TRIOMEL 9 GL NITROGEN 1070 KcalL WITH ELECTROLYTES

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

."רשואו קדבנ ונכותו תואירבה דרשמ י"ע עבקנ הז ןולע טמרופ

רשואמ ןולע

.6.4.2017

“This leaflet format has been determined by the Ministry of Health and the content thereof has been checked

and approved.” Date of approval: 6.4.2017.

SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion is presented in the form of

a 3-compartment bag.

Each bag contains a glucose solution with calcium, a lipid emulsion and an amino acid solution with

other electrolytes.

Contents per bag

1000 ml

1500 ml

2000 ml

27.5 % Glucose solution

(corresponding to 27.5 g/100 ml)

400 ml

600 ml

800 ml

14.2 % Amino acid solution

(corresponding to 14.2 g/100 ml)

400 ml

600 ml

800 ml

20 % Lipid emulsion

(corresponding to 20 g/100 ml)

200 ml

300 ml

400 ml

Composition of the reconstituted emulsion after mixing the contents of the 3 compartments:

Active substances

1000 ml

1500 ml

2000 ml

Refined olive oil+ refined soybean oil

40.00 g

60.00 g

80.00 g

Alanine

8.24 g

12.36 g

16.48 g

Arginine

5.58 g

8.37 g

11.16 g

Aspartic acid

1.65 g

2.47 g

3.30 g

Glutamic acid

2.84 g

4.27 g

5.69 g

Glycine

3.95 g

5.92 g

7.90 g

Histidine

3.40 g

5.09 g

6.79 g

Isoleucine

2.84 g

4.27 g

5.69 g

Leucine

3.95 g

5.92 g

7.90 g

Lysine

(equivalent to lysine acetate)

4.48 g

(6.32 g)

6.72 g

(9.48 g)

8.96 g

(12.64 g)

Methionine

2.84 g

4.27 g

5.69 g

Phenylalanine

3.95 g

5.92 g

7.90 g

Proline

3.40 g

5.09 g

6.79 g

Serine

2.25 g

3.37 g

4.50 g

Threonine

2.84 g

4.27 g

5.69 g

Tryptophan

0.95 g

1.42 g

1.90 g

Tyrosine

0.15 g

0.22 g

0.30 g

Valine

3.64 g

5.47 g

7.29 g

Sodium acetate, trihydrate

1.50 g

2.24 g

2.99 g

Sodium glycerophosphate, hydrated

3.67 g

5.51 g

7.34 g

Potassium chloride

2.24 g

3.35 g

4.47 g

Magnesium chloride, hexahydrate

0.81 g

1.22 g

1.62 g

Calcium chloride, dihydrate

0.52 g

0.77 g

1.03 g

Glucose anhydrous

(equivalent to glucose monohydrate)

110.00 g

(121.00 g)

165.00 g

(181.50 g)

220.00 g

(242.00 g)

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

a: Mixture of refined olive oil (approximately 80%) and refined soybean oil (approximately

20%) corresponding to a ratio essential fatty acids/total fatty acids of 20%.

For a full list of excipients, see section 6.1.

Nutritional intakes of reconstituted emulsion for each of the bag sizes:

1000 ml

1500 ml

2000 ml

Lipids

40 g

60 g

80 g

Amino acids

56.9 g

85.4 g

113.9 g

Nitrogen

9.0 g

13.5 g

18.0 g

Glucose

110.0 g

165.0 g

220.0 g

Energy:

Total calories approx.

1070 kcal

1600 kcal

2140 kcal

Non-protein calories

840 kcal

1260 kcal

1680 kcal

Glucose calories

440 kcal

660 kcal

880 kcal

Lipid calories

400 kcal

600 kcal

800 kcal

Non-protein calories / nitrogen ratio

93 kcal/g

93 kcal/g

93 kcal/g

Glucose / lipid calories ratio

52/48

52/48

52/48

Lipid / total calories

Electrolytes:

Sodium

35.0 mmol

52.5 mmol

70.0 mmol

Potassium

30.0 mmol

45.0 mmol

60.0 mmol

Magnesium

4.0 mmol

6.0 mmol

8.0 mmol

Calcium

3.5 mmol

5.3 mmol

7.0 mmol

Phosphate

15.0 mmol

22.5 mmol

30.0 mmol

Acetate

54 mmol

80 mmol

107 mmol

Chloride

45 mmol

68 mmol

90 mmol

Osmolarity

1310 mosm/l

1310 mosm/l

1310 mosm/l

a: Includes calories from purified egg phosphatide

b:Includes phosphate provided by the lipid emulsion

3.

PHARMACEUTICAL FORM

After reconstitution:

Emulsion for infusion.

Appearance prior to reconstitution:

The amino acids and glucose solutions are clear, colourless or slightly yellow,

The lipid emulsion is homogenous with a milky appearance.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion is indicated for parenteral

nutrition for adults and children above 2 years of age when oral or enteral nutrition is impossible,

insufficient or contraindicated.

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

4.2

Posology and method of administration

Posology

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion is not recommended for

use in children less than 2 years of age due to inadequate composition and volume (see sections 4.4; 5.1

and 5.2).

The maximum daily dose mentioned below should not be exceeded. Due to the static composition of the

multi-chamber bag, the ability to simultaneously meet all nutrient needs of the patient may not be

possible. Clinical situations may exist where patients require amounts of nutrients varying from the

composition

static

bag.

this

situation

volume

(dose)

adjustments

must

take

into

consideration the resultant effect this will have on the dosing of all other nutrient components of

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion. For example, paediatric

patients may require greater than 0.2 mmol/kg/day of phosphate. In those situations, health care

professionals may consider adjusting the volume (dose) of TRIOMEL 9 g/l nitrogen 1070 kcal/l with

electrolytes, emulsion for infusion,in order to meet these increased requirements.

In adults

The dosage depends on the patient’s energy expenditure, clinical status, body weight, and the ability to

metabolise the constituents of TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for

infusion, as well as additional energy or proteins provided orally/enterally; therefore, the bag size should

be chosen accordingly.

The average daily requirements are:

0.16 to 0.35 g nitrogen /kg body weight (1 to 2 g of amino acids/kg), depending on the patient's

nutritional status and degree of catabolic stress,

20 to 40 kcal/kg,

20 to 40 ml fluid /kg, or 1 to 1.5 ml per expended kcal.

For TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion the maximal daily

dose is defined by amino acids intake, 35 ml/kg corresponding to 2.0 g/kg amino acids, 3.9 g/kg

glucose, 1.4 g/kg lipids, 1.2 mmol/kg sodium, and 1.1 mmol/kg potassium. For a 70 kg patient, this

would be equivalent to 2450 ml TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for

infusion, per day, resulting in an intake of 140 g amino acids, 270 g glucose, and 98 g lipids (i.e., 2058

non-protein kcal and 2622 total kcal).

Normally, the flow rate must be increased gradually during the first hour and then be adjusted to take

into account the dose being administered, the daily volume intake, and the duration of the infusion.

For TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, the maximal infusion

rate is 1.8 ml/kg/hour, corresponding to 0.10 g/kg/hour amino acids, 0.19 g/kg/hour glucose, and

0.07g/kg/hour lipids.

In children greater than 2 years of age

There have been no studies performed in the paediatric population.

The dosage depends on the patient’s energy expenditure, clinical status, body weight, and the ability to

metabolise constituents of 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, as well as

additional

energy

proteins

given

orally/enterally;

therefore,

size

should

chosen

accordingly.

In addition, daily fluid, nitrogen, and energy requirements continuously decrease with age. Two groups,

ages 2 to 11 years and 12 to 18 years, are considered.

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

For TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion in the 2 to 11 year age

group, the limiting factors are phosphate concentration for daily dose (0.2 mmol/kg/day)

and lipid

concentration for hourly rate. In the 12 to 18 year age group, the limiting factors are phosphate

concentration for daily dose (0.2 mmol/kg/day)

and amino acid concentration for hourly rate. The

resulting intakes are displayed below:

Constituent

2 to 11 years

12 to 18 years

Recommended

TRIOMEL 9 g/l

nitrogen 1070

kcal/l with

electrolytes Max

Recommended

TRIOMEL 9 g/l

nitrogen 1070

kcal/l with

electrolytes Max

Maximum Daily Dose

Fluids (ml/kg/d)

60 – 120

50 – 80

Amino acids (g/kg/d)

1 – 2 (up to 3)

1 – 2

Glucose (g/kg/d)

12 – 14 (up to

3 – 10 (up to

Lipids (g/kg/d)

0.5 – 3

0.5 – 2 (up to

Total energy (kcal/kg/d)

60 – 90

30 – 75

Maximum Hourly Rate

TRIOMEL 9 g/l nitrogen

1070 kcal/l with

electrolytes (ml/kg/h)

Amino acids (g/kg/h)

0.20

0.19

0.12

0.12

Glucose (g/kg/h)

0.36

0.23

Lipids (g/kg/h)

0.13

0.13

0.13

0.08

a: Recommended values from 2005 ESPGHAN/ESPEN Guidelines

Normally, the flow rate must be increased gradually during the first hour and then be adjusted to take

into account the dose being administered, the daily volume intake, and the duration of the infusion.

In general, it is recommended to start the infusion for small children with low dose (i.e., 12.5 to 25

ml/kg) and gradually increase it up to the maximal dosage (see above).

Method and duration of administration

For single use only.

It is recommended that, after opening the bag, the contents are used immediately and not stored for

subsequent infusion.

After reconstitution, the mixture is homogenous with a milky appearance.

For instructions for preparation and handling of the emulsion for infusion, see section 6.6.

Due to its high osmolarity, TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for

infusion, can only be administered through a central vein.

The recommended duration of infusion for a parenteral nutrition bag is between 12 and 24 hours.

Treatment with parenteral nutrition may be continued for as long as required by the patient’s clinical

conditions.

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

4.3

Contraindications

TRIOMEL

nitrogen

1070

kcal/l

with

electrolytes,

emulsion

infusion,

contraindicated in the following situations:

In premature neonates, infants, and children less than 2 years of age,

Hypersensitivity to egg, soybean, or peanut proteins, or to any of the active

substances or

excipients, listed in section 6.1

Congenital abnormalities of amino acid metabolism,

Severe hyperlipidaemia or severe disorders of lipid metabolism characterized by

hypertriglyceridemia,

Severe hyperglycemia,

Pathologically-elevated plasma concentrations of sodium, potassium, magnesium, calcium, and/or

phosphorus.

4.4

Special warnings and precautions for use

An excessively fast administration of total parenteral nutrition (TPN) solutions may result in severe or

fatal consequences.

The infusion must be stopped immediately if any signs or symptoms of an allergic reaction (such as

sweating,

fever, chills, headache, skin rashes, or dyspnea) develop. This medicinal product contains

soybean oil and egg phosphatide. Soybean and egg proteins may cause hypersensitivity reactions.

Cross-allergic reactions between soybean and peanut proteins have been observed.

Ceftriaxone

must

mixed

administered

simultaneously

with

calcium-containing

solutions even via different infusion lines or different infusion sites. Ceftriaxone and calcium-containing

solutions may be administered sequentially one after another if infusion lines at different sites are used

or if the infusion lines are replaced or thoroughly flushed between infusions with physiological salt

solution to avoid precipitation. In patients requiring continuous infusion with calcium-containing TPN

solutions, healthcare professionals may wish to consider the use of alternative antibacterial treatments

which do not carry a similar risk of precipitation. If use of ceftriaxone is considered necessary in

patients

requiring

continuous

nutrition,

solutions

ceftriaxone

administered

simultaneously, albeit via different infusion lines at different sites. Alternatively, infusion of TPN

solution could be stopped for the period of ceftriaxone infusion, considering the advice to flush infusion

lines between solutions (see sections 4.5 and 6.2).

Pulmonary vascular precipitates causing pulmonary vascular embolism and respiratory distress have

been reported in patients receiving parenteral nutrition. In some cases, fatal outcomes have occurred.

Excessive addition of calcium and phosphate increases the risk of formation of calcium phosphate

precipitates (see section 6.2).

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).

Formation of precipitates or destabilization of the lipid emulsion could result in vascular occlusion (see

sections 6.2 and 6.6).

Severe water and electrolyte equilibration disorders, severe fluid overload states, and severe metabolic

disorders must be corrected before starting the infusion.

Specific clinical monitoring is required when an intravenous infusion is started.

Vascular-access infection and sepsis are complications that may occur in patients receiving parenteral

nutrition, particularly in case of poor maintenance of catheters, immunosuppressive effects of illness or

drugs. Careful monitoring of signs, symptoms, and laboratory test results for fever/chills, leukocytosis,

technical complications with the access device, and hyperglycemia can help recognize early infections.

Patients who require parenteral nutrition are often predisposed to infectious complications due to

malnutrition and/or their underlying disease state. The occurrence of septic complications can be

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

decreased with heightened emphasis on aseptic techniques in catheter placement and maintenance, as

well as aseptic techniques in the preparation of the nutritional formula.

Monitor water and electrolyte balance, serum osmolarity, serum triglycerides, acid/base balance, blood

glucose,

liver

kidney

function

tests,

coagulation

tests,

blood

count,

including

platelets,

throughout treatment.

Elevated liver enzymes and cholestasis have been reported with similar products. Monitoring of serum

ammonia should be considered if hepatic insufficiency is suspected.

Metabolic complications may occur if the nutrient intake is not adapted to the patient's requirements, or

the metabolic capacity of any given dietary component is not accurately assessed. Adverse metabolic

effects may arise from administration of inadequate or excessive nutrients or from inappropriate

composition of an admixture for a particular patient's needs.

Administration of amino acid solutions may precipitate acute folate deficiency; folic acid is, therefore,

recommended to be given daily.

Extravasation

Catheter site should be monitored regularly to identify signs of extravasation.

If extravasation occurs the administration should be stopped immediately, keeping the inserted catheter

cannula in

place

immediate management of the patient.

If possible, aspiration should be

performed through the inserted catheter/cannula in order to reduce the amount of fluid present in the

tissues before removing the catheter/cannula.

Depending on

the extravasated product (including the product(s) being mixed with TRIOMEL 9 g/l

nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, if applicable) and the

stage/extent of any

injury,

appropriate specific measures should be taken.

Options for management may include non-

pharmacologic, pharmacologic and/or surgical intervention. In case of large extravasation,

plastic surgeon advice should be sought within the first 72 hours.

The extravasation site should be monitored at least every 4 hours during the first 24 hours,

then once daily.

The infusion should not be restarted in the same central vein.

Hepatic Insufficiency

Use with caution in patients with hepatic insufficiency because of the risk of developing or worsening

neurological disorders associated with hyperammonaemia. Regular clinical and laboratory tests are

required, particularly liver function parameters, blood glucose, electrolytes and triglycerides.

Renal Insufficiency

Use with caution in patients with renal insufficiency, particularly if hyperkalaemia is present, because

of the risk of developing or worsening metabolic acidosis and hyperazotemia if extra-renal waste

removal is not being performed. Fluid, triglycerides and electrolyte status should be closely monitored in

these patients.

Hematologic

Use with caution in patients with coagulation disorders and anaemia.- Blood count and coagulation

parameters should be closely monitored.

Endocrine and Metabolism

Use with caution in patients with:

Metabolic acidosis. Administration of carbohydrates is not recommended in the presence of lactic

acidosis. Regular clinical and laboratory tests are required.

Diabetes mellitus. Monitor glucose concentrations, glucosuria, ketonuria and, where applicable

adjust insulin dosages.

Hyperlipidaemia due to the presence of lipids in the emulsion for infusion. Regular clinical and

laboratory tests are required.

Amino acid metabolism disorders.

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

Serum

triglyceride concentrations and the ability of the body to remove lipids must be checked

regularly.

Serum triglyceride concentrations must not exceed 3 mmol/l during the infusion.

If a lipid metabolism abnormality is suspected, it is recommended to measure daily serum triglyceride

levels after a period of 5 to 6 hours without administering lipids. In adults, the serum must be clear in

less than 6 hours after stopping the infusion containing the lipid emulsion. The next infusion must only

be administered when the serum triglyceride concentrations have returned to baseline values.

Fat overload syndrome has been reported with similar products. The reduced or limited ability to

metabolise the lipids contained in TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for

infusion, may result in a "fat overload syndrome", which may be caused by overdose; however, the signs

symptoms of

this syndrome may also occur when the product is administered according to

instructions (see also section 4.8).

event of

hyperglycemia,

infusion rate

of TRIOMEL 9 g/l

nitrogen 1070 kcal/l

with

electrolytes, emulsion for infusion, must be adjusted and/or insulin administered.

DO NOT ADMINISTER THROUGH A PERIPHERAL VEIN.

When making additions, the final osmolarity of the mixture must be measured before administration.

The mixture obtained must be administered through a central or peripheral venous line depending on its

final osmolarity. If the final mixture administered is hypertonic, it may cause irritation of the vein when

administered into a peripheral vein.

Although there is a natural content of trace elements and vitamins in the product, the levels are

insufficient

meet

body

requirements,

these should

added

prevent deficiencies from

developing. See instructions for making additions to this product.

Caution should be exercised in administering TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes,

emulsion for infusion, to patients with increased osmolarity, adrenal insufficiency, heart failure or

pulmonary dysfunction.

In malnourished patients, initiation of parenteral nutrition can precipitate fluid shifts resulting in

pulmonary oedema and congestive heart failure, as well as a decrease in the serum concentration of

potassium, phosphorus, magnesium, or water-soluble vitamins. These changes can occur within 24 to

48 hours; therefore, careful and slow initiation of parenteral nutrition is recommended together with

close monitoring and appropriate adjustments of fluid, electrolytes, trace elements, and vitamins.

Do not connect bags in series in order to avoid the possibility of air embolism due to residual gas

contained in the primary bag.

Special precautions in paediatrics

When administered to children greater than 2 years of age, it is essential to use a bag that has a volume

corresponding to the daily dosage.

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, is not suitable for use in

children less than 2 years of age because:

The glucose intake is too low, leading to a low glucose/lipid ratio,

The absence of cysteine makes the amino acid profile inadequate,

Calcium is too low,

The bag volumes are not appropriate.

In children greater than 2 years of age, the amount of phosphate limits the daily intakes; therefore, all

macronutrients and calcium should be supplemented.

Maximal infusion rate is 3.3 ml/kg/hour in children 2 to 11 years of age and 2.1 ml/kg/hour in children

12 to 18 years of age.

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

Vitamin and trace elements supplementation is always required. Paediatric formulations must be used.

To avoid risks associated with excessively rapid infusion rates, it is recommended to use a continuous

and controlled infusion.

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, must be administered

with caution to patients with a tendency towards electrolyte retention.

Intravenous infusion of amino acids is accompanied by increased urinary excretion of trace elements, in

particular copper and zinc. This should be taken into account in the dosing of trace elements, especially

during long-term intravenous nutrition.

4.5

Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, must not be administered

simultaneously

with

blood

through

same

infusion

tubing

because

possibility

pseudoagglutination.

The lipids contained in this emulsion may interfere with the results of certain laboratory tests (for

example, bilirubin, lactate dehydrogenase, oxygen saturation, blood haemoglobin) if the blood sample is

taken before the lipids are eliminated (these are generally eliminated after a period of 5 to 6 hours

without receiving lipids).

Precipitation of ceftriaxone-calcium can occur when ceftriaxone is mixed with calcium-containing

solutions in the same intravenous administration line. Ceftriaxone must not be mixed or administered

simultaneously with calcium-containing intravenous solutions, including TRIOMEL 9 g/l nitrogen

1070 kcal/l with electrolytes, emulsion for infusion, through the same infusion line (e.g., via Y-site).

However, ceftriaxone and calcium-containing solutions may be administered sequentially of one another

if the infusion lines are thoroughly flushed between infusions with a compatible fluid (see sections 4.4

and 6.2).

If the same infusion line is used for sequential administration, the line must be thoroughly flushed with a

compatible fluid (e.g., physiological salt solution) to avoid precipitation.

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, contains vitamin K,

naturally present in lipid emulsions. The amount of vitamin K in recommended doses of TRIOMEL 9

g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, is not expected to influence effects of

coumarin derivatives.

Due to the potassium content of TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for

infusion,

special

care

should

be taken

in patients treated with

potassium-sparing diuretics (e.g.,

amiloride, spironolactone, triamterene), angiotensin converting enzyme (ACE) inhibitors, angiotensin II

receptor antagonists, or the immunosuppressants tacrolimus or cyclosporine in view of the risk of

hyperkalemia.

4.6

Fertility, pregnancy and lactation

There are no clinical data from the use of TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes,

emulsion for infusion, in pregnant or lactating women. Taking into account the use and indications of

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, the product may be

considered during pregnancy and breastfeeding, if necessary.

4.7

Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

4.8

Undesirable effects

Potential undesirable effects may occur as a result of inappropriate use (for example: overdose,

excessively fast infusion rate) (see sections 4.4 and 4.9).

At the beginning of the infusion, any of the following abnormal signs (sweating,

fever, shivering,

headache, skin rashes, dyspnoea) should be cause for immediate discontinuation of the infusion.

The following adverse drug reactions (ADRs) were reported with TRIOMEL 9g/l nitrogen 1070 kcal/l

in a randomized, double-blind, active-controlled, efficacy and safety study. Twenty-eight patients with

various medical conditions (i.e., postsurgical fasting, severe malnutrition, enteral intake insufficient or

forbidden) were included and treated; patients in the TRIOMEL 9g/l nitrogen 1070 kcal/l group

received drug product up to 40 ml/kg/d over 5 days.

System Organ Class

MedDRA Preferred Term

Frequency

a

Cardiac Disorders

Tachycardia

Common

Metabolism and Nutrition Disorders

Anorexia

Common

Hypertriglyceridemia

Common

Gastrointestinal Disorders

Abdominal pain

Common

Diarrhea

Common

Nausea

Common

Vascular Disorders

Hypertension

Common

General disorders and

administration site conditions

Extravasation which may

result at infusion site level

in: pain, irritation,

swelling/oedema,

erythema/warmth, skin

necrosis, blisters

Not known

a: Frequency is defined as very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon

(≥ 1/1,000 to < 1/100);

rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); or not known (cannot be estimated from

the available data).

b: ADRs reported during post-marketing experience with

TRIOMEL 9 g/l nitrogen 1070 kcal/l

with electrolytes, emulsion for infusion.

The following class-like adverse drug reactions (ADRs) have been described in other sources in relation

to similar parenteral nutrition products; the frequency of these events is not known.

Blood and lymphatic system disorders: thrombocytopenia

Hepatobiliary disorders: cholestasis, hepatomegaly, jaundice

Immune system disorders: hypersensitivity

Investigations:

blood

alkaline

phosphatase

increased,

transaminases

increased,

blood

bilirubin

increased, elevated liver enzymes

Renal and urinary disorders: azotemia

Vascular disorders: Pulmonary vascular precipitates (pulmonary vascular embolism and respiratory

distress) (see section 4.4).

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

Fat overload syndrome (very rare)

Fat overload syndrome has been reported with similar products. This may be caused by inappropriate

administration (e.g., overdose and/or infusion rate higher than recommended, see section 4.9); however,

the signs and symptoms of this syndrome may also occur at the start of an infusion when the product is

administered according to instructions. The reduced or limited ability to metabolize the lipids contained

in TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, accompanied by

prolonged plasma clearance may result in a “fat overload syndrome”. This syndrome is associated with

a sudden deterioration in the patient’s clinical condition and is characterized by findings such as fever,

anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia, liver fatty infiltration

(hepatomegaly), deteriorating liver function, and central nervous system manifestations (e.g., coma).

The syndrome is usually reversible when infusion of the lipid emulsion is stopped.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It

allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse

events should be reported to the Ministry of Health according to the National Regulation by using an

online form

http://forms.gov.il/globaldata/getsequence/getsequence.

aspx?formType=AdversEffectMedic@moh.gov.il

4.9

Overdose

In the event of inappropriate administration (overdose and/or infusion rate higher than recommended),

signs of hypervolaemia and acidosis may occur.

An excessively fast infusion or administration of an inappropriately large volume of the product may

cause nausea, vomiting, chills and electrolyte disturbances. In such situations the infusion must be

stopped immediately.

Hyperglycaemia, glucosuria,

and a hyperosmolar syndrome may develop if glucose infusion rate

exceeds clearance.

The reduced or limited ability to metabolise lipids may result in a "fat overload syndrome", the results of

which are usually reversible after the infusion of the lipid emulsion is stopped (see also section 4.8).

In some serious cases, haemodialysis, haemofiltration or haemodiafiltration may be necessary.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Solutions for parenteral nutrition/combinations

ATC code: B05 BA10.

TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion’s content in nitrogen (L

series

amino

acids)

energy

(glucose

triglycerides)

enables

maintaining

adequate

nitrogen/energy balance.

This formulation also contains electrolytes.

The lipid emulsion included in TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for

infusion, is an association of refined olive oil and refined soybean oil (ratio 80/20), with the following

approximate distribution of fatty acids:

15% saturated fatty acids (SFA)

65% monounsaturated fatty acids (MUFA)

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

20% polyunsaturated essential fatty acids (PUFA)

The phospholipid/triglyceride ratio is 0.06.

Olive oil contains significant amounts of alpha-tocopherol which, combined with a moderate PUFA

intake, contribute to improved vitamin E status and the reduction of lipid peroxidation.

The amino acid solution contains 17 L series amino acids (including 8 essential amino acids), which are

required for protein synthesis.

Amino acids also represent an energy source. Their oxidation results in excretion of nitrogen in the form

of urea.

The amino acid profile is as follows:

Essential amino acids/total amino acids: 44.8%

Essential amino acids (g)/total nitrogen (g): 2.8%

Branched-chain amino acids/total amino acids: 18.3%

The carbohydrate source is glucose.

5.2

Pharmacokinetic properties

The ingredients of TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, (amino

acids, electrolytes, glucose and lipids) are distributed, metabolised and removed in the same way as if

they had been administered individually.

5.3

Preclinical safety data

No preclinical studies with TRIOMEL 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for

infusion, have been performed.

Preclinical toxicity studies performed using the lipid emulsion contained in TRIOMEL 9 g/l nitrogen

1070

kcal/l

with

electrolytes,

emulsion

infusion,

have

identified

changes,

which

conventionally found with a high intake of a lipid emulsion: fatty liver, thrombocytopaenia and elevated

cholesterol.

Preclinical studies performed using the solutions of amino acids and glucose contained in TRIOMEL 9

g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, of different qualitative compositions

and concentrations have not, however, revealed any specific toxicity.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Lipid emulsion compartment:

Purified egg phosphatide, 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

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

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 (Ca

and Mg

), 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 9 g/l nitrogen 1070 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 9 g/l nitrogen 1070 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).

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 after reconstitution

After reconstitution

It is recommended that the product be used immediately after the nonpermanent seals between the

3 compartments have been reconstituted. However, the stability of the reconstituted emulsion has been

demonstrated for 7 days (between 2°C and 8°C) and maximum 48 hours at a 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

microbiological

point

view,

admixture should be used

immediately. If

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

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.

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

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:

1000 ml bag: 1 carton with 6 bags

1500 ml bag: 1 carton with 4 bags

2000 ml bag: 1 carton with 4 bags

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 9 g/l nitrogen 1070 kcal/l with electrolytes, emulsion for infusion, may be supplemented

with electrolytes according to the table below:

Per 1000 ml

Included level

Maximal further addition

Maximal total level

Sodium

35 mmol

115 mmol

150 mmol

Potassium

30 mmol

50 mmol

80 mmol

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

(except for patients

that are in Intensive

Care Unit)

Magnesium

4.0 mmol

1.6 mmol

5.6 mmol

Calcium

3.5 mmol

1.5 (0.0

) mmol

5.0 (3.5

)mmol

Inorganic Phosphate

0 mmol

3.0 mmol

3.0 mmol

Organic Phosphate

15 mmol

10 mmol

25 mmol

a: Value corresponding to the addition of inorganic phosphate.

b: Including phosphate provided by the lipid emulsion.

Trace elements and vitamins:

Stability

been

demonstrated

with

commercially-available

preparations

vitamins

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

149.51.33419.00

8.

MANUFACTURER

TRIOMEL 9 g/L nitrogen 1,070 kcal/L with electrolytes, Emulsion for infusion, March 2018 ME

Baxter Healthcare Limited,

Thetford, Norfolk,

United Kingdom.

9

LICENCE HOLDER

Teva Medical Marketing Ltd.,

Haorgim St. 8, Ashdod 77100

The content of this leaflet was approved by the Ministry of Health in April 2017 and updated according

to the guidelines of the Ministry of Health in March 2018.