Drug · FAERS side-effect profile with label screen
Theophylline Anhydrous side effects: what 12,326 FDA adverse event reports show
Drug class
Not stated in label
Who reports
12,326 reports · 82% serious · 1,787 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. 1,116 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 | 19,797.8 7,947.2–49,319.9ROR 19,893.1 · χ² 89,706 / p <1e-300 | 1,027.3 EB05 825.6 · 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 | 88 | 6,711.1 4,207.7–10,704.1ROR 6,759.4 · χ² 116,742 / p <1e-300 | 1,037.4 EB05 867.8 · IC025 +6.9 3/3 methods agree | Not in label — unassessed | serious n=88 · ♀ 0% (drug 60%) | not reported in cached trials |
| Antasthmatic drug level above therapeutic | 17 | 4,074.6 1,690.0–9,823.9ROR 4,080.2 · χ² 19,022 / p <1e-300 | 507.1 EB05 335.3 · IC025 +4.3 3/3 methods agree | Lab value / disease marker | serious n=17 | not reported in cached trials |
| Heart sounds | 61 | 2,924.1 1,930.5–4,429.3ROR 2,938.7 · χ² 63,925 / p <1e-300 | 797.7 EB05 643.4 · IC025 +6.4 3/3 methods agree | Not in label — unassessed | serious n=61 · ♀ 100% (drug 60%) | not reported in cached trials |
| Decreased bronchial secretion | 15 | 1,094.2 571.1–2,096.5ROR 1,095.5 · χ² 9,265 / p <1e-300 | 358.8 EB05 230.8 · IC025 +4.0 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=15 | not reported in cached trials |
| Antacid therapy | 44 | 984.3 678.7–1,427.5ROR 987.8 · χ² 26,624 / p <1e-300 | 488.3 EB05 378.8 · IC025 +5.8 3/3 methods agree | Reporting / coding artifact | serious n=44 · 100% clinician | not reported in cached trials |
| Occupational asthma | 21 | 952.3 557.6–1,626.3ROR 953.9 · χ² 12,130 / p <1e-300 | 390.8 EB05 269.7 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=21 | not reported in cached trials |
| Bronchial neoplasm | 46 | 867.2 607.7–1,237.3ROR 870.4 · χ² 25,669 / p <1e-300 | 461.7 EB05 360.2 · IC025 +5.8 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=46 · ♀ 100% (drug 60%) | not reported in cached trials |
| Rhinitis perennial | 26 | 807.8 506.1–1,289.3ROR 809.5 · χ² 13,603 / p <1e-300 | 389.0 EB05 279.0 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=26 · ♀ 0% (drug 60%) | not reported in cached trials |
| Sleep disorder therapy | 53 | 678.8 493.6–933.5ROR 681.7 · χ² 25,058 / p <1e-300 | 411.5 EB05 326.6 · IC025 +6.0 3/3 methods agree | Reporting / coding artifact | serious n=53 · ♀ 13% (drug 60%) · 100% clinician | not reported in cached trials |
| Prolonged expiration | 62 | 522.7 393.3–694.8ROR 525.4 · χ² 24,220 / p <1e-300 | 355.0 EB05 286.8 · IC025 +6.2 3/3 methods agree | Not in label — unassessed | serious n=62 · ♀ 100% (drug 60%) | not reported in cached trials |
| Product administration issue | 18 | 511.9 302.1–867.4ROR 512.6 · χ² 6,646 / p <1e-300 | 277.0 EB05 185.4 · IC025 +4.3 3/3 methods agree | Reporting / coding artifact | serious n=18 | not reported in cached trials |
| Analgesic therapy | 60 | 414.3 312.5–549.2ROR 416.3 · χ² 19,508 / p <1e-300 | 300.6 EB05 242.0 · IC025 +6.0 3/3 methods agree | Reporting / coding artifact | serious n=60 · ♀ 31% (drug 60%) · 97% clinician | not reported in cached trials |
| Adulterated product | 34 | 365.7 252.4–529.7ROR 366.7 · χ² 9,855 / p <1e-300 | 257.1 EB05 192.4 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious n=34 · ♀ 0% (drug 60%) · 100% clinician | not reported in cached trials |
| Appendicolith | 67 | 365.0 280.4–475.1ROR 367.0 · χ² 19,677 / p <1e-300 | 276.3 EB05 225.1 · IC025 +6.1 3/3 methods agree | Not in label — unassessed | serious n=67 · ♀ 28% (drug 60%) · 100% clinician | not reported in cached trials |
| Drug therapy | 56 | 361.4 270.9–482.1ROR 363.0 · χ² 16,263 / p <1e-300 | 270.1 EB05 215.8 · IC025 +5.9 3/3 methods agree | Reporting / coding artifact | serious n=56 · ♀ 31% (drug 60%) · 100% clinician | not reported in cached trials |
| Bronchial haemorrhage | 49 | 313.8 231.4–425.5ROR 315.0 · χ² 12,608 / p <1e-300 | 239.8 EB05 188.6 · IC025 +5.7 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=49 · ♀ 100% (drug 60%) | not reported in cached trials |
| Anticoagulant therapy | 41 | 295.2 211.9–411.3ROR 296.2 · χ² 9,975 / p <1e-300 | 224.9 EB05 172.9 · IC025 +5.4 3/3 methods agree | Reporting / coding artifact | serious n=41 · 100% clinician | not reported in cached trials |
| Bronchial wall thickening | 98 | 266.1 215.1–329.0ROR 268.2 · χ² 22,108 / p <1e-300 | 220.0 EB05 185.8 · IC025 +6.4 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=98 · ♀ 6% (drug 60%) | not reported in cached trials |
| Nasal oedema | 237 | 259.4 226.5–297.1ROR 264.4 · χ² 52,614 / p <1e-300 | 220.8 EB05 198.2 · IC025 +7.0 3/3 methods agree | Not in label — unassessed | serious n=237 · ♀ 100% (drug 60%) · 94% clinician | not reported in cached trials |
| Endometrial ablation | 45 | 247.5 181.1–338.3ROR 248.4 · χ² 9,415 / p <1e-300 | 197.8 EB05 153.9 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious n=45 · ♀ 100% (drug 60%) | not reported in cached trials |
| Nasal turbinate hypertrophy | 47 | 243.4 179.3–330.3ROR 244.3 · χ² 9,697 / p <1e-300 | 195.8 EB05 153.2 · IC025 +5.6 3/3 methods agree | Not in label — unassessed | serious n=47 · ♀ 100% (drug 60%) | not reported in cached trials |
| Vital capacity decreased | 45 | 188.8 138.8–256.7ROR 189.4 · χ² 7,386 / p <1e-300 | 158.5 EB05 123.3 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious n=45 | not reported in cached trials |
| Right ventricular hypertrophy | 88 | 182.1 146.2–226.7ROR 183.4 · χ² 14,132 / p <1e-300 | 158.7 EB05 132.8 · IC025 +6.1 3/3 methods agree | Not in label — unassessed | serious n=88 · ♀ 0% (drug 60%) | not reported in cached trials |
| Airway peak pressure increased | 14 | 172.7 99.7–299.3ROR 172.9 · χ² 2,014 / p <1e-300 | 129.5 EB05 82.0 · IC025 +3.7 3/3 methods agree | Lab value / disease marker | serious n=14 | not reported in cached trials |
| Intubation | 22 | 162.6 105.0–251.8ROR 162.9 · χ² 3,076 / p <1e-300 | 131.6 EB05 91.6 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=22 | not reported in cached trials |
| Reversible airways obstruction | 41 | 147.3 107.1–202.6ROR 147.8 · χ² 5,343 / p <1e-300 | 127.6 EB05 98.0 · IC025 +5.2 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=41 · ♀ 0% (drug 60%) · 78% consumer | not reported in cached trials |
| Bronchial secretion retention | 97 | 141.4 115.0–173.8ROR 142.5 · χ² 12,342 / p <1e-300 | 127.3 EB05 107.4 · IC025 +6.0 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=97 · ♀ 6% (drug 60%) | not reported in cached trials |
| Oligoarthritis | 15 | 141.4 83.5–239.4ROR 141.6 · χ² 1,801 / p <1e-300 | 112.2 EB05 72.2 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Malignant melanoma stage 0 | 13 | 131.4 74.7–231.0ROR 131.5 · χ² 1,441 / p <1e-300 | 103.8 EB05 64.5 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Chronic obstructive airways disease exacerbated | 25 | 130.7 87.0–196.2ROR 130.9 · χ² 2,865 / p <1e-300 | 111.2 EB05 79.2 · IC025 +4.5 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=25 · 100% clinician | not reported in cached trials |
| Status asthmaticus | 33 | 126.1 88.6–179.6ROR 126.5 · χ² 3,694 / p <1e-300 | 110.1 EB05 82.0 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious n=32 | not reported in cached trials |
| Congenital hiatus hernia | 15 | 123.4 73.0–208.3ROR 123.5 · χ² 1,584 / p <1e-300 | 100.6 EB05 64.7 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Pulmonary function test abnormal | 90 | 104.0 84.1–128.6ROR 104.8 · χ² 8,548 / p <1e-300 | 96.0 EB05 80.5 · IC025 +5.6 3/3 methods agree | Reporting / coding artifact | serious n=90 · ♀ 0% (drug 60%) | not reported in cached trials |
| Breast conserving surgery | 29 | 102.2 70.3–148.6ROR 102.5 · χ² 2,645 / p <1e-300 | 90.8 EB05 66.3 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=29 · ♀ 100% (drug 60%) | not reported in cached trials |
| Aortic valve stenosis | 98 | 98.6 80.5–120.8ROR 99.4 · χ² 8,849 / p <1e-300 | 91.5 EB05 77.3 · IC025 +5.7 3/3 methods agree | Not in label — unassessed | serious n=98 · ♀ 9% (drug 60%) | not reported in cached trials |
| Nikolsky's sign | 10 | 98.1 51.9–185.6ROR 98.2 · χ² 819 / p 2e-180 | 79.2 EB05 46.0 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Trisomy 18 | 20 | 93.5 59.6–146.6ROR 93.6 · χ² 1,647 / p <1e-300 | 81.9 EB05 56.0 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=20 | not reported in cached trials |
| Rhonchi | 71 | 91.8 72.4–116.6ROR 92.4 · χ² 5,963 / p <1e-300 | 85.2 EB05 69.8 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious n=70 | not reported in cached trials |
| Oesophageal dilatation | 21 | 85.9 55.4–133.2ROR 86.1 · χ² 1,597 / p <1e-300 | 76.3 EB05 52.7 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=21 | 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) | 2,440 | 7.4 7.1–7.6ROR 8.9 · χ² 13,732 / p <1e-300 | 7.3 EB05 7.1 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 6.3 | not reported in cached trials |
| Asthma | 2,100 | 32.5 31.2–33.8ROR 38.9 · χ² 63,135 / p <1e-300 | 31.9 EB05 30.7 · IC025 +4.9 3/3 methods agree | Likely indication confounding term in indications | serious PRR 30.3 | not reported in cached trials |
| Pneumonia (lung infection) | 1,468 | 7.8 7.4–8.1ROR 8.7 · χ² 8,729 / p <1e-300 | 7.7 EB05 7.4 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 5.6 | NCT01794780: 2/276 (0.7%) on Theophylline (serious AE) |
| Wheezing | 1,418 | 41.8 39.7–43.9ROR 47.1 · χ² 55,165 / p <1e-300 | 40.8 EB05 39.0 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious PRR 38.2 | not reported in cached trials |
| Vomiting | 1,231 | 4.5 4.2–4.7ROR 4.9 · χ² 3,386 / p <1e-300 | 4.5 EB05 4.3 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.5 · ♀ 84% (drug 60%) | not reported in cached trials |
| Cough | 1,118 | 6.8 6.4–7.2ROR 7.4 · χ² 5,600 / p <1e-300 | 6.8 EB05 6.5 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 7.8 | not reported in cached trials |
| Drug hypersensitivity | 940 | 8.3 7.8–8.8ROR 8.9 · χ² 6,026 / p <1e-300 | 8.2 EB05 7.8 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 14.4 · ♀ 92% (drug 60%) | not reported in cached trials |
| Malaise (feeling unwell) | 825 | 3.2 3.0–3.4ROR 3.4 · χ² 1,268 / p 6e-278 | 3.2 EB05 3.0 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 3.5 · ♀ 87% (drug 60%) | not reported in cached trials |
| Drug ineffective (drug did not work) | 805 | 1.0 1.0–1.1ROR 1.0 · χ² 1 / p 0.128 | 1.0 EB05 1.0 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.4 | not reported in cached trials |
| Oedema | 770 | 24.5 22.9–26.3ROR 26.1 · χ² 17,155 / p <1e-300 | 24.2 EB05 22.8 · IC025 +4.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 21.2 · ♀ 95% (drug 60%) | not reported in cached trials |
| Pain | 765 | 2.1 2.0–2.3ROR 2.2 · χ² 463 / p 7e-103 | 2.1 EB05 2.0 · IC025 +1.0 | Labeled adverse reaction exact term | serious PRR 2.2 · ♀ 85% (drug 60%) | not reported in cached trials |
| Chest pain | 686 | 6.3 5.9–6.8ROR 6.6 · χ² 3,075 / p <1e-300 | 6.3 EB05 5.9 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 5.6 · ♀ 86% (drug 60%) | not reported in cached trials |
| Nausea | 668 | 1.4 1.3–1.6ROR 1.5 · χ² 93 / p 3e-22 | 1.4 EB05 1.4 · IC025 +0.4 | Labeled adverse reaction exact term | serious PRR 1.6 | not reported in cached trials |
| Chronic obstructive pulmonary disease | 661 | 21.8 20.3–23.5ROR 23.0 · χ² 12,984 / p <1e-300 | 21.6 EB05 20.2 · IC025 +4.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 17.2 | not reported in cached trials |
| Fatigue (tiredness) | 505 | 1.1 1.0–1.2ROR 1.1 · χ² 5 / p 0.011 | 1.1 EB05 1.0 · IC025 -0.0 PRR-only: not supported by EBGM or IC | Not in label — unassessed | serious PRR 1.2 | 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 19,797.8
- Right atrial hypertrophy — n=88, PRR 6,711.1
- Heart sounds — n=61, PRR 2,924.1
- Occupational asthma — n=21, PRR 952.3
- Rhinitis perennial — n=26, PRR 807.8
- Prolonged expiration — n=62, PRR 522.7
- Adulterated product — n=34, PRR 365.7
- Appendicolith — n=67, PRR 365.0
- Nasal oedema — n=237, PRR 259.4
- Endometrial ablation — n=45, PRR 247.5
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 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, 1,156 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.