NITROCINE Solution for infusion Ref.[50442] Active ingredients: Glyceryl trinitrate

Posology

Adults

The dose of Nitrocine should be adjusted to meet the individual needs of the patient.

The recommended dosage range is 10-200 mcg/min but up to 400 mcg/min may be necessary during some surgical procedures.

Elderly

There is no evidence that a posology adjustment is required in the elderly.

Paediatric population

The safety and efficacy of Nitrocine has not yet been established in children.

Surgery

A starting dose of 25 mcg/min is recommended for the control of hypertension, or to produce hypotension during surgery.

This may be increased by increments of 25 mcg/min at 5 minute intervals until the blood pressure is stabilized. Doses between 10-200 mcg/min are usually sufficient during surgery, although doses of up to 400 mcg/min have been required in some cases.

The treatment of perioperative myocardial ischaemia may be started with a dose of 15-20 mcg/min, with subsequent increments of 10-15 mcg/min until the required effect is obtained.

Unresponsive congestive heart failure

The recommended starting dose is 20-25 mcg/min. This may be decreased to 10 mcg/min, or increased in steps of 20-25 mcg/min every 15-30 minutes until the desired effect is obtained.

Unstable angina

An initial dose of 10 mcg/min is recommended with increments of 10mcg/min being made at approximately 30 minute intervals according to the needs of the patient.

Patients with renal and hepatic impairment

Additional dose adjustments in patients with severe hepatic insufficiency or severe renal failure may be necessary and require additional monitoring.

Method of Administration

Nitrocine solution may be used either diluted or undiluted, refer to section 6.6.

Nitrocine can be administered undiluted by slow intravenous infusion using a syringe pump incorporating a glass or rigid plastic syringe.

Alternatively, Nitrocine may be administered intravenously as an admixture using a suitable vehicle such as Sodium Chloride Injection B.P. or Dextrose Injection B.P. In case of dilution, Nitrocine must be mixed under aseptic conditions immediately after opening.

Prepared admixtures should be given by intravenous infusion or with the aid of a syringe pump to ensure a constant rate of infusion.

During Nitrocine administration there should be close haemodynamic monitoring of the patient. The posology of Nitrocine i.v. should be adjusted to achieve the desired clinical response.

Example of admixture preparation

To obtain an admixture of GTN at a concentration of 100 mcg/ml, add 50 ml Nitrocine solution (containing 50 mg glyceryl trinitrate) to 450 ml of infusion vehicle to give a final volume of 500 ml.

A dosage of 100 mcg/min. can be obtained by giving 60 ml of the admixture per hour. This is equivalent to a drip rate of 60 microdrops per minute or 20 standard drops per minute. At this drip rate the admixture provides enough solution for an infusion time of 8 hours 20 minutes.

For full details it is advisable to consult the following dosage chart:

1 ml = 60 microdrops = 20 standard drops

Bottles of Nitrocine are for single use only and should not be regarded as multi-dose containers.

Animal experience

In rats and mice, significant lethality (LD50) at single intravenous doses of 23.2 mg/kg and 10.6 mg/kg, respectively, was observed.

In rats and mice, significant lethality (LD50) at single subcutaneous doses of 94 mg/kg and 110 mg/kg, respectively, was observed

Human experience

Symptoms could include the following:

• Fall in blood pressure ≤90 mmHg-
• Pallor
• Sweating
• Weak pulse
• Reflex tachycardia
• Collapse
• Syncope
• Dizziness postural
• Headache
• Asthenia
• Dizziness
• Nausea
• Vomiting
• Diarrhoea
• Methaemoglobinaemia has been reported in patients receiving other organic nitrates. During glyceryl trinitrate biotransformation nitrite ions are released, which may induce methaemoglobinaemia and cyanosis with subsequent tachypnoea, anxiety, loss of consciousness and cardiac arrest. It cannot be excluded that an overdose of glyceryl trinitrate may cause this adverse reaction
• In very high doses the intracranial pressure may be increased. This might lead to cerebral symptoms

General procedure:

• Stop delivery of the drug.
• General procedures in the event of nitrate-related hypotension

Patient should be kept horizontal with the head lowered and legs raised or, if necessary, compression bandaging of the patient’s legs

Supply oxygen

Expand plasma volume

For specific shock treatment admit patient to intensive care unit

Special procedure:

• Raising the blood pressure if the blood pressure is very low
• Treatment of methaemoglobinaemia

Treatment with intravenous methylene blue

• Initially 1 to 2 mg/kg, not exceeding 4 mg/kg of a 1% solution over 5 minutes.
• Repeat dose in 60 minutes if there is no response.
• Administer oxygen (if necessary)
• Initiate artificial ventilation

Treatment of methaemoglobinemia with methylene blue is contraindicated in patients with glucose-6-phosphate deficiency or methemoglobin-reductase deficiency (see also section 4.4). Where this treatment is contraindicated or not effective, exchange transfusion and/or transfusion of packed red blood cells is recommended.

Resuscitation measures:

In case of signs of respiratory and circulatory arrest, initiate resuscitation measures immediately.

As packaged for sale:

Nitrocine may be stored unopened for 5 years.

The product should be used immediately after opening.

Admixture:

Chemical and physical in-use stability of the admixture when prepared as in Section 6.6 has been demonstrated for 24 hours at 25°C in suitable containers. From a microbiological point of view, the admixture should be used immediately. If not used immediately, the in-use storage conditions prior use are the responsibility of the user and would normally not be longer than 24hrs at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

As packaged for sale:

This medicinal product does not require any special storage conditions.

For storage of open or admixed product, see Section 6.3.

Clear glass (type II) vials with rubber closure (Bromobutyl polymer) and aluminium cap containing 50ml. The vials are packed singly in an outer carton.

Not all pack sizes may be marketed.

Vials of Nitrocine are for single use only and should not be regarded as multi-dose containers.

Nitrocine contains glyceryl trinitrate in isotonic sterile solution and is compatible with commonly employed infusion solutions, Sodium Chloride Injection BP and Dextrose Injection BP. No incompatibilities have so far been demonstrated.

Nitrocine is compatible with glass infusion bottles and with rigid infusion packs made of polyethylene. Nitrocine may also be infused slowly using a syringe pump with a glass or plastic syringe.

Admixtures are prepared by replacing a given volume of infusion vehicle with an equal volume of the product to produce the final infusion solution. For admixture storage precautions, refer to Section 6.3. For further information on preparation of different concentrations, refer to the User Information Leaflet.