Asfotase Alfa side effects: what 9,932 FDA adverse event reports show
Drug class
Tissue-nonspecific Alkaline Phosphatase
Brand names
Strensiq
Who reports
9,932 reports · 31% serious · 72 with death outcome · 73% female
Used for
STRENSIQ ® is indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP). STRENSIQ is a tissue nonspecific alkaline phosphatase indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP). ( 1 )
What it is
Asfotase alfa is a tissue nonspecific alkaline phosphatase (TNSALP) produced by recombinant DNA technology in a Chinese hamster ovary cell line. Asfotase alfa is a soluble glycoprotein composed of two identical polypeptide chains. Each chain contains 726 amino acids with a theoretical mass of 161 kDa.
Boxed warning
HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.
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. 960 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 |
|---|---|---|---|---|---|---|
| Vitamin b6 decreased | 151 | 3,689.4 2,830.4–4,809.0ROR 3,746.1 · χ² 199,214 / p <1e-300 | 1,136.2 EB05 992.1 · IC025 +7.7 3/3 methods agree | Lab value / disease marker | serious n=44 | no trial data cached |
| Vitamin b6 abnormal | 20 | 3,195.1 1,589.8–6,421.2ROR 3,201.5 · χ² 23,914 / p <1e-300 | 569.3 EB05 389.2 · IC025 +4.6 3/3 methods agree | Lab value / disease marker | serious n=9 · 75% consumer | no trial data cached |
| Vitamin b6 increased | 87 | 1,771.4 1,331.6–2,356.4ROR 1,787.0 · χ² 82,124 / p <1e-300 | 789.1 EB05 659.5 · IC025 +6.9 3/3 methods agree | Lab value / disease marker | serious n=39 | no trial data cached |
| Hypophosphatasia | 38 | 1,127.4 759.9–1,672.6ROR 1,131.7 · χ² 26,993 / p <1e-300 | 533.6 EB05 405.8 · IC025 +5.6 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=38 | no trial data cached |
| Injection site hypertrophy | 50 | 402.5 297.5–544.5ROR 404.5 · χ² 16,439 / p <1e-300 | 298.7 EB05 235.5 · IC025 +5.8 3/3 methods agree | Labeled adverse reaction exact term | serious n=14 | no trial data cached |
| Injection site deformation | 13 | 364.8 202.4–657.6ROR 365.3 · χ² 3,709 / p <1e-300 | 213.5 EB05 132.8 · IC025 +3.7 3/3 methods agree | Labeled (related wording) related wording | serious n=3 | no trial data cached |
| Blood alkaline phosphatase decreased | 108 | 269.3 220.6–328.7ROR 272.2 · χ² 25,316 / p <1e-300 | 228.8 EB05 194.9 · IC025 +6.5 3/3 methods agree | Likely indication confounding term in indications | serious n=31 | no trial data cached |
| Injection site atrophy | 163 | 230.9 196.6–271.1ROR 234.7 · χ² 33,376 / p <1e-300 | 203.0 EB05 178.1 · IC025 +6.7 3/3 methods agree | Labeled adverse reaction exact term | serious n=43 | no trial data cached |
| Rickets | 15 | 179.0 105.7–303.3ROR 179.3 · χ² 2,284 / p <1e-300 | 136.6 EB05 87.9 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=15 | no trial data cached |
| Vitamin b6 deficiency | 18 | 176.3 109.0–285.2ROR 176.6 · χ² 2,733 / p <1e-300 | 139.0 EB05 93.0 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=9 | no trial data cached |
| Blood alkaline phosphatase abnormal | 53 | 132.3 100.3–174.5ROR 133.0 · χ² 6,370 / p <1e-300 | 119.2 EB05 94.6 · IC025 +5.4 3/3 methods agree | Likely indication confounding term in indications | serious n=8 · ♀ 52% (drug 73%) · 91% consumer | no trial data cached |
| Lipohypertrophy | 30 | 106.3 73.7–153.4ROR 106.6 · χ² 2,878 / p <1e-300 | 95.2 EB05 69.9 · IC025 +4.6 3/3 methods agree | Labeled adverse reaction exact term | serious n=7 | no trial data cached |
| Craniosynostosis | 41 | 104.1 76.1–142.4ROR 104.5 · χ² 3,889 / p <1e-300 | 94.9 EB05 72.9 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious n=41 · ♀ 29% (drug 73%) · 71% consumer | no trial data cached |
| Nephrocalcinosis | 50 | 92.9 70.0–123.2ROR 93.3 · χ² 4,263 / p <1e-300 | 86.1 EB05 67.9 · IC025 +5.1 3/3 methods agree | Labeled adverse reaction exact term | serious n=47 | no trial data cached |
| Walking distance test abnormal | 16 | 91.0 55.2–150.1ROR 91.2 · χ² 1,280 / p 1e-280 | 79.3 EB05 51.7 · IC025 +3.8 3/3 methods agree | Reporting / coding artifact | serious n=7 | no trial data cached |
| Lipodystrophy acquired | 81 | 83.1 66.6–103.6ROR 83.7 · χ² 6,237 / p <1e-300 | 78.5 EB05 65.2 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious n=73 · 72% consumer | no trial data cached |
| Blood urea nitrogen/creatinine ratio increased | 22 | 74.7 48.8–114.2ROR 74.8 · χ² 1,473 / p <1e-300 | 68.0 EB05 47.4 · IC025 +4.1 3/3 methods agree | Lab value / disease marker | serious n=9 | no trial data cached |
| Calcinosis | 72 | 70.0 55.4–88.4ROR 70.5 · χ² 4,669 / p <1e-300 | 66.6 EB05 54.6 · IC025 +5.1 3/3 methods agree | Labeled adverse reaction exact term | serious n=35 | no trial data cached |
| Urine calcium increased | 10 | 69.0 36.8–129.5ROR 69.1 · χ² 584 / p 2e-129 | 59.6 EB05 34.6 · IC025 +2.9 3/3 methods agree | Lab value / disease marker | serious n=3 | no trial data cached |
| Blood phosphorus increased | 75 | 59.6 47.4–74.9ROR 60.0 · χ² 4,142 / p <1e-300 | 57.1 EB05 47.1 · IC025 +5.0 3/3 methods agree | Lab value / disease marker | serious n=34 | no trial data cached |
| Bone deformity | 18 | 57.9 36.2–92.4ROR 58.0 · χ² 924 / p 3e-203 | 53.3 EB05 35.7 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial data cached |
| Ehlers-danlos syndrome | 11 | 51.2 28.2–93.1ROR 51.3 · χ² 481 / p 7e-107 | 46.3 EB05 27.6 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=6 | no trial data cached |
| Injection site discolouration | 263 | 45.6 40.4–51.5ROR 46.8 · χ² 11,193 / p <1e-300 | 44.5 EB05 40.2 · IC025 +5.2 3/3 methods agree | Labeled (related wording) related wording | serious n=55 · 81% consumer | no trial data cached |
| Vitamin d increased | 13 | 45.5 26.2–78.7ROR 45.5 · χ² 510 / p 3e-113 | 42.0 EB05 26.1 · IC025 +3.2 3/3 methods agree | Lab value / disease marker | serious n=5 | no trial data cached |
| Chondrocalcinosis | 13 | 44.3 25.6–76.8ROR 44.4 · χ² 498 / p 2e-110 | 41.0 EB05 25.5 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=7 | no trial data cached |
| Hypercalciuria | 10 | 43.5 23.3–81.4ROR 43.6 · χ² 366 / p 5e-82 | 39.7 EB05 23.0 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=8 | no trial data cached |
| Hypermobility syndrome | 10 | 43.4 23.2–81.1ROR 43.4 · χ² 365 / p 1e-81 | 39.5 EB05 22.9 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=7 | no trial data cached |
| Blood bilirubin decreased | 12 | 41.5 23.5–73.5ROR 41.6 · χ² 427 / p 5e-95 | 38.5 EB05 23.4 · IC025 +3.0 3/3 methods agree | Lab value / disease marker | serious n=8 | no trial data cached |
| Carbon dioxide decreased | 21 | 39.5 25.7–60.8ROR 39.6 · χ² 736 / p 2e-162 | 37.6 EB05 25.9 · IC025 +3.6 3/3 methods agree | Lab value / disease marker | serious n=16 | no trial data cached |
| Injection related reaction | 23 | 30.5 20.2–46.0ROR 30.6 · χ² 619 / p 8e-137 | 29.4 EB05 20.7 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=14 | no trial data cached |
| Vitamin b12 increased | 11 | 29.7 16.4–53.8ROR 29.7 · χ² 273 / p 1e-61 | 27.9 EB05 16.5 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious n=6 | no trial data cached |
| Alanine aminotransferase decreased | 10 | 29.6 15.9–55.3ROR 29.7 · χ² 245 / p 1e-55 | 27.7 EB05 15.9 · IC025 +2.6 3/3 methods agree | Lab value / disease marker | serious n=5 | no trial data cached |
| Corneal deposits | 10 | 29.0 15.5–54.0ROR 29.0 · χ² 239 / p 3e-54 | 27.1 EB05 15.6 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=6 | no trial data cached |
| Knee deformity | 20 | 28.7 18.5–44.6ROR 28.8 · χ² 501 / p 3e-111 | 27.7 EB05 18.9 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=12 · ♀ 50% (drug 73%) · 75% consumer | no trial data cached |
| Blood albumin increased | 12 | 28.7 16.2–50.7ROR 28.7 · χ² 289 / p 3e-65 | 27.2 EB05 16.5 · IC025 +2.8 3/3 methods agree | Lab value / disease marker | serious n=8 | no trial data cached |
| Arnold-chiari malformation | 12 | 26.6 15.1–47.0ROR 26.7 · χ² 267 / p 2e-60 | 25.3 EB05 15.3 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial data cached |
| Blood alkaline phosphatase increased | 304 | 26.0 23.3–29.1ROR 26.8 · χ² 7,212 / p <1e-300 | 25.7 EB05 23.4 · IC025 +4.4 3/3 methods agree | Likely indication confounding term in indications | serious PRR 18.1 · 89% consumer | no trial data cached |
| Blood creatinine decreased | 35 | 23.8 17.1–33.2ROR 23.9 · χ² 733 / p 9e-162 | 23.3 EB05 17.5 · IC025 +3.6 3/3 methods agree | Lab value / disease marker | serious n=16 | no trial data cached |
| Injection site reaction | 747 | 23.2 21.6–24.8ROR 25.0 · χ² 15,696 / p <1e-300 | 22.9 EB05 21.6 · IC025 +4.4 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 42.9 · 73% consumer | no trial data cached |
| Vitamin d decreased | 93 | 23.1 18.8–28.3ROR 23.3 · χ² 1,924 / p <1e-300 | 22.8 EB05 19.1 · IC025 +4.0 3/3 methods agree | Lab value / disease marker | serious n=46 | 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 |
|---|---|---|---|---|---|---|
| Injection site pain (pain where injected) | 1,327 | 9.2 8.8–9.7ROR 10.5 · χ² 9,845 / p <1e-300 | 9.2 EB05 8.8 · IC025 +3.1 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 17.0 · 84% consumer | no trial data cached |
| Fatigue (tiredness) | 952 | 2.6 2.4–2.7ROR 2.7 · χ² 956 / p 4e-210 | 2.6 EB05 2.4 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious PRR 3.5 · 73% consumer | no trial data cached |
| Injection site erythema (redness where injected) | 869 | 14.9 14.0–15.9ROR 16.3 · χ² 11,259 / p <1e-300 | 14.8 EB05 14.0 · IC025 +3.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 24.0 · 84% consumer | no trial data cached |
| Pain | 811 | 2.8 2.6–3.0ROR 2.9 · χ² 948 / p 2e-208 | 2.8 EB05 2.6 · IC025 +1.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.0 · 75% consumer | no trial data cached |
| Injection site reaction | 747 | 23.2 21.6–24.8ROR 25.0 · χ² 15,696 / p <1e-300 | 22.9 EB05 21.6 · IC025 +4.4 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 42.9 · 73% consumer | no trial data cached |
| Arthralgia (joint pain) | 665 | 3.4 3.1–3.6ROR 3.6 · χ² 1,135 / p 5e-249 | 3.4 EB05 3.2 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 4.9 | no trial data cached |
| Pain in extremity | 542 | 3.9 3.6–4.2ROR 4.0 · χ² 1,166 / p 8e-256 | 3.9 EB05 3.6 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 4.3 · 73% consumer | no trial data cached |
| Injection site bruising | 501 | 13.5 12.4–14.7ROR 14.1 · χ² 5,749 / p <1e-300 | 13.4 EB05 12.4 · IC025 +3.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 22.6 · 85% consumer | no trial data cached |
| Injection site swelling | 438 | 12.2 11.2–13.4ROR 12.8 · χ² 4,498 / p <1e-300 | 12.1 EB05 11.2 · IC025 +3.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 21.8 · 82% consumer | no trial data cached |
| Headache | 394 | 1.3 1.2–1.5ROR 1.3 · χ² 32 / p 8e-9 | 1.3 EB05 1.2 · IC025 +0.2 | Labeled — boxed warning exact term | serious PRR 2.2 · 72% consumer | no trial data cached |
| Injection site pruritus | 336 | 10.7 9.6–11.9ROR 11.0 · χ² 2,932 / p <1e-300 | 10.6 EB05 9.7 · IC025 +3.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 23.0 · 86% consumer | no trial data cached |
| Bone pain | 304 | 11.0 9.8–12.3ROR 11.3 · χ² 2,737 / p <1e-300 | 10.9 EB05 9.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 15.8 | no trial data cached |
| Blood alkaline phosphatase increased | 304 | 26.0 23.3–29.1ROR 26.8 · χ² 7,212 / p <1e-300 | 25.7 EB05 23.4 · IC025 +4.4 3/3 methods agree | Likely indication confounding term in indications | serious PRR 18.1 · 89% consumer | no trial data cached |
| Nausea | 303 | 0.8 0.7–0.9ROR 0.8 · χ² 14 / p 9e-5 | 0.8 EB05 0.7 · IC025 -0.5 PRR-only: not supported by EBGM or IC | Labeled — boxed warning exact term | serious PRR 1.1 · 79% consumer | no trial data cached |
| Malaise (feeling unwell) | 299 | 1.4 1.3–1.6ROR 1.4 · χ² 39 / p 2e-10 | 1.4 EB05 1.3 · IC025 +0.3 | Not in label — unassessed | serious PRR 1.5 · 84% 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.
- Craniosynostosis — n=41, PRR 104.1
- Lipodystrophy acquired — n=81, PRR 83.1
- Injection related reaction — n=23, PRR 30.5
- Knee deformity — n=20, PRR 28.7
✓ A hand-written Bradford Hill causality assessment exists for this drug: Erythropoiesis-stimulating agents (darbepoetin alfa) ↔ Mortality / cardiovascular risk.
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 Asfotase Alfa?
In FDA FAERS, the most frequently co-reported reaction terms for Asfotase Alfa are injection site pain, fatigue, injection site erythema, pain, injection site reaction, arthralgia. 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 Asfotase Alfa have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.
Do FAERS signals prove that Asfotase Alfa 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 3387574f-5eaa-4501-a71d-4cbfbd563031, effective 20251212; matched on
openfda.generic_name.exact:"ASFOTASE ALFA") - 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, 1,000 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.