CS244433_A

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention 

Division of Tuberculosis Elimination

TB Elimination

Treatment of Multidrug-Resistant Tuberculosis: Bedaquiline

Introduction

Bedaquiline fumarate (SirturoTM) is approved by the U.S. 

Food and Drug Administration (FDA) for use as part of a 

combination therapy in adults with pulmonary multidrugresistant tuberculosis (MDR TB) when an effective treatment 

regimen cannot otherwise be provided. 

The effectiveness and safety of this drug in different patient 

populations is unknown at this time.

For more detailed information, refer to the Provisional CDC 

Guidelines for the Use and Safety Monitoring of Bedaquiline 

Fumarate (Sirturo TM) for the Treatment of Multidrug-Resistant 

Tuberculosis. 

www.cdc.gov/mmwr/pdf/rr/rr6209.pdf

Dosage and Administration

Due to the potential for serious adverse events,

bedaquiline is not recommended for all MDR TB patients. 

Patients treated with bedaquiline should be managed

by, or in close consultation with, local health departments

and experts in the management of drug-resistant TB. 

Bedaquiline may be used to treat adults (> 18 years) with

a confirmed diagnosis of pulmonary MDR TB. 

CAUTION: Bedaquiline may be considered for children, 

HIV-infected persons, pregnant women, persons with 

extrapulmonary TB, and persons with co-morbid conditions 

on concomitant medications when an effective treatment 

regimen cannot otherwise be provided. Further study 

is required before general use of bedaquiline can be 

recommended in these populations.

Expert Clinical Consultation 

Medical consultation is available through some state TB

programs or CDC’s TB Regional Training and Medical 

Consultation Centers (RTMCCs). 

Visit the CDC website to obtain contact information for

each RTMCC. 

www.cdc.gov/tb/education/rtmc/default.htm 

Visit the CDC website to obtain contact information for

each state TB program office. 

www.cdc.gov/tb/links/tboffices.htm 

Recommended Dose

The recommended dose of bedaquiline for the treatment of 

pulmonary MDR TB in adults is:

• Weeks 1 – 2: 400 mg (4 tablets of 100 mg) given orally, 

once daily 

• Weeks 3 – 24: 200 mg (2 tablets of 100 mg) three times 

per week, for a total dose of 600 mg per week

Initiation and Discontinuation 

Bedaquiline is to be used for a period of 24 weeks. 

• Bedaquiline may be used on a case-by-case basis 

for durations longer than 24 weeks when treatment 

options are limited.

This drug has a half-life of 4-5 months. Consider 

discontinuing bedaquiline 4–5 months prior to discontinuing 

other drugs in the treatment regimen to reduce or avoid an 

extended period of exposure to low levels of bedaquiline as 

a single drug and subsequent acquired resistance.

Administration 

All doses should be used in combination with at least three 

other anti-TB drugs to which the patient’s MDR TB isolate has 

been shown to be susceptible through laboratory testing. 

Each dose should only be given by directly observed therapy 

(DOT) and with case management strategies to ensure 

treatment adherence. Each dose should be taken with food 

to maximize drug absorption. 

Missed Doses

If a dose is missed during the first 2 weeks of treatment, 

patients should not be given the missed dose but should 

continue the usual dosing schedule. From Week 3 onwards, 

if a 200 mg dose is missed, patients should be given the 

missed dose as soon as possible, and then resume the 3 

times a week regimen. Do not exceed 600 mg in a 7-day 

period of time.

Adverse Reactions

To date, adverse drug reactions associated with bedaquiline 

include:

• Nausea / Vomiting

• Dizziness

• Headache

• Hemoptysis

• Increased blood amylase

• Increased serum transaminases

• Rash

• Arthralgia (joint pain) / Myalgia 

(muscle pain)

• Chest pain

• Anorexia, fatigue, dark or colacolored urine, jaundice
Page 2 of 2 

Patient Counseling

Patients should be advised:

• To eat food before taking bedaquiline 

• To abstain from alcohol and other hepatotoxic drugs 

• To report any signs and symptoms of adverse drug 

reactions to their health care provider

• Of the potential benefits and harms of bedaquiline 

• That treatment non-adherence could result in treatment 

failure, relapse, or acquired drug resistance 

Drug Interactions

Bedaquiline is metabolized through the cytochrome P450 

(CYP) system. Co-administration with rifamycins (e.g., rifampin, 

rifapentine, and rifabutin) or other strong CYP3A4 inducers 

should be avoided. 

Among the limited studies to date, no significant 

pharmacokinetic interactions have been observed between 

bedaquiline and the anti-TB drugs isoniazid, pyrazinamide, 

ethambutol, kanamycin, ofloxacin, or cycloserine.

Patient Monitoring 

Monitoring for Cardiac Toxicity

Bedaquiline can affect the heart’s electrical activity, which could 

lead to an abnormal and potentially fatal heart rhythm. Patients 

should be monitored for symptoms of cardiac toxicity and by 

electrocardiogram (ECG).

• Serum potassium, calcium, and magnesium should be 

obtained at baseline and whenever clinically indicated, 

especially if QTcF prolongation is detected. 

• ECG should be obtained at baseline and repeated at least 

2, 12, and 24 weeks after treatment is started. 

• Weekly ECGs are recommended for persons prescribed 

bedaquiline and (1) other QTcF prolonging drugs 

including fluorquinolones, macrolide antibacterial drugs, 

and clofazimine; (2) have a history of Torsade de Pointes,

congenital long QTcF syndrome, hypothyroidism and 

bradyarrhythmias, or uncompensated heart failure; or 

(3) have serum calcium, magnesium, or potassium levels 

below the lower limits of normal.

• If syncope occurs, obtain an ECG to evaluate for QTcF 

prolongation.

Monitoring for Hepatotoxicity

Hepatic-related adverse drug reactions have been reported with 

the use of bedaquiline. Patients’ aspartate aminotransferase 

(AST), alanine aminotransferase (ALT), bilirubin, and alkaline 

phosphatase should be tested at baseline, monthly, and if 

symptomatic.

Monitoring for Renal Toxicity

Bedaquiline does not require dosage adjustment in patients 

with mild to moderate renal impairment (not requiring dialysis). 

Use caution when administering bedaquiline to patients with 

severe renal impairment requiring dialysis. Serum drug levels in 

patients with renal impairment should be considered.

Therapeutic Drug Monitoring

If bedaquiline is given with rifamycins or any other drugs that 

induce or suppress CYP3A4, monitoring of serum drug levels 

should be performed to ensure adequate therapy and minimize 

the risk of acquired drug resistance.

Microbiologic Monitoring

Treatment should be accompanied by microbiologic monitoring 

with one sputum specimen submitted for culture monthly 

throughout and at the end of treatment, even after conversion 

to negative culture. 

Monitoring for Additional Side Effects

Patients should also be assessed weekly for nausea, headache, 

hemoptysis, chest pain, arthralgia, and rash. Monitoring for 

additional side effects should be tailored to the other drugs 

used to treat the patient’s MDR TB.

Patient Registry and Surveillance of Drug 

Resistance

As required by the FDA, a registry for persons treated with 

bedaquiline will be maintained by Janssen Therapeutics to 

track patient outcomes, adverse reactions, laboratory testing 

results, use of concomitant medications, and presence of other 

comorbid conditions. This registry will collect data prospectively 

on all patients started on bedaquiline.

Any monthly specimen that grows M. tuberculosis, including one 

before treatment initiation with bedaquiline, should be referred 

to a laboratory for surveillance of bedaquiline resistance in 

consultation with the state public health laboratory. CDC will 

assist in identifying a laboratory that can perform bedaquiline 

susceptibility testing.

Suspected adverse reactions (i.e., any adverse event for which 

there is a reasonable possibility that the drug caused the 

adverse event) and serious adverse events (i.e., any adverse 

event which results in death, hospitalization, permanent 

disability, or a life-threatening situation) should be reported

to Janssen Therapeutics (1-800-526-7736), the FDA 

(1-800-332-1088 or www.fda.gov/medwatch), and to CDC’s 

Emergency Operations Center (1-770-488-7100).

Additional Information 

1. Provisional CDC Guidelines for the Use and Safety Monitoring 

of Bedaquiline Fumarate (Sirturo TM) for the Treatment of 

Multidrug-Resistant Tuberculosis. MMWR 2013; 62 (No. 9):

www.cdc.gov/mmwr/pdf/rr/rr6209.pdf

2. Janssen Therapeutics. SirturoTM Webpage 

www.sirturo.com/

3. U.S. Food and Drug Administration. SIRTUROTM (bedaquiline) 

Tablets label. US Food and Drug Administration website.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/

ucm368240.htm.

http://www.cdc.gov/tb