Neuromidin®

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

Composition:

Active substance: ipidacrine hydrochloride;

Neuromidin® 5 mg/ml solution for injection: 1 ml of injection solution (one ampoule) contains 5 mg of ipidacrine hydrochloride calculated as anhydrous substance;

Excipients: water for injections.

Neuromidin® 15 mg/ml solution for injection: 1 ml of injection solution (one ampoule) contains 15 mg of ipidacrine hydrochloride calculated as anhydrous substance;

Excipients: water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group.

Other agents acting on the nervous system. Parasympathomimetics. Anticholinesterase agents. ATC code N07AA.

Pharmacological Properties

Pharmacodynamics

Neuromidin® is a reversible cholinesterase inhibitor.

Neuromidin® exerts a direct stimulatory effect on impulse conduction along nerve fibers, interneuronal and neuromuscular synapses of the peripheral and central nervous systems.

The pharmacological action of Neuromidin® is based on a combination of two mechanisms:

• blockade of potassium channels in neuronal and muscular cell membranes;
• reversible inhibition of cholinesterase at synapses.

Neuromidin® enhances the effect on smooth muscles not only of acetylcholine, but also of adrenaline, serotonin, histamine, and oxytocin.

Neuromidin® exhibits the following significant pharmacological effects:

• restores and stimulates impulse conduction in the nervous system and neuromuscular transmission;
• enhances contractility of smooth-muscle organs under the influence of all antagonists of acetylcholine, adrenaline, serotonin, histamine, and oxytocin receptors, except potassium chloride;
• improves memory and inhibits the progressive development of dementia;
• restores impulse conduction in the peripheral nervous system impaired by various factors such as trauma, inflammation, local anesthetics, certain antibiotics, potassium chloride, toxins, etc.;
• moderately stimulates the central nervous system in combination with some sedative effects;
• exhibits analgesic effect;
• exhibits antiarrhythmic effect.

The medicinal product has no teratogenic, embryotoxic, mutagenic or carcinogenic effects, nor does it have allergenic or immunotoxic activity. It also does not affect the endocrine system.

Pharmacokinetics

Neuromidin® is rapidly absorbed after subcutaneous or intramuscular administration. Maximum blood concentration is reached within 25–30 minutes. Approximately 40–50% of the active substance binds to plasma proteins. Neuromidin® rapidly distributes into tissues; the elimination half-life in the phase is 40 minutes. The drug is metabolized in the liver. It is excreted by the kidneys and also extrarenally (via the gastrointestinal tract). The elimination half-life after parenteral administration is 2–3 hours. Excretion occurs mainly through tubular secretion, while only one-third of the dose is eliminated via glomerular filtration. After parenteral administration, 34.8% of the administered dose is excreted unchanged in urine.

Clinical characteristics.

Indications.

Diseases of the peripheral nervous system: mono- and polyneuropathies, polyradiculopathies, myasthenia and myasthenic syndrome of various etiologies.

Diseases of the central nervous system (CNS): bulbar palsies and pareses; recovery period of organic CNS lesions accompanied by motor disturbances.

Contraindications.

Hypersensitivity to ipidacrine.

Epilepsy.

Extrapyramidal disorders with hyperkinesia.

Angina pectoris.

Marked bradycardia.

Bronchial asthma.

Vestibular disorders.

Mechanical obstruction of the intestine and urinary tract.

Peptic ulcer of the stomach or duodenum in the stage of exacerbation.

Pregnancy.

Breastfeeding period.

Interaction with other medicinal products and other types of interactions.

Neuromidin® enhances the sedative effect when used in combination with agents that depress the central nervous system. The action and adverse effects are enhanced when used concomitantly with other cholinesterase inhibitors and m-cholinomimetic agents. In patients with myasthenia, the risk of developing a "cholinergic" crisis increases if Neuromidin® is used simultaneously with cholinergic agents. The risk of developing bradycardia increases if β-adrenoblockers were used prior to initiation of treatment with Neuromidin®.

Neuromidin® can be used in combination with nootropic agents.

Alcohol enhances the adverse effects of the drug.

Special precautions for use.

Use with caution in patients with a history of gastric and duodenal peptic ulcer, respiratory tract diseases including acute respiratory infections, cardiovascular disorders unrelated to coronary pain, and in patients with thyrotoxicosis.

Use during pregnancy or breastfeeding.

Neuromidin® increases uterine tone and may provoke preterm labor; therefore, the use of the medicinal product during pregnancy is contraindicated.

The use of the drug is contraindicated during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

During treatment, patients should refrain from driving vehicles and from engaging in other potentially hazardous activities requiring increased attention and rapid psychomotor reactions.

Method of Administration and Dosage

The injection solution should be administered intramuscularly or subcutaneously. The dosage and duration of treatment should be determined individually depending on the severity of the disease.

Disorders of the peripheral nervous system:

Mono- and polyneuropathies of various etiologies: 5–15 mg administered subcutaneously or intramuscularly once or twice daily; treatment course lasts 10–15 days (up to 30 days in severe cases); thereafter, treatment should be continued with the tablet form of the drug.

Myasthenia and myasthenic syndrome: 5–30 mg administered subcutaneously or intramuscularly 1–3 times daily, followed by transition to the tablet form. Total treatment duration is 1–2 months. If necessary, treatment may be repeated several times with intervals of 1–2 months between courses.

Disorders of the central nervous system:

bulbar palsies and pareses: 5–15 mg administered subcutaneously or intramuscularly once or twice daily; treatment course lasts 10–15 days; transition to tablet form is recommended when possible.

Recovery period after organic CNS lesions:

10–15 mg administered intramuscularly once or twice daily for up to 15 days, followed by 1–2 times daily if possible.

Children

There are no systematic data on the use of the parenteral form of the medicinal product Neuromidin® in children (under 18 years of age); therefore, the drug should not be used in children.

Overdose

Symptoms

In severe overdose, a "cholinergic crisis" may develop, characterized by bronchospasm, lacrimation, increased sweating, miosis, nystagmus, enhanced gastrointestinal peristalsis, spontaneous defecation and urination, vomiting, jaundice, bradycardia, disturbances in intracardiac conduction, arrhythmias, decreased arterial pressure, restlessness, anxiety, excitement, fear sensations, ataxia, seizures, coma, speech disturbances, drowsiness, and general weakness.

Treatment: symptomatic therapy should be administered; use M-cholinoblockers such as atropine, cyclopol, metacine, etc.

Adverse Reactions

Neuromidin®, like other medicinal products, may cause adverse reactions, although they do not occur in all patients.

Frequency of adverse reactions according to the MedDRA classification (Medical Dictionary for Regulatory Activities):

very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); frequency not known (cannot be estimated from available data).

Cardiac disorders:
common – palpitations, bradycardia.

Nervous system disorders:
uncommon – dizziness, headache, drowsiness (when high doses are administered).

Respiratory, thoracic and mediastinal disorders:
uncommon – increased bronchial secretion, bronchospasm.

Gastrointestinal disorders:
common – increased salivation, nausea;
uncommon – vomiting (when high doses are administered);
rare – diarrhea, epigastric pain.

Hepatic disorders:
frequency not known – jaundice.

Skin and subcutaneous tissue disorders:
common – increased sweating;
uncommon – allergic reactions, including rash, pruritus, urticaria, angioneurotic edema.

Reproductive system disorders:
increased uterine tone.

Musculoskeletal and connective tissue disorders:
uncommon – muscle cramps (when high doses are administered).

Immune system disorders:
frequency not known – hypersensitivity reactions (including allergic dermatitis, anaphylactic shock, asthma, toxic epidermal necrolysis, erythema, urticaria, wheezing, laryngeal edema, injection site rash).

General disorders and administration site conditions:
uncommon – weakness (when high doses are administered).

Anticholinergic agents such as atropine may reduce salivation and bradycardia.

If adverse reactions occur, the dose should be reduced or the administration of the medicinal product should be temporarily interrupted (for 1–2 days).

Shelf life.

2 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

1 ml of injection solution (5 mg/ml or 15 mg/ml) in an ampoule.

10 ampoules in a blist er pack, in a cardboard carton.

Incompatibilities.

The medicinal product should not be mixed with other solutions except those specified in the section "Administration and dosage".

Prescription status.

Prescription only.

Manufacturer.

JSC "Olfa" / Olpha AS.

Manufacturer's address and place of business.

Rupnicu iela 5, Olaine, Olaines novads, LV-2114, Latvia.