- Approval Id
- 8c62f2e501441a1b
- Drug Approval Emc Name
- Isosorbide Dinitrate Tablets 10 mg
- Drug Name
- Isosorbide Dinitrate Tablets 10 mg
- Company Name
- Chemidex Pharma Ltd
- Company Address
- 7 Egham Business Village, Crabtree Road, Egham, Surrey, TW20 8 RB, UK
- Company Website
- http://www.chemidex.co.uk
- Company Telephone
- +44 (0)1784 477 167
- Company Medical Info Direct Line
- +44 (0)1784 477167
- Company Medical Info Email
- info@chemidex.co.uk
- Atc Code
- C01DA14
- Legal Category
- Pharmacy
- Authorisation Holder
- CHEMIDEX PHARMA LIMITED
8a CRABTREE ROAD
EGHAM
SURREY
TW20 8RN
UNITED KINGDOM
- Authorisation Number
- PL 17736/0107
- Authorisation Date
- 03/04/2009
- Instruction Authorisation Holder
- CHEMIDEX PHARMA LIMITED
8a CRABTREE ROAD
EGHAM
SURREY
TW20 8RN
UNITED KINGDOM
- Instruction Authorisation Number
- PL 17736/0107
- Instruction Authorisation Date
- 03/04/2009
- Instruction Composition
- Each tablet contains diluted isosorbide dinitrate equivalent to 10 mg isosorbide dinitrate.
Excipients with known effect:
One tablet contains 30 mg lactose and 80 mg sucrose.
For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- Tablets
White round tablets marked 'IDN 10' on one side
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
Prophylaxis of angina pectoris; congestive cardiac failure.4.2 Posology and method of administration
Posology
\*Adults and elderly patients\*
One or two tablets taken three or four times daily.
\*Paediatric population\*
The safety and efficacy of Isosorbide Dinitrate Tablets 10 mg has not yet been established in children.
Method of administration
For oral administration.4.3 Contraindications
Hypersensitivity to the active substance, other nitrates or to any of the excipients.
Acute myocardial infarction with low filling pressures, acute circulatory failure (shock, vascular collapse), severe hypotension, hypertrophic obstructive cardiomyopathy (HOCM), constrictive pericarditis, cardiac tamponade, low cardiac filling pressures, aortic/mitral valve stenosis and disease associated with a raised intra-cranial pressure e.g. following a head trauma and including cerebral haemorrhage, marked anaemia, hypovolaemia.
Phosphodiesterase inhibitors (e.g.sildenafil, tadalafil and vardenafil) have been shown to potentiate the hypotensive effects of nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contraindicated.4.4 Special warnings and precautions for use
These tablets should be used with caution in patients who are suffering from hypothyroidism, hypothermia, malnutrition, angle closure glaucoma, severe hepatic or renal impairment.
Symptoms of circulatory collapse may arise after the first dose, particularly in patients with labile circulation.
This product may give rise to symptoms of postural hypotension and syncope in some patients.
Tolerance and cross-tolerance to other nitrates and nitrites may occur.
This medicine contains lactose and sucrose. Patients with rare hereditary problems of fructose intolerance, galactose intolerance, galactosaemia, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.4.5 Interaction with other medicinal products and other forms of interaction
The hypotensive effects of nitrates are potentiated by concurrent administration of phosphodiestearase inhibitors (e.g. sildenafil, tadalafil and vardenafil). This might lead to life threatening cardiovascular complications. Concurrent use is contraindicated (see Section 4.3).
Concurrent intake of drugs with blood pressure lowering properties e.g. betablockers, calcium antagonists, vasodilators, alprostadil, aldesleukin, angiotensin II receptor antagonists etc. and/or alcohol may potentiate the hypotensive effect of the tablets. This may also occur with neuroleptics and tricyclic antidepressants.
Symptoms of circulatory collapse can arise in patients already taking ACE inhibitors. Nitrate preparations can act as physiological antagonists to noradrenaline, acetylcholine, histamine and other agents.4.6 Fertility, pregnancy and lactation
Pregnancy and breast-feeding
Safety in pregnancy has not been established for isosorbide dinitrate. There is data that nitrates are excreted in breast milk and may cause methemoglobinemia in infants. Therefore, Isosorbide Dinitrate Tablets 10 mg should only be used in pregnancy and during lactation if, in the opinion of the physician, the possible benefits of treatment outweigh the hazards.
Breast-feeding
The extent of excretion of isosorbide dinitrate in human breast milk has not been determined. Therefore, caution should be exercised when administered to nursing women.
Fertililty
No data on effects of fertility are available.4.7 Effects on ability to drive and use machines
Isosorbide Dinitrate Tablets 10 mg has minor influence on the ability to drive and use machines. Headache, tiredness and dizziness may occur. Patients are advised not to drive or operate machinery if so affected.4.8 Undesirable effects
Headache, dizziness, fatigue, palpitations, orthostatic hypotension, and flushing may occur at the beginning of treatment. These reactions are usually controlled by lowering the dose; and tend to decline with time.
Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/100,000), not known (cannot be estimated from the available data).
\*\*Immune system disorders\*\*
\*\*Uncommon:\*\* allergic skin reaction (e.g. rash) which may sometimes be severe.
\*\*Nervous system disorders\*\*
\*\*Very common:\*\* headache. The incidence of headache diminishes gradually with time and continued use.
\*\*Cardiac disorders\*\*
\*\*Not known:\*\* hypoxaemia. During treatment with these tablets, a temporary hypoxaemia may occur due to a relative redistribution of the blood flow in hypoventilated alveolar areas. Particularly in patients with coronary artery disease this may lead to a myocardial hypoxia.
\*\*Vascular disorders\*\*
\*\*Common:\*\* hypotension. At start of therapy or when the dosage is increased, hypotension and/or light-headedness on standing may occur. These symptoms may be associated with dizziness, drowsiness, reflex tachycardia, and a feeling of weakness.
\*\*Uncommon:\*\* flushing.
Collapse may occur (sometimes accompanied by bradyarrhythmia and syncope).
Severe hypotension may lead to enhanced angina symptoms.
\*\*Not known:\*\* severe hypotensive responses have been reported for organic nitrates and include nausea, vomiting, restlessness, pallor and excessive perspiration.
\*\*Gastrointestinal disorders and administration site conditions\*\*
\*\*Uncommon:\*\* nausea, vomiting
\*\*Not known:\*\* a few reports of heartburn, most likely due to a nitrate induced sphincter relaxation have been recorded.
\*\*Skin and subcutaneous tissue disorders\*\*
\*\*Very rare:\*\* Stevens-Johnson syndrome, angioedema
\*\*Not known:\*\* exfoliative dermatitis.
\*\*Reporting of suspected adverse reactions\*\*
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose
Overdose should be treated symptomatically. Symptoms of hypotension may be treated by elevation of the legs.
If large numbers of tablets have recently been swallowed, gastric lavage may be employed.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vasodilators used in cardiac diseases, ATC Code: CO1D A 14
Isosorbide Dinitrate produces venodilatation by relaxing the smooth muscle of the walls of the veins. Venodilatation allows blood to pool in the veins so reducing venous return to the heart. A reduced venous return improves perfusion of the myocardium. Myocardial wall tension is also reduced so the oxygen demand of the heart is decreased. Improved myocardial perfusion and reduced oxygen decrease the incidence and severity of anginal attacks.
Preload reduction is of benefit in congestive cardiac failure.5.2 Pharmacokinetic properties
Isosorbide Dinitrate is rapidly and consistently absorbed following oral administration and exhibits dose-proportional bioavailability in the 10-120mg dosage range following single doses with the following kinetic parameters:
| | | |
| --- | --- | --- |
| | Tmax: T½, Elim: Cmax: | 0.5-1 hrs Approx 1 hr 0.5-1.5ng/ml per 1mg administered |
Isosorbide Dinitrate is rapidly and extensively converted to the pharmacologically active 2 and 5 Mononitrate derivatives following oral administration.5.3 Preclinical safety data
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
- Instruction Pharmaceutical Particulars
- 6.1 List of excipients
Lactose monohydrate
Compressible sugar
Colloidal silicon dioxide
Magnesium stearate6.2 Incompatibilities
Not applicable.6.3 Shelf life
5 years.6.4 Special precautions for storage
Store below 25°C6.5 Nature and contents of container
Tamper evident containers composed of:
A white or grey polypropylene body, and white or grey low-density polyethylene closure.
Pack sizes: 30, 56, 60, 90, 100, 120, 180 and 240 tablets.
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling
No special precautions.
- Instruction Content
- ## Composition
Each tablet contains diluted isosorbide dinitrate equivalent to 10 mg isosorbide dinitrate.
Excipients with known effect:
One tablet contains 30 mg lactose and 80 mg sucrose.
For the full list of excipients, see section 6.1.
## Pharmaceutical Form
Tablets
White round tablets marked 'IDN 10' on one side
## Clinical Particulars
4.1 Therapeutic indications
Prophylaxis of angina pectoris; congestive cardiac failure.4.2 Posology and method of administration
Posology
\*Adults and elderly patients\*
One or two tablets taken three or four times daily.
\*Paediatric population\*
The safety and efficacy of Isosorbide Dinitrate Tablets 10 mg has not yet been established in children.
Method of administration
For oral administration.4.3 Contraindications
Hypersensitivity to the active substance, other nitrates or to any of the excipients.
Acute myocardial infarction with low filling pressures, acute circulatory failure (shock, vascular collapse), severe hypotension, hypertrophic obstructive cardiomyopathy (HOCM), constrictive pericarditis, cardiac tamponade, low cardiac filling pressures, aortic/mitral valve stenosis and disease associated with a raised intra-cranial pressure e.g. following a head trauma and including cerebral haemorrhage, marked anaemia, hypovolaemia.
Phosphodiesterase inhibitors (e.g.sildenafil, tadalafil and vardenafil) have been shown to potentiate the hypotensive effects of nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contraindicated.4.4 Special warnings and precautions for use
These tablets should be used with caution in patients who are suffering from hypothyroidism, hypothermia, malnutrition, angle closure glaucoma, severe hepatic or renal impairment.
Symptoms of circulatory collapse may arise after the first dose, particularly in patients with labile circulation.
This product may give rise to symptoms of postural hypotension and syncope in some patients.
Tolerance and cross-tolerance to other nitrates and nitrites may occur.
This medicine contains lactose and sucrose. Patients with rare hereditary problems of fructose intolerance, galactose intolerance, galactosaemia, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.4.5 Interaction with other medicinal products and other forms of interaction
The hypotensive effects of nitrates are potentiated by concurrent administration of phosphodiestearase inhibitors (e.g. sildenafil, tadalafil and vardenafil). This might lead to life threatening cardiovascular complications. Concurrent use is contraindicated (see Section 4.3).
Concurrent intake of drugs with blood pressure lowering properties e.g. betablockers, calcium antagonists, vasodilators, alprostadil, aldesleukin, angiotensin II receptor antagonists etc. and/or alcohol may potentiate the hypotensive effect of the tablets. This may also occur with neuroleptics and tricyclic antidepressants.
Symptoms of circulatory collapse can arise in patients already taking ACE inhibitors. Nitrate preparations can act as physiological antagonists to noradrenaline, acetylcholine, histamine and other agents.4.6 Fertility, pregnancy and lactation
Pregnancy and breast-feeding
Safety in pregnancy has not been established for isosorbide dinitrate. There is data that nitrates are excreted in breast milk and may cause methemoglobinemia in infants. Therefore, Isosorbide Dinitrate Tablets 10 mg should only be used in pregnancy and during lactation if, in the opinion of the physician, the possible benefits of treatment outweigh the hazards.
Breast-feeding
The extent of excretion of isosorbide dinitrate in human breast milk has not been determined. Therefore, caution should be exercised when administered to nursing women.
Fertililty
No data on effects of fertility are available.4.7 Effects on ability to drive and use machines
Isosorbide Dinitrate Tablets 10 mg has minor influence on the ability to drive and use machines. Headache, tiredness and dizziness may occur. Patients are advised not to drive or operate machinery if so affected.4.8 Undesirable effects
Headache, dizziness, fatigue, palpitations, orthostatic hypotension, and flushing may occur at the beginning of treatment. These reactions are usually controlled by lowering the dose; and tend to decline with time.
Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/100,000), not known (cannot be estimated from the available data).
\*\*Immune system disorders\*\*
\*\*Uncommon:\*\* allergic skin reaction (e.g. rash) which may sometimes be severe.
\*\*Nervous system disorders\*\*
\*\*Very common:\*\* headache. The incidence of headache diminishes gradually with time and continued use.
\*\*Cardiac disorders\*\*
\*\*Not known:\*\* hypoxaemia. During treatment with these tablets, a temporary hypoxaemia may occur due to a relative redistribution of the blood flow in hypoventilated alveolar areas. Particularly in patients with coronary artery disease this may lead to a myocardial hypoxia.
\*\*Vascular disorders\*\*
\*\*Common:\*\* hypotension. At start of therapy or when the dosage is increased, hypotension and/or light-headedness on standing may occur. These symptoms may be associated with dizziness, drowsiness, reflex tachycardia, and a feeling of weakness.
\*\*Uncommon:\*\* flushing.
Collapse may occur (sometimes accompanied by bradyarrhythmia and syncope).
Severe hypotension may lead to enhanced angina symptoms.
\*\*Not known:\*\* severe hypotensive responses have been reported for organic nitrates and include nausea, vomiting, restlessness, pallor and excessive perspiration.
\*\*Gastrointestinal disorders and administration site conditions\*\*
\*\*Uncommon:\*\* nausea, vomiting
\*\*Not known:\*\* a few reports of heartburn, most likely due to a nitrate induced sphincter relaxation have been recorded.
\*\*Skin and subcutaneous tissue disorders\*\*
\*\*Very rare:\*\* Stevens-Johnson syndrome, angioedema
\*\*Not known:\*\* exfoliative dermatitis.
\*\*Reporting of suspected adverse reactions\*\*
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose
Overdose should be treated symptomatically. Symptoms of hypotension may be treated by elevation of the legs.
If large numbers of tablets have recently been swallowed, gastric lavage may be employed.
## Pharmacological Properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vasodilators used in cardiac diseases, ATC Code: CO1D A 14
Isosorbide Dinitrate produces venodilatation by relaxing the smooth muscle of the walls of the veins. Venodilatation allows blood to pool in the veins so reducing venous return to the heart. A reduced venous return improves perfusion of the myocardium. Myocardial wall tension is also reduced so the oxygen demand of the heart is decreased. Improved myocardial perfusion and reduced oxygen decrease the incidence and severity of anginal attacks.
Preload reduction is of benefit in congestive cardiac failure.5.2 Pharmacokinetic properties
Isosorbide Dinitrate is rapidly and consistently absorbed following oral administration and exhibits dose-proportional bioavailability in the 10-120mg dosage range following single doses with the following kinetic parameters:
| | | |
| --- | --- | --- |
| | Tmax: T½, Elim: Cmax: | 0.5-1 hrs Approx 1 hr 0.5-1.5ng/ml per 1mg administered |
Isosorbide Dinitrate is rapidly and extensively converted to the pharmacologically active 2 and 5 Mononitrate derivatives following oral administration.5.3 Preclinical safety data
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
## Pharmaceutical Particulars
6.1 List of excipients
Lactose monohydrate
Compressible sugar
Colloidal silicon dioxide
Magnesium stearate6.2 Incompatibilities
Not applicable.6.3 Shelf life
5 years.6.4 Special precautions for storage
Store below 25°C6.5 Nature and contents of container
Tamper evident containers composed of:
A white or grey polypropylene body, and white or grey low-density polyethylene closure.
Pack sizes: 30, 56, 60, 90, 100, 120, 180 and 240 tablets.
Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling
No special precautions.
