Monocord 20, 40 mg

/ Dexcel

Adults
One tablet to be taken asymmetrically (to allow a nitrate low period) two times a day. The dosage may be increased up to 120 mg per day. Dosage regime should be designed according to the clinical response of the patient.
Tablets should be taken with water on an empty stomach about an hour before or two hours after a meal.
The lowest effective dose should be used.
In patients taking Monocord twice daily, the second dose should be taken 8 hours after the 1st dosage.
Elderly
There is no evidence to suggest that an adjustment of the dosage is necessary in elderly.
Paediatric population
The safety and efficacy of Monocord has yet to be established in children.
Treatment with Monocord, as with any other nitrate, should not be stopped suddenly.
Both the dosage and frequency should be tapered gradually.
Method of administration: For oral administration.

For the treatment of angina pectoris and prevention of anginal attacks, treatment of congestive heart failure.

Hypersensitivity to the active substance or to any of the excipients.
Monocord should not be used in cases of acute myocardial infarction with low filling pressure, acute circulatory failure (shock, vascular collapse), or very low blood pressure (systolic blood pressure below 90 mmHg), 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.
Monocord should not be used in patients with severe anaemia, severe hypotension, closed angle glaucoma or severe 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.
During nitrate therapy, the soluble guanylate cyclase stimulator riociguat must not be use.

This product may give rise to symptoms of postural hypotension and syncope in some patients. Severe postural hypotension with light-headedness and dizziness is frequently observed after the consumption of alcohol.
Monocord should be used with caution in patients who have a recent history of myocardial infarction low filling pressures e.g. in acute myocardial infarction, impaired left ventricular function (left ventricular failure), or orthostatic dysfunction.
Reducing systolic blood-pressure below 90 mmHg must be avoided.
It should also be used with caution in patients who are suffering from hypothyroidism, hypothermia, malnutrition and severe liver or renal disease.
Symptoms of circulatory collapse may arise after the first dose, particularly in patients with labile circulation.
Hypotension induced by nitrates may be accompanied by paradoxical bradycardia and increased angina.
Monocord tablets contain lactose and therefore should not be used in patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
Monocord tablets also contain sucrose and therefore patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
In the event of an acute angina attack, a sublingual treatment such as a GTN spray or tablet should be used instead of Monocord tablets. The onset of action of Monocord is not sufficiently rapid to be useful to treat an acute anginal attack.
If the tablets are not taken as indicated tolerance to the medication could develop. In some patients being treated with slow release preparations, attenuation of effect is observed. In such patients, intermittent therapy may be more appropriate. The lowest effective dose should be used.
Treatment with Monocord, as with any other nitrate, should not be stopped suddenly.
Both the dosage and frequency should be tapered gradually.
In patients with decreased gastrointestinal transit time, a decrease in release of the active ingredient may occur.
Patients who undergo a maintenance treatment with Monocord should be informed that they must not use phosphodiesterase inhibitor-containing products (e.g. sildenafil, tadalafil, vardenafil).
Monocord 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.
Hypoxaemia
Caution should be exercised in patients with hypoxaemia and ventilation/perfusion imbalance due to lung disease or ischaemic heart failure. As a potent vasodilator, isosorbide mononitrate could result in increased perfusion of poorly ventilated areas, worsening of the ventilation/perfusion imbalance, and a further decrease in the arterial partial pressure of oxygen.
During treatment with isosorbide mononitrate alcohol should be avoided as it may potentiate the hypotensive effect of isosorbide mononitrate.

Very common: Headache.
Common: Dizziness (including dizziness postural), somnolence, tachycardia, orthostatic hypotension, asthenia.

Concurrent administration of drugs with blood pressure lowering properties, e.g. beta-blockers, calcium channel blockers, vasodilators, alprostadil, aldesleukin, ACE-inhibitors, monoamine oxidase inhibitors, angiotensin II receptor antagonists etc. and/or alcohol may potentiate the hypotensive effect of Monocord. This may also occur with neuroleptics and tricyclic antidepressants.
The concurrent intake of isosorbide mononitrate with ACE-inhibitors or arterial vasodilators could be a desirable interaction, unless the antihypertensive effects are excessive in which case consider reducing the dose of one or both drugs.
Any blood pressure lowering effect of Monocord will be increased if used together with phosphodiesterase type-5 inhibitors which are used for erectile dysfunction. This might lead to life threatening cardiovascular complications. Patients who are on Monocord therapy therefore must not use phosphodiesterase type-5 inhibitors (e.g. sildenafil, tadalafil, vardenafil).
The use of isosorbide mononitrate with riociguat, a soluble guanylate cyclase stimulator, is contraindicated since concomitant use can cause hypotension.
Reports suggest that concomitant administration of Monocord may increase the blood level of dihydroergotamine and its hypertensive effect.
Sapropterine (Tetrahydrobiopterine, BH4) is a cofactor for nitric oxide synthetase.
Caution is recommended during concomitant use of sapropterine-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).

Pregnancy
Safety in pregnancy has not been established for isosorbide mononitrate. There is data that nitrates are excreted in breast milk and may cause methemoglobinemia in infants. Therefore Monocord 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 mononitrate in human breast milk has not been determined. Therefore caution should be exercised when administered to nursing women.

Animal experience:
In rats and mice, significant lethality at oral doses of 1965 mg/kg and 2581 mg/kg, respectively, was observed.
Human experience:
Symptoms:
– Fall of blood pressure ≤ 90 mmHg
– Paleness
– Sweating
– Weak pulse
– Tachycardia
– Light-headedness on standing
– Headache
– Weakness
– Dizziness
– Nausea
– Vomiting
– Diarrhoea
Methaemoglobinaemia has been reported in patients receiving other organic nitrates.
During isosorbide mononitrate biotransformation nitrite ions are released, which may induce methaemoglobinaemia and cyanosis with subsequent tachypnoea, anxiety, loss of consciousness and cardiac arrest. It cannot be excluded that an overdose of isosorbide mononitrate may cause this adverse reaction.
In very high doses the intracranial pressure may be increased. This might lead to cerebral symptoms.
General procedure:
Stop intake of the drug
-General procedures in the event of nitrate-related hypotension
Patients should be kept horizontal with the head lowered and legs raised
Supply oxygen
Expand plasma volume (i.v. fluids)
Specific treatment for shock (admit patient to intensive care unit)
Special procedure:
Raising the blood pressure if the blood pressure is very low.
Treatment of methaemoglobinaemia
Reduction therapy of choice with vitamin C, methylene-blue or toluidine-blue
Administer oxygen (if necessary)
Initiate artificial ventilation
Hemodialysis (if necessary)
Resuscitation measures
In case of signs of respiratory and circulatory arrest, initiate resuscitation measures immediately.

Contains lactose and sucrose.