Nefam

for medical use of the medicinal product NEFAM

Composition:

active substance: nefopam hydrochloride;

1 ml of solution contains 10 mg of nefopam hydrochloride;

excipients: sodium dihydrogen phosphate dihydrate; sodium hydrogen phosphate dodecahydrate; water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group. Analgesics and antipyretics. ATC code N02B G06.

Pharmacological properties.

Pharmacodynamics.

Neofam is a central non-narcotic analgesic, structurally unrelated to other analgesics. In vitro experimental studies indicate a central action involving inhibition of the reuptake of catecholamines and serotonin at the synaptic level. In vivo animal studies have demonstrated the antinociceptive properties of nefopam. Nefopam has shown a positive effect on postoperative shivering in clinical trials. Nefopam has no anti-inflammatory or antipyretic activity, does not depress respiration, and does not affect intestinal peristalsis. Nefopam exhibits anticholinergic effects.

Pharmacokinetics.

After administration of a single 20 mg intramuscular dose, the time to reach maximum plasma concentration (Tmax) ranges from 30 to 60 minutes, and the maximum concentration (Cmax) averages 25 ng/mL. The elimination half-life averages 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%.

Extensive biotransformation occurs, with three metabolites identified: desmethylnefopam, nefopam N-oxide, and nefopam N-glucuronide.

Desmethylnefopam and nefopam N-oxide are non-conjugated 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.

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

Clinical characteristics.

Indications.

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

Symptomatic treatment of acute pain conditions (trauma, post-surgical pain, relief of renal and hepatic colic).

Contraindications.

• Hypersensitivity to nefopam or to other components of the medicinal product.
• Pediatric age under 15 years – due to lack of clinical studies.
• Seizures or history of seizures.
• Risk of urinary retention associated with urethroprostatic disorders.
• Risk of acute glaucoma attack.
• Concomitant use of MAO inhibitors.

Interaction with other medicinal products and other types of interactions.

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

Special precautions for use

There is a risk of developing dependence on the medicinal product. The medicinal product Neffam does not belong to opioids or opioid antagonists. Therefore, discontinuation of opioid treatment in patients dependent on opioids who are already receiving Neffam increases the risk of developing withdrawal syndrome. The benefit-risk ratio of using this medicinal product should be continuously evaluated.

Neffam should not be prescribed for the treatment of chronic pain syndromes.

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

Caution is also advised when prescribing the medicinal product to patients with cardiovascular disorders, as there is a possibility of developing tachycardia.

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

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

This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding

Pregnancy

There are no data on the use of the medicinal product in pregnant women. Animal studies do not indicate a direct or indirect harmful effect on reproductive function. For safety reasons, Neffam should not be used during pregnancy.

Breastfeeding

Nefopam is excreted in breast milk in amounts that may affect newborns/infants who are breastfed. The medicinal product Neffam should not be used during breastfeeding.

Ability to influence reaction speed while driving or operating machinery

The risk of drowsiness during treatment with the medicinal product 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. The drug Neffam should be administered deep intramuscularly. The recommended dose per injection is 20 mg. If necessary, administration may be repeated every 6 hours. Maximum daily dose – 120 mg.

Intravenous administration. Neffam should be administered as a prolonged intravenous infusion lasting at least 15 minutes; the patient should be in a lying position to avoid adverse reactions such as nausea, dizziness, and increased sweating. The single dose per injection is 20 mg. If necessary, administration may be repeated every 4 hours. Maximum daily dose – 120 mg.

Administration method

The drug Neffam can be administered diluted 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.

Treatment duration – no more than 8–10 days.

Children. Do not use in children under 15 years of age.

Overdose.

Symptoms of anticholinergic origin: tachycardia, coma, seizures, hallucinations.

Treatment: symptomatic therapy with cardiac and respiratory monitoring in a hospital setting.

Adverse Reactions

Reported adverse reactions are classified 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), frequency not known (cannot be estimated from available data).

Central nervous system: very common: somnolence; common: dizziness*; rare: seizures*; frequency not known: coma.

Cardiac disorders: common: tachycardia*, palpitations*.

Gastrointestinal disorders: very common: nausea, vomiting; common: dry mouth*.

Renal and urinary disorders: common: urinary retention.

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

General disorders: very common: hyperhidrosis*; rare: malaise.

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

*Other anticholinergic-like reactions may occur, even if they have never been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report any suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions. Store in the original packaging at a temperature not exceeding 25°C.

Keep out of reach and sight of children.

Packaging. 2 mL in an ampoule. 5 or 10 ampoules per pack. 5 ampoules in a blister. 1 or 2 blisters per pack.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Address of manufacturer and location of business operations.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.