Kalimin 60 N, tablets 60 mg 100 pcs.

Pharmacotherapeutic group: cholinesterase inhibitor

ATX code: N07AA02

Pharmacological properties

Pharmacodynamics

Pyridostigmine bromide has a cholinomimetic effect through reversible inhibition of cholinesterase and enhancement of acetylcholine action. It improves neuromuscular transmission, increases gastrointestinal motility, increases bladder and bronchial tone, secretion of exocrine glands, causes bradycardia, mild miosis, spasm of accommodation. It has no central action.

Pharmacokinetics

Bioavailability 8-20%, in myasthenia gravis may decrease to 4%. Time to reach maximum concentration (C_max) in blood plasma is 1.5-3 h, concomitant meal does not reduce bioavailability, but may delay time to maximum concentration. The elimination half-life (T_1/2) is 2.5 h. Does not penetrate the blood-brain barrier. Practically does not bind with plasma proteins. Partially metabolized in the liver to form inactive metabolites. It is excreted unchanged by the kidneys and as metabolites. Average plasma clearance in healthy people is 0.36-0.65 l/kg/h.

Indications

Myasthenia gravis.

Pharmacological effect

Pharmacotherapeutic group: cholinesterase inhibitor

ATX code: N07AA02

Pharmacological properties

Pharmacodynamics

Pyridostigmine bromide has a cholinomimetic effect due to reversible inhibition of cholinesterase and enhancing the action of acetylcholine. Improves neuromuscular transmission, enhances motility of the gastrointestinal tract, increases the tone of the bladder, bronchi, secretion of exocrine glands, causes bradycardia, weak miosis, spasm of accommodation. Does not have a central effect.

Pharmacokinetics

Bioavailability is 8-20%, with myasthenia gravis it can decrease to 4%. The time to reach maximum concentration (Cmax) in blood plasma is 1.5-3 hours; simultaneous food intake does not reduce bioavailability, but may delay the time to reach maximum concentration. Half-life (T1/2) 2.5 hours. Does not penetrate the blood-brain barrier. Practically not bound by plasma proteins. Partially metabolized in the liver to form inactive metabolites. It is excreted by the kidneys unchanged and in the form of metabolites. The average plasma clearance in healthy people is 0.36-0.65 l/kg/h.

Special instructions

During treatment, patients are strictly prohibited from drinking alcohol.

If the patient forgot to take the next dose of the drug in a timely manner, do not take a double dose of the drug during the next dose.

The need for pyridostigmine bromide is usually significantly reduced after thymectomy or additional therapy (steroids, immunosuppressants), and therefore it is necessary to adjust the dose of the drug.

Influence on the ability to drive vehicles and machinery

Pyridostigmine bromide reduces visual acuity, so during treatment with the drug you should avoid driving vehicles or using other mechanisms.

Active ingredient

Pyridostigmine bromide

Composition

1 tablet contains:
active ingredient: pyridostigmine bromide 60.00 mg; excipients: microcrystalline cellulose 336.00 mg, corn starch 120.00 mg, povidone-K25 60.00 mg, colloidal silicon dioxide 63.00 mg, purified water 16.00 mg, magnesium stearate 3.00 mg, glutamic acid hydrochloride 2.00 mg.

Pregnancy

Pyridostigmine bromide does not have teratogenic effects, but is fetotoxic. The drug can cause premature birth, especially when used in the last weeks of pregnancy.
Pyridostigmine bromide passes into breast milk. When prescribing the drug, breastfeeding should be interrupted.

Contraindications

Hypersensitivity to the active substance or to any excipient of the drug;
previous administration of depolarizing muscle relaxants (suxamethonium, decamethonium bromide);
iritis;
chronic obstructive bronchitis, bronchial asthma;
mechanical intestinal obstruction;
obstruction of the biliary and urinary tract;
spastic conditions of the gastrointestinal tract;
myotonia;
shock in the postoperative period;
pregnancy, breastfeeding period;
children under 18 years of age.

With caution

Arterial hypotension, decompensated heart failure, renal failure, acute myocardial infarction, gastric ulcer, bradycardia, diabetes mellitus, parkinsonism, cholelithiasis in the absence of obstruction, urolithiasis in the absence of obstruction, conditions after operations on the gastrointestinal tract, liver failure, hyperthyroidism.

Side Effects

According to WHO, adverse reactions are classified according to their frequency of occurrence as follows: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10,000 to <1/1000), very rare (<1/10,000); frequency unknown (cannot be determined from available data).

Immune system disorders

Frequency unknown – hypersensitivity.

Visual disorders

Frequency unknown – miosis; lacrimation; violation of accommodation.

Heart disorders

Frequency unknown – arrhythmia (including bradycardia, tachycardia, atrioventricular block).

Vascular disorders

Frequency unknown – decreased blood pressure; fainting.

Respiratory, thoracic and mediastinal disorders

Frequency unknown – increased secretion of the bronchial glands in combination with bronchospasm.

Gastrointestinal disorders

Frequency unknown – nausea; vomit; diarrhea; spasmodic pain in the abdomen; gastrointestinal hyperkinesia; increased salivation.

Skin and subcutaneous tissue disorders

Rarely – skin rash (usually disappears soon after stopping treatment).

Frequency unknown – intense sweating.

Musculoskeletal and connective tissue disorders

Frequency unknown – increased muscle weakness; tremor and myofibrillation or muscle hypotonia.

Renal and urinary tract disorders

Frequency unknown – urge to urinate.

These side effects may be signs of overdose or cholinergic crisis. Therefore, it is imperative to find out the cause of the symptoms and, if necessary, use atropine sulfate to eliminate the cholinomimetic effects.

Cholinergic crisis, among other symptoms, can cause a sudden or gradual increase in myasthenia gravis symptoms to the point of paralysis. There is a risk of developing life-threatening respiratory paralysis. Other associated effects, accompanied by a decrease in blood pressure, can lead to vascular insufficiency, bradycardia and cause cardiac arrest or paradoxical reflex tachycardia. In this case, after immediate cessation of use of the drug Kalimin® 60 N, 1-2 mg of atropine sulfate should be administered.

Interaction

Atropine weakens the m-cholinomimetic effect of pyridostigmine bromide (bradycardia and hypersecretion), but not its effect on skeletal muscle. Pyridostigmine bromide enhances the effect of depolarizing muscle relaxants, morphine and its derivatives, barbiturates. Incompatible with ethanol. M-anticholinergics, ganglion blockers, quinidine, procainamide, local anesthetics, tricyclic antidepressants, antiepileptic and antiparkinsonian drugs reduce the severity of the action of pyridostigmine bromide.

Overdose

Symptoms: increased secretion of lacrimal, salivary and sweat glands, skin hyperemia, severe weakness, blurred vision, miosis, dizziness, nausea, vomiting, involuntary defecation and urination, intestinal colic, bronchospasm, pulmonary edema, severe or increasing muscle weakness, paralysis of the respiratory muscles, decreased blood pressure, collapse, bradycardia, paradoxical tachycardia or cardiac arrest.

Treatment: a specific antidote is atropine sulfate, which is administered intravenously (slowly) at a dose of 1-2 mg. Depending on the pulse rate, if necessary, the initial dose is administered again after 2-4 hours. Activated carbon, other enterosorbents and gastric lavage should also be used. It is necessary to control the water and electrolyte balance of the body, monitor respiration and cardiac activity. In case of pulmonary failure or cardiac arrest, appropriate resuscitation measures must be taken.

Storage conditions

Store at a temperature not exceeding 25 °C.
Keep out of the reach of children.

Shelf life

3 years.
After the first opening – 6 months.
Do not use after expiration date.

Manufacturer

Kloke Pharma-Service GmbH, Germany