Drugs List

Therapeutic Indications

Uses

Maintenance of venous patency at peripheral infusion sites
Prophylaxis of angina pectoris

Administration

Application period
Application can either be for a continuous period of 24 hours or intermittently, incorporating a patch free interval (usually at night).
Patients already receiving continuous 24 hour nitrate therapy without signs of nitrate tolerance may continue on this regimen provided clinical response is maintained.
Attenuation of effect has occurred in some patients being treated with sustained release nitrate preparations. On the basis of clinical studies it is recommended that in such cases the patch should be applied daily, for a period of approximately 12 hours, with a patch free interval of 8 to 12 hours.
Overnight treatment may be beneficial in nocturnal angina with a nitrate-free interval during the day. These patients may require additional anti-anginal therapy during the day.
Patients with severe angina may need additional anti-anginal therapy during nitrate-free intervals.

Application site for maintenance of venous patency
Apply one 5 mg/24 hour patch distally and close to the site of intravenous cannulation at the time of venepuncture. Ideally, the patch should be changed daily (some manufacturers recommend every three to four days) and a replacement patch applied to a different area of skin.

Contraindications

Systolic blood pressure < 90mmHg
Aortic stenosis
Cardiac tamponade
Cerebrovascular haemorrhage
Constrictive pericarditis
Head trauma
Hypertrophic obstructive cardiomyopathy
Mitral stenosis
Narrow angle glaucoma
Raised intracranial pressure
Severe anaemia
Severe hypovolaemia
Toxic pulmonary oedema

Precautions and Warnings

Children under 18 years
Hypothermia
Ventilation-perfusion mismatch
Acute cardiac failure
Breastfeeding
Hypotension
Hypothyroidism
Hypoxia
Malnutrition
Postural hypotension
Pregnancy
Recent myocardial infarction
Severe hepatic impairment
Severe renal impairment

Not for treatment of acute attacks of angina
Advise ability to drive/operate machinery may be affected by side effects
Not all presentations are licensed for all indications
Discard used patches safely - fold with adhesive edges together
Remove metal containing patch prior to MRI scan
Rotate application sites - avoid applying patch to the same site
Advise patient that postural hypotension may occur
Cross tolerance to other nitrates may develop
Tolerance may develop - consider 8-12hr drug-free interval each day
Withdraw gradually after long-term use
Consider removing patch before cardioversion, defibrillation or diathermy
Discontinue if sensitisation occurs
Discontinue immediately if severe hypotension occurs
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effect enhanced by alcohol

Patients should be advised to dispose of patches carefully to avoid accidental application or use.

Pregnancy and Lactation

Pregnancy

Glyceryl trinitrate should be used with caution during pregnancy.

Glyceryl trinitrate is primarily used for treatment and prevention of angina and therefore experience of use in pregnancy is limited. Glyceryl trinitrate should not be used during pregnancy particularly during the first trimester unless the potential benefits outweigh the unknown risks to the foetus. Schaefer (2007) comments that nitrates may be used in pregnancy for appropriate indications and toxic affects on the foetus have not been reported. Briggs (2011) adds that with smaller doses of nitrates a transient decrease in the mother's blood pressure may occur but does not seem to be sufficient to affect placental perfusion. The use of transdermal glyceryl trinitrate patch may also be effective when longer periods of tocolysis are required.

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 14-17 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

Glyceryl trinitrate should be used with caution during breastfeeding.

It is not known if glyceryl trinitrate passes into breast milk. The benefits for the mother must be weighed against the risks for the child. Studies with other topical preparations (ointment) have been used to treat anal fissures on nursing mothers and there were no reported effects in the breastfed infant whilst a number of the known side effects (headache, dizziness, lightheaded) where reported in the mothers.

Observe infants for flushing/discomfort after breastfeeding following use of glyceryl trinitrate ointment. Hale (2010) recommends monitoring for methemoglobinemia and breastfeeding with caution at increased dosages with prolonged exposure, particularly in infants younger than 6 months.

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

Aggravation of angina
Application site reaction
Bradycardia-paradoxical
Burning sensation (local)
Collapse
Contact dermatitis
Dizziness
Erythema at application site
Exfoliative dermatitis
Faintness
Flushing
Glaucoma (closed angle)
Headache
Heartburn
Hypersensitivity reactions
Hypotension
Irritation (localised)
Itching sensation (local)
Light-headedness
Myocardial hypoxia
Nausea
Pallor
Palpitations
Perspiration
Postural hypotension
Pruritus
Purpura
Rash
Reflex tachycardia
Skin reactions
Skin reddening
Syncope
Tachycardia
Transient hypoxaemia
Vomiting
Weakness

Presentation

Transdermal patch formulations of glyceryl trinitrate.

Drugs List

Therapeutic Indications

Uses

Maintenance of venous patency at peripheral infusion sites
Prophylaxis of angina pectoris

Dosage

Adults

Administration

Application period
Application can either be for a continuous period of 24 hours or intermittently, incorporating a patch free interval (usually at night).
Patients already receiving continuous 24 hour nitrate therapy without signs of nitrate tolerance may continue on this regimen provided clinical response is maintained.
Attenuation of effect has occurred in some patients being treated with sustained release nitrate preparations. On the basis of clinical studies it is recommended that in such cases the patch should be applied daily, for a period of approximately 12 hours, with a patch free interval of 8 to 12 hours.
Overnight treatment may be beneficial in nocturnal angina with a nitrate-free interval during the day. These patients may require additional anti-anginal therapy during the day.
Patients with severe angina may need additional anti-anginal therapy during nitrate-free intervals.

Application site for maintenance of venous patency
Apply one 5 mg/24 hour patch distally and close to the site of intravenous cannulation at the time of venepuncture. Ideally, the patch should be changed daily (some manufacturers recommend every three to four days) and a replacement patch applied to a different area of skin.

Contraindications

Systolic blood pressure < 90mmHg
Aortic stenosis
Cardiac tamponade
Cerebrovascular haemorrhage
Constrictive pericarditis
Head trauma
Hypertrophic obstructive cardiomyopathy
Mitral stenosis
Narrow angle glaucoma
Raised intracranial pressure
Severe anaemia
Severe hypovolaemia
Toxic pulmonary oedema

Precautions and Warnings

Children under 18 years
Hypothermia
Ventilation-perfusion mismatch
Acute cardiac failure
Breastfeeding
Hypotension
Hypothyroidism
Hypoxia
Malnutrition
Postural hypotension
Pregnancy
Recent myocardial infarction
Severe hepatic impairment
Severe renal impairment

Not for treatment of acute attacks of angina
Advise ability to drive/operate machinery may be affected by side effects
Not all presentations are licensed for all indications
Discard used patches safely - fold with adhesive edges together
Remove metal containing patch prior to MRI scan
Rotate application sites - avoid applying patch to the same site
Advise patient that postural hypotension may occur
Cross tolerance to other nitrates may develop
Tolerance may develop - consider 8-12hr drug-free interval each day
Withdraw gradually after long-term use
Consider removing patch before cardioversion, defibrillation or diathermy
Discontinue if sensitisation occurs
Discontinue immediately if severe hypotension occurs
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effect enhanced by alcohol

Patients should be advised to dispose of patches carefully to avoid accidental application or use.

Pregnancy and Lactation

Pregnancy

Glyceryl trinitrate should be used with caution during pregnancy.

Glyceryl trinitrate is primarily used for treatment and prevention of angina and therefore experience of use in pregnancy is limited. Glyceryl trinitrate should not be used during pregnancy particularly during the first trimester unless the potential benefits outweigh the unknown risks to the foetus. Schaefer (2007) comments that nitrates may be used in pregnancy for appropriate indications and toxic affects on the foetus have not been reported. Briggs (2011) adds that with smaller doses of nitrates a transient decrease in the mother's blood pressure may occur but does not seem to be sufficient to affect placental perfusion. The use of transdermal glyceryl trinitrate patch may also be effective when longer periods of tocolysis are required.

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 14-17 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

Glyceryl trinitrate should be used with caution during breastfeeding.

It is not known if glyceryl trinitrate passes into breast milk. The benefits for the mother must be weighed against the risks for the child. Studies with other topical preparations (ointment) have been used to treat anal fissures on nursing mothers and there were no reported effects in the breastfed infant whilst a number of the known side effects (headache, dizziness, lightheaded) where reported in the mothers.

Observe infants for flushing/discomfort after breastfeeding following use of glyceryl trinitrate ointment. Hale (2010) recommends monitoring for methemoglobinemia and breastfeeding with caution at increased dosages with prolonged exposure, particularly in infants younger than 6 months.

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

Counselling

Advise patient that severe postural hypotension with light-headedness and dizziness is frequently observed after the consumption of alcohol.

Advise patient that the ability to drive or operate machinery may be affected by side effects such as dizziness, blurred vision and postural hypotension.

Advise patient to dispose of patches carefully to avoid accidental application or use.

Advise patients that the use of NSAID's might diminish the therapeutic response to glyceryl trinitrate. NSAID's should only be self administered under the guidance of a clinician.

Advise patients that patches should be applied to any convenient clean, dry and preferably hairless skin area except the distal part of the extremities. The recommended site is the chest or the outer arm. The site of application should be changed daily, and suitable areas may be shaved if necessary. Subsequent patches should not be applied to the same area of skin until several days have elapsed.
Skincare products should not be used before applying the patch.

Side Effects

Aggravation of angina
Application site reaction
Bradycardia-paradoxical
Burning sensation (local)
Collapse
Contact dermatitis
Dizziness
Erythema at application site
Exfoliative dermatitis
Faintness
Flushing
Glaucoma (closed angle)
Headache
Heartburn
Hypersensitivity reactions
Hypotension
Irritation (localised)
Itching sensation (local)
Light-headedness
Myocardial hypoxia
Nausea
Pallor
Palpitations
Perspiration
Postural hypotension
Pruritus
Purpura
Rash
Reflex tachycardia
Skin reactions
Skin reddening
Syncope
Tachycardia
Transient hypoxaemia
Vomiting
Weakness

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: July 2013

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, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Deponit 5. UCB Pharma Limited. Revised February 2008.
Summary of Product Characteristics: Deponit 10. UCB Pharma Limited. Revised February 2008.

Summary of Product Characteristics: Minitran 5. Meda Pharmaceuticals Ltd. Revised June 2013.
Summary of Product Characteristics: Minitran 10. Meda Pharmaceuticals Ltd. Revised June 2013.
Summary of Product Characteristics: Minitran 15. Meda Pharmaceuticals Ltd. Revised June 2013.

Summary of Product Characteristics: Nitro-Dur 0.2mg/h; 0.4mg/h and 0.6mg/h transdermal patch. Schering-Plough Ltd. Revised January 2011.

Summary of Product Characteristics: Transiderm-Nitro 5 and 10. Novartis Pharmaceuticals UK Limited. Revised November 2012.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 25 August 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
Nitroglycerin Last revised: May 03, 2012
Last accessed: July 5, 2013