Is it safe to use naproxen and toradol (Ketorolac) together in patients taking amitriptyline?

Naproxen and Ketorolac Combination: Safety Concerns in Patients Taking Amitriptyline

Using naproxen and ketorolac together is contraindicated due to the significantly increased risk of gastrointestinal bleeding and renal toxicity, especially in patients taking amitriptyline. 1, 2

Safety Concerns with Combining NSAIDs

Overlapping Toxicity

• Both naproxen and ketorolac are NSAIDs with similar mechanisms of action
• Ketorolac has been shown to have 5 times higher gastrotoxicity than other NSAIDs (RR 24.7 vs. 4.4 for other NSAIDs) 2
• Combining two NSAIDs provides no additional analgesic benefit but significantly increases risk of adverse effects

Specific Risks

1. Gastrointestinal complications:

   • Increased risk of ulceration, bleeding, and perforation
   • Elderly patients may develop ulcers even after short-term use of ketorolac or naproxen 3
   • Risk increases with higher doses and longer duration of therapy

2. Renal complications:

   • Both drugs can cause acute kidney injury
   • Combined use increases nephrotoxicity risk
   • Amitriptyline may further compromise renal clearance

3. Cardiovascular risks:

   • Both NSAIDs can increase blood pressure and fluid retention
   • May worsen heart failure in susceptible patients 1

Special Considerations with Amitriptyline

Amitriptyline, a tricyclic antidepressant, adds additional concerns:

• Often used for neuropathic pain and fibromyalgia 4
• May increase bleeding risk through serotonergic effects
• Can cause anticholinergic side effects that may worsen NSAID-induced gastrointestinal symptoms
• Drug interactions may alter metabolism of NSAIDs

Safer Alternatives

If pain management is needed for a patient on amitriptyline:

1. Use a single NSAID with gastroprotection:

   • Choose either naproxen OR ketorolac (not both)
   • Add a proton pump inhibitor for gastroprotection 1
   • Limit ketorolac use to maximum 5 days 5

2. Consider non-NSAID alternatives:

   • Acetaminophen (paracetamol) for mild to moderate pain
   • Topical analgesics where appropriate
   • Adjunctive therapies like physical therapy or heat/cold application

3. For neuropathic pain components:

   • Optimize amitriptyline dosing (if being used for pain)
   • Consider gabapentin or pregabalin as alternatives 1

Monitoring Recommendations

If any NSAID must be used in a patient taking amitriptyline:

• Monitor renal function before and during therapy
• Watch for signs of GI bleeding (dark stools, abdominal pain)
• Limit duration of therapy, especially with ketorolac
• Use the lowest effective dose
• Educate patient about warning signs requiring immediate medical attention

Remember that ketorolac is approved only for short-term use (≤5 days) due to its high risk profile, and combining it with another NSAID like naproxen creates an unacceptable risk level, particularly in patients taking medications like amitriptyline that may further complicate the safety profile.