Cholinergic symptoms and QTc prolongation following donepezil overdose

Pourmand, Ali; Shay, Courtney; Redha, Waddaa; Aalam, Ahmad; Mazer‐Amirshahi, Maryann

doi:10.1016/j.ajem.2017.06.044

Cited by 17 publications

(7 citation statements)

References 10 publications

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“…All cases but one involved therapeutic doses of donepezil, with the remaining case involving an accidental overdose. 56 This case occurred in an 84-year-old male with previous cardiac pathology. He presented with a QT c interval of 502 ms, but no episode of TdP was recorded after he took seven times his usual 5 mg dose.…”

Section: Resultsmentioning

confidence: 97%

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QT interval prolongation andTorsades de Pointeswith donepezil, rivastigmine and galantamine

Malone

Hancox

2020

Therapeutic Advances in Drug Safety

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Background: Acetylcholinesterase inhibitors (AChEis) including donepezil, galantamine and rivastigmine are used to treat Alzheimer’s disease (AD). This study aimed to evaluate evidence from the case report literature for an association between these agents and risk of QT interval prolongation and Torsades de Pointes (TdP) arrhythmia. Methods: Published literature was mined with predetermined MeSH terms for each of donepezil, galantamine and rivastigmine, to identify cases of QT interval prolongation and TdP. Case reports were analysed using causality scales and a QT interval nomogram. Results: A total of 13 case reports were found (10 for donepezil, 2 for galantamine and 1 for rivastigmine) with rate corrected QT interval (QTc) prolongation. Five cases with donepezil exhibited TdP. TdP was not reported in the cases with galantamine and rivastigmine. The use of a QT heart rate nomogram highlighted risk with donepezil compared with the other two drugs and the application of the Naranjo causality scale suggested probable or possible causation for all donepezil cases. All patients had at least two other risk factors for TdP, including modifiable risk factors such as electrolyte disturbances, bradycardia, co-administration of QT prolonging drugs. A number of recent cases involved recent changes in medication. Conclusion: Our evaluation of the case report literature suggests that there is evidence for a causal association between donepezil and QTc/TdP risk. Attention to risk factors for QTc prolongation/TdP should be exercised when prescribing donepezil and modifiable risk factors corrected. Owing to the low number of cases with galantamine and rivastigmine, further work is needed to establish whether these drugs may be more suitable than donepezil for patients with other risk factors for TdP.

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Section: Resultsmentioning

confidence: 97%

“…Including this initial report, ten cases of QT c prolongation with donepezil were identified, of which five had clearly identified episodes of TdP. 33 , 49 , 52 – 58 Salient features of these cases are summarised in Table 2 . Eight of the ten cases were in women and two in men.…”

Section: Resultsmentioning

confidence: 99%

QT interval prolongation andTorsades de Pointeswith donepezil, rivastigmine and galantamine

Malone

Hancox

2020

Therapeutic Advances in Drug Safety

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“…These findings are compatible with previous reports ( Table 2 (B)). Excessive doses of donepezil, a central acetylcholinesterase inhibitor, induces bradycardia [27][28][29]; therefore, cholinesterase inhibition in the central nervous system may not participate in the mechanism by which rivastigmine cause tachycardia. A standard dose of rivastigmine was shown not to be associated with any changes in BP or PR [30,31].…”

Section: Discussionmentioning

confidence: 99%

Opposite changes in blood pressure and pulse rate in two patients with distigmine and rivastigmine intoxication

Sedogawa

Matsuo

2020

JA Clin Rep

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Background: Cholinergic crisis caused by cholinesterase inhibitors is rare but life-threatening. Clinical manifestations are thought to be similar to those caused by organophosphates. Case presentation: A 77-year-old woman on a standard dose of distigmine presented with impaired consciousness, blood pressure (BP) of 69/40 mmHg, a pulse rate (PR) of 60 beats/min, miosis, bronchorrhea, and serum cholinesterase (ChE) of 8 IU/L. After discontinuation of distigmine, altered mental status and pupil miosis were gradually resolved in 5 days with a concomitant increase of serum ChE. A 91-year-old woman presented with a headache, BP of 202/86 mmHg, PR of 83 beats/min, miosis, 9 rivastigmine patches on her knees, and ChE of 22 IU/L. The day after close observation without rivastigmine use, her symptoms were almost resolved with a concomitant increase of serum ChE. Conclusion: Our cases and a literature review suggested that, in contrast to distigmine, rivastigmine-induced cholinergic crisis caused hypertension and tachycardia.

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“…Since its approval in 1996 for use in Alzheimer disease (AD), there have been postmarketing reports of QTc prolongation and development of TdP with donepezil use 5. However, most published cases6-11 have been in older adults with additional risk factors, including structural heart disease and concomitant QTc-prolonging drugs. We report a case of suspected donepezil-induced QTc prolongation in a 26-year-old female patient with a history of TBI.…”

Section: Introductionmentioning

confidence: 99%

“…We report a case of suspected donepezil-induced QTc prolongation in a 26-year-old female patient with a history of TBI. Currently available case reports6-11 are limited to individuals over the age of 65. Additionally, use of donepezil for cognitive rehabilitation following TBI is considered off label.…”

Section: Introductionmentioning

confidence: 99%

Donepezil-induced QTc prolongation: A case report

Vogel¹,

Mican²,

Smith³

2019

Mental Health Clinician

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Background Several psychoactive medications are known to cause QTc prolongation. Patient factors also increase the risk for QTc prolongation, including bradycardia, female sex, older age, metabolic abnormalities, and polypharmacy. Donepezil, a cholinesterase inhibitor, prolongs the QTc interval through a multimodal mechanism. Patient History A 26-year-old African American female was admitted to the inpatient psychiatric hospital following a suicide attempt that was not an overdose. Past medical history was significant for major depression, traumatic brain injury, seizures, hemiplegia, gastroesophageal reflux disease, and tachycardia. Two baseline electrocardiograms (EKGs) were obtained showing normal QTc intervals. After several weeks, donepezil (5 mg by mouth once daily) was initiated for cognitive rehabilitation and titrated over 3 weeks to a dose of 20 mg. An EKG performed after the last dose change showed a prolonged QTc of 463 ms. Another follow-up EKG performed 9 days later showed further prolongation to 528 ms. Laboratory values were within normal limits during her hospital stay. Donepezil was discontinued completely, leading to normalization of the QTc interval. Discussion QTc prolongation and torsades de pointes have been identified in postmarketing case reports of donepezil. Instances of QTc prolongation have predominantly been documented in the geriatric population, primarily in those with additional risk factors. Additionally, current literature does not support the use of donepezil for neurocognitive rehabilitation in daily doses exceeding 10 mg. A temporal and causal relationship was observed between the initiation and titration of donepezil and development of QTc prolongation.

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Cholinergic symptoms and QTc prolongation following donepezil overdose

Cited by 17 publications

References 10 publications

QT interval prolongation andTorsades de Pointeswith donepezil, rivastigmine and galantamine

QT interval prolongation andTorsades de Pointeswith donepezil, rivastigmine and galantamine

Opposite changes in blood pressure and pulse rate in two patients with distigmine and rivastigmine intoxication

Donepezil-induced QTc prolongation: A case report

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