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 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.
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 (Ref). Alternatively, a regimen of 200 mg once daily for 8 weeks, followed by 100 mg once daily for 18 weeks, has been studied in combination with linezolid and pretomanid (Ref).
Missed doses: 400 mg once daily for 2 weeks, followed by 200 mg 3 times weekly regimen: 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 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
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.
Refer to adult dosing.
(For additional information see "Bedaquiline: Pediatric drug information")
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 (Ref). 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.
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.
Children ≥5 years and Adolescents:
Baseline (at initiation of therapy):
Mild or moderate impairment: No dosage adjustment necessary.
Severe impairment: 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.
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
There are no contraindications listed in the manufacturer's labeling.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Sirturo: 20 mg
Sirturo: 100 mg [contains corn starch]
No
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.
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.
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.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/204384s017lbl.pdf#page=27, must be dispensed with this medication.
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, TB infection (latent TB), 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).
Substrate of CYP2C19 (minor), CYP2C8 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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 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 increase 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 Bedaquiline. Encorafenib may decrease serum concentrations of the active metabolite(s) of Bedaquiline. Encorafenib may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination
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
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
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). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider therapy modification
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 (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). 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
Mycophenolate: Antibiotics may decrease serum concentrations of the active metabolite(s) of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor therapy
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
Quizartinib: 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
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
Terbutaline: 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
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
Administration with a standard meal (~22 g fat; 558 calories) increases bioavailability by approximately twofold. Management: Administer with food.
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).
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).
Tuberculosis (TB) disease (active TB) 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).
Bedaquiline is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 27.5 months after the last bedaquiline dose, unless infant formula is not available. Infants exposed to bedaquiline via breast milk should be monitored for adverse events, such as hepatotoxicity.
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).
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.
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%)
Hepatic function impairment: Mean exposure is ~20% lower in patients with moderate impairment (Child-Pugh class B).
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