DEFITELIO Concentrate for solution for infusion Ref.[114767] Active ingredients: Defibrotide

Defitelio must be prescribed and administered to patients by specialised physicians experienced in the diagnosis and treatment of complications of HSCT.

Posology

The recommended dose is 6.25 mg/kg body weight every 6 hours (25 mg/kg/day).

There is limited efficacy and safety data on doses above this level and consequently it is not recommended to increase the dose above 25 mg/kg/day.

The treatment should be administered for a minimum of 21 days and continued until the symptoms and signs of severe VOD resolve.

Renal impairment

Dose adjustment is not required for patients with renal impairment or who are on intermittent haemodialysis (see section 5.2).

Hepatic impairment

No formal pharmacokinetic studies have been performed in patients with hepatic impairment; however, the medicinal product has been used in clinical studies of patients developing hepatic impairment without dose adjustment with no safety issues identified. No dose adjustment is therefore recommended but careful monitoring of patients should be undertaken (see section 5.2).

Paediatric population

The recommended dose for children aged 1 month to 18 years is the same mg/kg dose as for adults i.e. 6.25 mg/kg body weight every 6 hours.

The safety and efficacy of defibrotide in children aged less than 1 month has not yet been established. No data are available. The use of Defitelio in children aged less than one month is not recommended.

Method of administration

Defitelio is for intravenous use. It is administered by intravenous infusion, over two hours.

Defitelio should always be diluted prior to use. It can be diluted with 5% glucose solution for infusion or sodium chloride 9 mg/mL (0.9%) solution for infusion to a suitable concentration to permit infusion over 2 hours. The total volume of infusion should be determined based on the individual’s patient weight. The final concentration of Defitelio should be in the range of 4 mg/mL to 20 mg/mL.

Vials are intended for a single use and unused solution from a single dose must be discarded (see section 6.6).

For instructions on dilution of the medicinal product before administration, see section 6.6.

There is no specific antidote for overdose and treatment should be symptomatic. Defibrotide is not removed by dialysis (see section 5.2).

Unopened vials:

3 years.

In-use stability after first opening and/or dilution:

From a microbiological point of view, after dilution, the reconstituted medicinal product should be used immediately. However, chemical and physical in-use stability has been demonstrated for 72 hours at 15-25°C for a concentration range of 4 mg/mL to 20 mg/mL in sodium chloride 9 mg/mL (0.9%) solution for infusion or 5% glucose solution for infusion.

If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not normally be expected to exceed 24 hours at 2-8°C.

Store below 25°C. Do not freeze.

For storage conditions after dilution of the medicinal product, see section 6.3.

2.5 mL vials (Type I clear glass), closed with a stopper (butyl rubber) and seal (aluminium).

Pack size of 10 vials.

Defitelio is for single use only.

The concentrate solution for infusion has to be diluted using aseptic technique.

Defitelio should be diluted with sodium chloride 9 mg/mL (0.9%) solution for infusion or 5% glucose solution for infusion (see section 6.3 for concentration range and stability of the diluted solution) to a suitable concentration to permit 2 hour infusion time (see section 4.2).

Preparation of Defitelio (use aseptic technique):

1. The number of vials to be diluted should be determined based on the individual patient’s weight (see section 4.2).

2. Before dilution, each vial should be inspected for particles. If particles are observed and/or the liquid in the vial is not clear, the vial must not be used.

3. The total volume of infusion should be determined based on the individual patient’s weight. The final concentration of Defitelio should be in the concentration range of 4 mg/mL – 20 mg/mL (see section 6.3).

4. A volume of the sodium chloride 9 mg/mL (0.9%) solution for infusion or glucose 5% solution for infusion from the infusion bag should be withdrawn and discarded, equal to the total volume of Defitelio solution to be added.

5. The required volume from the Defitelio vials should be withdrawn and combined.

6. The combined volumes of Defitelio should be added to the sodium chloride 9 mg/mL (0.9%) solution for infusion or glucose 5% solution for infusion.

7. The solution for infusion should be mixed gently.

8. Prior to use the solution should be visually inspected for particulate matter. Only clear solutions without visible particles should be used. Depending on the type and amount of diluent the colour of the diluted solution may vary from colourless to light yellow. It is recommended that the diluted Defitelio solution be administered to patients using an infusion set equipped with a 0.2 μm in-line filter.

9. After the infusion is complete, the intravenous line should be flushed with sodium chloride 9 mg/mL (0.9%) solution for infusion or glucose 5% solution for infusion.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.