Nefopein^® (Solution) Instructions for Use

Marketing Authorization Holder

Aspectus Pharma LLC (Russia)

Manufactured By

Armavir Biopharmaceutical Plant, FSE (Russia)

ATC Code

N02BG06 (Nefopam)

Active Substance

Nefopam (Rec.INN registered by WHO)

Dosage Form

Nefopein®

Solution for infusion and intramuscular injection 10 mg/ml: amp. 2 ml 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for infusion and intramuscular injection transparent, colorless, odorless.

Excipients : sodium dihydrogen phosphate dihydrate – 16.1075 mg, disodium hydrogen phosphate dodecahydrate – 1.72 mg, water for injections – up to 1 ml.

2 ml – ampoules (5) – blister packs (1) – cardboard boxes.
2 ml – ampoules (10) – blister packs (1) – cardboard boxes.

Clinical-Pharmacological Group

Non-opioid centrally acting analgesic

Pharmacotherapeutic Group

Centrally acting analgesic agent

Pharmacological Action

Non-narcotic centrally acting analgesic agent.

In vitro, Nefopam inhibited the reuptake of dopamine, noradrenaline, and serotonin in rat synaptosomes.

In vivo, Nefopam demonstrated antinociceptive activity in animals, possibly by reducing glutamate release at the presynaptic level and activating N-methyl-D-aspartate receptors at the postsynaptic level. Nefopam showed a positive effect on postoperative shivering in clinical studies. Nefopam does not have anti-inflammatory or antipyretic effects, does not depress respiration, and does not affect intestinal peristalsis. Nefopam has a slight m-cholinolytic effect. During studies, a temporary and moderate increase in heart rate and blood pressure was observed.

Pharmacokinetics

After a single 20 mg intramuscular dose, the maximum serum concentration is observed after 30-60 minutes and averages 25 ng/ml. T_1/2 averages 5 hours. After a 20 mg intravenous dose, T_1/2 averages 4 hours. Plasma protein binding is 71-76%. Biotransformation is significant; three main metabolites have been identified: desmethylnefopam, Nefopam N-oxide, Nefopam N-glucuronide.

Desmethylnefopam and Nefopam N-oxide are not glucuronidated in the liver and do not exhibit analgesic activity in animal studies.

Excretion is primarily renal: 87% of the administered dose is present in the urine, less than 5% of the administered dose is excreted unchanged.

The metabolites found in urine account for 6%, 3%, and 36% respectively of the intravenously administered dose.

Indications

Symptomatic treatment of acute pain syndrome, including postoperative pain.

ICD codes

Dosage Regimen

The dose is set individually. The dose should correspond to the intensity of the pain syndrome and the patient’s response.

Intramuscularly – 20 mg 3-4 times/day.

Intravenously administered as an infusion. The recommended single dose is 20 mg. If necessary, the administration is repeated every 4 hours. During the administration of nefopam and for 15-20 minutes after the injection, the patient should be in a lying position.

The maximum daily dose is 120 mg.

Adverse Reactions

From the nervous system, psyche very common – drowsiness; common – dizziness; rare – convulsions, irritability, agitation, hallucinations, drug dependence; frequency unknown – confusion, coma.

From the digestive system very common – nausea, vomiting; common – dry mouth.

Allergic reactions rare – hypersensitivity, urticaria, angioedema, anaphylactic shock.

Other very common – increased sweating; common – tachycardia, urinary retention; rare – malaise.

Contraindications

Hypersensitivity to nefopam; children under 15 years of age (due to lack of clinical data); convulsions or history of convulsions, epilepsy; risk of urinary retention caused by diseases of the urethra and/or prostate gland; risk of acute glaucoma; pregnancy, breastfeeding period.

Caution should be exercised in hepatic insufficiency; in renal insufficiency (due to the risk of accumulation and, consequently, an increased risk of adverse events); in patients with cardiovascular pathology, as the drug may cause tachycardia; the use of nefopam in elderly patients is not recommended due to its anticholinergic effect.

Use in Pregnancy and Lactation

Due to the lack of animal studies and clinical data in humans, the risk of using the drug is not established, therefore Nefopam is contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

Contraindicated in children under 15 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

When using nefopam, there is a risk of drug dependence.

Nefopam is not a narcotic analgesic or an opioid antagonist. Thus, discontinuation of treatment with narcotic analgesics in patients dependent on them who are already receiving nefopam therapy increases the risk of withdrawal syndrome.

The benefit/risk ratio during treatment with the drug is subject to constant re-evaluation.

Should not be prescribed for the treatment of chronic pain syndromes.

Should not be used concomitantly with alcohol, ethanol-containing and sedative drugs.

Effect on ability to drive vehicles and operate machinery

During treatment, it is not recommended to drive vehicles or engage in other activities requiring increased concentration and speed of psychomotor reactions due to the possible occurrence of drowsiness and, consequently, reduced alertness.

Drug Interactions

Concomitant use with narcotic drugs (analgesics, antitussives and drugs for substitution therapy of dependence), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (such as meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H₁-histamine receptor blockers, centrally acting antihypertensive drugs, baclofen, thalidomide and other sedatives is not recommended, as this may enhance CNS depression and lead to reduced alertness.

Ethanol and ethanol-containing drugs enhance the sedative effect of nefopam.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.