Prostigmin

Prostigmin

neostigmine

Manufacturer:

A. Menarini

Distributor:

Zuellig
Full Prescribing Info
Contents
Neostigmine methylsulfate.
Description
Each ampule contains neostigmine methylsulfate 0.5 mg.
Action
Pharmacology: Properties, Effects: Neostigmine acts as a reversible, competitive acetylcholinesterase inhibitor. The result is an indirect parasympathomimetic effect. This prolongs and increases the effect of acetylcholine. Neostigmine also has a direct cholinergic effect on the skeletal muscles and possibly, also on autonomous gangliocytes and neurons of the central nervous system (CNS).
Neostigmine increases contraction and peristalsis in the gastrointestinal tract, in the urogenital system and in other organs with smooth musculature. It is suited for promoting defecation and urination. In the nervous system, neostigmine facilitates the transmission of motor and sensory impulses. In patients with myasthenia gravis syndrome, it eliminates muscular fatigue and restores normal muscle activity for several hours. Neostigmine only has antagonistic action against curare and curariform agents eg, nondepolarising synthetic muscle relaxants. It has a synergistic effect on depolarising agents. Neostigmine has no significant effect on muscle relaxants that have ganglions as site of action.
Pharmacokinetics: Distribution: Neostigmine is rapidly distributed in the extracellular space after intravenous (IV) injection. Red cell anticholinesterase activity is almost completely suppressed within 2-3 min. Peak pharmacological activity is generally achieved 7-15 min after IV administration. Plasma half-life (t½) after IV injection is 47-60 min, with an average of 53 min.
Enzyme activity recovers to about 28% of control values after 40 min, and to 55%, after 60 min. The apparent volume of distribution is 0.5-1 L/kg.
In a study with 5 patients suffering from myasthenia gravis syndrome, peak plasma values were observed 30 min after intramuscular (IM) injection. The t½ was between 51 and 90 min.
The clinical effect of neostigmine after IM injection usually sets on within 20-30 min and lasts for 2.5-4 hrs.
The protein binding (human serum albumin) of neostigmine amounts to 15-25%.
Metabolism: Neostigmine is metabolised by cholinesterase primarily to 3-hydroxyphenyl-trimethylamine and by microsomal hepatic enzymes to various unidentified compounds.
Elimination: The elimination t½ of neostigmine varies markedly about a mean value of roughly 1 hr. Total body clearance is reported to be about 8-14 mL/kg/min. Neostigmine is eliminated by renal and extrarenal mechanisms. 60-80% of a dose is eliminated within 24 hrs in the urine, either as unchanged neostigmine (approximately 50%) or in the form of metabolites (approximately 30%).
Indications/Uses
Atonic constipation, meteorism eg, before radiographic examinations; postoperative intestinal atony and urine retention; myasthenia gravis pseudoparalytica; curare antagonism (reversal of the effects of curare and curare-like, nondepolarizing muscle relaxants).
Dosage/Direction for Use
Standard Dosage: Atonic Constipation, Meteorism (eg, before radiographic examination): Adults: ½ to one 1 mL ampule (0.25-0.5 mg) SC or IM. Children: ¼-½ of a 1 mL ampoule (0.125-0.25 mg) SC or IM. In children, it may be advisable to administer a glycerin (50 mL, 10%) or saline (20 mL, 10%) enema a ½-hr after injection of Prostigmin.
Postoperative Intestinal Atony and Urine Retention: Prophylaxis: ½ of a 1 mL ampule (0.25 mg) SC or IM immediately after surgery; repeat this dose every 4-6 hrs as required.
Treatment: Adults: One 1 mL ampule (0.5 mg) SC, IM or by very slow IV injection; if necessary, repeat this dose at 4- to 5-hr intervals. Children: ¼-½ of a 1 mL ampule (0.125-2.5 mg) SC or IM.
Myasthenia Gravis Pseudoparalytica: Parenteral doses adjusted to the degree of disability. Oral co-medication with Mestinon (pyridostigmine) may be advisable.
Curare Antagonism (reversal of the effects of curare and curare-like, nondepolarizing muscle relaxants): 1-5 mg IM and/or slow IV injection, possibly with prior combination of 0.4-1.2 mg atropine sulfate to reduce cholinergic side effects eg, bradycardia and hypersecretion.
Atropine and neostigmine must not be injected with the same syringe. (see Incompatibilities under Interactions).
The above doses must not be exceeded even in cases of curare overdosage.
Special Dosage Instructions: Longer dosage intervals or lower repeat doses may be indicated in patients with impaired renal function.
Overdosage
As with other cholinesterase inhibitors, overdosage of neostigmine may lead to cholinergic crisis, characterized by bradycardia, or paradoxically, tachycardia, and marked muscular weakness. Affection of respiratory musculature may cause death. On the other hand, patients with myasthenia may also experience increased muscular weakness.
It is very important to distinguish between these 2 conditions, myasthenic and cholinergic crisis. They can be differentiated by administration of edrophonium chloride. The treatment of these 2 types is radically different. While patients with myasthenia require treatment with cholinesterase inhibitors, a cholinergic crisis requires strict withdrawal of all drugs of this type and slow IV administration of 1-2 mg atropine sulfate. Depending on the pulse rate, administration of this dose should be repeated in 2- to 4-hr intervals.
Atropine may also be used to suppress gastrointestinal side effects or other muscarine reactions. However, administration of atropine may cloud signs of overdosage and cause an abrupt outbreak of a cholinergic crisis.
Contraindications
Known hypersensitivity to Prostigmin or in patients with mechanical obstruction of the intestine or urinary tract.
Prostigmin must not be given in conjunction with depolarizing muscle relaxants eg, suxamethonium (≤succinylcholine).
Special Precautions
Prostigmin should be used with caution in patients with epilepsy, recent coronary artery occlusion, arrhythmia, bradycardia, bronchial asthma, hyperthyroidism, diabetes mellitus vagotonia, gastric ulcer and after gastrointestinal surgery. It is important to distinguish between myasthenic and cholinergic crises, the latter being caused by neostigmine overdosage. Both crises cause extreme amyosthenia, but require different treatment (see Overdosage).
Use in pregnancy & lactation: No data are available from controlled studies of Prostigmin in animals or pregnant women. Accordingly, Prostigmin should not be used during pregnancy unless the potential benefits outweigh the risk to the fetus. After IV administration, cholinesterase inhibitors may cause contractions of the uterus and premature labour.
It is uncertain whether neostigmine methylsulfate is excreted in breast milk. Nursing mothers who need neostigmine should take the precaution of weaning their infants.
Use In Pregnancy & Lactation
No data are available from controlled studies of Prostigmin in animals or pregnant women. Accordingly, Prostigmin should not be used during pregnancy unless the potential benefits outweigh the risk to the fetus. After IV administration, cholinesterase inhibitors may cause contractions of the uterus and premature labour.
It is uncertain whether neostigmine methylsulfate is excreted in breast milk. Nursing mothers who need neostigmine should take the precaution of weaning their infants.
Adverse Reactions
Prostigmin can have undesirable functional effects on the autonomic nervous system (ANS). Muscarinic effects can include nausea, vomiting, diarrhea, stomach cramps, increased peristalsis and bronchial secretion, salivation and lacrimation, bradycardia and miosis. The primary nicotinic effects are muscle spasms, fasciculations and muscular weakness.
Cholinergic reactions to Prostigmin can be particularly troublesome when Prostigmine is used to reverse the action of nondepolarising muscle relaxants. For this reason, combined injection of Prostigmin and atropine sulfate is recommended (see Dosage, Overdosage).
In addition, the following adverse effects were observed in patients that were given neostigmine: Allergy: Allergic reactions and anaphylaxis. Neurologic: Vertigo, convulsions, unconsciousness, tiredness, headache, dysarthria and visual disturbance. Cardiovascular: Arrhythmia [including bradycardia, tachycardia, atrioventricular (AV) block and nodal rhythm] and unspecified electrocardiogram (ECG) variations, as well as cardiac arrest, syncope, and hypotension. This was observed particularly in patients that were given neostigmine parenterally. Respiratory: Increased oral and bronchial secretion, dyspnea, respiratory depression, apnea and bronchospasm. Dermatologic: Redness of skin, urticaria and rash. Gastrointestinal: Nausea, vomiting, flatulence and increased peristalsis. Urogenital: Increased urination. Bones and Muscles: Muscle cramps and arthralgia. Miscellaneous: Diaphoresis, facial redness, adynamia.
Drug Interactions
Neostigmine antagonises the effect of curare-like, nondepolarising muscle relaxants. Atropine counteracts cholinergic reactions to neostigmine, notably bradycardia and hypersecretion. Neostigmine does not antagonise the phase I blockade of depolarising muscle relaxants eg, suxamethonium (≤succinylcholine) or decamethonium, but it has a prolonging effect. Certain antibiotics eg, neomycine, streptomycine and kanamycine, have a nondepolarising effect, which may increase the neuromuscular block. These antibiotics should only be used with extreme caution in myasthenic patients. The neostigmine dose should be carefully adjusted in these cases.
Local and some systemic anesthetic agents, anti-arrhythmic agents and other drugs that impair the neuromuscular transmission, should be used with caution, particularly in patients with myasthenia gravis syndrome. The neostigmine dose must be adjusted accordingly.
Incompatibilities: Neostigmine and atropine must not be injected with the same syringe.
Storage
Store in original package at room temperature (25°C).
Do not use after the expiration date identified by <EXP> on the package.
ATC Classification
N07AA01 - neostigmine ; Belongs to the class of anticholinesterase. Used as parasympathomimetics.
Presentation/Packing
Inj (amp) 0.5 mg/mL x 5's.
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