Mediatorn®

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

Composition:

Active substance: ipidacrine hydrochloride monohydrate;

1 ml of solution contains ipidacrine hydrochloride monohydrate equivalent to ipidacrine hydrochloride – 15 mg;

Excipient: 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.

Mediatorn® is a reversible cholinesterase inhibitor.

The medicinal product exerts a direct stimulatory effect on impulse conduction along nerve fibers, interneuronal, and neuromuscular synapses of the peripheral and central nervous systems (CNS).

The pharmacological action of the medicinal product is based on a combination of two mechanisms:

• blockade of potassium channels in the membranes of neurons and muscle cells;
• reversible inhibition of cholinesterase at synapses.

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

The medicinal product demonstrates 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, adrenergic, serotonergic, histaminergic, and oxytocin receptors, except potassium chloride;
• improves memory and inhibits the progressive development of dementia;
• restores impulse conduction in the peripheral nervous system impaired due to various factors such as trauma, inflammation, local anesthetics, certain antibiotics, potassium chloride, and toxins;
• moderately stimulates the CNS combined with some sedative effects;
• exhibits analgesic effect;
• exhibits antiarrhythmic effect.

The medicinal product does not have teratogenic, embryotoxic, mutagenic, or carcinogenic effects, nor does it have allergenic or immunotoxic effects. It also does not affect the endocrine system.

Pharmacokinetics.

The medicinal product is rapidly absorbed after subcutaneous or intramuscular administration. Maximum blood concentration is reached within 25–30 minutes; 40–50% of the active substance binds to plasma proteins. The medicinal product rapidly distributes into tissues; the elimination half-life in the phase is 40 minutes. It is metabolized in the liver. The drug is excreted by the kidneys as well as extrarenally (via the gastrointestinal tract). The elimination half-life after parenteral administration is 2–3 hours. Excretion occurs mainly via tubular secretion, with only 1/3 of the dose eliminated by 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 polyneuropathy, polyradiculopathy, myasthenia and myasthenic syndrome of various etiologies.

Diseases of the CNS: bulbar paralysis and paresis; 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 intestinal or urinary tract obstruction.

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

Pregnancy and breastfeeding.

Interaction with other medicinal products and other types of interactions.

Mediatorn® enhances the sedative effect when used in combination with medicinal products that suppress the CNS. The effect and adverse reactions 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 Mediatorn® is used simultaneously with cholinergic agents. The risk of developing bradycardia increases if β-adrenoblockers were used prior to the initiation of treatment with Mediatorn®.

Mediatorn® can be used in combination with nootropic medicinal products.

Alcohol enhances the adverse effects of the drug.

Special precautions for use.

Use with caution in patients with a history of peptic ulcer of the stomach and duodenum, respiratory tract diseases including acute respiratory infections, cardiovascular disorders not related to coronary pain, and in patients with thyrotoxicosis.

Use during pregnancy or breastfeeding.

The medicinal product Mediator® increases uterine tone and may cause premature labor; therefore, the use of the drug is contraindicated during pregnancy.

The use of the drug is contraindicated during breastfeeding.

Ability to affect reaction rate when driving or operating machinery.

During treatment, patients should refrain from driving vehicles and from engaging in 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.

Peripheral Nervous System Disorders

Mono- and polyneuropathy of various etiologies: 5–15 mg administered subcutaneously or intramuscularly 1–2 times daily; treatment course lasts 10–15 days (up to 30 days in severe cases); thereafter, treatment should be continued with oral ipidacrine.

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

Central Nervous System (CNS) Disorders

Bulbar palsies and paresis: 5–15 mg administered subcutaneously or intramuscularly 1–2 times daily; treatment course lasts 10–15 days; transition to tablet form is recommended when possible.

Recovery period in organic CNS lesions: 10–15 mg administered intramuscularly 1–2 times daily; treatment course up to 15 days.

Children

There are no systematic data on the use of parenteral ipidacrine 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, impaired cardiac conduction, arrhythmia, decreased arterial blood pressure, restlessness, anxiety, excitement, fear, ataxia, seizures, coma, speech disturbances, drowsiness, and general weakness.

Treatment: symptomatic therapy should be administered; use m-cholinoblockers (atropine, cyclodol, metacyne).

Side effects

Mediator®, like other medicinal products, may cause adverse reactions, although not all patients experience them.

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

Cardiac disorders: common – palpitations, bradycardia.

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

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

Gastrointestinal disorders: common – increased salivation, nausea; uncommon – vomiting (when using high doses); 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, angioedema.

Reproductive system disorders: increased uterine tone.

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

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 using high doses).

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 discontinued (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.

Incompatibility.

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

Packaging. 1 ml in an ampoule, 10 ampoules in a blister pack, 1 blister pack in a carton.

Prescription category. Prescription only.

Manufacturer. JSC "Halychpharm".

Manufacturer's address and location of business activity.

6/8 Opryshkivska Street, Lviv, 79024, Ukraine.