Drug · FAERS side-effect profile with label screen
Epinephrine Hydrochloride side effects: what 461 FDA adverse event reports show
Drug class
alpha-Adrenergic Agonist, beta-Adrenergic Agonist, Catecholamine
FDA label (Established Pharmacologic Class) · compare the class
Who reports
461 reports · 89% serious · 38 with death outcome · 48% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Epinephrine is a non-selective alpha and beta adrenergic agonist indicated: • To increase mean arterial blood pressure in adult patients with hypotension associated with septic shock. ( 1.1 ) • For emergency treatment of allergic reactions (Type 1), including anaphylaxis. ( 1.2 ) • For induction and maintenance of mydriasis during intraocular surgery.
FDA label, Indications and Usage
What it is
Epinephrine Injection USP, 1 mg/mL is supplied as a sterile aqueous solution with a pH range of 2.2 to 5.0, that is colorless and nonpyrogenic. Each milliliter contains 1 mg epinephrine, sodiu.
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 1Labeled (related wording) 4Reporting / coding artifact 5Lab value / disease marker 1Not in label — unassessed 29
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.
- 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. 19 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 |
|---|---|---|---|---|---|---|
| Impaired quality of life | 56 | 177.7 138.9–227.3ROR 202.1 · χ² 9,632 / p <1e-300 | 167.0 EB05 133.4 · IC025 +5.7 3/3 methods agree | Not in label — unassessed | serious PRR 167.1 · ♀ 0% (drug 48%) · 95% clinician | no trial data cached |
| Tubulointerstitial nephritis | 71 | 173.1 139.7–214.5ROR 204.4 · χ² 11,939 / p <1e-300 | 164.8 EB05 135.1 · IC025 +5.9 3/3 methods agree | Not in label — unassessed | serious PRR 111.9 · ♀ 0% (drug 48%) · 94% clinician | no trial data cached |
| Impaired work ability | 68 | 144.7 116.1–180.3ROR 169.5 · χ² 9,538 / p <1e-300 | 138.7 EB05 113.1 · IC025 +5.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 119.6 · ♀ 0% (drug 48%) · 96% clinician | no trial data cached |
| Frequent bowel movements | 72 | 122.0 98.7–150.9ROR 144.4 · χ² 8,511 / p <1e-300 | 118.0 EB05 96.8 · IC025 +5.7 3/3 methods agree | Not in label — unassessed | serious PRR 121.6 · ♀ 0% (drug 48%) · 96% clinician | no trial data cached |
| Loss of personal independence in daily activities | 122 | 117.0 100.4–136.3ROR 158.7 · χ² 13,909 / p <1e-300 | 114.6 EB05 98.6 · IC025 +6.0 3/3 methods agree | Not in label — unassessed | serious PRR 99.5 · ♀ 17% (drug 48%) | no trial data cached |
| Swollen tongue | 71 | 103.5 83.6–128.3ROR 122.2 · χ² 7,101 / p <1e-300 | 100.6 EB05 82.4 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious PRR 93.8 · ♀ 2% (drug 48%) · 96% clinician | no trial data cached |
| Obstructive airways disorder | 24 | 98.0 66.4–144.7ROR 103.3 · χ² 2,205 / p <1e-300 | 90.9 EB05 64.3 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious PRR 65.8 · ♀ 92% (drug 48%) | no trial data cached |
| Full blood count abnormal | 22 | 95.1 63.2–143.0ROR 99.8 · χ² 1,952 / p <1e-300 | 87.9 EB05 61.2 · IC025 +4.2 3/3 methods agree | Lab value / disease marker | serious PRR 81.6 · ♀ 100% (drug 48%) | no trial data cached |
| Systemic lupus erythematosus | 73 | 94.1 76.2–116.1ROR 111.6 · χ² 6,625 / p <1e-300 | 91.7 EB05 75.3 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious PRR 62.3 · ♀ 0% (drug 48%) · 95% clinician | no trial data cached |
| Nightmare | 71 | 93.1 75.1–115.3ROR 109.9 · χ² 6,374 / p <1e-300 | 90.7 EB05 74.3 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious PRR 102.2 · ♀ 0% (drug 48%) · 96% clinician | no trial data cached |
| Accidental overdose | 73 | 91.0 73.7–112.4ROR 108.0 · χ² 6,408 / p <1e-300 | 88.8 EB05 73.0 · IC025 +5.4 3/3 methods agree | Reporting / coding artifact | serious PRR 96.7 · ♀ 0% (drug 48%) · 95% clinician | no trial data cached |
| Colitis ulcerative | 75 | 76.6 62.3–94.3ROR 91.3 · χ² 5,524 / p <1e-300 | 75.1 EB05 61.9 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious PRR 53.2 · ♀ 2% (drug 48%) · 95% clinician | no trial data cached |
| Rectal haemorrhage | 71 | 75.0 60.6–92.9ROR 88.5 · χ² 5,114 / p <1e-300 | 73.5 EB05 60.2 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious PRR 52.0 · ♀ 0% (drug 48%) · 96% clinician | no trial data cached |
| Tinnitus (ringing in the ears) | 70 | 69.3 55.8–86.0ROR 81.5 · χ² 4,647 / p <1e-300 | 68.0 EB05 55.6 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious PRR 69.0 · ♀ 0% (drug 48%) · 94% clinician | no trial data cached |
| Eczema | 72 | 65.2 52.7–80.6ROR 77.1 · χ² 4,492 / p <1e-300 | 64.0 EB05 52.6 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious PRR 123.5 · ♀ 0% (drug 48%) · 94% clinician | no trial data cached |
| Respiratory tract congestion | 22 | 63.0 41.9–94.7ROR 66.1 · χ² 1,280 / p 1e-280 | 59.8 EB05 41.6 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious PRR 94.2 · ♀ 100% (drug 48%) | no trial data cached |
| Premature delivery | 22 | 62.6 41.6–94.2ROR 65.7 · χ² 1,272 / p 5e-279 | 59.5 EB05 41.4 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious PRR 41.5 · ♀ 100% (drug 48%) · 100% clinician | no trial data cached |
| Haematochezia (blood in stool) | 72 | 59.5 48.1–73.6ROR 70.3 · χ² 4,089 / p <1e-300 | 58.6 EB05 48.1 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious PRR 42.3 · ♀ 0% (drug 48%) · 96% clinician | no trial data cached |
| Medication error | 68 | 55.8 44.8–69.5ROR 65.3 · χ² 3,610 / p <1e-300 | 54.9 EB05 44.8 · IC025 +4.9 3/3 methods agree | Reporting / coding artifact | serious PRR 58.5 · ♀ 0% (drug 48%) · 94% clinician | no trial data cached |
| Vertigo (spinning dizziness) | 72 | 53.8 43.5–66.5ROR 63.5 · χ² 3,682 / p <1e-300 | 53.0 EB05 43.5 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious PRR 48.2 · ♀ 0% (drug 48%) · 96% clinician | no trial data cached |
| Poor venous access | 12 | 52.9 30.3–92.6ROR 54.3 · χ² 560 / p 4e-124 | 49.0 EB05 29.9 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial data cached |
| Deep vein thrombosis (leg blood clot) | 73 | 50.9 41.2–62.8ROR 60.3 · χ² 3,528 / p <1e-300 | 50.2 EB05 41.3 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious PRR 33.6 · ♀ 0% (drug 48%) · 94% clinician | no trial data cached |
| Sinus disorder | 22 | 50.5 33.6–76.0ROR 53.0 · χ² 1,019 / p 8e-224 | 48.5 EB05 33.7 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious PRR 70.4 · ♀ 100% (drug 48%) | no trial data cached |
| Arthritis | 84 | 48.5 40.0–58.9ROR 59.1 · χ² 3,874 / p <1e-300 | 48.0 EB05 40.0 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious PRR 48.8 · ♀ 18% (drug 48%) · 95% clinician | no trial data cached |
| Stress | 74 | 46.8 38.0–57.7ROR 55.6 · χ² 3,282 / p <1e-300 | 46.3 EB05 38.1 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious PRR 50.2 · ♀ 2% (drug 48%) · 96% clinician | no trial data cached |
| Dysgeusia (altered taste) | 70 | 42.7 34.4–53.0ROR 50.1 · χ² 2,814 / p <1e-300 | 42.2 EB05 34.5 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious PRR 77.2 · ♀ 0% (drug 48%) · 96% clinician | no trial data cached |
| Chronic obstructive pulmonary disease | 46 | 40.2 30.5–52.8ROR 44.5 · χ² 1,721 / p <1e-300 | 39.5 EB05 30.8 · IC025 +4.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 30.3 · ♀ 0% (drug 48%) · 78% consumer | no trial data cached |
| Respiratory tract infection | 22 | 38.6 25.6–58.0ROR 40.5 · χ² 768 / p 2e-169 | 37.4 EB05 26.0 · IC025 +3.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 30.5 · ♀ 100% (drug 48%) | no trial data cached |
| Intentional product use issue | 72 | 37.3 30.1–46.1ROR 44.0 · χ² 2,513 / p <1e-300 | 36.9 EB05 30.3 · IC025 +4.5 3/3 methods agree | Reporting / coding artifact | serious PRR 35.0 · ♀ 2% (drug 48%) · 93% clinician | no trial data cached |
| Therapeutic product effect incomplete | 56 | 36.0 28.2–46.1ROR 40.9 · χ² 1,878 / p <1e-300 | 35.6 EB05 28.5 · IC025 +4.3 3/3 methods agree | Reporting / coding artifact | serious PRR 43.9 | no trial data cached |
| Migraine | 74 | 35.5 28.8–43.8ROR 42.1 · χ² 2,456 / p <1e-300 | 35.2 EB05 29.0 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious PRR 44.4 · ♀ 2% (drug 48%) · 95% clinician | no trial data cached |
| Pulmonary embolism (lung blood clot) | 73 | 34.8 28.2–43.0ROR 41.2 · χ² 2,372 / p <1e-300 | 34.5 EB05 28.4 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious PRR 22.6 · ♀ 2% (drug 48%) · 96% clinician | no trial data cached |
| Ulcer | 12 | 34.3 19.6–59.9ROR 35.2 · χ² 355 / p 2e-79 | 32.6 EB05 19.9 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 28.0 | no trial data cached |
| Asthma | 75 | 30.5 24.8–37.5ROR 36.2 · χ² 2,117 / p <1e-300 | 30.2 EB05 24.9 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 27.7 | no trial data cached |
| Middle insomnia | 12 | 29.4 16.8–51.3ROR 30.1 · χ² 301 / p 1e-67 | 28.1 EB05 17.1 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 41.4 | no trial data cached |
| Palpitations (pounding heartbeat) | 75 | 29.2 23.7–35.9ROR 34.6 · χ² 2,023 / p <1e-300 | 29.0 EB05 23.9 · IC025 +4.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 29.2 · ♀ 8% (drug 48%) · 95% clinician | no trial data cached |
| Dyspnoea exertional | 24 | 29.1 19.7–43.0ROR 30.6 · χ² 624 / p 5e-138 | 28.5 EB05 20.1 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 23.8 · ♀ 100% (drug 48%) | no trial data cached |
| Adverse drug reaction | 56 | 28.5 22.3–36.4ROR 32.3 · χ² 1,463 / p <1e-300 | 28.2 EB05 22.6 · IC025 +4.1 3/3 methods agree | Reporting / coding artifact | serious PRR 53.2 · ♀ 0% (drug 48%) · 96% clinician | no trial data cached |
| Metabolic acidosis | 16 | 23.0 14.2–37.2ROR 23.8 · χ² 315 / p 7e-71 | 22.4 EB05 14.5 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 15.0 | no trial data cached |
| Fibromyalgia | 12 | 22.5 12.9–39.3ROR 23.1 · χ² 225 / p 3e-51 | 21.6 EB05 12.8 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 19.1 | 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 |
|---|---|---|---|---|---|---|
| Loss of personal independence in daily activities | 122 | 117.0 100.4–136.3ROR 158.7 · χ² 13,909 / p <1e-300 | 114.6 EB05 98.6 · IC025 +6.0 3/3 methods agree | Not in label — unassessed | serious PRR 99.5 · ♀ 17% (drug 48%) | no trial data cached |
| Arthritis | 84 | 48.5 40.0–58.9ROR 59.1 · χ² 3,874 / p <1e-300 | 48.0 EB05 40.0 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious PRR 48.8 · ♀ 18% (drug 48%) · 95% clinician | no trial data cached |
| Covid-19 | 75 | 19.3 15.7–23.7ROR 22.8 · χ² 1,293 / p 2e-283 | 19.2 EB05 15.8 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious PRR 22.1 · ♀ 6% (drug 48%) · 92% clinician | no trial data cached |
| Cerebrovascular accident (stroke) | 75 | 20.1 16.3–24.7ROR 23.8 · χ² 1,350 / p 6e-296 | 20.0 EB05 16.5 · IC025 +3.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 13.1 · ♀ 2% (drug 48%) · 92% clinician | no trial data cached |
| Palpitations (pounding heartbeat) | 75 | 29.2 23.7–35.9ROR 34.6 · χ² 2,023 / p <1e-300 | 29.0 EB05 23.9 · IC025 +4.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 29.2 · ♀ 8% (drug 48%) · 95% clinician | no trial data cached |
| Asthma | 75 | 30.5 24.8–37.5ROR 36.2 · χ² 2,117 / p <1e-300 | 30.2 EB05 24.9 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 27.7 | no trial data cached |
| Colitis ulcerative | 75 | 76.6 62.3–94.3ROR 91.3 · χ² 5,524 / p <1e-300 | 75.1 EB05 61.9 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious PRR 53.2 · ♀ 2% (drug 48%) · 95% clinician | no trial data cached |
| Migraine | 74 | 35.5 28.8–43.8ROR 42.1 · χ² 2,456 / p <1e-300 | 35.2 EB05 29.0 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious PRR 44.4 · ♀ 2% (drug 48%) · 95% clinician | no trial data cached |
| Stress | 74 | 46.8 38.0–57.7ROR 55.6 · χ² 3,282 / p <1e-300 | 46.3 EB05 38.1 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious PRR 50.2 · ♀ 2% (drug 48%) · 96% clinician | no trial data cached |
| Inappropriate schedule of product administration | 73 | 18.8 15.2–23.2ROR 22.1 · χ² 1,221 / p 6e-268 | 18.7 EB05 15.4 · IC025 +3.7 3/3 methods agree | Reporting / coding artifact | serious PRR 30.5 · ♀ 2% (drug 48%) · 93% clinician | no trial data cached |
| Pulmonary embolism (lung blood clot) | 73 | 34.8 28.2–43.0ROR 41.2 · χ² 2,372 / p <1e-300 | 34.5 EB05 28.4 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious PRR 22.6 · ♀ 2% (drug 48%) · 96% clinician | no trial data cached |
| Deep vein thrombosis (leg blood clot) | 73 | 50.9 41.2–62.8ROR 60.3 · χ² 3,528 / p <1e-300 | 50.2 EB05 41.3 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious PRR 33.6 · ♀ 0% (drug 48%) · 94% clinician | no trial data cached |
| Accidental overdose | 73 | 91.0 73.7–112.4ROR 108.0 · χ² 6,408 / p <1e-300 | 88.8 EB05 73.0 · IC025 +5.4 3/3 methods agree | Reporting / coding artifact | serious PRR 96.7 · ♀ 0% (drug 48%) · 95% clinician | no trial data cached |
| Systemic lupus erythematosus | 73 | 94.1 76.2–116.1ROR 111.6 · χ² 6,625 / p <1e-300 | 91.7 EB05 75.3 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious PRR 62.3 · ♀ 0% (drug 48%) · 95% clinician | no trial data cached |
| Intentional product use issue | 72 | 37.3 30.1–46.1ROR 44.0 · χ² 2,513 / p <1e-300 | 36.9 EB05 30.3 · IC025 +4.5 3/3 methods agree | Reporting / coding artifact | serious PRR 35.0 · ♀ 2% (drug 48%) · 93% clinician | 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.
- Impaired quality of life — n=56, PRR 177.7
- Tubulointerstitial nephritis — n=71, PRR 173.1
- Frequent bowel movements — n=72, PRR 122.0
- Loss of personal independence in daily activities — n=122, PRR 117.0
- Swollen tongue — n=71, PRR 103.5
- Obstructive airways disorder — n=24, PRR 98.0
- Systemic lupus erythematosus — n=73, PRR 94.1
- Nightmare — n=71, PRR 93.1
- Colitis ulcerative — n=75, PRR 76.6
- Rectal haemorrhage — n=71, PRR 75.0
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 Epinephrine?
In FDA FAERS, the most frequently co-reported reaction terms for Epinephrine are loss of personal independence in daily activities, arthritis, covid-19, cerebrovascular accident, palpitations, asthma. 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 Epinephrine have an FDA boxed warning?
No. The FDA label retrieved for Epinephrine has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Epinephrine 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 01fd19cd-190c-4989-b733-60ba95941297, effective 20251218; matched on
openfda.generic_name.exact:"EPINEPHRINE") - 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, 59 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.