- Post-operative analgesia
- For prevention of shivering during or following surgery
- For treatment of severe hiccoughs
Nefopam
Nefopam
- Nefopam is a non-opioid, non-NSAID, centrally-acting benzoxazocine analgesic
Presentation
- 30mg tablets of nefopam hydrochloride for oral use
- IM and IV preparations are not available in the UK
Dosing
- Initially:
- Adult: 60mg TDS PO
- Elderly: 30mg TDS PO
- Regular dosing:
- 30 - 90mg TDS PO
- Precise mechanism not fully understood
- Mechanisms seem to involve:
- Inhibition of monoamine re-uptake (dopamine and noradrenaline)
- Inhibition of serotonin re-uptake (5-HT2)
- Reduction of NMDA-mediated glutamate signalling and long-term potentiation via:
- Modulation of voltage-gated sodium channels
- Inhibition of calcium channels
vs. opioids
- Compared to IV (PCA) morphine alone, addition of IV nefopam 20mg reduced median morphine use by approximately 50% (21mg vs. 43mg) following hepatic resection
- This was associated with a greater patient satisfaction (97% vs. 82%)
- There was statistically significant higher rates of hyperhidrosis (17%) in the nefopam group, but no other significant differences in adverse events
- Nefopam alone reduces cumulative 24hr post-operative morphine consumption by 10.3mg (95%CI 3.7 - 16.9mg)
- This effect was more pronounced when nefopam was combined with either an NSAID (13.4mg) or paracetamol (23.9mg)
- These findings were not robustly associated with a reduction in pain score (as measured by VAS) nor rates of nausea or vomiting
- Use of nefopam following various surgeries reduced:
- Cumulative 24hr morphine consumption by 13mg (WMD; 95% CI 8.2mg - 17.9mg)
- Pain intensity at 24hrs by 11.5mm on VAS (95% CI 7.9mmg to 15mm) and
- Pain intensity on coughing
- 24hr and 48hr cumulative morphine consumption was significantly lower in patients who received nefopam, either alone or as part of a multimodal analgesic regimen
vs. non-opioid analgesics
- Nefopam alone was not as effective as either diclofenac alone or a diclofenac/nefopam combination at reducing 24hr morphine requirement or pain scores following elective upper abdominal surgery
- IV nefopam 20mg reduced supplemental IV morphine requirements to a similar extent as IV ketamine 10mg after a variety of urological, general and orthopaedic surgeries (although there were statistically significant higher rates of tachycardia and hyperhidrosis in the nefopam group)
Absorption
- Oral bioavailability 40% (1st pass metabolism)
Distribution
- 75% protein bound
- Plasma peak concentration;
- 15 - 20mins after IV injection
- 30mins after continuous IV infusion
Metabolism
- Hepatic metabolism
- Primarily via N-demethylation to the active metabolite desmethylnefopam
- N-oxide-nefopam
- Terminal half-life 3 - 8hrs
- Terminal half-life of desmethylnefopam 10 - 15hrs
Excretion
- Renal 80 - 90%
- Faeces 8 - 13%
- Unchanged ≤5%
Respiratory
- Does not cause respiratory depression (unlike opioids)
Cardiovascular
- Can cause CVS side-effects such as tachycardia and palpitations
Neurological
- Contraindicated in those with seizure disorders
- May cause headache or drowsiness
Renal
- Use with caution in renal impairment; reduce daily dose in end-stage renal disease
Gastrointestinal
- Anti-muscarinic effects such as:
- Hyperhidrosis
- Visual blurring
- Vomiting
Haematological
- Does not have an anti-platelet effect (unlike NSAIDs)
Endocrine
Drug interactions
- Nefopam can cause anti-muscarinic effects so 'interacts' with other anti-muscarinic drugs
- Decreases absorption of Levodopa but no manufacturer recommendation about avoiding
- Predicted to increase the risk of serious elevations in blood pressure when given with irreversible monoamine oxidase inhibitors
- E.g. Isocarboxazid, Phenelzine or Tranylcypromine