Adult Dosing

Multidrug resistant pulmonary tuberculosis

• Initiate 400 mg PO qday x 2 wk, followed by 200 mg 3 times/wk for 22 wk with food

Pediatric Dosing

• Safety and effectiveness in children <18 years of age have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Multidrug resistant pulmonary tuberculosis
• Indicated as part of combination therapy in adults (=>18 years) with pulmonary multi-drug resistant tuberculosis (MDR-TB)

Note:

• Reserved for use when an effective treatment regimen cannot otherwise be provided
• Should be administered by directly observed therapy (DOT)
• Not indicated to treat latent, extrapulmonary, drug-sensitive tuberculosis, or non-tuberculous mycobacteria (NTM)
• Use in combination with at least 3 other drugs to which the patient's MDR-TB isolate is likely to be susceptible

• Hypersensitivity to any of the ingredients of the product

• 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
• Only use when an effective treatment regimen cannot otherwise be provided
• QT prolongation may occur; coadministration with drugs that prolong the QT interval may cause additive QT prolongation

Renal Dose Adjustment (Based on CrCl)

• Mild-moderate renal impairment: No dose adjustments
• Severe renal impairment: Dose adjustments not defined; caution advised

Hepatic Dose Adjustment

• Mild-moderate hepatic impairment: No dose adjustments
• Severe hepatic impairment: Dose adjustments not defined; caution advised; administer only when the benefits outweigh the risks

• 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 [US black box warning]
• Only use when an effective treatment regimen cannot otherwise be provided [US black box warning]
• Therapy may lead to QT prolongation; coadministration with drugs that prolong the QT interval may cause additive QT prolongation [US black box warning]
• Therapy may lead to QT prolongation. An ECG should be obtained before initiation of therapy, and at least 2, 12, and 24 weeks after starting therapy. Obtain baseline serum levels for potassium, calcium, and magnesium and correct if abnormal; follow-up electrolyte monitoring is recommended if QT prolongation is detected
• Concomitant use with other QT prolonging drugs including fluoroquinolones and macrolide antibacterial drugs and the antimycobacterial drug, clofazimine may increase the risk for QT prolongation
• Use in patients with a history of Torsade de Pointes, congenital long QT syndrome, hypothyroidism, bradyarrhythmias, uncompensated heart failure, serum calcium, magnesium, or potassium levels deficiency may increase risk of QT prolongation
• Discontinue therapy if the patient develops clinically significant ventricular arrhythmia and QTcF interval of > 500 ms (confirmed by repeat ECG)
• Monitor ECGs frequently to confirm that QT interval returned to baseline
• Closely monitor symptoms and laboratory tests such as ALT, AST, alkaline phosphatase, and bilirubin at baseline, monthly while on treatment, and as needed
• If serum aminotransferases increase to > 3 x ULN, repeat testing within 48 hours should be performed alongwith testing for viral hepatitis
• If symptoms of worsening liver dysfunction such as clinically significant elevation of aminotransferases and/or bilirubin and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly occur, therapy should be promptly reevaluated by the physician
• Discontinue therapy if aminotransferase elevations are accompanied by total bilirubin elevation > 2 x ULN, aminotransferase elevations are > 8xULN or aminotransferase elevations persist beyond 2 weeks
• Clinical data on the combined use of antiretroviral agents and bedaquiline in HIV/MDR-TB co-infected patients is unavailable
• Therapy should only be administered in combination with at least 3 drugs active against the patient’s TB isolate

Sirturo interacts with :

	Agenerase
	Akne-mycin
	Amiodarone
	Amprenavir
	Aprepitant
	Atazanavir
	Barbiturates
	Biaxin
	Biaxin XL
	Boceprevir
	Bosentan
	Calan
	Calan SR
	Carbamazepine
	Carbatrol
	Cardizem
	Cardizem CD
	Cardizem LA
	Cartia XT
	Cetraxal
	Ciloxan
	Cipro
	Cipro IV
	Cipro XR
	Ciprofloxacin
	Clarithromycin
	Cobicistat
	Conivaptan
	Cordarone
	Covera-HS
	Crixivan
	Cyclosporine
	Dabrafenib
	Darunavir
	Decadron
	Delavirdine
	Dexamethasone
	Diflucan
	Dilacor XR
	Dilantin
	Dilantin Infatabs
	Dilantin-125
	Dilt-CD
	Diltiazem
	Diltzac
	Dronedarone
	E-Mycin
	E.E.S.
	Efavirenz
	Emend
	Epitol
	Equetro
	Ery-Tab
	Eryc
	Erygel
	Eryped
	Erythra-Derm
	Erythro-statin
	Erythrocin
	Erythromycin
	Extina
	Fluconazole
	Fluvoxamine
	Gengraf
	Gleevec
	Grapefruit
	Imatinib
	Incivek
	Indinavir
	Invirase
	Isoptin
	Isoptin SR
	Itraconazole
	Juxtapid
	Ketek
	Ketoconazole
	Korlym
	Lapatinib
	Lomitapide
	Lumacaftor
	Luvox
	Luvox CR
	Maxidex
	Mifepristone
	Multaq
	Mycobutin
	Mysoline
	Nefazodone
	Nelfinavir
	Neoral
	Nexterone
	Nizoral
	Nizoral A-D Shampoo
	Nizoral Shampoo
	Norvir
	Noxafil
	Onmel
	Orkambi
	Oxcarbazepine
	Oxtellar XR
	Ozudrex
	Pacerone
	PCE
	Pediamycin
	Phenytek
	Phenytoin
	Posaconazole
	Prezista
	Priftin
	Primidone
	Proquin XR
	Quinupristin
	Rescriptor
	Restasis
	Reyataz
	Rifabutin
	Rifadin
	Rifampin
	Rifapentine
	Rimactane
	Ritonavir
	Sandimmune
	Saquinavir
	Sporanox
	St. John's wort
	Stribild
	Sustiva
	Synercid
	Tafinlar
	TAO
	Taztia XT
	Tegretol
	Tegretol XR
	Telaprevir
	Telithromycin
	Teril
	Tiazac
	Tracleer
	Trileptal
	Troleandomycin
	Tykerb
	Vaprisol
	Veralan
	Verapamil
	Verelan PM
	Vfend
	Victrelis
	Viracept
	Voriconazole
	Xolegel

Pregnancy Category:B

Breastfeeding: It is not known whether bedaquiline or its metabolites are excreted in human milk. Because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• CNS: Headache
• GI: Nausea, anorexia
• MUSC: Arthralgia
• CV: Chest pain, prolonged QT interval
• HEPA: Transaminases increased
• RESP: Hemoptysis

• Diarylquinoline antimycobacterial; inhibits mycobacterial adenosine 5'-triphosphate (ATP) synthase, an enzyme essential for the generation of energy in Mycobacterium tuberculosis
• Metabolism: Metabolized primarily by CYP3A4 to form N-monodesmethyl metabolite (M2)
• Excretion: Excreted mainly in feces; urinary excretion: (<0.001%)
• Half-life: 5.5 months (mean terminal half-life of bedaquiline and the M2 metabolite)

US Trade Name(s)

• Sirturo

US Availability

Sirturo

• TABS: 100 mg

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Antimicrobials

Antituberculosis Agents

Diarylquinoline Antimycobacterial