Drug information of bedaquiline

bedaquiline


Bedaquiline is an antibiotic that is used together with other medications to treat tuberculosis of the lungs that has been resistant to other antibacterial medications.

Mechanism of effect

Diarylquinoline; inhibits mycobacterial adenosine 5'-triphosphate (ATP) synthase, an enzyme essential for the generation of energy in Mycobacterium tuberculosis

Pharmacokinetics

Absorption:Bioavailability: Increased 2-fold when taken with standard meal compared with fasted conditions

Peak plasma time:

Adults: 5 hr

Age 14-18 years: 4 hr

Plasma concentrations Peak

Adults: 1659 ng/mL

Age 14-18 years: 1800 ng/mL

Minimum

Adults: 654 ng/mL

Age 14-18 years: 544 ng/mL

AUC

Adults: 25,863 ng⋅hr/mL

Age 14-18 years: 26,300 ng⋅hr/mL

Distribution

Protein Bound: >99.9%

Vd: 164 L

Metabolism

Metabolized primarily by CYP3A4 to form N-monodesmethyl metabolite (M2) which is 4- to 6-times less active

Elimination

Half-life: 5.5 months

Renal clearance: <0.001%

Excretion: Mainly in feces

Drug indications

tuberculosis

-Multidrug Resistant Pulmonary Tuberculosis

Dosage

Weeks 1-2: 400 mg PO qDay for 2 weeks, THEN

Weeks 3-24: 200 mg 3 times/week with at least 48 hr between doses

Drug contraindications

None

Side effects

Headache , nausea , chest pain , abdominal pain , anorexia , ECG prolonged QT , Rash

Nausea-Arthralgia-Headache-Chest pain-Abdominal pain-Anorexia-Rash-Transaminases increased-Blood amylase increased-QT prolongation

Interactions

Palonosetron , vandetanib , Promazine , Tipranavir , Etravirine , Halofantrine , Grepafloxacin , Nicardipine , Terfenadine , Abarelix , Asenapine , Alfuzosin , Perflutren , Apalutamide , Pitolisant , atovaquone/proguanil , Lopinavir and Ritonavir , gilteritinib , glasdegib , Romidepsin , Atomoxetine , Amitriptyline , Amiodarone , Epirubicin , Adenosine , Erythromycin , cenobamate , st. john's wort , Eslicarbazepine acetate , lefamulin , lofexidine , macimorelin , methotrimeprazine , osilodrostat , selpercatinib , Bepridil , Pasireotide , levomethadyl acetate , nafcillin , Typhoid vaccine (live), oral , ozanimod , Lomefloxacin , Ceritinib , Nilutamide , norfloxacin , rilpivirine , bosutinib , Deutetrabenazine , Entrectinib , cholera vaccine live , Cabozantinib , Lorlatinib , Siponimod , midostaurin , pexidartinib , Triclabendazole , ivosidenib , Crizotinib , Telavancin , Iloperidone , Pimavanserin , Degarelix , Foscarnet , lenvatinib , encorafenib , Trimeprazine , Triflupromazine , Amisulpride , Paliperidone , Pazopanib , ezogabine , probucol , Abiraterone , Arsenic trioxide , Efavirenz , Dabrafenib , Gatifloxacin , Eribulin , Inotuzumab‎ , Idarubicin , Goserelin , Anagrelide , Fosphenytoin , Polyethylene glycol , Mefloquine , Panobinostat , Ribociclib , Dofetilide , Ibutilide , Osimertinib , Quinine , Chloroquine , sparfloxacin , Mesoridazine , Procainamide , Ivabradine , Mifepristone , Dolasetron , Telithromycin , Droperidol , Halothane , saquinavir , mitotane , Mirtazapine , primaquine , Apomorphine , valbenazine , Histrelin , teriflunomide , propoxyphene , protriptyline , ISOPROTERENOL , dronedarone , Prochlorperazine , Quinidine , Amoxapine , Ziprasidone , Lomitapide , Mipomersen , Quetiapine , lithium , Buprenorphine , Toremifene , Tamoxifen , Metaproterenol , Clofazimine , Rifabutin , Rifapentine , Ranolazine , astemizole , Pentamidine , Enzalutamide , Flecainide , Bicalutamide , ritodrine , Leuprolide acetate , escitalopram , Ketoconazole , Clarithromycin , Chlorpromazine , Clozapine , Clomipramine , Solifenacin , Nortriptyline , Nilotinib , Haloperidol , Hydroxychloroquine , Voriconazole , Carbamazepine , Lapatinib , Levofloxacin , Maprotiline , Methadone , Modafinil , Moxifloxacin , Fluoxetine , Fluconazole , Phenobarbital , Phenytoin , Fingolimod , Granisetron , Sevoflurane , Ciprofloxacin , Citalopram , Cisapride , Flutamide , Fluphenazine , Risperidone , Rifampin , Sunitinib , Sertraline , Sotalol , Sorafenib , Daunorubicin , Desipramine , Dexamethasone , Doxepin , Doxorubicin , Disopyramide , Trifluoperazine , Triptorelin , Trimipramine , Tizanidine , Thioridazine , Gemifloxacin , Pimozide , Tacrolimus , Tetrabenazine , Trazodone , Tramadol , Terbutaline , Papaverine , perphenazine , Propafenone , Promethazine , Primidone , Posaconazole , Ofloxacin , Oxaliplatin , Ondansetron , Oxytocin , Imipramine , Bosentan , Gefitinib , Dasatinib , Gemtuzumab , Remdesivir

Alerts

-An increased risk of death was seen in the bedaquiline treatment group compared to the placebo treatment group in 1 clinical trial

-QT prolongation can occur; coadministration with drugs that prolong the QT interval may cause additive QT prolongation

-Potential for development of resistance to bedaquiline in M tuberculosis exists; must only be used in an appropriate combination regimen fo treatment of pulmonary MDR-TB to reduce risk of developing resistance

-Hepatic-related adverse effects increased when bedaquiline added to multidrug regimen

-Discontinue if

  • Aminotransferase increases are accompanied by total bilirubin elevation >2x ULN
  • Aminotransferase elevations >8x ULN
  • Aminotransferase elevations persist beyond 2 weeks

-ncreased risk for QT prolongation with:Coadministration with QT prolonging drugs,History of Torsade de Pointes, congenital long-QT syndrome, uncompensated heart failure, or hypothyroidism with bradyarrhythmias

-Discontinue bedaquiline if :Clinically significant ventricular arrhythmia, QTcF interval >500 ms

-Safety and efficacy not established in patients <18 years of age.

-Use with caution in HIV-infected individuals

 

Points of recommendation

-avoid alcohol and other hepatotoxic drugs, especially in patients with hepatic impairment

-Monitor symptoms and laboratory tests at baseline, monthly while on treatment, and as needed

- obtain ECG before initiating treatment and at least 2, 12, and 24 weeks after starting treatment

-Obtain baseline serum levels for potassium, calcium, and magnesium and correct if abnormal; follow-up electrolyte monitoring if QT prolongation detected

-Only use in combination with at least 3 other drugs to which the patient’s MDR-TB isolate has been shown to be susceptible in vitro; if in vitro testing results are unavailable, may be initiated in combination with at least 4 other drugs to which the patient’s MDR-TB isolate is likely to be susceptible

-May be used on a case-by-case basis for durations longer than 24 weeks when an effective treatment regimen cannot be provided otherwise

-Severe or end-stage renal disease requiring hemodialysis or peritoneal dialysis: Use with caution; if used, monitor for adverse reactions of bedaquiline

-Limitations of use

  • Latent infection due to Mycobacterium tuberculosis
  • Drug-sensitive tuberculosis
  • Extra-pulmonary tuberculosis
  • Infections cause by nontuberculous mycobacteria

 

Pregnancy level

HAVE NOT BEEN ESTABLISHED

There are no data available on use of this drug in pregnant women to inform regarding drug-related risk of birth defects, miscarriage, or adverse maternal/fetal outcomes. Active tuberculosis is associated with adverse maternal and/or neonatal outcomes. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.

Breast feeding warning

-The effects in the nursing infant are unknown.

-Breastfed infants should be monitored for signs/symptoms of adverse reactions (e.g., arthralgia, chest pain, headache, hemoptysis, hepatotoxicity, nausea).

-The effects of this drug on milk production are unknown.

Related drugs

Capreomycin , Pyrazinamide

Drug forms

Sirturo

Ask a Pharmacist


User's questions
    No comments yet.