NITRONAL Solution for infusion Ref.[7278] Active ingredients: Glyceryl trinitrate

Caution should be exercised in patients with severe liver or renal disease, hypothermia, hypothyroidism.

Nitronal should not be given by bolus injection.

Nitronal contains glucose monohydrate (49mg/ml). This should be considered if Nitronal is to be administered to patients with diabetes mellitus.

Glyceryl Trinitrate 1 mg/ml solution for infusion should be administered using polyethylene or polytetrafluorethylene tubings. Use of polyvinylchloride tubings may lead to a considerable loss of active substance due to adsorption.

Caution should be exercised when glyceryl trinitrate is administered to patients with:

• Hypertrophic obstructive cardiomyopathy, constrictive pericarditis and pericardial tamponade.
• Low filling pressures arising from conditions including acute myocardial infarction, and left ventricular failure. A reduction of the systolic blood pressure below 90 mmHg must be avoided in such situations.
• Aortic and/or mitral stenosis.
• A tendency to orthostatic disturbances of circulatory regulation.
• In volume depleted patients, adequate volume replacement is required at the start of treatment.

Glyceryl trinitrate may potentiate the action of other hypotensive drugs, and the hypotensive and anticholinergic effects of tricyclic anti-depressants.

It may also slow the metabolism of morphine-like analgesics.

The hypotensive effects of glyceryl trinitrate solution for infusion are potentiated by concurrent administration of:

• Phosphodiesterase inhibitors used for the treatment of erectile dysfunction or pulmonary arterial hypertension. A severe and possibly dangerous fall in blood pressure may occur. This can result in collapse, unconsciousness and may be fatal. Such use is therefore contra-indicated (section 4.3). If a patient treated with these drugs for erectile dysfunction or pulmonary arterial hypertension needs a rapidly effective nitrate, he/she should be closely monitored.
• Other vasodilators, β-blockers, calcium antagonists, neuroleptics, alcohol and sapropterin.

If used concomitantly with dihydroergotamine, glyceryl trinitrate solution for infusion may lead to an increase in the DHE level and thus potentiate its hypertensive action.

When heparin and glyceryl trinitrate are used simultaneously, the effects of heparin are reduced. The heparin dosage must be adjusted accordingly while closely monitoring blood coagulation parameters. After discontinuation of glyceryl trinitrate, blood coagulation may be considerably reduced (sharp increase in the PTT), which may necessitate a reduction of the heparin dose.

In patients previously treated with organic nitrates, e.g. isosorbide dinitrate, isosorbide-5-mononitrate, a higher dose of glyceryl trinitrate may be necessary to achieve the desired haemodynamic effect.

Fertility

Animal studies did not indicate harmful effects with respect to fertility. However, the relevance of these animal findings to man is unknown.

Pregnancy

For glyceryl trinitrate no clinical data on exposed pregnancies are available.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.

Lactation

It is unknown if glyceryl trinitrate or its metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue/abstain from breast-feeding or to discontinue/abstain from glyceryl trinitrate therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Even when used as directed, this drug may affect the ability to drive or operate machinery.

This can occur in particular at the beginning of the treatment, with an increase of the dosage, when changing the medicinal product or when used in combination with alcohol.

Adverse reactions are listed below in descending order by frequency of occurrence.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Very common (≥1/10), Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Very rare: Methaemoglobinaemia

Psychiatric disorder

Very rare: Restlessness

Nervous system disorders

Very common: Headache*

Common: Dizziness, Drowsiness

Uncommon: Syncope

Very rare: Cerebral ischaemia**

Cardiac disorders

Common: Tachycardia

Uncommon: Enhanced angina pectoris symptoms, Bradycardia, Cyanosis, Cardiac disorders

Vascular disorders

Common: Orthostatic hypotension*

Uncommon: Facial flushing, Circulatory collapse

Gastrointestinal disorders

Uncommon: Nausea, vomiting

Respiratory, thoracic and mediastinal disorders

Very rare: Impairment of respiration***

Skin and subcutaneous tissue disorders

Very rare: Exfoliative dermatitis, Drug rash

General disorders and administration site conditions

Common: Asthenia

Not known: Drug tolerance****, Diaphoresis

Investigations

Common: Blood pressure decreased*

* Particularly upon initiation of therapy and following an increase in dose.
** Glyceryl trinitrate-induced hypotension may cause cerebral ischaemia.
*** During the administration of Nitronal, a transient hypoxaemia may occur due to relative redistribution of the blood flow in hypoventilated alveolar regions, which, in patients with coronary heart disease, may lead to ischaemia.
**** The development of tolerance and the occurrence of cross tolerance to other nitro compounds have been described. In order to avoid attenuation or loss of effect, high continuous dosage should be avoided.

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: Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.

Glyceryl trinitrate is adsorbed onto administration systems composed of polyvinyl chloride, see 6.6.