SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Isosorbide Dinitrate 0.05% Solution for Injection.

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Isosorbide Dinitrate 25mg in 50ml. Equivalent to 0.5mg isosorbide dinitrate per ml.

3. PHARMACEUTICAL FORM

Solution for injection.

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

•    Treatment of unresponsive left ventricular failure, secondary to acute myocardial

infarction.

•    Unresponsive left ventricular failure of various aetiologies.

•    Severe or unstable angina pectoris.

•    To facilitate or prolong balloon inflation and to prevent or relieve coronary spasm during

percutaneous transluminal coronary angioplasty.

4.2 Posology and method of administration

Avoid administration through PVC tubing and giving sets, because of adsorption of ISDN into plastic.

Intravenous administration: Dosage should be adjusted according to patient response. Typically, a dose of between 2mg and 12mg per hour is suitable, although doses of up to 20mg per hour may be necessary.

Isosorbide Dinitrate 0.05% can be administered undiluted by slow intravenous infusion using a syringe pump.

Intracoronary administration: Isosorbide Dinitrate 0.05% can be injected directly by this route according to the proposed dosage schedule. The usual dose is 1mg given as a bolus injection prior to balloon inflation. Additional doses may be given, not exceeding 5mg over 30 minutes.

The safety and efficacy of Isosorbide Dinitrate 0.05% has not been established in children.

No modifications to the dosage are necessary for elderly patients.

Isosorbide Dinitrate 0.05% is presented in 50ml vials intended for single use only.

4.3 Contraindications

Use of Isosorbide Dinitrate 0.05% is contra-indicated in patients with known hypersensitivity to nitrates, marked anaemia, cerebral haemorrhage, trauma, hypovolaemia and severe hypotension.

Isosorbide Dinitrate 0.05% must not be used in cases of circulatory collapse or low filling pressure.

Treatment of cardiogenic shock with Isosorbide Dinitrate 0.05% should only be undertaken if means of maintaining an adequate diastolic pressure is available.

Sildenafil has been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contraindicated.

4.4 Special warnings and precautions for use

Isosorbide Dinitrate 0.05% should be used with caution in patients who are predisposed to closed angle glaucoma, and in patients suffering from hypothyroidism, malnutrition, severe liver or renal disease or hypothermia.

4.5 Interactions with other medicinal products and other forms of interaction

Some of the effects of alcohol may be potentiated by this medication. The effects of anti-hypertensive drugs may be enhanced.

Hypotensive effects of nitrates are potentiated by concurrent administration of sildenafil (Viagra). This might also occur with neuroleptics and tricyclic antidepressants.

4.6 Pregnancy and lactation

The safety of this medicinal product for human use in pregnancy has not been established. However, no data have been reported that suggest adverse effects occur as a result of using isosorbide dinitrate during pregnancy. Isosorbide dinitrate should only be used during pregnancy and lactation if the benefits of treatment outweigh the possible hazards.

4.7 Effects on ability to drive and use machines

None stated.

4.8 Undesirable effects

Headache, nausea and tachycardia may occur during administration. Consistent with the known vasodilatory effects of isosorbide dinitrate, a sharp fall in the systemic arterial pressure may occur requiring close attention to pulse and blood pressure during administration.

4.9 Overdose

If arterial blood pressure drops below 99mmHg and if heart rate increases above 10% of its initial value, administration should be discontinued to allow a return to pretreatment levels. If hypotension persists, measures should be taken to increase blood pressure.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Isosorbide dinitrate is a potent venodilator and arterial dilator. It reduces systemic arterial pressure in a dose-related manner and, by causing peripheral venous pooling, reduces venous return and hence ventricular filling pressure and cardiac workload. Like all other nitrates, isosorbide dinitrate dilates coronary arteries and relieves coronary artery spasm. An attenuation of the hypotensive and venodilator effects may be observed during long term therapy.

5.2 Pharmacokinetic properties

Plasma protein binding of isosorbide dinitrate is about 30% and the volume of distribution is large (reported at between 100 and 600 litres). Mean half-life is about 1 hour but will be prolonged after chronic dosing. Metabolism of isosorbide dinitrate occurs in the liver by denitration and glucuronidation. Both the 2- and the 5-mononitrates are biologically active. Only traces of the unchanged drug are eliminated in the urine. About 80% of the dose of isosorbide dinitrate can be recovered as metabolites in the urine within 24 hours.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride Water for injections

6.2 Incompatibilities

The use of PVC giving sets and containers should be avoided as significant losses of the active ingredient by adsorption can occur.

6.3 Shelf life

Unopened: 24 months.

After first opening: once opened, the product should be used immediately and any unused drug discarded.

6.4 Special precautions for storage

Keep container (vials) in the outer carton. Store vials upright.

6.5 Nature and contents of container

Isosorbide Dinitrate 0.05% is presented in a 50ml vial made from clear Type II glass, sealed with a bromobutyl rubber stopper and an aluminium tamper proof flip-top cap. Each outer carton contains 10 vials.

6.6 Instructions for use/handling

The injection is for single dose use only.

The injection should not be used if particles are present.

Isosorbide Dinitrate 0.05% may be administered undiluted. Once opened, the product should be used immediately and any unused drug discarded.

Isosorbide Dinitrate 0.05% is compatible with commonly employed infusion fluids. It is compatible with glass infusion bottles and infusion packs made from polyethylene. A syringe pump with a glass or plastic syringe may also be used for infusion.

Isosorbide Dinitrate solutions diluted with Sodium Chloride Injection BP or Glucose Injection BP have been shown to be chemically and physically stable for 72 hours at 25°C, when stored in polypropylene or glass containers, protected from light.

From a microbiological point of view, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

South Devon Healthcare

Torbay PMU

Long Road

Paignton

Devon

TQ47TW

8.    MARKETING AUTHORISATION NUMBER

PL 13079/0002

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10/06/2010

10    DATE OF REVISION OF THE TEXT

16/12/1999