1. Name Of The Medicinal Product
Nitronal®
2. Qualitative And Quantitative Composition
Glyceryl trinitrate 1 mg/ml.
3. Pharmaceutical Form
Solution for infusion.
4. Clinical Particulars
4.1 Therapeutic Indications
(1) Unresponsive congestive heart failure, including that secondary to acute myocardial infarction.
(2) Refractory unstable angina pectoris and coronary insufficiency, including Prinzmetal's angina.
(3) Control of hypertensive episodes and / or myocardial ischaemia during and after cardiac surgery. For the induction of controlled hypotension for surgery.
4.2 Posology And Method Of Administration
For intravenous use. Nitronal® should be administered by means of a micro-drip set infusion pump or similar device which permits maintenance of constant infusion rate.
Adults and the elderly - the dose should be titrated against the individual clinical response.
(1) Unresponsive congestive heart failure. The normal dose range is 10-100 micrograms / minute administered as a continuous intravenous infusion with frequent monitoring of blood pressure and heart rate. The infusion should be started at the lower rate and increased cautiously until the desired clinical response is achieved. Other haemodynamic measurements are extremely important in monitoring response to the drug: These may include pulmonary capillary wedge pressure, cardiac output and precordial electrocardiogram depending on the clinical picture.
(2) Refractory unstable angina pectoris. An initial infusion rate of 10-15 micrograms / minute is recommended; this may be increased cautiously in increments of 5-10 micrograms until either relief of angina is achieved, headache prevents further increase in dose, or the mean arterial pressure falls by more than 20 mm Hg.
(3) Use in surgery. An initial infusion rate of 25 micrograms / minute is recommended; this should be increased gradually until the desired systolic arterial pressure is attained. The usual dose is 25-200 micrograms / minute.
Children - Not recommended for use in children.
4.3 Contraindications
Hypersensitivity to nitrates. Hypotensive shock, severe anaemia, cerebral haemorrhage, arterial hypoxaemia, uncorrected hypovolaemia and angina caused by hypertrophic obstructive cardiomyopathy. Concomitant administration of sildenafil (section 4.5).
4.4 Special Warnings And Precautions For Use
Caution should be exercised in patients with severe liver or renal disease, hypothermia, hypothyroidism.
Nitronal® should not be given by bolus injection.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
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 nitrates are potentiated by concurrent administration of sildenafil. 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).
4.6 Pregnancy And Lactation
This product should not be used in pregnancy or in women who are breast feeding infants unless considered essential by the physician.
4.7 Effects On Ability To Drive And Use Machines
No information available.
4.8 Undesirable Effects
Nitronal® is generally well tolerated because a minimum dose is administered in unit time. Headache, dizziness, flushing, hypotension and tachycardia may be encountered, particularly if the infusion is administered too rapidly. Nausea, diaphoresis, restlessness, retrosternal discomfort, abdominal pain and paradoxical bradycardia have been reported. These symptoms should be readily reversible on reducing the rate of infusion or, if necessary, discontinuing treatment.
4.9 Overdose
Signs and symptoms: Vomiting, restlessness, hypotension, syncope, cyanosis, coldness of the skin, impairment of respiration, bradycardia, psychosis and methaemoglobinaemia may occur.
Treatment: The symptoms may be readily reversed by discontinuing treatment; if hypotension persists, raising the foot of the bed and the use of vasoconstrictors such as intravenous methoxamine or phenylephrine are recommended. Methaemoglobinaemia should be treated by intravenous methylene blue. Oxygen and assisted respiration may be required.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Glyceryl trinitrate exerts a spasmolytic action on smooth muscle, particularly in the vascular system. The predominant effect is an increase in venous capacitance resulting in marked diminution of both the left ventricular filling pressure and volume (preload). There is also a reduction in afterload due to moderate dilation of the arteriolar resistance vessels. These haemodynamic changes lower the myocardial oxygen demand. By direct action and through the reduction of myocardial wall tension glyceryl trinitrate also lowers the resistance to flow in the coronary collateral channels and allows re-distribution of blood flow to ischaemic areas of the myocardium.
Administration of Nitronal® by intravenous infusion to patients with congestive heart failure results in a marked improvement in haemodynamics, reduction of elevated left ventricular filling pressure and systolic wall tension, and an increase in the depressed cardiac output. It reduces the imbalance that exists between myocardial oxygen demand and delivery, thereby diminishing myocardial ischaemia and controlling ischaemia-induced ventricular arrhythmias.
5.2 Pharmacokinetic Properties
It is important that the dose of Nitronal® be titrated against the individual clinical response.
After intravenous administration, glyceryl trinitrate is widely distributed in the body with an estimated apparent volume of distribution of approximately 200 litres, and is rapidly metabolised to dinitrate and mononitrate with an estimated half life of 1 to 4 minutes, resulting in plasma levels of less than 1 microgram / ml.
5.3 Preclinical Safety Data
None, of relevance to the prescriber, which are not given elsewhere in this document.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Glucose, water for injections, hydrochloric acid.
6.2 Incompatibilities
Glyceryl trinitrate is adsorbed onto administration systems composed of polyvinyl chloride, - see 6.6.
6.3 Shelf Life
Ampoules: 4 years
Vial: 2 years
The diluted solution should be administered as soon as possible; it is stable for up to 24 hours in the recommended infusion system.
6.4 Special Precautions For Storage
Do not store above 25°C. Store in the original container.
6.5 Nature And Contents Of Container
Cartons of 10 ampoules or single vials.
Amber glass ampoule (containing 5ml or 25ml).
Clear glass vial (containing 50ml).
6.6 Special Precautions For Disposal And Other Handling
Nitronal® need not be diluted before use but can be diluted with Dextrose Injection BP, Sodium Chloride and Dextrose Injection BP, 0.9% Sodium Chloride Injection BP or other protein-free infusion solution, if required.
The solution, whether or not diluted, should be infused slowly (see dosage section) and not given by bolus injection.
To ensure a constant infusion rate of glyceryl trinitrate it is recommended that Nitronal® be administered by means of a syringe pump or polyethylene infusion bag with a counter, or with a glass or rigid polyethylene syringe and polyethylene tubing. Systems made of polyvinyl chloride may absorb up to 50% of the glyceryl trinitrate from the solution, thus reducing the efficacy of the infusion. If the recommended type of system is unavailable, a 1:10 dilution of Nitronal® should be used and the infusion rate modified according to the haemodynamic response of the patient, until the required parameters are attained.
7. Marketing Authorisation Holder
Merck Serono Limited
Bedfont Cross, Stanwell Road
Feltham, Middlesex
TW14 8NX
United Kingdom
8. Marketing Authorisation Number(S)
PL 11648 / 0093
9. Date Of First Authorisation/Renewal Of The Authorisation
24 June 2010
10. Date Of Revision Of The Text
1st August 2010
Legal Category
POM
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