Bedaquiline


Concise Prescribing Info
Indications/Uses
Pulmonary multidrug-resistant TB.
Dosage/Direction for Use
Adult : PO Combined with ≥3 other anti-TB agents: Week 1-2: 400 mg once daily. Week 3-24: 200 mg 3 times a week (with at least 48 hours between doses).
Dosage Details
Oral
Pulmonary multidrug-resistant tuberculosis
Adult: In combination with ≥3 other anti-TB agents: Week 1-2: 400 mg once daily. Week 3-24: 200 mg 3 times a week (with at least 48 hours between doses). Administer by directly observed therapy (DOT).
Administration
Tab: Should be taken with food.
Contraindications
Hypersensitivity. Concomitant use with moderate or strong CYP3A4 inducers.
Special Precautions
Patients with or history of heart failure, hypothyroidism, bradyarrhythmia, family history of congenital QT prolongation, ventricular arrhythmia, history of torsade de pointes, syncope, hypokalaemia, HIV infection. Not indicated for latent, extra-pulmonary (e.g. CNS, bone), drug-sensitive TB, or infections due to non-tuberculosis mycobacteria. Severe renal and moderate to severe hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Significant: QT interval prolongation, hepatotoxicity, increased risk of mortality.
Cardiac disorders: Chest pain.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea.
Investigations: Transient increase in serum transaminases (AST, ALT), increased serum amylase.
Metabolism and nutrition disorders: Anorexia.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia.
Nervous system disorders: Headache, dizziness.
Respiratory, thoracic and mediastinal disorders: Haemoptysis.
Skin and subcutaneous tissue disorders: Rash.
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor ECG (prior to initiation of therapy then at weeks 2, 12, and 24); K, Ca, and Mg (at baseline, correct if necessary); AST, ALT, alkaline phosphatase and bilirubin (at baseline, monthly during treatment, and as necessary). Sputum specimens must also be evaluated monthly throughout and at the end of treatment even if the cultures become negative.
Drug Interactions
Concomitant use with moderate or strong CYP3A4 inhibitors (e.g. ketoconazole, lopinavir/ritonavir) may pronounce plasma exposure and prolong therapeutic effects. Use with fluoroquinolones (e.g. ciprofloxacin, gatifloxacin), macrolide antibiotics (e.g. clarithromycin, erythromycin), and clofazimine may increase the risk of QT interval prolongation, avoid systemic concomitant use for >14 consecutive days. Hepatotoxic drugs may increase the risk of liver impairment.
Potentially Fatal: Moderate or strong CYP3A4 inducers (e.g. rifabutin, rifampicin, efavirenz, etravirine) decreases the plasma concentration of bedaquiline which may result to treatment failure.
Food Interaction
Administration with food increases bioavailability. Avoid combination with St. John’s wort due to decrease in plasma concentration and reduced therapeutic effect. Alcohol may enhance the hepatotoxic effects of bedaquiline, avoid concomitant use.
Action
Description: Bedaquiline is a diarylquinoline antimycobacterial which inhibits the proton transfer chain of mycobacterial ATP synthase essential for energy generation in M. tuberculosis. This leads to the bactericidal effects for replicating and non-replicating tubercle bacilli.
Pharmacokinetics:
Absorption: Increased absorption with food. Time to peak plasma concentration: Approx 5 hours.
Distribution: Extensively distributed to most tissues except the brain (low uptake). Volume of distribution: Approx 164 L. Plasma protein binding: >99.9%.
Metabolism: Metabolised in the liver mainly by CYP3A4 isoenzyme to form less active N-monodesmethyl (M2) metabolite.
Excretion: Mainly via faeces; urine (<0.001% as unchanged drug). Terminal elimination half-life: Approx 4-5.5 months.
Chemical Structure

Chemical Structure Image
Bedaquiline

Source: National Center for Biotechnology Information. PubChem Database. Bedaquiline, CID=5388906, https://pubchem.ncbi.nlm.nih.gov/compound/Bedaquiline (accessed on Jan. 21, 2020)

Storage
Store between 15-30°C. Protect from light.
MIMS Class
ATC Classification
J04AK05 - bedaquiline ; Belongs to the class of other drugs used in the systemic treatment of tuberculosis.
References
Anon. Bedaquiline. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 15/02/2019.

Anon. Bedaquiline. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 15/02/2019.

Buckingham R (ed). Bedaquiline. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/02/2019.

Janssen-Cilag (New Zealand) Ltd. Sirturo 100 mg Tablets data sheet 7 June 2017. Medsafe. http://www.medsafe.govt.nz/. Accessed 15/02/2019.

Joint Formulary Committee. Bedaquiline. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/02/2019.

Sirturo (Janssen Products LP). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 15/02/2019.

Disclaimer: This information is independently developed by MIMS based on Bedaquiline from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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