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Long-term adverse effects of paracetamol - a review.

ABSTRACT: Paracetamol (acetaminophen) is the most commonly used drug in the world, with a long record of use in acute and chronic pain. In recent years, the benefits of paracetamol use in chronic conditions has been questioned, notably in the areas of osteoarthritis and lower back pain. Over the same period, concerns over the long-term adverse effects of paracetamol use have increased, initially in the field of hypertension, but more recently in other areas as well. The evidence base for the adverse effects of chronic paracetamol use consists of many cohort and observational studies, with few randomized controlled trials, many of which contradict each other, so these studies must be interpreted with caution. Nevertheless, there are some areas where the evidence for harm is more robust, and if a clinician is starting paracetamol with the expectation of chronic use it might be advisable to discuss these side effects with patients beforehand. In particular, an increased risk of gastrointestinal bleeding and a small (~4 mmHg) increase in systolic blood pressure are adverse effects for which the evidence is particularly strong, and which show a degree of dose dependence. As our estimation of the benefits decreases, an accurate assessment of the harms is ever more important. The present review summarizes the current evidence on the harms associated with chronic paracetamol use, focusing on cardiovascular disease, asthma and renal injury, and the effects of in utero exposure.

SUBMITTER: McCrae JC

PROVIDER: S-EPMC6138494 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Long-term adverse effects of paracetamol - a review.

McCrae J C JC Morrison E E EE MacIntyre I M IM Dear J W JW Webb D J DJ

British journal of clinical pharmacology 20180720 10

Paracetamol (acetaminophen) is the most commonly used drug in the world, with a long record of use in acute and chronic pain. In recent years, the benefits of paracetamol use in chronic conditions has been questioned, notably in the areas of osteoarthritis and lower back pain. Over the same period, concerns over the long-term adverse effects of paracetamol use have increased, initially in the field of hypertension, but more recently in other areas as well. The evidence base for the adverse effec ...[more]

PMID: 29863746

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Project description:Background: Older adults with intellectual disability are exposed to a higher anticholinergic burden compared to general older adults. This is due to a higher rate of both mental and neurological disorders among people with intellectual disability. The use of medications with a high anticholinergic burden is associated with adverse effects including daytime dozing, constipation and higher dependence level in the Barthel index for measuring activities of daily living. This scoping review aims to map and examine the existing research on physical and cognitive adverse effects associated with the long-term impact of anticholinergics among people with intellectual disabilities. Methods: The search was conducted in: PubMed, Cochrane library, EMBASE, Medline, Science Direct, CINAHL Complete and PsycINFO. Preliminary studies, grey literature, and conference papers were searched in related electronic databases. The search terms included terms related to 'anticholinergic', 'long-term exposure', 'intellectual disability' and 'adverse drug reaction' with Boolean operator 'and'. Studies with at least three months' exposure to anticholinergics were included. The search was restricted to research papers on people with intellectual disability aged 40 or over and publication in the English language only. Initially, it was conducted in May and June 2021 and covered the publication period between 1970 and 2021. It was re-run in October 2021. Results: The conducted search provided 509 records of publications and grey literature. Duplicates were removed using EndNote 20 and resulted in 432 remaining records. Then, 426 further records were excluded because they were deemed irrelevant, or non-longitudinal studies or conducted on different populations. Only six full articles were retrieved to assess their eligibility and all were excluded due to different study populations. This resulted in no studies meeting the stated inclusion criteria. Conclusions: Further research is urgently required to examine the long-term adverse effects associated with higher anticholinergic scores among older people with intellectual disability.

Project description:BackgroundCurrently, melatonin is used to treat children and adolescents with insomnia without knowing the full extent of the short-term and long-term consequences. Our aim was to provide clinicians and guideline panels with a systematic assessment of serious-and non-serious adverse events seen in continuation of melatonin treatment and the impact on pubertal development and bone health following long-term administration in children and adolescents with chronic insomnia.MethodsWe searched PubMed, Embase, Cinahl and PsycINFO via Ovid, up to March 17, 2023, for studies on melatonin treatment among children and adolescents (aged 5-20 years) with chronic insomnia. The language was restricted to English, Danish, Norwegian, and Swedish. Outcomes were non-serious adverse events and serious adverse events assessed 2-4 weeks after initiating treatment and pubertal development and bone health, with no restriction on definition or time of measurement. Observational studies were included for the assessment of long-term outcomes, and serious and non-serious adverse events were assessed via randomised studies. The certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The protocol is registered with the Danish Health Authority.FindingsWe identified 22 randomised studies with 1350 patients reporting on serious-and non-serious adverse events and four observational studies with a total of 105 patients reporting on pubertal development. Melatonin was not associated with serious adverse events, yet the number of patients experiencing non-serious adverse events was increased (Relative risk 1.56, 95% CI 1.01-2.43, 17 studies, I2 = 47%). Three studies reported little or no influence on pubertal development following 2-4 years of treatment, whereas one study registered a potential delay following longer treatment durations (>7 years). These findings need further evaluation due to several methodological limitations.InterpretationChildren who use melatonin are likely to experience non-serious adverse events, yet the actual extent to which melatonin leads to non-serious adverse events and the long-term consequences remain uncertain. This major gap of knowledge on safety calls for caution against complacent use of melatonin in children and adolescents with chronic insomnia and for more research to inform clinicians and guideline panels on this key issue.FundingThe Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.

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Long-term adverse effects of paracetamol - a review.

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Long-term adverse effects of paracetamol - a review.

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