ISOKET RETARD Prolonged release tablet Ref.[28019] Active ingredients: Isosorbide dinitrate

These tablets should be used with caution in patients who are suffering from hypothyroidism, hypothermia, malnutrition, severe liver disease or renal disease.

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.

These tablets should be used with particular caution and under medical supervision in the following:

• 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 patients with aortic/mitral valve stenosis

Hypertrophic obstructive cardiomyopathy (HOCM), constrictive pericarditis, cardiac tamponade, low cardiac filling pressures, aortic/mitral valve stenosis, and diseases associated with raised intracranial pressure.

Treatment with these tablets must not be interrupted or stopped to take phosphodiestearase inhibitor products due to the increased risk of inducing an attack of angina pectoris

If these tablets are not taken as indicated with the appropriate dosing interval (see section 4.2) tolerance to the medication could develop.

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, ISDN 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 ISDN alcohol should be avoided as it may potentiate the hypotensive and vasodilating effect of ISDN (see section 4.5).

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Concurrent intake of drugs with blood pressure lowering properties e.g. beta-blockers, calcium antagonists, vasodilators, ACE-inhibitors, monoamine oxidase inhibitors etc. and/or alcohol may potentiate the hypotensive effect of the tablets. Symptoms of circulatory collapse can arise in patients already taking ACE inhibitors.

The concurrent intake of ISDN 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.

The hypotensive effect of nitrates is potentiated by concurrent administration of phosphodiesterase inhibitors (e.g. sildenafil). This might also occur with neuroleptics and tricyclic antidepressants.

Reports suggest that when administered concomitantly, nitrates may increase the blood level of dihydroergotamine and its hypertensive effect.

Saproterin (Tetrahydrobioterine, BH4) is a cofactor for nitric oxide sythetase. Caution is recommended during concomitant use of saproterin-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 mononitrate (ISMN) and others).

The use of isosorbide dinitrate with riociguat, a soluble guanylate cyclase stimulator, is contraindicated (see section 4.3) since concomitant use can cause hypotension.

Pregnancy and lactation

This product should not be used during pregnancy or lactation unless considered essential by the physician.

Fertility

There is no data available on the effect of ISDN on fertility in humans.

Headaches, tiredness, dizziness. These may affect the ability to drive and operate machinery. Patients should not drive or operate machinery if their ability is impaired.

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 (<1/10,000), not known (cannot be estimated from the available data).

During administration of Isoket the following undesirable effects may be observed.

Nervous system disorders

Very common: headache

Common: dizziness, somnolence

Cardiac disorders

Common: tachycardia

Uncommon: angina pectoris aggravated

Vascular disorders

Common: orthostatic hypotension

Uncommon: circulatory collapse (sometimes accompanied by bradyarrhythmia and syncope)

Not known: hypotension

Gastrointestinal disorders

Uncommon: nausea, vomiting

Very rare: heartburn

Skin and subcutaneous tissue disorders

Uncommon: allergic skin reaction (e.g. rash), flushing

Very rare: angioedema, Stevens-Johnson-Syndrome

Not known: exfoliative dermatitis

General disorders and administration site conditions

Common: asthenia

Severe hypotensive responses have been reported for organic nitrates and include nausea, vomiting, restlessness, pallor and excessive perspiration.

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.

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, www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.