Latent TB Infection: Adverse Effects of Drugs Used to Treat LTBI

Latent TB Infection: Guide for Diagnosis and Treatment

Adverse Effects of Drugs Used to Treat LTBI

Some health care providers have concerns about treating patients for LTBI. These concerns are generally related to the length of treatment and the potential side effects of medications. As with any treatment, the health care provider must weigh the risks and benefits for each individual. Obtaining a detailed and accurate medical history, and updating information at frequent intervals, will identify persons who require close monitoring; this will aid the health care provider in determining the most appropriate course of action. In addition, CDC guidelines, drug package inserts, and other authoritative medical sources should be consulted whenever there is a question about side effects or drug-drug interactions.

The sections that follow discuss some of the adverse effects of INH and rifamycins, as well as recommendations for monitoring during treatment and for assessing and ensuring adherence.

Possible Adverse Effects of Isoniazid (INH)

• Asymptomatic elevation of serum liver enzyme concentrations occurs in 10%–20% of people taking INH; and liver enzyme concentrations usually return to normal even when treatment is continued. It is generally recommended that INH be withheld if a patient’s transaminase level exceeds 3 times the upper limit of normal if associated with symptoms or 5 times the upper limit of normal if the patient is asymptomatic.
• Clinical hepatitis occurs in about 0.1% of people taking INH, and is more common when INH is combined with other hepatotoxic agents. Factors that may increase either of these rates or the severity of hepatitis include daily alcohol consumption, underlying liver disease or risks for liver disease, and the concurrent use of other medications which are metabolized in the liver. Symptomatic hepatitis is rare in patients younger than 20 years of age, but severe and fatal cases have been reported. Younger patients with underlying risk factors for liver disease should be monitored clinically with the same precautions as older patients.
• Peripheral neuropathy occurs in less than 0.2% of people taking INH at conventional doses. It is more likely in the presence of other conditions associated with neuropathy such as diabetes, HIV, renal failure, and alcoholism. Pyridoxine (vitamin B6) supplementation is recommended only in such conditions or to prevent neuropathy in pregnant or breastfeeding women.

Possible adverse effects of Rifampin (RIF) and Rifapentine (RPT)

• Hepatotoxicity, evidenced by transient asymptomatic hyperbilirubinemia, may occur in 0.6% of persons taking RIF. Hepatitis is more likely when RIF is combined with INH.
• Cutaneous reactions, such as pruritis (with or without a rash), may occur in 6% of persons taking RIF. They are generally self-limited and may not be a true hypersensitivity; continued treatment may be possible.
• Rarely, rifamycins can be associated with hypersensitivity reactions, including hypotension, nephritis or thrombocytopenia, and manifested by symptoms such as fever, headache, dizziness/lightheadedness, musculoskeletal pain, petechiae, and pruritis.
• Gastrointestinal symptoms such as nausea, anorexia, and abdominal pain are rarely severe enough to discontinue treatment.
• Orange discoloration of body fluids is expected and harmless, but patients should be advised beforehand. Soft contact lenses and dentures may be permanently stained.
• RIF and RPT interact with a number of drugs, causing drug-drug interactions. They are known to reduce concentrations of methadone, warfarin, hormonal contraceptives, and phenytoin. Women using hormonal contraceptives should be advised to consider an alternative method of contraception (e.g., a barrier method).
• RIF is contraindicated, or should be used with caution, in HIV-infected individuals being treated with certain antiretroviral medications. Substitution of rifabutin for RIF in the 4-month regimen many be considered for such patients. RPT should not be used in HIV-infected persons taking antiretroviral therapy.