Drug · FAERS side-effect profile with label screen
Ledipasvir and Sofosbuvir side effects: what 19,115 FDA adverse event reports show
Drug class
Hepatitis C Virus NS5A Inhibitor, Hepatitis C Virus Nucleotide Analog NS5B Polymerase Inhibitor
FDA label (Established Pharmacologic Class) · compare the class
Who reports
19,115 reports · 39% serious · 779 with death outcome · 43% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Ledipasvir and sofosbuvir is indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic hepatitis C virus (HCV) : genotype 1, 4, 5, or 6 inf.
FDA label, Indications and Usage
What it is
Ledipasvir and sofosbuvir tablets (90 mg/400 mg) are fixed-dose combination tablets containing ledipasvir and sofosbuvir for oral administration. Ledipasvir is an HCV NS5A inhibitor and sofosbuvir is a nucleotide analog inhibitor of HCV NS5B polymerase.
FDA label, Description section
Boxed warning
RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with ledipasvir and sofosbuvir.
FDA 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 — boxed warning 2Labeled adverse reaction 2Labeled (related wording) 2Likely indication confounding 2Reporting / coding artifact 2Lab value / disease marker 6Not in label — unassessed 24
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. 974 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 |
|---|---|---|---|---|---|---|
| Hepatitis c virus test positive | 105 | 237.1 192.0–292.7ROR 238.4 · χ² 20,053 / p <1e-300 | 188.0 EB05 159.7 · IC025 +6.3 3/3 methods agree | Lab value / disease marker | serious n=35 | no trial data cached |
| Hepatic cancer recurrent | 45 | 206.2 150.0–283.6ROR 206.7 · χ² 7,547 / p <1e-300 | 161.6 EB05 125.7 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious n=45 · 100% clinician | no trial data cached |
| Genotype drug resistance test positive | 112 | 132.7 109.1–161.4ROR 133.5 · χ² 12,921 / p <1e-300 | 116.0 EB05 99.1 · IC025 +6.0 3/3 methods agree | Lab value / disease marker | serious n=112 · 95% clinician | no trial data cached |
| Hepatitis c rna positive | 14 | 95.8 55.5–165.5ROR 95.9 · χ² 1,121 / p 4e-246 | 79.0 EB05 50.0 · IC025 +3.6 3/3 methods agree | Lab value / disease marker | serious n=12 | no trial data cached |
| Hepatitis c | 885 | 85.7 80.1–91.6ROR 89.8 · χ² 68,599 / p <1e-300 | 79.3 EB05 75.0 · IC025 +6.1 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 123.7 | no trial data cached |
| Hepatocellular carcinoma | 402 | 61.0 55.2–67.4ROR 62.3 · χ² 22,405 / p <1e-300 | 57.6 EB05 53.1 · IC025 +5.6 3/3 methods agree | Not in label — unassessed | serious PRR 85.2 · 95% clinician | no trial data cached |
| Laryngomalacia | 13 | 43.8 25.2–76.2ROR 43.8 · χ² 482 / p 4e-107 | 39.9 EB05 24.8 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=13 | no trial data cached |
| Cryoglobulinaemia | 23 | 37.0 24.4–56.0ROR 37.0 · χ² 744 / p 5e-164 | 34.8 EB05 24.4 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=23 | no trial data cached |
| Oesophageal varices haemorrhage | 49 | 25.3 19.0–33.5ROR 25.3 · χ² 1,092 / p 8e-240 | 24.5 EB05 19.3 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=49 · 94% clinician | no trial data cached |
| Product difficult to swallow | 18 | 19.5 12.2–31.1ROR 19.5 · χ² 293 / p 7e-66 | 18.7 EB05 12.3 · IC025 +2.9 3/3 methods agree | Reporting / coding artifact | – | no trial data cached |
| Viral mutation identified | 58 | 17.4 13.4–22.5ROR 17.4 · χ² 866 / p 1e-190 | 17.0 EB05 13.6 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=58 · ♀ 14% (drug 43%) · 97% clinician | no trial data cached |
| Hepatic encephalopathy | 121 | 14.4 12.0–17.2ROR 14.5 · χ² 1,475 / p <1e-300 | 14.1 EB05 12.1 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 20.7 | no trial data cached |
| Hepatitis b reactivation | 37 | 12.9 9.3–17.8ROR 12.9 · χ² 390 / p 4e-87 | 12.4 EB05 9.2 · IC025 +2.9 3/3 methods agree | Labeled — boxed warning synonym match | serious n=37 · 100% clinician | no trial data cached |
| Liver transplant | 37 | 11.3 8.2–15.6ROR 11.3 · χ² 334 / p 6e-75 | 10.7 EB05 7.9 · IC025 +2.8 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=37 | no trial data cached |
| Cholangiocarcinoma | 15 | 11.2 6.7–18.6ROR 11.2 · χ² 128 / p 6e-30 | 9.7 EB05 5.8 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious n=15 | no trial data cached |
| Varices oesophageal | 28 | 10.3 7.1–14.9ROR 10.3 · χ² 223 / p 1e-50 | 9.5 EB05 6.6 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=28 | no trial data cached |
| Hepatorenal syndrome | 15 | 9.8 5.9–16.3ROR 9.8 · χ² 109 / p 1e-25 | 8.3 EB05 5.1 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious n=15 | no trial data cached |
| Hepatic mass | 16 | 9.2 5.6–15.0ROR 9.2 · χ² 108 / p 1e-25 | 7.8 EB05 4.9 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious n=16 | no trial data cached |
| Ammonia increased | 39 | 8.4 6.2–11.6ROR 8.5 · χ² 247 / p 7e-56 | 7.9 EB05 5.9 · IC025 +2.4 3/3 methods agree | Lab value / disease marker | serious n=27 | no trial data cached |
| Hepatic cirrhosis | 141 | 8.3 7.1–9.8ROR 8.4 · χ² 896 / p 3e-197 | 8.1 EB05 7.0 · IC025 +2.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 12.0 | no trial data cached |
| Hepatic pain | 32 | 8.3 5.8–11.7ROR 8.3 · χ² 196 / p 1e-44 | 7.6 EB05 5.5 · IC025 +2.3 3/3 methods agree | Labeled (related wording) related wording | serious n=13 | no trial data cached |
| Portal vein thrombosis | 23 | 7.9 5.2–11.9ROR 7.9 · χ² 131 / p 2e-30 | 7.0 EB05 4.8 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious n=23 · 90% clinician | no trial data cached |
| Ascites | 203 | 7.6 6.6–8.7ROR 7.7 · χ² 1,154 / p 4e-253 | 7.5 EB05 6.6 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 11.2 · 93% clinician | no trial data cached |
| Headache | 3,707 | 6.5 6.3–6.7ROR 7.9 · χ² 17,775 / p <1e-300 | 6.5 EB05 6.3 · IC025 +2.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.0 | no trial data cached |
| Fanconi syndrome acquired | 10 | 6.3 3.4–11.7ROR 6.3 · χ² 39 / p 2e-10 | 5.0 EB05 2.9 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious n=10 | no trial data cached |
| Glomerular filtration rate decreased | 69 | 6.3 5.0–8.0ROR 6.3 · χ² 299 / p 2e-67 | 6.0 EB05 4.9 · IC025 +2.2 3/3 methods agree | Lab value / disease marker | serious PRR 9.6 · 100% clinician | no trial data cached |
| Fatigue (tiredness) | 4,131 | 5.9 5.7–6.0ROR 7.2 · χ² 17,192 / p <1e-300 | 5.8 EB05 5.7 · IC025 +2.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.5 | no trial data cached |
| Energy increased | 30 | 5.6 3.9–8.0ROR 5.6 · χ² 107 / p 2e-25 | 5.1 EB05 3.8 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious n=3 | no trial data cached |
| Fibrosis | 15 | 5.4 3.2–8.9ROR 5.4 · χ² 49 / p 1e-12 | 4.6 EB05 3.0 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious n=14 | no trial data cached |
| Treatment failure | 374 | 5.0 4.5–5.5ROR 5.1 · χ² 1,198 / p 8e-263 | 5.0 EB05 4.6 · IC025 +2.1 3/3 methods agree | Reporting / coding artifact | serious PRR 13.7 · ♀ 22% (drug 43%) | no trial data cached |
| Endotracheal intubation | 12 | 4.7 2.7–8.3ROR 4.7 · χ² 31 / p 1e-8 | 4.1 EB05 2.5 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial data cached |
| Hepatitis b | 26 | 4.7 3.2–6.9ROR 4.7 · χ² 72 / p 1e-17 | 4.4 EB05 3.1 · IC025 +1.5 3/3 methods agree | Labeled — boxed warning exact term | serious n=26 | no trial data cached |
| Hepatic cancer | 103 | 4.7 3.8–5.7ROR 4.7 · χ² 292 / p 7e-66 | 4.6 EB05 3.9 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 6.8 | no trial data cached |
| Viral load increased | 16 | 4.5 2.8–7.4ROR 4.5 · χ² 40 / p 1e-10 | 4.0 EB05 2.6 · IC025 +1.2 3/3 methods agree | Lab value / disease marker | serious n=10 | no trial data cached |
| Virologic failure | 22 | 4.5 3.0–6.8ROR 4.5 · χ² 56 / p 4e-14 | 4.1 EB05 2.9 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious n=21 · 100% clinician | no trial data cached |
| Congestive cardiomyopathy | 17 | 4.4 2.7–7.1ROR 4.4 · χ² 42 / p 6e-11 | 4.0 EB05 2.6 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious n=17 | no trial data cached |
| Immune thrombocytopenic purpura | 11 | 4.2 2.3–7.6ROR 4.2 · χ² 24 / p 5e-7 | 3.6 EB05 2.2 · IC025 +0.9 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial data cached |
| B-cell lymphoma | 12 | 3.9 2.2–6.8ROR 3.9 · χ² 23 / p 1e-6 | 3.4 EB05 2.1 · IC025 +0.8 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial data cached |
| Hepatic lesion | 15 | 3.8 2.3–6.3ROR 3.8 · χ² 28 / p 5e-8 | 3.5 EB05 2.2 · IC025 +0.9 3/3 methods agree | Not in label — unassessed | serious n=13 | no trial data cached |
| Hepatic neoplasm | 11 | 3.7 2.1–6.7ROR 3.7 · χ² 19 / p 6e-6 | 3.3 EB05 2.0 · IC025 +0.7 | Not in label — unassessed | serious n=10 | 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 |
|---|---|---|---|---|---|---|
| Fatigue (tiredness) | 4,131 | 5.9 5.7–6.0ROR 7.2 · χ² 17,192 / p <1e-300 | 5.8 EB05 5.7 · IC025 +2.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.5 | no trial data cached |
| Headache | 3,707 | 6.5 6.3–6.7ROR 7.9 · χ² 17,775 / p <1e-300 | 6.5 EB05 6.3 · IC025 +2.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.0 | no trial data cached |
| Nausea | 1,242 | 1.7 1.6–1.8ROR 1.8 · χ² 395 / p 4e-88 | 1.7 EB05 1.6 · IC025 +0.7 | Labeled adverse reaction exact term | serious PRR 0.9 | no trial data cached |
| Drug ineffective (drug did not work) | 1,138 | 0.9 0.9–1.0ROR 0.9 · χ² 3 / p 0.033 | 0.9 EB05 0.9 · IC025 -0.2 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 3.8 | no trial data cached |
| Diarrhoea (diarrhea) | 913 | 1.6 1.5–1.7ROR 1.6 · χ² 187 / p 6e-43 | 1.6 EB05 1.5 · IC025 +0.5 | Labeled adverse reaction exact term | serious PRR 0.8 | no trial data cached |
| Hepatitis c | 885 | 85.7 80.1–91.6ROR 89.8 · χ² 68,599 / p <1e-300 | 79.3 EB05 75.0 · IC025 +6.1 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 123.7 | no trial data cached |
| Insomnia (trouble sleeping) | 835 | 3.4 3.2–3.7ROR 3.6 · χ² 1,458 / p <1e-300 | 3.4 EB05 3.2 · IC025 +1.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.0 | no trial data cached |
| Vomiting | 442 | 1.0 0.9–1.1ROR 1.0 · χ² 0 / p 0.245 | 1.0 EB05 1.0 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Not in label — unassessed | serious PRR 1.0 | no trial data cached |
| Dizziness | 440 | 1.0 0.9–1.1ROR 1.0 · χ² 0 / p 0.263 | 1.0 EB05 0.9 · IC025 -0.2 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 0.9 | no trial data cached |
| Drug dose omission | 436 | 2.9 2.6–3.1ROR 2.9 · χ² 527 / p 5e-117 | 2.8 EB05 2.6 · IC025 +1.4 3/3 methods agree | Reporting / coding artifact | serious PRR 3.7 · 92% clinician | no trial data cached |
| Hepatocellular carcinoma | 402 | 61.0 55.2–67.4ROR 62.3 · χ² 22,405 / p <1e-300 | 57.6 EB05 53.1 · IC025 +5.6 3/3 methods agree | Not in label — unassessed | serious PRR 85.2 · 95% clinician | no trial data cached |
| Treatment failure | 374 | 5.0 4.5–5.5ROR 5.1 · χ² 1,198 / p 8e-263 | 5.0 EB05 4.6 · IC025 +2.1 3/3 methods agree | Reporting / coding artifact | serious PRR 13.7 · ♀ 22% (drug 43%) | no trial data cached |
| Rash | 362 | 0.9 0.8–1.0ROR 0.9 · χ² 3 / p 0.048 | 0.9 EB05 0.8 · IC025 -0.3 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 0.7 | no trial data cached |
| Asthenia (weakness) | 337 | 1.0 0.9–1.1ROR 1.0 · χ² 0 / p 0.387 | 1.0 EB05 0.9 · IC025 -0.2 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 1.2 | no trial data cached |
| Arthralgia (joint pain) | 330 | 0.9 0.8–1.0ROR 0.9 · χ² 6 / p 0.007 | 0.9 EB05 0.8 · IC025 -0.4 PRR-only: not supported by EBGM or IC | Not in label — unassessed | serious PRR 0.7 | 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.
- Hepatic cancer recurrent — n=45, PRR 206.2
- Hepatocellular carcinoma — n=402, PRR 61.0
- Cryoglobulinaemia — n=23, PRR 37.0
- Oesophageal varices haemorrhage — n=49, PRR 25.3
- Viral mutation identified — n=58, PRR 17.4
- Hepatic encephalopathy — n=121, PRR 14.4
- Varices oesophageal — n=28, PRR 10.3
- Portal vein thrombosis — n=23, PRR 7.9
- Ascites — n=203, PRR 7.6
- Energy increased — n=30, PRR 5.6
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 Ledipasvir and Sofosbuvir?
In FDA FAERS, the most frequently co-reported reaction terms for Ledipasvir and Sofosbuvir are fatigue, headache, nausea, diarrhoea, hepatitis c, insomnia. 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 Ledipasvir and Sofosbuvir have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with ledipasvir and sofosbuvir.
Do FAERS signals prove that Ledipasvir and Sofosbuvir 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 46f4a73b-0cd6-4902-9092-3ac79e882c1a, effective 20250110; matched on
openfda.generic_name.exact:"LEDIPASVIR AND SOFOSBUVIR") - 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, 1,014 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.