Alzinef

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

Composition:

Active substance: nefopam hydrochloride;

1 ml of solution contains 10 mg of nefopam hydrochloride;

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

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group. Analgesics and antipyretics. ATC code N02BG06.

Pharmacological properties.

Pharmacodynamics.

Alzinef**®** is a non-narcotic central analgesic, structurally unrelated to other analgesics.

In vitro experimental studies indicate a central action involving inhibition of catecholamine and serotonin reuptake at the synaptic level.

In vivo animal studies have demonstrated the antinociceptive properties of nefopam.

The medicinal product Alzinef**®** has shown a positive effect on postoperative shivering in clinical studies.

Alzinef**®** has no anti-inflammatory or antipyretic effects, does not depress respiration, and does not affect intestinal peristalsis.

The medicinal product exhibits anticholinergic effects.

Pharmacokinetics.

After administration of a single 20 mg intramuscular dose, the time to reach maximum plasma concentration (Tmax) is 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 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. The metabolites identified 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 any of the excipients.

Children 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 reduce alertness, namely: opioids (analgesics, antitussives, opioid substitution therapies), 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 drug. The medicinal product Alzinef**®** does not belong to opioid-like drugs or opioid antagonists. Therefore, discontinuation of opioid therapy in patients dependent on such drugs, who are already using Alzinef**®**, increases the risk of withdrawal syndrome. The risk/benefit ratio of using this medicinal product must be continuously evaluated.

Alzinef**®** should not be prescribed for the treatment of chronic pain.

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

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

Due to the anticholinergic effect, the use of Alzinef**®** is not recommended in elderly patients.

Alcohol consumption and the use of medicinal products containing alcohol should be avoided, as alcohol enhances 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 Alzinef**®** in pregnant women. Animal studies do not indicate a direct or indirect harmful effect on reproductive toxicity. For safety reasons, this medicinal product should not be used during pregnancy.

Breastfeeding period

Nefopam is excreted into breast milk to an extent that effects on newborns/infants who are breastfed are probable. Alzinef**®** should not be used during breastfeeding.

Ability to affect reaction speed when driving or operating machinery

The possible risk of drowsiness during treatment with Alzinef**®** 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. Alzinef**®** should be administered by deep intramuscular injection. The recommended dose per administration is 20 mg. If necessary, administration may be repeated every 6 hours. Maximum daily dose – 120 mg.

Intravenous administration. Alzinef**®** should be administered as a prolonged intravenous infusion lasting at least 15 minutes. The patient should be in a lying position to avoid certain 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 technique

Alzinef**®** can be administered diluted in standard infusion solutions (0.9% sodium chloride solution or 5% glucose solution). The optimal dilution ratio is 1 vial of the drug in 50 mL of infusion solution.

Treatment duration – no more than 8–10 days.

Children.

Not recommended for 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.

Adverse reactions.

Reported adverse reactions are classified by organ system and frequency as follows: 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 (frequency cannot be determined from available data).

Central nervous system disorders: 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 (Quincke's edema), anaphylactic shock.

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

Psychiatric disorders: rare – excitement*, 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 adverse reactions after marketing authorization of the medicinal product is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua

Shelf life. 2 years.

Storage conditions.

Store in the original packaging to protect from light at a temperature not exceeding 25 °C.

Keep out of reach of children.

Incompatibilities.

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

Packaging. 2 ml in an ampoule, 5 ampoules in a blister pack, 1 blister pack in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address.

36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.

Marketing Authorization Holder. Limited Liability Company "Butykovska Pharmaceutical Company "Salyutaris".

Address of the Marketing Authorization Holder. 9 Druzhby Narodiv Boulevard, Kyiv, 01042, Ukraine.