Drugs List

Therapeutic Indications

Uses

Prophylaxis of angina pectoris
Treatment of angina pectoris

Contraindications

Children under 18 years
Aortic stenosis
Cardiac tamponade
Cerebrovascular haemorrhage
Circulatory failure
Constrictive pericarditis
Galactosaemia
Head trauma
Hypertrophic obstructive cardiomyopathy
Hypotension
Hypovolaemia
Low filling pressure - if treating acute myocardial infarction
Mitral stenosis
Narrow angle glaucoma
Raised intracranial pressure
Severe anaemia
Toxic pulmonary oedema

Precautions and Warnings

Hypothermia
Predisposition to narrow angle glaucoma
Breastfeeding
G6PD deficiency
Glucose-galactose malabsorption syndrome
Hypothyroidism
Hypoxia
Lactose intolerance
Malnutrition
Pregnancy
Recent myocardial infarction
Severe hepatic impairment
Severe renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Contains lactose
Assess patient's tolerance to treatment
Cross tolerance to other nitrates may develop
Tolerance may occur with prolonged use of large doses
Avoid abrupt withdrawal
Maintain treatment at the lowest effective dose
Advise patient to moderate alcohol intake during treatment
Hypotensive effect enhanced by alcohol
Advise patient not to use for relief of acute attacks

Pregnancy and Lactation

Pregnancy

Isosorbide dinitrate should only be used in pregnancy if it is considered essential.

At the time of writing there is limited published experience concerning the use of isosorbide dinitrate during human pregnancy, however there are no reports of adverse effects occurring. The molecular weight (about 236) is low enough that passage to the foetus should be expected. Dose related toxicity has been observed in rabbits at doses 35 and 150 times the maximum recommended human doses. Studies have shown that isosorbide dinitrate may be effective in reversing the effects of endothelial cell dysfunction which is observed in preeclampsia, but further studies are required (Briggs, 2011). Schaefer (2007) concludes that nitrates may be used in pregnancy for the appropriate indications.

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 isosorbide dinitrate with caution in breastfeeding.

At the time of writing there is limited published experience concerning the use of isosorbide dinitrate during breastfeeding, however there are no reports of adverse effects occurring. The molecular weight (about 236) is low enough that passage into the breast milk should be expected, but effects on the nursing infant are unknown. Schaefer (2007) concludes that the short half life and usually brief use, argue against a toxic risk for the breastfed infant.

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

Allergic skin reactions
Angioedema
Bradyarrhythmias
Cardiac arrhythmias
Cerebral ischaemia
Collapse
Cutaneous vasodilation
Decrease in blood pressure
Dizziness
Drowsiness
Exfoliative dermatitis
Flushing
Glaucoma (closed angle)
Headache
Heartburn
Hypoventilation
Hypoxaemia
Light-headedness
Myocardial hypoxia
Nausea
Pallor
Peripheral oedema
Perspiration
Postural hypotension
Reflex tachycardia
Restlessness
Stevens-Johnson syndrome
Syncope
Tolerance to this drug and cross tolerance to other nitrates
Vomiting
Weakness

Presentation

Modified release formulations of isosorbide dinitrate

Drugs List

Therapeutic Indications

Uses

Prophylaxis of angina pectoris
Treatment of angina pectoris

Dosage

Adults

Elderly

Contraindications

Children under 18 years
Aortic stenosis
Cardiac tamponade
Cerebrovascular haemorrhage
Circulatory failure
Constrictive pericarditis
Galactosaemia
Head trauma
Hypertrophic obstructive cardiomyopathy
Hypotension
Hypovolaemia
Low filling pressure - if treating acute myocardial infarction
Mitral stenosis
Narrow angle glaucoma
Raised intracranial pressure
Severe anaemia
Toxic pulmonary oedema

Precautions and Warnings

Hypothermia
Predisposition to narrow angle glaucoma
Breastfeeding
G6PD deficiency
Glucose-galactose malabsorption syndrome
Hypothyroidism
Hypoxia
Lactose intolerance
Malnutrition
Pregnancy
Recent myocardial infarction
Severe hepatic impairment
Severe renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Contains lactose
Assess patient's tolerance to treatment
Cross tolerance to other nitrates may develop
Tolerance may occur with prolonged use of large doses
Avoid abrupt withdrawal
Maintain treatment at the lowest effective dose
Advise patient to moderate alcohol intake during treatment
Hypotensive effect enhanced by alcohol
Advise patient not to use for relief of acute attacks

Pregnancy and Lactation

Pregnancy

Isosorbide dinitrate should only be used in pregnancy if it is considered essential.

At the time of writing there is limited published experience concerning the use of isosorbide dinitrate during human pregnancy, however there are no reports of adverse effects occurring. The molecular weight (about 236) is low enough that passage to the foetus should be expected. Dose related toxicity has been observed in rabbits at doses 35 and 150 times the maximum recommended human doses. Studies have shown that isosorbide dinitrate may be effective in reversing the effects of endothelial cell dysfunction which is observed in preeclampsia, but further studies are required (Briggs, 2011). Schaefer (2007) concludes that nitrates may be used in pregnancy for the appropriate indications.

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 isosorbide dinitrate with caution in breastfeeding.

At the time of writing there is limited published experience concerning the use of isosorbide dinitrate during breastfeeding, however there are no reports of adverse effects occurring. The molecular weight (about 236) is low enough that passage into the breast milk should be expected, but effects on the nursing infant are unknown. Schaefer (2007) concludes that the short half life and usually brief use, argue against a toxic risk for the breastfed infant.

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

Allergic skin reactions
Angioedema
Bradyarrhythmias
Cardiac arrhythmias
Cerebral ischaemia
Collapse
Cutaneous vasodilation
Decrease in blood pressure
Dizziness
Drowsiness
Exfoliative dermatitis
Flushing
Glaucoma (closed angle)
Headache
Heartburn
Hypoventilation
Hypoxaemia
Light-headedness
Myocardial hypoxia
Nausea
Pallor
Peripheral oedema
Perspiration
Postural hypotension
Reflex tachycardia
Restlessness
Stevens-Johnson syndrome
Syncope
Tolerance to this drug and cross tolerance to other nitrates
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: September 2013

Reference Sources

British National Formulary, 66th Edition (September 2013 - March 2014) Pharmaceutical Press, London.

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.

Summary of Product Characteristics: Isoket Retard 20. UCB pharma Ltd. June 2008.
Summary of Product Characteristics: Isoket Retard 40. UCB pharma Ltd. June 2008.