ISOKET Solution for infusion or injection Ref.[28020] Active ingredients: Isosorbide dinitrate

Adults, including the elderly

Intravenous route

Isoket 0.5 mg/ml (undiluted) is intended for intravenous administration by slow infusion via a syringe pump. Alternatively it can be administered as an admixture with a suitable vehicle such as Sodium Chloride Injection B.P. or Dextrose Injection B.P.

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

Intra-coronary Route

Isoket 0.5 mg/ml 10ml prefilled syringes may be used for direct administration (through a catheter by means of an adaptor, if necessary) during percutaneous transluminal coronary angioplasty.

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

Children

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

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.

50ml glass bottles (glass type 1): 5 years as packaged for sale.

50ml glass bottles (glass type 2): 2 years as packaged for sale.

Open 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 are 2-8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Prefilled glass syringes: 3 years.

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.

50 ml glass bottles (glass type 1 or 2) with a laminated rubber stopper. The stopper consists of butyl rubber. The inner side of the stopper, coming into contact with the product is laminated with a film, consisting of a copolymer of tetrafluorethylene, ethylene and a fluorine containing vinyl monomer.

10 ml prefilled glass syringes with rubber plunger, stopper and cap and polystyrene plunger rod.

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, 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.