- Approval Id
- d0f89ef3bb9a6284
- Drug Approval Emc Name
- Monomax XL 60 mg Prolonged Release Tablets
- Drug Name
- Monomax XL 60 mg Prolonged Release Tablets
- Company Name
- Chiesi Limited
- Company Address
- Chiesi Limited, 333 Styal Road, Manchester, M22 5LG
- Company Website
- http://www.chiesi.uk.com
- Company Telephone
- +44 (0) 161 488 5555
- Company Medical Info Direct Line
- +44 (0)1748 827 271
- Company Medical Info Email
- medinfo.uk@chiesi.com
- Atc Code
- C01DA14
- Legal Category
- Pharmacy
- Authorisation Holder
- Chiesi Limited
333 Styal Road
Manchester
M22 5LG
United Kingdom
- Authorisation Number
- PL 08829/0102
- Authorisation Date
- 24th February 2000
- Instruction Authorisation Holder
- Chiesi Limited
333 Styal Road
Manchester
M22 5LG
United Kingdom
- Instruction Authorisation Number
- PL 08829/0102
- Instruction Authorisation Date
- 24th February 2000
- Instruction Composition
- Each prolonged release tablet contains 60mg of isosorbide mononitrate.
For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- Prolonged release tablets
White, oval convex tablets with a score line between "SL" and "60", which are embossed on one side
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
For the prophylactic treatment of angina pectoris4.2 Posology and method of administration
\*\*Method of administration\*\*
Oral use
Tablets may be taken with or without food, and should be swallowed whole and not chewed.
\*\*Posology\*\*
\*Adults\*: Usual adult dose is one isosorbide mononitrate XL 60 mg tablet per day (taken in the morning). If necessary, the dosage may be increased to 120 mg once daily (i.e. 2 x 60mg tablets taken in the morning). The dosage can be titrated to minimise the possibility of headache by initiating treatment with 30mg (half a tablet), for the first two to four days.
\*Paediatric Population\*: Safety and efficacy in children have not been established.
\*Older People\*: There is no evidence of a need for routine dosage adjustment in older people, but special care may be needed in those with increased susceptibility to hypotension or marked hepatic or renal insufficiency.4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
This product should not be given to patients with a known sensitivity to nitrates and a known hypersensitivity to the constituents of the tablets.
Relative contraindications to the use of isosorbide mononitrate are severe cerebral vascular insufficiency and hypotension
Sildenafil has been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contraindicated.
Isosorbide mononitrate is contraindicated in patients with constrictive cardiomyopathy and pericarditis, aortic stenosis, cardiac tamponade, mitral stenosis and severe anaemia.
Patients treated with Monomax XL must not be given Phosphodiesterase Type 5 Inhibitors (e.g. sildenafil).4.4 Special warnings and precautions for use
Isosorbide mononitrate XL 60 mg tablets are not indicated for relief of acute angina attacks; in the event of an acute attack, sublingual or buccal glyceryl trinitrate tablets / sprays should be used.
Isosorbide mononitrate should be used with caution in patients who are predisposed to closed angle glaucoma.
Isosorbide mononitrate should be used with caution in patients suffering from head trauma, cerebral haemorrhage, recent history of myocardial infarction, hypothyroidism, hypothermia, malnutrition, severe liver or renal disease.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.4.5 Interaction with other medicinal products and other forms of interaction
Only limited information is available on the possible interaction between isosorbide mononitrate and other drugs.
Some of the effects of alcohol may be potentiated by this agent.
Vasodilators, antihypertensives and diuretics may potentiate the hypotension caused by nitrates particularly in the elderly.
The hypotensive effects of nitrates are potentiated by concurrent administration of sildenafil.
Concomitant administration of Monomax XL and Phosphodiesterase Type 5 Inhibitors can potentiate the vasodilatory effect of Monomax XL with the potential result of serious side effects such as syncope or myocardial infarction. Therefore, Monomax XL and Phosphodiesterase Type 5 Inhibitors (e.g. sildenafil) must not be given concomitantly.
There is no evidence of interaction with food.4.6 Fertility, pregnancy and lactation
Since its safety and efficacy have not been established, this product should not be used during pregnancy or lactation unless considered essential by the physician.4.7 Effects on ability to drive and use machines
Since postural hypotension with symptoms such as dizziness has been reported, patients should be advised to be careful when driving or operating machinery if they suffer from these symptoms.4.8 Undesirable effects
Most of the adverse reactions are pharmacodynamically mediated and dose dependent. Side effects including flushing and dry skin rashes may occur occasionally. Headache may occur at the onset of treatment which usually disappears after 1-2 weeks of treatment but may be minimised by commencing with low doses of 30mg and gradually increasing the dose. Hypotension, with symptoms such as dizziness and nausea with syncope in isolated cases, has occasionally been reported. These symptoms generally disappear during continued treatment. Pruritis has been reported rarely and myalgia, reported very rarely.
The following definitions of frequencies are used: 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) and Very Rare (<1/10,000).
\*\*Adverse drug reactions by frequency and system organ class (SOC)\*\*
| | | |
| --- | --- | --- |
| \*\*System Organ Class\*\* | \*\*Frequency\*\* | \*\*Reaction\*\* |
| Nervous system disorders | Common | Headache, dizziness |
| | Rare | Fainting |
| Cardiac and vascular disorders | Common | Hypotension, tachycardia |
| Gastrointestinal disorders | Common | Nausea |
| | Uncommon | Vomiting, diarrhoea |
| Skin and subcutaneous tissue disorders | Rare | Rash, pruritus |
| Musculoskeletal and connective tissue disorders | Very rare | Myalgia |
\*\*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.4.9 Overdose
\*\*Symptoms\*\*
A pulsating headache is the commonest.
More serious symptoms are excitation, flushing, cold perspiration, nausea, vomiting, vertigo, syncope, tachycardia and a fall in blood pressure.
\*\*Management\*\*
Induce emesis. Use activated charcoal.
If pronounced hypotension, place the patient in the supine position with legs raised. If necessary, intravenous fluids should be administered.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
Anatomical Therapeutic Chemical (ATC) code: C01D A14;
Vasodilators used in cardiac diseases, organic nitrates
The principal pharmacological action of isosorbide mononitrate, an active metabolite of isosorbide dinitrate, is relaxation of vascular smooth muscle, producing vasodilation of both arteries and veins with the venous effect predominating. The effect of the treatment is dependent on the dose. Low plasma concentrations lead to venous dilation, resulting in peripheral pooling of blood, decreased venous return and reduction in left ventricular end-diastolic pressure (preload). High plasma concentration also dilate the arteries, reducing systemic vascular resistance and arterial pressure and thus a reduction in cardiac after-load. Isosorbide mononitrate may also dilate the coronary arteries directly. By reducing the end-diastolic pressure and volume, the preparation lowers the intramural pressure, this in turn leading to an improvement in subendocardial bloodflow.
The net effect, when administering isosorbide mononitrate, is therefore a reduced workload on the heart and an improved oxygen supply/demand balance in the myocardium.5.2 Pharmacokinetic properties
In man, isosorbide mononitrate is absorbed completely and rapidly following oral administration.
Isosorbide mononitrate is not subject to first pass metabolism by the liver. This reduces the intra- and inter-individual variations in plasma levels, leading to predictable and reproducible clinical effects.
The elimination half-life of isosorbide mononitrate is around 5 hours. The plasma protein binding is less than 5%. The volume of distribution for isosorbide mononitrate is about 0.6 l/kg and total clearance around 115 ml/minute. Elimination is primarily by denitration and conjugation in the liver. The metabolites are excreted mainly via the kidneys. Only about 2% of the dose given is excreted intact via the kidneys.
Impaired liver or kidney functions have no major influence on the pharmacokinetic properties.
Monomax XL is an extended release formulation (Durules). The active substance is released independently of pH, over a 10-hour period. Compared to ordinary tablets the absorption phase is prolonged and the duration of effect is extended. Thus compared to ordinary tablets, the absorption phase is prolonged and the duration of effect is extended.
The extent of bioavailability of Monomax XL is about 90% compared to immediate release tablets. Absorption is not significantly affected by food intake and there is no accumulation during steady state. Monomax XL exhibits dose proportional kinetics up to 120mg. After repeated peroral administration with 60mg once daily, maximal plasma concentration (around 3000 nmol/l) is achieved after around 4 hours. The plasma concentration then gradually falls to under 500 nmol/l at the end of the dosage interval (24 hours after dose intake). The tablets are divisible.
In placebo-controlled studies, Monomax XL once daily has been shown to effectively control angina pectoris both in terms of exercise capacity and symptoms, and also in reducing signs of myocardial ischaemia. The duration of the effect is at least 12 hours; at this point the plasma concentration is at the same level as at around 1 hour after dose intake (around 1300 nmol/l).
Isosorbide mononitrate is effective in monotherapy as well as in combination with chronic β-blocker therapy.
The clinical effects of nitrates may be reduced following repeated administration due to too high and / or constant plasma levels. This can be avoided by allowing low plasma levels for a certain period between doses. Isosorbide mononitrate XL 60mg tablets, when administered once daily in the morning, produces a plasma profile of high levels during the day and low levels during the night. Thus, no development of tolerance with respect to antianginal effect should be seen with Isosorbide mononitrate XL, when 60mg or 120mg is taken once daily in the morning. Rebound phenomenon between doses as described with intermittent nitrate patch therapy has not been seen with Monomax XL.5.3 Preclinical safety data
The accessible data indicate that isosorbide mononitrate has expected pharmacodynamic properties of an organic nitrate ester, has simple pharmacokinetic properties, and is devoid of toxic, mutagenic or oncogenic effects.
- Instruction Pharmaceutical Particulars
- 6.1 List of excipients
Lactose monohydrate
Hypromellose (E.464)
Glyceryl palmitostearate
Maize starch
Magnesium stearate6.2 Incompatibilities
Not applicable6.3 Shelf life
36 months6.4 Special precautions for storage
Store in the original container. Do not store above 25°C.6.5 Nature and contents of container
The tablets are enclosed in blisters composed of 250μm PVC film/25μm aluminium foil.
The blisters are packed into folded printed cardboard cartons with a patient information leaflet. Packs contain 28 or 30 prolonged release tablets.6.6 Special precautions for disposal and other handling
None
- Instruction Content
- ## Composition
Each prolonged release tablet contains 60mg of isosorbide mononitrate.
For the full list of excipients, see section 6.1.
## Pharmaceutical Form
Prolonged release tablets
White, oval convex tablets with a score line between "SL" and "60", which are embossed on one side
## Clinical Particulars
4.1 Therapeutic indications
For the prophylactic treatment of angina pectoris4.2 Posology and method of administration
\*\*Method of administration\*\*
Oral use
Tablets may be taken with or without food, and should be swallowed whole and not chewed.
\*\*Posology\*\*
\*Adults\*: Usual adult dose is one isosorbide mononitrate XL 60 mg tablet per day (taken in the morning). If necessary, the dosage may be increased to 120 mg once daily (i.e. 2 x 60mg tablets taken in the morning). The dosage can be titrated to minimise the possibility of headache by initiating treatment with 30mg (half a tablet), for the first two to four days.
\*Paediatric Population\*: Safety and efficacy in children have not been established.
\*Older People\*: There is no evidence of a need for routine dosage adjustment in older people, but special care may be needed in those with increased susceptibility to hypotension or marked hepatic or renal insufficiency.4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
This product should not be given to patients with a known sensitivity to nitrates and a known hypersensitivity to the constituents of the tablets.
Relative contraindications to the use of isosorbide mononitrate are severe cerebral vascular insufficiency and hypotension
Sildenafil has been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contraindicated.
Isosorbide mononitrate is contraindicated in patients with constrictive cardiomyopathy and pericarditis, aortic stenosis, cardiac tamponade, mitral stenosis and severe anaemia.
Patients treated with Monomax XL must not be given Phosphodiesterase Type 5 Inhibitors (e.g. sildenafil).4.4 Special warnings and precautions for use
Isosorbide mononitrate XL 60 mg tablets are not indicated for relief of acute angina attacks; in the event of an acute attack, sublingual or buccal glyceryl trinitrate tablets / sprays should be used.
Isosorbide mononitrate should be used with caution in patients who are predisposed to closed angle glaucoma.
Isosorbide mononitrate should be used with caution in patients suffering from head trauma, cerebral haemorrhage, recent history of myocardial infarction, hypothyroidism, hypothermia, malnutrition, severe liver or renal disease.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.4.5 Interaction with other medicinal products and other forms of interaction
Only limited information is available on the possible interaction between isosorbide mononitrate and other drugs.
Some of the effects of alcohol may be potentiated by this agent.
Vasodilators, antihypertensives and diuretics may potentiate the hypotension caused by nitrates particularly in the elderly.
The hypotensive effects of nitrates are potentiated by concurrent administration of sildenafil.
Concomitant administration of Monomax XL and Phosphodiesterase Type 5 Inhibitors can potentiate the vasodilatory effect of Monomax XL with the potential result of serious side effects such as syncope or myocardial infarction. Therefore, Monomax XL and Phosphodiesterase Type 5 Inhibitors (e.g. sildenafil) must not be given concomitantly.
There is no evidence of interaction with food.4.6 Fertility, pregnancy and lactation
Since its safety and efficacy have not been established, this product should not be used during pregnancy or lactation unless considered essential by the physician.4.7 Effects on ability to drive and use machines
Since postural hypotension with symptoms such as dizziness has been reported, patients should be advised to be careful when driving or operating machinery if they suffer from these symptoms.4.8 Undesirable effects
Most of the adverse reactions are pharmacodynamically mediated and dose dependent. Side effects including flushing and dry skin rashes may occur occasionally. Headache may occur at the onset of treatment which usually disappears after 1-2 weeks of treatment but may be minimised by commencing with low doses of 30mg and gradually increasing the dose. Hypotension, with symptoms such as dizziness and nausea with syncope in isolated cases, has occasionally been reported. These symptoms generally disappear during continued treatment. Pruritis has been reported rarely and myalgia, reported very rarely.
The following definitions of frequencies are used: 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) and Very Rare (<1/10,000).
\*\*Adverse drug reactions by frequency and system organ class (SOC)\*\*
| | | |
| --- | --- | --- |
| \*\*System Organ Class\*\* | \*\*Frequency\*\* | \*\*Reaction\*\* |
| Nervous system disorders | Common | Headache, dizziness |
| | Rare | Fainting |
| Cardiac and vascular disorders | Common | Hypotension, tachycardia |
| Gastrointestinal disorders | Common | Nausea |
| | Uncommon | Vomiting, diarrhoea |
| Skin and subcutaneous tissue disorders | Rare | Rash, pruritus |
| Musculoskeletal and connective tissue disorders | Very rare | Myalgia |
\*\*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.4.9 Overdose
\*\*Symptoms\*\*
A pulsating headache is the commonest.
More serious symptoms are excitation, flushing, cold perspiration, nausea, vomiting, vertigo, syncope, tachycardia and a fall in blood pressure.
\*\*Management\*\*
Induce emesis. Use activated charcoal.
If pronounced hypotension, place the patient in the supine position with legs raised. If necessary, intravenous fluids should be administered.
## Pharmacological Properties
5.1 Pharmacodynamic properties
Anatomical Therapeutic Chemical (ATC) code: C01D A14;
Vasodilators used in cardiac diseases, organic nitrates
The principal pharmacological action of isosorbide mononitrate, an active metabolite of isosorbide dinitrate, is relaxation of vascular smooth muscle, producing vasodilation of both arteries and veins with the venous effect predominating. The effect of the treatment is dependent on the dose. Low plasma concentrations lead to venous dilation, resulting in peripheral pooling of blood, decreased venous return and reduction in left ventricular end-diastolic pressure (preload). High plasma concentration also dilate the arteries, reducing systemic vascular resistance and arterial pressure and thus a reduction in cardiac after-load. Isosorbide mononitrate may also dilate the coronary arteries directly. By reducing the end-diastolic pressure and volume, the preparation lowers the intramural pressure, this in turn leading to an improvement in subendocardial bloodflow.
The net effect, when administering isosorbide mononitrate, is therefore a reduced workload on the heart and an improved oxygen supply/demand balance in the myocardium.5.2 Pharmacokinetic properties
In man, isosorbide mononitrate is absorbed completely and rapidly following oral administration.
Isosorbide mononitrate is not subject to first pass metabolism by the liver. This reduces the intra- and inter-individual variations in plasma levels, leading to predictable and reproducible clinical effects.
The elimination half-life of isosorbide mononitrate is around 5 hours. The plasma protein binding is less than 5%. The volume of distribution for isosorbide mononitrate is about 0.6 l/kg and total clearance around 115 ml/minute. Elimination is primarily by denitration and conjugation in the liver. The metabolites are excreted mainly via the kidneys. Only about 2% of the dose given is excreted intact via the kidneys.
Impaired liver or kidney functions have no major influence on the pharmacokinetic properties.
Monomax XL is an extended release formulation (Durules). The active substance is released independently of pH, over a 10-hour period. Compared to ordinary tablets the absorption phase is prolonged and the duration of effect is extended. Thus compared to ordinary tablets, the absorption phase is prolonged and the duration of effect is extended.
The extent of bioavailability of Monomax XL is about 90% compared to immediate release tablets. Absorption is not significantly affected by food intake and there is no accumulation during steady state. Monomax XL exhibits dose proportional kinetics up to 120mg. After repeated peroral administration with 60mg once daily, maximal plasma concentration (around 3000 nmol/l) is achieved after around 4 hours. The plasma concentration then gradually falls to under 500 nmol/l at the end of the dosage interval (24 hours after dose intake). The tablets are divisible.
In placebo-controlled studies, Monomax XL once daily has been shown to effectively control angina pectoris both in terms of exercise capacity and symptoms, and also in reducing signs of myocardial ischaemia. The duration of the effect is at least 12 hours; at this point the plasma concentration is at the same level as at around 1 hour after dose intake (around 1300 nmol/l).
Isosorbide mononitrate is effective in monotherapy as well as in combination with chronic β-blocker therapy.
The clinical effects of nitrates may be reduced following repeated administration due to too high and / or constant plasma levels. This can be avoided by allowing low plasma levels for a certain period between doses. Isosorbide mononitrate XL 60mg tablets, when administered once daily in the morning, produces a plasma profile of high levels during the day and low levels during the night. Thus, no development of tolerance with respect to antianginal effect should be seen with Isosorbide mononitrate XL, when 60mg or 120mg is taken once daily in the morning. Rebound phenomenon between doses as described with intermittent nitrate patch therapy has not been seen with Monomax XL.5.3 Preclinical safety data
The accessible data indicate that isosorbide mononitrate has expected pharmacodynamic properties of an organic nitrate ester, has simple pharmacokinetic properties, and is devoid of toxic, mutagenic or oncogenic effects.
## Pharmaceutical Particulars
6.1 List of excipients
Lactose monohydrate
Hypromellose (E.464)
Glyceryl palmitostearate
Maize starch
Magnesium stearate6.2 Incompatibilities
Not applicable6.3 Shelf life
36 months6.4 Special precautions for storage
Store in the original container. Do not store above 25°C.6.5 Nature and contents of container
The tablets are enclosed in blisters composed of 250μm PVC film/25μm aluminium foil.
The blisters are packed into folded printed cardboard cartons with a patient information leaflet. Packs contain 28 or 30 prolonged release tablets.6.6 Special precautions for disposal and other handling
None
