Drug · FAERS side-effect profile with label screen
Lumacaftor and Ivacaftor side effects: what 8,519 FDA adverse event reports show
Drug class
Cystic Fibrosis Transmembrane Conductance Regulator Potentiator
FDA label (Established Pharmacologic Class) · compare the class
Brand names
Orkambi
openFDA label
Who reports
8,519 reports · 63% serious · 158 with death outcome · 52% female
openFDA FAERS counts, all years, deduplication not applied
Used for
ORKAMBI is indicated for the treatment of cystic fibrosis (CF) in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.
FDA label, Indications and Usage
What it is
The active ingredients in ORKAMBI tablets are lumacaftor, which has the following chemical name: 3-[6-({[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl}amino)-3-methylpyridin-2-yl]b.
FDA label, Description section
Boxed warning
None in the current label
How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation.
Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)?
That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.
Causality screen of the 40 strongest signals
Labeled adverse reaction 5Labeled (related wording) 6Likely indication confounding 4Reporting / coding artifact 3Lab value / disease marker 4Not in label — unassessed 18
What the badges mean
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 548 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
Show:
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Infective pulmonary exacerbation of cystic fibrosis | 1,462 | 898.3 849.3–950.2ROR 1,084.2 · χ² 956,101 / p <1e-300 | 650.4 EB05 622.8 · IC025 +9.0 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=1,282 | no trial data cached |
| Cystic fibrosis lung | 24 | 554.9 356.3–864.2ROR 556.5 · χ² 10,355 / p <1e-300 | 332.1 EB05 234.9 · IC025 +4.8 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=23 | no trial data cached |
| Cystic fibrosis respiratory infection suppression | 162 | 541.7 457.5–641.5ROR 552.2 · χ² 71,046 / p <1e-300 | 421.0 EB05 369.3 · IC025 +7.3 3/3 methods agree | Labeled (related wording) related wording | serious n=161 | no trial data cached |
| Pulmonary function test decreased | 397 | 244.2 220.8–270.2ROR 256.1 · χ² 87,180 / p <1e-300 | 219.7 EB05 202.1 · IC025 +7.3 3/3 methods agree | Not in label — unassessed | serious n=309 | no trial data cached |
| Cystic fibrosis related diabetes | 10 | 182.5 96.0–347.0ROR 182.7 · χ² 1,515 / p <1e-300 | 128.8 EB05 74.8 · IC025 +3.2 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=9 | no trial data cached |
| Distal intestinal obstruction syndrome | 23 | 178.4 116.9–272.3ROR 178.9 · χ² 3,616 / p <1e-300 | 146.3 EB05 102.7 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=20 | no trial data cached |
| Cystic fibrosis | 327 | 153.7 137.8–171.6ROR 159.8 · χ² 46,532 / p <1e-300 | 143.4 EB05 130.9 · IC025 +6.7 3/3 methods agree | Likely indication confounding term in indications | serious n=303 | no trial data cached |
| Forced expiratory volume decreased | 120 | 108.7 90.6–130.4ROR 110.2 · χ² 12,155 / p <1e-300 | 102.4 EB05 87.9 · IC025 +5.9 3/3 methods agree | Lab value / disease marker | serious n=88 | no trial data cached |
| Infective exacerbation of bronchiectasis | 12 | 104.8 58.8–186.7ROR 104.9 · χ² 1,085 / p 3e-238 | 87.0 EB05 53.0 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial data cached |
| Respiratory symptom | 82 | 74.2 59.6–92.3ROR 74.9 · χ² 5,676 / p <1e-300 | 70.9 EB05 58.9 · IC025 +5.3 3/3 methods agree | Labeled adverse reaction exact term | serious n=77 · 91% clinician | no trial data cached |
| Respiration abnormal | 191 | 70.8 61.4–81.6ROR 72.4 · χ² 12,700 / p <1e-300 | 68.3 EB05 60.6 · IC025 +5.6 3/3 methods agree | Labeled adverse reaction exact term | serious n=107 | no trial data cached |
| Pseudomonas test positive | 22 | 67.4 44.2–103.0ROR 67.6 · χ² 1,337 / p 5e-293 | 62.3 EB05 43.3 · IC025 +4.0 3/3 methods agree | Lab value / disease marker | serious n=9 | no trial data cached |
| Sputum increased | 50 | 59.6 45.0–78.8ROR 59.9 · χ² 2,753 / p <1e-300 | 57.0 EB05 44.9 · IC025 +4.7 3/3 methods agree | Labeled adverse reaction exact term | serious n=36 | no trial data cached |
| Lower respiratory tract infection bacterial | 12 | 58.7 33.1–104.1ROR 58.8 · χ² 610 / p 6e-135 | 52.8 EB05 32.2 · IC025 +3.2 3/3 methods agree | Labeled (related wording) related wording | serious n=10 | no trial data cached |
| Lung infection pseudomonal | 10 | 44.3 23.7–82.8ROR 44.4 · χ² 374 / p 1e-83 | 40.4 EB05 23.5 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=4 | no trial data cached |
| Lung transplant | 63 | 44.3 34.5–56.7ROR 44.6 · χ² 2,574 / p <1e-300 | 43.0 EB05 34.8 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=62 | no trial data cached |
| Bronchopulmonary aspergillosis allergic | 16 | 43.7 26.7–71.6ROR 43.8 · χ² 614 / p 6e-136 | 41.0 EB05 26.8 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=16 | no trial data cached |
| Pulmonary function test abnormal | 24 | 38.4 25.7–57.4ROR 38.5 · χ² 824 / p 2e-181 | 36.8 EB05 26.0 · IC025 +3.7 3/3 methods agree | Reporting / coding artifact | serious n=19 | no trial data cached |
| Bronchial secretion retention | 18 | 35.5 22.3–56.6ROR 35.6 · χ² 562 / p 2e-124 | 33.9 EB05 22.7 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial data cached |
| Sinus operation | 33 | 34.6 24.6–48.8ROR 34.8 · χ² 1,030 / p 3e-226 | 33.6 EB05 25.0 · IC025 +3.9 3/3 methods agree | Reporting / coding artifact | serious n=32 | no trial data cached |
| Pseudomonas infection | 100 | 29.4 24.2–35.8ROR 29.8 · χ² 2,685 / p <1e-300 | 28.9 EB05 24.5 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 18.0 | no trial data cached |
| Increased bronchial secretion | 30 | 29.1 20.3–41.7ROR 29.2 · χ² 777 / p 3e-171 | 28.3 EB05 20.8 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=23 | no trial data cached |
| Weight gain poor | 20 | 21.5 13.8–33.3ROR 21.5 · χ² 367 / p 5e-82 | 20.9 EB05 14.1 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=9 | no trial data cached |
| Pneumonia staphylococcal | 16 | 20.1 12.3–32.9ROR 20.2 · χ² 270 / p 6e-61 | 19.4 EB05 12.4 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=14 | no trial data cached |
| Gastrostomy | 12 | 19.4 11.0–34.1ROR 19.4 · χ² 189 / p 2e-43 | 18.3 EB05 10.5 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial data cached |
| Drug screen false positive | 21 | 18.6 12.1–28.6ROR 18.7 · χ² 330 / p 5e-74 | 18.1 EB05 12.3 · IC025 +3.0 3/3 methods agree | Lab value / disease marker | serious n=3 | no trial data cached |
| Pneumonia pseudomonal | 11 | 17.9 9.9–32.4ROR 18.0 · χ² 158 / p 1e-36 | 16.7 EB05 9.0 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious n=10 | no trial data cached |
| Steatorrhoea | 19 | 17.6 11.2–27.6ROR 17.6 · χ² 279 / p 7e-63 | 17.0 EB05 11.2 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=8 | no trial data cached |
| Staphylococcus test positive | 15 | 17.5 10.5–29.1ROR 17.5 · χ² 215 / p 4e-49 | 16.7 EB05 10.2 · IC025 +2.6 3/3 methods agree | Lab value / disease marker | serious n=10 | no trial data cached |
| Lung infection | 110 | 17.3 14.4–20.8ROR 17.5 · χ² 1,662 / p <1e-300 | 17.1 EB05 14.6 · IC025 +3.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 12.7 | no trial data cached |
| Respiratory tract infection viral | 16 | 17.1 10.5–27.9ROR 17.1 · χ² 225 / p 4e-51 | 16.3 EB05 10.2 · IC025 +2.7 3/3 methods agree | Labeled (related wording) related wording | serious n=9 | no trial data cached |
| Rhinovirus infection | 24 | 15.6 10.5–23.3ROR 15.7 · χ² 312 / p 3e-70 | 15.1 EB05 10.4 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=20 | no trial data cached |
| Hospitalisation | 887 | 14.4 13.5–15.3ROR 16.0 · χ² 11,068 / p <1e-300 | 14.3 EB05 13.5 · IC025 +3.7 3/3 methods agree | Reporting / coding artifact | serious PRR 13.2 | no trial data cached |
| Liver function test increased | 116 | 13.5 11.2–16.1ROR 13.6 · χ² 1,319 / p 4e-289 | 13.3 EB05 11.4 · IC025 +3.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 11.0 | no trial data cached |
| Haemoptysis | 117 | 10.3 8.6–12.4ROR 10.5 · χ² 975 / p 3e-214 | 10.1 EB05 8.7 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.3 | no trial data cached |
| Viral upper respiratory tract infection | 19 | 9.8 6.2–15.4ROR 9.8 · χ² 141 / p 8e-33 | 8.7 EB05 5.6 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | serious n=10 | no trial data cached |
| Bronchiectasis | 24 | 8.9 6.0–13.3ROR 8.9 · χ² 160 / p 6e-37 | 8.0 EB05 5.5 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious n=24 | no trial data cached |
| Emergency care | 10 | 8.3 4.5–15.4ROR 8.3 · χ² 57 / p 2e-14 | 6.5 EB05 3.6 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious n=8 | no trial data cached |
| Chest discomfort | 343 | 8.3 7.5–9.2ROR 8.6 · χ² 2,199 / p <1e-300 | 8.2 EB05 7.5 · IC025 +2.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.0 | no trial data cached |
| Pneumothorax | 53 | 8.3 6.3–10.8ROR 8.3 · χ² 330 / p 5e-74 | 7.8 EB05 6.2 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 7.3 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
Trial cross-check not yet run for this drug (ClinicalTrials.gov pull covers the 800 most-reported drugs first).
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Infective pulmonary exacerbation of cystic fibrosis | 1,462 | 898.3 849.3–950.2ROR 1,084.2 · χ² 956,101 / p <1e-300 | 650.4 EB05 622.8 · IC025 +9.0 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=1,282 | no trial data cached |
| Hospitalisation | 887 | 14.4 13.5–15.3ROR 16.0 · χ² 11,068 / p <1e-300 | 14.3 EB05 13.5 · IC025 +3.7 3/3 methods agree | Reporting / coding artifact | serious PRR 13.2 | no trial data cached |
| Dyspnoea (shortness of breath) | 557 | 2.4 2.2–2.6ROR 2.5 · χ² 478 / p 4e-106 | 2.4 EB05 2.3 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.7 | no trial data cached |
| Pulmonary function test decreased | 397 | 244.2 220.8–270.2ROR 256.1 · χ² 87,180 / p <1e-300 | 219.7 EB05 202.1 · IC025 +7.3 3/3 methods agree | Not in label — unassessed | serious n=309 | no trial data cached |
| Cough | 395 | 3.5 3.2–3.8ROR 3.6 · χ² 703 / p 3e-155 | 3.5 EB05 3.2 · IC025 +1.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.7 | no trial data cached |
| Infection | 370 | 6.3 5.7–7.0ROR 6.6 · χ² 1,662 / p <1e-300 | 6.3 EB05 5.8 · IC025 +2.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.3 | no trial data cached |
| Chest discomfort | 343 | 8.3 7.5–9.2ROR 8.6 · χ² 2,199 / p <1e-300 | 8.2 EB05 7.5 · IC025 +2.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.0 | no trial data cached |
| Cystic fibrosis | 327 | 153.7 137.8–171.6ROR 159.8 · χ² 46,532 / p <1e-300 | 143.4 EB05 130.9 · IC025 +6.7 3/3 methods agree | Likely indication confounding term in indications | serious n=303 | no trial data cached |
| Pneumonia (lung infection) | 269 | 2.0 1.8–2.3ROR 2.1 · χ² 146 / p 8e-34 | 2.0 EB05 1.8 · IC025 +0.8 | Labeled adverse reaction exact term | serious PRR 1.8 | no trial data cached |
| Malaise (feeling unwell) | 224 | 1.3 1.1–1.4ROR 1.3 · χ² 12 / p 3e-4 | 1.3 EB05 1.1 · IC025 +0.1 | Not in label — unassessed | serious PRR 1.1 | no trial data cached |
| Nasopharyngitis (common cold) | 202 | 2.7 2.3–3.1ROR 2.7 · χ² 215 / p 6e-49 | 2.7 EB05 2.4 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.9 | no trial data cached |
| Fatigue (tiredness) | 200 | 0.6 0.6–0.7ROR 0.6 · χ² 44 / p 2e-11 | 0.6 EB05 0.6 · IC025 -0.9 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 0.5 | no trial data cached |
| Diarrhoea (diarrhea) | 194 | 0.7 0.6–0.9ROR 0.7 · χ² 18 / p 1e-5 | 0.7 EB05 0.7 · IC025 -0.7 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 0.5 | no trial data cached |
| Respiration abnormal | 191 | 70.8 61.4–81.6ROR 72.4 · χ² 12,700 / p <1e-300 | 68.3 EB05 60.6 · IC025 +5.6 3/3 methods agree | Labeled adverse reaction exact term | serious n=107 | no trial data cached |
| Pyrexia (fever) | 186 | 1.3 1.1–1.5ROR 1.3 · χ² 15 / p 7e-5 | 1.3 EB05 1.2 · IC025 +0.2 | Not in label — unassessed | serious PRR 1.1 | no trial data cached |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Pulmonary function test decreased — n=397, PRR 244.2
- Distal intestinal obstruction syndrome — n=23, PRR 178.4
- Lung transplant — n=63, PRR 44.3
- Pseudomonas infection — n=100, PRR 29.4
- Increased bronchial secretion — n=30, PRR 29.1
- Weight gain poor — n=20, PRR 21.5
- Rhinovirus infection — n=24, PRR 15.6
- Bronchiectasis — n=24, PRR 8.9
- Pneumothorax — n=53, PRR 8.3
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Lumacaftor and Ivacaftor?
In FDA FAERS, the most frequently co-reported reaction terms for Lumacaftor and Ivacaftor are infective pulmonary exacerbation of cystic fibrosis, dyspnoea, pulmonary function test decreased, cough, infection, chest discomfort. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Lumacaftor and Ivacaftor have an FDA boxed warning?
No. The FDA label retrieved for Lumacaftor and Ivacaftor has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Lumacaftor and Ivacaftor causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 3fc1c40e-cfac-47a1-9e1a-61ead3570600, effective 20260324; matched on
openfda.generic_name.exact:"LUMACAFTOR AND IVACAFTOR") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 588 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.