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Latent tuberculosis infection (LTBI) treatment recommendations (revised)

The Centers for Disease Control and Prevention (CDC) and the American Thoracic Society have issued revised treatment guidelines for treatment of latent tuberculosis infection after investigating 23 reports of severe liver injury associated with the rifampin and pyrazinamide regimen. Seventeen (17) of the patients survived and 6 died. While latent TB (LTBI) treatment is generally well-tolerated, health care providers and their patients should be aware of rare life-threatening side effects and use any medication regimen with caution. The revised treatment guidelines for LTBI should limit the circumstances in which the combination of rifampin and pyrazinamide (RIF-PZA) is prescribed and strengthen the level of patient counseling and monitoring recommended for LTBI treatment regimens.

Important considerations when using RIF-PZA for LTBI treatment

  • Patients should be counseled about the risks and benefits of latent TB treatment and monitored closely.
  • Nine months of an isoniazid (INH) regimen should be used when feasible.
  • Use rifampin and pyrazinamide with caution in persons at high-risk for TB disease who are unlikely to complete a 9-month regimen.
  • Exercise extreme caution when using a rifampin and pyrazinamide (RIF-PZA) regimen in those with a history of alcoholism or those who are currently taking medications associated with liver injury.
  • RIF-PZA is NOT recommended for persons with underlying liver disease or for those who have had INH-associated liver injury.
  • The PZA dose in the RIF-PZA regimen should be <20 mg/kg per day with a maximum of 2 grams daily
  • No more than a 2 week supply of RIF-PZA should be delivered to the patient to facilitate periodic clinical assessments.
  • Patients taking RIF-PZA should be reassessed in person by a health-care provider at 2, 4, and 6 weeks of treatment for adherence, tolerance, and adverse effects. At each visit, health-care providers conversant in the patient's language should instruct the patient to stop taking RIF-PZA immediately and seek medical consultation if abdominal pain, emesis, jaundice, or other hepatitis symptoms develop. Provider continuity is recommended for monitoring.
  • Serum aminotransferase (ASTand/or ALT) and bilirubin should be measured at baseline and at 2, 4, and 6 weeks of treatment in patients taking RIF-PZA.
  • Treatment should be stopped and not resumed for any of these findings: aminotransferase (AST or ALT) greater than five times the upper limit of normal range in an asymptomatic person, aminotransferase (AST or ALT) greater than normal range when accompanied by symptoms of hepatitis, or a serum bilirubin greater than normal range.
  • Patients taking RIF-PZA should be reassessed at 8 weeks to document treatment completion.

Related articles on the CDC website

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Last Revised: March 26, 2014