Mediatorn®

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

Composition:

Active substance: ipidacrine;

One tablet contains ipidacrine hydrochloride monohydrate equivalent to 20 mg of anhydrous substance;

Excipients: lactose monohydrate; potato starch; calcium stearate.

Pharmaceutical form. Tablets.

Main physico-chemical properties: tablets are white or almost white, round-shaped with a flat surface and bevelled edges.

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

Pharmacological Properties

Pharmacodynamics

Mediatorn® is a drug that combines two molecular effects in a biologically favorable manner – blockade of membrane potassium permeability and inhibition of cholinesterase. In this combination, blockade of membrane potassium permeability plays the decisive role.

Blockade of membrane potassium permeability primarily prolongs the repolarization phase of the action potential of the excited membrane and increases presynaptic axon activity. This leads to increased calcium ion influx into the presynaptic terminal, which in turn enhances neurotransmitter release into the presynaptic cleft in all synapses. Elevated neurotransmitter concentration in the synaptic cleft promotes stronger stimulation of the postsynaptic cell due to enhanced mediator-receptor interaction. In cholinergic synapses, cholinesterase inhibition leads to even greater accumulation of neurotransmitter in the synaptic cleft and enhanced functional activity of the postsynaptic cell (muscle contraction, impulse conduction).

Ipideacrine potentiates the effects of acetylcholine, adrenaline, serotonin, histamine, and oxytocin on smooth muscles.

Ipideacrine exhibits the following pharmacological effects:

• stimulation and restoration of neuromuscular transmission;
• restoration of impulse conduction in the peripheral nervous system after its blockade by various agents (trauma, inflammation, local anesthetics, certain antibiotics, potassium chloride, toxins);
• enhanced contractility of smooth-muscle organs;
• specific, moderately pronounced stimulation of the central nervous system (CNS) with some manifestations of sedative effect;
• improved memory and learning ability;
• analgesic effect.

The drug does not exert teratogenic, embryotoxic, mutagenic, carcinogenic, allergenic, or immunotoxic effects, nor does it affect the endocrine system.

Pharmacokinetics

After oral administration, the drug is rapidly absorbed from the gastrointestinal tract. Maximum concentration of the active substance in blood plasma is reached within 1 hour after administration. From blood, ipideacrine rapidly distributes into tissues; during the stabilization phase, only 2% of the drug remains in blood serum. The half-life in the distribution phase is 40 minutes.
40–50% of the active substance binds to plasma proteins. Ipideacrine is predominantly absorbed from the duodenum, to a lesser extent from the small and ileal intestine, and only 3% of the dose is absorbed from the stomach. Elimination of ipideacrine from the body occurs through a combination of renal and extrarenal mechanisms (biotransformation, biliary secretion), with urinary excretion being predominant. Only 3.7% of ipideacrine is excreted unchanged in urine, indicating rapid metabolism of the drug in the body.

Clinical characteristics.

Indications.

• Diseases of the peripheral nervous system (neuropathy, neuritis, polyneuritis, and polyneuropathy, myeloradiculoneuritis);
• myasthenia and myasthenic syndrome of various etiologies;
• bulbar palsies and paresis;
• memory disorders of various etiologies (Alzheimer's disease and other forms of senile dementia); mental retardation in children;
• recovery period after organic CNS lesions accompanied by motor disturbances;
• in complex therapy of multiple sclerosis and other forms of demyelinating diseases of the nervous system;
• intestinal atony.

Contraindications.

• Hypersensitivity to ipidacrine and other components of the drug;
• epilepsy;
• extrapyramidal disorders with hyperkinesia;
• angina pectoris;
• pronounced bradycardia;
• bronchial asthma;
• vestibular disorders;
• mechanical obstruction of the intestine and urinary tract;
• gastric or duodenal ulcer in the stage of exacerbation;
• pregnancy;
• breastfeeding period.

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 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 Mediatorn® is used simultaneously with cholinergic agents. The risk of bradycardia increases if β-adrenoblockers are used prior to the initiation of treatment with Mediatorn®.

Mediatorn® can be used in combination with nootropic drugs.

Alcohol enhances the adverse effects of the drug.

Cerebrolysin improves the mental effects of Mediatorn®.

Special precautions for use.

The drug should be administered with caution to patients with a history of gastric or duodenal peptic ulcer, respiratory tract disorders, including acute respiratory conditions, cardiovascular diseases not related to coronary pain, and thyrotoxicosis.

The drug contains lactose; therefore, it should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Mediatorn® increases uterine tone and may cause premature delivery; therefore, the use of the drug during pregnancy is contraindicated.

The use of the drug is contraindicated during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Mediatorn® may exert a sedative effect; therefore, caution should be exercised when using the drug while driving or operating machinery.

Method of Administration and Dosage

Mediatorn® tablets are taken orally.

For neuritis – 1 tablet 2–3 times daily. Treatment duration ranges from 10–15 days for acute neuritis to 20–30 days for chronic neuritis. If necessary, the treatment course should be repeated 2–3 times with intervals of 2–4 weeks until maximum therapeutic effect is achieved.

For polyradiculoneuritis and paresis – 1 tablet 2–3 times daily for 30–40 days. Treatment courses should be repeated multiple times with 1–2 month intervals until therapeutic effect is achieved.

For myasthenia and myasthenic syndromes – 1–2 tablets 2–3 times daily. In severe cases, the dose may be increased up to 200 mg daily (2 tablets 5 times daily every 2–3 hours). Treatment is administered in courses, alternating with classical anticholinesterase agents.

For multiple sclerosis and other forms of demyelinating nervous system disorders, bulbar palsy – 1 tablet 3–5 times daily for 60 days, repeated 2–3 times per year.

For Alzheimer's disease and other forms of senile cognitive impairment – start with a dose of 1–2 tablets daily, divided into 2 doses, gradually increasing the dose by 2 tablets per week up to 6–10 tablets daily (2 tablets 3–5 times daily). Treatment duration ranges from 4 months to 1 year. Course therapy is possible – 4–5 months of treatment followed by a 1–2 month break.

For organic CNS lesions accompanied by motor disturbances – 1 tablet 2–3 times daily. The average treatment course is 30 days. If necessary, the course may be repeated.

For intestinal atony – 1–3 tablets daily, divided into 3 doses. Treatment duration is 1–3 weeks.

Children aged 12 years and older with delayed mental development and peripheral nervous system disorders – Mediatorn® should be prescribed at 1 tablet (20 mg) 2–3 times daily. Treatment duration is 1–2 months (depending on clinical presentation).

Children

The drug may be used in children aged 12 years and older.

Overdose

In cases of severe intoxication, a cholinergic crisis may develop.

Symptoms: bronchospasm, lacrimation, excessive sweating, miosis, nystagmus, increased gastrointestinal peristalsis, spontaneous defecation and urination, vomiting, jaundice, bradycardia, cardiac conduction disturbances, arrhythmia, decreased arterial pressure, restlessness, anxiety, excitement, fear, ataxia, seizures, coma, speech disturbances, drowsiness, general weakness.

Treatment: symptomatic therapy. Use of M-cholinoblockers (atropine, cyclodol, metacyne).

Side effects

Classification of side effect frequencies: very common (≥ 1/10); common (from 1/100 to 1/10); uncommon (from 1/1000 to 1/100); rare (from 1/10000 to 1/1000); very rare (< 1/10000), including isolated cases; frequency not known (cannot be estimated from available data).

Mediatorn® is generally well tolerated. Possible adverse effects are associated with stimulation of M-cholinoreceptors.

Cardiac disorders: common – palpitations, bradycardia, chest pain.

Nervous system disorders: uncommon (with high doses) – dizziness, headache, drowsiness, general weakness, muscle cramps.

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

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

Hepatobiliary disorders: frequency not known – jaundice.

Skin and subcutaneous tissue disorders: common – increased sweating; uncommon (after high doses) – possible allergic reactions, including itching, rash.

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

Reproductive system disorders: increased uterine tone.

Salivation and bradycardia may be reduced by cholinolytic agents (e.g., atropine). If adverse effects occur, the dose should be reduced or a short treatment interruption (1–2 days) should be implemented.

Shelf life. 2 years.

Storage conditions.

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

Keep out of reach of children.

Packaging. 10 tablets per blister, 5 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and place of business.

139 Saksahanskoho Street, Kyiv, 01032, Ukraine.