Bureau of Tuberculosis Control

The Importance of Rifampin

Minor Side Effects | Rifabutin | Serious Adverse Reactions | Notes and References

Rifampin plays a fundamental role in the treatment of patients with active tuberculosis (TB). Although rifampin and isoniazid (INH) are by far the most effective antituberculosis agents, rifampin is the one medication that is crucial for ensuring success of short-course (6-month) chemotherapy.¹ Patients with INH-resistant TB can respond well to 6-month treatment without INH (on a regimen of rifampin, pyrazinamide, and ethambutol), but patients with rifampin-resistant TB do not respond well to short-course chemotherapy without rifampin or another rifamycin (e.g., rifabutin).²

• • Without rifampin (or rifabutin), most antituberculosis regimens require at least 18 months of treatment.³
• • Every attempt should be made to use rifampin (or rifabutin) in initial antituberculosis treatment—unless the patient has an isolate documented to be resistant to rifamycins or has had a documented adverse drug reaction due to rifamycins.

In addition, antituberculosis drug regimens for patients infected with the human immunodeficiency virus (HIV) pose a special challenge when certain antiretroviral medications are also indicated. Rifampin cannot be taken together with most protease inhibitors or non-nucleoside reverse transcriptase inhibitors. Rifabutin, however, can often be used in these patients.⁴

Minor Side Effects

Patients should not be denied the benefits of rifampin because of minor side effects. According to a study of all patients diagnosed with TB in New York City over a 20-month period, fewer than 1% of patients needed to discontinue rifampin because of serious adverse effects.⁵ This rate is similar to that found in a longitudinal study of a large sample of comparable patients.⁶

Rifampin can usually be continued in spite of the following side effects:

• • Rash. Pyrazinamide, rather than rifampin, is the usual cause of rash during anti-TB treatment. If rifampin causes minor rashes and acneiform reactions, they are virtually always self-limiting or can be treated symptomatically.
• • Gastritis. Rifampin sometimes causes gastritis, but this is rarely a valid reason to discontinue rifampin. If gastritis is severe, rifampin can be given with food (although this may decrease absorption), or the dose may be gradually increased from 150 mg/day to 600 mg/day over a 7–10 day period.
• • Mild hepatitis. Asymptomatic elevation of liver enzymes (= 5 times normal) is generally not a reason to discontinue anti-TB medications.⁶
• • Methadone interaction. Rifampin accelerates the clearance of methadone by the liver. Therefore, patients on methadone who take rifampin will need, on average, a 50% increase in their methadone dose to prevent opiate withdrawal. When patients receive this increased dose of methadone, however, they risk overdosing on methadone if they do not take the rifampin. Therefore, directly observed therapy (DOT) to ensure adherence to TB treatment is essential for all patients who take methadone and rifampin together.

Rifabutin

Rifabutin may be better tolerated than rifampin in some patients who have experienced idiosyncratic reactions, and it also reduces interactions with other drugs, including methadone and various HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors.4 Recent studies indicate that rifabutin and rifampin have equivalent in vitro antituberculosis activity and are similarly effective and safe in 6-month chemotherapy regimens.^7,8 However, rifampin remains the drug of choice when it can be used.

Serious Adverse Reactions

Although true intolerance to rifampin (even among HIV-infected persons) is rare, patients should be carefully monitored for severe adverse effects such as the following:^5,9

• • Hepatitis, particularly with a cholestatic picture
• • Thrombocytopenia
• • Renal failure
• • Other serious reactions, such as flu-like symptoms or persistent drug fever

DOT—the standard of care for TB patients in New York City—helps providers monitor patients for drug-drug interactions and severe adverse reactions.

Notes and references

1. NYC DOH, Bureau of Tuberculosis Control. Clinical Policies and Protocols, 3rd edition, July 1999.
2. Mitchison DA and Nunn AJ. Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis 1986;133:423-30.
3. A 9-month regimen of isoniazid, pyrazinamide, and streptomycin is an acceptable alternative, but patients may find this regimen difficult.
4. For recommended treatment regimens in HIV-infected persons with TB, see the most recent edition of Clinical Policies and Protocols.
5. Cook SV, Fujiwara PI, Frieden TR. Rates and risk factors for discontinuation of rifampicin. Int J Tuberc Lung Dis. In press.
6. Døssing M, Wilcke JTR, Askgaard DS, et al. Liver injury during antituberculosis treatment: an 11-year study. Tubercle and Lung Disease 1996;77:335-40.
7. McGregor MM, Olliaro P, Wolmarans L, et al. Efficacy and safety of rifabutin in the treatment of patients with newly diagnosed pulmonary tuberculosis. Am J Respir Crit Care Med 1996;154:1462-67.
8. Centers for Disease Control and Prevention (CDC). Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: principles of therapy and revised recommendations. Morbidity and Mortality Weekly Report (MMWR) 1998;47(No.RR-20).