Drug · FAERS side-effect profile with label screen

Levonorgestrel and Ethinyl Estradiol side effects: what 1,034 FDA adverse event reports show

Levonorgestrel/Ethinyl Estradiol · 15 reaction terms · 812 drug–reaction co-reports · data 2026-09-14

Drug class

Progestin, Progestin-containing Intrauterine System

FDA label (Established Pharmacologic Class) of the closest related product

Label matched

Levonorgestrel (Liletta)

closest FDA label found for this product string; brand list suppressed because the label is a related product, not an exact match

Who reports

1,034 reports · 3% serious · 0 with death outcome · 100% female

openFDA FAERS counts, all years, deduplication not applied

Used for

LILETTA is a progestin-containing intrauterine system indicated for: Prevention of pregnancy for up to 8 years ( 1.1 ) Treatment of heavy menstrual bleeding for up to 5 years in patients who choose intrauterine contraception as their method of contraception ( 1.2 ) 1.1 Contraception LILETTA is indicated for prevention of pregnancy for up to 8 years.

FDA label, Indications and Usage

What it is

the following structural formula: Levonorgestrel USP, (-)-13-ethyl-17-hydroxy-18,19-dinor-17-pregn-4-en-20-yn-3-one, the active ingredient in LILETTA, is the levorotatory form of norgestrel, which consists of a racemic mixture of D-(–)-norgestrel (levonorgestrel) and L-(+)-norgestrel (dextronorgestrel).

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 15 strongest signals

Labeled (related wording) 2Reporting / coding artifact 7Not in label — unassessed 6

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.
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.
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. 0 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.

Show: hide coding/lab/outcome terms hide indication terms unlabeled only hide PRR-only

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Product adhesion issue	539	313.1 295.1–332.3ROR 652.9 · χ² 165,075 / p <1e-300	305.0 EB05 284.0 · IC025 +7.8 3/3 methods agree	Reporting / coding artifact	91% consumer	no trial data cached
Application site rash	37	54.5 39.7–74.8ROR 56.5 · χ² 1,887 / p <1e-300	53.0 EB05 40.1 · IC025 +4.4 3/3 methods agree	Not in label — unassessed	serious n=2	no trial data cached
Product administration error	49	49.9 38.0–65.6ROR 52.3 · χ² 2,296 / p <1e-300	48.9 EB05 38.4 · IC025 +4.6 3/3 methods agree	Reporting / coding artifact	100% consumer	no trial data cached
Application site irritation	23	37.5 25.1–56.3ROR 38.4 · χ² 781 / p 4e-172	36.4 EB05 25.6 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Dysmenorrhoea	17	26.4 16.5–42.3ROR 26.8 · χ² 390 / p 4e-87	25.7 EB05 16.9 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Application site pruritus	27	24.1 16.6–35.0ROR 24.8 · χ² 576 / p 1e-127	23.8 EB05 17.1 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Incorrect product administration duration	23	23.0 15.4–34.5ROR 23.5 · χ² 462 / p 7e-103	22.6 EB05 15.8 · IC025 +3.3 3/3 methods agree	Reporting / coding artifact	95% consumer	no trial data cached
Product administered at inappropriate site	18	20.1 12.7–31.8ROR 20.5 · χ² 308 / p 3e-69	19.6 EB05 12.9 · IC025 +2.9 3/3 methods agree	Reporting / coding artifact	–	no trial data cached
Product prescribing issue	14	14.0 8.3–23.5ROR 14.1 · χ² 156 / p 5e-36	12.8 EB05 7.4 · IC025 +2.4 3/3 methods agree	Reporting / coding artifact	serious PRR 91.8	no trial data cached
Menstruation delayed	7	13.7 6.5–28.6ROR 13.8 · χ² 70 / p 3e-17	10.7 EB05 4.5 · IC025 +1.6 3/3 methods agree	Labeled (related wording) related wording	–	no trial data cached
Application site erythema	16	12.3 7.6–20.1ROR 12.5 · χ² 156 / p 5e-36	11.2 EB05 6.7 · IC025 +2.4 3/3 methods agree	Not in label — unassessed	serious n=1	no trial data cached
Menstruation irregular	16	12.2 7.5–19.9ROR 12.4 · χ² 154 / p 1e-35	11.1 EB05 6.7 · IC025 +2.3 3/3 methods agree	Labeled (related wording) related wording	–	no trial data cached
Product dose omission in error	11	8.3 4.6–15.0ROR 8.4 · χ² 64 / p 7e-16	6.6 EB05 3.8 · IC025 +1.6 3/3 methods agree	Reporting / coding artifact	–	no trial data cached
Product prescribing error	8	6.9 3.4–13.7ROR 6.9 · χ² 34 / p 2e-9	5.2 EB05 2.8 · IC025 +1.1 3/3 methods agree	Reporting / coding artifact	–	no trial data cached
Application site pain	7	6.4 3.1–13.5ROR 6.5 · χ² 27 / p 1e-7	4.7 EB05 2.5 · IC025 +0.9 3/3 methods agree	Not in label — unassessed	–	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
Product adhesion issue	539	313.1 295.1–332.3ROR 652.9 · χ² 165,075 / p <1e-300	305.0 EB05 284.0 · IC025 +7.8 3/3 methods agree	Reporting / coding artifact	91% consumer	no trial data cached
Product administration error	49	49.9 38.0–65.6ROR 52.3 · χ² 2,296 / p <1e-300	48.9 EB05 38.4 · IC025 +4.6 3/3 methods agree	Reporting / coding artifact	100% consumer	no trial data cached
Application site rash	37	54.5 39.7–74.8ROR 56.5 · χ² 1,887 / p <1e-300	53.0 EB05 40.1 · IC025 +4.4 3/3 methods agree	Not in label — unassessed	serious n=2	no trial data cached
Application site pruritus	27	24.1 16.6–35.0ROR 24.8 · χ² 576 / p 1e-127	23.8 EB05 17.1 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Incorrect product administration duration	23	23.0 15.4–34.5ROR 23.5 · χ² 462 / p 7e-103	22.6 EB05 15.8 · IC025 +3.3 3/3 methods agree	Reporting / coding artifact	95% consumer	no trial data cached
Application site irritation	23	37.5 25.1–56.3ROR 38.4 · χ² 781 / p 4e-172	36.4 EB05 25.6 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Product administered at inappropriate site	18	20.1 12.7–31.8ROR 20.5 · χ² 308 / p 3e-69	19.6 EB05 12.9 · IC025 +2.9 3/3 methods agree	Reporting / coding artifact	–	no trial data cached
Dysmenorrhoea	17	26.4 16.5–42.3ROR 26.8 · χ² 390 / p 4e-87	25.7 EB05 16.9 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Menstruation irregular	16	12.2 7.5–19.9ROR 12.4 · χ² 154 / p 1e-35	11.1 EB05 6.7 · IC025 +2.3 3/3 methods agree	Labeled (related wording) related wording	–	no trial data cached
Application site erythema	16	12.3 7.6–20.1ROR 12.5 · χ² 156 / p 5e-36	11.2 EB05 6.7 · IC025 +2.4 3/3 methods agree	Not in label — unassessed	serious n=1	no trial data cached
Product prescribing issue	14	14.0 8.3–23.5ROR 14.1 · χ² 156 / p 5e-36	12.8 EB05 7.4 · IC025 +2.4 3/3 methods agree	Reporting / coding artifact	serious PRR 91.8	no trial data cached
Product dose omission in error	11	8.3 4.6–15.0ROR 8.4 · χ² 64 / p 7e-16	6.6 EB05 3.8 · IC025 +1.6 3/3 methods agree	Reporting / coding artifact	–	no trial data cached
Product prescribing error	8	6.9 3.4–13.7ROR 6.9 · χ² 34 / p 2e-9	5.2 EB05 2.8 · IC025 +1.1 3/3 methods agree	Reporting / coding artifact	–	no trial data cached
Application site pain	7	6.4 3.1–13.5ROR 6.5 · χ² 27 / p 1e-7	4.7 EB05 2.5 · IC025 +0.9 3/3 methods agree	Not in label — unassessed	–	no trial data cached
Menstruation delayed	7	13.7 6.5–28.6ROR 13.8 · χ² 70 / p 3e-17	10.7 EB05 4.5 · IC025 +1.6 3/3 methods agree	Labeled (related wording) related wording	–	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.

Application site rash — n=37, PRR 54.5
Application site irritation — n=23, PRR 37.5
Application site pruritus — n=27, PRR 24.1

✓ A hand-written Bradford Hill causality assessment exists for this drug: Drospirenone/ethinyl estradiol ↔ Pulmonary embolism (venous thromboembolism).

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 Levonorgestrel and Ethinyl Estradiol?

In FDA FAERS, the most frequently co-reported reaction terms for Levonorgestrel and Ethinyl Estradiol are application site rash, application site pruritus, application site irritation, dysmenorrhoea, menstruation irregular, application site erythema. 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 Levonorgestrel and Ethinyl Estradiol have an FDA boxed warning?

No. The FDA label retrieved for Levonorgestrel and Ethinyl Estradiol has no boxed warning; see the label's Warnings and Precautions for the recognised risks.

Do FAERS signals prove that Levonorgestrel and Ethinyl Estradiol 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 aaf0eb2a-f88a-4f26-a445-0fd30176c326, effective 20230629; matched on openfda.generic_name.exact:"LEVONORGESTREL" AND openfda.product_type:"HUMAN PRESCRIPTION DRUG")
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, field patient.drug.openfda.generic_name.exact, 15 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.