FREAMINE 8.5 % Infusion solution

Зміст інструкції

1. FREAMINE III 8,5 % solution for infusion
   1. What is FREAMINE III and what is it used for
   2. What you need to know before using FREAMINE III
   3. How to use FREAMINE III
   4. Possible side effects
   5. How to store FREAMINE III
   6. Contents of the pack and other information

FREAMINE III 8,5 % solution for infusion

Read this leaflet carefully before you are given this medicine
because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What FREAMINE III is and what it is used for
• 2. What you need to know before you use FREAMINE III
• 3. How to use FREAMINE III
• 4. Possible side effects
• 5. How to store FREAMINE III
• 6. Contents of the pack and other information

1. What is FREAMINE III and what is it used for

FREAMINE III contains amino acids (substances used by the body for protein production).
FREAMINE III is a solution for parenteral nutrition, meaning it is administered through a
vein.
FREAMINE III is indicated for patients in whom:

• 1) oral feeding is not possible;
• 2) there is malabsorption of proteins taken orally
• 3) the nutritional requirement is significantly increased, for example due to the presence of extensive burns.

2. What you need to know before using FREAMINE III

Do not use FREAMINE III

• if you are allergic to the active ingredients or any of the other ingredients of this medicine (listed in section 6);
• if you do not produce urine (anuria);
• if you suffer from a severe liver or brain disease (encephalopathy or hepatic coma);
• if you suffer from a congenital disease (present from birth) that does not allow for correct metabolism of amino acids
• if you have high levels of sodium, potassium, magnesium, and phosphorus in the blood.

Warnings and precautions
Consult your doctor, pharmacist or nurse before using FREAMINE III.
When used in newborns and children under 2 years of age, the solution (in bottles and administration sets) must be protected from exposure to light until the administration is completed. Exposure of Freamine III to ambient light, especially after the addition of trace elements and/or vitamins, generates peroxides and other degradation products that can be reduced by protecting it from light exposure.
The doctor will subject you to frequent blood tests/checks during treatment, especially in the first few days.
Inform your doctor if:

• if you suffer from liver problems (hepatic insufficiency)
• if you suffer from severe lung problems (pulmonary embolism) and heart problems, such as heart attack and heart failure
• if fever, chills and reactions at the access site (where the infusion needle is inserted) occur during treatment.

Other medicines and FREAMINE III
Tell your doctor if you are taking, have recently taken or might take any other medicines.
Tell your doctor if you are being treated with:

• medicines that promote urine production and reduce potassium loss (amiloride, spironolactone, triamterene);
• medicines used to lower blood pressure (ACE inhibitors, and angiotensin II receptor antagonists);
• medicines that reduce the activity of the immune system (tacrolimus and cyclosporine). Pregnancy, breastfeeding and fertilityIf you are pregnant, suspect you are pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor for advice before using this medicine. No clinical data are available for the risk in pregnancy and during breastfeeding. Your doctor will prescribe FREAMINE III only if absolutely necessary.

Driving and using machines
There is no information on the effects of FREAMINE III on the ability to drive or operate machinery.

FREAMINE III contains sodium bisulfite
Rarely, it can cause severe hypersensitivity reactions and bronchospasm.
This medicine contains 115 mg of sodium per 500 ml bottle. This is equivalent to 6%
of the maximum daily intake recommended with the diet of an adult.
This medicine contains 30 mmol of potassium per 500 ml bottle.
To be taken into consideration in patients with reduced kidney function or in patients following a
low-content diet.
May cause pain at the injection site.

3. How to use FREAMINE III

Use this medicine following the doctor's instructions exactly at all times.
If you have any doubts, consult your doctor.
The duration of treatment and the dose will be established by the doctor based on the following characteristics:
your age, your weight, your state of health and your nutritional status, your daily requirement for substances such as
proteins and nitrogen, and your ability to metabolize the components of FREAMINE III.
Method of administration
When used in newborns and children under 2 years of age, the solution (in vials and administration sets) must be
protected from light exposure until the administration is completed (see section 2).
You will receive this medicine via infusion into a peripheral or central vein

If you take more FREAMINE III than you should
In case of overdose, hypervolemia (increased fluid volume in the body), electrolyte disturbances (alteration of salt
levels in the blood), acidosis (alteration of blood pH), and increased urea in the blood (azotemia) may occur.
In this case, the doctor will subject you to specific laboratory tests and institute appropriate therapy.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The frequency of the following side effects is not known (cannot be estimated based on available data):
hot flushes,
redness of the skin (erythema).

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. You can also report side effects directly through the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store FREAMINE III

Prolonged storage under critical conditions (temperatures above 40  C; below 0  C) may
alter the appearance of the solution - discoloration up to dark brown, cloudy - and cause the formation of
crystalline precipitate.
Keep this medicine out of the sight and reach of children.
When used in neonates and children under 2 years of age, the solution (in vials and administration sets) must be protected from light exposure until the completion of
administration (see paragraph 2).
Do not use this medicine after the expiry date which is reported on the bag after SCAD. The expiry date refers to the last day of that month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What FREAMINE III contains
The active ingredients contained in 100 ml are:
The other components are magnesium chloride hexahydrate, potassium acetate, sodium bisulfite,
water for injections, glacial acetic acid.

Description of the appearance of FREAMINE III and contents of the pack

FREAMINE III 8.5% in vials of 250, 500 and 1000 ml is a sterile, clear solution, with a light yellow
colour, free from particles.
It is available in:

• pack of 10 vials of 500 ml
• pack of 1 vial of 250, 500 or 1000 ml. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Baxter S.p.A.
Via Del Serafico 89
00142 Rome

Manufacturer
Bieffe Medital S.p.A.
Via Nuova Provinciale s.n.c.-
Grosotto (So)
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The following information is intended for healthcare professionals only:
Dosage and Administration
Freamine III is intended for intravenous use.
The start and duration of parenteral nutrition, as well as the dosage (dose and frequency of
administration) depend on the following patient characteristics:

• age, weight, clinical condition,
• nitrogen requirement,
• ability to metabolize the constituents of Freamine III,
• daily protein requirement. The daily intake of protein with the diet is approximately 0.9 g per Kg of body weight in a healthy adult and 1.4-2.2 g per Kg in a growing child and in infants. However, it should be noted that the requirement for proteins and calories can be significantly higher in traumatized or malnourished patients. Daily amino acid doses of approximately 1.0-1.5 g per Kg of body weight for adults and 2-3 g/Kg for children, with adequate calories, are generally sufficient to meet the protein requirement and promote a positive nitrogen balance in these patients, although higher doses may be required in severe catabolic states. When administering these higher than normal doses, especially in children, more frequent laboratory tests are necessary. For protein sparing in well-nourished patients who do not receive additional calories in significant amounts, amino acid doses of 1-1.7 g/Kg/day significantly reduce nitrogen losses and spare body proteins. If the increase in BUN exceeds 20 mg% in 48 hours, the amino acid infusion should be suspended or the administration rate reduced. For optimal utilization of amino acids, adequate amounts of intracellular electrolytes, especially potassium, magnesium and phosphate, should also be provided. Approximately 60-180 mEq of potassium, 10-30 mEq of magnesium and 20-80 mEq of phosphate per day are administered to achieve an optimal metabolic response. Sufficient amounts of the major extracellular electrolytes: sodium, calcium and chloride, should also be administered. In patients with hyperchloremia or affected by other types of metabolic acidosis, sodium and potassium

should be added as acetates or lactates, to provide bicarbonate precursors. The electrolyte content of
Freamine III should be taken into account when calculating the daily electrolyte intake. Serum
electrolytes, including magnesium and phosphorus, should be monitored frequently.

Central Venous Nutrition
Central venous nutrition should be considered in patients who are severely
catabolic and severely depleted, or if total parenteral nutrition is indicated for prolonged periods. To achieve a positive nitrogen balance in these patients, a calorie-nitrogen ratio of at least 100-150 non-protein calories per gram of nitrogen is recommended.
These ratios are easily and conveniently achieved with the use of concentrated glucose solutions and, if
required, also with supplementary administrations of fat emulsions for parenteral use.
Total parenteral nutrition should be started with mixtures containing glucose at lower
concentrations; the glucose content should then be gradually increased to reach the expected
calorie needs as patient tolerance increases.
In adults, highly hypertonic mixtures of amino acids and glucose can be administered
safely only by continuous infusion via a central venous catheter inserted into the vena
cava.
For optimal utilization of nitrogen, infuse 500 ml of Freamine III 8.5% in 8 hours, mixed
with concentrated glucose, electrolytes and vitamins.
If the administration is less than the programmed doses, do not try to make up for lost time. In addition to meeting the protein requirement, especially during the first days of therapy, the
administration should also be regulated based on the patient's glucose tolerance.
The daily intake of amino acids and glucose should be gradually increased to reach the maximum
dose; frequent determinations of sugar levels in urine and blood will indicate the necessary
graduality.
In many patients, the administration of adequate calories in the form of hypertonic glucose may
require the addition of exogenous insulin to prevent hyperglycemia and glucosuria.
When the administration of hypertonic glucose is abruptly stopped, infuse a
solution containing 5% glucose, to prevent rebound hypoglycemia.

Peripheral Venous Parenteral Nutrition
In patients who are moderately catabolic and moderately depleted who require parenteral nutrition and in whom central venous administration is not indicated, Freamine III
can be mixed with 5% glucose solutions and administered into a peripheral vein.
The osmolarity of a specific infusion solution must be taken into consideration when
considering peripheral administration. Highly hypertonic parenteral nutrition solutions
must be administered through a central venous catheter with the tip placed in a large
central vein.
For example, to prepare a 4.25% Freamine III solution in 2.25% glucose, aseptically transfer
500 ml of Freamine III 8.5% into a one-liter bottle containing 500 ml of
5% glucose. Each liter of the resulting solution provides 42.5 grams of protein equivalent to 100
calories of carbohydrates, with an osmolarity of approximately 569 mOsm/liter.
Parenteral fat emulsions provide approximately 9 calories per gram and can be
administered, for additional caloric intake, together with the amino acid +
glucose mixture via a "Y" connector.
Fat emulsions should not be the sole source of calories as various studies have
shown that glucose better spares nitrogen in the stressed patient.

Protein Sparing
In well-nourished, mildly catabolic patients, such as, for example, post-surgical patients
who require parenteral nutrition only for short periods, protein sparing can be
obtained by administering amino acid solutions, with or without carbohydrates, via the periphery.
These mixtures can be prepared by diluting Freamine III 8.5% with "Water for
injections" or with 5% Glucose Solutions in order to obtain an isotonic
or slightly hypertonic solution to be administered into a peripheral vein. For example, a
4.25% Freamine III solution can be prepared by aseptically transferring 500 ml of Freamine III 8.5% into a
one-liter bottle containing 500 ml of "Water for injections". The resulting solution
will contain 42.5 g of amino acids with an osmolarity of approximately 430 mOsm/liter.
A nearly isotonic 3% solution of Freamine III can be prepared by aseptically transferring
350 ml of Freamine II 8.5% into a one-liter bottle partially filled with 650 ml of "Water
for injections". The resulting solution will provide 29 grams of total amino acids per liter with
an osmolarity of approximately 305 mOsm/l.

Special populations
Children
Exposure to light of parenteral nutrition solutions, especially after
the addition of trace elements and/or vitamins, can have adverse effects on clinical outcome in neonates, due to
the generation of peroxides and other degradation products. When used in neonates and
children under 2 years of age, Freamine III must be protected from ambient light until
completion of administration (see section 2).
Small children (up to 10 Kg of body weight), treated with parenteral nutrition, generally receive
from 2 to 3 g of protein, from 120 to 150 calories and 120-150 ml of fluid per kg of body
weight per day. This requirement is met by administering a solution
containing approximately 2.12% Freamine III and 20% Glucose. Less hypertonic mixtures can
be administered into peripheral veins.
Concomitant administrations of fat emulsions can be performed in a central vein or
in a peripheral vein with a "Y" administration connector, to provide essential fatty acids
and increase caloric intake.
Due to the rapid physiological changes that occur in small children, the daily
dose of nutrient mixture should be increased slowly at the beginning, with frequent checks of clinical and metabolic parameters.
Children weighing more than 10 Kg require less calories and slightly less protein: in
general, 50 to 80 calories and 2 grams of protein per Kg of body weight per day are sufficient.
Elderly
The dosage must be established with caution, as it must take into account a possible reduction
of cardiac, renal or hepatic function, concomitant pathologies or pharmacological therapies.
Patients with renal insufficiency
Administer with caution as nitrogen tolerance may be altered and it may be necessary to adjust the dosage. In these patients, fluid and electrolyte status must be carefully
monitored.
Patients with impaired hepatic function
Amino acid solutions should be used with caution in patients with pre-existing hepatic
disease or hepatic insufficiency. Careful monitoring is necessary to identify possible symptoms of
hyperammonemia.
Incompatibilities

• Additives may be incompatible.
• Higher concentrations should be added with caution and with adequate mixing (avoiding stratification). Additional amounts of calcium and phosphate can be added to alternate vials.
• Excessive addition of calcium and phosphate increases the risk of calcium phosphate precipitation. Special precautions for disposal and handlingWhen used in neonates and children under 2 years of age, the solution (in vials and administration sets) must be protected from exposure to light until completion of administration (see section 2).

Confirm the integrity of the container. Use only if the container is not damaged and if
the solution is clear and colorless or slightly yellow.
Visually inspect the vial to check that it is not cracked.
If substances are added to the container, it is necessary:

• Observe aseptic conditions.
• Ensure the stability and compatibility of the additives.
• Prepare the injection site of the container.
• Puncture the injection site and inject the additives with a syringe needle or a reconstitution device.
• Thoroughly mix the contents of the container and the additives.
• Check the final solution for any color change and particles.
• Check the container for any leaks.
• Ensure that the storage requirements of the additives are respected.
• The administration of the infusion is for single use only.
• Do not reconnect any partially used container.
• Do not connect containers in series. Re-check the bottle at least once every hour during administration.