Elexacaftor and Tezacaftor and Ivacaftor side effects: what 12,353 FDA adverse event reports show
Drug class
Combination of ivacaftor, a cftr potentiator, tezacaftor, and elexacaftor
Label matched
Elexacaftor, Tezacaftor, And Ivacaftor (Trikafta)
Who reports
12,353 reports · 42% serious · 241 with death outcome · 58% female
Used for
TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in adult and pediatric patients aged 2 years and older who have a clinical diagnosis of CF and who have at least one variant in the cystic fibrosis transmembrane conductance regulator ( CF.
What it is
TRIKAFTA is a co-package of elexacaftor, tezacaftor and ivacaftor fixed-dose combination tablets or granules and ivacaftor tablets or granules. Both tablets and granules are for oral administration.
Boxed warning
DRUG-INDUCED LIVER INJURY AND LIVER FAILURE TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Cases of liver failure leading to transplantation and death have been reported in patients with and without a history of liver disease taking TRIKAFTA, in both clinical trials and the postmarketing setting [see Adverse Reactions (6) ].
Causality screen of the 40 strongest signals
What the badges mean
- 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. 958 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Cystic fibrosis related diabetes | 60 | 1,205.7 865.4–1,679.9ROR 1,211.6 · χ² 41,223 / p <1e-300 | 571.8 EB05 460.3 · IC025 +6.3 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=30 | no trial data cached |
| Adverse event following immunisation | 17 | 746.2 421.3–1,321.6ROR 747.2 · χ² 8,233 / p <1e-300 | 326.3 EB05 215.7 · IC025 +4.2 3/3 methods agree | Labeled (related wording) related wording | serious n=11 | no trial data cached |
| Sweat test abnormal | 16 | 567.8 322.1–1,001.0ROR 568.5 · χ² 6,337 / p <1e-300 | 281.4 EB05 183.6 · IC025 +4.1 3/3 methods agree | Reporting / coding artifact | serious n=4 | no trial data cached |
| Vitamin a increased | 11 | 470.4 241.0–918.3ROR 470.9 · χ² 3,661 / p <1e-300 | 224.5 EB05 133.8 · IC025 +3.4 3/3 methods agree | Lab value / disease marker | serious n=7 | no trial data cached |
| Distal intestinal obstruction syndrome | 51 | 298.5 221.7–401.9ROR 299.7 · χ² 12,574 / p <1e-300 | 231.4 EB05 182.8 · IC025 +5.7 3/3 methods agree | Not in label — unassessed | serious n=42 | no trial data cached |
| Infective pulmonary exacerbation of cystic fibrosis | 812 | 294.4 273.8–316.5ROR 314.9 · χ² 201,588 / p <1e-300 | 248.9 EB05 234.8 · IC025 +7.6 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=624 | no trial data cached |
| Cystic fibrosis respiratory infection suppression | 119 | 258.1 213.0–312.8ROR 260.6 · χ² 26,171 / p <1e-300 | 215.9 EB05 185.3 · IC025 +6.6 3/3 methods agree | Labeled (related wording) related wording | serious n=118 · 84% consumer | no trial data cached |
| Cystic fibrosis | 502 | 167.8 153.4–183.6ROR 174.9 · χ² 75,506 / p <1e-300 | 151.7 EB05 140.9 · IC025 +6.9 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=478 · 83% consumer | no trial data cached |
| Pulmonary function test decreased | 216 | 87.3 76.2–100.0ROR 88.8 · χ² 17,431 / p <1e-300 | 82.4 EB05 73.6 · IC025 +5.9 3/3 methods agree | Not in label — unassessed | serious n=119 | no trial data cached |
| Increased viscosity of bronchial secretion | 30 | 84.2 58.4–121.5ROR 84.4 · χ² 2,270 / p <1e-300 | 76.5 EB05 56.1 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial data cached |
| Body dysmorphic disorder | 17 | 81.0 49.8–131.8ROR 81.1 · χ² 1,206 / p 2e-264 | 71.4 EB05 47.2 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=7 | no trial data cached |
| Sputum increased | 92 | 76.9 62.4–94.7ROR 77.4 · χ² 6,515 / p <1e-300 | 72.5 EB05 60.9 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious n=15 | no trial data cached |
| Defiant behaviour | 12 | 69.5 39.0–123.8ROR 69.6 · χ² 713 / p 2e-157 | 60.6 EB05 37.0 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=5 | no trial data cached |
| Pseudomonas test positive | 25 | 52.8 35.5–78.7ROR 53.0 · χ² 1,183 / p 2e-259 | 49.4 EB05 35.2 · IC025 +4.0 3/3 methods agree | Lab value / disease marker | serious n=10 | no trial data cached |
| Lung transplant rejection | 15 | 39.0 23.4–65.0ROR 39.0 · χ² 506 / p 3e-112 | 36.5 EB05 23.5 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=15 | no trial data cached |
| Morning sickness | 12 | 38.3 21.6–67.9ROR 38.4 · χ² 391 / p 3e-87 | 35.6 EB05 21.7 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=2 | no trial data cached |
| Paranasal sinus hypersecretion | 75 | 33.6 26.8–42.2ROR 33.8 · χ² 2,297 / p <1e-300 | 32.7 EB05 27.0 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=10 | no trial data cached |
| Hordeolum | 77 | 31.5 25.1–39.4ROR 31.7 · χ² 2,201 / p <1e-300 | 30.7 EB05 25.4 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=27 · ♀ 81% (drug 58%) | no trial data cached |
| Pancreatic failure | 31 | 31.2 21.9–44.5ROR 31.3 · χ² 861 / p 2e-189 | 30.2 EB05 22.3 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=15 | no trial data cached |
| Attention deficit hyperactivity disorder | 75 | 31.1 –ROR 31.3 · χ² – | – | Not in label — unassessed | serious n=28 | no trial data cached |
| Behaviour disorder | 91 | 29.5 24.0–36.3ROR 29.7 · χ² 2,434 / p <1e-300 | 28.8 EB05 24.2 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=25 | no trial data cached |
| Bronchial secretion retention | 21 | 28.5 18.6–43.9ROR 28.6 · χ² 522 / p 7e-116 | 27.5 EB05 18.9 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=14 | no trial data cached |
| Intensive care | 23 | 28.3 18.8–42.8ROR 28.4 · χ² 570 / p 3e-126 | 27.3 EB05 19.2 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=23 | no trial data cached |
| Weight gain poor | 38 | 28.2 20.5–38.9ROR 28.3 · χ² 955 / p 5e-210 | 27.4 EB05 20.9 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=11 · 76% consumer | no trial data cached |
| Mycobacterium abscessus infection | 11 | 26.8 14.8–48.6ROR 26.8 · χ² 244 / p 3e-55 | 25.2 EB05 14.8 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious n=6 | no trial data cached |
| Increased bronchial secretion | 39 | 26.1 19.0–35.8ROR 26.2 · χ² 902 / p 2e-198 | 25.4 EB05 19.4 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=8 | no trial data cached |
| Brain fog | 213 | 25.0 21.9–28.6ROR 25.5 · χ² 4,824 / p <1e-300 | 24.6 EB05 22.0 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 16.0 | no trial data cached |
| Sinus operation | 34 | 24.5 17.5–34.4ROR 24.6 · χ² 733 / p 9e-162 | 23.9 EB05 17.9 · IC025 +3.6 3/3 methods agree | Reporting / coding artifact | serious n=32 | no trial data cached |
| Bronchopulmonary aspergillosis allergic | 13 | 24.3 14.1–42.0ROR 24.3 · χ² 264 / p 1e-59 | 23.1 EB05 14.2 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=9 | no trial data cached |
| Blood bilirubin unconjugated increased | 10 | 24.0 12.9–44.9ROR 24.1 · χ² 195 / p 1e-44 | 22.5 EB05 12.6 · IC025 +2.4 3/3 methods agree | Lab value / disease marker | serious n=3 | no trial data cached |
| Pneumonia pseudomonal | 21 | 23.7 15.4–36.4ROR 23.7 · χ² 428 / p 3e-95 | 22.9 EB05 15.8 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=14 | no trial data cached |
| Forced expiratory volume decreased | 38 | 22.9 16.7–31.6ROR 23.0 · χ² 765 / p 9e-169 | 22.4 EB05 17.0 · IC025 +3.6 3/3 methods agree | Lab value / disease marker | serious n=23 | no trial data cached |
| Testicular pain | 42 | 22.7 16.8–30.8ROR 22.8 · χ² 839 / p 9e-185 | 22.2 EB05 17.1 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=8 · ♀ 0% (drug 58%) | no trial data cached |
| Nasal inflammation | 14 | 22.7 13.4–38.5ROR 22.7 · χ² 266 / p 5e-60 | 21.7 EB05 13.5 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial data cached |
| Steatorrhoea | 34 | 21.7 15.5–30.5ROR 21.8 · χ² 644 / p 2e-142 | 21.2 EB05 15.9 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial data cached |
| Lung transplant | 45 | 21.6 16.1–29.0ROR 21.7 · χ² 853 / p 8e-188 | 21.2 EB05 16.5 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=45 | no trial data cached |
| Sputum retention | 12 | 21.0 11.9–37.1ROR 21.0 · χ² 206 / p 4e-47 | 19.9 EB05 11.6 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious n=5 | no trial data cached |
| Pseudomonas infection | 97 | 19.6 16.1–23.9ROR 19.7 · χ² 1,674 / p <1e-300 | 19.3 EB05 16.3 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious PRR 20.9 · 70% consumer | no trial data cached |
| Productive cough (cough with phlegm) | 535 | 19.3 17.8–21.0ROR 20.1 · χ² 9,192 / p <1e-300 | 19.1 EB05 17.8 · IC025 +4.1 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 6.1 | no trial data cached |
| Emergency care | 33 | 19.0 13.5–26.7ROR 19.0 · χ² 538 / p 3e-119 | 18.6 EB05 13.8 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=8 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
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 | 812 | 294.4 273.8–316.5ROR 314.9 · χ² 201,588 / p <1e-300 | 248.9 EB05 234.8 · IC025 +7.6 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=624 | no trial data cached |
| Headache | 767 | 2.1 1.9–2.2ROR 2.1 · χ² 437 / p 2e-97 | 2.1 EB05 2.0 · IC025 +0.9 | Labeled adverse reaction exact term | serious PRR 1.0 | no trial data cached |
| Anxiety | 614 | 3.6 3.4–3.9ROR 3.8 · χ² 1,190 / p 5e-261 | 3.6 EB05 3.4 · IC025 +1.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.5 | no trial data cached |
| Cough | 594 | 3.6 3.3–3.9ROR 3.7 · χ² 1,123 / p 2e-246 | 3.6 EB05 3.3 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 2.2 | no trial data cached |
| Rash | 569 | 2.2 2.0–2.4ROR 2.3 · χ² 388 / p 1e-86 | 2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.0 | no trial data cached |
| Fatigue (tiredness) | 537 | 1.2 1.1–1.3ROR 1.2 · χ² 13 / p 1e-4 | 1.2 EB05 1.1 · IC025 +0.1 | Not in label — unassessed | serious PRR 0.9 | no trial data cached |
| Productive cough (cough with phlegm) | 535 | 19.3 17.8–21.0ROR 20.1 · χ² 9,192 / p <1e-300 | 19.1 EB05 17.8 · IC025 +4.1 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 6.1 | no trial data cached |
| Weight increased (weight gain) | 511 | 3.9 3.6–4.2ROR 4.0 · χ² 1,101 / p 8e-242 | 3.9 EB05 3.6 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 1.7 | no trial data cached |
| Cystic fibrosis | 502 | 167.8 153.4–183.6ROR 174.9 · χ² 75,506 / p <1e-300 | 151.7 EB05 140.9 · IC025 +6.9 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=478 · 83% consumer | no trial data cached |
| Abdominal pain upper | 474 | 3.9 3.6–4.3ROR 4.0 · χ² 1,031 / p 2e-226 | 3.9 EB05 3.6 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.5 | no trial data cached |
| Depression | 451 | 3.3 3.1–3.7ROR 3.4 · χ² 745 / p 3e-164 | 3.3 EB05 3.1 · IC025 +1.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.7 | no trial data cached |
| Hospitalisation | 432 | 4.8 4.4–5.3ROR 4.9 · χ² 1,304 / p 8e-286 | 4.8 EB05 4.4 · IC025 +2.1 3/3 methods agree | Reporting / coding artifact | serious PRR 6.7 | no trial data cached |
| Pneumonia (lung infection) | 393 | 2.1 1.9–2.3ROR 2.1 · χ² 216 / p 4e-49 | 2.1 EB05 1.9 · IC025 +0.9 | Labeled (related wording) related wording | serious PRR 2.5 | no trial data cached |
| Diarrhoea (diarrhea) | 385 | 1.0 0.9–1.1ROR 1.0 · χ² 0 / p 0.414 | 1.0 EB05 0.9 · IC025 -0.2 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 0.6 | no trial data cached |
| Mental disorder | 350 | 13.7 12.3–15.2ROR 14.0 · χ² 4,076 / p <1e-300 | 13.6 EB05 12.4 · IC025 +3.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 7.1 | 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.
- Distal intestinal obstruction syndrome — n=51, PRR 298.5
- Pulmonary function test decreased — n=216, PRR 87.3
- Increased viscosity of bronchial secretion — n=30, PRR 84.2
- Sputum increased — n=92, PRR 76.9
- Paranasal sinus hypersecretion — n=75, PRR 33.6
- Hordeolum — n=77, PRR 31.5
- Pancreatic failure — n=31, PRR 31.2
- Attention deficit hyperactivity disorder — n=75, PRR 31.1
- Behaviour disorder — n=91, PRR 29.5
- Bronchial secretion retention — n=21, PRR 28.5
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 Elexacaftor and Tezacaftor and Ivacaftor?
In FDA FAERS, the most frequently co-reported reaction terms for Elexacaftor and Tezacaftor and Ivacaftor are infective pulmonary exacerbation of cystic fibrosis, headache, anxiety, cough, rash, fatigue. 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 Elexacaftor and Tezacaftor and Ivacaftor have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Cases of liver failure leading to transplantation and death have been reported in patients with and without a history of liver disease taking TRIKAFTA, in both clinical trials and the postmarketing setting [see Adverse Reactions (6) ].
Do FAERS signals prove that Elexacaftor and Tezacaftor 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 f354423a-85c2-41c3-a9db-0f3aee135d8d, effective 20260622; matched on
openfda.generic_name.exact:"ELEXACAFTOR, TEZACAFTOR, 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, 998 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.