Is nefopam safe for pain management in a patient with endometriosis taking codeine and Gonadotropin-Releasing Hormone (GnRH) agonist while awaiting laparoscopic surgery?

Nefopam for Endometriosis Pain Management While Awaiting Surgery

Nefopam can be used as an adjunctive analgesic in this patient already taking codeine and GnRH agonist, but requires careful monitoring for cardiovascular and neuropsychiatric side effects, particularly tachycardia and potential seizures.

Rationale for Use in This Clinical Context

Multimodal Analgesia Benefits

• Nefopam provides opioid-sparing analgesia without the adverse effects of NSAIDs or additional opioids, making it a reasonable option when codeine alone provides inadequate pain control 1, 2.
• The drug has no detrimental effects on hemostasis, gastric mucosa, renal function, hepatic function, vigilance, ventilatory drive, or intestinal motility—advantages over NSAIDs and opioids 2.
• When combined with opioids like codeine, nefopam can reduce overall opioid consumption by approximately 13 mg morphine equivalents over 24 hours 3.

Compatibility with Current Medications

• Continue the codeine as recommended for patients on long-term opioid therapy awaiting surgery 1.
• There are no documented contraindications to combining nefopam with codeine or GnRH agonists 2, 3.
• Patients on chronic opioids typically require adjunctive nonopioid analgesia perioperatively, making nefopam a logical addition 1.

Critical Safety Considerations

Cardiovascular Monitoring Required

• Tachycardia is the most common side effect and requires monitoring 2.
• Check baseline heart rate and blood pressure before initiating therapy 2.
• Monitor cardiovascular parameters regularly, especially during dose titration 2.

Neuropsychiatric Risks

• Seizures can occur unpredictably and are not dose-related, potentially progressing to status epilepticus 2.
• Delirium is a significant concern, particularly relevant if the patient has severe chronic pain affecting mental status 2.
• Screen for seizure history or risk factors before prescribing 2.

Dosing Considerations

• The standard recommended dose is 20 mg, though evidence suggests the median effective dose may be higher (62.1 mg in some surgical contexts) 4, 3.
• Start with 20 mg intravenously or orally to assess tolerance, as this dose combined with fentanyl 50 µg showed reduced side effects compared to higher doses 5.
• The dose range studied in trials is 20-160 mg cumulative over 24 hours 3.

Practical Implementation Strategy

Initiation Protocol

• Begin with nefopam 20 mg orally or intravenously while continuing codeine at current dose 3, 5.
• Administer over 1 hour if given intravenously to reduce injection site reactions 4.
• Monitor for pain relief at 30 minutes and 2 hours post-administration 4, 5.

Monitoring Parameters

• Assess pain scores using numerical rating scale before and 30 minutes after each dose 4, 6.
• Check heart rate and blood pressure before each dose and 30 minutes after 2.
• Watch for sweating (number needed to harm = 13) and tachycardia (number needed to harm = 7) 3.

Optimization While Awaiting Surgery

• Consider this as part of a multimodal approach rather than monotherapy 1.
• The GnRH agonist addresses the underlying endometriosis pathophysiology, while nefopam and codeine manage breakthrough pain 1.
• If pain remains inadequately controlled, consider adding acetaminophen (paracetamol) 1 gram every 6 hours rather than escalating opioid doses 1.

Important Caveats

Limited Evidence Base

• No randomized controlled trials specifically evaluate nefopam in endometriosis pain 3, 7.
• Oral nefopam has insufficient evidence for acute postoperative pain efficacy, though intravenous formulations show better results 7.
• Most evidence comes from surgical settings rather than chronic pain management 3, 6.

Geographic Availability

• Nefopam is not available in the United States or Canada but is used in nearly 30 other countries 2.
• Verify local availability before prescribing 2.

Injection Site Reactions

• If using intravenous route, be aware that injection pain and phlebitis can occur 4.
• Slow infusion over 1 hour reduces this risk 4.

Alternative Considerations if Nefopam Unavailable or Poorly Tolerated

• NSAIDs (if no contraindications) combined with codeine provide superior morphine-sparing effects compared to other nonopioid combinations 1.
• Acetaminophen 1 gram every 6 hours is safe and effective as adjunctive therapy 1.
• Consider gabapentinoids (gabapentin or pregabalin) for neuropathic pain components of endometriosis 1.