Nefopam

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NEFOPAM (NEFOPAM)

Composition:

Active substance: nefopam;

1 ml of solution contains 20 mg of nefopam hydrochloride;

Excipients: sodium phosphate dihydrate, anhydrous sodium hydrogen phosphate, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group.

Analgesics and antipyretics. ATC code N02BG06.

Pharmacological Properties

Pharmacodynamics

Nefopam is a non-narcotic analgesic structurally unrelated to other analgesics. Experimental studies indicate a central action involving inhibition of the reuptake of dopamine, noradrenaline, and serotonin at the synaptic level. In animals, nefopam demonstrated antinociceptive activity, which may be explained by reduced glutamate release at the presynaptic level and activation of N-methyl-D-aspartate (NMDA) receptors at the postsynaptic level. In clinical studies, nefopam showed a beneficial effect on postoperative shivering. Nefopam has no anti-inflammatory or antipyretic effects, does not depress respiration, and does not affect gastrointestinal motility. It has a negligible anticholinergic effect.

Pharmacokinetics

After administration of a single 20 mg intramuscular dose, peak plasma concentration is observed within 30–60 minutes, with a maximum concentration of 25 ng/mL. The mean elimination half-life is approximately 5 hours. After intravenous administration of a 20 mg dose, the elimination half-life is 4 hours. Plasma protein binding ranges from 71% to 76%. Biotransformation is significant, with three metabolites identified: desmethylnefopam, nefopam N-oxide, and nefopam N-glucuronide.

Desmethylnefopam and nefopam N-oxide are unconjugated and have shown no analgesic activity in animal studies. Approximately 87% of the administered dose is excreted by the kidneys, with less than 5% excreted unchanged. The metabolites identified in urine account for 6%, 3%, and 36% of the intravenously administered dose, respectively.

Clinical characteristics.

Indications.

For postoperative analgesia as part of multimodal analgesia (nefopam also has a beneficial effect in preventing postoperative shivering).

For symptomatic treatment of acute pain conditions (injuries, post-surgical pain, renal and hepatic colic).

Contraindications.

Hypersensitivity to nefopam or to any of the excipients.

Seizures or history of seizures.

Risk of urinary retention associated with urethro-prostatic disorders.

Risk of acute glaucoma attack.

Concomitant use of monoamine oxidase inhibitors (MAOIs).

Children under 15 years of age, due to lack of clinical data.

Interaction with other medicinal products and other forms of interaction.

It should be noted that a significant number of medicinal products may enhance central nervous system depression due to additive effects and may impair alertness. Medicinal products to which this applies include: opioids (analgesics, antitussives, opioid substitution therapy agents), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (meprobamate), hypnotics, antidepressants with sedative effects (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-histamine receptor antagonists, centrally-acting antihypertensives, baclofen, thalidomide.

Special precautions for use

There is a risk of developing dependence on the medicinal product. Nefopam does not belong to opioid-like drugs or opioid antagonists. Therefore, discontinuation of opioid treatment in patients dependent on opioids who are already receiving Nefopam increases the risk of withdrawal syndrome; furthermore, nefopam does not promote patient detoxification. The risk/benefit ratio during treatment with Nefopam must be continuously evaluated.

Nefopam should not be prescribed for the treatment of chronic pain syndromes, such as headache.

Caution should be exercised when prescribing the drug to patients with hepatic or renal insufficiency due to the risk of accumulation, which increases the likelihood of adverse reactions.

The drug should be prescribed cautiously to patients with cardiovascular disorders, as there is a possibility of tachycardia development.

Due to the anticholinergic effect, treatment with Nefopam is not recommended for elderly patients.

There is a risk of pharmacological dependence in patients with depression and in patients with any history of pharmacological dependence.

Do not use in patients for the treatment of myocardial infarction.

Alcohol and medicinal products containing alcohol should be avoided, as alcohol consumption may enhance the sedative effect.

The medicinal product contains sodium compounds; therefore, Nefopam should be prescribed with caution to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

The medicinal product is not used during pregnancy or breastfeeding.

Ability to influence reaction rate while driving or operating machinery

The risk of drowsiness during treatment with the drug should be considered, as it may affect the ability to drive or operate machinery.

Dosage and Administration

Therapy should be adjusted according to the intensity of pain and the patient's response.

Intramuscular administration.
Nefopam should be administered by deep intramuscular injection. The recommended dose per administration is 20 mg. If necessary, the dose may be repeated every 6 hours. Maximum daily dose is 120 mg.

Intravenous administration.
Nefopam should be administered as a prolonged intravenous infusion at a rate not exceeding 5 mg/min over at least 15 minutes. The patient should remain in a supine position during administration to minimize certain adverse reactions such as nausea, dizziness, and sweating. The single dose per infusion is 20 mg. If necessary, administration may be repeated every 4 hours. Maximum daily dose is 120 mg.

Administration method.
Nefopam can be administered in a standard infusion solution (0.9% sodium chloride solution or 5% glucose solution). The optimal dilution ratio is 1 ampoule of the drug in 50 ml of infusion solution.

Duration of treatment: not more than 8–10 days.

Children.
Not recommended for children under 15 years of age.

Overdose.

Symptoms: tachycardia, seizures, hallucinations, excitation, coma.

Treatment: symptomatic treatment, continuous cardiac and respiratory monitoring in a hospital setting.

Side effects.

The reported side effects are listed by organ systems and frequency: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), not known (frequency cannot be estimated from available data).

Central nervous system: very common – drowsiness; common – dizziness*; rare – syncope, seizures*, tremor, blurred vision, insomnia, headache, paresthesia; not known – coma.

Psychiatric disorders: rare – excitement*, irritability*, hallucinations, drug dependence, drug abuse; not known – confusion.

Cardiac disorders: common – tachycardia*, arterial hypotension, palpitations*.

Gastrointestinal disorders: very common – nausea, vomiting; common – dry mouth*, abdominal pain, diarrhea.

Renal and urinary disorders: rare – change in urine color, urinary retention.

Immune system disorders: rare – hypersensitivity reactions, including urticaria, angioedema, anaphylactic shock.

General disorders: very common – hyperhidrosis*; rare – malaise, injection site reactions.

*Other anticholinergic-like effects may occur, even if never previously reported.

Shelf life. 3 years.

Storage conditions.

Store in a dry place at a temperature of 15–25 °C.

Avoid freezing.

Keep out of reach of children.

Incompatibilities.

The medicinal product should not be mixed with other medicinal products in the same container.

Packaging.

1 ml in an ampoule, 3 ampoules in a blister, 1 blister in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

KUPER E.S.E.

Manufacturer's address and location of operations.

64, Aristovoulou Street, Athens, 11853, Greece