What is the appropriate dosing and administration of paracetamol (acetaminophen), ibuprofen, tramadol, and diclofenac for pain management?

From the Guidelines

Paracetamol, ibuprofen, tramadol, and diclofenac can be given for pain management, with paracetamol typically dosed at 500-1000mg every 4-6 hours, ibuprofen at 200-400mg every 4-6 hours, tramadol at 50-100mg every 4-6 hours, and diclofenac at 50mg 2-3 times daily or 75mg twice daily, as supported by the most recent evidence from 1.

Key Considerations

• Paracetamol should not exceed 4000mg daily, and ibuprofen should not exceed 2400mg daily.
• Tramadol should not exceed 400mg daily and should be used for short durations due to its potential for dependence.
• Diclofenac should be used at the lowest effective dose for the shortest duration possible to minimize cardiovascular and gastrointestinal risks.
• Combining paracetamol with either ibuprofen or diclofenac can provide more effective pain relief, but tramadol should generally not be combined with other opioids.

Dosage Adjustments

• Elderly patients, those with renal or hepatic impairment, and patients with cardiovascular disease, peptic ulcers, or asthma may require dosage adjustments.
• The European Society for Paediatric Anaesthesiology recommends specific dosage suggestions for children, including ibuprofen at 10 mg kg-1 every 8 hours, diclofenac at 0.5-1 mg kg-1 every 8 hours, and tramadol at 1 to 1.5 mg kg-1 every 4 to 6 hours, as stated in 1 and 1.

Administration

• Paracetamol can be taken with or without food, while ibuprofen and diclofenac should be taken with food to minimize gastrointestinal side effects.
• Tramadol should be tapered when discontinuing due to its potential for dependence.

Evidence-Based Recommendations

• The American College of Physicians recommends using paracetamol, ibuprofen, or the combination of an NSAID and acetaminophen to treat acute, episodic, moderate to severe migraine headaches, as stated in 1.
• The North of England Non-Steroidal Anti-Inflammatory Drug Guideline Development Group recommends initial treatment with paracetamol, followed by ibuprofen if symptoms persist, as stated in 1.

From the FDA Drug Label

DOSAGE & ADMINISTRATION Adults (17 years of age and over) For patients with moderate to moderately severe chronic pain not requiring rapid onset of analgesic effect, the tolerability of tramadol hydrochloride tablets, USP can be improved by initiating therapy with a titration regimen: The total daily dose may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg q.i.d.) After titration, tramadol hydrochloride tablets, USP 50 to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day In all patients with creatinine clearance less than 30 mL/min, it is recommended that the dosing interval of tramadol hydrochloride tablets be increased to 12 hours, with a maximum daily dose of 200 mg. The recommended dose for adult patients with cirrhosis is 50 mg every 12 hours. In general, dose selection for an elderly patient over 65 years old should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. For elderly patients over 75 years old, total dose should not exceed 300 mg/day.

The dosing and administration of tramadol for pain management is as follows:

• Adults: 50-100 mg every 4-6 hours, not to exceed 400 mg/day
• Patients with creatinine clearance < 30 mL/min: 50-100 mg every 12 hours, not to exceed 200 mg/day
• Patients with cirrhosis: 50 mg every 12 hours
• Elderly patients (65-75 years old): start at the low end of the dosing range
• Elderly patients (> 75 years old): total dose should not exceed 300 mg/day However, the FDA drug label does not provide information on the dosing and administration of paracetamol, ibuprofen, and diclofenac 2.

From the Research

Appropriate Dosing and Administration

• Paracetamol (acetaminophen) is a first-line treatment option for most patients with acute mild to moderate pain, and it is generally well tolerated at recommended doses (≤4 g/day) in healthy adults 3.
• Ibuprofen is consistently superior to paracetamol at conventional doses in a range of painful conditions, including acute post-operative pain, dysmenorrhoea, tension-type headache, migraine, osteoarthritis, and rheumatoid arthritis 4.
• Tramadol is used to treat severe or refractory acute pain, and it can be combined with diclofenac to provide adequate pain relief and reduce side effects 5.
• Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that can be used to treat acute pain, but it should be used with caution in patients with a history of gastrointestinal bleeding, cardiovascular disease, or chronic renal disease 6.

Special Considerations

• Patients with advanced hepatic disease, malnutrition, or severe alcohol use disorder should use lower doses of paracetamol 6.
• Patients with liver, kidney, or cardiovascular disease, gastrointestinal disorders, asthma, or who are older can use paracetamol as a first-line analgesic, but dosing should be individualized in consultation with their physician 3.
• Tramadol/diclofenac fixed-dose combination is a valuable treatment option for patients with acute severe pain, including musculoskeletal pain, postoperative pain, and acute flare-up of osteoarthritis or rheumatoid arthritis 5.

Safety Concerns

• Paracetamol can cause hepatotoxicity, but this is rare among adults who use paracetamol as directed, including people with cirrhotic liver disease 3, 7.
• NSAIDs, including ibuprofen and diclofenac, can cause gastrointestinal, renal, and cardiovascular effects, and should be used with caution in patients with a history of these conditions 6, 4.
• Tramadol can cause opioid-related side effects, and should be used with caution in patients with a history of opioid use disorder 6, 5.