Rifampin hepatotoxicity

Acetaminophen may alter blood glucose test results, causing falsely lower blood glucose values. Use with the barbiturates, hydantoins, isoniazid, and rifampin may increase the toxic effects and possibly decrease the therapeutic effects of acetaminophen. The effects of the loop diuretics may be decreased when administered with acetaminophen. Hepatotoxicity has occurred in chronic alcoholics who are taking moderate doses of acetaminophen. 

Rifabutin Adults0 5 mg/kg (300 mg) Children Appropriate dosing unknown Hematologic toxicity, uveitis, gastrointestinal symptoms, polyarthralgias, hepatotoxicity, pseudojaundice (skin discoloration with normal bilirubin), rash, flulike syndrome, orange discoloration of bodily fluids (sputum, urine, sweat, tears) Drug interactions are less problematic than rifampin... 

Concurrent administration of rifampin is recommended at doses of 10 to 20 mg/kg/day (maximum 600 mg/day) for children and 600 mg/day for adults. The addition ofpyrazinamide (children and adults, 15 to 30 mg/kg/ day maximum in both, 2 g/day) to the regimen of isoniazid and rifampin is now recommended. The duration of concomitant pyrazinamide therapy should be limited to 2 months to avoid hepatotoxicity. 

Hepatotoxicity There have been fatalities associated with jaundice in patients with liver disease or patients receiving rifampin concomitantly with other hepatotoxic agents. Carefully monitor liver function, especially AST and ALT, prior to therapy and then every 2 to 4 weeks during therapy. 

The most commonly observed side effects are GI disturbances and nervous system symptoms, such as nausea, vomiting, headache, dizziness, and fatigue. Hepatitis is a major adverse effect, and the risk is highest in patients with underlying liver diseases and in slow isoniazid acetylators the rate of hepatotoxicity is increased if isoniazid and rifampin are combined. 

Rare reactions include hepatotoxicity (risk is increased when rifampin is taken with isoniazid), hepatitis, blood dyscrasias, Stevens-Johnson syndrome, and antibiotic-associated colitis. 

Rifampin 300 mg b.i.d. Beneficial in some, but not aU controlled trials to date Inducer of hepatic drug metabolizing enzymes, potential hepatotoxicity, red-orange discoloration of urine and secretions... 

Lee AM, Mennone JZ, Jones RC, Paul WS. Risk factors for hepatotoxicity associated with rifampin and pyrazmamide for the treatment of latent tuberculosis infection experience from three pubhc health tuberculosis clinics. Int J Tuberc Lung Dis 2002 6(11) 995-1000. 

Pattyn SR, Janssens L, Bourland J, Saylan T, Davies EM, Grillone S, Feracci C. Hepatotoxicity of the combination of rifampin-ethionamide in the treatment of multibacillary leprosy. Int J Lepr Other Mycobact Dis 1984 52(l) l-6. 

However, Roche Pharma have recommended that rifampicin should not be used in patients who are taking ritonavir + saquinavir, because of the results of a study in which 11 of 28 patients who took rifampicin 300 mg/day with ritonavir 100 mg bd + saquiniavir 1000 mg bd developed severe hepatotoxicity [http //www.fda.gov/medwatch/ safety/2005/Saquinavir-Rifampin deardoc Feb05]. 

Side effects caused by isoniazid, rifampin, pyrazinamide, and ethambutol are common and can include hepatotoxic-ity, peripheral neuropathy, optic neuritis, and Gl side effects. All four agents can potentially be hepatotoxic, but this side effect is most frequently associated with isoniazid and rifampin. Peripheral neuropathy is most commonly associated with isoniazid, whereas optic neuritis is associated with ethambutol. The metabolism of isoniazid is genetically predetermined. Patients of Scandinavian, European, and African descent metabolize isoniazid slower (slow acetylators) and are therefore more predisposed to hepatotoxicity and peripheral neuropathy due to isoniazid. Fast acetylators include people of Asian or American Indian descent and are less predisposed to these adverse effects. 

I iiJmme docs not appear to intcrt erc with the antitubercu-<1 dleei of isoniazid. Severe hepatotoxicity rarely occurs. .lii iMiniuzid alone the incidence is much higher, however, Vn ii is used in combination with rifampin. 

Tsagaropoou-Stinga H, Mataki-Emmanouilidon R, Karida-Kavalioti S, et al. Hepatotoxic reactions in children with severe tuberculosis treated with isoniazid-rifampin. Pediatr Infect Dis 1985 4 270-273. 

HIV-1 infection. Like indinavir, atazanavir frequently causes unconjugated hyperbilirubinemia, although this is mainly a cosmetic side effect and is not associated with other hepatotoxicity. Because atazanavir is metabolized by cytochrome (CYP3A4), concomitant administration of agents that induce this enzyme (e.g., rifampin) is contraindicated. 

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. 

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