Nefam

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NEFAM® (NEFAM)

Composition:

Active substance: nefopam hydrochloride;

1 ml of injectable solution contains 20 mg of nefopam hydrochloride;

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

Pharmaceutical form. Injectable solution.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group. Analgesics and antipyretics. ATC code N02BG06.

Pharmacological Properties

Pharmacodynamics

Neffam® is a central non-narcotic analgesic that is structurally unrelated to other analgesics. In vitro experimental studies indicate a central action involving inhibition of reuptake of catecholamines and serotonin at the synaptic level. In vivo animal studies have demonstrated the antinociceptive properties of nefopamide. Clinical studies have shown that nefopamide has a positive effect on postoperative shivering. Nefopamide has no anti-inflammatory or antipyretic activity, does not suppress respiration, and does not affect intestinal peristalsis. Nefopamide has 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%.

Metabolism is extensive. Three metabolites have been identified: desmethylnefopamide, nefopamide N-oxide, and N-glucuronide of nefopamide.

Desmethylnefopamide and nefopamide N-oxide are non-conjugated and have not shown 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, pain relief in renal and hepatic colic).

Contraindications.

• Hypersensitivity to nefopam or to any of the excipients.
• Pediatric use under 15 years of age – due to lack of clinical data.
• Seizures or history of seizures.
• Risk of urinary retention associated with urethroprostatic disorders.
• Risk of acute glaucoma attack.
• Concomitant use of monoamine oxidase inhibitors (MAOIs).

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 reduce alertness, namely: opioids (analgesics, antitussives, opioid substitution therapy agents), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (meprobamate), hypnotics, antidepressants with sedative effects (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedating H1-histamine receptor antagonists, centrally-acting antihypertensives, baclofen, thalidomide.

Special precautions for use.

There is a risk of developing dependence on the medicinal product. Neffam**®** does not belong to opioid-like drugs 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 risk-benefit ratio during treatment with Neffam**®** must 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 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 and medicinal products containing alcohol should be avoided, as alcohol consumption may enhance the sedative effect.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, 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.

Lactation.

Neofopam passes into breast milk in quantities sufficient to affect newborns/infants who are breastfed. Neffam**®** should not be used during breastfeeding.

Ability to influence reaction speed while driving or operating machinery.

The risk of drowsiness during treatment should be taken into account, as it may affect the ability to drive or operate machinery.

Method of Administration and Dosage

Therapy should be adjusted according to the intensity of pain and the patient's response. Intramuscular administration. Neffam**®** should be administered by deep intramuscular injection. The recommended dose per injection is 20 mg. If necessary, the dose may be repeated every 6 hours. Maximum daily dose – 120 mg.

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

Administration technique

Neffam**®** may be administered diluted in standard infusion solutions (0.9% sodium chloride solution or 5% glucose solution). The optimal dilution ratio is 1 ampoule of the medicinal product in 50 ml of infusion solution.

Duration of treatment – 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 treatment with cardiac and respiratory monitoring in a hospital setting.

Side effects.

The reported side effects 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), not known (frequency cannot be determined from available data).

From the central nervous system: very common: drowsiness; common: dizziness*; rare: seizures*; not known: coma.

From the cardiac system: common: tachycardia*, palpitations*.

From the gastrointestinal tract: very common: nausea, vomiting; common: dry mouth*.

From the renal and urinary system: common: urinary retention.

From the immune system: rare: hypersensitivity reactions, including urticaria, angioedema (Quincke's edema), anaphylactic shock.

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

Psychiatric disorders: rare: excitement*, irritability*, hallucinations, drug dependence, drug abuse; 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 the medicine has been authorized is important. It allows ongoing monitoring of the benefit/risk balance of the medicine. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report any suspected adverse reactions and lack of efficacy of the medicine via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life. 18 months.

Do not use the medicine after the expiry date stated on the packaging.

Storage conditions.

No special storage conditions required. Do not freeze.

Keep out of reach and sight of children.

Packaging. 1 mL in a pre-filled glass syringe with needle; 1 or 2 syringes with needle in a blister; 1 blister per carton; or 1 syringe with needle in a tube; 1 or 10 tubes per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's name and address of the place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.