Paraplexin®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PARAPLEXIN®

Composition:

Active substance: ipidacrine hydrochloride monohydrate;

1 ml of solution contains 5 mg or 15 mg of ipidacrine hydrochloride monohydrate calculated as anhydrous substance;

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.

Paraplexin® is a reversible cholinesterase inhibitor.

Paraplexin® exerts a direct stimulatory effect on impulse conduction along nerve fibers and across interneuronal and neuromuscular synapses of both the peripheral and central nervous systems (CNS).

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

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

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

The medicinal product exhibits the following pharmacological effects:

• restores and stimulates impulse conduction in the nervous system and neuromuscular transmission;
• enhances contractility of smooth-muscle organs in response to 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, and toxins;
• moderately stimulates the CNS, combined with some sedative effects;
• exhibits analgesic activity;
• exhibits antiarrhythmic effects.

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

Pharmacokinetics.

Paraplexin® is rapidly absorbed after subcutaneous or intramuscular administration. Maximum plasma concentration is reached within 25–30 minutes. Approximately 40–50% of the active substance binds to plasma proteins. Paraplexin® rapidly distributes into tissues, with a half-life in the distribution phase of 40 minutes. The drug is metabolized in the liver. It is excreted by the kidneys and also via extrarenal pathways (through the gastrointestinal tract). The elimination half-life after parenteral administration is 2–3 hours. Excretion occurs primarily through tubular secretion, with only one-third 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 disorders.

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.

Lactation period.

Interaction with other medicinal products and other types of interactions.

Paraplexin® enhances the sedative effect when used in combination with CNS depressants. 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 Paraplexin® is used simultaneously with cholinergic agents. The risk of bradycardia increases if β-adrenoblockers were used prior to the initiation of treatment with Paraplexin®.

Paraplexin® may be used in combination with nootropic agents.

Alcohol enhances the adverse effects of the drug.

Special precautions for use.

This medicinal product should be used with caution in patients with a history of gastric and duodenal peptic ulcer, respiratory tract disorders, including acute respiratory infections, cardiovascular disorders not related to coronary pain, and in thyrotoxicosis.

Use during pregnancy or breastfeeding.

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

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 a vehicle and from engaging in potentially hazardous activities requiring increased attention and rapid psychomotor reactions.

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: administer subcutaneously or intramuscularly 5–15 mg 1–2 times daily; treatment course lasts 10–15 days (up to 30 days in severe cases); thereafter, treatment should continue with the tablet form of the drug.

Myasthenia and myasthenic syndrome: administer subcutaneously or intramuscularly 5–30 mg 1–3 times daily, followed by transition to the tablet form. The total treatment course is 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 pareses: administer subcutaneously or intramuscularly 5–15 mg 1–2 times daily; treatment course is 10–15 days; transition to tablet form is recommended when possible.

Recovery Period in Organic CNS Lesions

Administer intramuscularly 10–15 mg 1–2 times 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 Paraplexin® in children (under 18 years of age); therefore, this medicinal product 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, arrhythmia, decreased arterial pressure, restlessness, anxiety, excitement, fear sensations, ataxia, seizures, coma, speech disturbances, drowsiness, and general weakness.

Treatment: symptomatic therapy should be used; apply m-cholinoblockers: atropine, cyclodol, metacyne.

Adverse reactions.

Paraplexin®, 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, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); frequency not known (cannot be estimated from the available data).

Cardiac disorders: common – palpitations, bradycardia.

Nervous system disorders: uncommon – dizziness, headache, somnolence (with high-dose administration).

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

Gastrointestinal disorders: common – increased salivation, nausea; uncommon – vomiting (with high-dose administration); 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 (with high-dose administration).

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 (with high-dose administration).

Anticholinergic agents such as atropine may reduce salivation and bradycardia.

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

Incompatibilities.

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

Shelf life.

2 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

1 ml of solution in ampoules, 5 ampoules in a blister. 2 blisters (10 ampoules) in a cardboard box.

Prescription status.

Prescription only.

Manufacturer's location and address of its business operations.

JSC "FC "SALUTARIS": 66-B, Verkhniy Val St., Kyiv, 04071, Ukraine.

Applicant.

JSC "FC "SALUTARIS".

Location of the applicant.

4, Odeska St., Koblevе, Mykolaiv district, Mykolaiv region, 57453, Ukraine.