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Bedaquiline: Drug information

Bedaquiline: Drug information
(For additional information see "Bedaquiline: Patient drug information" and see "Bedaquiline: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Increased mortality:

An increased risk of death was seen in the bedaquiline treatment group (9/79, 11.4%) compared to the placebo treatment group (2/81, 2.5%) in one placebo-controlled trial in adults. Only use bedaquiline in patients ≥5 years of age when an effective treatment regimen cannot otherwise be provided.

QT prolongation:

QT prolongation can occur with bedaquiline. Use with drugs that prolong the QT interval may cause additive QT prolongation. Monitor ECGs. Discontinue bedaquiline if significant ventricular arrhythmia or QTcF interval prolongation >500 msec develops.

Brand Names: US
  • Sirturo
Pharmacologic Category
  • Antitubercular Agent
Dosing: Adult
Tuberculosis, multidrug resistant, pulmonary

Tuberculosis, multidrug resistant, pulmonary:

Note: Expert consultation for optimal regimen and duration of treatment is advised.

Oral: Directly observed therapy: 400 mg once daily for 2 weeks, followed by 200 mg 3 times weekly with doses spaced ≥48 hours apart; use as part of an appropriate combination regimen (ATS/CDC/ERS/IDSA [Nahid 2019]; Conradie 2020; manufacturer’s labeling).

Missed doses: If a dose is missed during the first 2 weeks, do not make up the missed dose, and continue the usual dosing schedule. From week 3 onward, if a dose is missed, administer the missed dose as soon as possible, and resume the 3 times a week schedule; the total dose during a 7-day period should not exceed the recommended weekly dose of 600 mg (with ≥24 hours between doses).

Duration: Individualize based on rapidity of culture conversion, extent of disease, and patient-specific factors, including clinical response and toxicity (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Mild-to-moderate renal impairment: No dosage adjustment necessary.

Severe renal impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution and monitor for adverse reactions.

End-stage renal disease (ESRD) on intermittent hemodialysis (IHD) or peritoneal dialysis (PD): There are no dosage adjustments provided in the manufacturer's labeling; use with caution and monitor for adverse reactions. Bedaquiline is highly protein bound and not likely to be removed by dialysis.

Dosing: Hepatic Impairment: Adult

Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution and monitor for adverse reactions.

Dosing: Pediatric

(For additional information see "Bedaquiline: Pediatric drug information")

Active tuberculosis, pulmonary

Active tuberculosis (multidrug-resistant), pulmonary: Note: Always administer as part of a multidrug therapy regimen of ≥3 to 4 additional drugs active against the patient's M. tuberculosis isolate (ATS/CDC/ERS/IDSA [Nahid 2019]). Administer as directly observed therapy (DOT).

Children ≥5 years and Adolescents:

15 to <30 kg:

Weeks 1 and 2: Oral: 200 mg once daily.

Weeks 3 to 24: Oral: 100 mg 3 times weekly with at least 48 hours between doses; total weekly dose: 300 mg/week.

≥30 kg:

Weeks 1 and 2: Oral: 400 mg once daily.

Weeks 3 to 24: Oral: 200 mg 3 times weekly with at least 48 hours between doses; total weekly dose: 600 mg/week.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity: Children ≥5 years and Adolescents: Arrhythmia, QT prolongation: If clinically significant ventricular arrhythmia or QTcF interval >500 msec (ECG confirmed): Discontinue therapy.

Dosing: Kidney Impairment: Pediatric

Children ≥5 years and Adolescents:

Mild to moderate renal impairment: No dosage adjustment necessary.

Severe renal impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution and monitor for adverse reactions.

End-stage renal disease (ESRD) on intermittent hemodialysis (IHD) or peritoneal dialysis (PD): There are no dosage adjustments provided in the manufacturer's labeling; use with caution and monitor for adverse reactions. Bedaquiline is highly protein bound and not likely to be removed by dialysis.

Dosing: Hepatic Impairment: Pediatric

Children ≥5 years and Adolescents:

Baseline (at initiation of therapy):

Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution and monitor for adverse reactions.

Hepatotoxicity during therapy: Discontinue therapy if any of the following presents: Aminotransferase elevation and total bilirubin >2 times ULN, aminotransferase elevation >8 times ULN, or aminotransferase elevation >5 times ULN and for >2 weeks.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Sirturo: 20 mg

Sirturo: 100 mg [contains corn starch]

Generic Equivalent Available: US

No

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/204384s016lbl.pdf#page=28, must be dispensed with this medication.

Administration: Adult

Administer by directly observed therapy. For dosing week 3 and beyond, space doses at least 48 hours apart.

Oral: Tablet-specific administration information:

100 mg tablets: Administer with food; swallow whole.

20 mg tablets:

For patients who can swallow intact tablets: Administer whole or divided in half with food.

For patients who cannot swallow intact tablets, administer using one of the following methods:

• Method 1: In a cup, disperse up to 5 tablets in 5 mL of water; mix well until tablets are completely dispersed, and then either administer the contents of the cup, or if desired, the dispersed mixture in water can be further mixed with ≥5 mL of a beverage (eg, water, milk products, apple juice, orange juice, cranberry juice, carbonated beverage) or 1 teaspoonful of soft food (eg, yogurt, applesauce, mashed banana, porridge) and then administered. If the total dose requires >5 tablets, repeat the preparation steps with the appropriate number of additional tablets until the desired dose is reached. Rinse remaining tablet residue from the cup (with more beverage or soft food) and consume immediately. Food should be consumed following administration of the final desired dose.

• Method 2: In a container, crush tablets and mix with soft food (eg, yogurt, applesauce, mashed banana, porridge) then administer immediately. Rinse remaining tablet residue from the container (with more soft food) and consume immediately.

Feeding tube: Using the 20 mg tablets only, disperse up to 5 tablets in 50 mL of noncarbonated water and mix well (mixture should be white to almost white with visible particles); administer immediately through a feeding tube (≥8 French). If the total dose requires >5 tablets, repeat the preparation steps with the appropriate number of additional tablets until the desired dose is reached. Rinse and flush with 25 mL of additional water to remove any remaining tablet residue in the items used for preparation or the feeding tube. Food should be consumed following administration of the final desired dose.

Administration: Pediatric

Note: Administer as directly observed therapy (DOT). During weeks 3 to 24 of treatment (3-times-per-week dosing), doses should be separated by ≥48 hours.

Oral:

100 mg tablets: Administer with food; swallow tablets whole with water.

20 mg tablets:

For patients who can swallow intact tablets: Administer with food; swallow tablets whole or divided in half with water.

For patients who cannot swallow intact tablets:

Method 1: In a cup, disperse up to 5 tablets in 5 mL of water; mix well until tablets are completely dispersed; administer the contents of the cup with food, or, if desired, the dispersed mixture in water can be further mixed with ≥5 mL of a beverage (eg, water, milk products, apple juice, orange juice, cranberry juice, carbonated beverage) or 1 teaspoonful of soft food (eg, yogurt, applesauce, mashed banana, porridge) and then administered. Rinse remaining tablet residue from the cup (with more beverage or soft food) and consume immediately. If the total dose requires >5 tablets, repeat the preparation steps with the appropriate number of additional tablets until the desired dose is reached. Food should be consumed following administration of the final desired dose.

Method 2: In a container, crush tablets and mix with soft food (eg, yogurt, applesauce, mashed banana, porridge) then administer immediately. Rinse remaining tablet residue from the container (with more soft food) and consume immediately.

Feeding tube: Using the 20 mg tablets only, disperse up to 5 tablets in 50 mL of noncarbonated water and mix well (mixture should be white to almost white with visible particles); administer through a feeding tube (≥8 French). If the total dose requires >5 tablets, repeat the preparation steps with the appropriate number of additional tablets until the desired dose is reached. Rinse and flush with 25 mL of additional water to remove any remaining tablet residue in the items used for preparation or the feeding tube. Food should be consumed following administration of the final desired dose.

Missed doses:

Weeks 1 and 2 (once-daily dosing): If a dose is missed, do not make up the missed dose and continue the usual dosing schedule.

Weeks 3 to 24 (3-times-weekly dosing): If a dose is missed, administer the missed dose as soon as possible and resume the 3-times-weekly schedule.

Use: Labeled Indications

Tuberculosis, multidrug resistant, pulmonary: Treatment of multidrug-resistant, pulmonary tuberculosis (MDR-TB) as part of combination therapy in pediatric patients ≥5 years of age (weighing ≥15 kg) and adults when an effective treatment regimen cannot otherwise be provided.

Limitations of use: Not for use in extrapulmonary TB, latent TB infection, drug-sensitive TB, or treatment of other mycobacteria. Clinical data in patients with HIV-1 and MDR-TB coinfection are limited (safety and efficacy have not been established).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Chest pain (11%)

Gastrointestinal: Nausea (38%)

Hepatic: Increased serum transaminases (9% to 11%)

Nervous system: Headache (28%)

Neuromuscular & skeletal: Arthralgia (33%)

Respiratory: Hemoptysis (18%)

1% to 10%:

Dermatologic: Skin rash (8%)

Gastrointestinal: Anorexia (9%), increased serum amylase (3%)

Frequency not defined:

Cardiovascular: Prolonged QT interval on ECG

Hepatic: Hepatotoxicity

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Hepatic effects: Increased risk of hepatic reactions; avoid alcohol intake and other known hepatotoxic drugs, especially in patients with impaired hepatic function. Monitor AST, ALT, alkaline phosphatase, bilirubin, and symptoms of liver dysfunction (eg, fatigue, nausea, anorexia, jaundice, dark urine, liver tenderness, and hepatomegaly) at baseline and monthly during therapy, and as needed. Monitor more frequently if patient has underlying hepatic disease or is receiving concomitant drugs (CDC 2013). Test for viral hepatitis and discontinue other hepatotoxic medications if evidence of new or worsening hepatic disease occurs. Discontinue use if aminotransferase elevations are accompanied by total bilirubin elevation >2 times ULN, aminotransferase elevations are >8 times ULN, or aminotransferase elevations are >5 times ULN and continue for >2 weeks.

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2C8 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): May enhance the hepatotoxic effect of Bedaquiline. Risk X: Avoid combination

Amiodarone: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even greater risk. Risk D: Consider therapy modification

Arsenic Trioxide: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Astemizole: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Astemizole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Carbetocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination

Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Risk X: Avoid combination

Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

ClomiPRAMINE: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

CloZAPine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bedaquiline. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit duration of concurrent use of bedaquiline with strong CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued use outweighs the possible risks. Monitor for toxic effects of bedaquiline, including QTc interval prolongation. Risk D: Consider therapy modification

Dabrafenib: May enhance the QTc-prolonging effect of Bedaquiline. Dabrafenib may decrease serum concentrations of the active metabolite(s) of Bedaquiline. Dabrafenib may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination

Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination

Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Dronedarone: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Dronedarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Droperidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Etelcalcetide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fingolimod: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias (including TdP) with a continuous overnight ECG when fingolimod is combined with QT prolonging drugs. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Flecainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Fluconazole: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluconazole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Fluorouracil Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Gemifloxacin: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification

Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Haloperidol: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

HydrOXYzine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk C: Monitor therapy

Imipramine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy

Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid combination

Levofloxacin-Containing Products (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Levoketoconazole: QT-prolonging CYP3A4 Substrates may enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination

Lofexidine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Lopinavir: May increase serum concentrations of the active metabolite(s) of Bedaquiline. Lopinavir may increase the serum concentration of Bedaquiline. Management: Consider alternatives to this combination. Concomitant use should only occur if the benefit of coadministration outweighs the risk. If combined, monitor for increased bedaquiline effects/toxicities (eg, QTc interval prolongation). Risk D: Consider therapy modification

Meglumine Antimoniate: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Methadone: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk X: Avoid combination

Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination

OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ondansetron: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Oxytocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pacritinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pacritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

PAZOPanib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of PAZOPanib. Risk X: Avoid combination

Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination

Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination

Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid combination

Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Risk X: Avoid combination

Propafenone: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Propofol: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Class III Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Miscellaneous Agents (Highest Risk): May enhance the QTc-prolonging effect of Bedaquiline. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for increased toxicities, including QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Bedaquiline. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Bedaquiline. Management: Consider alternatives to this drug combination and avoid use for more than 14 days. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination

Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Risk X: Avoid combination

RisperiDONE: QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Risk X: Avoid combination

SUNItinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of SUNItinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Thioridazine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination

Toremifene: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Food Interactions

Administration with a standard meal (~22 g fat; 558 calories) increases bioavailability by approximately twofold. Management: Administer with food.

Reproductive Considerations

Evaluate pregnancy status prior to treatment of multidrug-resistant tuberculosis in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment for multidrug-resistant tuberculosis (Esmail 2018).

Pregnancy Considerations

Information related to bedaquiline use during pregnancy is limited. An increased risk of low birth weight infants was found following in utero bedaquiline exposure; however, this was found not to be clinically significant over time (Jaspard 2017; Loveday 2020; WHO 2020).

Active tuberculosis infection is associated with adverse fetal outcomes, including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020), as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020).

Data are limited for use of second-line drugs during pregnancy (ie, bedaquiline). The treatment of multidrug-resistant tuberculosis in pregnant patients should be individualized; evidence to support a specific regimen is not available (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020). Bedaquiline should be reserved for use during pregnancy when an effective treatment regimen cannot otherwise be provided (CDC 2013).

Breastfeeding Considerations

It is not known if bedaquiline is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, benefits of breastfeeding to the infant, and benefits of treatment to the mother. Breastfed infants should be monitored for adverse events, such as hepatotoxicity.

Monitoring Parameters

Susceptibility information for the background regimen against M. tuberculosis isolate should be obtained if possible. ECG should be obtained at baseline, after the initial 2 weeks, and monthly thereafter during therapy (ATS/CDC/ERS/IDSA [Nahid 2019]). Monitor ECG weekly with concurrent administration of other medications known to prolong the QTc interval (including fluoroquinolones, macrolide antibiotics, or clofazimine) or if the patient has ongoing or a history of conditions predisposing them to QTc prolongation (torsade de pointes, congenital long QT syndrome, hypothyroidism, uncompensated heart failure, bradyarrhythmias) (CDC 2013). If QTc prolongation is detected during therapy, monitor ECG frequently to confirm QTc return to baseline. Baseline potassium, calcium, and magnesium should be obtained and corrected, if abnormal, and monitored during therapy (ATS/CDC/ERS/IDSA [Nahid 2019]). Discontinue therapy (and all other QT prolonging drugs) if patient develops confirmed QTcF interval of >500 ms (confirmed by repeat ECG) or ventricular arrhythmia.

Monitor AST, ALT, alkaline phosphatase, and bilirubin at baseline, monthly during treatment, and as needed. Monitor more frequently if patient has underlying hepatic disease or is receiving concomitant hepatotoxic drugs (CDC 2013). Further evaluate patients with evidence of liver dysfunction (AST/ALT and/or bilirubin elevations, and/or symptoms [eg fatigue, nausea, anorexia, hepatomegaly]). Discontinue if AST or ALT elevations are >5 times ULN and persist >2 weeks, are >8 times ULN, or if elevations also include total bilirubin >2 times ULN.

Monitor weekly for arthralgias, chest pain, headache, hemoptysis, nausea, and rash. Monitoring serum bedaquiline levels may be considered in patients with renal impairment. Sputum specimens should be evaluated monthly throughout treatment and at the end of treatment, even if cultures become negative. Specimens positive for M. tuberculosis (including pretreatment specimen) should be evaluated further by a laboratory (in conjunction with a state public health laboratory) that performs bedaquiline resistance testing (CDC 2013).

Mechanism of Action

As a diarylquinoline antimycobacterial, inhibits the proton transfer chain of mycobacterial ATP synthase required for energy generation in M. tuberculosis. It is not active against human ATP synthase.

Pharmacokinetics

Note: Pharmacokinetic data in pediatric patients (age range: 5 to 17 years; weight: 14 to 75 kg) reported to be similar to in adults; may be variable in some patients.

Absorption: Significantly increased with food

Distribution: Vd: ~164 L

Protein binding: >99.9%

Metabolism: Hepatic via CYP3A4; forms N-monodesmethyl metabolite (M2) which has 4 to 6 times less antimycobacterial potency than parent drug

Half-life elimination: Terminal: ~5.5 months (bedaquiline and M2 metabolite)

Time to peak, serum: Oral: Adolescents: ~4 hours; Adults: ~5 hours

Excretion: Feces; urine (≤0.001%)

Pharmacokinetics: Additional Considerations

Hepatic function impairment: Mean exposure is ~20% lower in patients with moderate impairment (Child-Pugh class B).

Pricing: US

Tablets (Sirturo Oral)

20 mg (per each): $38.30

100 mg (per each): $191.49

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Sirturo (AT, BB, BE, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HK, HR, HU, IE, JP, KR, LT, LU, LV, MT, NL, NO, NZ, PL, PT, RO, RU, SE, SI, SK)


For country code abbreviations (show table)
  1. Centers for Disease Control and Prevention (CDC). Provisional CDC guidelines for the use and safety monitoring of bedaquiline fumarate (Sirturo) for the treatment of multidrug-resistant tuberculosis. MMWR Recomm Rep. 2013;62(RR-09):1-12. [PubMed 24157696]
  2. Centers for Disease Control and Prevention (CDC), “Treatment of Tuberculosis. American Thoracic Society, CDC, and Infectious Diseases Society of America,” 2003, MMWR Recomm Rep, 52(RR-11):3-5. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm [PubMed 12836625]
  3. Conradie F, Diacon AH, Ngubane N, et al; Nix-TB Trial Team. Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med. 2020;382(10):893-902. doi:10.1056/NEJMoa1901814 [PubMed 32130813]
  4. Diacon AH, Donald PR, Pym A, et al, “Randomized Pilot Trial of Eight Weeks of Bedaquiline (TMC207) Treatment for Multidrug-Resistant Tuberculosis: Long Term Outcome, Tolerability, and Effect on Emergence of Drug Resistance,” Antimicrob Agents Chemother, 2012, 56(6):3271-6. [PubMed 22391540]
  5. Diacon AH, Dawson R, von Groote-Bidlingmaier F, et al, “14-Day Bactericidal Activity of PA-824, Bedaquiline, Pyrazinamide and Moxifloxacin Combinations: A Randomised Trial,” Lancet, 2012, 380(9846):986-93. [PubMed 22828481]
  6. Diacon AH, Pym A, Grobusch M, et al, “The Diarylquinoline TMC207 for Multidrug-Resistant Tuberculosis,” N Engl J Med, 2009, 360(23):2397-405. [PubMed 19494215]
  7. Dooley KE, Park JG, Swindells S, et al, “Safety, Tolerability and Pharmacokinetic Interaction of the Antituberculous Agent TMC207 (Bedaquiline) With Efavirenz in Healthy Volunteers: AIDS Clinical Trials Group Study A5267,” J Acquir Immune Defic Syndr, 2012, 59(5):455-62. [PubMed 22126739]
  8. Esmail A, Sabur NF, Okpechi I, Dheda K. Management of drug-resistant tuberculosis in special sub-populations including those with HIV co-infection, pregnancy, diabetes, organ-specific dysfunction, and in the critically ill. J Thorac Dis. 2018;10(5):3102-3118. doi:10.21037/jtd.2018.05.11 [PubMed 29997980]
  9. Jaspard M, Elefant-Amoura E, Melonio I, De Montgolfier I, Veziris N, Caumes E. Bedaquiline and linezolid for extensively drug-resistant tuberculosis in pregnant woman. Emerg Infect Dis. 2017;23(10). [PubMed 28792382]
  10. Loveday M, Hughes J, Sunkari B, et al. Maternal and infant outcomes among pregnant women treated for multidrug/rifampicin-resistant tuberculosis in South Africa. Clin Infect Dis. Published online March 6, 2020. doi:10.1093/cid/ciaa189 [PubMed 32141495]
  11. Miele K, Bamrah Morris S, Tepper NK. Tuberculosis in pregnancy. Obstet Gynecol. 2020;135(6):1444-1453. doi:10.1097/AOG.0000000000003890 [PubMed 32459437]
  12. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63(7):e147-e195. doi:10.1093/cid/ciw376 [PubMed 27516382]
  13. Nahid P, Mase SR, Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med. 2019;200(10):e93-e142. doi:10.1164/rccm.201909-1874ST [PubMed 31729908]
  14. Rustomjee R, Diacon AH, Allen J, et al, “Early Bactericidal Activity and Pharmacokinetics of Diarylquinoline TMC207 in Treatment of Pulmonary Tuberculosis,” Antimicrob Agents Chemother, 2008, 52(8):2831-5. [PubMed 18505852]
  15. Sirturo (bedaquiline) [prescribing information]. Titusville, NJ: Janssen Therapeutics; September 2021.
  16. Villemagne B, Crauste C, Flipo M, et al, “Tuberculosis: The Drug Development Pipeline at a Glance,” Eur J Med Chem, 2012, 51:1-16. [PubMed 22421275]
  17. World Health Organization (WHO). WHO consolidated guidelines on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment. https://www.who.int/publications/i/item/9789240007048. Published 2020.
Topic 87509 Version 193.0