Pain Management

Non-Opioid Analgesics

For mild to moderate pain, non-opioid analgesics such as NSAIDs are recommended over acetaminophen-codeine combinations due to superior efficacy and safety profile, as suggested by the American College of Critical Care 1
Acetaminophen is the first-line choice for mild to moderate pain, particularly musculoskeletal pain, according to the American Geriatrics Society and the European League Against Rheumatism 2, 3
The standard adult dose of acetaminophen is 1000 mg every 6-8 hours, with a maximum daily dose of 3000-4000 mg, as suggested by guidelines from the American College of Clinical Pharmacology, the American College of Rheumatology, and the FDA label 4, 5, 6, 2
Ibuprofen can be used at a dose of 400-800 mg every 6-8 hours, with a maximum daily dose of 2400 mg, and the lowest effective dose should be used for the shortest duration, with a moderate strength of evidence 7
For mild to moderate pain without inflammation, start with acetaminophen 1000 mg every 6-8 hours, and consider switching to ibuprofen if inadequate relief after 24 hours 2
For pain with an inflammatory component, start with ibuprofen 400-800 mg every 6 hours, and use acetaminophen if ibuprofen is contraindicated 8

Oxycodone-acetaminophen is marginally superior to codeine-acetaminophen for acute pain, with a slightly more effective pain relief 1
Codeine has a maximum daily dose of 240 mg, as recommended by the Annals of Oncology guidelines 9
First-line treatment should be non-opioid analgesics, such as acetaminophen alone or NSAIDs, according to the Annals of Oncology guidelines 9
For moderate pain with inadequate response, the European Society for Medical Oncology recommends considering adding NSAIDs if not contraindicated, or weak opioids such as codeine or tramadol 9
For severe pain, the European Society for Medical Oncology suggests considering strong opioids in addition to paracetamol 9
Opioids should only be added if pain is poorly controlled with acetaminophen and NSAIDs, and a short course of oxycodone (maximum 30 mg daily) can be used if needed, as recommended by the CDC and the American College of Clinical Pharmacology 10, 11

CYP2D6 polymorphisms affect codeine metabolism, leading to poor efficacy in some patients and increased risk of toxicity in others 1
Codeine has CNS depressing effects that NSAIDs do not have, which should be considered when prescribing pain management medications 1
Patients taking an average dose of 10.6 g/day for 34 hours are at risk of hepatotoxicity, as demonstrated by a Class II study by Daly et al. 12
Even therapeutic doses of 4 g/day for 14 days can cause elevations of liver transaminases in 31-41% of healthy adults, according to a study by Watkins et al. 12
Absolute contraindication for acetaminophen use is liver failure, as stated by the American Geriatrics Society 2
Relative contraindications for acetaminophen use include hepatic insufficiency and chronic alcohol abuse, as noted by the American Geriatrics Society 2
The following table summarizes recommended acetaminophen doses for different patient populations:

Patient Population	Recommended Acetaminophen Dose
Adult patients	1000 mg every 8 hours (3000 mg total daily)
Patients with liver disease	2000-3000 mg daily
Elderly patients	Start at lower doses and titrate as needed

Patients with liver cirrhosis should not exceed 2000-3000 mg of paracetamol daily, according to the Clinical and Molecular Hepatology guidelines 4
A more conservative approach recommends a maximum daily dose of 3000 mg, as advised by the American College of Clinical Pharmacology and the CDC 5, 11

Patients with liver disease should start at lower doses (2000-3000 mg daily) and titrate as needed, with specific guidance varying by organization, including the National Institute for Health and Care Excellence 5, 13
Patients with cirrhosis are generally recommended a daily dose of 2-3g of acetaminophen, as patients with liver cirrhosis are at risk of metabolic disorders and prolonged half-life of acetaminophen, according to the Clinical and Molecular Hepatology 4
Elderly patients should start with lower doses and be monitored closely for side effects, as suggested by the American College of Clinical Pharmacology and the CDC 11, 13
Monitor liver function in patients receiving regular acetaminophen, especially at maximum doses, due to the risk of liver damage, with a high strength of evidence 14
For patients on NSAIDs, monitor renal function, blood pressure, and GI symptoms, due to the increased risk of gastrointestinal, renal, and cardiovascular adverse effects, with a high strength of evidence 7, 15, 16
Regularly assess pain control using validated tools to determine treatment efficacy, with a moderate strength of evidence 14, 15
Patients should avoid alcohol consumption while taking acetaminophen and be aware that many combination products, especially those with opioids, contain acetaminophen, which could lead to unintentional overdose, as cautioned by the CDC and the American College of Clinical Pharmacology 11, 17

Duloxetine is conditionally recommended for OA pain, with a moderate strength of evidence 14, 15
Tramadol can be considered for patients with contraindications to NSAIDs or when other therapies are ineffective, with a low strength of evidence 14, 15
Intra-articular glucocorticoid injections are strongly recommended for knee and hip OA, and conditionally for hand OA, with a high strength of evidence 14, 15
For high-risk patients, start with acetaminophen at an appropriate dose based on risk factors, and avoid ibuprofen if possible or use the lowest effective dose for the shortest duration 2