Lumacaftor

ORKAMBI with ivacaftor

Open Lumacaftor in the interactive console ↗

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

What it isCFTR corrector used only with ivacaftor for cystic fibrosis in patients homozygous for F508del; improves folding and trafficking of mutant CFTR.

Why this oneTreats the protein defect rather than symptoms and improves pulmonary outcomes in the eligible genotype.

What limits itLumacaftor is a strong CYP3A inducer, making hormonal contraception unreliable and lowering many drug exposures; chest tightness and liver injury also require monitoring.

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

FDA-approved for

cystic fibrosis homozygous for F508del, with ivacaftor (2015)

FDA label

Read the full label on DailyMed ↗

FDA dosing	Population	Start	Target	Max
Cystic fibrosis (F508del homozygous)	1–5 yr (granules, weight-based)	1 packet BID	1 packet BID (luma 75/iva 94, 100/125, or 150/188 mg by weight)	1 packet BID
Cystic fibrosis (F508del homozygous)	6–11 yr	luma 200/iva 250 mg (2 tabs) BID	luma 200/iva 250 mg (2 tabs) BID	luma 200/iva 250 mg (2 tabs) BID
Cystic fibrosis (F508del homozygous)	≥12 yr	luma 400/iva 250 mg (2 tabs) BID	luma 400/iva 250 mg (2 tabs) BID	luma 400/iva 250 mg (2 tabs) BID

Renal No adjustment for mild–moderate; caution in severe (CrCl ≤30 mL/min) or ESRD (not studied).

Hepatic Mild (Child-Pugh A): no adjustment. Moderate (B): dose reduction (age-based). Severe (C): not studied; use caution at reduced max dose.

Instructions

Take with fat-containing food (meal or snack just before/after dosing).
Granules: mix full packet with 5 mL soft food or liquid at room temperature or below; consume within 1 hour.
Missed dose: take with fat food if within 6 h, otherwise skip; do not double.
When starting with a strong CYP3A inhibitor, reduce dose for the first week.

Available strengths

tab 125/100, 125/200 mg
granules 94/75, 125/100, 188/150 mg/packet

Cautions

Advanced liver disease — liver decompensation/failure has been reported
Elevated transaminases/bilirubin — monitor LFTs before, q3 months first year, then annually
Hypersensitivity, including angioedema and anaphylaxis
Intracranial hypertension
Neuropsychiatric events, including suicidal ideation/behavior
Respiratory events (chest discomfort, dyspnea) during initiation, esp. ppFEV1 <40
Increased blood pressure — monitor periodically
Cataracts in pediatric patients — baseline/follow-up eye exams
Reduces hormonal contraceptive effectiveness

Adverse reactions

Dyspnea
Nasopharyngitis
Nausea
Diarrhea
Upper respiratory tract infection
Fatigue
Abnormal respiration
Increased blood CPK
Rash
Flatulence
Rhinorrhea
Influenza

Pregnancy Limited human data; no adverse fetal effects in animals at multiples of the MRHD.

Lactation No human data; both components excreted in rat milk.

Cost

Lumacaftor (ORKAMBI WITH IVACAFTOR)

Strength		#/mo	CostPlus
125/100 mg	tab	60 BID	not offered
125/200 mg	tab	60 BID	not offered
94/75 mg/packet	granules	per unit	not offered
125/100 mg/packet	granules	per unit	not offered
188/150 mg/packet	granules	per unit	not offered

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

NO BOXED WARNINGS

Principal riskstrong CYP3A induction causing major drug interactions and contraceptive failure

Classes and tags

Clinical profile

Direct muscarinic antagonism0 / 4

Embryofetal risk1 / 4

Legacy pregnancy categoryB

Defining liabilityDrug induction, hepatic and respiratory adverse effects

Open Lumacaftor in the interactive console ↗