According to the US Food and Drug Administration, the drug may cause rare and possibly fatal skin reactions such as Stevens–Johnson syndrome and toxic epidermal necrolysis, although an analysis of the French Pharmacovigilance Database indicated no obvious risk of these reactions.In clinical trials for osteoarthritis, the number of participants reporting adverse effects were similar for those on paracetamol and on placebo. However, the abnormal liver function tests (meaning there was some inflammation or damage to the liver) were almost four times more likely in those on paracetamol, although the clinical importance of this effect is uncertain. After 13 weeks of paracetamol therapy for knee pain, a drop in hemoglobin level indicating gastrointestinal bleeding was observed in 20% of participants, this rate being similar to ibuprofen group.Due to the absence of controlled studies, most of the information about the long-term safety of paracetamol comes from observational studies. These indicate a consistent pattern of increased mortality as well as cardiovascular (stroke, myocardial infarction), gastrointestinal (ulcers, bleeding) and renal adverse effects with increased dose of paracetamol. Use of paracetamol is associated with 1.9 times higher risk of peptic ulcer. Those who take it regularly at a higher dose (more than 2–3 g daily) are at much higher risk (3.6–3.7 times) of gastrointestinal bleeding and other bleeding events. Meta-analyses suggest that paracetamol may increase the risk of kidney impairment by 23% and kidney cancer by 28%.
Based on this, some physicians advocate using higher doses that may decrease the temperature by as much as 0.7 °C. Meta-analyses showed that paracetamol is less effective than ibuprofen in children (marginally less effective, according to another analysis), including children younger than 2 years old, with equivalent safety. Exacerbation of asthma occurs with similar frequency for both medications. Giving paracetamol and ibuprofen together at the same time to children under 5 is not recommended, however doses may be alternated if required. Pain
Paracetamol is used for the relief of mild to moderate pain such as headache, muscle aches, minor arthritis pain, toothache as well as pain caused by cold, flu, sprains, and dysmenorrhea. It is recommended, in particular, for acute mild to moderate pain, since the evidence for the treatment of chronic pain is insufficient. Musculoskeletal pain
The benefits of paracetamol in musculoskeletal conditions, such as osteoarthritis and backache, are uncertain.It appears to provide only small and not clinically important benefits in osteoarthritis. American College of Rheumatology and Arthritis Foundation guideline for the management of osteoarthritis notes that the effect size in clinical trials of paracetamol has been very small, which suggests that for most individuals it is ineffective. The guideline conditionally recommends paracetamol for short-term and episodic use to those who do not tolerate nonsteroidal anti-inflammatory drugs. For people taking it regularly, monitoring for liver toxicity is required. Essentially the same recommendation was issued by EULAR for hand osteoarthritis.