Levomilnacipran side effects: what 1,905 FDA adverse event reports show
Drug class
Serotonin and norepinephrine reuptake inhibitor (snri)
Label matched
Levomilnacipran Hydrochloride (Fetzima)
Who reports
1,905 reports · 53% serious · 168 with death outcome · 77% female
Used for
FETZIMA ® is indicated for the treatment of major depressive disorder (MDD) in adults . Limitation of Use: FETZIMA is not approved for the management of fibromyalgia. The efficacy and safety of FETZIMA for the management of fibromyalgia have not been established.
What it is
FETZIMA contains levomilnacipran, a selective serotonin and norepinephrine reuptake inhibitor (SNRI), in the form of hydrochloride salt with the chemical name of levomilnacipran hydrochloride is (1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide hydrochloride.
Boxed warning
SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions ( 5.1 ) ] .
Causality screen of the 40 strongest signals
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- 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.
- 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. 90 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 |
|---|---|---|---|---|---|---|
| Taste disorder | 165 | 91.4 78.9–105.8ROR 99.9 · χ² 14,551 / p <1e-300 | 89.7 EB05 78.8 · IC025 +5.9 3/3 methods agree | Not in label — unassessed | serious PRR 197.5 · ♀ 100% (drug 77%) | no trial data cached |
| Epilepsy | 164 | 59.5 51.4–68.9ROR 65.0 · χ² 9,332 / p <1e-300 | 58.8 EB05 51.6 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious PRR 64.5 · ♀ 100% (drug 77%) | no trial data cached |
| Wound infection | 34 | 34.5 24.7–48.2ROR 35.1 · χ² 1,071 / p 3e-235 | 33.8 EB05 25.3 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious PRR 38.9 · ♀ 100% (drug 77%) · 94% clinician | no trial data cached |
| Hypercholesterolaemia | 27 | 31.1 21.4–45.3ROR 31.6 · χ² 756 / p 1e-166 | 30.5 EB05 22.0 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious PRR 35.8 · ♀ 100% (drug 77%) · 96% clinician | no trial data cached |
| Folliculitis | 29 | 31.0 21.6–44.5ROR 31.4 · χ² 810 / p 2e-178 | 30.3 EB05 22.2 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious PRR 39.4 · ♀ 100% (drug 77%) · 97% clinician | no trial data cached |
| Back injury | 27 | 27.5 18.9–40.0ROR 27.9 · χ² 662 / p 2e-146 | 27.0 EB05 19.5 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious PRR 35.0 · 92% clinician | no trial data cached |
| Synovitis | 44 | 26.9 20.1–36.0ROR 27.5 · χ² 1,070 / p 7e-235 | 26.6 EB05 20.6 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious PRR 30.5 · ♀ 100% (drug 77%) · 98% clinician | no trial data cached |
| Pericarditis | 39 | 25.8 18.9–35.2ROR 26.3 · χ² 904 / p 6e-199 | 25.5 EB05 19.4 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious PRR 28.2 · 97% clinician | no trial data cached |
| Pemphigus | 29 | 25.7 17.9–36.9ROR 26.1 · χ² 664 / p 1e-146 | 25.3 EB05 18.5 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious PRR 27.9 · ♀ 100% (drug 77%) · 97% clinician | no trial data cached |
| Gastrooesophageal reflux disease (acid reflux) | 181 | 24.9 21.7–28.6ROR 27.4 · χ² 4,135 / p <1e-300 | 24.8 EB05 21.9 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 42.5 · ♀ 99% (drug 77%) | no trial data cached |
| Red blood cell sedimentation rate increased | 24 | 23.9 16.0–35.5ROR 24.2 · χ² 502 / p 1e-111 | 23.4 EB05 16.5 · IC025 +3.3 3/3 methods agree | Lab value / disease marker | serious PRR 29.3 · ♀ 100% (drug 77%) · 96% clinician | no trial data cached |
| Bursitis | 24 | 21.9 14.7–32.7ROR 22.2 · χ² 458 / p 6e-102 | 21.5 EB05 15.2 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious PRR 28.0 · ♀ 100% (drug 77%) · 96% clinician | no trial data cached |
| Migraine | 179 | 20.8 18.1–23.9ROR 22.9 · χ² 3,364 / p <1e-300 | 20.7 EB05 18.3 · IC025 +4.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 42.4 · ♀ 98% (drug 77%) | no trial data cached |
| Helicobacter infection | 19 | 20.5 13.1–32.2ROR 20.7 · χ² 334 / p 8e-75 | 20.1 EB05 13.4 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 23.5 | no trial data cached |
| Laryngitis | 20 | 20.3 13.1–31.4ROR 20.5 · χ² 348 / p 7e-78 | 19.9 EB05 13.4 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=20 · 95% clinician | no trial data cached |
| Drug intolerance | 173 | 19.8 17.2–22.8ROR 21.7 · χ² 3,081 / p <1e-300 | 19.7 EB05 17.4 · IC025 +4.0 3/3 methods agree | Reporting / coding artifact | serious PRR 33.6 · ♀ 99% (drug 77%) | no trial data cached |
| Joint range of motion decreased | 24 | 19.8 13.3–29.5ROR 20.0 · χ² 409 / p 3e-91 | 19.4 EB05 13.6 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 27.3 · ♀ 100% (drug 77%) · 96% clinician | no trial data cached |
| Prescribed overdose | 30 | 17.1 12.0–24.4ROR 17.3 · χ² 438 / p 1e-97 | 16.8 EB05 12.2 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 26.3 | no trial data cached |
| Irritable bowel syndrome | 32 | 16.5 11.7–23.3ROR 16.8 · χ² 451 / p 3e-100 | 16.2 EB05 11.9 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 22.7 · ♀ 100% (drug 77%) · 91% clinician | no trial data cached |
| Autoimmune disorder | 14 | 16.1 9.6–27.2ROR 16.2 · χ² 184 / p 4e-42 | 15.2 EB05 8.9 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 18.7 | no trial data cached |
| Memory impairment | 200 | 16.0 14.1–18.3ROR 17.8 · χ² 2,817 / p <1e-300 | 16.0 EB05 14.2 · IC025 +3.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 29.1 · ♀ 98% (drug 77%) | no trial data cached |
| Hand deformity | 19 | 16.0 10.2–25.0ROR 16.2 · χ² 252 / p 4e-57 | 15.4 EB05 10.0 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 18.9 | no trial data cached |
| Wound | 40 | 15.9 11.7–21.6ROR 16.2 · χ² 542 / p 4e-120 | 15.6 EB05 11.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 20.5 · ♀ 97% (drug 77%) · 90% clinician | no trial data cached |
| Contraindicated product administered | 41 | 15.0 11.1–20.3ROR 15.3 · χ² 521 / p 1e-115 | 14.8 EB05 11.2 · IC025 +3.2 3/3 methods agree | Reporting / coding artifact | serious PRR 19.7 · ♀ 100% (drug 77%) | no trial data cached |
| Fibromyalgia | 33 | 15.0 10.7–21.0ROR 15.2 · χ² 416 / p 7e-93 | 14.7 EB05 10.8 · IC025 +3.0 3/3 methods agree | Likely indication confounding term in indications | serious PRR 20.7 · ♀ 97% (drug 77%) | no trial data cached |
| Hypoaesthesia (numbness) | 191 | 14.0 12.3–16.1ROR 15.5 · χ² 2,315 / p <1e-300 | 14.0 EB05 12.4 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 23.8 · ♀ 99% (drug 77%) | no trial data cached |
| Maternal exposure during pregnancy | 110 | 13.7 11.5–16.5ROR 14.5 · χ² 1,291 / p 6e-283 | 13.7 EB05 11.6 · IC025 +3.4 3/3 methods agree | Reporting / coding artifact | serious PRR 19.0 · ♀ 100% (drug 77%) · 90% clinician | no trial data cached |
| Sleep disorder due to a general medical condition | 20 | 13.6 8.8–21.1ROR 13.8 · χ² 221 / p 2e-50 | 12.9 EB05 8.4 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 29.2 · 95% clinician | no trial data cached |
| Paraesthesia (tingling/numbness) | 189 | 13.2 11.5–15.1ROR 14.6 · χ² 2,134 / p <1e-300 | 13.1 EB05 11.6 · IC025 +3.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 23.9 | no trial data cached |
| Glossodynia (burning tongue/mouth pain) | 26 | 12.8 8.7–18.8ROR 13.0 · χ² 271 / p 3e-61 | 12.3 EB05 8.4 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 17.0 | no trial data cached |
| Prescribed underdose | 23 | 12.7 8.5–19.1ROR 12.8 · χ² 236 / p 1e-53 | 12.0 EB05 8.0 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 22.5 · 91% clinician | no trial data cached |
| Hepatic cirrhosis | 21 | 12.4 8.1–18.9ROR 12.5 · χ² 208 / p 2e-47 | 11.6 EB05 7.6 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 13.6 · 95% clinician | no trial data cached |
| Serotonin syndrome | 21 | 12.1 7.9–18.5ROR 12.2 · χ² 203 / p 3e-46 | 11.3 EB05 7.4 · IC025 +2.5 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 12.6 | no trial data cached |
| Gait inability | 34 | 11.3 8.1–15.8ROR 11.5 · χ² 310 / p 1e-69 | 10.8 EB05 7.9 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 14.8 · ♀ 97% (drug 77%) | no trial data cached |
| Lower limb fracture | 18 | 10.4 6.6–16.4ROR 10.5 · χ² 143 / p 2e-33 | 9.2 EB05 5.8 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 12.4 | no trial data cached |
| Obesity | 15 | 10.4 6.3–17.1ROR 10.4 · χ² 118 / p 1e-27 | 9.0 EB05 5.4 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 13.0 | no trial data cached |
| C-reactive protein increased | 34 | 10.3 7.4–14.4ROR 10.5 · χ² 276 / p 2e-62 | 9.7 EB05 7.1 · IC025 +2.6 3/3 methods agree | Lab value / disease marker | serious PRR 11.3 · ♀ 97% (drug 77%) · 91% clinician | no trial data cached |
| Night sweats | 30 | 10.3 7.2–14.6ROR 10.4 · χ² 242 / p 8e-55 | 9.6 EB05 6.8 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 17.2 · ♀ 100% (drug 77%) · 93% clinician | no trial data cached |
| Ear pain | 18 | 10.2 6.4–16.2ROR 10.3 · χ² 140 / p 1e-32 | 9.0 EB05 5.7 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 17.8 | no trial data cached |
| Abdominal pain upper | 189 | 10.1 8.9–11.6ROR 11.1 · χ² 1,561 / p <1e-300 | 10.0 EB05 8.9 · IC025 +3.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 19.6 | 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 |
|---|---|---|---|---|---|---|
| Memory impairment | 200 | 16.0 14.1–18.3ROR 17.8 · χ² 2,817 / p <1e-300 | 16.0 EB05 14.2 · IC025 +3.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 29.1 · ♀ 98% (drug 77%) | no trial data cached |
| Hypoaesthesia (numbness) | 191 | 14.0 12.3–16.1ROR 15.5 · χ² 2,315 / p <1e-300 | 14.0 EB05 12.4 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 23.8 · ♀ 99% (drug 77%) | no trial data cached |
| Abdominal pain upper | 189 | 10.1 8.9–11.6ROR 11.1 · χ² 1,561 / p <1e-300 | 10.0 EB05 8.9 · IC025 +3.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 19.6 | no trial data cached |
| Paraesthesia (tingling/numbness) | 189 | 13.2 11.5–15.1ROR 14.6 · χ² 2,134 / p <1e-300 | 13.1 EB05 11.6 · IC025 +3.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 23.9 | no trial data cached |
| Gastrooesophageal reflux disease (acid reflux) | 181 | 24.9 21.7–28.6ROR 27.4 · χ² 4,135 / p <1e-300 | 24.8 EB05 21.9 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 42.5 · ♀ 99% (drug 77%) | no trial data cached |
| Migraine | 179 | 20.8 18.1–23.9ROR 22.9 · χ² 3,364 / p <1e-300 | 20.7 EB05 18.3 · IC025 +4.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 42.4 · ♀ 98% (drug 77%) | no trial data cached |
| Drug intolerance | 173 | 19.8 17.2–22.8ROR 21.7 · χ² 3,081 / p <1e-300 | 19.7 EB05 17.4 · IC025 +4.0 3/3 methods agree | Reporting / coding artifact | serious PRR 33.6 · ♀ 99% (drug 77%) | no trial data cached |
| Taste disorder | 165 | 91.4 78.9–105.8ROR 99.9 · χ² 14,551 / p <1e-300 | 89.7 EB05 78.8 · IC025 +5.9 3/3 methods agree | Not in label — unassessed | serious PRR 197.5 · ♀ 100% (drug 77%) | no trial data cached |
| Epilepsy | 164 | 59.5 51.4–68.9ROR 65.0 · χ² 9,332 / p <1e-300 | 58.8 EB05 51.6 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious PRR 64.5 · ♀ 100% (drug 77%) | no trial data cached |
| Depression | 130 | 6.3 5.3–7.4ROR 6.7 · χ² 576 / p 1e-127 | 6.1 EB05 5.3 · IC025 +2.3 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 6.7 | no trial data cached |
| Product use in unapproved indication | 111 | 5.0 4.2–6.0ROR 5.3 · χ² 356 / p 1e-79 | 4.9 EB05 4.2 · IC025 +2.0 3/3 methods agree | Reporting / coding artifact | serious PRR 11.5 | no trial data cached |
| Maternal exposure during pregnancy | 110 | 13.7 11.5–16.5ROR 14.5 · χ² 1,291 / p 6e-283 | 13.7 EB05 11.6 · IC025 +3.4 3/3 methods agree | Reporting / coding artifact | serious PRR 19.0 · ♀ 100% (drug 77%) · 90% clinician | no trial data cached |
| Hyperhidrosis (excessive sweating) | 83 | 7.1 5.7–8.7ROR 7.4 · χ² 430 / p 7e-96 | 6.9 EB05 5.7 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.3 · 74% consumer | no trial data cached |
| Suicidal ideation (thoughts of suicide) | 71 | 8.5 6.8–10.7ROR 8.8 · χ² 466 / p 1e-103 | 8.2 EB05 6.7 · IC025 +2.6 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 9.5 | no trial data cached |
| Sleep disorder | 55 | 8.7 6.7–11.2ROR 8.9 · χ² 366 / p 7e-82 | 8.3 EB05 6.5 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 12.4 | 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.
- Taste disorder — n=165, PRR 91.4
- Epilepsy — n=164, PRR 59.5
- Wound infection — n=34, PRR 34.5
- Hypercholesterolaemia — n=27, PRR 31.1
- Folliculitis — n=29, PRR 31.0
- Back injury — n=27, PRR 27.5
- Synovitis — n=44, PRR 26.9
- Pericarditis — n=39, PRR 25.8
- Pemphigus — n=29, PRR 25.7
- Gastrooesophageal reflux disease — n=181, PRR 24.9
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 Levomilnacipran?
In FDA FAERS, the most frequently co-reported reaction terms for Levomilnacipran are memory impairment, hypoaesthesia, abdominal pain upper, paraesthesia, gastrooesophageal reflux disease, migraine. 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 Levomilnacipran have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions ( 5.1 ) ] .
Do FAERS signals prove that Levomilnacipran 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 f371258d-91b3-4b6a-ac99-434a1964c3af, effective 20240430; matched on
openfda.generic_name.exact:"LEVOMILNACIPRAN HYDROCHLORIDE") - 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, 130 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.