Proserin (Tablets, Solution) Instructions for Use

ATC Code

N07AA01 (Neostigmine bromide)

Active Substance

Neostigmine methylsulphate (USP United States Pharmacopoeia)

Clinical-Pharmacological Group

Cholinesterase inhibitor

Pharmacotherapeutic Group

Anticholinesterase agent

Pharmacological Action

It is an inhibitor of acetylcholinesterase and pseudocholinesterase. It has an indirect cholinomimetic effect due to reversible inhibition of cholinesterase and potentiation of the action of endogenous acetylcholine.

It improves neuromuscular transmission, enhances gastrointestinal motility, increases the tone of the urinary bladder and bronchi, and increases the secretion of exocrine glands.

It causes bradycardia and a decrease in blood pressure. It constricts the pupil, reduces intraocular pressure, and causes accommodation spasm.

Pharmacokinetics

After parenteral administration, Neostigmine methylsulphate undergoes hydrolysis and is also metabolized in the liver to form inactive metabolites.

Plasma protein binding is 15-25%. It is excreted in the urine (80% within 24 hours) as unchanged substance (about 50%) and metabolites. It poorly penetrates the blood-brain barrier.

Indications

For oral administration: myasthenia gravis, motor disorders after brain injury, paralyses, recovery period after meningitis, poliomyelitis, encephalitis.

For parenteral administration: myasthenia; motor disorders after brain injuries; paralyses; recovery period after meningitis, poliomyelitis, encephalitis; neuritis; prevention and treatment of atony of the gastrointestinal tract and urinary bladder; weakness of labor (rarely).

As an antidote after anesthesia using non-depolarizing muscle relaxants for muscle weakness and respiratory depression. In pediatrics, it is used only for myasthenia.

ICD codes

Dosage Regimen

Administer orally, subcutaneously, intramuscularly, or intravenously. Determine the dose, route, and schedule individually based on indication, clinical status, and patient age.

For oral administration in adults with myasthenia gravis, initiate with 15 mg. Administer subsequent doses of 15 mg at 3-4 hour intervals. Adjust the total daily dosage based on individual response; the typical range is 75 mg to 150 mg.

For parenteral administration in adults, use a 0.05% solution. The typical subcutaneous or intramuscular dose is 1-2 mL (0.5-1.0 mg). Administer 1-3 times per day as required. The maximum single dose is 2 mL (1.0 mg); the maximum daily dose is 6 mL (3.0 mg).

As an antidote for non-depolarizing muscle relaxants, administer 0.5-2.0 mg intravenously. Precede or co-administer with 0.5-1.0 mg of atropine sulfate to mitigate muscarinic side effects.

For pediatric use in myasthenia gravis, calculate the parenteral dose as 0.04 mg per kg of body weight. Administer subcutaneously or intramuscularly. For oral administration, the dose is 2 mg per kg of body weight, divided into 6-8 doses over 24 hours.

For postoperative bladder or gastrointestinal atony in adults, administer 1 mL (0.5 mg) of the 0.05% solution subcutaneously or intramuscularly. Repeat as necessary, following institutional protocols.

Closely monitor patients for signs of cholinergic crisis (muscle fasciculations, weakness, excessive secretions) or myasthenic crisis. Differentiate between the two conditions carefully, as they require opposing therapeutic interventions.

Adverse Reactions

From the digestive system: nausea, vomiting, diarrhea, hypersalivation, flatulence, spastic contraction and increased peristalsis.

From the central and peripheral nervous system: headache, dizziness, weakness, loss of consciousness, drowsiness, miosis, visual disturbances, tremor, spasms and twitching of skeletal muscles (including tongue muscles), convulsions, dysarthria.

From the cardiovascular system: arrhythmias, brady- or tachycardia, AV block, nodal rhythm, nonspecific ECG changes, decreased blood pressure, cardiac arrest.

From the respiratory system: shortness of breath, bronchospasm, respiratory depression, increased secretion of bronchial glands.

Allergic reactions: skin rash, itching, facial flushing, anaphylactic reactions are possible.

Other: arthralgias, increased urination, increased sweating.

Contraindications

For oral administration: hypersensitivity to neostigmine methylsulphate; epilepsy, hyperkinesis, vagotomy, coronary artery disease, bradycardia, arrhythmias, angina pectoris, bronchial asthma, severe atherosclerosis, thyrotoxicosis, peptic ulcer of the stomach and duodenum, peritonitis, mechanical obstruction of the gastrointestinal tract and urinary tract, prostatic hyperplasia, period of acute infectious disease; children under 18 years of age.

With caution: arterial hypotension, recently suffered coronary occlusion, Addison’s disease.

For parenteral administration: hypersensitivity to neostigmine methylsulphate; epilepsy, hyperkinesis, coronary artery disease, bradycardia, arrhythmias, angina pectoris, bronchial asthma, severe atherosclerosis, hyperthyroidism, peptic ulcer of the stomach and duodenum, peritonitis, mechanical obstruction of the gastrointestinal tract and urinary tract, prostatic hyperplasia; acute infectious diseases, intoxication in debilitated children.

Use in Pregnancy and Lactation

Neostigmine methylsulphate crosses the placental barrier and is excreted in breast milk in very small amounts.

Contraindicated for use during pregnancy and lactation (breastfeeding).

Pediatric Use

It is possible to use in children according to indications, in doses and dosage forms recommended for the respective age. It is necessary to strictly follow the instructions in the drug labels for neostigmine methylsulphate regarding contraindications for the use of specific dosage forms of neostigmine methylsulphate in children of different ages.

Special Precautions

When administered parenterally in high doses, preliminary or simultaneous administration of atropine is necessary.

If a myasthenic (due to insufficient therapeutic dose) or cholinergic (due to overdose) crisis occurs during therapy, careful differential diagnosis is required due to the similarity of symptoms.

Effect on ability to drive vehicles and machinery

During the treatment period, patients should exercise caution when driving vehicles and machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Neostigmine methylsulphate is an antagonist of non-depolarizing muscle relaxants and restores impaired neuromuscular conduction. Therefore, if muscle weakness and respiratory depression persist after anesthesia with non-depolarizing muscle relaxants, Neostigmine methylsulphate is used as an antidote for this group of muscle relaxants (atracurium besilate, rocuronium bromide, tubocurarine chloride, etc.).

With simultaneous use, M-cholinoblockers, ganglion blockers, quinidine, procainamide, local anesthetics, tricyclic antidepressants, antiepileptic and antiparkinsonian drugs reduce the effect of neostigmine methylsulphate.

Ephedrine potentiates the effect of neostigmine methylsulphate, therefore, in myasthenic crises, it is administered together with neostigmine methylsulphate.

With simultaneous use of neostigmine methylsulphate with beta-blockers, bradycardia may be enhanced.

For myasthenia, it is prescribed in combination with corticosteroids and anabolic hormones.

Atropine, methoctine iodide and other M-cholinoblockers weaken the M-cholinomimetic effects (pupil constriction, bradycardia, increased gastrointestinal motility, hypersalivation and others).

It is prescribed with caution against the background of cholinoblockers, in patients (with myasthenia) against the background of neomycin, streptomycin, kanamycin and other antibiotics with anti-depolarizing effect, local anesthetics and general anesthetics, antiarrhythmic and a number of other drugs that impair cholinergic transmission.

Neostigmine methylsulphate and depolarizing muscle relaxants (suxamethonium iodide, etc.) are pharmacologically incompatible, since with direct interaction the effect of suxamethonium iodide is enhanced.

M-cholinoblockers (atropine, homatropine hydrobromide, platyphylline, etc.), ganglion blockers (pachycarpine hydroiodide), quinidine, procainamide, local anesthetics are pharmacological antagonists of neostigmine methylsulphate.

There is relative antagonism between tricyclic antidepressants, antiepileptic and antiparkinsonian drugs.

Cyanocobalamin in high doses weakens the effect of neostigmine methylsulphate. When neostigmine methylsulphate interacts with pyridoxine, the activity of the latter decreases.

Cholinesterase inhibitors in combination with strychnine significantly increase the tone of the vagus nerve; with laxatives – enhance their effect; with antiarrhythmic drugs (beta-blockers) are synergists (aggravation of bradycardia).

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.