotoxicity of isoniazid and rifampicin is through liver enzyme induction in the hydrolase system enhancing the toxicity of some of the isoniazid metabolites. Isoniazid maypblood levels and effectiveness of ketoconazole. Ethambutol emb can be used safely in patients with hepatic disease. Among the 4 standard antitb drugs, isoniazid inh is the most likely to cause drug induced liver toxicity. This paper aimed to evaluate the feasibility of gel entrapped hepatocytes for isoniazidinduced hepatotoxicity studies. An approach to the management of drug induced liver injury. A recent small nonrandomized report suggested that monitoring may decrease the severity of pyrazinamideinducedliverinjury19. The effectiveness of oestrogencontaining oral preparations is reduced.
It is a small molecule mw7 that is freely soluble in water. Since this drug has been associated with hepatic dysfunction in adults, the present study was undertaken to evaluate its effect on liver function in teenagers. From 29th day onwards isoniazid was stopped and therapeutic agents normal. A 65yearold female diagnosed with latent mycobacterium tuberculosis infection was receiving oral isoniazid 300 mg daily. Hepatotoxicity was defined as ast levels more than five times the upper limit of normal uln. More than 30 years after its introduction, 1 isoniazid preventive therapy for latent tuberculosis tb infection is still a subject of debate, mainly because of continuing concerns about hepatotoxicity.
Management of common sign effects of inh final draft. She was admitted to the hospital for epigastric and right sided flank pain of oneweek duration. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment, american. Concomitant intake of phenytoin or carbamazepine may increase the hepatotoxicity of isoniazid. Isoniazid inh is the most likely tb drug to cause drug induced liver toxicity. Previous mechanistic hypotheses have classified this type of drug.
Treatment of isoniazid induced hepatotoxicity as regards the treatment of inh induced hepatotoxicity, it presents a difficult challenge to manage due to a number of factors such as, patients affected are often on other potentially hepatotoxic drugs, making it more difficult to determine which is responsible for causing the damage. Evaluation of inh hepatotoxicity in adults aged 25 years from a database maintained from fall 1996 to 2003 in a public health department clinic. All relevant data are within the paper and its supporting information files. Pdf isoniazid inhinduced hepatotoxicity remains a significant clinical problem, and the current mechanistic hypothesis is incomplete.
Isoniazid inh remains a mainstay for the treatment of tuberculosis despite the fact that it can cause liver failure. Aging and hepatotoxicity of isoniazid and rifampin in pulmonary tuberculosis article pdf available in american journal of respiratory and critical care medicine 1525 pt. Isoniazid hepatitis, isoniazid psychosis advertisement applied. Antituberculosis drug induced hepatitis a case report. The frequency of occurrence of isoniazidassociated hepatitis depends on age. Pdf a fresh look at the mechanism of isoniazidinduced.
Patients should be monitored closely for signs of hepatotoxicity and should be strongly advised to restrict intake of alcoholic beverages see section 4. Inhibition of isoniazidinduced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor. Tb drug induced hepatoxicity hepatotoxicity is one of the most important adverse drug reactions associated with anti tb drugs. The incidence rate of antitb induced hepatotoxicity is found to be 2% to 28%. Dili complicates tb treatment in 5 33% of patients. Nearly 20% of patients treated with the standard fourdrug regimen show asymptomatic increase in ast concentration. Hepatoprotective effect of rutin against oxidative stress.
Isoniazid isonicotinylhydrazine, inh is the most active drug for the treatment of tuberculosis caused by susceptible strains. Druginduced liver injury dili is a wellrecognised adverse drug reaction of tb treatment and art. Hepatotoxicity during isoniazid preventive therapy and. In the pre sent study, we aimed to investigate the funct. Management of druginduced liver injury in hivpositive patients.
Isoniazid inh monotherapy has gained widespread acceptance as an efficacious therapy for latent tuberculosis infection ltbi especially in lowprevalence settings. Isoniazid is the most reliable and most commonly used medication for tuberculosis. Isoniazid, rifampicin, gsp method, mannitol, tuberculosis, hepatotoxicity. These include patients with preexisting liver diseases, particularly those associated. Pharmacogenetic association between nat2 gene polymorphisms and isoniazid induced hepatotoxicity. Hepatotoxicity of isoniazid was observed in gel entrapped hepatocytes at a low concentration of 0. In this study, ast was measured at baseline and 1, 3, and 6 months after treatment initiation. Electronic supporting information files are available without a subscription to acs web editions. Objective to determine the rate of isoniazid hepatotoxicity in patients managed. Hepatotoxicity associated with isoniazid preventive therapy. Isoniazidinduced hepatotoxicity in rat hepatocytes of gel. Hepatotoxicity induced by antituberculosis drugs among. The standard therapies for tb include a combination treatment of isoniazid inh, rifampicin, pyrazinamide, and ethambutol 2.
Pdf aging and hepatotoxicity of isoniazid and rifampin. This article focuses on the acute and chronic isoniazid isonicotinic acid hydrazide inh toxicity. Cytochrome p450 2e1 cyp2e1 is thought to contribute to the synergistic effects of rif and inh. Despite the beneficial effects of inh, severe adverse effects especially peripheral neuropathy and hepatotoxicity are associated with inh therapies4. February 6 1996 accepted after revision june 21 1996 the most effective antituberculosis antitb therapy is a combination of isoniazid, rifampin and pyrazinamide for 8 weeks, followed by isoniazid and rifampin for a further 47 months standard therapy 1. However, inh is associated with druginduced liver injury dili that can range. Hepatotoxicity of rifampinpyrazinamide and isoniazid preventive therapy and tuberculosis treatment. Hepatotoxicity of rifampinpyrazinamide and isoniazid.
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