Sofosbuvir side effects: what 19,615 FDA adverse event reports show
Drug class
Hepatitis C Virus Nucleotide Analog NS5B Polymerase Inhibitor
Brand names
Sovaldi
Who reports
19,615 reports · 72% serious · 1,797 with death outcome · 39% female
Used for
SOVALDI is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor indicated for the treatment of: Adult patients with genotype 1, 2, 3 or 4 chronic HCV infection without cirrhosis or with compensated cirrhosis as a component of a combination antiviral treatment regimen.
What it is
SOVALDI (sofosbuvir) is a nucleotide analog inhibitor of HCV NS5B polymerase. The IUPAC name for sofosbuvir is ( S )-isopropyl 2-(( S )-(((2 R ,3 R ,4 R ,5 R )-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2 H )-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)-(phenoxy)phosphorylamino)propanoate.
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 SOVALDI. HBV reacti.
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.
- 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. 989 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 |
|---|---|---|---|---|---|---|
| Hepatic hydrothorax | 25 | 487.9 303.8–783.8ROR 488.6 · χ² 7,974 / p <1e-300 | 266.0 EB05 189.5 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious n=25 · ♀ 0% (drug 39%) · 100% clinician | not reported in cached trials |
| Hepatitis c rna positive | 47 | 396.3 283.5–554.0ROR 397.2 · χ² 13,182 / p <1e-300 | 258.1 EB05 201.9 · IC025 +5.7 3/3 methods agree | Lab value / disease marker | serious n=46 · 100% clinician | not reported in cached trials |
| Genotype drug resistance test positive | 223 | 293.1 252.8–339.7ROR 296.4 · χ² 50,559 / p <1e-300 | 225.1 EB05 201.4 · IC025 +7.0 3/3 methods agree | Lab value / disease marker | serious n=222 · ♀ 16% (drug 39%) · 95% clinician | not reported in cached trials |
| Amaurosis fugax | 208 | 258.5 222.3–300.7ROR 261.3 · χ² 42,642 / p <1e-300 | 203.9 EB05 181.7 · IC025 +6.9 3/3 methods agree | Not in label — unassessed | serious n=208 · 96% clinician | not reported in cached trials |
| Remission not achieved | 98 | 200.9 162.0–249.3ROR 202.0 · χ² 16,208 / p <1e-300 | 163.6 EB05 138.2 · IC025 +6.2 3/3 methods agree | Not in label — unassessed | serious n=98 · 100% clinician | not reported in cached trials |
| Hepatitis c | 1,736 | 177.3 168.8–186.2ROR 194.4 · χ² 260,518 / p <1e-300 | 151.7 EB05 145.8 · IC025 +7.1 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 127.1 | not reported in cached trials |
| Hepatitis c rna increased | 48 | 173.3 127.7–235.0ROR 173.7 · χ² 6,913 / p <1e-300 | 140.7 EB05 110.4 · IC025 +5.4 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=42 | not reported in cached trials |
| Hepatic cancer recurrent | 38 | 164.8 117.1–231.9ROR 165.1 · χ² 5,210 / p <1e-300 | 133.2 EB05 101.3 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=38 · 100% clinician | not reported in cached trials |
| Hepatocellular carcinoma | 911 | 145.0 135.5–155.2ROR 152.1 · χ² 114,464 / p <1e-300 | 127.3 EB05 120.5 · IC025 +6.8 3/3 methods agree | Not in label — unassessed | serious PRR 101.1 · 90% clinician | not reported in cached trials |
| Cryoglobulinaemia | 74 | 125.4 98.6–159.5ROR 125.9 · χ² 8,050 / p <1e-300 | 109.1 EB05 89.8 · IC025 +5.6 3/3 methods agree | Not in label — unassessed | serious n=74 · ♀ 68% (drug 39%) · 94% clinician | not reported in cached trials |
| Hepatitis c virus test positive | 41 | 79.6 58.0–109.3ROR 79.7 · χ² 2,885 / p <1e-300 | 71.7 EB05 55.1 · IC025 +4.8 3/3 methods agree | Lab value / disease marker | serious n=33 | not reported in cached trials |
| Chronic hepatitis c | 27 | 78.4 53.0–115.9ROR 78.5 · χ² 1,849 / p <1e-300 | 69.6 EB05 50.2 · IC025 +4.3 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=27 · ♀ 15% (drug 39%) · 93% clinician | not reported in cached trials |
| Therapeutic embolisation | 20 | 72.4 46.1–113.9ROR 72.5 · χ² 1,252 / p 1e-274 | 63.9 EB05 43.7 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=20 · ♀ 15% (drug 39%) | not reported in cached trials |
| Glomerulonephritis membranoproliferative | 33 | 71.6 50.3–101.8ROR 71.7 · χ² 2,085 / p <1e-300 | 64.7 EB05 48.2 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=33 · 100% clinician | not reported in cached trials |
| Bleeding varicose vein | 34 | 71.5 50.6–101.2ROR 71.6 · χ² 2,149 / p <1e-300 | 64.7 EB05 48.4 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=29 · ♀ 14% (drug 39%) · 100% clinician | not reported in cached trials |
| Complications of transplanted lung | 19 | 71.0 44.6–113.0ROR 71.1 · χ² 1,164 / p 2e-255 | 62.6 EB05 42.4 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Genital herpes simplex | 11 | 58.8 32.1–108.0ROR 58.9 · χ² 539 / p 2e-119 | 51.1 EB05 30.5 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Oesophageal varices haemorrhage | 108 | 55.8 46.0–67.7ROR 56.1 · χ² 5,471 / p <1e-300 | 52.6 EB05 44.8 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=108 | not reported in cached trials |
| Hepatitis b reactivation | 137 | 48.1 40.6–57.1ROR 48.5 · χ² 6,002 / p <1e-300 | 45.8 EB05 39.7 · IC025 +5.0 3/3 methods agree | Labeled — boxed warning synonym match | serious n=137 · 97% clinician | not reported in cached trials |
| Hepatectomy | 13 | 47.6 27.3–82.9ROR 47.6 · χ² 523 / p 4e-116 | 42.9 EB05 26.7 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Urinary tract disorder | 186 | 46.1 39.8–53.3ROR 46.5 · χ² 7,818 / p <1e-300 | 44.0 EB05 39.0 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=186 · 98% clinician | not reported in cached trials |
| Hepatic encephalopathy | 364 | 43.3 39.1–48.1ROR 44.1 · χ² 14,424 / p <1e-300 | 41.6 EB05 38.1 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious PRR 33.2 | not reported in cached trials |
| Hepatorenal syndrome | 66 | 43.3 33.8–55.3ROR 43.4 · χ² 2,577 / p <1e-300 | 41.1 EB05 33.5 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=66 | not reported in cached trials |
| Liver transplant | 133 | 40.7 34.3–48.4ROR 41.0 · χ² 4,925 / p <1e-300 | 39.0 EB05 33.8 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious n=133 · ♀ 19% (drug 39%) | not reported in cached trials |
| Gastric varices haemorrhage | 12 | 40.2 22.6–71.4ROR 40.2 · χ² 404 / p 3e-90 | 36.7 EB05 22.3 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Viral test positive | 13 | 39.3 22.6–68.3ROR 39.3 · χ² 431 / p 5e-96 | 36.1 EB05 22.4 · IC025 +3.1 3/3 methods agree | Lab value / disease marker | serious n=6 | not reported in cached trials |
| Abdominal cavity drainage | 14 | 36.5 21.4–62.2ROR 36.5 · χ² 434 / p 1e-96 | 33.9 EB05 21.4 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Viral load increased | 120 | 33.9 28.3–40.6ROR 34.1 · χ² 3,678 / p <1e-300 | 32.7 EB05 28.1 · IC025 +4.6 3/3 methods agree | Lab value / disease marker | serious n=98 | not reported in cached trials |
| Choroiditis | 11 | 32.2 17.7–58.7ROR 32.2 · χ² 293 / p 5e-66 | 29.8 EB05 17.7 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Hyperbilirubinaemia | 296 | 31.6 28.2–35.4ROR 32.1 · χ² 8,490 / p <1e-300 | 30.7 EB05 27.8 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious PRR 24.7 | not reported in cached trials |
| Exposure via direct contact | 27 | 31.1 21.2–45.5ROR 31.1 · χ² 734 / p 5e-162 | 29.6 EB05 21.4 · IC025 +3.7 3/3 methods agree | Reporting / coding artifact | 100% consumer | not reported in cached trials |
| Haemorrhagic stroke | 218 | 30.5 26.7–34.8ROR 30.8 · χ² 6,013 / p <1e-300 | 29.6 EB05 26.4 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious PRR 23.5 · 95% clinician | not reported in cached trials |
| Portal hypertensive gastropathy | 15 | 29.6 17.7–49.4ROR 29.6 · χ² 376 / p 5e-84 | 27.9 EB05 17.9 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Viral mutation identified | 96 | 28.4 23.2–34.7ROR 28.5 · χ² 2,441 / p <1e-300 | 27.5 EB05 23.2 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=96 · 96% clinician | not reported in cached trials |
| Virologic failure | 131 | 26.6 22.4–31.6ROR 26.7 · χ² 3,121 / p <1e-300 | 25.9 EB05 22.4 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=122 · 94% clinician | not reported in cached trials |
| Porphyria non-acute | 10 | 24.9 13.3–46.5ROR 24.9 · χ² 201 / p 6e-46 | 23.1 EB05 13.0 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Portal vein thrombosis | 73 | 24.8 19.7–31.2ROR 24.9 · χ² 1,605 / p <1e-300 | 24.1 EB05 19.8 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=73 | not reported in cached trials |
| Ascites | 643 | 23.9 22.1–25.8ROR 24.6 · χ² 13,776 / p <1e-300 | 23.4 EB05 21.9 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious PRR 18.8 | not reported in cached trials |
| Hepatic cirrhosis | 386 | 22.5 20.4–24.9ROR 23.0 · χ² 7,760 / p <1e-300 | 22.1 EB05 20.3 · IC025 +4.3 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 17.6 | not reported in cached trials |
| Ocular discomfort | 215 | 21.6 18.9–24.7ROR 21.8 · χ² 4,116 / p <1e-300 | 21.1 EB05 18.9 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=209 · 94% clinician | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Sofosbuvir as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (0 of 40 signal terms matched).
- NCT02292706 — A Registry for Participants With Cirrhosis Who Achieve a Sustained Virologic Response Following Treatment With (N=1609, phase n/a; 8 AE terms posted; arms: SOF+RBV; LDV/SOF; LDV/SOF+RBV; SOF/VEL)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
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) | 2,314 | 3.2 3.1–3.3ROR 3.5 · χ² 3,602 / p <1e-300 | 3.2 EB05 3.1 · IC025 +1.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.2 | not reported in cached trials |
| Drug ineffective (drug did not work) | 1,931 | 1.6 1.5–1.6ROR 1.6 · χ² 424 / p 2e-94 | 1.6 EB05 1.5 · IC025 +0.6 | Reporting / coding artifact | serious PRR 3.4 | not reported in cached trials |
| Hepatitis c | 1,736 | 177.3 168.8–186.2ROR 194.4 · χ² 260,518 / p <1e-300 | 151.7 EB05 145.8 · IC025 +7.1 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 127.1 | not reported in cached trials |
| Headache | 1,644 | 2.8 2.7–2.9ROR 3.0 · χ² 1,971 / p <1e-300 | 2.8 EB05 2.7 · IC025 +1.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.2 | not reported in cached trials |
| Nausea | 1,395 | 1.9 1.8–2.0ROR 2.0 · χ² 607 / p 2e-134 | 1.9 EB05 1.8 · IC025 +0.8 | Labeled adverse reaction exact term | serious PRR 1.6 | not reported in cached trials |
| Off label use (used outside approved label) | 1,388 | 1.7 1.6–1.8ROR 1.8 · χ² 426 / p 5e-95 | 1.7 EB05 1.6 · IC025 +0.7 | Reporting / coding artifact | serious PRR 1.5 | not reported in cached trials |
| Anaemia (low red blood cells) | 1,188 | 6.7 6.3–7.1ROR 7.1 · χ² 5,760 / p <1e-300 | 6.6 EB05 6.3 · IC025 +2.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.8 | not reported in cached trials |
| Insomnia (trouble sleeping) | 1,061 | 4.3 4.0–4.5ROR 4.5 · χ² 2,672 / p <1e-300 | 4.2 EB05 4.0 · IC025 +2.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.7 | not reported in cached trials |
| Hepatocellular carcinoma | 911 | 145.0 135.5–155.2ROR 152.1 · χ² 114,464 / p <1e-300 | 127.3 EB05 120.5 · IC025 +6.8 3/3 methods agree | Not in label — unassessed | serious PRR 101.1 · 90% clinician | not reported in cached trials |
| Treatment failure | 837 | 11.0 10.3–11.8ROR 11.5 · χ² 7,554 / p <1e-300 | 10.9 EB05 10.3 · IC025 +3.3 3/3 methods agree | Reporting / coding artifact | serious PRR 15.4 | not reported in cached trials |
| Dyspnoea (shortness of breath) | 786 | 1.5 1.4–1.6ROR 1.5 · χ² 128 / p 6e-30 | 1.5 EB05 1.4 · IC025 +0.5 | Labeled (related wording) related wording | serious PRR 1.2 | not reported in cached trials |
| Asthenia (weakness) | 779 | 2.2 2.1–2.4ROR 2.3 · χ² 528 / p 5e-117 | 2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.9 | not reported in cached trials |
| Diarrhoea (diarrhea) | 743 | 1.2 1.2–1.3ROR 1.2 · χ² 34 / p 3e-9 | 1.2 EB05 1.2 · IC025 +0.2 | Labeled adverse reaction exact term | serious PRR 1.2 | not reported in cached trials |
| Dizziness | 712 | 1.5 1.4–1.6ROR 1.5 · χ² 133 / p 4e-31 | 1.5 EB05 1.4 · IC025 +0.5 | Labeled adverse reaction exact term | serious PRR 1.5 | NCT02292706: 1/275 (0.4%) on Sofosbuvir |
| Pruritus (itching) | 709 | 2.0 1.9–2.2ROR 2.0 · χ² 363 / p 3e-81 | 2.0 EB05 1.9 · IC025 +0.9 | Labeled adverse reaction exact term | serious PRR 2.8 | not reported in cached trials |
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 hydrothorax — n=25, PRR 487.9
- Amaurosis fugax — n=208, PRR 258.5
- Remission not achieved — n=98, PRR 200.9
- Hepatic cancer recurrent — n=38, PRR 164.8
- Hepatocellular carcinoma — n=911, PRR 145.0
- Cryoglobulinaemia — n=74, PRR 125.4
- Therapeutic embolisation — n=20, PRR 72.4
- Glomerulonephritis membranoproliferative — n=33, PRR 71.6
- Bleeding varicose vein — n=34, PRR 71.5
- Oesophageal varices haemorrhage — n=108, PRR 55.8
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 Sofosbuvir?
In FDA FAERS, the most frequently co-reported reaction terms for Sofosbuvir are fatigue, hepatitis c, headache, nausea, anaemia, 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 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 SOVALDI. HBV reacti.
Do FAERS signals prove that 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 80beab2c-396e-4a37-a4dc-40fdb62859cf, effective 20241226; matched on
openfda.generic_name.exact:"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, 1,029 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 - ClinicalTrials.gov API v2 (query
SOFOSBUVIR, results-bearing studies sorted by enrollment)
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.