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)
Principal riskstrong CYP3A induction causing major drug interactions and contraceptive failure
Classes and tags
Clinical profile
Legacy pregnancy categoryB
Defining liabilityDrug induction, hepatic and respiratory adverse effects
FDA label
Read the full label on DailyMed ↗
NO BOXED WARNINGS
| 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
| Strength | #/mo | generic $ | 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 |
Open Lumacaftor in the interactive console ↗
Self-check
- Which CF genotype is eligible for lumacaftor with ivacaftor?
Homozygous F508del. - Why can lumacaftor make hormonal contraception unreliable?
Strong CYP3A induction.