Opioid-Paracetamol Combination for Pain Management
For moderate pain (NRS 5-7), the recommended combination is tramadol 37.5 mg with paracetamol 325 mg, taken as 1-2 tablets every 4-6 hours, not exceeding 8 tablets daily (maximum tramadol 300 mg/day). 1, 2
Standard Dosing Regimen
- Initial dose: 1-2 tablets (tramadol 37.5 mg/paracetamol 325 mg) every 4-6 hours as needed 2, 3
- Maximum daily dose: 8 tablets (tramadol 300 mg + paracetamol 2600 mg) 2
- Onset of action: 17 minutes for the combination, faster than tramadol alone (51 minutes) 4
- Duration: Longer than either agent alone, typically 4-6 hours 4, 5
Alternative Opioid-Paracetamol Combinations
Codeine with paracetamol is an equally valid option for moderate pain, with typical dosing of codeine 30 mg combined with paracetamol 300-500 mg, up to a maximum of 240 mg codeine and 4000 mg paracetamol daily. 1
Other weak opioid combinations include:
- Dihydrocodeine 60-120 mg with paracetamol, maximum 240 mg dihydrocodeine daily 1
- Hydrocodone 10 mg with paracetamol 650 mg provides similar efficacy to tramadol/paracetamol 5
Special Population Dosing
Elderly patients (≥75 years) require dose reduction:
- Start with tramadol 25-50 mg every 8-12 hours combined with paracetamol 2, 6
- Monitor closely for cognitive impairment and delirium 2, 6
Hepatic or renal impairment:
- Maximum tramadol 50 mg every 12 hours with paracetamol 2, 6
- Consider reducing paracetamol to 3000 mg daily maximum in hepatic dysfunction 1
Critical Safety Screening Before Initiation
Mandatory exclusion criteria before prescribing tramadol/paracetamol:
- Active seizure disorder or history of seizures (tramadol lowers seizure threshold) 2, 6
- Current use of SSRIs, SNRIs, or MAOIs (risk of serotonin syndrome) 2, 6
- Baseline cognitive impairment (tramadol increases delirium risk) 2, 6
Monitoring Requirements
During treatment, monitor for:
- Seizure activity 2, 6
- Cognitive changes, memory problems, or delirium 2, 6
- Signs of serotonin syndrome (agitation, confusion, tremor, hyperthermia) 2, 6
- Gastrointestinal side effects (nausea, vomiting, constipation) 7, 3
Evidence for Efficacy
The tramadol/paracetamol combination demonstrates:
- Superior analgesia compared to either agent alone in postoperative and musculoskeletal pain 3, 4
- Similar efficacy to codeine/paracetamol 30/300 mg in chronic pain 5
- Similar efficacy to hydrocodone/paracetamol in dental pain 5
- Faster onset (17 minutes) than tramadol alone (51 minutes) 4
Important Clinical Caveats
Ceiling effect limitation: Tramadol has a maximum effective dose beyond which increasing the dose only increases side effects without improving analgesia. 2, 7
Time-limited effectiveness: The WHO Step II analgesics (including tramadol combinations) typically remain effective for only 30-40 days in most patients, after which escalation to strong opioids becomes necessary. 1, 7
Not for severe pain: For moderate to severe cancer pain or severe acute pain, strong opioids like morphine are preferred over tramadol combinations. 1, 7
Drug interaction risk: Tramadol's serotonergic effects create significant interaction potential with commonly prescribed antidepressants, requiring careful medication review before initiation. 2, 6
Prophylactic laxatives: Prescribe a combination stool softener and stimulant laxative when initiating tramadol to prevent constipation. 7