Drugs List

Therapeutic Indications

Uses

Reversal of residual competitive neuromuscular block

Contraindications

Neonates under 1 month
Mechanical gastrointestinal obstruction
Mechanical obstruction of urinary tract

Precautions and Warnings

Pyrexia
Vagotonia
Benign prostatic hyperplasia
Breastfeeding
Bronchospasm
Cardiac arrhythmias
Congestive cardiac failure
Epileptic disorder
Gastrointestinal anastomosis
Hypertension
Hypotension
Ischaemic heart disease
Myasthenia gravis
Narrow angle glaucoma
Paralytic ileus
Parkinsonism
Peptic ulcer
Pregnancy
Pyloric stenosis
Recent bladder surgery
Renal impairment
Severe bradycardia
Thyrotoxicosis

Admin. during inhalation anaesthesia may cause ventricular arrhythmias
Do not mix with other drugs or substances

Glycopyrronium bromide with neostigmine should be used with caution in patients with anastomosis as rupture of the anastomosis or leakage of intestinal contents may occur.
Glycopyrronium bromide with neostigmine should be used with caution in pyrexial patients due to inhibition of sweating.
Glycopyrronium bromide with neostigmine is associated with less confusion and reduced impact on the cardiovascular system compared to atropine-neostigmine. However, caution should still be exercised in elderly patients and patients with coronary artery disease, congestive heart failure and cardiac dysrythmias.
Quaternary ammonium anticholinergic compounds in large doses may block the nicotinic muscle end plate receptors. This effect should be evaluated prior to its administration to patients with myasthenia gravis.

Pregnancy and Lactation

Pregnancy

Use glycopyrronium bromide with neostigmine with caution in pregnancy.

At the time of writing, the effects of glycopyrronium bromide on the foetus/newborn are unknown. Animal studies have shown a decrease in the rate of conception and survival at weaning of rats. The significance of this in relation to humans is unknown. Glycopyrrolate is a quaternary ammonium agent and is highly ionised at physiological pH therefore penetrates the placental barrier poorly (Briggs, 2015).

Although neostigmine is ionised at physiologic pH, the low molecular weight of neostigmine (about 223) suggests that transfer of non-ionised fraction to the embryo/foetus should be expected. Neostigmine given orally has been used for the treatment of myasthenia gravis during pregnancy, but caution should be exercised in the use of parenteral neostigmine because of the risk of inducing vaginal bleeding or premature labour (Briggs, 2015). Possible effects on the foetal heart rate must also be considered. Schaefer (2007) notes that anticholinergics may be used during pregnancy when strongly indicated.

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

Use glycopyrronium bromide with neostigmine with caution in breastfeeding.

At the time of writing there is insufficient information to assess the effects of glycopyrronium bromide with neostigmine on a breast fed infant. The manufacturer suggests the drug may reach breast milk but in amounts too small to be harmful.

There are no data available regarding the transfer of glycopyrrolate into human milk. The poor oral bioavailability and short half life (1.7 hours) of glycopyrronium bromide mean that significant quantities are unlikely to penetrate milk and any risk due to glycopyrronium bromide is likely to be minimal (Hale, 2014).

Although neostigmine is ionised at physiologic pH, the molecular weight (about 223) is low enough that the non-ionised fraction is expected to be excreted in milk (Briggs, 2015). One possible effect of neostigmine is post-feeding stomach cramps therefore infants should be observed for abdominal discomfort post-feeding (Schaefer, 2007).

LactMed indicates that anticholinergics have been shown to inhibit lactation in animals by inhibiting growth hormone and oxytocin secretion. In animals, cholinergic drugs increase oxytocin release and have variable effects on serum prolactin. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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

Arrhythmias
Bradycardia
Bronchospasm
Cardiac conduction disturbances
Confusion
Constipation
Decreased bronchial secretions
Decreased sweating
Difficulty in micturition
Dilatation of pupils
Dry mouth
Dry skin
Dysrhythmia
Flushing
Giddiness
Hypersensitivity reactions
Increased bowel action
Increased oropharyngeal secretions
Narrow angle glaucoma
Nausea
Photophobia
Visual disturbances
Vomiting

Presentation

Solution for injection containing glycopyrronium bromide and neostigmine metilsulfate

Drugs List

Therapeutic Indications

Uses

Reversal of residual competitive neuromuscular block

Dosage

Adults

Children

Patients with Renal Impairment

Contraindications

Neonates under 1 month
Mechanical gastrointestinal obstruction
Mechanical obstruction of urinary tract

Precautions and Warnings

Pyrexia
Vagotonia
Benign prostatic hyperplasia
Breastfeeding
Bronchospasm
Cardiac arrhythmias
Congestive cardiac failure
Epileptic disorder
Gastrointestinal anastomosis
Hypertension
Hypotension
Ischaemic heart disease
Myasthenia gravis
Narrow angle glaucoma
Paralytic ileus
Parkinsonism
Peptic ulcer
Pregnancy
Pyloric stenosis
Recent bladder surgery
Renal impairment
Severe bradycardia
Thyrotoxicosis

Admin. during inhalation anaesthesia may cause ventricular arrhythmias
Do not mix with other drugs or substances

Glycopyrronium bromide with neostigmine should be used with caution in patients with anastomosis as rupture of the anastomosis or leakage of intestinal contents may occur.
Glycopyrronium bromide with neostigmine should be used with caution in pyrexial patients due to inhibition of sweating.
Glycopyrronium bromide with neostigmine is associated with less confusion and reduced impact on the cardiovascular system compared to atropine-neostigmine. However, caution should still be exercised in elderly patients and patients with coronary artery disease, congestive heart failure and cardiac dysrythmias.
Quaternary ammonium anticholinergic compounds in large doses may block the nicotinic muscle end plate receptors. This effect should be evaluated prior to its administration to patients with myasthenia gravis.

Pregnancy and Lactation

Pregnancy

Use glycopyrronium bromide with neostigmine with caution in pregnancy.

At the time of writing, the effects of glycopyrronium bromide on the foetus/newborn are unknown. Animal studies have shown a decrease in the rate of conception and survival at weaning of rats. The significance of this in relation to humans is unknown. Glycopyrrolate is a quaternary ammonium agent and is highly ionised at physiological pH therefore penetrates the placental barrier poorly (Briggs, 2015).

Although neostigmine is ionised at physiologic pH, the low molecular weight of neostigmine (about 223) suggests that transfer of non-ionised fraction to the embryo/foetus should be expected. Neostigmine given orally has been used for the treatment of myasthenia gravis during pregnancy, but caution should be exercised in the use of parenteral neostigmine because of the risk of inducing vaginal bleeding or premature labour (Briggs, 2015). Possible effects on the foetal heart rate must also be considered. Schaefer (2007) notes that anticholinergics may be used during pregnancy when strongly indicated.

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

Use glycopyrronium bromide with neostigmine with caution in breastfeeding.

At the time of writing there is insufficient information to assess the effects of glycopyrronium bromide with neostigmine on a breast fed infant. The manufacturer suggests the drug may reach breast milk but in amounts too small to be harmful.

There are no data available regarding the transfer of glycopyrrolate into human milk. The poor oral bioavailability and short half life (1.7 hours) of glycopyrronium bromide mean that significant quantities are unlikely to penetrate milk and any risk due to glycopyrronium bromide is likely to be minimal (Hale, 2014).

Although neostigmine is ionised at physiologic pH, the molecular weight (about 223) is low enough that the non-ionised fraction is expected to be excreted in milk (Briggs, 2015). One possible effect of neostigmine is post-feeding stomach cramps therefore infants should be observed for abdominal discomfort post-feeding (Schaefer, 2007).

LactMed indicates that anticholinergics have been shown to inhibit lactation in animals by inhibiting growth hormone and oxytocin secretion. In animals, cholinergic drugs increase oxytocin release and have variable effects on serum prolactin. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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

Arrhythmias
Bradycardia
Bronchospasm
Cardiac conduction disturbances
Confusion
Constipation
Decreased bronchial secretions
Decreased sweating
Difficulty in micturition
Dilatation of pupils
Dry mouth
Dry skin
Dysrhythmia
Flushing
Giddiness
Hypersensitivity reactions
Increased bowel action
Increased oropharyngeal secretions
Narrow angle glaucoma
Nausea
Photophobia
Visual disturbances
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 ).

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) 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.

Medications and Mother's Milk, 16th edition (2014) Hale, T.W. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Glycopyrronium Bromide and Neostigmine Metilsulfate injection. Concordia International. Revised September 2012.

Summary of Product Characteristics: Glycopyrronium Bromide and Neostigmine Metilsulfate injection. Martindale Pharmaceuticals. Revised June 2016.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 Septemebr 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
Glycopyrrolate. Last revised: 10 March 2015
Last accessed: 16 August 2016