Lumacaftor
ORKAMBI with ivacaftor
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.
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.
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.
NO BOXED WARNINGS
Principal riskstrong CYP3A induction causing major drug interactions and contraceptive failure
Classes and tags
Clinical profile
Mechanism of action: Lumacaftor ballicule
