Pyridostigmine bromide - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

M-, N-holinomimetiki, incl. anticholinesterase agents

Stimulators of gastrointestinal motility, including emetics

Included in the formulation

Kalimin® 60 N

pills inwards

Teva Pharmaceutical Enterprises Co., Ltd. Israel

Pyridostigmine bromide

pills inwards

FARMZASCHITA NPC, FSUE Russia

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

ONLS

АТХ:

N.07.A.A.02 Pyridostigmine bromide

Pharmacodynamics:

Pharmacological action - anticholinesterase.

Reversibly inhibits cholinesterase, increases the content of acetylcholine in the area of cholinergic synapses. It improves neuromuscular transmission, reduces the effects of nondepolarizing muscle relaxants, increases motility of the gastrointestinal tract, raises the tone of the bladder, bronchi, secretes the exocrine glands, causes bradycardia.

Eyes (m-holinoretseptory): reduction of the sphincter of the pupil and ciliary muscle - narrowing of the pupil and spasm of accommodation. Decreased intraocular pressure.

Effect on the central nervous system: excitation of the vasomotor and respiratory centers; in low doses - excitation, in high - inhibition.

Pharmacokinetics:

After ingestion, it is poorly absorbed from the digestive tract. Unlike neostigmine and physostigmine, it is not hydrolyzed by cholinesterase.

When taken orally, the time to reach the maximum concentrationis 1.5-3 hours, bioavailability is 8-20%, with myasthenia gravis it can drop to 4%. Penetration into the central nervous system is insignificant (due to low solubility in lipids). Partially metabolized in the liver to inactive metabolites. It is excreted mainly by the kidneys in unchanged form and in the form of metabolites, half-life2.5 hours

Indications:

Myasthenia gravis and myasthenic syndrome, atony of the gastrointestinal tract and bladder, including postoperative intestinal atony, atonic constipation, impaired emptying of the bladder after gynecological operations and childbirth.

Elimination of the effect of nondepolarizing curare-like drugs, for cessation of muscle relaxation during anesthesia.

ICD-10

VI.G70-G73.G70 Myasthenia gravis and other disorders of the neuromuscular synapse

XI.K90-K93.K91.3 Postoperative intestinal obstruction

XVIII.R30-R39.R39.1 Other difficulties associated with urination

XIV.N30-N39.N31.2 Neurogenic weakness of the bladder, not elsewhere classified

XIV.N30-N39.N31 Neuromuscular dysfunction of the bladder, not elsewhere classified

XIX.T80-T88.T88.8 Other specified complications of surgical and therapeutic interventions, not elsewhere classified

Contraindications:

Hypersensitivity, obturation intestinal obstruction, obstruction of the urinary tract, increased bronchial muscle tonus (bronchial asthma, chronic obstructive bronchitis), previous or combined use of depolarizing muscle relaxants (eg suxamethonium) due to the possibility of synergism, iritis; spasm of the digestive tract, bile excretory and urinary tract; myotonia, parkinsonism, thyrotoxicosis.

Carefully:

Particular caution should be exercised when used in patients with liver disease and patients with kidney disease.

In patients with gastric ulcer, hyperthyroidism, heart failure in the phase of decompensation and with myocardial infarction pyridostigmine bromide apply only after a careful comparison of the risk of side effects and the expected beneficial effect. Particular caution should be exercised when used in patients with bradycardia, diabetes, Parkinsonism, and also after operations on the digestive tract.

Pregnancy and lactation:

Recommendations FDA category B. Adequate and well-controlled studies in humans have not been conducted.Human disturbances have not been reported, but 20% of newborns have had transient muscle weakness. The animals caused some delay in ossification of the skeleton of newborns and a slight increase in the frequency of hydronephrosis. Carefully!

Poorly penetrates into breast milk. Violations are not registered. Application according to strict indications.

Dosing and Administration:

Myasthenia gravis, myasthenic syndrome. Inside for 60-180 mg 2-4 times a day.

Postoperative atony of the intestine, atonic constipation, atony of the bladder, impaired emptying of the bladder after gynecological operations and childbirth. Inside for 60 mg with an interval of 4 hours.

Post-traumatic movement disorders; flaccid paralysis; the residual phenomena of poliomyelitis (not different from placebo), encephalitis. Cessation of muscle relaxation caused by nondepolarizing muscle relaxants, with anesthesia. Intravenous slowly 5 mg, sometimes in combination with 0.5 mg atropine in 1-2 injections.

Overdose of nondepolarizing muscle relaxants. Intoxication with anticholinergics (with prevalence of peripheral symptoms). Intravenously slow or intramuscularly for 3-5 mg.Inside, parenterally (subcutaneously, intramuscularly, intravenously) 5 mg to 5 times a day. The onset of action: intravenously - after 2-3 minutes, intramuscularly - after 15 minutes, inside - after 30-60 minutes; maximum effect: inside - after 60-120 minutes; duration of action: intravenously, intramuscularly - 2-4 hours, inside - 3-12 hours.

Side effects:

From the side of cardio-vascular system: bradycardia.

From the side digestive system: nausea, vomiting, diarrhea, stomach cramps, increased salivation.

From the side CNS: muscle twitching, muscle lethargy, miosis.

From the side respiratory system: an increase in the tone and secretion of the bronchi.

Allergic reactions: skin rash.

Overdose:

Symptoms: dizziness, hypersalivation, increased lachrymation, rhinorrhea, sweating, redness of the skin, difficulty breathing, pronounced miosis, impaired vision, nausea, vomiting, intestinal colic, diarrhea, involuntary discharge of urine and feces, fatigue, severe weakness, bronchospasm, pulmonary edema, lowering blood pressure down to vascular collapse, bradycardia up to cardiac arrest; sometimes reflex tachycardia; cholinergic crisis (pronounced or increasing muscle weakness until the onset of muscle paralysis, including paralysis of the respiratory muscles).

Treatment: gastric lavage and the use of activated charcoal. Specific antidote - atropine sulfate (intravenously slowly at a dose of 1-2 mg), depending on the pulse rate, if necessary, the initial dose is re-introduced after 2-4 hours. It should be ensured that the airways are free, if necessary, ventilation; cardiac arrest; it is necessary to control the water-electrolyte balance.

Interaction:

Pyridostigmine bromide is an antagonist of nondepolarizing muscle relaxants and enhances the effect of depolarizing muscle relaxants.

M-cholinoblockers, ganglion blockers, quinidine, novocainamide, local anesthetics, tricyclic antidepressants, antiepileptic and antiparkinsonian drugs reduce the action of pyridostigmine bromide.

Atropine is able to neutralize the m-cholinergic effect of pyridostigmine (but not its effect on skeletal muscles).

Pyridostigmine bromide can enhance the action of derivatives of morphine and barbiturates.

The combined use of amisulpride with pyridostigmine bromide is not recommended (cause bradycardia and increase the risk of potentially lethal polymorphic ventricular torsade de pointes).

With simultaneous appointment hydroxychloroquine can enhance the symptoms of myasthenia gravis and thus eliminate the effect of pyridostigmine bromide.

When combined application clindamycin weaken the effects of pyridostigmine bromide.

With simultaneous application pyridostigmine bromide strengthens the action of morphine.

Pilocarpine. Additive pharmacological effect.

With simultaneous application procainamide reduces the severity of the action of pyridostigmine bromide.

Propaphenone probably attenuates the effects of pyridostigmine bromide.

When combined application propranolol weaken the effects of pyridostigmine bromide.

The effect of rocuronium bromide decreases with simultaneous use with pyridostigmine.

With the joint intravenous administration of spiramycin (which may lead to the development of torsade de pointes) and pyridostigmine causing bradycardia, the risk of ventricular arrhythmias, in particular torsade de pointes, increases. It is recommended to conduct clinical and ECG monitoring, as well as monitoring the level of electrolytes.

With simultaneous application quinidine reduces the severity of the action of pyridostigmine bromide.

With simultaneous appointment chloroquine can enhance the symptoms of myasthenia gravis and thus eliminate the effect of pyridostigmine bromide.

Pyridostigmine bromide is incompatible with ethanol.

Special instructions:

The dosage regimen and duration of treatment are determined strictly individually depending on the indications, the severity of the disease and the patient's response to treatment.

It is recommended to select the time of taking pyridostigmine bromide in such a way that its maximum effect coincides with the cycle of physical activity of the patient. It should be remembered that the lack of an expected response to treatment may be a consequence of an overdose.

When using pyridostigmine bromide, you should avoid driving the car and other activities that require high concentration of attention, rapid psychomotor reactions.

Instructions

Pyridostigmine bromide (Pyridostigmini bromidum)