ISOKET 1 mg/ml Concentrate for solution for injection / infusion Ref.[7875] Active ingredients: Isosorbide dinitrate

Posology

Adults, including the elderly population

Intravenous route

A dose of between 2 mg and 12 mg per hour is usually satisfactory. However, dosages up to 20 mg per hour administered should be adjusted to the patient response.

Intra-coronary Route

The usual dose is 1 mg given as a bolus injection prior to balloon inflation. Further doses maybe given not exceeding 5 mg within a 30 minute period.

Paediatric population

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

Method of administration

Isoket is a concentrated solution and must be diluted prior use. The diluted solution should never be injected directly in the form of a bolus except via the intra-coronary route prior to balloon inflation. A dilution of 50% is advocated for intracoronary administration.

Isoket can be administered as an intravenous admixture with a suitable vehicle, see Section 6.6.

Prepared Isoket admixtures should be given by intravenous infusion or with the aid of a syringe pump incorporating a glass or rigid plastic syringe. During administration the patient’s blood pressure and pulse should be closely monitored.

Symptoms:

• Fall of blood pressure ≤90 mmHg
• Pallor
• Sweating
• Weak pulse
• Tachycardia
• Postural dizziness
• Headache
• Asthenia
• Dizziness
• Nausea
• Vomiting
• Diarrhoea
• Methaemoglobinaemia has been reported in patients receiving other organic nitrates. During isosorbide dinitrate 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 Isoket 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:
  • The patient must be laid down with lowered head and raised legs
  • Supply oxygen
  • Expand plasma volume (i.v. fluids)
  • Specific shock treatment (admit patient to intensive care unit)

Special procedure:

• Raise the blood pressure if the blood pressure is very low.
• Vasopressors should be used only in patients who do not respond to adequate fluid resuscitation.
• Additional administration of noradrenaline or other vasoconstrictors.
• Treatment of methaemoglobinaemia
  • Reduction therapy of choice with vitamin C, methylene-blue, or toluidine-blue
  • Administer oxygen (if necessary)
  • Initiate artificial ventilation
• Resuscitation measures

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

5 years, as packaged for sale.

Open ampoules or bottles should be used immediately and any unused drug discarded.

Once diluted, chemical and physical in-use stability for 24 hours at 2-8°C has been demonstrated.

From a microbiological point of view, the product must be used immediately once opened/diluted. 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 2-8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Unopened: There are no special precautions for storage of the product as packaged for sale.

Once diluted: See Section 6.3 for storage conditions of the diluted solution.

Ten 10 ml clear glass ampoules.

Clear, Type I glass vials sealed with a grey stopper and a red flip-off aluminium cap, containing 50ml or 100ml of concentrate and packed in a cardboard carton.

Clear, Type I glass vials sealed with a grey stopper and a red flip-off aluminium cap, containing 50ml or 100ml of concentrate and packed in a cardboard carton containing a Sterifix Minispike to aid withdrawal of the product from the bottle.

Not all pack sizes may be marketed.

Isoket contains isosorbide dinitrate in isotonic solution and is compatible with commonly employed infusion fluids, such as sodium chloride solution, dextrose solution, 5-30% glucose solution, Ringer’s solution and solutions containing albumin. No incompatibilities have so far been demonstrated.

Isoket must be diluted under aseptic conditions immediately after opening. The diluted solution is to be used immediately. Any unused contents of the container should be discarded.

Isoket may be infused slowly using a syringe pump with glass or plastic syringe, see Section 6.2 for suitable materials.

Example of admixture preparation

To obtain a dose of 6 mg per hour, add 50 ml of Isoket 1 mg/ml to 450 ml of a suitable vehicle, under aseptic conditions. The resultant admixture (500ml) contains 100 µg/ml (1mg/10ml) isosorbide dinitrate. An infusion rate of 60ml per hour (equivalent to 60 paediatric microdrops per minute or 20 standard drops per minute) will deliver the required dose of 6mg per hour.

Should it be necessary to reduce fluid intake, 100ml of Isoket 1 mg/ml may be diluted to 500ml using a suitable vehicle. The resultant solution now contains 200 µg/ml (2mg/10ml) isosorbide dinitrate. An infusion rate of 30ml per hour (equivalent to 30 paediatric microdrops per minute or 10 standard drops per minute), will deliver the required dose of 6 mg per hour.

A dilution of 50% is advocated to produce a solution containing 0.5 mg/ml where fluid intake is strictly limited.