Evaluation of toxicity after acute accidental methotrexate ingestions in children under 6 years old: a 16-year multi-center review

Hays, Hannah L.; Beuhler, Michael C.; Spiller, Henry A.; Weber, Julie A; Mowry, James B.; Ryan, Mark L.; Spiller, Natalie; Webb, Ashley N.

doi:10.1080/15563650.2017.1349319

Cited by 11 publications

(8 citation statements)

References 16 publications

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“…Previous pediatric studies report low-dose ingestions, and most patients have good clinical outcomes. 7 As new methotrexate formulations are developed, such as new "sweet-flavored" solutions, and dispensed in larger bottles, pediatric exposures with higher-dose ingestions may potentially increase. Poison centers should be prepared for triaging these exposures and referring them for medical evaluation.…”

Section: Discussionmentioning

confidence: 99%

Methotrexate Toxicity from Unintentional Dosing Errors: Calls to a Poison Center and Death Descriptions

2021

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Section: Discussionmentioning

confidence: 99%

Methotrexate Toxicity from Unintentional Dosing Errors: Calls to a Poison Center and Death Descriptions

2021

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“…Few studies reported the dosage information using the NPDS data. 24,25 Some drugs/products may have had a higher missing rate of dose information than other products. Another limitation is using national drug utilization as denominators for children, assuming who experience side effects that in NPDS are the patients for whom the medication was prescribed.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Trend changes of national zolpidem users and exposure cases after FDA drug safety communications

Zhou

Feng

Pinnow

et al. 2021

Pharmacoepidemiology and Drug

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Purpose: To evaluate the impact of FDA's 2013 zolpidem Drug Safety Communications (DSCs), which recommended lowering the initial dose to mitigate drowsiness, on national estimates of zolpidem users and zolpidem exposure cases. Methods:We analyzed trend changes of national zolpidem users from the IQVIA Total Patient Tracker (TPT) and zolpidem exposure cases reported to the National Poison Data System (NPDS), 2009-2018. To control for time varying confounding, the adjusted trends were analyzed using simple and controlled interrupted time series (ITS). We also adjusted for seasonal changes. Three sedating antidepressants were used together as a control. Results:The national estimates of high-dose zolpidem users in TPT decreased significantly in the month immediately post-DSC; the absolute level decrease was À12.51 (95% CI: À14.12, À10.89) per 10 000 U.S. population relative to sedating antidepressants. The trend continuously decreased post-DSC, resulting in a 59% overall decrease by the end of the study period. There was a larger decrease in high-dose zolpidem use in females than in males. There was a level decrease of zolpidem exposure cases in the NPDS immediately post-DSC, À0.37 absolute decline (95% CI, À0.53, À0.20) per 10 000 national zolpidem users; or À1.33 absolute decline (95% CI, À1.54, À1.13) per 1000 total NPDS exposure cases relative to sedating antidepressants. Similar patterns were observed for cases reporting drowsiness. The results from the single ITS and controlled ITS were similar.Conclusions: Zolpidem users and exposure cases decreased significantly post-DSC, suggesting practitioners and patients became aware of and responded to the zolpidem DSCs. K E Y W O R D S controlled interrupted time series, drug safety communication, regulatory impact Key Points• A controlled interrupted time series analysis was performed to evaluate the impact of the FDA's zolpidem DSCs in 2013, which recommended lowering the initial dose to mitigate drowsiness.

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“…By examiniation of its pharmacokinetics it is be possible to decrease the risk of toxicity during the therapy. One common pattern of exposure to methotrexate is repeated oral daily dosing [ 3 , 4 ]; a second is accidental acute ingestion [ 5 , 6 , 7 ]. According to a large series of studies carried out at poisons information centers in Australia [ 3 ], France [ 4 ], Denmark [ 8 ], Spain [ 9 ], and the USA [ 10 ], the death rate after mistakes in methotrexate dosing range from 5.2% to 24%.…”

Section: Introductionmentioning

confidence: 99%

Toxicological Aspects of Methotrexate Intoxication: Concentrations in Postmortem Biological Samples and Autopsy Findings

Szpot

Wachełko²,

Zawadzki³

2022

Toxics

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The aim of this study was the establishment of a UHPLC-QqQ-MS/MS method to determine methotrexate in postmortem biological samples and quantify the postmortem distribution of methotrexate in a case of fatal intoxication of this drug. A volume of 100 µL or 100 mg of postmortem specimens was precipitated with 400 µL of cold methanol and then analyzed using UHPLC-QqQ-MS/MS. The validation parameters of the method were as follows: limit of quantification: 0.1–1.0 ng/mL or ng/g, coefficient of determination: >0.998 (R2), matrix effect, intra- and inter-day accuracies and precisions: not greater than 13.6%, 14.8% and 17.4%, respectively. The recoveries were: 89.0–113.6%. The postmortem distribution studies revealed methotrexate concentrations as follows: blood—7.2 ng/mL, vitreous humor—0.8 ng/mL, liver—43.7 ng/g, kidney—20.6 ng/g, bone marrow—29.9 ng/g, lumbar vertebra—20.0 ng/g. The highest concentrations of methotrexate after poisoning were found in the tissues with the most rapidly dividing cells. The method described is simple, precise and selective. Methotrexate concentrations can be routinely determined in postmortem specimens. Determination of methotrexate in the postmortem biological material is possible after a few days of intensive treatment.

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Evaluation of toxicity after acute accidental methotrexate ingestions in children under 6 years old: a 16-year multi-center review

Cited by 11 publications

References 16 publications

Methotrexate Toxicity from Unintentional Dosing Errors: Calls to a Poison Center and Death Descriptions

Methotrexate Toxicity from Unintentional Dosing Errors: Calls to a Poison Center and Death Descriptions

Trend changes of national zolpidem users and exposure cases after FDA drug safety communications

Toxicological Aspects of Methotrexate Intoxication: Concentrations in Postmortem Biological Samples and Autopsy Findings

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