Nefopam + Paracetamol

Usage

Nefopam + Paracetamol is a fixed-dose combination medication primarily indicated for the relief of moderate to severe acute pain, such as postoperative pain, dental pain, musculoskeletal pain, and pain associated with trauma or cancer. It can also be used for other types of chronic pain when weaker painkillers are ineffective.

• Pharmacological Classification: Analgesic (centrally acting non-opioid analgesic for Nefopam and peripheral analgesic with central effects for Paracetamol.)

• Mechanism of Action: Nefopam acts centrally by inhibiting the reuptake of serotonin, norepinephrine, and dopamine, and by modulating glutamatergic pathways. Paracetamol’s mechanism involves inhibition of cyclooxygenase (COX) enzymes, predominantly COX-2, in the central nervous system, reducing prostaglandin synthesis, thereby mitigating pain and fever. The combination of these two analgesics provides synergistic pain relief, allowing for lower doses of each component compared to using them individually.

Alternate Names

No widely recognized alternate names exist for the combination itself. However, the individual components have alternate names:

• Nefopam: Acupan (brand name)
• Paracetamol: Acetaminophen (International Nonproprietary Name - INN), APAP

How It Works

Nefopam

• Pharmacodynamics: Nefopam primarily affects the central nervous system, leading to analgesia through the mechanisms mentioned above. It does not have significant anti-inflammatory properties.
• Pharmacokinetics: Nefopam is well-absorbed orally, reaching peak plasma concentrations within 1-2 hours. It is metabolized in the liver and excreted primarily via the kidneys.

Paracetamol

• Pharmacodynamics: Paracetamol’s analgesic and antipyretic effects are primarily mediated through central COX inhibition. It has weak peripheral anti-inflammatory activity.
• Pharmacokinetics: Paracetamol is rapidly absorbed after oral administration, reaching peak plasma levels in 30-60 minutes. It is metabolized in the liver by glucuronidation and sulfation, with a small fraction undergoing oxidation by CYP enzymes, forming a potentially hepatotoxic metabolite. It’s primarily excreted by the kidneys.

Combination

The combination of Nefopam and Paracetamol exhibits synergistic analgesic effects through their complementary mechanisms, providing enhanced pain relief compared to either drug alone. The co-administration does not appear to significantly alter the pharmacokinetics of either drug.

Dosage

Standard Dosage

Adults:

The typical starting dose is one tablet containing 30mg Nefopam and 500mg Paracetamol, taken three times a day. The dosage can be adjusted based on the severity of pain and patient response, up to a maximum of three tablets (90mg Nefopam and 1500mg Paracetamol) three times a day.

Children:

The safety and efficacy of this combination have not been established in children under 12 years of age. Therefore, it is not recommended for use in this population.

Special Cases:

• Elderly Patients: Reduced dosage is recommended for elderly patients, starting with one tablet containing 30 mg Nefopam and 500 mg Paracetamol three times a day, due to age-related decline in renal and hepatic function.
• Patients with Renal Impairment: Dose reduction is recommended for patients with end-stage renal disease, as they may experience increased serum concentrations of Nefopam. Dosage adjustments should be made based on creatinine clearance.
• Patients with Hepatic Dysfunction: Patients with hepatic impairment should be monitored closely and may require dosage adjustments due to potential paracetamol accumulation.
• Patients with Comorbid Conditions: Caution should be exercised in patients with convulsive disorders, epilepsy, angle-closure glaucoma, and difficulty urinating.

Clinical Use Cases

The dosages mentioned in the “Standard Dosage” and “Special Cases” sections are applicable to the following clinical use cases:

• Intubation: Preemptive analgesia.
• Surgical Procedures: Post-operative pain.
• Mechanical Ventilation:
• Intensive Care Unit (ICU) Use:
• Emergency Situations: Initial pain management

Dosage Adjustments

Dose modifications are necessary for patients with renal and hepatic dysfunction as outlined in the “Special Cases” section. Always consider individual patient factors, such as age, weight, and comorbidities, when determining the appropriate dosage.

Side Effects

Common Side Effects:

Nausea, dizziness, lightheadedness, nervousness, dry mouth, difficulty urinating, sweating.

Rare but Serious Side Effects:

Allergic reactions (rash, itching, swelling), hallucinations, confusion, seizures, tachycardia, coma, serotonin syndrome (when combined with other serotonergic drugs).

Long-Term Effects:

Potential for dependence with prolonged Nefopam use. Chronic paracetamol use at high doses may increase the risk of liver damage.

Adverse Drug Reactions (ADR):

Severe allergic reactions (anaphylaxis), Stevens-Johnson syndrome, hepatotoxicity (with excessive paracetamol intake).

Contraindications

• Hypersensitivity to nefopam or paracetamol.
• History of convulsive disorders or epilepsy.
• Concurrent use of monoamine oxidase inhibitors (MAOIs).
• Severe hepatic impairment.
• Myocardial infarction pain.

Drug Interactions

• MAOIs: Concomitant use is contraindicated due to the risk of serotonin syndrome.
• Tricyclic antidepressants: May potentiate anticholinergic effects.
• CNS depressants: Additive sedative effects.
• Alcohol: Increased risk of CNS depression.
• Anticoagulants: Paracetamol may enhance the anticoagulant effect of warfarin.
• Anticonvulsants: May alter paracetamol metabolism.

Pregnancy and Breastfeeding

• Pregnancy: Nefopam + Paracetamol is generally not recommended during pregnancy due to limited safety data. Paracetamol is considered the preferred analgesic option during pregnancy.
• Breastfeeding: Both drugs are excreted in breast milk. While limited data suggests minimal risk to the infant, it’s advisable to use caution and consider potential infant exposure. Paracetamol is generally considered compatible with breastfeeding.

Drug Profile Summary

• Mechanism of Action: Nefopam: Centrally acting, inhibits monoamine reuptake, modulates glutamatergic pathways. Paracetamol: Inhibits COX enzymes, primarily centrally.
• Side Effects: Nausea, dizziness, dry mouth, nervousness, urinary retention; rarely hallucinations, seizures.
• Contraindications: Hypersensitivity, seizures, MAOI use, severe liver disease.
• Drug Interactions: MAOIs, tricyclic antidepressants, CNS depressants, alcohol.
• Pregnancy & Breastfeeding: Generally not recommended during pregnancy; caution during breastfeeding.
• Dosage: Adults: 30mg Nefopam/500mg Paracetamol, 1-3 tablets three times daily. Elderly/renal impairment: Reduced dosage.
• Monitoring Parameters: Liver function tests (with prolonged paracetamol use).

Popular Combinations

While nefopam/paracetamol is itself a combination, it may be used alongside non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen for enhanced pain control in certain cases. However, this should be done cautiously due to increased risk of side effects.

Precautions

• Evaluate renal and hepatic function before initiating treatment.
• Monitor for allergic reactions.
• Use caution in elderly patients and those with comorbid conditions.
• Avoid alcohol during treatment.
• Counsel patients on potential side effects and drug interactions.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Nefopam + Paracetamol?

A: The usual starting dose is 30mg Nefopam/500mg Paracetamol, one tablet taken three times a day. This can be increased up to three tablets three times a day based on pain severity and patient response. Dose adjustments are necessary for elderly individuals and those with hepatic or renal impairment.

Q2: Can this combination be used in children?

A: No, the safety and efficacy in children under 12 have not been established.

Q3: What are the common side effects?

A: Nausea, dizziness, lightheadedness, dry mouth, nervousness, and difficulty urinating.

Q4: What are the serious side effects?

A: Allergic reactions, hallucinations, confusion, seizures, and serotonin syndrome (if used with other serotonergic drugs).

Q5: Are there any contraindications?

A: Hypersensitivity, history of seizures, concurrent MAOI use, and severe liver disease.

Q6: Can it be used during pregnancy or breastfeeding?

A: Not generally recommended during pregnancy; caution advised during breastfeeding.

Q7: Does it interact with other medications?

A: Yes, interacts with MAOIs, tricyclic antidepressants, CNS depressants, alcohol, and others. Consult a drug interaction resource for details.

Q8: What precautions should be taken?

A: Monitor liver and kidney function, assess for allergies, adjust dosage in the elderly and those with renal or hepatic impairment, and avoid alcohol.

Q9: How does it compare to other pain medications?

A: Nefopam + Paracetamol offers synergistic analgesia and might be preferable for certain patients who do not respond well to single-agent therapy, but caution is advised due to potential side effects. Its efficacy relative to other analgesics depends on the specific type and severity of pain.