We report three patients who experienced hepatotoxic reactions in association with acetaminophen ingestion while undergoing treatment for active tuberculosis with isoniazid.

We report three patients who experienced hepatotoxic reactions in association with acetaminophen ingestion while undergoing treatment for active tuberculosis with isoniazid, rifampin, and other agents. All were young adult women single in kind patient intentionally took a large amount of acetaminophen and had typical signs and symptoms of acetaminophen overdosage; another took acetaminophen in combination form for a minor upper respiratory illness. She experienced no symptoms. The remaining patient took acetaminophen to ameliorate the symptoms of agitation and malaise that were subsequently attributed to tuberculosis. She had the rapid storming of signs and symptoms of isoniazid hepatotoxicity. The patterns of liver function abnormalities were similar: each patient experienced pronounced serum elevations of hepatocellular enzyme with at mostly only modest rises in those of bilirubin. All antituberculous remedys were withheld until symptoms resolv and laboratory values became normal; then treatment for tuberculosis was resum without isoniazid and was favorably completed in all three patients. These cases plus similar reports in the literature hint that isoniazid or rifampin, or the two may potentiate the hepatotoxicity of acetaminophen, perhaps at induction of cytochrome P450 isozymes that oxidize acetaminophen to its toxic metabolites.

Hepatotoxicity is a well-known side validity of drugs used for tuberculosis treatment and prophylaxis. Isoniazid, the historic mainstay of mix with drugs therapy against tuberculosis, was determined to be hepatotoxic shortly after its introduction,[1,2] and this propensity has been an impediment to its use, particularly as preventive therapy for individuals who are not ill.[3-5]

Acetaminophen, a widely used analgesic and antipyretic medicine also has hepatotoxic potential, mainly when taken in supratherapeutic amounts, like as with intentional or unintentional overdosing.[6] lately it has been proposed, upon the basis of two reports,[7,8] that there may be an interaction between isoniazid and acetaminophen that consequence s in a more severe hepatotoxicity than that which would be count uponed when either drug is taken alone. Furthermore, rifampin, of equal importance to that of isoniazid in the present chemotherapy of tuberculosis, seems to potentiate the hepatotoxicity of isoniazid.[9,10]

not long ago we have observed hepatotoxic reactions in temporal association with acetaminophen ingestion in three individuals who were receiving therapy with isoniazid and rifampin, in addition to other agents, for active tuberculosis. We report these cases in order to expand information on a possible adverse interaction between acetaminophen and antituberculosis put drugs intos and to offer a hypothetical mechanism for the synergistic hepatotoxicity of isoniazid, rifampin, and acetaminophen.

CASE REPORTS

CASE 1

A woman born in 1960 had been receiving treatment for drug-resistant tuberculosis with isoniazid, rifampin, pyrazinamide, and streptomycin since her immigration from the Philippines in December 1990 In May 1991 she was hospitalized 24 h after ingesting 15 to 20 tablets of acetaminophen (300 mg acetaminophen by tablet); an ingestion of 45 to 60 g of acetaminophen. She complained of abdominal pain.

in succession physical examination, the liver was palpable 2 cm below the right costal margin. Admission laboratory values included a prothrombin time of 141 s total bilirubin level of 188 micromole/L (11 mg/dl); aspartate aminotransferase (AST), 490 U/L; alanine aminotransferase (ALT), 248 U/L; and alkaline phosphatase, 58 U/L The relations acetaminophen level was 11 [micro]/ml.

The admission diagnosis was hepatotoxicity befitting to acetaminophen overdosage. Administration of antituberculous medications was stopped, and the patient received a course of treatment with N-acetylcysteine, 12 g each 4 h for 3 days.

Liver function abnormalities were at their worst 24 to 48 h after admission, with the bilirubin value being 188 [micro]mol/L (11 mg/dl); prothrombin time, 172 s; AST, 1200 U/L; and ALT, 1616 U/L The patient experienced no further symptoms and was discharged forward the eighth hospital day. At the time of discharge, the bilirubin flat was 6.8 [micro]mol/L (0.4 mg/dl); the prothrombin time, 118 s; AST, 23 U/L; ALT, 271 U/L; and alkaline phosphatase, 43 U/L

Treatment for tuberculosis was resum 3 days after discharge from hospital, 12 days after the ingestion of acetaminophen. remedys chosen for further therapy were pyrazinamide, ethambutol hydrochloride, ciproflaxacin hydrochloride, and capreomycin sulfate. The patient had no further difficulty, and treatment for active tuberculosis was complet in July 1992

CASE 2

A Filipino woman born in 1949 immigrated to the United States in 1980 In November 1991 she began to receive treatment for tuberculous cervical adenitis with isoniazid, rifampin, pyrazinamide, and ethambutol. Liver function studies at that time were within normal limits.

At a recur appointment for a refill of antituberculous medications 30 days later, she had no complaints. However, liver functions studies, done routinely after 1 month of treatment with multiple antituberculous put drugs intos showed serum levels of AST to be 256 U/L and of ALT to be 517 U/L

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