Ipigrix

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT IPICRIKS® (IPIGRIKS)

Composition:

Active substance: ipidacrine;

1 tablet contains 20 mg of ipidacrine hydrochloride (calculated as anhydrous substance);

Excipients: lactose monohydrate; potato starch; calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: round, flat-cylindrical tablets of white or almost white color with a bevel.

Pharmacotherapeutic group.

Agents acting on the nervous system. Parasympathomimetics. Anticholinesterase agents.

ATC code N07AA.

Pharmacological Properties

Pharmacodynamics

Ipidacrine is a drug that has a biologically favorable combination of two molecular effects: 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 leads to prolongation of the repolarization phase of the action potential of the excited membrane and enhances the activity of the presynaptic axon. This increases calcium ion influx into the presynaptic terminal, which in turn results in increased release of neurotransmitter into the synaptic cleft in all synapses. Elevated neurotransmitter concentration in the synaptic cleft promotes stronger stimulation of the postsynaptic cell due to neurotransmitter-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 (contraction, impulse conduction).

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

Ipidacrine exhibits the following pharmacological effects:

• Stimulation and restoration of neuromuscular transmission;
• Restoration of impulse conduction in the peripheral nervous system following its blockade by various agents (trauma, inflammation, local anesthetics, certain antibiotics, potassium chloride, toxins);
• Enhanced contractility of smooth-muscle organs;
• Moderately specific stimulation of the central nervous system (CNS) with some manifestations of sedative effect;
• Improvement of memory and learning ability;
• Analgesic effect.

Ipidacrine has no teratogenic, embryotoxic, mutagenic, carcinogenic, allergenic, or immunotoxic effects and does not 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. It rapidly distributes from blood into tissues; during the stabilization phase, only 2% remains in blood serum. The elimination half-life in the distribution phase is 40 minutes. 40–50% of ipidacrine is bound to plasma proteins. Absorption occurs predominantly in the duodenum, to a lesser extent in the small and ileal intestine, and only 3% of the dose is absorbed in the stomach. Elimination from the body occurs through a combination of renal and non-renal mechanisms (biotransformation, biliary secretion), with urinary excretion being predominant. Only 3.7% of the drug is excreted unchanged in urine, indicating rapid metabolism in the body.

Clinical characteristics.

Indications.

• Diseases of the peripheral nervous system (neuropathy, neuritis, polyneuritis and polyneuropathy, myelopolyradiculoneuritis), myasthenia and myasthenic syndrome of various etiologies.
• Bulbar palsies and paresis.
• Memory disorders of various etiologies (Alzheimer's disease and other forms of senile cognitive impairment); delayed mental development in children.
• Recovery period after organic CNS lesions accompanied by motor disorders.
• As part of combination therapy for multiple sclerosis and other forms of demyelinating diseases of the nervous system.
• Intestinal atony.

Contraindications.

• Hypersensitivity to ipidacrine and/or any component of the drug.
• 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 acute phase.

Interaction with other medicinal products and other types of interactions.

Ipidacrine enhances the sedative effect when used in combination with CNS depressants. The effect and adverse reactions are intensified when used concomitantly with other cholinesterase inhibitors and m-cholinomimetic agents.

When used simultaneously with cholinergic agents in patients with myasthenia, the risk of developing a cholinergic crisis increases. The risk of bradycardia increases if β-adrenoblockers are used prior to starting ipidacrine treatment.

Ipidacrine may be used in combination with nootropic agents.

Alcohol enhances the adverse effects of the drug.

Cerebrolysin improves the effect of ipidacrine on mental functions.

Special precautions for use.

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

IPIDRIX® tablets contain lactose and therefore should not be used in patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Ipidacrine increases uterine tone and may cause premature labor; therefore, its use during pregnancy is contraindicated.

Ipidacrine is contraindicated during breastfeeding.

Ability to affect reaction rate when driving or operating machinery.

Ipidacrine may produce sedative effects; therefore, caution should be exercised when driving or operating machinery.

Dosage and Administration

The drug is taken orally.

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

For polyradiculoneuritis and paresis – 1 tablet 2–3 times a day for 30–40 days. The treatment course may 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 a day. In severe cases, the dose may be increased up to 200 mg per day (2 tablets 5 times a day every 2–3 hours). Treatment is administered in courses, alternating with standard anticholinesterase therapy.

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

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

For organic CNS disorders associated with motor disturbances – 1 tablet 2–3 times a day. Average treatment duration is 30 days. The course may be repeated if necessary.

For intestinal atony – 1 tablet 1–3 times a day. Treatment duration is 1–3 weeks.

Children aged 12 years and older with delayed mental development and peripheral nervous system disorders – 1 tablet (20 mg) 2–3 times a day. Treatment duration is 1–2 months depending on the clinical picture.

Children

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

Overdose

Severe intoxication may lead to cholinergic crisis.

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-cholinergic blockers (atropine, cyclopentolate, methacycline).

Adverse Reactions

Classification of adverse reaction frequencies: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000), including isolated cases; frequency not known (cannot be estimated from the available data).

Possible adverse reactions are associated with stimulation of M-cholinergic receptors.

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).

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

Nervous system disorders: uncommon (with high-dose administration) – 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-dose administration) – vomiting; rare – diarrhea, epigastric pain.

Hepatobiliary disorders: frequency not known – jaundice.

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

Reproductive system disorders: frequency not known – increased uterine tone.

Salivation and bradycardia can be reduced by anticholinergic 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. 5 years.

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

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging.

25 tablets in a blister; 2 or 4 blisters per cardboard box.

Prescription category.

Prescription-only medicine.

Manufacturer.

JSC "Grindex".

Manufacturer's address and location of operations.

53 Krustpils Street, Riga, LV-1057, Latvia.