Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Milpharm Limited, Ares, Odyssey Business Park, West End Road, South Ruislip HA4 6QD, United Kingdom
Isosorbide mononitrate tablets should not be used in cases of acute myocardial infarction with low filling pressures, acute circulatory failure (shock, vascular collapse), or very low blood pressure, hypertrophic obstructive cardiomyopathy (HOCM), constrictive pericarditis, cardiac tamponade, low cardiac filling pressures, aortic/mitral valve stenosis and diseases associated with a raised intra-cranial pressure e.g. following a head trauma and including cerebral haemorrhage.
Hypersensitivity to the active substance, other nitrates or to any of the excipients listed in section 6.1.
Isosorbide mononitrate Tablets should not be used in patients with severe anaemia, severe hypotension, closed angle glaucoma or hypovolaemia.
Phosphodiesterase type-5 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 (see section 4.5)
During nitrate therapy, the soluble guanylate cyclase stimulator riociguat must not be used (see section 4.5).
Isosorbide mononitrate Tablets should be used with caution in patients who have recent history of myocardial infarction, low filling pressures e.g. in acute myocardial infarction, impaired left ventricular function (left ventricular failure). Reducing systolic blood-pressure below 90 mmHg must be avoided. Also in patients who are suffering from hypothyroidism, hypothermia, malnutrition and severe liver or renal disease.
Symptoms of circulatory collapse may arise after the initial dose, particularly in patients with labile circulation.
This product may give rise to postural hypotension and syncope in some patients. Severe postural hypotension with light-headedness and dizziness is frequently observed after the consumption of alcohol.
Hypotension induced by nitrates may be accompanied by paradoxical bradycardia and increased angina.
Isosorbide mononitrate Tablets contain lactose and therefore should not be used in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
In the event of an acute angina attack, a sublingual treatment such as a GTN spray or tablet should be used instead of Isosorbide mononitrate Tablets.
If the tablets are not taken as indicated (see section 4.2), tolerance to the medication could develop. The lowest effective dose should be used.
Treatment with Isosorbide mononitrate, as with any other nitrate, should not be stopped suddenly. Both the dosage and frequency should be tapered gradually (see section 4.2)
Patients who undergo a maintenance treatment with Isosorbide mononitrate tablets would be informed that they must not use phosphodiesterase inhibitor-containing products (e.g. sildenafil, tadalafil, vardenafil).
Isosorbide mononitrate tablets therapy should not be interrupted to take phosphodiesterase inhibitor-containing products (e.g. sildenafil, tadalafil, vardenafil), because the risk of inducing an attack of angina pectoris could increase by doing so (see section 4.3 and 4.5).
Concurrent administration of drugs with blood pressure lowering properties, e.g. beta-blockers, calcium channel blockers, vasodilators, alprostadil, aldesleukin, angiotensin II receptor antagonists etc. and/or alcohol may potentiate the hypotensive effects of Isosorbide mononitrate Tablets. This may occur with neuroleptics and tricyclic antidepressants.
The hypotensive effects of nitrates are potentiated by concurrent administration of phosphodiesterase type-5-inhibitors, which are used for erectile dysfunction (see special warning and contraindications). This may lead to life threatening cardiovascular complications. Patients who are on Isosorbide mononitrate therapy therefore must not use phosphodiesterase type-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil).
Reports suggest that concomitant administration of Isosorbide mononitrate tablets may increase the blood levels of dihydroergotamine and its hypertensive effects.
Saproterine (Tetrahydropterine, BH4) is a cofactor for nitric oxide synthetase. Caution is recommended during concomitant use of saproterine-containing medicine with all agents that cause vasodilation by affecting nitric oxide (NO) metabolism or action, including classical NO donors (e.g. glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), isosorbide 5-mononitrate (5-ISMN) and others).
The use of isosorbide mononitrate with riociguat, a soluble guanylate cyclase stimulator, is contraindicated (see section 4.3) since concomitant use can cause hypotension.
No data have been reported which would indicate the possibility of adverse effects resulting from the use of isosorbide mononitrate in pregnancy. Safety in pregnancy however has not been established, Isosorbide mononitrate should only be used in pregnancy and during lactation if, in the opinion of the physician, the possible benefits of treatment outweigh the hazards.
It is not known whether nitrates are excreted in human milk and therefore caution should be exercised when administered to nursing women.
There is no data available on the effect of isosorbide mononitrate on fertility in humans.
Dizziness, tiredness or blurred vision might occur at the start of the treatment. The patient should therefore be advised that if affected, they should not drive or operate machinery. This effect may be increased by alcohol.
Undesirable effects frequencies are defined as: very common (≥1/10), common (≥1/100<1/10), uncommon (≥1/1,000<1/100), rare (≥1/10,000<1/1,000), very rare (<10,000), not known (cannot be estimated from the available data).
Very common: headache
Common: dizziness (including dizziness postural), somnolence
Common: tachycardia
Uncommon: angina pectoris aggravated
Common: orthostatic hypotension
Uncommon: circulatory collapse (sometimes accompanied by bradyarrhythmia and syncope)
Not known: hypotension
Uncommon: nausea, vomiting
Very rare: heartburn
Uncommon: allergic skin reactions (e.g. rash), flushing
Not known: dermatitis exfoliative
Not known: angioedema
Common: asthenia
A very common (>10% of patients) adverse reaction to Isosorbide mononitrate Tablets is throbbing headache. The incidence of headache diminishes gradually with time and continued use.
At the start of therapy or when the dosage is increased, hypotension and/or light-headedness in the upright position are commonly observed (i.e. in 1-10% of patients). These symptoms may be associated with dizziness, drowsiness, reflex tachycardia and a feeling of weakness.
Infrequently (i.e. in less than 1% patients) nausea, vomiting, flushing and allergic skin reactions (e.g. rash) may occur sometimes severely.
Severe hypotensive responses have been reported for organic nitrates and include nausea, vomiting, restlessness pallor and excessive perspiration. During treatment with Isosorbide Mononitrate Tablets, a temporary hypoxemia 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. Uncommonly severe hypotension may lead to enhanced angina symptoms.
A few reports of heartburn most likely due to a nitrate induced sphincter relaxation have been reported.
Tachycardia and paroxysmal bradycardia have been reported.
Reporting suspected adverse reactions after authorisation of the medicinal products 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.
None known.
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