Data mining study on adverse events of cinacalcet based on JADER database

doi:10.21203/rs.3.rs-5302434/v1

Download PDF

Research Article

Data mining study on adverse events of cinacalcet based on JADER database

https://doi.org/10.21203/rs.3.rs-5302434/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background

Cinacalcet is the first calcium-sensing receptor agonist (calcimimetic) primarily indicated for the management of secondary hyperparathyroidism in patients with chronic kidney disease. This study aims to evaluate the safety profile of cinacalcet in real-world clinical settings.

Methods

Data on adverse events (AEs) associated with cinacalcet, reported from the second quarter of 2004 to the fourth quarter of 2023, were extracted from the Japanese Adverse Drug Event Report (JADER) database. Data mining was performed using the reporting odds ratio (ROR) method, and the time to onset was analyzed using the Weibull Shape Parameter (WSP).

Results

A total of 663 AE reports related to cinacalcet were identified, involving 284 Preferred Terms (PTs) and 24 System Organ Classes (SOCs). Six noteworthy SOCs qualified based on criteria. Additionally, 67 AEs were identified with positive signals, comprising 41 significant AEs and 36 unexpected AEs. Notable signals that warrant particular attention include parathyroid haemorrhage, electrocardiogram QT shortened, sphincter of Oddi dysfunction, nephrolithiasis, intestinal obstruction, pancreatitis, ascites, gastrointestinal necrosis. The majority of AEs occurred within the first month of treatment. The WSP was calculated to be 0.66, indicating an early failure type.

Conclusion

This study has identified several significant and unexpected AEs associated with cinacalcet use, highlighting the need for careful monitoring, especially during the early stages of therapy.

cinacalcet

adverse events

data mining

JADER database

reporting odds ratio

Chronic Kidney Disease (CKD) has a global prevalence of approximately 10–15% across different regions. In 2017, CKD was responsible for 1.2 million deaths worldwide, and the all-age mortality rate associated with CKD increased by 41.5% from 1990 to 2017, underscoring its impact as a major public health concern [1, 2]. Secondary hyperparathyroidism (SHPT) is a common yet serious complication of CKD, characterized by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone (PTH). Persistent elevation of PTH levels, along with abnormalities in serum calcium and phosphorus, not only adversely affect the skeletal, nervous, and cardiovascular systems but also increase the risk of hospitalization and mortality, thereby imposing significant economic and psychological burdens on patients undergoing dialysis [3, 4].

Current treatments for SHPT include both pharmacological and surgical approaches. For patients with refractory SHPT who do not have contraindications to surgery, parathyroidectomy is considered the preferred treatment option. In contrast, for patients who are either unable or unwilling to undergo surgical resection, calcimimetic therapy is recommended as the initial treatment strategy. Calcimimetics modulate parathyroid function by mimicking the action of calcium ions on calcium-sensing receptors (CaSRs) in the parathyroid glands, thereby activating cellular signaling pathways mediated by CaSRs [5]. Currently, three calcimimetics have been globally approved for clinical use: cinacalcet, etelcalcetide, and evocalcet [6]. Cinacalcet, the first oral calcimimetic, was approved in the United States in March 2004, followed by approval in Europe in December of the same year. It was subsequently approved in Japan in October 2007 and entered the Chinese market in February 2015. Cinacalcet has been shown to effectively control serum PTH levels in patients with SHPT, reducing the risk of bone disease and cardiovascular events [7].

Despite its efficacy in managing PTH levels, cinacalcet's clinical application has been limited by its adverse effects, including hypocalcemia, nausea, vomiting, arrhythmia, and severe dehydration [8–11]. However, there is a lack of comprehensive analysis of cinacalcet-associated adverse events (AEs). While previous studies have utilized the US FDA Adverse Event Reporting System (FAERS) database for safety analysis of AEs [12, 13], the use of the Japanese Adverse Drug Event Reporting (JADER) database has not been documented in the literature. The JADER database, managed by the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan, is a spontaneous reporting system (SRS) that collects AE data primarily from healthcare professionals, as well as serious AEs reported in post-marketing clinical trials, drug use outcome surveys, and specific drug use surveys [14]. Thus, this study aims to explore the incidence, onset time, and post-hoc outcomes of cinacalcet-associated AEs with high risk using the JADER database.

2.1. Data source

The study data is sourced from the JADER database (https://www.pmda.go.jp), encompassing AE reports from the second quarter of 2004 (2004Q2) through to the fourth quarter of 2023 (2023Q4). The JADER database is stored in the form of Comma-Separated Values (CSV) files and comprises four tables: a demographic information table (DEMO), a medication record table (DRUG), an adverse event information table (REAC), and a past medical history table (HIST).

2.2. Data Acquisition

The DEMO, DRUG, REAC, and HIST tables were imported into SAS 9.4 software for analysis. To enhance the accuracy of the study, cinacalcet was identified using its generic name “シナカルセト” or its trade name “レグパラ” as search terms. The screening for relevant drug-AE combinations was conducted by focusing on reports where cinacalcet was a suspected drug. AEs recorded in the REAC table and primary diseases listed in the HIST table were coded according to the Preferred Term (PT) and the System Organ Class (SOC) from the Medical Dictionary for Regulatory Activities (MedDRA) version 26.1.

2.3. Data mining

Signal detection was carried out using the reporting odds ratio (ROR) method, a disproportionality analysis technique. The key metrics for the ROR method include the ROR value and its 95% two-sided confidence interval (95% CI), calculated based on a contingency table (as shown in Table 1). The formulas and criteria for this method are provided in Table 2. Significant AEs are signals documented in the Important Medical Event (IME) list 27.0, released by the European Union; Unexpected AEs are signals not listed in any of the labels.

Table 1

Four-grid table for analysis.
Drugs	Target AEs	Non-target AEs	Total
cinacalcet	a	b	a + b
Non-cinacalcet	c	d	c + d
Total	a + c	b + d	N = a + b + c + d
a, number of reports containing both the target drug and target adverse drug reaction; b, number of reports containing other adverse drug reaction of the target drug; c, number of reports containing the target adverse drug reaction of other drugs; d, number of reports containing other drugs and other adverse drug reactions.

2.4. The analysis of onset time

The time-to-onset (TTO) of cinacalcet-related AEs was defined as the time interval between the date of the AE recorded in the REAC table and the date of initiation of cinacalcet dosing recorded in the DEMO table. Reports with input errors or incomplete dates were excluded from the analysis. TTO was assessed using the median, interquartile range (IQR), and the Weibull distribution shape parameter (β). If β < 1 and its 95% CI < 1, the incidence of AEs is considered to decrease over time (early failure type). If β is equal to or near 1 and its 95% CI includes 1, the incidence of AEs is considered to occur randomly over time (random failure type). If β > 1 and its 95% CI excludes 1, the incidence of AEs is considered to increase over time (wear-out failure type). Data processing and analysis were conducted using Microsoft Excel 2019, Prism 8.0, and R version 4.4.0.

3.1. Basic information on AE reports

From 2004Q2 to 2023Q4, the JADER database recorded a total of 663 AE reports related to cinacalcet, involving 1,222 cases and 284 PTs. Table 3 provides a summary of the clinical characteristics of these AEs. Among the reported cases, 52.94% occurred in males and 45.10% in females, with the majority of AEs observed in patients aged 45–65 years (58.87%) and those over 65 years (40.12%). The reports were predominantly from research studies (64.25%), with physicians being the primary reporters (93.82%). The annual number of reports initially increased, peaking in 2016 (25.34%), and subsequently declined.

Table 3

Characteristics of AE reports related to cinacalcet from JADER databases.
Characteristics	Number (%)
Gender
Male	351 (52.94)
Female	299 (45.10)
Unknown	13 (1.96)
Age
< 18	1 (0.15)
18≥, < 45	68 10.26)
45≥, < 65	324 (48.87)
65≥	266 (40.12)
Missing	4 (0.60)
Report type
Spontaneous reports	219 (33.03)
Research reports	426 (64.25)
Other	18 (2.71)
Reporter ^a
Physician	622 (93.82)
Pharmacist	36 (5.43)
Other health-professional	74 (11.16)
Consumer	3 (0.45)
Unknown	10 (1.51)
Report year
2007	11 (1.66)
2008	64 (9.65)
2009	37 (5.58)
2010	24 (3.62)
2011	21 (3.17)
2012	14 (2.11)
2013	10 (1.51)
2014	15 (2.26)
2015	48 (7.24)
2016	168 (25.34)
2017	115 (17.35)
2018	89 (13.42)
2019	24 (3.62)
2020	12 (1.81)
2021	2 (0.30)
2022	7 (1.06)
2023	2 (0.30)

3.2. Signals of cinacalcet-related AEs at the SOC Level

As shown in Table 4, cinacalcet-related AEs were distributed across 24 SOCs. Six SOCs met the criteria for significant association: gastrointestinal disorders (SOC: 10017947, 203 reports), cardiac disorders (SOC: 10007541, 160 reports), injury, poisoning, and procedural complications (SOC: 10022117, 141 reports), metabolism and nutrition disorders (SOC: 10027433, 89 reports), surgical and medical procedures (SOC: 10042613, 72 reports), and product issues (SOC: 10077536, 4 reports). The top three categories, based on intensity, were surgical and medical procedures, product issues, and injury, poisoning, and procedural complications.

Table 4

Signal values of reports related to cinacalcet at the SOC level.
SOC	N	ROR (95% CI)
Endocrine disorders	4439	17.20 (16.62–17.81)*
Respiratory, thoracic and mediastinal disorders	3896	2.13 (2.06–2.21)*
Neoplasms benign, malignant and unspecified (incl cysts and polyps)	2653	2.84 (2.73–2.96)*
Gastrointestinal disorders	2503	1.31 (1.25–1.36)*
Hepatobiliary disorders	1680	1.45 (1.38–1.53)*
Infections and infestations	1500	0.61 (0.58–0.64)
Metabolism and nutrition disorders	1231	1.12 (1.05–1.18)*
Skin and subcutaneous tissue disorders	1196	0.70 (0.66–0.74)
Nervous system disorders	1092	0.44 (0.42–0.47)
Renal and urinary disorders	1067	1.09 (1.03–1.16)*
Blood and lymphatic system disorders	1036	0.45 (0.42–0.48)
General disorders and administration site conditions	1001	0.70 (0.66–0.75)
Cardiac disorders	737	0.71 (0.66–0.77)
Musculoskeletal and connective tissue disorders	694	1.09 (1.01–1.18)*
Investigations	635	0.21 (0.2–0.23)
Immune system disorders	267	0.32 (0.29–0.36)
Vascular disorders	260	0.41 (0.36–0.46)
Eye disorders	221	0.61 (0.53–0.69)
Injury, poisoning and procedural complications	170	0.24 (0.21–0.28)
Psychiatric disorders	90	0.16 (0.13–0.19)
Reproductive system and breast disorders	23	0.22 (0.15–0.34)
Ear and labyrinth disorders	18	0.33 (0.21–0.53)
Surgical and medical procedures	16	0.20 (0.12–0.33)
Congenital, familial and genetic disorders	5	0.09 (0.04–0.21)
Pregnancy, puerperium and perinatal conditions	3	0.03 (0.01–0.09)
N, the number of adverse event reports; ROR, the reporting odds ratio; CI, confidence interval.
* Indicates a statistically significant signal in the algorithm.

3.3. Signals of cinacalcet-related AEs at the PT level

Based on the established thresholds and excluding signals related to cinacalcet’s indications, a total of 67 positive risk signals involving 19 SOCs were identified (Fig. 1). Among these, 41 were significant AEs (61.19%), and 36 were unexpected AEs (53.73%). Notably, the top three AEs were parathyroid hemorrhage (ROR = 1114.49, 95% CI: 266.05–4668.68), electrocardiogram QT shortening (ROR = 928.74, 95% CI: 232.01–3717.82), and sphincter of Oddi dysfunction (ROR = 619.16, 95% CI: 167.42–2289.83), all of which were significant and unexpected.

3.4. Timing of cinacalcet-associated AE onset

A total of 455 records with documented AE onset times were analyzed. Figure 2 illustrates the distribution of AE onset times, categorized into eight intervals. The findings indicate that the majority of AEs occurred within the first month of cinacalcet use and after more than one year of use. Additionally, Fig. 3 presents the histogram and Weibull distribution of AE onset times related to cinacalcet, with a Weibull Shape Parameter (WSP) of 0.66, suggesting an early failure type.

3.5. Outcomes of cinacalcet-related AEs

Figure 4 presents a bar chart illustrating the outcomes of AEs associated with cinacalcet, as reported in the JADER database. The results demonstrated that the majority of outcomes were classified as remission and recovery. Conversely, death, unrecovery, and after-effects constituted a smaller proportion of the overall data.

This study utilized data from the JADER database to conduct a comprehensive, large-scale real-world analysis of cinacalcet, thereby enhancing the evidence base for its clinical use beyond clinical trials, case reports, and other study types. The AEs were predominantly reported among males (52.94%), aligning with findings that indicate males as a high-risk group for developing secondary hyperparathyroidism (SHPT) [15]. Reports were mainly from individuals aged over 45 years, which is consistent with the age distribution observed in the FAERS database [12]. The number of annual reports showed a trend of initially increasing and then decreasing, suggesting that healthcare professionals have been vigilant about the safe use of cinacalcet and have implemented effective measures to mitigate risks.

At the SOC level, our analysis identified six noteworthy SOCs qualified based on criteria, with notable signals in surgical and medical procedures, product issues, injury, poisoning and procedural complications exhibiting being more pronounced signals. It is noteworthy that our comprehensive evaluation indicates that these AEs are predominantly attributable to procedural related injuries and complications, bone and joint injuries, device issues and therapeutic procedures. These findings imply that such AEs associated with cinacalcet are largely preventable, rather than an inherent property of the drug. This underscores the necessity for differentiating between pharmacological side effects and complications resulting from procedural errors.

The signal for cardiac disorders was notably strong. CaSRs are widely distributed in β-cells, enteroendocrine cells, adipocytes, and myocytes, providing a basis for calcium ions' involvement in regulating cardiac function and metabolism [16]. Calcimimetics can induce cardiac-related AEs by mimicking calcium ions' actions on CaSRs, warranting clinical attention. The prescribing information indicates that cardiotoxicity associated with cinacalcet is primarily manifested by myocardial infarction, myocardial ischemia, atrial fibrillation, palpitations, tachycardia, and cardiac failure. The use of calcimimetics can affect blood calcium levels, potentially impacting the cardiac system. One study showed that cinacalcet-induced transient hypocalcemia was associated with an increased risk of cardiovascular mortality [17]. Another study suggested that cinacalcet dosing regimens exceeding eight weeks may heighten the risk of cardiac-related AEs, which should be considered in clinical practice [13]. Therefore, it is recommended that clinicians closely monitor patients' blood calcium levels to adjust medication regimens as needed and enhance surveillance for cardiac AE signals.

Signals from the gastrointestinal system were also pronounced. A meta-analysis indicated that gastrointestinal AEs are among the most frequent AEs linked to cinacalcet treatment, significantly contributing to poor medication compliance and discontinuation among patients with SHPT [18]. In this study, positive signals for gastrointestinal hemorrhage, gastritis, nausea, vomiting, and abdominal pain were detected, consistent with the drug's specifications. Additionally, this study identified unexpected significant AEs such as intestinal obstruction, pancreatitis, ascites, and gastrointestinal necrosis. Studies have shown that deoxynivalenol (vomitoxin) can cause food refusal and vomiting, with its secretion being associated with CaSR activation, which might be a potential mechanism for gastrointestinal toxicity induced by calcimimetics [19]. Ceglia et al. [20] found that cinacalcet might increase basal gastric acid production in healthy adults, leading to gastric ulcers, gastritis, and other disorders, suggesting a potential risk of inducing gastrointestinal AEs such as gastric ulcers and bleeding.

Metabolic and nutritional disorders also showed strong signals, with hypocalcaemia being the most frequent. A machine learning-based systematic evaluation indicated that cinacalcet is associated with an increased risk of hypocalcemia (RR = 4.05, 95% CI = 2.33 to 7.04, p = 0.001) [21]. Additionally, new positive signals for hypercalcaemia and hyperphosphataemia caused by cinacalcet were detected in this study. These signals may relate to disease progression and indirectly suggest that the patient's condition is not being effectively controlled, potentially providing evidence to support drug efficacy evaluation. It is recommended that clinicians regularly monitor serum calcium, phosphorus, and PTH levels when administering calcimimetics to timely assess treatment efficacy and prevent serious AEs.

Notably, this study identified several significant and unexpected signals, with parathyroid haemorrhage being the most prominent. Nagasawa et al. [22] reported a case of parathyroid hemorrhage in a rare SHPT patient on cinacalcet. The authors suggested a potential mechanism where partial loss of thyroid hyperplastic cells responsive to cinacalcet might reduce intracapsular pressure, leading to an oversupply of blood, potentially resulting in vessel rupture and haemorrhage. We identified three cases of electrocardiogram QT prolongation; however, literature reviews revealed more reports of cinacalcet causing QT prolongation [23–25]. Interestingly, cinacalcet has been shown to reverse short QT intervals in familial hypocalciuric hypercalcemia type 1 [26]. Further clinical studies are necessary to fully understand cinacalcet's effect on the QT interval. Additionally, Bernardor et al. [27] reported a case of a child wiath SHPT treated with cinacalcet who developed nephrolithiasis secondary to hypercalciuria. While other signals, such as cataract, bile duct stone, gangrene, diverticulitis, osteonecrosis, malignant neoplasm, facial paralysis, and renal haemorrhage, have not been reported in clinical studies or case reports, caution should be exercised when interpreting these findings due to the limited number of cases included. It is imperative for clinicians to recognize and manage potential AEs early to prevent serious outcomes.

The onset time analysis in our study indicated that AEs could occur at any time during the one-year treatment period, with a notable proportion (21.89%) occurring within the first month. Long-term AEs were also a concern, with 40.56% of patients reporting AEs more than one year after initiating cinacalcet treatment. The Weibull Shape Parameter (WSP) was 0.66, indicating an early failure type, meaning the incidence of AEs declines over time. This analysis provides insight into cinacalcet's risk profile over time, which can inform the development of monitoring strategies for patients on this medication. As shown in Fig. 4, while cinacalcet is generally regarded as having a favorable safety profile, there have been instances of serious AEs. Notably, deaths constituted 7.53% of the reported cases. The diversity within this category may provide insights into various health challenges facing the population. However, it is crucial to consider the high proportion of missing data when interpreting these results, as it could significantly impact the understanding of the drug's safety profile.

This study has several limitations. First, the JADER database is a self-reporting system prone to omissions, duplicate reporting, and incomplete case information, which may introduce bias. Second, the database does not record the total number of medicine users, preventing calculations of AE incidence rates. Third, the data analysis did not account for unmeasured confounders such as drug-drug interactions, comorbidities, and concurrent medications. Furthermore, the ROR method reflects statistical correlations rather than cause-and-effect relationships, which require validation through large-scale clinical studies. Despite these limitations, this study provides critical insights into cinacalcet's safety profile, which can guide clinical practice and inform risk management strategies.

This study represents the most comprehensive analysis of cinacalcet-related AEs using data from the JADER database. We identified several serious and novel AE signals related to cinacalcet, such as parathyroid haemorrhage, electrocardiogram QT shortened, sphincter of Oddi dysfunction, nephrolithiasis, intestinal obstruction, pancreatitis, ascites, gastrointestinal necrosis. etc. These findings highlight the need for increased vigilance for potential adverse reactions across various systems, particularly during the early stages of treatment. Ongoing pharmacovigilance and regularly updated safety information are essential for optimizing the clinical use of cinacalcet.

Funding

This research was funded by the Kunming Health Science and Technology Talent Cultivation "Thousand Project" Programme (2023-SW (back-up)-84), Kunming Health Care Commission's Health Research Project (2023-13-01-017), The Scientific Research Fund Project of the Yunnan Provincial Department of Education (2024J0371), and Yunnan Provincial Association of Pharmacists in Healthcare Facilities Scientific Research Special Fund Project (2024YSXH06).

Declaration of interests

The authors thank the JADER database for providing the data and the FastSignal team for technical support.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors acknowledge the data provided by JADER database.

Author contributions

Feilong Tan: conception and design the study. Feilong Tan, Hongying Xia: acquisition, analysis and interpretation of the data. Feilong Tan, Wenjie Yin: draft and revision of the paper. All authors agree to be accountable for all aspects of the work.

GBD Chronic Kidney Disease Collaboration (2020) Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 395(10225):709–733. 10.1016/S0140-6736(20)30045-3
Levin A, Tonelli M, Bonventre J et al (2017) Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy. Lancet 390(10105):1888–1917. 10.1016/S0140-6736(17)30788-2
Salam SN, Khwaja A, Wilkie ME (2016) Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease. Drugs 76(8):841–852. 10.1007/s40265-016-0575-2
Franklyn JA, Sheppard MC, Maisonneuve P (2005) Thyroid function and mortality in patients treated for hyperthyroidism. JAMA 294(1):71–80. 10.1001/ jama.294.1.71
Harrington PE, Fotsch C (2007) Calcium sensing receptor activators: calcimimetics. Curr Med Chem 14(28):3027–3034. 10.2174/092986707782794096
Liu X, Liu Y, Zheng P et al (2024) Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis. Eur J Clin Pharmacol Published online July 13. 10.1007/s00228-024-03730-5
Evans M, Methven S, Gasparini A et al (2018) Cinacalcet use and the risk of cardiovascular events, fractures and mortality in chronic kidney disease patients with secondary hyperparathyroidism. Sci Rep. ;8(1):2103. Published 2018 Feb 1. 10.1038/s41598-018-20552-5
Zamoner SMS, Takase HM, Riyuzo MC et al (2024) Safety of cinacalcet in children and adolescents with chronic kidney disease-mineral bone disorder: systematic review and proportional meta-analysis of case series. Int Urol Nephrol 56(5):1669–1676. 10.1007/s11255-023-03844-2
Wang G, Liu H, Wang C et al (2018) Cinacalcet versus Placebo for secondary hyperparathyroidism in chronic kidney disease patients: a meta-analysis of randomized controlled trials and trial sequential analysis. Sci Rep. ;8(1):3111. Published 2018 Feb 15. 10.1038/s41598-018-21397-8
Sun Y, Tian B, Sheng Z et al (2020) Efficacy and safety of cinacalcet compared with other treatments for secondary hyperparathyroidism in patients with chronic kidney disease or end-stage renal disease: a meta-analysis. BMC Nephrol. ;21(1):316. Published 2020 Jul 31. 10.1186/s12882-019-1639-9
Manaka K, Sato J, Kinoshita Y et al (2019) Effectiveness and safety of cinacalcet for primary hyperparathyroidism: a single center experience. Endocr J 66(8):683–689. 10.1507/endocrj.EJ19-0034
Wang H, Zhong G, Li D et al (2024) Mining and analysis of adverse drug event signals of cinacalcet and etelcalcetide. China Pharm 35(8):986–990. 10.6039/j.issn.1
Wen X, Guo T, Han S et al (2024) Signal analysis of adverse drug event related to cardiac disorders in cinacalcet and etelcalcetide. Chin J New Drugs Clin Remedies 43(03):236–240. 10.14109/j.cnki.xyylc.2024.0 3.14
Tsuchiya M, Obara T, Sakai T et al (2020) Quality evaluation of the Japanese Adverse Drug Event Report database (JADER). Pharmacoepidemiol Drug Saf 29(2):173–181. 10.1002/pds.4944
Xu Y, Evans M, Soro M et al (2021) Secondary hyperparathyroidism and adverse health outcomes in adults with chronic kidney disease. Clin Kidney J 14(10):2213–2220 Published 2021 Jan 20. 10.1093/ckj/sfab006
Vahe C, Benomar K, Espiard S et al (2017) Diseases associated with calcium-sensing receptor. Orphanet J Rare Dis 12(1):19 1186 /s13023-017-0570-z
Goto S, Hamano T, Fujii H et al (2024) Hypocalcemia and cardiovascular mortality in cinacalcet users. Nephrol Dial Transpl 39(4):637–647. 10.1093/ndt/gfad 213
Sekercioglu N, Busse JW, Sekercioglu MF et al (2016) Cinacalcet versus standard treatment for chronic kidney disease: a systematic review and meta-analysis. Ren Fail 38(6):857–874. 10.3109/0886022X.2016.1172468
Wu W, Zhou HR, Bursian SJ et al (2017) Calcium-Sensing Receptor and Transient Receptor Ankyrin-1 Mediate Emesis Induction by Deoxynivalenol (Vomitoxin). Toxicol Sci 155(1):32–42. 10.1093/toxsci/kfw191
Ceglia L, Harris SS, Rasmussen HM et al (2009) Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants. Osteoporos Int 20(1):71–78. 10.1007/s00198-008-0637-8
Li X, Ding W, Zhang H (2023) Cinacalcet use in secondary hyperparathyroidism: a machine learning-based systematic review. Front Endocrinol (Lausanne) 14:1146955 Published 2023 Jul 19. 10.3389/fendo.2023.1146955
Nagasawa M, Ubara Y, Suwabe T et al (2012) Parathyroid hemorrhage occurring after administration of cinacalcet in a patient with secondary hyperparathyroidism. Intern Med 51(24):3401–3404. 10.2169/internalmedicine. 51.8055
Yuan N, Oesterle A, Botting P et al (2023) High-Throughput Assessment of Real-World Medication Effects on QT Interval Prolongation: Observational Study. JMIR Cardio 7:e41055 Published 2023 Jan 20. 10.2196/41055
Temiz G, Yalçın AU, Mutluay R et al (2016) Effects of cinacalcet treatment on QT interval in hemodialysis patients. Anatol J Cardiol 16(7):520–523. 10.5152/AnatolJCardiol.2015.6284
Borrego-Utiel FJ, Pérez-del Barrio Mdel P, Biechy-Baldan Mdel M et al (2013) Cinacalcet may prolong the QT interval in patients on haemodialysis with secondary hyperparathyroidism. Nefrologia 33(2):272–273. 10.3265/Nefrologia.pre2012.Oct.11679
Cuny T, Romanet P, Goldsworthy M et al (2024) Cinacalcet Reverses Short QT Interval in Familial Hypocalciuric Hypercalcemia Type 1. J Clin Endocrinol Metab 109(2):549–556. 10.1210/clinem/dgad494
Bernardor J, Flammier S, Salles JP et al (2022) Off-label use of cinacalcet in pediatric primary hyperparathyroidism: A French multicenter experience. Front Pediatr 10:926986 Published 2022 Aug 24. 10.3389/fped.2022.926986

Table 2 is available in the Supplementary Files section.

No competing interests reported.

Table2.docx

Download PDF

Reviewers invited by journal
25 Oct, 2024
Editor assigned by journal
23 Oct, 2024
Submission checks completed at journal
23 Oct, 2024
First submitted to journal
21 Oct, 2024

You are reading this latest preprint version

Data mining study on adverse events of cinacalcet based on JADER database

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

1. Introduction

2. Methods

2.1. Data source

2.2. Data Acquisition

2.3. Data mining

2.4. The analysis of onset time

3. Results

3.1. Basic information on AE reports

3.2. Signals of cinacalcet-related AEs at the SOC Level

3.3. Signals of cinacalcet-related AEs at the PT level

3.4. Timing of cinacalcet-associated AE onset

3.5. Outcomes of cinacalcet-related AEs

4. Discussion

5. Conclusion

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1