What is the best treatment option for a patient with moderate to severe pain who is allergic to ibuprofen, Vicodin (hydrocodone) and codeine?

Pain Management for Patients Allergic to Ibuprofen, Vicodin, and Codeine

For moderate to severe pain in patients allergic to ibuprofen, hydrocodone (Vicodin), and codeine, acetaminophen should be the first-line agent, with escalation to strong opioids such as morphine, hydromorphone, or fentanyl if pain remains uncontrolled. 1, 2

First-Line Treatment: Acetaminophen

• Start with acetaminophen 500-1000 mg every 4-6 hours (maximum 4000 mg/day) for moderate pain. 2, 1
• Acetaminophen is well-tolerated and has fewer side effects than NSAIDs, making it the preferred non-opioid option when NSAIDs are contraindicated. 2, 3
• Reduce the maximum daily dose in patients with liver disease, malnutrition, or severe alcohol use disorder. 4, 3

When to Escalate: Strong Opioids (WHO Level III)

If acetaminophen alone fails to control moderate to severe pain, bypass weak opioids entirely and move directly to strong opioids, since the patient cannot use codeine-based products (WHO Level II). 2, 1

Morphine as First-Line Strong Opioid

• Oral morphine is the first-line WHO Level III opioid of choice for moderate to severe pain. 2
• Start with immediate-release morphine tablets or solution, with typical dosing of 0.1 mg/kg IV initially, then 0.05 mg/kg at 30 minutes (maximum 10 mg). 1
• The oral route is preferred when possible; if parenteral administration is needed, use one-third of the oral dose. 2, 1
• Always prescribe an immediate-release formulation concurrently for breakthrough pain in patients on baseline opioid therapy. 2

Alternative Strong Opioids

Hydromorphone is recommended as comparable or potentially superior to morphine, with quicker onset and higher potency (0.015 mg/kg IV). 1

Fentanyl is particularly useful for:

• Patients unable to swallow (transdermal route). 2
• Those with renal impairment, as it is one of the safest opioids in chronic kidney disease stages 4-5. 1
• Patients with morphine allergies—fentanyl does not cross-react with morphine allergies. 1
• Dosing: 1 mcg/kg IV, then approximately 30 mcg every 5 minutes. 1

Oxycodone (in normal-release or modified-release formulations) is an effective alternative to oral morphine. 2

Buprenorphine (transdermal or IV) is safe for patients with renal impairment. 1

Methadone is an alternative but requires expertise due to marked inter-individual differences in plasma half-life and duration of action. 2

Tramadol: Use with Extreme Caution

• Tramadol (50-100 mg every 4-6 hours) may be considered for moderate pain, but use with caution due to potential cross-sensitivity with codeine. 1
• Avoid tramadol in patients with epilepsy risk or those taking monoamine oxidase inhibitors or antidepressants. 2, 1
• Tramadol taken for up to 3 months may decrease pain in osteoarthritis (dosing range: 37.5 mg with 325 mg acetaminophen once daily to 400 mg in divided doses). 2

Critical Management Considerations

Opioid Side Effect Prophylaxis

• Prescribe laxatives routinely for prophylaxis and management of opioid-induced constipation. 1
• Use metoclopramide or antidopaminergic drugs for opioid-related nausea/vomiting. 1

Renal Impairment

• All opioids should be used with caution at reduced doses and frequency in renal impairment. 1
• Fentanyl and buprenorphine are the safest opioids for patients with chronic kidney disease stages 4 or 5. 1

Pain Assessment

• Assess pain severity using visual analog scales (VAS), numerical rating scales (NRS), or verbal rating scales (VRS) at every visit. 2, 1
• Use pain-related behaviors and discomfort observation in patients with cognitive impairment. 1

Common Pitfalls to Avoid

• Do not assume all opioids cross-react with codeine allergy—fentanyl is safe in patients with morphine allergies. 1
• Never stop opioid treatment abruptly; taper by 30-50% over about a week. 1
• Avoid dihydrocodeine due to potential cross-sensitivity with codeine. 1
• Do not use the lowest effective dose for the shortest duration principle as an excuse to undertreat severe pain—escalate appropriately when indicated. 2
• Remember that weak opioids like codeine have a ceiling effect where increasing doses only increases side effects without improving analgesia. 1

Urgent Severe Pain

For patients presenting with severe pain requiring urgent relief, administer parenteral opioids via intravenous or subcutaneous route. 2