Neostigmine metilsulfate parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of neostigmine metilsulfate
Drugs List
Therapeutic Indications
Uses
Myasthenia gravis
Paralytic ileus
Paroxysmal supra-ventricular tachyarrhythmias
Post operative distention
Post operative urinary retention
Reversal of residual competitive neuromuscular block
Dosage
A syringe of atropine sulfate should always be available to counteract possible excessive muscarinic effects.
Dosages should be individually determined.
Adults
Myasthenia gravis - Subcutaneous or intramuscular injection
1mg to 2.5mg at intervals throughout the day.
Duration of action of dose is 2 to 4 hours.
Total daily dose: 5mg to 20mg, but higher doses may be required by some patients.
Antagonist to non-depolarising neuromuscular blockade - Slow intravenous injection
Do not attempt reversal of neuromuscular blockade with neostigmine unless there has been a spontaneous recovery from paralysis.
A single dose of neostigmine 50micrograms/kg to 70micrograms/kg and atropine 20micrograms/kg to 30micrograms/kg over 1 minute.
Atropine and neostigmine may be given simultaneously, but in patients with bradycardia, the pulse rate should be increased to 80 per minute with atropine before administering neostigmine.
The following alternative dosing schedule may be suitable:
A single dose of 2.5mg over 1 minute in conjunction with atropine or glycopyrronium. Repeat, if necessary.
Maximum dose: 5mg.
Other indications - Subcutaneous or intramuscular injection
0.5mg to 2.5mg.
Children
Myasthenia gravis - Subcutaneous or intramuscular injection
Children aged 12 to 18 years
1mg to 2.5mg at intervals throughout the day.
Duration of action of dose is 2 to 4 hours.
Total daily dose: 5mg to 20mg.
Children aged 1 month to 12 years
200micrograms to 500micrograms as required.
Antagonist to non-depolarising neuromuscular blockade - Intravenous injection
Do not attempt reversal of neuromuscular blockade with neostigmine unless there has been a spontaneous recovery from paralysis.
Children aged under 18 years
A single dose of neostigmine 50micrograms/kg to 70micrograms/kg and atropine 20micrograms/kg to 30micrograms/kg over 1 minute.
Maximum dose: 2.5mg.
Atropine and neostigmine may be given simultaneously, but in patients with bradycardia, the pulse rate should be increased to 80 per minute with atropine before administering neostigmine.
The following unlicensed alternative dosing schedule may be suitable:
Children aged 1 month to 18 years
50micrograms/kg (up to 2.5mg per dose) over 1 minute in conjunction with or after atropine or glycopyrronium. A further dose at 25micrograms/kg (maximum 2.5mg) may be necessary.
Other indications - Injection
0.125mg to 1mg.
Neonates
Myasthenia gravis - Subcutaneous or intramuscular injection
Initial dose: 100micrograms intramuscularly. Then titrate based on individual response.
Maintenance dose: 50micrograms to 250micrograms or 30micrograms/kg intramuscularly every 2 to 4 hours.
When withdrawing reduce dose gradually.
The following unlicensed alternative dosing schedule may be suitable:
150micrograms/kg every 6 to 8 hours, 30 minutes before feeds.
Maximum daily dose: 300micrograms/kg every 4 hours, if necessary.
Contraindications
Mechanical gastrointestinal obstruction
Mechanical obstruction of urinary tract
Peritonitis
Precautions and Warnings
Elderly
Restricted sodium intake
Vagotonia
Asthma
Bradycardia
Breastfeeding
Cardiac arrhythmias
Epileptic disorder
Hyperthyroidism
Hypotension
Myotonic dystrophy
Parkinson's disease
Peptic ulcer
Pregnancy
Recent bladder surgery
Recent gastrointestinal surgery
Recent myocardial infarction
Renal impairment
Distinguish between cholinergic and myasthenia crisis
Sodium content of formulation may be significant
Advise impaired alertness may affect ability to drive or operate machinery
Administer IV injection slowly
Resuscitation facilities must be immediately available
Treatment to be administered by or under supervision of specialist
Breastfeeding: Monitor infant for systemic effects of treating the mother
Monitor cardio-respiratory function
Monitor closely for signs of overdosage:possible risk of cholinergic crisis
Cholinergic syndrome should be treated with subcutaneous atropine
Careful dose titration may minimise incidence of side effects
Dosage must be individualised for each patient, especially children
When used in conjunction with depolarising muscle relaxants, such as suxamethonium, neuromuscular blockade may be potentiated.
Neostigmine by intravenous injection may cause bradycardia, with potential to progress into asystole, unless atropine is given simultaneously.
Patients with intestinal anastomoses who are administered anticholinesterase agents may produce rupture of the anastomosis or leakage of intestinal contents.
Neostigmine metilsulfate should not be administered when the anaesthetics cyclopropane or halothane are being used; but may be used after cessation of these agents.
Pregnancy and Lactation
Pregnancy
Use neostigmine metilsulfate with caution in pregnancy.
The use of neostigmine metilsulfate has not yet been established in pregnancy. Schaefer (2015) states that neostigmine can cross the placenta, however no teratogenic effects have been reported. Experience with myasthenia gravis has shown no unexpected effects of the drug when used in pregnancy. Briggs (2015) states that multiple studies on neostigmine metilsulfate in pregnancy for reversing muscle relaxation from competitive muscle relaxants also did not observe any embryo or foetal harm. However the manufacturer suggests neostigmine metilsulfate should only be used in pregnancy if the potential benefit to the mother outweighs the potential risk to the foetus.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
In breastfeeding neostigmine metilsulfate should only be used with caution and with monitoring of the infant.
At the time of writing there is limited published information regarding the use of neostigmine metilsulfate during breastfeeding. Briggs (2015) states that two reports have shown neostigmine is not excreted into breast milk, however the molecular weight of non-ionized fractions of neostigmine (approximately 223) is low enough to be excreted into breast milk. Schaefer (2015) suggests neostigmine is the preferred choice to use during breastfeeding for the appropriate indications such as treating myasthenia gravis. The manufacturer suggests neostigmine metilsulfate should be used with caution in breastfeeding as although negligible amounts are excreted into breast milk, the infant should be monitored due to the increased risk of experiencing side effects.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Abdominal cramps
Anorexia
Bradycardia
Bronchospasm
Diarrhoea
Dizziness
Drowsiness
Dysrhythmia
Heart block
Hyperhidrosis
Hypersalivation
Hypotension
Lacrimation
Miosis
Muscle spasm
Nausea
Urinary incontinence
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: December 2016
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Neostigmine Methylsulfate Injection BP 2.5 mg in 1 ml. Hameln Pharmaceuticals Ltd. Revised March 2015.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 14 September 2017
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last accessed: 06 December 2016
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