Usage
Nefopam is a non-opioid analgesic prescribed for the relief of moderate to severe acute and chronic pain. This includes postoperative pain, dental pain, musculoskeletal pain, acute traumatic pain, and cancer pain. Its pharmacological classification is “centrally-acting analgesic,” distinct from opioids and NSAIDs. Nefopam’s mechanism of action involves multiple pathways, including inhibiting the reuptake of monoamines (norepinephrine, serotonin, and dopamine) and modulating sodium channels, affecting pain signal transmission in the central nervous system.
Alternate Names
Nefopam hydrochloride is the chemical name. Acupan is a common brand name.
How It Works
Pharmacodynamics: Nefopam primarily affects the central nervous system, acting on multiple pathways to exert its analgesic effects. It’s believed to inhibit the reuptake of monoamines like norepinephrine, serotonin, and dopamine, thereby increasing their concentration in the synaptic cleft. Additionally, it modulates sodium channels, influencing neuronal excitability and pain signal transmission.
Pharmacokinetics:
- Absorption: Nefopam is readily absorbed after oral administration.
- Metabolism: It’s extensively metabolized in the liver, primarily via N-demethylation, N-oxidation, and glucuronidation. Desmethylnefopam, nefopam N-oxide, and N-glucuronide are the major metabolites.
- Elimination: Primarily eliminated through renal excretion (about 87%, with less than 5% as unchanged drug), and to a lesser extent via feces (around 8%).
- Half-life: Approximately 4 hours.
Mode of Action: Nefopam binds to and inhibits the reuptake of norepinephrine, serotonin, and dopamine. This increases their concentrations in the synaptic cleft, modulating pain transmission pathways. It also modulates sodium channels, reducing neuronal excitability and further attenuating pain signal propagation.
Dosage
Standard Dosage
Adults:
Initial dose: 60 mg three times a day. The usual dosage range is 30-90 mg three times a day, adjusted based on the patient’s response to therapy and pain intensity.
Children:
Not recommended for children under 12 years of age. For children 12 years and older, the dosage is the same as for adults.
Special Cases:
- Elderly Patients: Initial dose: 30 mg three times a day. Due to age-related changes in metabolism and potential increased sensitivity to CNS side effects, a lower starting dose is recommended.
- Patients with Renal Impairment: Dose reduction may be necessary for patients with end-stage renal disease.
- Patients with Hepatic Dysfunction: Dose adjustment may be necessary due to reduced metabolism.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, angle-closure glaucoma, or urinary retention.
Clinical Use Cases
Nefopam’s clinical use focuses primarily on pain management. While it can be administered intravenously or intramuscularly, these routes are less common in routine practice and primarily used in hospital settings for postoperative pain. Dosage recommendations for these specific clinical cases are not typically detailed in standard guidelines.
Dosage Adjustments
Dose adjustments are made based on patient response, age, and renal/hepatic function. Close monitoring for efficacy and side effects is necessary, especially in elderly patients and those with organ dysfunction.
Side Effects
Common Side Effects
Nausea, dizziness, dry mouth, nervousness, lightheadedness, and urinary retention.
Rare but Serious Side Effects
Hallucinations, confusion (especially in elderly patients), seizures, tachycardia, palpitations, allergic reactions (including angioedema), and serotonin syndrome (when combined with other serotonergic drugs).
Long-Term Effects
Potential for drug dependence and abuse with prolonged use.
Adverse Drug Reactions (ADR)
Serotonin syndrome, seizures, severe allergic reactions.
Contraindications
History of convulsive disorders, concomitant use of MAO inhibitors, myocardial infarction pain, hypersensitivity to nefopam.
Drug Interactions
MAO inhibitors (contraindicated), tricyclic antidepressants (use with caution due to additive anticholinergic effects), SSRIs and other serotonergic drugs (risk of serotonin syndrome), anticholinergic drugs (additive anticholinergic effects), sympathomimetic agents (additive sympathomimetic effects), opioid drugs (additive side effects like nausea, dizziness, and confusion). Alcohol should be avoided as it may increase dizziness and drowsiness. Nefopam may interfere with screening tests for benzodiazepines and opioids, producing false-positive results.
Pregnancy and Breastfeeding
Nefopam is not recommended during pregnancy due to potential risks to the fetus. It’s excreted in breast milk, posing potential risks to the nursing infant. Breastfeeding should be discontinued while taking nefopam.
Drug Profile Summary
- Mechanism of Action: Inhibits monoamine reuptake, modulates sodium channels.
- Side Effects: Nausea, dizziness, dry mouth, nervousness, confusion, hallucinations, seizures.
- Contraindications: Convulsive disorders, MAO inhibitor use, myocardial infarction pain.
- Drug Interactions: MAOIs, TCAs, SSRIs, anticholinergics, sympathomimetics.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 30-90 mg TID; Elderly: Start with 30 mg TID; Children (12+): Same as adults.
- Monitoring Parameters: Renal and hepatic function, cardiovascular status.
Popular Combinations
While nefopam can be used with other analgesics like paracetamol and NSAIDs (e.g., ibuprofen, naproxen), caution is advised when combining it with opioid analgesics due to additive side effects. The decision to combine nefopam with other analgesics should be made on a case-by-case basis, carefully considering the potential benefits and risks.
Precautions
- General Precautions: Evaluate for allergies, renal/hepatic dysfunction, glaucoma, and urinary retention before initiating treatment.
- Specific Populations: Avoid use in pregnancy and breastfeeding. Exercise caution in children and the elderly.
- Lifestyle Considerations: Avoid alcohol and driving or operating machinery if experiencing dizziness or drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nefopam?
A: Adults: Initial dose is 60 mg three times a day. Usual range: 30-90 mg three times a day. Elderly: Start with 30 mg three times a day. Children (12+): Same as adult dose.
Q2: How does Nefopam work?
A: Nefopam inhibits monoamine reuptake and modulates sodium channels, reducing pain signal transmission.
Q3: What are the common side effects of Nefopam?
A: Nausea, dizziness, dry mouth, nervousness, lightheadedness, urinary retention.
Q4: Is Nefopam safe to use during pregnancy or breastfeeding?
A: No, it’s not recommended during pregnancy or breastfeeding.
Q5: Can Nefopam be used with other painkillers?
A: It can be used with paracetamol and NSAIDs, but caution is needed with opioids.
Q6: What are the contraindications for Nefopam?
A: History of convulsive disorders, concurrent MAOI use, and myocardial infarction pain.
Q7: Are there any serious side effects I should be aware of?
A: Yes, although rare, serious side effects can include hallucinations, confusion, seizures, and serotonin syndrome.
Q8: How should I adjust the Nefopam dose for elderly patients?
A: Start with a lower dose of 30 mg three times daily and titrate cautiously based on response and tolerance.
Q9: Can Nefopam be administered intravenously?
A: Yes, but it is less common and typically used in hospital settings for postoperative pain.
Q10: Does Nefopam interact with antidepressants?
A: Yes, it can interact with MAOIs (contraindicated) and TCAs (use with caution). It can also interact with SSRIs, increasing the risk of serotonin syndrome.
