Drugs List

Therapeutic Indications

Uses

Anal fissure

Administration

For rectal administration.

A finger covering, such as cling film or a finger cot may be placed on the finger to be used for application of the ointment.

Contraindications

Children under 18 years
Frequent headaches
Aortic stenosis
Cardiac tamponade
Cerebrovascular haemorrhage
Cerebrovascular insufficiency
Constrictive pericarditis
Head trauma
Hypersensitivity to lanolin
Hypertrophic obstructive cardiomyopathy
Hypotension
Hypovolaemia
Migraine
Mitral stenosis
Narrow angle glaucoma
Postural hypotension
Raised intracranial pressure
Severe anaemia

Precautions and Warnings

Breastfeeding
Congestive cardiac failure
Hypothyroidism
Myocardial infarction
Pregnancy
Severe hepatic impairment
Severe renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Contains lanolin
Contains propylene glycol: may cause irritation
Monitor patients with cardiac disorders
May cause postural hypotension especially in elderly
May interfere with certain laboratory measurements
Hypotensive effects may be potentiated by alcohol

The risk/benefit ratio of glyceryl trinitrate has to be established on an individual basis. Re-evaluation of the correct dosing may be required in some patients. Excessive hypotension, especially for prolonged periods of time, must be avoided because of possible deleterious effects on the brain, heart, liver and kidney from poor perfusion and the attendant risk of ischaemia, thrombosis and altered function of these organs. Consequently, patients should be advised to change position slowly when changing from lying or sitting to upright. This advice is particularly important for those patients with low blood volume and under diuretic treatment. Paradoxical bradycardia and increased angina pectoris may accompany glyceryl trinitrate-induced hypotension. The elderly may be more susceptible to the development of postural hypotension, particularly on sudden rising. In the event that glyceryl trinitrate ointment is prescribed to patients with cardiac disorders, careful clinical and haemodynamic monitoring is recommended to avoid the potential hazards of hypotension and tachycardia. Consider discontinuation of glyceryl trinitrate if bleeding associated with haemorrhoids increases. If anal pain persists, differential diagnosis may be required to exclude other causes of the pain.

Pregnancy and Lactation

Pregnancy

Use glyceryl trinitrate with caution during pregnancy.

There is limited available data on the use of glyceryl trinitrate in pregnant women. Animal studies are inconclusive with respect to effects of glyceryl trinitrate on pregnancy, embryonal/foetal parturition and postnatal development

Schaefer (2015) suggests that, at the time of writing, toxic effects on the foetus have not been reported and nitrates may be used during pregnancy for appropriate indications, if considered essential.

Briggs (2015) suggests that the use of glyceryl trinitrate during pregnancy appears to be risk free. However, the number of women studied is limited, especially with regards to the use of glyceryl trinitrate in the first trimester. At low doses, a temporary decrease in maternal blood pressure may occur, but this does not appear to have an impact on placental perfusion.

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 glyceryl trinitrate with caution during breastfeeding.

It is not known whether glyceryl trinitrate is excreted in human milk. Therefore the manufacturer does not recommend the use of glyceryl trinitrate 0.4% rectal ointment in a woman who is breastfeeding due to the potential harmful effects on the infant. Briggs (2015) suggests that the small molecular weight (about 227) indicated that the drug may be expressed in breast milk.

However, Schaefer (2015) suggests that the short half-lives of nitrates and the usually brief usage argue against a toxic risk for the breastfed infant.

LactMed suggests the use of glyceryl trinitrate for anal fissures by nursing mothers appears to have no adverse effects on the breastfed infants.

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

Anaphylactoid reaction
Angina
Diarrhoea
Dizziness
Flushing
Headache
Hypersensitivity reactions
Hypotension
Irritation with burning (application site)
Itching at application site
Light-headedness
Methaemoglobinaemia
Nausea
Orthostatic hypotension
Pain at application site
Pruritus
Rebound hypertension
Rectal bleeding
Rectal disorders
Syncope
Tachycardia
Vomiting

Presentation

Rectal ointment containing glyceryl trinitrate

Drugs List

Therapeutic Indications

Uses

Anal fissure

Dosage

Adults

Elderly

Administration

For rectal administration.

A finger covering, such as cling film or a finger cot may be placed on the finger to be used for application of the ointment.

Contraindications

Children under 18 years
Frequent headaches
Aortic stenosis
Cardiac tamponade
Cerebrovascular haemorrhage
Cerebrovascular insufficiency
Constrictive pericarditis
Head trauma
Hypersensitivity to lanolin
Hypertrophic obstructive cardiomyopathy
Hypotension
Hypovolaemia
Migraine
Mitral stenosis
Narrow angle glaucoma
Postural hypotension
Raised intracranial pressure
Severe anaemia

Precautions and Warnings

Breastfeeding
Congestive cardiac failure
Hypothyroidism
Myocardial infarction
Pregnancy
Severe hepatic impairment
Severe renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Contains lanolin
Contains propylene glycol: may cause irritation
Monitor patients with cardiac disorders
May cause postural hypotension especially in elderly
May interfere with certain laboratory measurements
Hypotensive effects may be potentiated by alcohol

The risk/benefit ratio of glyceryl trinitrate has to be established on an individual basis. Re-evaluation of the correct dosing may be required in some patients. Excessive hypotension, especially for prolonged periods of time, must be avoided because of possible deleterious effects on the brain, heart, liver and kidney from poor perfusion and the attendant risk of ischaemia, thrombosis and altered function of these organs. Consequently, patients should be advised to change position slowly when changing from lying or sitting to upright. This advice is particularly important for those patients with low blood volume and under diuretic treatment. Paradoxical bradycardia and increased angina pectoris may accompany glyceryl trinitrate-induced hypotension. The elderly may be more susceptible to the development of postural hypotension, particularly on sudden rising. In the event that glyceryl trinitrate ointment is prescribed to patients with cardiac disorders, careful clinical and haemodynamic monitoring is recommended to avoid the potential hazards of hypotension and tachycardia. Consider discontinuation of glyceryl trinitrate if bleeding associated with haemorrhoids increases. If anal pain persists, differential diagnosis may be required to exclude other causes of the pain.

Pregnancy and Lactation

Pregnancy

Use glyceryl trinitrate with caution during pregnancy.

There is limited available data on the use of glyceryl trinitrate in pregnant women. Animal studies are inconclusive with respect to effects of glyceryl trinitrate on pregnancy, embryonal/foetal parturition and postnatal development

Schaefer (2015) suggests that, at the time of writing, toxic effects on the foetus have not been reported and nitrates may be used during pregnancy for appropriate indications, if considered essential.

Briggs (2015) suggests that the use of glyceryl trinitrate during pregnancy appears to be risk free. However, the number of women studied is limited, especially with regards to the use of glyceryl trinitrate in the first trimester. At low doses, a temporary decrease in maternal blood pressure may occur, but this does not appear to have an impact on placental perfusion.

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 glyceryl trinitrate with caution during breastfeeding.

It is not known whether glyceryl trinitrate is excreted in human milk. Therefore the manufacturer does not recommend the use of glyceryl trinitrate 0.4% rectal ointment in a woman who is breastfeeding due to the potential harmful effects on the infant. Briggs (2015) suggests that the small molecular weight (about 227) indicated that the drug may be expressed in breast milk.

However, Schaefer (2015) suggests that the short half-lives of nitrates and the usually brief usage argue against a toxic risk for the breastfed infant.

LactMed suggests the use of glyceryl trinitrate for anal fissures by nursing mothers appears to have no adverse effects on the breastfed infants.

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

Anaphylactoid reaction
Angina
Diarrhoea
Dizziness
Flushing
Headache
Hypersensitivity reactions
Hypotension
Irritation with burning (application site)
Itching at application site
Light-headedness
Methaemoglobinaemia
Nausea
Orthostatic hypotension
Pain at application site
Pruritus
Rebound hypertension
Rectal bleeding
Rectal disorders
Syncope
Tachycardia
Vomiting

Effects on Laboratory Tests

Glyceryl trinitrate can interfere with the measurement of catecholamines and vanilmandelic acid in urine as it increases the excretion of these products.

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: May 2017

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.

Joint Formulary Committee. British National Formulary. 73rd ed. London: BMJ Group and Pharmaceutical Press; 2017.

Summary of Product Characteristics: Rectogesic 4 mg/g Rectal Ointment. Kyowa Kirin Ltd. Revised May 2016.

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
Nitroglycerin. Last revised: 07 September 2013
Last accessed: 26 April 2017