Drug · FAERS side-effect profile with label screen
Sapropterin Dihydrochloride side effects: what 6,330 FDA adverse event reports show
Drug class
Phenylalanine hydroxylase activator
FDA label, Indications wording
Who reports
6,330 reports · 17% serious · 74 with death outcome · 61% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Sapropterin dihydrochloride powder for oral solution is indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin-(BH4-) responsive Phenylketonuria (PKU). Sapropterin dihydrochloride powder for oral solution is to be used in conjunction with a Phe-restricted diet.
FDA label, Indications and Usage
What it is
Sapropterin dihydrochloride is an orally administered Phenylalanine Hydroxylase activator (or PAH activator). Sapropterin dihydrochloride, the active pharmaceutical ingredient in sapropterin d.
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 40 strongest signals
Labeled adverse reaction 6Labeled (related wording) 3Reporting / coding artifact 7Not in label — unassessed 24
What the badges mean
- 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.
- 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. 76 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 |
|---|---|---|---|---|---|---|
| Therapy non-responder | 364 | 27.3 24.7–30.1ROR 28.9 · χ² 9,122 / p <1e-300 | 27.0 EB05 24.8 · IC025 +4.5 3/3 methods agree | Reporting / coding artifact | serious PRR 1.6 · 88% consumer | no trial data cached |
| Psychomotor hyperactivity | 134 | 26.8 22.7–31.7ROR 27.4 · χ² 3,281 / p <1e-300 | 26.5 EB05 23.0 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 6.6 · 78% consumer | no trial data cached |
| Product prescribing error | 143 | 20.1 17.1–23.7ROR 20.6 · χ² 2,565 / p <1e-300 | 19.9 EB05 17.3 · IC025 +4.0 3/3 methods agree | Reporting / coding artifact | serious PRR 19.6 | no trial data cached |
| Gastroenteritis viral | 75 | 13.8 11.0–17.2ROR 13.9 · χ² 872 / p 6e-192 | 13.6 EB05 11.1 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious PRR 1.2 · 83% consumer | no trial data cached |
| Maternal exposure during pregnancy | 301 | 11.3 10.1–12.7ROR 11.8 · χ² 2,828 / p <1e-300 | 11.3 EB05 10.2 · IC025 +3.3 3/3 methods agree | Reporting / coding artifact | serious PRR 16.7 · ♀ 99% (drug 61%) | no trial data cached |
| Pharyngitis streptococcal | 28 | 8.6 5.9–12.4ROR 8.6 · χ² 180 / p 3e-41 | 7.8 EB05 5.6 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious n=1 · 79% consumer | no trial data cached |
| Seasonal allergy | 30 | 7.0 4.9–10.1ROR 7.1 · χ² 149 / p 1e-34 | 6.4 EB05 4.7 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | 83% consumer | no trial data cached |
| Pregnancy | 42 | 6.9 5.1–9.3ROR 6.9 · χ² 205 / p 8e-47 | 6.5 EB05 5.0 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 11.2 · ♀ 100% (drug 61%) · 79% consumer | no trial data cached |
| Ear infection | 54 | 6.7 5.2–8.8ROR 6.8 · χ² 258 / p 2e-58 | 6.4 EB05 5.1 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.8 · 78% consumer | no trial data cached |
| Abnormal behaviour | 71 | 5.9 4.7–7.4ROR 6.0 · χ² 284 / p 4e-64 | 5.7 EB05 4.7 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 4.2 | no trial data cached |
| Abortion spontaneous | 67 | 5.5 4.3–7.0ROR 5.6 · χ² 244 / p 3e-55 | 5.3 EB05 4.3 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 18.3 · ♀ 100% (drug 61%) | no trial data cached |
| Aggression | 83 | 5.5 4.4–6.8ROR 5.5 · χ² 300 / p 1e-67 | 5.3 EB05 4.4 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 2.5 | no trial data cached |
| Exposure during pregnancy | 93 | 5.0 4.1–6.1ROR 5.0 · χ² 290 / p 2e-65 | 4.8 EB05 4.1 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 7.0 · ♀ 100% (drug 61%) · 80% consumer | no trial data cached |
| Mood altered | 39 | 4.8 3.5–6.5ROR 4.8 · χ² 112 / p 2e-26 | 4.5 EB05 3.4 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 2.2 | no trial data cached |
| Rhinorrhoea (runny nose) | 85 | 4.4 3.5–5.4ROR 4.4 · χ² 218 / p 1e-49 | 4.3 EB05 3.6 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 2.1 · 88% consumer | no trial data cached |
| Anger | 44 | 4.3 3.2–5.8ROR 4.3 · χ² 108 / p 1e-25 | 4.1 EB05 3.2 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 3.8 · 74% consumer | no trial data cached |
| Nasal congestion (stuffy nose) | 74 | 4.2 3.3–5.3ROR 4.2 · χ² 177 / p 1e-40 | 4.1 EB05 3.4 · IC025 +1.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.6 · 86% consumer | no trial data cached |
| Appendicitis | 11 | 3.9 2.2–7.1ROR 3.9 · χ² 21 / p 2e-6 | 3.4 EB05 2.1 · IC025 +0.8 3/3 methods agree | Not in label — unassessed | serious PRR 13.3 | no trial data cached |
| Viral infection | 36 | 3.6 2.6–5.0ROR 3.6 · χ² 65 / p 4e-16 | 3.4 EB05 2.6 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 1.4 · 80% consumer | no trial data cached |
| Abdominal discomfort | 179 | 3.5 3.1–4.1ROR 3.6 · χ² 327 / p 2e-73 | 3.5 EB05 3.1 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 1.5 · 81% consumer | no trial data cached |
| Increased appetite | 20 | 3.5 2.3–5.5ROR 3.5 · χ² 34 / p 3e-9 | 3.3 EB05 2.3 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 1.5 | no trial data cached |
| Gastrooesophageal reflux disease (acid reflux) | 85 | 3.5 2.8–4.3ROR 3.5 · χ² 151 / p 6e-35 | 3.5 EB05 2.9 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 3.3 · 81% consumer | no trial data cached |
| Abdominal pain upper | 217 | 3.5 3.1–4.0ROR 3.6 · χ² 388 / p 1e-86 | 3.5 EB05 3.1 · IC025 +1.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 1.6 · 85% consumer | no trial data cached |
| Product taste abnormal | 14 | 3.4 2.0–5.8ROR 3.5 · χ² 22 / p 1e-6 | 3.2 EB05 2.0 · IC025 +0.8 3/3 methods agree | Reporting / coding artifact | – | no trial data cached |
| Irritability | 61 | 3.4 2.6–4.3ROR 3.4 · χ² 99 / p 1e-23 | 3.3 EB05 2.7 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.0 · 72% consumer | no trial data cached |
| Gastritis | 26 | 3.3 2.2–4.8ROR 3.3 · χ² 39 / p 2e-10 | 3.1 EB05 2.3 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.4 · ♀ 90% (drug 61%) · 81% consumer | no trial data cached |
| Oropharyngeal pain (sore throat) | 89 | 3.2 2.6–3.9ROR 3.2 · χ² 132 / p 9e-31 | 3.1 EB05 2.6 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.9 · 86% consumer | no trial data cached |
| Gastroenteritis | 14 | 3.2 1.9–5.4ROR 3.2 · χ² 19 / p 7e-6 | 2.9 EB05 1.9 · IC025 +0.7 | Not in label — unassessed | serious PRR 4.9 | no trial data cached |
| Dyspepsia (indigestion) | 94 | 3.2 2.6–3.9ROR 3.2 · χ² 138 / p 3e-32 | 3.1 EB05 2.6 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 0.9 · 74% consumer | no trial data cached |
| Product dose omission | 63 | 3.2 2.5–4.0ROR 3.2 · χ² 91 / p 9e-22 | 3.1 EB05 2.5 · IC025 +1.2 3/3 methods agree | Reporting / coding artifact | serious PRR 4.1 · 87% consumer | no trial data cached |
| Mood swings | 30 | 3.1 2.2–4.5ROR 3.1 · χ² 41 / p 8e-11 | 3.0 EB05 2.2 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 0.6 · 83% consumer | no trial data cached |
| Flatulence (gas) | 53 | 3.1 2.4–4.1ROR 3.1 · χ² 74 / p 5e-18 | 3.0 EB05 2.4 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 0.9 · 85% consumer | no trial data cached |
| Injection site reaction | 62 | 3.0 2.3–3.8ROR 3.0 · χ² 80 / p 1e-19 | 2.9 EB05 2.4 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 1.7 · 77% consumer | no trial data cached |
| Pharyngitis | 11 | 2.9 1.6–5.3ROR 2.9 · χ² 12 / p 3e-4 | 2.7 EB05 1.6 · IC025 +0.4 | Labeled adverse reaction exact term | serious PRR 2.3 | no trial data cached |
| Hypophagia | 22 | 2.9 1.9–4.4ROR 2.9 · χ² 25 / p 3e-7 | 2.7 EB05 1.9 · IC025 +0.7 | Not in label — unassessed | serious PRR 4.2 · 77% consumer | no trial data cached |
| Nasopharyngitis (common cold) | 160 | 2.9 2.5–3.3ROR 2.9 · χ² 194 / p 2e-44 | 2.8 EB05 2.5 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 1.2 · 83% consumer | no trial data cached |
| Injection site rash | 26 | 2.8 1.9–4.2ROR 2.8 · χ² 29 / p 3e-8 | 2.7 EB05 2.0 · IC025 +0.8 | Labeled (related wording) related wording | serious n=2 | no trial data cached |
| Hiatus hernia | 11 | 2.8 1.6–5.1ROR 2.8 · χ² 11 / p 4e-4 | 2.6 EB05 1.6 · IC025 +0.4 | Not in label — unassessed | serious PRR 7.8 | no trial data cached |
| Treatment noncompliance | 46 | 2.8 2.1–3.7ROR 2.8 · χ² 52 / p 3e-13 | 2.7 EB05 2.1 · IC025 +1.0 3/3 methods agree | Reporting / coding artifact | serious PRR 4.5 | no trial data cached |
| Disturbance in attention | 44 | 2.7 2.0–3.6ROR 2.7 · χ² 45 / p 8e-12 | 2.6 EB05 2.1 · IC025 +0.9 3/3 methods agree | Not in label — unassessed | serious PRR 1.5 · 80% consumer | 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 |
|---|---|---|---|---|---|---|
| Headache | 378 | 2.0 1.8–2.2ROR 2.1 · χ² 193 / p 3e-44 | 2.0 EB05 1.8 · IC025 +0.8 | Labeled adverse reaction exact term | serious PRR 1.0 · 79% consumer | no trial data cached |
| Therapy non-responder | 364 | 27.3 24.7–30.1ROR 28.9 · χ² 9,122 / p <1e-300 | 27.0 EB05 24.8 · IC025 +4.5 3/3 methods agree | Reporting / coding artifact | serious PRR 1.6 · 88% consumer | no trial data cached |
| Vomiting | 314 | 2.2 2.0–2.5ROR 2.3 · χ² 213 / p 1e-48 | 2.2 EB05 2.0 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.7 · 85% consumer | no trial data cached |
| Maternal exposure during pregnancy | 301 | 11.3 10.1–12.7ROR 11.8 · χ² 2,828 / p <1e-300 | 11.3 EB05 10.2 · IC025 +3.3 3/3 methods agree | Reporting / coding artifact | serious PRR 16.7 · ♀ 99% (drug 61%) | no trial data cached |
| Abdominal pain upper | 217 | 3.5 3.1–4.0ROR 3.6 · χ² 388 / p 1e-86 | 3.5 EB05 3.1 · IC025 +1.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 1.6 · 85% consumer | no trial data cached |
| Anxiety | 189 | 2.2 1.9–2.5ROR 2.2 · χ² 123 / p 6e-29 | 2.2 EB05 1.9 · IC025 +0.9 | Not in label — unassessed | serious PRR 1.8 · 71% consumer | no trial data cached |
| Abdominal discomfort | 179 | 3.5 3.1–4.1ROR 3.6 · χ² 327 / p 2e-73 | 3.5 EB05 3.1 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 1.5 · 81% consumer | no trial data cached |
| Cough | 166 | 2.0 1.7–2.3ROR 2.0 · χ² 79 / p 4e-19 | 2.0 EB05 1.7 · IC025 +0.7 | Labeled adverse reaction exact term | serious PRR 1.4 · 85% consumer | no trial data cached |
| Nasopharyngitis (common cold) | 160 | 2.9 2.5–3.3ROR 2.9 · χ² 194 / p 2e-44 | 2.8 EB05 2.5 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 1.2 · 83% consumer | no trial data cached |
| Overdose | 153 | 2.3 2.0–2.7ROR 2.4 · χ² 117 / p 1e-27 | 2.3 EB05 2.0 · IC025 +1.0 3/3 methods agree | Reporting / coding artifact | serious PRR 1.6 | no trial data cached |
| Product prescribing error | 143 | 20.1 17.1–23.7ROR 20.6 · χ² 2,565 / p <1e-300 | 19.9 EB05 17.3 · IC025 +4.0 3/3 methods agree | Reporting / coding artifact | serious PRR 19.6 | no trial data cached |
| Decreased appetite (loss of appetite) | 141 | 2.0 1.7–2.4ROR 2.0 · χ² 72 / p 1e-17 | 2.0 EB05 1.7 · IC025 +0.7 | Not in label — unassessed | serious PRR 2.2 · 79% consumer | no trial data cached |
| Psychomotor hyperactivity | 134 | 26.8 22.7–31.7ROR 27.4 · χ² 3,281 / p <1e-300 | 26.5 EB05 23.0 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 6.6 · 78% consumer | no trial data cached |
| Product dose omission issue | 106 | 1.2 1.0–1.5ROR 1.2 · χ² 4 / p 0.017 | 1.2 EB05 1.0 · IC025 -0.0 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 2.4 | no trial data cached |
| Memory impairment | 101 | 2.4 2.0–3.0ROR 2.5 · χ² 84 / p 2e-20 | 2.4 EB05 2.0 · IC025 +0.9 3/3 methods agree | Not in label — unassessed | serious PRR 0.3 · 71% consumer | 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.
- Psychomotor hyperactivity — n=134, PRR 26.8
- Gastroenteritis viral — n=75, PRR 13.8
- Pharyngitis streptococcal — n=28, PRR 8.6
- Seasonal allergy — n=30, PRR 7.0
- Pregnancy — n=42, PRR 6.9
- Abnormal behaviour — n=71, PRR 5.9
- Abortion spontaneous — n=67, PRR 5.5
- Aggression — n=83, PRR 5.5
- Mood altered — n=39, PRR 4.8
- Rhinorrhoea — n=85, PRR 4.4
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 Sapropterin Dihydrochloride?
In FDA FAERS, the most frequently co-reported reaction terms for Sapropterin Dihydrochloride are headache, vomiting, abdominal pain upper, anxiety, abdominal discomfort, cough. 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 Sapropterin Dihydrochloride have an FDA boxed warning?
No. The FDA label retrieved for Sapropterin Dihydrochloride has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Sapropterin Dihydrochloride 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 3f0d6820-ff59-40c0-882f-aeea2dd1d1ad, effective 20260305; matched on
openfda.generic_name.exact:"SAPROPTERIN DIHYDROCHLORIDE") - 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, 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.