Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Lipid emulsion compartment:
Purified egg phospholipids, Glycerol, Sodium oleate, Sodium hydroxide (for pH adjustment), Nitrogen, Water for injections.

Compartment of amino-acid solution with electrolytes:
Glacial acetic acid (for pH adjustment), Nitrogen, Water for injections.

Compartment of glucose solution with calcium:
Hydrochloric acid (for pH adjustment), Nitrogen, Water for injections.

6.2   Incompatibilities

Do not add other medicinal products or substances to any components of the bag or to the reconstituted emulsion without first confirming their compatibility and the stability of the resulting preparation (in particular, the stability of the lipid emulsion).

Incompatibilities may be produced, for example, by excessive acidity (low pH) or inappropriate content of divalent cations (Ca2+ and Mg2+), which may destabilize the lipid emulsion.

As with any parenteral nutrition admixture, calcium and phosphate ratios must be considered. Excess addition of calcium and phosphate, especially in the form of mineral salts, may result in the formation of calcium phosphate precipitates.

TRIOMEL 5 g/l nitrogen 990 kcal/l with electrolytes, emulsion for infusion contains calcium ions which pose additional risk of coagulation precipitated in citrate anticoagulated/preserved blood or components.

Ceftriaxone must not be mixed or administered simultaneously with intravenous calcium-containing solutions, including TRIOMEL 5 g/l nitrogen 990 kcal/l with electrolytes, emulsion for infusion, through the same infusion line (e.g., via Y-connector) because of the risk of precipitation of ceftriaxone-calcium salt (see sections 4.4 and 4.5).

Due to the risk of precipitation, TRIOMEL 5 g/l nitrogen 990 kcal/l with electrolytes, emulsion for infusion should not be administered through the same infusion line or admixed together with ampicillin or fosphenytoin.
Check compatibility with solutions administered simultaneously through the same administration set, catheter, or cannula.

Do not administer before, simultaneously with, or after blood through the same equipment because of the risk of pseudoagglutination.

6.3   Shelf life

The expiry date of the product is indicated on the packaging materials.
After reconstitution

It is recommended that the product be used immediately after the non-permanent seals between the 3 compartments have been opened. However, the stability of the reconstituted emulsion has been demonstrated for 7 days (between 2°C and 8°C) and maximum 48 hours at temperature not exceeding 25°C.

After addition of supplements (electrolytes, trace elements and vitamins; see section 6.6) 
For specific admixtures, in-use stability has been demonstrated for 7 days (between 2°C and 8°C) followed by 48 hours at temperature not exceeding 25°C.

From a microbiological point of view, any admixture should be used immediately. If not used immediately, storage times and conditions, after mixing and prior to use, are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless addition of supplements has taken place in controlled and validated aseptic conditions.

6.4   Special precautions for storage

Store below 25°C
Do not freeze.
Store in the overpouch.
For storage conditions of the reconstituted medicinal product, see section 6.3.
6.5   Nature and contents of container

The 3-compartment bag is a multilayer plastic bag. The inner (contact) layer of the bag material is made of a blend of polyolefinic copolymers and is compatible with amino acid solutions, glucose solutions, and lipid emulsions. Other layers are made of polyethylene vinyl acetate (EVA), and of copolyester.

The glucose compartment is fitted with an injection site to be used for addition of supplements.
The amino acid compartment is fitted with an administration site for insertion of the spike of the infusion set.

The bag is packaged in an oxygen barrier overpouch with an oxygen absorber sachet Pack sizes:

2,000 ml bag: 1 carton with 4 bags
2,500 ml bag: 1 carton with 2 bags

Not all pack sizes may be marketed.
6.6   Special precautions for disposal and other handling.


To open
Remove the protective overpouch.
Discard the oxygen absorber sachet.

Confirm the integrity of the bag and of the nonpermanent seals. Use only if the bag is not damaged; if the nonpermanent seals are intact (i.e., no mixture of the contents of the 3 compartments); if the amino acid solution and the glucose solution are clear, colourless, or slightly yellow, and practically free of visible particles; and if the lipid emulsion is a homogeneous liquid with a milky appearance.

Mixing the solutions and the emulsion

Ensure that the product is at room temperature when breaking the nonpermanent seals.
Manually roll the bag onto itself, starting at the top of the bag (hanger end). The nonpermanent seals will disappear from the side near the inlets. Continue to roll the bag until the seals are open along approximately half of their length.

Mix by inverting the bag at least 3 times.

After reconstitution, the mixture is a homogeneous emulsion with a milky appearance.
Additions

The capacity of the bag is sufficient to enable additions such as vitamins, electrolytes, and trace elements.

Any additions (including vitamins) may be made into the reconstituted mixture (after the nonpermanent seals have been opened and after the contents of the 3 compartments have been mixed).

Vitamins may also be added into the glucose compartment before the mixture is reconstituted (before opening the nonpermanent seals and before mixing the 3 compartments).

When making additions to formulations containing electrolytes, the amount of electrolytes already present in the bag should be taken into account.

Additions must be performed by qualified personnel under aseptic conditions.

TRIOMEL 5 g/l nitrogen 990 kcal/l with electrolytes, emulsion for infusion may be supplemented with electrolytes according to the tables below:

Per 1,000 ml
Included level        Maximal further addition        Maximal total level Sodium                          35 mmol                    115 mmol                 150 mmol Potassium                       30 mmol                    120 mmol                 150 mmol Magnesium                      4.0 mmol                     1.6 mmol                 5.6 mmol Calcium                        3.5 mmol              1.5 (0.0a) mmol           5.0 (3.5a)mmol Inorganic Phosphate              0 mmol                     3.0 mmol                 3.0 mmol b
Organic Phosphate              15 mmol                       10 mmol                 25 mmol b a: Value corresponding to the addition of inorganic phosphate.
b: Including phosphate provided by the lipid emulsion.

Trace elements and vitamins:
Stability has been demonstrated with commercially-available preparations of vitamins and trace elements (containing up to 1 mg of iron).
Compatibility for other additives is available upon request.
When making additions, the final osmolarity of the mixture must be measured before administration via a peripheral vein.

To perform an addition:
-     Aseptic conditions must be observed.
-     Prepare the injection site of the bag.
-     Puncture the injection site and inject the additives using an injection needle or a reconstitution device.
-     Mix content of the bag and the additives.

Preparation of the infusion

Aseptic conditions must be observed.
Suspend the bag.
Remove the plastic protector from the administration outlet.
Firmly insert the spike of the infusion set into the administration outlet.
Administration

For single use only.

Only administer the product after the nonpermanent seals between the 3 compartments have been broken and the contents of the 3 compartments have been mixed.

Ensure that the final emulsion for infusion does not show any evidence of phase separation.

After opening the bag, the contents must be used immediately. The opened bag must never be stored for a subsequent infusion. Do not reconnect any partially used-bag.

Do not connect bags in series in order to avoid the possibility of air embolism due to gas contained in the primary bag.

Any unused product or waste material and all necessary devices must be discarded.

7     REGISTRATION NUMBER
149 49 33417 00