Recommendation

Nefopam appears no more potent than non-steroidal anti-inflammatory drugs (NSAIDs), but is commonly associated with adverse drug reactions and is toxic in overdose. It may sometimes be preferred when alternatives are contraindicated or ineffective, or used as add-on therapy when pain is inadequately controlled.

Prescribers should carefully consider whether the potential benefits outweigh the risks of adverse effects in individual patients. Treatment should be reviewed regularly and stopped if benefits are not seen in the short term.

Use in practice

Full prescribing information for nefopam can be found in the BNF and Summary of Product Characteristics

Indication and dosage

Nefopam is licensed for pain relief in acute and chronic pain. The recommended starting dose is 30mg to 60mg three times a day. This can be increased to a maximum of 90mg three times a day.

Mechanism of action

Nefopam is a non-opioid, centrally-acting analgesic. The mechanism of action is not well understood. It is known to inhibit the re-uptake of neurotransmitters including serotonin, noradrenaline and dopamine. Additionally, it blocks sodium and calcium channels in the central nervous system.

Adverse effects

The most common adverse effects are nausea and vomiting, drowsiness, hypotension and abdominal pain. Tachycardia can occur and this is more common in critical care patients.

Less common adverse effects include diarrhoea, confusion and hallucinations (particularly in the elderly), tremor, paraesthesia, dizziness, headache, syncope, seizures and palpitations. Anticholinergic effects such as dry mouth, constipation, blurred vision and urinary retention can also occur.

Overdose is characterised by neurological symptoms (seizures, hallucination and agitation) and cardiovascular symptoms (coma and tachycardia). Serotonin toxicity can also occur in overdose, particularly if taken with other serotonergic drugs such as selective serotonin reuptake inhibitors (SSRIs).

Interactions

Use with caution with tricyclic antidepressants due to additive risk of anticholinergic effects.

Combination with monoamine oxidase inhibitors (MAOIs) (for example phenelzine, isocarboxazid and tranylcypromine) is contra-indicated due to increased risk of severe hypertension.

Guidelines

NICE guidelines for chronic pain do not list nefopam as a treatment option.

SIGN guidelines for the management of chronic pain advises that the evidence to support the use of nefopam is insufficient to make any recommendations.

Evidence

Most evidence for nefopam relates to short-term use in a post-operative setting. Evidence for use in this setting is still limited and conflicting.

Evidence for use in chronic pain is restricted to several small studies.

Additional benefit demonstrated

A 1986 study evaluated the effectiveness of nefopam to manage pain in rheumatoid arthritis. Patients included were already taking a maximum dose of an NSAID. Nefopam was more effective than placebo in reducing pain and morning stiffness, although subjective measures were used. Joint tenderness also improved with nefopam.

Similar benefit demonstrated

A 1989 study comparing nefopam to flurbiprofen in osteoarthritic pain found no significant difference in effectiveness. More side-effects were experienced with nefopam.

Another 1989 study comparing nefopam to diclofenac and codeine plus aspirin for cancer pain found similar effectiveness between the treatments. More patients on nefopam withdrew from the study due to side-effects, predominantly nausea.

No additional benefit demonstrated

A 1988 study evaluated the effectiveness of nefopam to manage pain in rheumatoid arthritis. No statistically significant improvement in pain was observed with nefopam when compared with placebo. The study had a high dropout rate with one main reason being adverse effects of nefopam.

Lack of evidence

No studies comparing nefopam to centrally-acting analgesics such as tricyclic antidepressants or gabapentinoids were identified.

Bibliography

Full referencing is available on request.

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