Drug · FAERS side-effect profile with label screen
Theophylline side effects: what 11,427 FDA adverse event reports show
Drug class
Not stated in label
Who reports
11,427 reports · 82% serious · 1,658 with death outcome · 60% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Theophylline extended-release tablets are indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.
FDA label, Indications and Usage
What it is
DESCRIPTION Theophylline, USP is structurally classified as a methylxanthine. It occurs as a white, odorless, crystalline powder with a bitter taste. Anhydrous theophylline has the chemical na.
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
Likely indication confounding 7Reporting / coding artifact 7Lab value / disease marker 2Not in label — unassessed 24
What the badges mean
- 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. 1,089 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 |
|---|---|---|---|---|---|---|
| Amyloid arthropathy | 59 | 21,356.3 8,572.9–53,201.6ROR 21,467.2 · χ² 96,768 / p <1e-300 | 1,079.5 EB05 867.5 · IC025 +6.4 3/3 methods agree | Not in label — unassessed | serious n=59 · ♀ 100% (drug 60%) | not reported in cached trials |
| Right atrial hypertrophy | 79 | 4,612.2 3,045.7–6,984.5ROR 4,644.3 · χ² 101,345 / p <1e-300 | 986.9 EB05 817.4 · IC025 +6.8 3/3 methods agree | Not in label — unassessed | serious n=79 · ♀ 0% (drug 60%) | not reported in cached trials |
| Antasthmatic drug level above therapeutic | 16 | 3,619.7 1,549.4–8,456.2ROR 3,624.8 · χ² 18,106 / p <1e-300 | 492.6 EB05 321.5 · IC025 +4.2 3/3 methods agree | Lab value / disease marker | serious n=16 | not reported in cached trials |
| Heart sounds | 59 | 2,886.0 1,914.1–4,351.3ROR 2,901.0 · χ² 64,473 / p <1e-300 | 816.0 EB05 655.7 · IC025 +6.3 3/3 methods agree | Not in label — unassessed | serious n=59 · ♀ 100% (drug 60%) | not reported in cached trials |
| Decreased bronchial secretion | 14 | 1,055.8 546.3–2,040.4ROR 1,057.0 · χ² 8,663 / p <1e-300 | 348.7 EB05 220.8 · IC025 +3.9 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=14 | not reported in cached trials |
| Antacid therapy | 43 | 1,024.0 704.8–1,487.8ROR 1,027.9 · χ² 27,417 / p <1e-300 | 506.2 EB05 391.5 · IC025 +5.8 3/3 methods agree | Reporting / coding artifact | serious n=43 · 100% clinician | not reported in cached trials |
| Occupational asthma | 19 | 881.7 509.7–1,525.3ROR 883.2 · χ² 10,655 / p <1e-300 | 371.1 EB05 251.1 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Bronchial neoplasm | 40 | 762.0 526.9–1,102.1ROR 764.7 · χ² 20,862 / p <1e-300 | 426.6 EB05 326.8 · IC025 +5.6 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=40 · ♀ 100% (drug 60%) | not reported in cached trials |
| Sleep disorder therapy | 51 | 694.0 502.8–957.9ROR 697.1 · χ² 25,012 / p <1e-300 | 422.1 EB05 333.6 · IC025 +6.0 3/3 methods agree | Reporting / coding artifact | serious n=51 · ♀ 14% (drug 60%) · 100% clinician | not reported in cached trials |
| Rhinitis perennial | 22 | 686.5 420.4–1,121.1ROR 687.8 · χ² 10,426 / p <1e-300 | 347.3 EB05 241.8 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=22 | not reported in cached trials |
| Product administration issue | 18 | 552.2 325.8–935.7ROR 553.0 · χ² 7,171 / p <1e-300 | 292.0 EB05 195.4 · IC025 +4.3 3/3 methods agree | Reporting / coding artifact | serious n=18 | not reported in cached trials |
| Prolonged expiration | 60 | 540.3 405.2–720.4ROR 543.1 · χ² 24,458 / p <1e-300 | 367.4 EB05 295.8 · IC025 +6.1 3/3 methods agree | Not in label — unassessed | serious n=60 · ♀ 100% (drug 60%) | not reported in cached trials |
| Analgesic therapy | 59 | 437.6 329.5–581.2ROR 439.9 · χ² 20,348 / p <1e-300 | 316.4 EB05 254.3 · IC025 +6.0 3/3 methods agree | Reporting / coding artifact | serious n=59 · ♀ 31% (drug 60%) · 97% clinician | not reported in cached trials |
| Appendicolith | 66 | 386.6 296.5–503.9ROR 388.8 · χ² 20,598 / p <1e-300 | 291.8 EB05 237.3 · IC025 +6.1 3/3 methods agree | Not in label — unassessed | serious n=66 · ♀ 28% (drug 60%) · 100% clinician | not reported in cached trials |
| Drug therapy | 55 | 381.4 285.3–509.8ROR 383.2 · χ² 16,922 / p <1e-300 | 284.1 EB05 226.5 · IC025 +5.9 3/3 methods agree | Reporting / coding artifact | serious n=55 · ♀ 32% (drug 60%) · 100% clinician | not reported in cached trials |
| Anticoagulant therapy | 40 | 309.4 221.3–432.4ROR 310.5 · χ² 10,239 / p <1e-300 | 234.8 EB05 179.8 · IC025 +5.4 3/3 methods agree | Reporting / coding artifact | serious n=40 · 100% clinician | not reported in cached trials |
| Bronchial haemorrhage | 43 | 290.4 210.6–400.5ROR 291.5 · χ² 10,438 / p <1e-300 | 225.4 EB05 174.3 · IC025 +5.5 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=43 · ♀ 100% (drug 60%) | not reported in cached trials |
| Adulterated product | 26 | 286.9 189.8–433.8ROR 287.6 · χ² 6,150 / p <1e-300 | 209.8 EB05 150.4 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious n=26 · ♀ 0% (drug 60%) · 100% clinician | not reported in cached trials |
| Nasal oedema | 233 | 274.4 239.3–314.5ROR 280.1 · χ² 54,875 / p <1e-300 | 233.8 EB05 209.7 · IC025 +7.1 3/3 methods agree | Not in label — unassessed | serious n=233 · ♀ 100% (drug 60%) · 94% clinician | not reported in cached trials |
| Bronchial wall thickening | 89 | 256.9 205.9–320.5ROR 258.9 · χ² 19,644 / p <1e-300 | 214.8 EB05 179.8 · IC025 +6.3 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=89 · ♀ 7% (drug 60%) | not reported in cached trials |
| Endometrial ablation | 39 | 227.0 162.8–316.5ROR 227.7 · χ² 7,597 / p <1e-300 | 183.7 EB05 140.2 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious n=39 · ♀ 100% (drug 60%) | not reported in cached trials |
| Nasal turbinate hypertrophy | 41 | 224.9 162.6–310.9ROR 225.7 · χ² 7,930 / p <1e-300 | 183.2 EB05 140.8 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious n=41 · ♀ 100% (drug 60%) | not reported in cached trials |
| Vital capacity decreased | 43 | 193.6 141.4–265.0ROR 194.3 · χ² 7,270 / p <1e-300 | 162.5 EB05 125.7 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious n=43 | not reported in cached trials |
| Airway peak pressure increased | 14 | 186.3 107.5–322.9ROR 186.5 · χ² 2,174 / p <1e-300 | 137.7 EB05 87.2 · IC025 +3.7 3/3 methods agree | Lab value / disease marker | serious n=14 | not reported in cached trials |
| Intubation | 22 | 175.4 113.3–271.6ROR 175.7 · χ² 3,321 / p <1e-300 | 140.7 EB05 97.9 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=22 | not reported in cached trials |
| Right ventricular hypertrophy | 79 | 174.4 138.5–219.5ROR 175.6 · χ² 12,263 / p <1e-300 | 153.3 EB05 127.0 · IC025 +5.9 3/3 methods agree | Not in label — unassessed | serious n=79 · ♀ 0% (drug 60%) | not reported in cached trials |
| Reversible airways obstruction | 40 | 154.7 112.1–213.5ROR 155.2 · χ² 5,486 / p <1e-300 | 133.6 EB05 102.3 · IC025 +5.2 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=40 · ♀ 0% (drug 60%) · 78% consumer | not reported in cached trials |
| Oligoarthritis | 14 | 141.6 82.2–243.8ROR 141.7 · χ² 1,684 / p <1e-300 | 111.8 EB05 70.7 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Bronchial secretion retention | 88 | 137.3 110.6–170.4ROR 138.4 · χ² 10,942 / p <1e-300 | 124.3 EB05 104.0 · IC025 +5.9 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=88 · ♀ 7% (drug 60%) | not reported in cached trials |
| Chronic obstructive airways disease exacerbated | 24 | 134.9 89.1–204.1ROR 135.2 · χ² 2,845 / p <1e-300 | 114.4 EB05 80.9 · IC025 +4.5 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=24 · 100% clinician | not reported in cached trials |
| Malignant melanoma stage 0 | 12 | 130.0 72.4–233.6ROR 130.2 · χ² 1,316 / p 2e-288 | 102.1 EB05 62.3 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Congenital hiatus hernia | 14 | 123.6 71.9–212.3ROR 123.8 · χ² 1,481 / p <1e-300 | 100.3 EB05 63.5 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Status asthmaticus | 30 | 122.8 84.9–177.7ROR 123.2 · χ² 3,282 / p <1e-300 | 107.4 EB05 78.9 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=29 | not reported in cached trials |
| Breast conserving surgery | 28 | 106.2 72.6–155.5ROR 106.5 · χ² 2,659 / p <1e-300 | 94.1 EB05 68.3 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=28 · ♀ 100% (drug 60%) | not reported in cached trials |
| Nikolsky's sign | 10 | 105.8 56.0–200.2ROR 105.9 · χ² 885 / p 1e-194 | 84.4 EB05 49.0 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Trisomy 18 | 20 | 100.8 64.3–158.1ROR 101.0 · χ² 1,779 / p <1e-300 | 87.8 EB05 60.0 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=20 | not reported in cached trials |
| Pulmonary function test abnormal | 81 | 100.3 80.3–125.4ROR 101.1 · χ² 7,455 / p <1e-300 | 93.1 EB05 77.3 · IC025 +5.5 3/3 methods agree | Reporting / coding artifact | serious n=81 · ♀ 0% (drug 60%) | not reported in cached trials |
| Aortic valve stenosis | 89 | 96.1 77.7–118.8ROR 96.8 · χ² 7,860 / p <1e-300 | 89.6 EB05 75.0 · IC025 +5.6 3/3 methods agree | Not in label — unassessed | serious n=89 · ♀ 10% (drug 60%) | not reported in cached trials |
| Rhonchi | 64 | 88.8 69.2–114.1ROR 89.3 · χ² 5,215 / p <1e-300 | 82.7 EB05 67.0 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious n=63 | not reported in cached trials |
| Oesophageal dilatation | 19 | 83.5 52.7–132.2ROR 83.6 · χ² 1,402 / p <1e-300 | 74.1 EB05 50.1 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Theophylline as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (0 of 40 signal terms matched).
- NCT01794780 — A 1-year Multi-center, Prospective, Cohort Study in Patients With Chronic Obstructive Pulmonary Disease Treate (N=2229, PHASE4; 45 AE terms posted; arms: Indacaterol; Tiotropium; Salemeterol/Fluticasone; Budesonide/Formoterol)
- NCT02261727 — Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study (N=1670, PHASE4; 3 AE terms posted; arms: Placebo; Low-dose Theophylline Arm; Theophylline and Prednisone Arm)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
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 |
|---|---|---|---|---|---|---|
| Dyspnoea (shortness of breath) | 2,303 | 7.5 7.2–7.8ROR 9.1 · χ² 13,269 / p <1e-300 | 7.5 EB05 7.2 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 6.5 | not reported in cached trials |
| Asthma | 1,988 | 33.1 31.8–34.5ROR 39.9 · χ² 61,110 / p <1e-300 | 32.5 EB05 31.4 · IC025 +4.9 3/3 methods agree | Likely indication confounding term in indications | serious PRR 31.0 | not reported in cached trials |
| Pneumonia (lung infection) | 1,388 | 7.9 7.5–8.3ROR 8.9 · χ² 8,466 / p <1e-300 | 7.9 EB05 7.5 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 5.7 | NCT01794780: 2/276 (0.7%) on Theophylline (serious AE) |
| Wheezing | 1,362 | 43.2 41.1–45.5ROR 48.9 · χ² 54,990 / p <1e-300 | 42.2 EB05 40.4 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious PRR 39.8 | not reported in cached trials |
| Vomiting | 1,180 | 4.6 4.4–4.9ROR 5.0 · χ² 3,420 / p <1e-300 | 4.6 EB05 4.4 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.7 · ♀ 85% (drug 60%) | not reported in cached trials |
| Cough | 1,065 | 7.0 6.6–7.4ROR 7.6 · χ² 5,532 / p <1e-300 | 7.0 EB05 6.6 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 8.1 | not reported in cached trials |
| Drug hypersensitivity | 925 | 8.8 8.3–9.3ROR 9.5 · χ² 6,395 / p <1e-300 | 8.7 EB05 8.3 · IC025 +3.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 15.3 · ♀ 92% (drug 60%) | not reported in cached trials |
| Malaise (feeling unwell) | 780 | 3.3 3.0–3.5ROR 3.4 · χ² 1,244 / p 9e-273 | 3.3 EB05 3.1 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 3.6 · ♀ 87% (drug 60%) | not reported in cached trials |
| Oedema | 759 | 26.1 24.3–28.0ROR 27.9 · χ² 18,071 / p <1e-300 | 25.7 EB05 24.2 · IC025 +4.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 22.5 · ♀ 96% (drug 60%) | not reported in cached trials |
| Drug ineffective (drug did not work) | 756 | 1.1 1.0–1.1ROR 1.1 · χ² 2 / p 0.071 | 1.1 EB05 1.0 · IC025 -0.0 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.4 | not reported in cached trials |
| Pain | 738 | 2.2 2.1–2.4ROR 2.3 · χ² 497 / p 2e-110 | 2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.3 · ♀ 85% (drug 60%) | not reported in cached trials |
| Chest pain | 664 | 6.6 6.1–7.1ROR 6.9 · χ² 3,157 / p <1e-300 | 6.5 EB05 6.1 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 5.9 · ♀ 86% (drug 60%) | not reported in cached trials |
| Chronic obstructive pulmonary disease | 626 | 22.3 20.6–24.1ROR 23.5 · χ² 12,586 / p <1e-300 | 22.0 EB05 20.6 · IC025 +4.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 17.5 | not reported in cached trials |
| Nausea | 624 | 1.5 1.3–1.6ROR 1.5 · χ² 91 / p 9e-22 | 1.5 EB05 1.4 · IC025 +0.4 | Labeled adverse reaction exact term | serious PRR 1.6 | not reported in cached trials |
| Dizziness | 466 | 1.7 1.6–1.9ROR 1.7 · χ² 142 / p 4e-33 | 1.7 EB05 1.6 · IC025 +0.6 | Not in label — unassessed | serious PRR 1.7 | not reported in cached trials |
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.
- Amyloid arthropathy — n=59, PRR 21,356.3
- Right atrial hypertrophy — n=79, PRR 4,612.2
- Heart sounds — n=59, PRR 2,886.0
- Rhinitis perennial — n=22, PRR 686.5
- Prolonged expiration — n=60, PRR 540.3
- Appendicolith — n=66, PRR 386.6
- Adulterated product — n=26, PRR 286.9
- Nasal oedema — n=233, PRR 274.4
- Endometrial ablation — n=39, PRR 227.0
- Nasal turbinate hypertrophy — n=41, PRR 224.9
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 Theophylline?
In FDA FAERS, the most frequently co-reported reaction terms for Theophylline are dyspnoea, asthma, pneumonia, wheezing, vomiting, cough. 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 Theophylline have an FDA boxed warning?
No. The FDA label retrieved for Theophylline has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Theophylline 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 25eabefa-518b-4030-9b72-01ac8b3deba9, effective 20220401; matched on
openfda.generic_name.exact:"THEOPHYLLINE") - 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, 1,129 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 - ClinicalTrials.gov API v2 (query
THEOPHYLLINE, results-bearing studies sorted by enrollment)
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.