Isoniazid adverse reaction

The incidence of adverse reactions appears to be higher when larger doses of isoniazid are prescribed. Adverse reactions include hypersensitivity reactions, hematologic changes, jaundice, fever, skin eruptions, nausea, vomiting, and epigastric distress. Severe, and sometimes fatal, hepatitis has been associated witii isoniazid tiierapy and may appear after many months of treatment. Peripheral neuropathy (numbness and tingling of the extremities) is the most common symptom of toxicity. 

Previous isoniazid-associated hepatic injury or other severe adverse reactions. 

Aminosalicylic acid may affect isoniazid, digoxin, and vitamin B- 2-Adverse Reactions... 

Isoniazid can induce a wide variety of potentially serious adverse reactions. Some hepatotoxicity can manifest itself as transient elevations of liver enzymes and this occurs in 10-20% of patients. Progressive and potentially fatal liver damage is age dependent with a very low incidence below the age of... 

The incidence and severity of adverse reactions to isoniazid are related to dosage and duration of therapy. Isoniazid-induced hepatitis and peripheral neuropathy are two major untoward effects. 

For example, it has been suggested that the adverse reactions caused by a number of drugs such as isoniazid, procainamide, hydralazine could be due to metabolic activation by myeloperoxidase in neutrophils. Thus neutrophils will metabolize procainamide (Fig. 4.38) to a hydroxylamine metabolite. In the presence of chloride ion, myeloperoxidase will produce hypochlorous acid, a strong oxidizing agent, which may be responsible for metabolic activation and toxicity. One of the products is N-chloroprocainamide (see also sect. "Hydralazine," chap. 7). 

Isoniazid (INH, Laniazid, Nydrazid, other names) is one of the primary drugs used to treat tuberculosis.24,61 Although the exact mechanism of action is unknown, this drug appears to interfere with several enzymatic pathways involving protein, lipid, carbohydrate, and nucleic acid metabolism in susceptible bacteria. Adverse reactions to isoniazid are common, and patients may develop disorders such as hepatitis and peripheral neuropathies. 

Race and ethnicity may also be risk factors for ADRs. Prior personal or family history of ADRs may be predictive of future adverse reactions. Genetic polymorphisms for many metabolic reactions are described in Chapter 13 and have been well documented (45). Prescribing some medications without regard to genetic differences in metabolism can result in therapeutic failures or drug toxicity (45, 46). For example, differences in acetylator phenotype can alter the metabolism of some drugs and influence the risk of certain adverse reactions. Slow acetylators, for example, may be more likely than rapid acetylators to develop he pa to toxicity from isoniazid treatment. The biochemical basis for this difference is described in Chapter 16. 

Treatment problems that can arise are mainly of two types adverse reactions (collateral, toxic, or hypersusceptibility reactions), and initial or acquired resistance of Mycobacterium tuberculosis, Mycobacterium bovis, or non-tuberculous mycobacteria to one or more of the antituberculosis drugs. The latter probably only occurs when the patient has not taken the full combination or the full doses of the drugs all the time. Combination formulations are thus particularly useful. Multidrug-resistant tuberculosis, defined as resistance against at least isoniazid and rifampicin, is the most clinically relevant form of resistance to treatment worldwide. 

Adverse reactions during treatment with isoniazid have been noted after ingestion of several kinds of cheese (60,61). Flushing, palpitation, tachycardia, and increased blood pressure have been observed 0.5-2 hours after cheese. The symptoms generally disappear within 2-4 hours. Interference by isoniazid with monoamine oxidase, and hence with tyramine metabolism, has been incriminated. 

However, in 531 eligible patients enrolled in a US Public Health Service Cooperative Trial of Short-Course Chemotherapy of Pulmonary Tuberculosis, of whom 58% were classified as alcoholic, although the alcoholics had more abnormal concentrations of aspartate transaminase before and during therapy, there was no significant difference between the alcoholics and non-alcoholics in the incidence of adverse reactions, including hepatotoxic reactions (92). The authors concluded that in the absence of clinically significant and persistent pretreatment abnormalities of hepatic function tests, rifampicin and isoniazid are not contraindicated in patients categorized as alcoholic. 

Isoniazid No important interaction appears to occur between isoniazid and the SSRIs or nefazo-done. However, adverse reactions have been seen... 

UNTOWARD EFFECTS Adverse reactions to isoniazid occur in 5%, including rash (2%), fever (1.2%), jaundice (0.6%), and peripheral neuritis (0.2%). Isoniazid hypersensitivity may result in fever, rashes, and hepatitis. Hematological reactions also may occur (e.g., agranulocytosis, eosinophilia, thrombocytopenia, and anemia). Vasculitis associated with antinuclear antibodies may appear but disappears when the drug is stopped. 

UNTOWARD EFFECTS In usual doses, <4% of patients with tuberculosis have significant adverse reactions to rifampin, most commonly rash (0.8%), fever (0.5%), and nausea and vomiting (1.5%). Rarely, hepatitis and deaths due to liver failure have been observed in patients who received other hepatotoxic agents, or who had preexisting liver disease. Hepatitis from rifampin rarely occurs in patients with normal hepatic function likewise, the combination of isoniazid and rifampin appears generally safe. Chronic liver disease, alcoholism, and old age increase the risk of severe hepatitis when rifampin is given alone or concurrently with isoniazid. 

Therapy for drug-sensitive pulmonary tuberculosis consists of isoniazid (5 mg/kg, up to 300 mg/day), rifampin (10 mg/tcg/day, up to 600 mg daily), pyrazinamide (15-30 mg/kg/day or a maximum of 2 g/day), and a fourth agent, typically either ethambutol (usual adult dose cf 15 mg/kg once per day) or streptomycin (1 g daily). The streptomycin dose is reduced to 1 g twice weekly after 2 months. Pyridoxine, 15-50 mg/day, also should be included for most adults to minimize adverse reactions to isoni(K,id. Isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin are given for 2 months isoniazid and rifampin are then continued for 4 more months. Doses in children are isoniazid, 10 mg/kg/day (300 mg maximum) rifampin, 10-20 mg/kg/day (600 mg maximum) pyrazinamide, 15-30 mg/kg/day (2 g maximum). Isoniazid, rifampin, and ethambutol are considered safe during pregnancy. 

Uragoda CG, Kott oda SR. Adverse reactions to isoniazid on ingestion of fish with a high histamine content. TtAercle (1977) 58, 83-9. 

Goldman AL, Braman SS (1972) Isoniazid A review with emphasis on adverse reactions. Chest 62 71... 

Berghem L, Lahnborg G, Schildt B (1977) does clofazimine (Lampren) affect the macro-and microphage function in man J Reticuloendothel Soc 21 171 Bernstein LS (1975) Adverse reactions to trimethoprim-sulfamethoxazole, with particular reference to long-term therapy. Can Med Assoc J 112 96 Bhandari B (1977) Isoniazid hepatotoxicity - report of two cases. Indian Pediatr 14 859 Birkett DA, Garretts M, Stevenson CJ (1969) Phototoxic bullous eruptions due to nalidixic acid. Br J Dermatol 81 342... 

Other adverse reactions to isoniazid An acquired inhibitor of fibrin stabilization was described in a patient who developed a serious bleeding tendency whilst taking isoniazid (14 ). Although the bleeding ceased soon after isoniazid was discontinued, the patient s plasma contained potent inhibitor activity which remained detectable for several weeks. This report is the fourth such case described within recent years. 

A Brazilian investigation (49 ) included 112 patients on one of three different antituberculosis regimes in which thiacetazone, at a dose of 150 mg daily, was combined with isoniazid and streptomycin, isoniazid and morfazinamid, or isoniazid and teriz-idone. An unacceptably high incidence (66.3%) of severe adverse effects was reported. The treatment had to be stopped in 13% of patients because of adverse reactions, and 6 of these patients died, 3 of them of exfoliative dermatitis. It is difficult to be sure of the exact role of thiacetazone in these particular adverse effects, but the... 

Other such enzyme deficiencies have been revealed through an individual s adverse reaction to drugs. More than 90% of Orientals are genetically rapid N-acetylators of isoniazid (6.12), whereas only 40% of black or white citizens of the United States showed this trait (Kalow, 1962). Rapid acetylators produce acetylhydrazine, which can cause liver damage. The same inheritance controls the acetylation (deactivation) of the sulphonamide antibacterials. The rise of intraocular pressure when glucocorticoids are placed in the eye is another pharmacogenetic effect. Low and high responses are shown by 66% and 5%, respectively, of a sample white population. 

Serum chemistry markers play an important role in hepatotoxicity evaluation in human and animal safety studies. The classic markers of hepatotoxicity are alanine aminotransferase (ALT), aspartate aminotrasnferase (AST) and alkaline phosphatase (ALP) [124—127]. Drug-induced hepatotoxicity can be difficult to assess in some circumstances. Hepatotoxic responses can be intrinsic (predictable, dose-related) or idiosyncratic (unpredictable, non-dose-related). ALT, AST and ALP are generally not useful for predicting idiosyncratic responses. The administration of some drugs, such as isoniazid, can lead to a high incidence of ALT elevation, but are tolerated by most patients without severe hepatotoxicity. Adverse drug reactions can be masked... 

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