Bedaquiline

SIRTURO

Open Bedaquiline in the interactive console ↗

Pronunciation: bed-AK-wi-leen (ser-TOOR-oe)

Bedaquiline ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Bedaquiline ballicule

What it isDiarylquinoline that inhibits mycobacterial ATP synthase, for multidrug-resistant tuberculosis.

Why this oneFirst new TB mechanism in four decades; anchors modern all-oral MDR-TB regimens.

What limits itQT prolongation adds to other QT-prolonging TB drugs; very long tissue half-life. Boxed mortality signal from the pivotal trial.

Bedaquiline molecular structure (skeletal formula) — Molecular structure: Bedaquiline

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Sedation liability0 / 4

QT / Torsades2 / 4

Direct muscarinic antagonism0 / 4

Legacy pregnancy categoryB

Defining liabilityQT prolongation, hepatic toxicity and prolonged tissue persistence

FDA label

Read the full label on DailyMed ↗

BOXED WARNING QTc prolongation — additive with other QTc-prolonging drugs; monitor ECGs; discontinue if significant ventricular arrhythmia or QTc >500 ms

FDA dosing	Population	Start	Target	Max
Pulmonary TB resistant to at least rifampin and isoniazid (combination therapy)	Adults	400 mg QD x 2 wks (with food)	then 200 mg 3x/wk (>=48 h between doses) x 22 wks; 24 wks total; may continue 200 mg 3x/wk beyond 24 wks if needed	400 mg/day (wks 1-2); weekly total not to exceed recommended weekly dose
Pulmonary TB resistant to at least rifampin and isoniazid (combination therapy)	Peds >=2 yr and >=8 kg, weight-banded	Wks 1-2 QD: 8-<10 kg 80 mg; 10-<15 kg 120 mg; 15-<30 kg 200 mg; >=30 kg 400 mg	Wks 3-24, 3x/wk (>=48 h apart): 8-<10 kg 40 mg; 10-<15 kg 60 mg; 15-<30 kg 100 mg; >=30 kg 200 mg	Per weight band; beyond 24 wks only if >=16 yr and >=30 kg (200 mg 3x/wk)

Renal Mild-moderate: no adjustment. Severe/ESRD on dialysis: use with caution; monitor for adverse reactions

Hepatic Mild-moderate: no adjustment. Severe: not studied — use with caution only if benefit outweighs risk; monitor

At least 48 h between 3x/wk doses; weekly total must not exceed recommended weekly dose with >=24 h between intakes

Instructions

Take with food; administer by directly observed therapy (DOT); complete full course
Use only with >=3 other drugs to which the isolate is susceptible (>=4 if susceptibility results unavailable)
Before starting: ECG, serum K/Ca/Mg, liver enzymes, susceptibility testing
100 mg tablet: swallow whole with water
20 mg tablet: whole or split at score (10 mg halves); or disperse in water (+/- beverage/soft food), crush into soft food, or give via feeding tube >=8 Fr
Missed dose wks 1-2: skip it. Wk 3 on: take ASAP, resume 3x/wk schedule
Avoid alcohol and other hepatotoxic drugs during treatment

Available strengths

tab 20, 100 mg

Cautions

QTc prolongation: ECG at baseline, 2 wks after start, and during treatment; correct electrolytes; added risk with other QTc drugs, TdP or congenital long-QT history, hypothyroidism, bradyarrhythmias, uncompensated heart failure, low K/Ca/Mg; discontinue if QTc >500 ms (repeat-confirmed) or significant ventricular arrhythmia; ECG if syncope
Unexplained mortality imbalance vs placebo in Study 1 (11.4% vs 2.5%)
Hepatotoxicity: monitor symptoms and ALT/AST/ALP/bilirubin at baseline, monthly, and prn; discontinue if AST/ALT >8x ULN, >5x ULN persisting >2 wks, or transaminase rise with bilirubin >2x ULN
Avoid moderate/strong CYP3A4 inducers (rifampin, rifapentine, rifabutin, efavirenz); monitor safety closely with CYP3A4 inhibitors
Use only in an appropriate combination regimen to limit bedaquiline resistance

Adverse reactions

Adults >=10%: nausea, arthralgia, headache, hemoptysis, chest pain (Study 1); QTc prolongation, vomiting, transaminase increase, abdominal pain, pruritus, dizziness, rash, insomnia, dry skin, palpitations (Study 4)
Peds >=10%: arthralgia, nausea, abdominal pain (12-<18 yr); liver-enzyme elevation (5-<12 yr); vomiting (2-<5 yr)

Pregnancy Insufficient human data; no fetal harm in rat/rabbit studies up to 6x clinical exposure. Untreated active TB in pregnancy carries maternal/neonatal risk

Lactation Accumulates in breast milk (concentrations exceed maternal plasma); breastfeeding not recommended during treatment and for 27.5 months after last dose unless formula unavailable; monitor breastfed infants for hepatotoxicity

Cost

Bedaquiline (SIRTURO)

Strength		#/mo	generic $/mo	CostPlus
20 mg	tab	30 qd		not offered
100 mg	tab	30 qd		not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Bedaquiline is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Open Bedaquiline in the interactive console ↗

Self-check

Which mycobacterial enzyme does bedaquiline inhibit?
ATP synthase.
What cardiac effect can bedaquiline add to other TB drugs?
QT prolongation.