bedaquiline

bedaquiline

(bed- ak-wi-leen) ,

Sirturo

(trade name)

Classification

Therapeutic: antituberculars
Pharmacologic: diarylquinolines
Pregnancy Category: B

Indications

Part of treatment (with at least three other drugs) of multi-drug resistant pulmonary tuberculosis in adults, when other treatment regimens cannot be provided. Not to be used for latent, extra-pulmonary or other-drug sensitive tuberculosis.

Action

Inhibits bacterial adenosine 5'triphosphate (ATP) synthase which is required for mycobacterial energy production.

Therapeutic effects

Shortened time to sputum conversion to negativity and resultant decrease in infectiousness and sequelae of tuberculosis.

Pharmacokinetics

Absorption: Absorption following oral administration is doubled by food.
Distribution: Unk
Protein Binding: >99.9%
Metabolism and Excretion: Mostly metabolized (CYP3A4 enzyme system) and eliminated in feces, negligable renal excretion
Half-life: 5.5 months (terminal elimination half-life)

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunk5 hrunk

Contraindications/Precautions

Contraindicated in: Systemic potent CYP3A4 inducers should be avoided. Use of potent CYP3A4 inhibitors for more than 14 consecutive days should be avoided[ Lactation: Avoid use during lactation.
Use Cautiously in: Concurrent use of lopinavir/ritonavir; Electrolyte abnormalities (correct prior to use); Severe hepatic or renal impairment; Concurrent use of other drugs that prolong the QT interval, history of Torsades de Pointes, prolonged QT interval, hypothyroidism and bradyarrhythmias, uncompensated CHF (↑ risk of QT prolongation and serious arrhythmias). Obstetric: Use during pregnancy only if clearly needed. Pediatric: Safe and effective use in children <18 yr has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)

Respiratory

  • hemoptysis

Cardiovascular

  • QT prolongation (life-threatening)
  • chest pain

Gastrointestinal

  • nausea (most frequent)
  • anorexia
  • hepatitis

Dermatologic

  • rash

Musculoskeletal

  • arthralgia (most frequent)

Interactions

Drug-Drug interaction

Systemic potent CYP3A4 inducers including rifampin, rifapentine and rifabution can ↓ levels and effectiveness and should be avoided. Potent CYP3A4 inhibitors including ketoconazole can ↑ levels and the risk of toxicity; avoid use for more than 14 consecutive days if possible.Concurrent use of lopinavir/ritonavir may ↑ blood levels and risk of adverse reactions. Concurrent use of other drugs that prolong the QT interval including fluoroquinolones, macrolides and clofazamine ) may ↑ risk of serious arrhythmias. Concurrent use of alcohol or hepatotoxic drugs may ↑ risk of adverse hepatic events.

Route/Dosage

Oral (Adults) 400 mg once daily for 2 wk, then 200 mg three times weekly (at least 48 hr between doses) for 22 wk.

Availability

Tablets: 100 mg

Nursing implications

Nursing assessment

  • Obtain ECG prior to starting therapy and at least 2, 12 and 24 wks after starting therapy to monitor for QT prolongation of >500 ms, clinically significant ventricular arrythmias, or if syncope occurs.
  • Lab Test Considerations: Monitor serum potassium, calcium, and magnesium at baseline and if Q-T prolongation is detected. Correct abnormalities.
    • Monitor liver function tests (ALT, AST, alkaline phosphatase, and bilirubin at baseline, monthly during therapy, and as needed. If serum AST and ALT ↑ to 3 times the upper limit of normal, repeat test within 48 hr and test for viral hepatitis and other hepatotoxic medications. If symptoms of liver dysfunction (clinically significant ↑ serum ALT, AST or bilirubin and/or symptoms of fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, and hepatomegaly) occur re-evaluate. If AST and ALT ↑ accompanied by total bilirubin ↑ >2 times upper limit of normal, or if AST and ALT ↑ 8 time upper limits of normal, or if AST and ALT ↑ persist beyond 2 wks, discontinue bedaquiline.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Only administer by direct observation therapy (DOT).
  • Must be taken in combination with 3–4 other antitubercular drugs.
  • Oral: Administer with food. Swallow tablet whole; do not crush, break, or chew.
    • Weeks 1–2: administer 400 mg once daily.
    • Weeks 3–24: administer two 100 mg tablets 3 times/wk with at least 48 hrs between doses for a total of 600 mg/wk.

Patient/Family Teaching

  • Instruct patient to take bedaquiline as direct for the complete 24 wk course of therapy. Do not stop without discussing with health care professional. If a dose is missed during first 2 wks, skip dose and return to usual schedule. If a dose is missed wks 3–24, take missed dose as soon as remembered, then resume 3 times/wk regimen. Emphasize that bedaquiline is always taken with 3–4 other antitubercular medications and these medications should be continued unless discussed with health care professional. If any medications are stopped may decrease effectiveness of therapy and may increase risk of mycobacterium resistance and disease becoming untreatable in future.
  • Caution patient to avoid alcohol during therapy.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications or alcohol.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Shortened time to sputum conversion to negativity and resultant decrease in infectiousness of patient and sequelae of tuberculosis.
References in periodicals archive ?
For children, limited data are available regarding use of 2 new TB drugs, bedaquiline and delamanid; thus, the shortened regimen could represent the best opportunity to improve their outcomes and access to treatment.
Here, there is some promising news: Bedaquiline recently became the first new TB drug to be approved by the US Food and Drug Administration in 40 years.
The three-drug regimen consists of bedaquiline (B), which received conditional regulatory approval in several high-TB disease burden countries; the novel antibacterial drug compound pretomanid (Pa), which is being tested in multiple clinical trials; and linezolid, an oxazolidinone, which has been used off-label to treat TB.
With the new alternative MDR-TB drug bedaquiline now being cautiously and slowly rolled out to decentralised MDR-TB treatment clinics nationwide, the timely use of a portable audiometer to diagnose early hearing loss enables a drug switch with far better outcomes.
STREAM Stage 2' is part of the post-approval requirements for bedaquiline from the U.
The Community Research Advisors Group (CRAG) argue that research into bedaquiline - a new drug, fast tracked for multidrug-resistant tuberculosis (MDR-TB) - should proceed cautiously in people with drug-sensitive tuberculosis and they urged researchers to balance the goal of shortening treatment for drug-sensitive TB with patient safety.
For example, the drug bedaquiline was developed in 2005 but almost 10 years later it is available to only 200 patients in South Africa in a monitored program with strict eligibility criteria.
Bedaquiline (Sirturo) is a new antituberculosis agent that can be used in pregnancy because of the low risk in animal studies and its indication.
19) Neither bedaquiline nor linezolid is currently available as part of the National Treatment Programme in South Africa.
After close to five decades of insufficient research and development into TB, two new drugs -- bedaquiline and delamanid -- have recently been or are about to be approved by the US Food and Drug Administration (FDA).
The experts said that two new drugs -- Bedaquiline and Delamanid -- had recently been or are about to be approved after close to five decades of insufficient research and development into TB.
Food and Drug Administration has approved Sirturo, or bedaquiline, as part of a combination therapy to treat adults with multidrug-resistant pulmonary tuberculosis.