What alternative pain medications can be considered for an adult patient with moderate to severe pain that is not adequately managed with tramadol (opioid analgesic) and paracetamol (acetaminophen)?

Alternative Pain Medications When Tramadol and Paracetamol Fail

When tramadol and paracetamol are inadequate for moderate to severe pain, the next step is to escalate to strong opioids, with oral morphine being the first-choice strong opioid. 1

Immediate Next Step: Strong Opioids

Oral Morphine as First-Line Strong Opioid

• Oral morphine is the opioid of first choice for moderate to severe pain that is uncontrolled by weak opioids (tramadol) and paracetamol. 1
• Start with immediate-release (IR) morphine administered every 4 hours, plus rescue doses available up to hourly for breakthrough pain. 1
• Once pain is controlled, convert to sustained-release formulations, adjusting the regular dose based on total rescue morphine requirements. 1

Alternative Strong Opioids

• As an alternative to weak opioids, consider low doses of strong opioids in combination with non-opioid analgesics rather than continuing with tramadol. 1
• Other strong opioid options include oxycodone, hydromorphone, fentanyl, or buprenorphine, though morphine remains the standard first choice. 1

Before Escalating: Optimize Current Regimen

Add NSAIDs if Not Already Tried

• If not contraindicated, add an NSAID (such as ibuprofen 400 mg three times daily) before escalating to strong opioids. 2
• NSAIDs are effective for all intensities of pain, at least in the short term, and can be combined with paracetamol and opioids. 1
• Caution: NSAIDs should be avoided in patients with peptic ulcer disease, advanced age (>60 years), renal insufficiency, or clinically significant portal hypertension. 1
• Use proton pump inhibitors to reduce gastrointestinal side effects when prescribing NSAIDs. 1

Ensure Adequate Dosing of Current Medications

• Verify tramadol is being used at maximum effective dose (400 mg/day for immediate-release formulations or 300 mg/day for extended-release). 1
• Confirm paracetamol is dosed at 1000 mg every 6 hours (maximum 4000 mg/day). 2

Special Considerations Based on Pain Type

For Neuropathic Pain

• Neuropathic pain is less responsive to opioids than other pain types and requires coanalgesics. 1
• Add anticonvulsants (gabapentin or pregabalin) or antidepressants (tricyclic antidepressants) as coanalgesics. 1
• Topical lidocaine patches can be considered for localized neuropathic pain. 1

For Bone Pain

• Consider external beam radiotherapy (8-Gy single dose) for painful bone metastases. 1
• Bisphosphonates may be helpful as coanalgesics for bone pain. 1

For Inflammatory Pain

• NSAIDs are particularly effective for inflammatory pain, especially bone pain. 1

Critical Safety Measures When Escalating to Strong Opioids

Mandatory Prophylaxis

• Laxatives must be routinely prescribed for both prophylaxis and management of opioid-induced constipation. 1
• Prescribe metoclopramide or antidopaminergic drugs for opioid-related nausea/vomiting. 1

Dosing Principles

• Analgesics for chronic pain should be prescribed on a regular basis, not "as required." 1
• Always prescribe rescue doses (immediate-release formulations) in addition to regular basal therapy for breakthrough pain episodes. 1
• The oral route should be the first choice for administration. 1

Special Populations

• In renal impairment, all opioids should be used with caution at reduced doses and frequency. 1
• Fentanyl and buprenorphine (transdermal or intravenous) are the safest opioids in patients with chronic kidney disease stages 4 or 5 (eGFR <30 ml/min). 1
• In hepatic impairment (such as cirrhosis), use paracetamol maximum 3 g/day and prescribe opioids with extreme caution, ensuring aggressive laxative prophylaxis. 1

Common Pitfalls to Avoid

• Do not combine tramadol with strong opioids - tramadol is a weak opioid and should be discontinued when escalating to morphine or other strong opioids. 1
• Do not delay strong opioid initiation - oral morphine should be given without delay to patients whose pain is uncontrolled by step 1 and 2 treatments. 1
• Do not prescribe analgesics "as needed" only - chronic pain requires scheduled, around-the-clock dosing with additional rescue doses available. 1
• Avoid NSAIDs in patients with significant portal hypertension, as they increase risk of gastrointestinal bleeding, ascites decompensation, and nephrotoxicity. 1