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

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 mmHg.
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.

Symptoms of overdose

Signs and symptoms of overdose are generally similar to the described adverse reactions: e.g. drop in blood pressure with orthostatic regulatory disturbances, reflex tachycardia and headaches, weakness, dizziness, somnolence, flush, nausea, vomiting and diarrhoea may occur.

At high doses (more than 20 mg/kg body-weight) methaemoglobinemia, cyanosis, dyspnoea and tachypnoea must be anticipated owing to nitrite ions formed during the metabolism of glyceryl trinitrate.

At very high doses an increase in intracranial pressure with cerebral symptoms may occur.

At chronic overdosage increased methaemoglobin levels were measured of which the clinical relevance is controversial.

Treatment in the event of overdose

In the case of overdose, the patient’s clinical status including vital signs and mental status should be assessed and supportive treatment of the cardiovascular and respiratory systems provided as clinically indicated or as recommended by the national poisons centre, where available.

In the event of mild hypotension, passive elevation of the patient’s legs and/or lowering of the head may be effective.

If there is pronounced hypotension and/or shock a volume replacement should be performed; in exceptional cases, norepinephrine (noradrenaline) and/or dopamine can be infused as a cardiovascular therapy. Administration of epinephrine and related substances is contraindicated.

Arterial blood gas estimation should be performed and if there is acidosis or the patient is clinically cyanosed, then severe methaemoglobinaemia must be assumed. Oxygen therapy should be given with 1–2 mg/kg bodyweight of IV Methylene Blue over five min unless the patient is known to have Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

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.

Do not store above 25°C. Store in the original container.

Cartons of 10 ampoules or single vials.

Amber glass ampoule (containing 5ml or 25ml).

Clear glass vial (containing 50ml).

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.