Isosorbide dinitrate Other names: Dilatrate

Use of alcohol may produce severe hypotension and collapse.

Othostatic hypotension may occur with the combined use of calcium channel blockers, anti-hypertensive agents, phenothiazines and tricyclic anti-depressants.

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.

Reports suggest that, when administered concomitantly, (isosorbide dinitrate) may increase the blood level of dihydroergotamine and its hypertensive effect.

Isosorbide dinitrate can act as a physiological antagonist to noradrenaline (norepinephrine), acetylcholine, histamine and other agents.

Sapropterin (Tetrahydrobiopterine, BH4) is a cofactor for nitric oxide synthetase. Caution is recommended during concomitant use of sapropterin-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).

There is a possibility of precipitating haemolysis in patients with G6PD deficiency.

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.

Isosorbide dinitrate should be used with caution and under medical supervision in patients who are suffering from:

• hypothyroidism
• malnutrition
• severe liver or renal disease
• hypothermia
• orthostatic syndrome

Oral administration

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

Intravenous / Intra-coronary administration

No data have been reported which would indicate the possibility of adverse effect resulting from the use of isosorbide dinitrate in pregnancy. Safety in pregnancy, however, has not been established. Isosorbide dinitrate should only be used in pregnancy and during lactation if, in the opinion of the physician, the possible benefits of treatment outweigh the possible hazards.

Oral administration

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

Intravenous / Intra-coronary administration

Available evidence is inconclusive or inadequate for determining infant risk when used during breastfeeding. There is data that nitrates are excreted in breast milk and may cause methemoglobinemia in infants. The extent of excretion of isosorbide dinitrate and its metabolites in human breast milk has not been determined. Therefore, caution is appropriate when administering this agent to lactating women.

Fertility

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

Headaches, tiredness, dizziness. These may affect the ability to drive and operate machinery. As for other drugs which produce changes in blood pressure, patients taking isosorbide dinitrate should be warned not to drive or operate machinery if they experience dizziness or related symptoms.

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 isosorbide dinitrate 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.