Ipigrix®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT IPIGRIX® (IPIGRIX)

Composition:

Active substance: ipidacrine (ipidacrine);

1 ml of solution (1 ampoule) contains 5 mg or 15 mg of ipidacrine hydrochloride monohydrate (calculated as ipidacrine hydrochloride);

Excipients: diluted hydrochloric acid, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group.
Anticholinesterase agents. ATC code N07AA.

Pharmacological Properties

Pharmacodynamics

Ipigriks® exerts a direct stimulatory effect on impulse conduction along nerve fibers, interneuronal and neuromuscular synapses of both the peripheral and central nervous systems (CNS). The pharmacological action of Ipigriks® is based on a combination of two mechanisms:

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

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

Ipigriks® improves and stimulates impulse conduction in the nervous system and neuromuscular transmission.

Ipigriks® enhances contractility of smooth-muscle organs under the influence of all antagonists of cholinergic, adrenergic, serotonergic, histaminergic, and oxytocin receptors, except potassium chloride.

Ipigriks® improves memory and inhibits the progressive development of dementia.

The drug 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.

It moderately stimulates the CNS, with some manifestations of sedative effect; it also exhibits analgesic and antiarrhythmic effects.

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

Pharmacokinetics

Ipidacrine is rapidly absorbed after subcutaneous or intramuscular administration. Maximum blood concentration is reached within 25–30 minutes; it rapidly distributes into tissues; the distribution half-life phase is 40 minutes. Approximately 40–55% of the active substance binds to plasma proteins. The drug is eliminated via the kidneys and extrarenally (through the gastrointestinal tract). It is metabolized in the liver.

The elimination half-life after parenteral administration is 2–3 hours. Excretion occurs mainly through tubular secretion, with only ⅓ of the dose eliminated via glomerular filtration. After parenteral administration, 34.8% of ipidacrine 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;
• CNS diseases: bulbar paralysis and paresis; recovery period of organic CNS lesions accompanied by motor disorders.

Contraindications.

• Hypersensitivity to ipidacrine or other components of the drug;
• epilepsy;
• extrapyramidal disorders with hyperkinesia;
• angina pectoris, pronounced bradycardia;
• bronchial asthma;
• vestibular disorders;
• peptic ulcer of the stomach or duodenum in the stage of exacerbation;
• mechanical intestinal obstruction and urinary tract obstruction.

Interaction with other medicinal products and other types of interactions.

Ipigrix® 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. In patients with myasthenia, the risk of developing a "cholinergic" crisis increases if Ipigrix® is used simultaneously with cholinergic agents. The risk of bradycardia increases if β-adrenoblockers were used prior to initiation of treatment with the drug.

Ipigrix® can be used in combination with nootropic agents.

Alcohol enhances the adverse effects of the drug.

Special precautions.

The course of bronchial asthma, epilepsy, thyrotoxicosis, and peptic ulcer of the stomach and duodenum may worsen. Caution is also advised in case of cardiovascular diseases.

Use during pregnancy or breastfeeding.

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

The use of the drug during breastfeeding is contraindicated.

Ability to affect reaction speed when driving or operating machinery.

During treatment, it is necessary to refrain from driving a vehicle and from engaging in potentially hazardous activities that require increased attention and fast psychomotor reactions.

Dosage and Administration

The dosage and duration of treatment are determined individually depending on the severity of the disease. Ipidacrine solutions containing 5 mg/mL and 15 mg/mL are administered intramuscularly or subcutaneously.

Peripheral Nervous System Disorders

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

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

Central Nervous System (CNS) Disorders

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

Recovery Period Following Organic CNS Lesions

Intramuscular administration: 10–15 mg once or twice daily for up to 15 days, followed by once or twice daily if possible.

Children

Due to lack of safety data regarding the use of Ipigriks® injection solution, the drug is not prescribed to patients in this age group.

Overdose

Symptoms: bronchospasm, excessive sweating, miosis (pupil constriction), nystagmus, increased gastrointestinal peristalsis, spontaneous defecation and urination, vomiting, jaundice, bradycardia, impaired cardiac conduction, arrhythmia, arterial hypotension, restlessness, anxiety, excitement, fear, ataxia, seizures, coma, speech disturbances, drowsiness, general weakness.

Treatment: symptomatic therapy is administered; M-cholinolytic agents such as atropine, cyclopentolate, and metacine are used.

Side effects

Ipidacrine is well tolerated; adverse effects occur rarely (in 6.5% of cases), are mild in severity, and usually do not affect all patients.

Cardiac disorders: Increased heart rate, decreased heart rate.

Nervous system disorders: At high doses – dizziness, headache, drowsiness, general weakness, seizures.

Respiratory system disorders: Increased bronchial secretion, bronchospasm.

Gastrointestinal disorders: Increased salivation, nausea; at high doses – vomiting, diarrhea, jaundice, substernal pain.

Skin and subcutaneous tissue disorders: Increased sweating; at high doses – skin allergic reactions (itching, rash), urticaria, angioneurotic edema.

Reproductive system disorders: Increased uterine tone.

If unwanted side effects occur, the dose should be reduced or the drug temporarily discontinued for 1–2 days. Salivation and decreased heart rate can be alleviated with M-cholinergic blockers (e.g., atropine).

Shelf life. 2 years.

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

Storage conditions.

Store at a temperature not exceeding 25 °C. Do not freeze!

Keep out of reach of children!

Packaging.

1 ml in a vial made of colorless glass of hydrolytic class I with two marking rings: yellow and red (for 5 mg/ml dosage) or green and red (for 15 mg/ml dosage), and with a break point or score line.

5 vials in a blister pack made of uncoated polyvinyl chloride film (blister).

2 blister packs (blisters) are placed in a cardboard carton.

Prescription status. By prescription only.

Manufacturer.

Manufacturer responsible for batch release, including batch control/testing:

JSC "Grindeks".

Manufacturer's address and place of business.

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

Marketing authorization holder.

JSC "Grindeks".

Address of the marketing authorization holder and/or its representative.

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

Tel./fax: +371 67083205 / +371 67083505.

E-mail: [email protected]