Phytonadione side effects: what 8,433 FDA adverse event reports show
Drug class
Vitamin K, Warfarin Reversal Agent
Who reports
8,433 reports · 80% serious · 1,581 with death outcome · 53% female
Used for
Phytonadione injectable emulsion is a vitamin K replacement indicated for the treatment of the following coagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity.
What it is
Phytonadione is a vitamin K replacement, which is a clear, yellow to amber, viscous, odorless or nearly odorless liquid. It is insoluble in water, soluble in chloroform and slightly soluble in ethanol. It has a molecular weight of 450.70. Phytonadione is 2-methyl-3-phytyl-1, 4-naphthoquinone.
Boxed warning
-HYPERSENSITIVITY REACTIONS WITH INTRAVENOUS AND INTRAMUSCULAR USE Fatal hypersensitivity reactions, including anaphylaxis, have occurred during and immediately after intravenous and intramuscular injection of phytonadione injectable emulsion. Reactions have occurred despite dilution to avoid rapid intravenous infusion and upon first dose.
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. 1,076 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 |
|---|---|---|---|---|---|---|
| Appendicolith | 265 | 5,908.3 4,735.4–7,371.6ROR 6,099.9 · χ² 457,390 / p <1e-300 | 1,539.1 EB05 1,389.8 · IC025 +8.5 3/3 methods agree | Not in label — unassessed | serious n=265 · ♀ 3% (drug 53%) · 97% clinician | no trial data cached |
| Sleep disorder therapy | 130 | 5,904.1 4,301.9–8,103.1ROR 5,996.5 · χ² 223,451 / p <1e-300 | 1,378.3 EB05 1,190.6 · IC025 +7.5 3/3 methods agree | Reporting / coding artifact | serious n=130 · ♀ 5% (drug 53%) · 98% clinician | no trial data cached |
| Antacid therapy | 84 | 5,886.0 3,970.2–8,726.1ROR 5,945.2 · χ² 143,643 / p <1e-300 | 1,238.5 EB05 1,031.7 · IC025 +6.9 3/3 methods agree | Reporting / coding artifact | serious n=84 · ♀ 8% (drug 53%) · 100% clinician | no trial data cached |
| Analgesic therapy | 125 | 1,722.3 1,371.5–2,162.7ROR 1,748.1 · χ² 125,314 / p <1e-300 | 875.4 EB05 754.0 · IC025 +7.4 3/3 methods agree | Reporting / coding artifact | serious n=125 · ♀ 5% (drug 53%) · 96% clinician | no trial data cached |
| Drug therapy | 112 | 1,346.5 1,070.3–1,693.8ROR 1,364.6 · χ² 96,344 / p <1e-300 | 756.4 EB05 645.9 · IC025 +7.2 3/3 methods agree | Reporting / coding artifact | serious n=112 · ♀ 6% (drug 53%) · 96% clinician | no trial data cached |
| Anticoagulant therapy | 82 | 1,047.4 809.5–1,355.3ROR 1,057.7 · χ² 59,339 / p <1e-300 | 626.2 EB05 520.5 · IC025 +6.7 3/3 methods agree | Reporting / coding artifact | serious n=82 · ♀ 8% (drug 53%) · 96% clinician | no trial data cached |
| Congenital hiatus hernia | 56 | 842.6 622.4–1,140.6ROR 848.2 · χ² 34,412 / p <1e-300 | 516.1 EB05 412.3 · IC025 +6.1 3/3 methods agree | Not in label — unassessed | serious n=56 · ♀ 0% (drug 53%) · 100% clinician | no trial data cached |
| Malignant melanoma stage 0 | 43 | 775.4 550.7–1,091.9ROR 779.4 · χ² 24,683 / p <1e-300 | 466.5 EB05 360.8 · IC025 +5.7 3/3 methods agree | Not in label — unassessed | serious n=43 · ♀ 0% (drug 53%) · 100% clinician | no trial data cached |
| Bacteroides infection | 39 | 440.8 313.7–619.4ROR 442.8 · χ² 14,135 / p <1e-300 | 315.8 EB05 241.1 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious n=39 · ♀ 0% (drug 53%) · 100% clinician | no trial data cached |
| Hyper ige syndrome | 17 | 434.3 259.4–727.1ROR 435.2 · χ² 5,881 / p <1e-300 | 260.9 EB05 172.6 · IC025 +4.2 3/3 methods agree | Labeled (related wording) related wording | serious n=17 | no trial data cached |
| Hyperphosphataemia | 164 | 208.6 178.1–244.3ROR 212.7 · χ² 31,041 / p <1e-300 | 188.1 EB05 165.2 · IC025 +6.7 3/3 methods agree | Not in label — unassessed | serious n=164 · ♀ 7% (drug 53%) · 96% clinician | no trial data cached |
| Bronchopulmonary aspergillosis allergic | 63 | 183.5 142.2–236.8ROR 184.9 · χ² 10,470 / p <1e-300 | 162.5 EB05 131.5 · IC025 +5.8 3/3 methods agree | Not in label — unassessed | serious n=63 · ♀ 0% (drug 53%) · 92% clinician | no trial data cached |
| Blood phosphorus increased | 183 | 179.0 154.3–207.7ROR 183.0 · χ² 30,030 / p <1e-300 | 164.1 EB05 145.1 · IC025 +6.6 3/3 methods agree | Lab value / disease marker | serious n=183 · ♀ 4% (drug 53%) · 96% clinician | no trial data cached |
| Factor v inhibition | 13 | 176.1 100.4–309.1ROR 176.4 · χ² 1,952 / p <1e-300 | 132.8 EB05 82.6 · IC025 +3.6 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=13 | no trial data cached |
| Cutaneous mucormycosis | 11 | 163.5 88.8–300.9ROR 163.7 · χ² 1,517 / p <1e-300 | 121.6 EB05 72.4 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial data cached |
| Vitamin k deficiency | 18 | 117.7 73.4–188.8ROR 118.0 · χ² 1,878 / p <1e-300 | 100.7 EB05 67.4 · IC025 +4.0 3/3 methods agree | Likely indication confounding term in indications | serious n=17 | no trial data cached |
| Total lung capacity decreased | 68 | 110.2 86.5–140.4ROR 111.1 · χ² 6,940 / p <1e-300 | 102.6 EB05 83.7 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious n=68 · ♀ 10% (drug 53%) · 100% clinician | no trial data cached |
| Restrictive cardiomyopathy | 11 | 92.7 50.8–169.2ROR 92.8 · χ² 875 / p 1e-192 | 77.7 EB05 46.3 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial data cached |
| Activated partial thromboplastin time prolonged | 153 | 77.2 65.8–90.5ROR 78.6 · χ² 11,082 / p <1e-300 | 74.2 EB05 64.8 · IC025 +5.6 3/3 methods agree | Lab value / disease marker | serious n=152 · ♀ 12% (drug 53%) · 96% clinician | no trial data cached |
| Appendicitis | 275 | 75.8 67.3–85.3ROR 78.3 · χ² 19,623 / p <1e-300 | 73.2 EB05 66.2 · IC025 +5.8 3/3 methods agree | Not in label — unassessed | serious PRR 53.4 · ♀ 3% (drug 53%) · 97% clinician | no trial data cached |
| Iron deficiency | 130 | 74.9 63.0–89.0ROR 76.0 · χ² 9,123 / p <1e-300 | 71.9 EB05 62.1 · IC025 +5.5 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=128 · ♀ 11% (drug 53%) · 93% clinician | no trial data cached |
| Infective pulmonary exacerbation of cystic fibrosis | 141 | 65.6 55.6–77.4ROR 66.7 · χ² 8,674 / p <1e-300 | 63.4 EB05 55.1 · IC025 +5.4 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=134 | no trial data cached |
| Blood uric acid increased | 147 | 65.0 55.3–76.5ROR 66.1 · χ² 8,965 / p <1e-300 | 62.9 EB05 54.8 · IC025 +5.4 3/3 methods agree | Lab value / disease marker | serious n=147 · ♀ 5% (drug 53%) · 97% clinician | no trial data cached |
| Necrotising enterocolitis neonatal | 10 | 63.4 33.8–118.7ROR 63.4 · χ² 539 / p 1e-119 | 55.6 EB05 32.3 · IC025 +2.9 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=10 | no trial data cached |
| Hypophosphataemia | 176 | 61.0 52.6–70.8ROR 62.3 · χ² 10,083 / p <1e-300 | 59.2 EB05 52.2 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious PRR 44.6 · ♀ 10% (drug 53%) · 96% clinician | no trial data cached |
| Aortic stenosis | 82 | 59.9 48.2–74.5ROR 60.5 · χ² 4,581 / p <1e-300 | 57.8 EB05 48.0 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=82 · ♀ 11% (drug 53%) · 96% clinician | no trial data cached |
| Lung opacity | 60 | 59.3 46.0–76.6ROR 59.7 · χ² 3,302 / p <1e-300 | 56.9 EB05 45.8 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=60 · ♀ 13% (drug 53%) · 93% clinician | no trial data cached |
| Myasthenia gravis | 181 | 58.5 50.5–67.7ROR 59.7 · χ² 9,935 / p <1e-300 | 56.8 EB05 50.2 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious PRR 41.8 · ♀ 4% (drug 53%) · 95% clinician | no trial data cached |
| Hyphaema | 12 | 58.2 32.8–103.1ROR 58.2 · χ² 604 / p 1e-133 | 52.4 EB05 31.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial data cached |
| Ventricular fibrillation | 249 | 56.8 50.2–64.3ROR 58.5 · χ² 13,303 / p <1e-300 | 55.4 EB05 49.8 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious PRR 39.9 · ♀ 3% (drug 53%) · 97% clinician | no trial data cached |
| Intraventricular haemorrhage neonatal | 10 | 52.0 27.8–97.2ROR 52.0 · χ² 441 / p 4e-98 | 46.7 EB05 27.1 · IC025 +2.8 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=10 | no trial data cached |
| Cardiogenic shock | 270 | 47.9 42.6–54.0ROR 49.5 · χ² 12,133 / p <1e-300 | 46.9 EB05 42.4 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious PRR 33.6 · ♀ 5% (drug 53%) · 97% clinician | no trial data cached |
| Pleuritic pain | 49 | 44.7 33.7–59.3ROR 45.0 · χ² 2,014 / p <1e-300 | 43.2 EB05 34.0 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=49 · ♀ 0% (drug 53%) · 94% clinician | no trial data cached |
| Cystic fibrosis respiratory infection suppression | 15 | 42.1 25.3–70.2ROR 42.2 · χ² 553 / p 2e-122 | 39.5 EB05 25.4 · IC025 +3.3 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=15 | no trial data cached |
| Jaundice neonatal | 28 | 37.2 25.6–54.0ROR 37.3 · χ² 937 / p 5e-206 | 35.9 EB05 26.0 · IC025 +3.9 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=28 · ♀ 27% (drug 53%) | no trial data cached |
| Respiratory symptom | 40 | 36.0 26.4–49.2ROR 36.2 · χ² 1,307 / p 1e-286 | 35.0 EB05 26.8 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=40 · ♀ 0% (drug 53%) · 100% clinician | no trial data cached |
| Enterococcal sepsis | 11 | 33.9 18.7–61.5ROR 34.0 · χ² 315 / p 9e-71 | 31.8 EB05 18.9 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial data cached |
| Troponin increased | 100 | 33.4 27.4–40.6ROR 33.8 · χ² 3,068 / p <1e-300 | 32.8 EB05 27.7 · IC025 +4.5 3/3 methods agree | Lab value / disease marker | serious PRR 24.3 · ♀ 9% (drug 53%) · 95% clinician | no trial data cached |
| Multiple organ dysfunction syndrome | 352 | 31.8 28.6–35.2ROR 33.1 · χ² 10,334 / p <1e-300 | 31.3 EB05 28.7 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious PRR 22.4 · ♀ 12% (drug 53%) · 95% clinician | no trial data cached |
| Ascites | 366 | 31.3 28.3–34.6ROR 32.7 · χ² 10,590 / p <1e-300 | 30.9 EB05 28.3 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious PRR 22.4 · ♀ 15% (drug 53%) · 92% clinician | 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 |
|---|---|---|---|---|---|---|
| Off label use (used outside approved label) | 705 | 2.0 1.9–2.2ROR 2.1 · χ² 378 / p 2e-84 | 2.0 EB05 1.9 · IC025 +0.9 | Reporting / coding artifact | serious PRR 2.4 | no trial data cached |
| Nausea | 679 | 2.1 2.0–2.3ROR 2.2 · χ² 427 / p 3e-95 | 2.1 EB05 2.0 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 2.5 | no trial data cached |
| Vomiting | 571 | 3.0 2.8–3.3ROR 3.2 · χ² 792 / p 2e-174 | 3.0 EB05 2.8 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 3.0 | no trial data cached |
| Fatigue (tiredness) | 564 | 1.8 1.7–2.0ROR 1.9 · χ² 210 / p 9e-48 | 1.8 EB05 1.7 · IC025 +0.7 | Not in label — unassessed | serious PRR 1.8 | no trial data cached |
| Dyspnoea (shortness of breath) | 544 | 2.4 2.2–2.6ROR 2.5 · χ² 451 / p 2e-100 | 2.4 EB05 2.2 · IC025 +1.1 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 2.1 | no trial data cached |
| Drug ineffective (drug did not work) | 520 | 1.0 0.9–1.1ROR 1.0 · χ² 0 / p 0.342 | 1.0 EB05 0.9 · IC025 -0.2 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.6 | no trial data cached |
| Sepsis (blood infection) | 481 | 10.8 9.9–11.7ROR 11.3 · χ² 4,252 / p <1e-300 | 10.7 EB05 9.9 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious PRR 7.7 · ♀ 26% (drug 53%) · 93% clinician | no trial data cached |
| Abdominal pain | 462 | 4.9 4.5–5.4ROR 5.2 · χ² 1,465 / p <1e-300 | 4.9 EB05 4.6 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 4.5 · ♀ 27% (drug 53%) | no trial data cached |
| Diarrhoea (diarrhea) | 458 | 1.8 1.6–1.9ROR 1.8 · χ² 158 / p 2e-36 | 1.8 EB05 1.6 · IC025 +0.7 | Not in label — unassessed | serious PRR 1.8 | no trial data cached |
| Constipation | 443 | 5.1 4.7–5.6ROR 5.3 · χ² 1,467 / p <1e-300 | 5.1 EB05 4.7 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.7 · ♀ 31% (drug 53%) | no trial data cached |
| Condition aggravated | 408 | 3.4 3.1–3.7ROR 3.5 · χ² 684 / p 5e-151 | 3.3 EB05 3.1 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | serious PRR 3.4 · ♀ 31% (drug 53%) | no trial data cached |
| Headache | 405 | 1.6 1.5–1.8ROR 1.6 · χ² 95 / p 8e-23 | 1.6 EB05 1.5 · IC025 +0.5 | Not in label — unassessed | serious PRR 1.7 | no trial data cached |
| Abdominal distension (bloating) | 399 | 9.6 8.7–10.5ROR 10.0 · χ² 3,059 / p <1e-300 | 9.5 EB05 8.7 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 11.6 · ♀ 19% (drug 53%) | no trial data cached |
| Anaemia (low red blood cells) | 384 | 5.0 4.5–5.5ROR 5.2 · χ² 1,237 / p 2e-271 | 5.0 EB05 4.6 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 3.9 · ♀ 32% (drug 53%) | no trial data cached |
| Ascites | 366 | 31.3 28.3–34.6ROR 32.7 · χ² 10,590 / p <1e-300 | 30.9 EB05 28.3 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious PRR 22.4 · ♀ 15% (drug 53%) · 92% 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.
- Appendicolith — n=265, PRR 5,908.3
- Congenital hiatus hernia — n=56, PRR 842.6
- Malignant melanoma stage 0 — n=43, PRR 775.4
- Bacteroides infection — n=39, PRR 440.8
- Hyperphosphataemia — n=164, PRR 208.6
- Bronchopulmonary aspergillosis allergic — n=63, PRR 183.5
- Total lung capacity decreased — n=68, PRR 110.2
- Appendicitis — n=275, PRR 75.8
- Hypophosphataemia — n=176, PRR 61.0
- Aortic stenosis — n=82, PRR 59.9
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 Phytonadione?
In FDA FAERS, the most frequently co-reported reaction terms for Phytonadione are nausea, vomiting, fatigue, dyspnoea, sepsis, abdominal pain. 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 Phytonadione have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: -HYPERSENSITIVITY REACTIONS WITH INTRAVENOUS AND INTRAMUSCULAR USE Fatal hypersensitivity reactions, including anaphylaxis, have occurred during and immediately after intravenous and intramuscular injection of phytonadione injectable emulsion. Reactions have occurred despite dilution to avoid rapid intravenous infusion and upon first dose.
Do FAERS signals prove that Phytonadione 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 1add4de5-0f9c-453e-9dd5-abb8077b566a, effective 20240712; matched on
openfda.generic_name.exact:"PHYTONADIONE") - 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, 1,116 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.