Impacts on practice
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Drug-induced anaphylaxis accounts for at least 12% of adverse drug event reports in Chinese hospitals collected by the Beijing Pharmacovigilance Database between 2004 to 2014, and the associated mortality rate is 3.3%.
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The top four drug categories implicated in drug induced anaphylaxis cases in China are antibiotics, traditional Chinese medicines, radiocontrast media and antineoplastic agents.
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Drug induced anaphylaxis most often presents with cardiovascular system symptoms, followed by mucocutaneous, respiratory and central nervous system symptoms.
Introduction
Aim of the study
Ethics approval
Method
Statistical analysis
Results
Demographic and clinical characteristics
Variable | Value, no. (%) | 95% CI |
---|---|---|
Demographics | ||
Age | ||
Mean—year | 47.6 ± 20.1 | |
< 18 year | 91 (7.7) | 6.2–9.3 |
18–59 year | 732 (61.6) | 58.8–64.4 |
≥60 year | 366 (30.8) | 28.2–33.5 |
Female | 627(52.7) | 50.0–55.5 |
Male | 562(47.3) | 44.5–50.0 |
Organ system involvement | ||
Cardiovascular | 996 (83.8) | 81.3–85.8 |
Respiratory | 659 (55.4) | 52.5–58.3 |
Central nervous system | 596 (50.1) | 47.4–53.1 |
Mucocutaneous | 563 (47.4) | 44.6–50.5 |
Gastrointestinal tract | 372 (31.3) | 28.8–33.9 |
Severity of anaphylaxis | ||
Mild to moderate | 160 (13.5) | 11.5–15.6 |
Severe | 1029 (86.5) | 84.4–88.5 |
Outcome | ||
ICU admission | 73 (6.1) | 4.9–7.8 |
Death | 39 (3.3) | 2.3–4.3 |
Drug triggers
Drugs | Value, no. (%) | 95% CI |
---|---|---|
Total | 1189 | |
Antibiotics | 467 (39.3) | 36.7–42.1 |
β-lactams | 275 (23.1) | 21.0–25.5 |
Fluoroquinolones | 138 (11.6) | 9.8–13.4 |
Macrolides | 28 (2.4) | 1.6–3.3 |
Other antibioticsa
| 26 (2.2) | 1.3–3.0 |
TCM | 141 (11.9) | 10.2–14.3 |
TCM (injection) | 135 (11.4) | 9.5–13.2 |
TCM (oral) | 5 (0.4) | 0.1–0.8 |
TCM (topical) | 1 (0.1) | 0.0–0.3 |
Radiocontrast agents | 141 (11.9) | 10.2–14.3 |
X-ray contrast media, iodinated | 113 (9.5) | 7.8–11.3 |
MRI contrast media | 12 (1.0) | 0.5–1.6 |
Ophthalmic medicines | 10 (0.8) | 0.3–1.4 |
Ultrasound contrast agents | 4 (0.3) | 0.1–0.8 |
Otherb
| 2 (0.2) | 0.0–0.4 |
Antineoplastics | 122 (10.3) | 8.8–12.4 |
Taxanes | 73 (6.1) | 4.9–7.6 |
Platinum compounds | 40 (3.4) | 2.4–4.5 |
Cytotoxic antibiotics | 5 (0.4) | 0.1–0.8 |
Alkylating agents | 2 (0.2) | 0.0–0.4 |
Teniposide | 1 (0.1) | 0.0–0.3 |
Asparaginase | 1 (0.1) | 0.0–0.3 |
Blood products, Biologics and plasma substitutes | 74 (6.2) | 4.9–7.7 |
Blood products and Biologics | 37 (3.1) | 2.2–4.2 |
Plasma substitutes | 25 (2.1) | 1.3–3.0 |
Monoclonal antibodies | 12 (1.0) | 0.5–1.6 |
Anesthetics | 25 (2.1) | 1.3–3.0 |
Local anesthetics | 10 (0.8) | 0.3–1.4 |
NMBAs | 12 (1.0) | 0.5–1.6 |
General anesthetics | 3 (0.3) | 0.0–0.6 |
Vaccines, immunoglobulins and antiserums | 23 (1.9) | 1.2–2.8 |
Immunoglobulins and antiserums | 19 (1.6) | 0.9–2.4 |
Vaccines | 4 (0.3) | 0.1–0.7 |
Nutrition and vitamins | 22 (1.9) | 1.1–2.7 |
Vitamins and minerals | 16 (1.3) | 0.8–2.1 |
Amino acids and fat emulsions | 6 (0.5) | 0.2–0.9 |
Immune-modulators | 21 (1.8) | 1.0–2.5 |
Immunostimulants | 16 (1.3) | 0.8–1.9 |
Immunosuppressants | 5 (0.4) | 0.1–0.8 |
Blood system medications | 20 (1.7) | 0.9–2.4 |
Antifibrinolytic agents and hemostatics | 11 (0.9) | 0.4–1.5 |
Iron (injection) | 6 (0.5) | 0.2–1.0 |
Anticoagulants | 2 (0.2) | 0.0–0.4 |
Antiplatelet agents | 1 (0.1) | 0.0–0.3 |
Analgesics, anti-inflammatory drugs and antipyretics | 17 (1.4) | 0.8–2.2 |
NSAIDs | 11 (0.9) | 0.4–1.6 |
Opioids | 5 (0.4) | 0.1–0.8 |
Paracetamol | 1 (0.1) | 0.0–0.3 |
Hormones, other endocrine medicines | 16 (1.3) | 0.8–2.1 |
Corticosteroids | 11 (0.9) | 0.4–1.5 |
Hypothalamic and pituitary hormones | 4 (0.3) | 0.1–0.7 |
Insulins | 1 (0.1) | 0.0–0.3 |
Prostaglandins | 10 (0.8) | 0.3–1.4 |
Cardiovascular medications | 11 (0.9) | 0.4–1.5 |
Vasodilators | 5 (0.4) | 0.1–0.8 |
Antiarrhythmics | 3 (0.3) | 0.0–0.6 |
ACEI/BB | 2 (0.2) | 0.0–0.4 |
Statins | 1 (0.1) | 0.0–0.3 |
Gastrointestinal medicines | 8 (0.7) | 0.3–1.1 |
H2 receptor blockers | 3 (0.3) | 0.0–0.6 |
Laxatives | 2 (0.2) | 0.0–0.4 |
PPI | 1 (0.1) | 0.0–0.3 |
Antacids | 1 (0.1) | 0.0–0.3 |
Antiemetics | 1 (0.1) | 0.0–0.3 |
Antidotes | 7 (0.6) | 0.3–1.1 |
Antivirals | 5 (0.4) | 0.1–0.8 |
Antifungals | 3 (0.3) | 0.0–0.6 |
Psychotherapeutic medicines | 3 (0.3) | 0.0–0.6 |
Antidementia medicines | 2 (0.2) | 0.0–0.4 |
Antipsychotic medications | 1 (0.1) | 0.0–0.3 |
Respiratory medications | 3 (0.3) | 0.0–0.6 |
Expectorants | 2 (0.2) | 0.0–0.4 |
Bronchodilators | 1 (0.1) | 0.0–0.3 |
Calcium regulating drugs | 1 (0.1) | 0.0–0.3 |
Associationsc
| 44 (3.7) | 2.7–4.9 |
Othersd
| 5 (0.4) | 0.1–0.8 |
Antibiotics | ATC-codes | All Patients (n = 467) Value, no. (%) |
---|---|---|
β-Lactam antibiotics | 275 (58.9) | |
Cephalosporins | 161 (34.5) | |
First-generation | J01DB | 13 (2.8) |
cefradine | J01DB09 | 4 (0.9) |
cefalexin | J01DB01 | 4 (0.9) |
cefazolin | J01DB04 | 3 (0.6) |
cefadroxil | J01DB05 | 1 (0.2) |
cefathiamidine | NA | 1 (0.2) |
Second-generation | J01DC | 86 (18.4) |
cefuroxime | J01DC02 | 54 (11.6) |
cefmetazole | J01DC09 | 18 (3.9) |
cefoxitin | J01DC01 | 6 (1.3) |
cefotiam | J01DC07 | 3 (0.6) |
cefminox | J01DC12 | 2 (0.4) |
cefamandole | J01DC03 | 2 (0.4) |
cefaclor | J01DC04 | 1 (0.2) |
Third-generation | J01DD | 58 (12.4) |
ceftriaxone | J01DD04 | 35 (7.5) |
ceftazidime | J01DD02 | 10 (2.1) |
ceftizoxime | J01DD07 | 6 (1.3) |
cefoperazone | J01DD12 | 4 (0.9) |
cefotaxime | J01DD01 | 2 (0.4) |
cefdinir | J01DD15 | 1 (0.2) |
Fourth-generation | J01DE | 4 (0.9) |
cefepime | J01DE01 | 4 (0.9) |
β-lactam + β-lactamase inhibitors | 72 (15.4) | |
cefoperazone + sulbactam | J01DD62 | 45 (9.6) |
piperacillin + sulbactam | J01CR05 | 12 (2.6) |
piperacillin + tazobactam | J01CR05 | 5 (1.1) |
ampicillin + sulbactam | J01CA51 | 5 (1.1) |
amoxicillin + clavulanic acid | J01CR02 | 3 (0.6) |
imipenem + cilastatin | J01DH51 | 1 (0.2) |
amoxicillin + sulbactam | J01CR02 | 1 (0.2) |
Penicillins | J01C | 37 (7.9) |
benzylpenicillin | J01CE01 | 23 (4.9) |
Penicillins with extended spectrum (aminopenicillins) | J01CA | 14 (3.0) |
azlocillin | J01CA09 | 5 (1.1) |
amoxicillin | J01CA04 | 5 (1.1) |
mezlocillin | J01CA10 | 4 (0.9) |
Others | 5 (1.1) | |
aztreonam | J01DF01 | 3 (0.6) |
latamoxef | J01DD06 | 2 (0.4) |
Fluoroquinolones | J01MA | 138 (29.6) |
levofloxacin | J01MA12 | 82 (17.6) |
moxifloxacin | J01MA14 | 23 (4.9) |
gatifloxacin | J01MA16 | 14 (3.0) |
pefloxacin | J01MA03 | 5 (1.1) |
ofloxacin | J01MA01 | 4 (0.9) |
fleroxacin | J01MA08 | 4 (0.9) |
ciprofloxacin | J01MA02 | 4 (0.9) |
lomefloxacin | J01MA07 | 2 (0.4) |
Macrolides | J01FA | 28 (6.0) |
azithromycin | J01FA10 | 28 (6.0) |
clindamycin | J01FF01 | 14 (3.0) |
Aminoglycosides | J01G | 8 (1.7) |
etimicin | NA | 7 (1.5) |
gentamicin | J01GB03 | 1 (0.2) |
vancomycin | J01XA01 | 3 (0.6) |
metronidazole | J01XD01 | 1 (0.2) |
Drugs | ATC-codes | Value, no. (%) |
---|---|---|
Radiocontrast agents (n = 141) | ||
iopromide | V08AB05 | 52 (36.9) |
iohexol | V08AB02 | 26 (18.4) |
iopamidol | V08AB04 | 16 (11.3) |
fluorescein sodium | NA | 10 (7.1) |
gadopentetic acid (gadopentetate dimeglumine) | V08CA01 | 9 (6.4) |
ioversol | V08AB07 | 7 (5.0) |
iobitridol | V08AB11 | 5 (3.5) |
iodixanol | V08AB09 | 5 (3.5) |
sulfur hexafluoride | V08DA05 | 4 (2.8) |
diatrizoic acid (meglumine diatrizoate) | V08AA01 | 2 (1.4) |
indocyanine green | NA | 2 (1.4) |
gadobenic acid (gadobenate dimeglumine) | V08CA08 | 1 (0.7) |
gadodiamide | V08CA03 | 1 (0.7) |
gadoteric acid (gadoterate meglumine) | V08CA02 | 1 (0.7) |
TCM injections (n = 135) | ||
Ciwujia | NA | 21 (15.6) |
Qingkailing | NA | 16 (11.9) |
Houttuynia cordata | NA | 12 (8.9) |
Shuxuening | NA | 11 (8.1) |
Shuanghuanglian | NA | 6 (4.4) |
Chuanhuning | NA | 6 (4.4) |
Safflower | NA | 5 (3.7) |
Yinxingdamo | NA | 5 (3.7) |
Othersa
| NA | 53 (39.3) |
Antineoplastics (n = 122) | ||
paclitaxel | L01CD01 | 68 (55.7) |
oxaliplatin | L01XA03 | 18 (14.8) |
carboplatin | L01XA02 | 13 (10.7) |
cisplatin | L01XA01 | 7 (5.7) |
docetaxel | L01CD02 | 5 (4.1) |
cyclophosphamide | L01AA01 | 2 (1.6) |
doxorubicin | L01DB01 | 2 (1.6) |
nedaplatin | NA | 2 (1.6) |
topotecan | L01XX17 | 1 (0.8) |
epirubicin | L01DB03 | 1 (0.8) |
bleomycin A5 | NA | 1 (0.8) |
mitomycin | L01DC03 | 1 (0.8) |
asparaginase | L01XX02 | 1 (0.8) |
Severity and anaphylaxis-related deaths
Variable | ATC-codes | All patients (n = 39) value, no. (%) |
---|---|---|
Age | ||
Mean—year | 53.8 ± 19.1 | |
< 18 year | 1 (2.6) | |
18–59 year | 20 (51.3) | |
≥60 year | 18 (46.1) | |
Female | 14 (35.9) | |
Antibiotics | 13 (33.3) | |
cefuroxime | J01DC02 | 5 (12.8) |
levofloxacin | J01MA12 | 3 (7.7) |
ceftriaxone | J01DD04 | 1 (2.6) |
ceftizoxime | J01DD07 | 1 (2.6) |
cefepime | J01DE01 | 1 (2.6) |
piperacillin + sulbactam | J01CR05 | 1 (2.6) |
clindamycin | J01FF01 | 1 (2.6) |
Radiocontrast agents | 12 (30.8) | |
ioversol | V08AB07 | 4 (10.3) |
iohexol | V08AB02 | 3 (7.7) |
iopromide | V08AB05 | 2 (5.1) |
iopamidol | V08AB04 | 1 (2.6) |
gadopentetic acid (gadopentetate dimeglumine) | V08CA01 | 1 (2.6) |
fluorescein sodium | NA | 1 (2.6) |
Antineoplastics | 4 (10.3) | |
paclitaxel | L01CD01 | 2 (5.1) |
oxaliplatin | L01XA03 | 1 (2.6) |
asparaginase | L01XX02 | 1 (2.6) |
TCM injections | 3 (7.7) | |
Houttuynia cordata | NA | 2 (5.1) |
Chuanhuning | NA | 1 (2.6) |
plasma substitutes | 2 (5.1) | |
hydroxyethyl starch | B05AA07 | 1 (2.6) |
dextran | B05AA05 | 1 (2.6) |
Vaccine | J07BB03 | 1 (2.6) |
protamine | V03AB14 | 1 (2.6) |
articaine | N01BB08 | 1 (2.6) |
doxofylline | R03DA11 | 1 (2.6) |
Associationsa
| 1 (2.6) |