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Paracetamol in older people : towards evidence-based dosing?

(2018) DRUGS & AGING. 35(7). p.603-624
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Abstract
Paracetamol is the most commonly used analgesic in older people, and is mainly dosed according to empirical dosing guidelines. However, the pharmacokinetics and thereby the effects of paracetamol can be influenced by physiological changes occurring with ageing. To investigate the steps needed to reach more evidence-based paracetamol dosing regimens in older people, we applied the concepts used in the paediatric study decision tree. A search was performed to retrieve studies on paracetamol pharmacokinetics and safety in older people (> 60 years) or studies that performed a (sub) analysis of pharmacokinetics and/or safety in older people. Of 6088 articles identified, 259 articles were retained after title and abstract screening. Further abstract and full-text screening identified 27 studies, of which 20 described pharmacokinetics and seven safety. These studies revealed no changes in absorption with ageing. A decreased (3.9–22.9%) volume of distribution (Vd) in robust older subjects and a further decreased Vd (20.3%) in frail older compared with younger subjects was apparent. Like Vd, age and frailty decreased paracetamol clearance (29–45.7 and 37.5%) compared with younger subjects. Due to limited and heterogeneous evidence, it was difficult to draw firm and meaningful conclusions on changed risk for paracetamol safety in older people. This review is a first step towards bridging knowledge gaps to move to evidence-based paracetamol dosing in older subjects. Remaining knowledge gaps are safety when using therapeutic dosages, pharmacokinetics changes in frail older people, and to what extent changes in paracetamol pharmacokinetics should lead to a change in dosage in frail and robust older people.
Keywords
NONSTEROIDAL ANTIINFLAMMATORY DRUGS, ELDERLY-PATIENTS, INTRAVENOUS PARACETAMOL, PHARMACOLOGICAL MANAGEMENT, ACETAMINOPHEN ABSORPTION, ORTHOPEDIC-SURGERY, PAIN MANAGEMENT, PHARMACOKINETICS, METABOLISM, AGE

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Citation

Please use this url to cite or link to this publication:

Chicago
Mian, Paola, Karel Allegaert, Isabel Spriet, Dick Tibboel, and Mirko Petrovic. 2018. “Paracetamol in Older People : Towards Evidence-based Dosing?” Drugs & Aging 35 (7): 603–624.
APA
Mian, P., Allegaert, K., Spriet, I., Tibboel, D., & Petrovic, M. (2018). Paracetamol in older people : towards evidence-based dosing? DRUGS & AGING, 35(7), 603–624.
Vancouver
1.
Mian P, Allegaert K, Spriet I, Tibboel D, Petrovic M. Paracetamol in older people : towards evidence-based dosing? DRUGS & AGING. 2018;35(7):603–24.
MLA
Mian, Paola, Karel Allegaert, Isabel Spriet, et al. “Paracetamol in Older People : Towards Evidence-based Dosing?” DRUGS & AGING 35.7 (2018): 603–624. Print.
@article{8566315,
  abstract     = {Paracetamol is the most commonly used analgesic in older people, and is mainly dosed according to empirical dosing guidelines. However, the pharmacokinetics and thereby the effects of paracetamol can be influenced by physiological changes occurring with ageing. To investigate the steps needed to reach more evidence-based paracetamol dosing regimens in older people, we applied the concepts used in the paediatric study decision tree. A search was performed to retrieve studies on paracetamol pharmacokinetics and safety in older people ({\textrangle}\,60 years) or studies that performed a (sub) analysis of pharmacokinetics and/or safety in older people. Of 6088 articles identified, 259 articles were retained after title and abstract screening. Further abstract and full-text screening identified 27 studies, of which 20 described pharmacokinetics and seven safety. These studies revealed no changes in absorption with ageing. A decreased (3.9--22.9\%) volume of distribution (Vd) in robust older subjects and a further decreased Vd (20.3\%) in frail older compared with younger subjects was apparent. Like Vd, age and frailty decreased paracetamol clearance (29--45.7 and 37.5\%) compared with younger subjects. Due to limited and heterogeneous evidence, it was difficult to draw firm and meaningful conclusions on changed risk for paracetamol safety in older people. This review is a first step towards bridging knowledge gaps to move to evidence-based paracetamol dosing in older subjects. Remaining knowledge gaps are safety when using therapeutic dosages, pharmacokinetics changes in frail older people, and to what extent changes in paracetamol pharmacokinetics should lead to a change in dosage in frail and robust older people.},
  author       = {Mian, Paola and Allegaert, Karel and Spriet, Isabel and Tibboel, Dick and Petrovic, Mirko},
  issn         = {1170-229X},
  journal      = {DRUGS \& AGING},
  language     = {eng},
  number       = {7},
  pages        = {603--624},
  title        = {Paracetamol in older people : towards evidence-based dosing?},
  url          = {http://dx.doi.org/10.1007/s40266-018-0559-x},
  volume       = {35},
  year         = {2018},
}

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