Mining of Risk Signals Adverse Events Related to Drug-Induced Salivary Gland Calculus Based on FAERS Database

doi:10.19803/j.1672-8629.20240508

Abstract

Abstract: Objective To conduct a disproportionality analysis of drug-induced salivary gland calculus by using the individual case safety reports in the FDA Adverse Event Reporting System (FAERS) in order to provide a reference for prevention of this disease. Methods Data on individual case safety reports collected between the fourth quarter of 2012 and the second quarter of 2023 in the FAERS was retrieved. The reporting odds ratio (ROR) method and Medicines and Healthcare Products Regulatory Agency (MHRA) method were used for detection of signals of adverse drug reactions related to salivary gland calculus. Results A total of 211 reports related to salivary gland calculus were retrieved, involving 135 primary suspected or secondary suspected drugs. Using the ROR method and MHRA method, signals of disproportionate reporting (SDR) were detected in 14 drugs, which were calcium, macitentan, metoprolol, levothyroxine, adalimumab, golimumab, tocilizumab, zoledronic acid, denosumab, topiramate, olanzapine, quetiapine, sodium oxybate and meclizine (sorted by the ATC code). Conclusion There are 14 types of drugs with SDR related to salivary gland calculus detected in this study. Clinicians should be aware of the potential risks of salivary gland calculus when prescribing drugs mentioned above. Active monitoring and appropriate precautions are required.

Key words: Salivary Gland Calculus, Adverse Drug Reaction, Spontaneous Reporting System, FDA Adverse Event Reporting System, Disproportionality Analysis

CLC Number:

R969.3

CAO Kai, QIAN Peipei, GAO Xin, YANG Futian, ZHAO Liang, XU Bingxin, ZHANG Xianjun. Mining of Risk Signals Adverse Events Related to Drug-Induced Salivary Gland Calculus Based on FAERS Database[J]. Chinese Journal of Pharmacovigilance, 2025, 22(7): 799-804.

Add to citation manager EndNote|Ris|BibTeX

URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20240508

https://zgywjj.magtechjournal.com/EN/Y2025/V22/I7/799

References

[1] KRAAIJ S, KARAGOZOGLU KH, KENTER YA, et al.Systemic Diseases and the Risk of Developing Salivary Stones: a Case Control Study[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2015, 119(5): 539-543.
[2] MORTAZAVI H, TIZNO A, AZADI A, et al.What Is the Impact of Previous Cholelithiasis on Sialolithiasis: a Systematic Review and Meta-Analysis[J]. Saudi Dent J, 2024, 36(1): 44-51.
[3] GAMALELDIN O, MAGDY EA, ZOHEIR H, et al.The Role of Magnetic Resonance Imaging and Magnetic Resonance Sialography in the Evaluation of Salivary Sialolithiasis: Radiologic-Endoscopic Correlation[J]. Pol J Radiol, 2022, 87: e430-e437.
[4] JONAS E, MUCHNIK D, RABINOVICH I, et al.Characteristics of Sialolithiasis in Israel, a Big-Data Retrospective Study of 5100 Cases[J]. Oral Dis, 2025, 31(2): 503-509.
[5] HUOH KC, EISELE DW.Etiologic Factors in Sialolithiasis[J]. Otolaryngol Head Neck Surg, 2011, 145(6): 935-939.
[6] GUO ZJ, GUO XJ, XU JF, et al.Analysis for Adverse Events of Apalu-tamide Based on FAERS Database[J]. Chin J Pharmacoepidemiol(药物流行病学杂志), 2021, 30(11): 744-749.
[7] HATAHIRA H, ABE J, HANE Y, et al.Drug-Induced Gingival Hyperplasia: a Retrospective Study Using Spontaneous Reporting System Databases[J]. J Pharm Health Care Sci, 2017, 3: 19.
[8] LI ZY, JING YX, LI CX, et al.Research and Experience Reference of Foreign Typical Pharmacovigilance Database[J]. Chinese Journal of Drug Evaluation(中国药物评价) , 2021, 38(4): 265-273.
[9] JIANG M, WU Y, SHAH A, et al.Extracting and Standardizing Medication Information in Clinical Text-the Medex-UIMA System[J]. AMIA Jt Summits Transl Sci Proc, 2014, 2014: 37-42.
[10] FDA. What Is a Serious Adverse Event[EB/OL]. (2023-05-18)[2025-05-09]. https://www.fda.gov/safety/reporting-serious-problems-fda/what-serious-adverse-event.
[11] YE XF.Progress and Thinking of Signal Detection Methodology on Post-Marketing Adverse Drug Reaction Surveillance[J]. Academic Journal of Naval Medical University(海军军医大学学报), 2022, 43(2): 117-122.
[12] FUSAROLI M, SALVO F, BEGAUD B, et al.The Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Development and Statement[J]. Drug Saf, 2024, 47(6): 575-584.
[13] ZHU ZP, LYU Q, YE XF, et al.Disproportionality of Adverse Events to KRAS G12C Inhibitors Based on the FAERS Database[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2025, 22(3): 297-304.
[14] ASHINDOITIANG JA, NWAGBARA VIC, UGBEM T, et al.Huge Sialolith of the Submandibular Gland: a Case Report and Review of Literature[J]. J Int Med Res, 2023, 51(1): 3000605221148443.
[15] YIU AJ, CALLAGHAN D, SULTANA R, et al.Vascular Calcification and Stone Disease: a New Look towards the Mechanism[J]. J Cardiovasc Dev Dis, 2015, 2(3): 141-164.
[16] SU YX, ZHANG K, KE ZF, et al.Increased Calcium and Decreased Magnesium and Citrate Concentrations of Submandibular/Sublingual Saliva in Sialolithiasis[J]. Arch Oral Biol, 2010, 55(1): 15-20.
[17] JUNG SY, CHANG SA, SONG JM, et al.Real-World Safety and Clinical Outcomes of Macitentan in Asian Patients with Pulmonary Arterial Hypertension: a Prospective Multicenter Study[J]. Drugs Real World Outcomes, 2023, 10(1): 41-49.
[18] VENTIMIGLIA MS, RODRIGUEZ MR, MORALES VP, et al.Endothelins Participate in the Central and Peripheral Regulation of Submandibular Gland Secretion in the Rat[J]. Am J Physiol Regul Integr Comp Physiol, 2011, 300(1): R109-R120.
[19] SCULLY C.Drug Effects on Salivary Glands: Dry Mouth[J]. Oral Dis, 2003, 9(4): 165-176.
[20] NEDERFORS T.Xerostomia: Prevalence and Pharmacotherapy with Special Reference to Beta-Adrenoceptor Antagonists[J]. Swed Dent J Suppl, 1996, 116: 1-70.
[21] NEDERFORS T, DAHLÖF C. Effects on Salivary Flow Rate and Composition of Withdrawal of and Re-Exposure to the Beta 1-Selective Antagonist Metoprolol in a Hypertensive Patient Population[J]. Eur J Oral Sci, 1996, 104(3): 262-268.
[22] NAIK MM, VASSANDACOUMARA V.Qualitative and Quantitative Salivary Changes and Subjective Oral Dryness among Patients with Thyroid Dysfunction[J]. Indian J Dent Res, 2018, 29(1): 16-21.
[23] XIAO YD, YANG HM, DAN HX.Adverse Reactions of Targeted Anticancer Agents in Oral Cavity: Manifestation and Management[J]. International Journal of Stomatology(国际口腔医学杂志) , 2018, 45(2): 140-144.
[24] BAKHTIARI S, SEHATPOUR M, MORTAZAVI H, et al.Orofacial Manifestations of Adverse Drug Reactions: a Review Study[J]. Clujul Med, 2018, 91(1): 27-36.
[25] ALSAKRAN ALTAMIMI M.Update Knowledge of Dry Mouth-a Guideline for Dentists[J]. Afr Health Sci, 2014, 14(3): 736-742.
[26] KREHER D, ERNST BLV, ZIEBOLZ D, et al.Dental Caries in Adult Patients with Rheumatoid Arthritis-a Systematic Review[J]. J Clin Med, 2023, 12(12): 4128.
[27] CHEN H, HE Y.Interpretation of Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline[J]. Chinese Journal of Stomatology(中华口腔医学杂志) , 2022, 57(2): 128-135.
[28] SURYANI IR, AHMADZAI I, THAT MT, et al.Are Medication-Induced Salivary Changes the Culprit of Osteonecrosis of the Jaw? a Systematic Review[J]. Front Med (Lausanne), 2023, 10: 1164051.
[29] BUHLER AV, HUYNH P, LOW P, et al.Possible Drug-Associated Sialolithiasis from the Bicarbonate Anhydrase Inhibitor Topiramate: a Case Report and Literature Review[J]. J Oral Maxillofac Surg, 2016, 74(12): 2447-2452.
[30] PARKKILA S, PARKKILA AK, JUVONEN T, et al.Distribution of the Carbonic Anhydrase Isoenzymes I,Ⅱ, and VI in the Human Alimentary Tract[J]. Gut, 1994, 35(5): 646-650.
[31] SEKINE Y, RIKIHISA T, OGATA H, et al.Correlations between in vitro Affinity of Antipsychotics to Various Central Neurotransmitter Receptors and Clinical Incidence of Their Adverse Drug Reactions[J]. Eur J Clin Pharmacol, 1999, 55(8): 583-587.
[32] DAUVILLIERS Y, BOGAN RK, ŠONKA K, et al.Calcium, Magnesium, Potassium, and Sodium Oxybates Oral Solution: a Lower-Sodium Alternative for Cataplexy or Excessive Daytime Sleepiness Associated with Narcolepsy[J]. Nat Sci Sleep, 2022, 14: 531-546.
[33] THORPY MJ, ARNULF I, FOLDVARY-SCHAEFER N, et al.Efficacy and Safety of Lower-Sodium Oxybate in an Open-Label Titration Period of a Phase 3 Clinical Study in Adults with Idiopathic Hypersomnia[J]. Nat Sci Sleep, 2022, 14: 1901-1917.
[34] WANG J, ZOU D, LI Y, et al.Drug-Induced Tooth Discoloration: an Analysis of the US Food and Drug Administration Adverse Event Reporting System[J]. Front Pharmacol, 2023, 14: 1161728.