What the label lists and what reports show
Ivacaftor and lumacaftor side effects
Ivacaftor and lumacaftor's FDA label: “The most common adverse reactions to ORKAMBI (occurring in ≥5% of patients with CF homozygous for the F508del mutation in the CFTR gene) were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood …” FAERS holds 8,520 reports naming it through July 30, 2026; the reaction reported most often, leaving out the conditions it is used for, product-use terms and outcomes, is infective pulmonary exacerbation of cystic fibrosis (1,462 reports).
- No generic listed
Check it at the source: the ivacaftor and lumacaftor FDA label on DailyMed (effective March 24, 2026, Vertex Pharmaceuticals Incorporated); the FDA FAERS public dashboard.
What does the patient leaflet say about side effects?
From the patient leaflet: What are the possible side effects of ORKAMBI?ORKAMBI can cause serious side effects, including: Worsening of liver function in people with severe liver disease. The worsening of liver function can be serious or cause death. Talk to your doctor if you have been told you have liver disease as your doctor may need to adjust the dose of ORKAMBI. High liver enzymes in the blood, which can be a sign of liver injury in people receiving ORKAMBI. […]
Source: FDA drug label, Vertex Pharmaceuticals Incorporated, effective March 24, 2026 (SPL set 3fc1c40e-cfac-47a1-9e1a-61ead3570600), via openFDA; the full label on DailyMed
What does the label list?
From the label: adverse reactionsThe most common adverse reactions to ORKAMBI (occurring in ≥5% of patients with CF homozygous for the F508del mutation in the CFTR gene) were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood creatine phosphokinase increased, rash, flatulence, rhinorrhea, influenza.
Table 3: Incidence of Adverse Drug Reactions in ≥5% of ORKAMBI-Treated Patients Aged 12 Years and Older Who are Homozygous for the F508del Mutation in the CFTR Gene in 2 Placebo-Controlled Phase 3 Clinical Trials of 24…
| Adverse Reaction (Preferred Term) | ORKAMBI N=369 (%) | Placebo N=370 (%) |
|---|---|---|
| Dyspnea | 48 (13) | 29 (8) |
| Nasopharyngitis | 48 (13) | 40 (11) |
| Nausea | 46 (13) | 28 (8) |
| Diarrhea | 45 (12) | 31 (8) |
| Upper respiratory tract infection | 37 (10) | 20 (5) |
| Fatigue | 34 (9) | 29 (8) |
| Respiration abnormal | 32 (9) | 22 (6) |
| Blood creatine phosphokinase increased | 27 (7) | 20 (5) |
| Rash | 25 (7) | 7 (2) |
| Flatulence | 24 (7) | 11 (3) |
| Rhinorrhea | 21 (6) | 15 (4) |
| Influenza | 19 (5) | 8 (2) |
Rows and numbers as the label prints them, under its own column headings (the first rows of a longer table where it runs on). A reaction in a trial table is not necessarily caused by the medicine, and trials differ from everyday use.
From the label: adverse reactions, continuedThe following adverse reactions are discussed in greater detail in other sections of the label: Use in Patients with Advanced Liver Disease [see Warnings and Precautions (5.1) ] Liver-related Events [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.3) ] Intracranial Hypertension [see Warnings and Precautions (5.4) ] Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.5) ] Respiratory Events [see Warnings and Precautions (5.6) ] Effect on Blood Pressure [see Warnings and Precautions (5.7) ] Cataracts [see Warnings and Precautions (5.9) ] The most common adverse reactions to ORKAMBI (occurring in ≥5% of patients with CF homozygous for the F508del mutation in the CFTR gene) were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood creatine phosphokinase increased, rash, flatulence, rhinorrhea, influenza. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vertex Pharmaceuticals Incorporated at 1-877-634-8789 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …
Source: FDA drug label, Vertex Pharmaceuticals Incorporated, effective March 24, 2026 (SPL set 3fc1c40e-cfac-47a1-9e1a-61ead3570600), via openFDA; the full label on DailyMed
What do FAERS reports show?
8,520 reports list ivacaftor and lumacaftor among the medicines taken, each a report of something that happened, not proof the medicine caused it; 158 are coded as a death and 4,457 as a hospital stay. Counts follow how widely a medicine is used and watched, and they are not a measure of how risky it is. Reports rose sharply in 2019 (1,989, against a median of 169 a year): FAERS counts follow reporting, which news, litigation and label changes can drive, not how often a reaction happens. Of the 22 reactions below, 14 are named by the same term (in US spelling) in the label's adverse reactions, warnings or patient leaflet; a reaction the label does not name may still be there under another word, and a report does not show that the medicine caused it.
Reports received each year
The 25 most reported reactions
Source: FDA Adverse Event Reporting System (FAERS) via openFDA, reports through July 30, 2026; reactions as MedDRA preferred terms
What next?
- Ivacaftor and lumacaftor: the full record
- label, generics, price, shortages, recalls
- Report a side effect to the FDA
- MedWatch
- Side effects hub
- the most reported medicines and reactions