CLINIMIX N17G35E

Package leaflet: Information for the user

CLINIMIX N17G35E
concentrate for solution for infusion
Please read all of this leaflet carefully before you are given the medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What CLINIMIX is and what it is used for

CLINIMIX is a concentrate for solution for infusion. It is supplied in dual-chamber bags. One chamber contains an amino acid solution with electrolytes, and the other chamber contains a glucose solution with calcium. The chambers are separated by a frangible seal. The contents of both chambers should be mixed immediately before administration by squeezing or rolling the bag from the top to break the seal.
CLINIMIX is administered intravenously to provide nutritional support in adults and children when oral nutrition is not suitable.
CLINIMIX must only be administered under medical supervision.

2. Important information before using CLINIMIX

When not to use CLINIMIX

• if the patient has a known allergy to any of the ingredients of this medicine (listed in section 6)
• if administration of certain amino acids causes problems for the patient's organism
• if the patient has excessively high blood sugar levels (severe hyperglycemia)
• if the patient's blood is too acidic (metabolic acidosis caused by elevated lactate levels)
• if the blood concentrations of sodium, potassium, magnesium, calcium and (or) phosphorus are too high (hypernatremia, hyperkalemia, hypermagnesemia, hypercalcemia and (or) hyperphosphatemia)
• in children below 28 days of age, ceftriaxone must not be administered together with intravenous fluids, as insoluble particles may form.

In each case, the decision by the physician on whether this medicine can be administered to the patient will depend on factors such as: age, body weight, clinical condition, including results of any tests performed.

Warnings and precautions

Before starting treatment with CLINIMIX, discuss it with your doctor or nurse.

If any unusual symptoms or signs of allergic reaction occur, such as fever, chills, skin rash or difficulty breathing, excessive sweating, nausea or headache, inform your doctor or nurse immediately: the infusion will be stopped immediately. The doctor will monitor the patient's condition during administration of the medicine and may recommend adjusting the dose or adding additional nutritional components such as fats, vitamins, electrolytes and trace elements, if considered necessary.

Certain medicines and diseases may increase the risk of developing infections or sepsis (presence of bacteria in the blood). The risk of infection or sepsis is particularly associated with the placement of an intravenous catheter (venous access device). The doctor will carefully monitor the patient for any signs of infection. Maintaining sterile procedures (aseptic technique) during catheter insertion and maintenance, as well as during preparation of the infusion mixture, may reduce the risk of infection.

CLINIMIX with electrolytes contains calcium. It should not be administered together with the antibiotic ceftriaxone, as this may lead to particle formation.

In cases of severe malnutrition requiring intravenous nutrient administration, parenteral nutrition should be initiated slowly and cautiously.

From the beginning of the infusion, the doctor will monitor the patient's condition, especially if the patient has liver, kidney, adrenal or circulatory problems. The doctor should also be informed about severe diseases affecting carbohydrate, fat, protein and salt metabolism (metabolic disorders).

If any unusual symptoms occur, including vein irritation, the infusion must be stopped immediately.

During administration of the medicine, the doctor will perform clinical tests and laboratory examinations to assess effectiveness and continuously monitor safety. If the patient receives the medicine for several weeks, blood tests will be performed regularly. In particular, in cases of glucose intolerance, blood and urine glucose levels require regular monitoring, and if the patient has diabetes, insulin dosage may need adjustment.

Children and adolescents

When administering to infants and children under 2 years of age, the solution (in the bag and administration set) must be protected from light until administration is completed. Exposure of CLINIMIX to light, particularly after addition of trace elements and (or) vitamins, leads to formation of peroxides and other degradation products, which can be minimized by protecting from light.

CLINIMIX with other medicines

Inform your doctor about all medicines currently used or recently taken, as well as any medicines the patient plans to take.

CLINIMIX with electrolytes contains calcium. It should not be administered together with the antibiotic ceftriaxone, as insoluble particles may form.

Due to the potassium content in CLINIMIX, particular caution is required in patients receiving potassium-sparing diuretics (e.g. amiloride, spironolactone, triamterene), angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, or immunosuppressive medicines such as tacrolimus or cyclosporine, due to the risk of hyperkalemia.

Pregnancy, breastfeeding and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.

3. How to use CLINIMIX

Before administration, the seal between the two chambers should be broken and the contents of both
chambers mixed thoroughly.
CLINIMIX may be administered to adults and children.
When used in infants and children under 2 years of age, the solution (in the bag and administration set)
must be protected from light until the end of administration (see section 2).
CLINIMIX is an infusion solution for intravenous administration via peripheral or central venous access.
Dosage – Adults and children
The physician will determine the required dose and duration of administration based on the patient's
age, body weight and height, clinical condition, daily fluid balance, energy requirements, and
nitrogen requirements.
CLINIMIX should always be administered exactly as prescribed by the physician. In case of doubt,
consult the physician.
Treatment may be continued as long as clinically necessary, depending on the patient's condition.
Infusion of one bag usually lasts between 8 and 24 hours.
Administration of a higher than recommended dose of CLINIMIX
If an excessive dose is administered or the infusion rate is too high, an increase in intravascular fluid
volume or excessive blood acidity may occur.
The glucose contained in the product may increase blood and urinary glucose levels. Excessive volume
of solution may cause nausea, vomiting, chills, and electrolyte disturbances. In such cases, the
infusion must be immediately stopped.
In some severe cases, the physician may perform temporary renal dialysis to assist the kidneys in
eliminating excess CLINIMIX.
To prevent such situations, the physician will regularly monitor the patient's condition and check blood
parameters.
In case of any further doubts regarding the use of this medicinal product, consult the physician.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If you notice any changes in your health condition during or after treatment, you should immediately inform your doctor or nurse.
Medical examinations performed by your doctor during treatment should minimize the risk of adverse reactions.
If any unusual signs or symptoms of an allergic reaction occur, such as abnormally low or high blood pressure, development of blue or purple skin discoloration, abnormally rapid heartbeat, breathing difficulties, vomiting, nausea, skin rash, elevated body temperature, excessive sweating, or chills, the infusion will be immediately stopped.
Other adverse reactions have also been observed, occurring with varying frequency:

• Anaphylaxis (severe, sudden allergic reaction that may be life-threatening)
• Increased blood levels of glucose, ammonia, and nitrogen-containing compounds
• Liver function disturbances, abnormal blood test results assessing liver function
• Gallbladder inflammation, presence of gallstones in the gallbladder
• Inflammation of the vein at the infusion site, vein irritation, pain, irritation, warmth, swelling
• Presence of glucose in urine
• Diabetic coma
• Formation of small particles (precipitate) blocking blood vessels in the lungs

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181 C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to gather more information on the safety of using this medicine.

5. How to store CLINIMIX

Keep out of the sight and reach of children.
When used in infants and children under 2 years of age, the solution (in the bag and administration set) must be protected from light until the end of administration (see section 2).
Do not use this medicine after the expiry date stated on the bag and outer packaging (MM/YYYY). The expiry date refers to the last day of the stated month.
Store at room temperature. Do not freeze.
Store in the outer cardboard packaging.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist what to do with medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What CLINIMIX N17G35E contains
The amount of active substances in each bag after mixing the contents of both chambers:

Other ingredients are:

• acetic acid, hydrochloric acid (for adjusting the solution pH),
• water for injections.

What CLINIMIX looks like and contents of the pack
CLINIMIX is an infusion solution supplied in a dual-chamber bag, which is a multilayer plastic bag. The inner (contact) layer of the bag is made of polymers (a blend of polyolefin copolymers) compatible with the solution components and permitted additives. The remaining layers are made of EVA (poly(ethylene-vinyl acetate)) and a copolyester.
Before mixing the contents of the chambers, the amino acid solution and glucose solution are clear, colourless or slightly yellow. After mixing, the solution is also clear, colourless or slightly yellow.
To protect against oxygen exposure, the bag is placed in a protective packaging containing an oxygen-absorbing sachet.
Pack sizes:
1000 ml bags – packed in packs of 8
1500 ml bags – packed in packs of 6
2000 ml bags – packed in packs of 4
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Baxter Polska Sp. z o.o.
ul. Kruczkowskiego 8
00-380 Warsaw, Poland
Manufacturer
Baxter S.A.,
Boulevard René Branquart, 80,
7860 Lessines,
Belgium
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Information intended exclusively for healthcare professionals:

1. QUANTITATIVE COMPOSITION

After mixing the contents of both chambers, the composition of the mixture in the available bag sizes is as follows:

2. DOSAGE AND ADMINISTRATION

Administer only after breaking the seal separating the two chambers and mixing the contents of both compartments.
Dosage and infusion rate
Dosage should be adjusted according to individual nutritional and fluid requirements, energy expenditure, clinical condition, body weight, and ability to metabolize the components of the medicinal product CLINIMIX, as well as any additional energy or protein administered orally or enterally. Furthermore, daily requirements for fluids, nitrogen, and energy decrease progressively with age.
In adults, nitrogen requirement ranges from 0.16 g nitrogen/kg body weight/day (approximately 1 g amino acids/kg body weight/day) to 0.32 g nitrogen/kg body weight/day (approximately 2 g amino acids/kg body weight/day).
In children under 2 years of age, nitrogen requirement ranges from 0.16 g nitrogen/kg body weight/day (approximately 1.0 g amino acids/kg body weight/day) to 0.40 g nitrogen/kg body weight/day (approximately 2.5 g amino acids/kg body weight/day).
In adults and patients aged 12 to 18 years, energy requirement ranges from 25 to 40 kcal/kg body weight/day, depending on the patient's nutritional status and degree of catabolism. Patients under 12 years of age may have higher requirements.
There may be clinical situations in which patients require different amounts of nutrients than those contained in the medicinal product CLINIMIX. In such cases, any adjustments in volume (dosage) must take into account the resulting impact on the dosing of all other nutritional components in CLINIMIX. The rate and volume of infusion should be determined by a physician experienced in pediatric parenteral nutrition and intravenous fluid therapy.
This product does not contain the amino acids cysteine and taurine, considered conditionally essential for infants and children under 2 years of age.
This medicinal product is not recommended for premature newborns, full-term newborns, or children under 2 years of age.
The infusion rate should be adjusted according to the dose, characteristics of the infused solution, total volume of fluids administered over 24 hours, and duration of infusion.
Infusion should last more than 8 hours. Typically, the infusion rate is gradually increased during the first hour to a maximum of 1.4 ml/kg body weight/hour, with a maximum daily dose of 30 ml/kg body weight/day.
Method of administration
When used in infants and children under 2 years of age, the solution (in the bag and administration set) must be protected from light until the end of administration.
Route of administration
The choice between peripheral or central vein depends on the final osmolarity of the mixture.
It is generally accepted that mixtures with an osmolarity of up to approximately 800 mOsm/l can be administered via peripheral veins; however, this varies significantly depending on age, general condition of the patient, status of peripheral veins, duration of infusion, and composition of the nutritional bag.

3. SPECIAL WARNINGS AND PRECAUTIONS FOR USE

WARNINGS
Hypersensitivity reactions/infusion reactions, including hypotension, hypertension, peripheral cyanosis, tachycardia, dyspnea, vomiting, nausea, urticaria, rash, pruritus, flushing, excessive sweating, fever, and chills, have been reported with the use of CLINIMIX products.
Anaphylactic reactions have been reported with other parenteral nutrition products.
Special clinical monitoring is required at the beginning of each intravenous infusion. If any unusual symptoms occur, such as a hypersensitivity reaction/infusion reaction, the infusion must be stopped immediately.
Caution is advised when administering glucose-containing solutions to patients allergic to corn or corn products, if such administration is performed at all.
Precipitation in pulmonary vessels has been reported in patients receiving parenteral nutrition. Some cases have been fatal. Excessive addition of calcium and phosphate increases the risk of calcium phosphate precipitation. Cases of precipitation have been reported even in the absence of phosphate salts in the solution. Precipitation distant from the filter on the infusion line and suspected in vivo precipitation have also been reported. Clinical complications related to pulmonary vessel precipitates may include acute respiratory distress syndrome, pulmonary embolism, and interstitial pneumonitis. In case of symptoms indicating acute respiratory disorders, infusion must be discontinued and a medical evaluation performed. In addition to solution inspection, the infusion set and catheter should be periodically checked for the presence of precipitates.
Ceftriaxone must not be administered simultaneously with intravenous solutions containing calcium, including the medicinal product CLINIMIX N17G35E, through the same infusion set (e.g., via a Y-connector) in patients over 28 days of age (including adults).
If the same infusion set is used for sequential administration, it must be thoroughly flushed with a compatible solution between infusions.
Infection and sepsis may occur in patients receiving parenteral nutrition due to the use of intravenous catheters, inadequate catheter care, or contaminated solutions. Immunosuppression and other factors such as hyperglycemia, malnutrition, and/or underlying disease may predispose patients to infectious complications.
Close monitoring of symptoms and laboratory results to detect fever/chills, leukocytosis, technical complications related to venous access devices, and hyperglycemia may help in early recognition of infection.
The frequency of infection-related complications can be reduced by emphasizing the use of aseptic techniques during catheter placement and maintenance, and during preparation of the nutritional product.
Repletion of nutritional deficiencies in severely malnourished patients may induce a refeeding syndrome characterized by intracellular shifts of potassium, phosphate, and magnesium as anabolic metabolism resumes. Thiamine deficiency and fluid retention may also occur. Careful monitoring and gradual increase in nutrient delivery, avoiding overfeeding, may prevent these complications.
Hypertonic solutions administered via peripheral veins may cause venous irritation. The choice between peripheral or central vein depends on the final osmolarity of the mixture.
Generally, mixtures with an osmolarity of up to approximately 800 mOsm/l can be administered via peripheral veins, although this varies significantly depending on age, general condition of the patient, status of peripheral veins, duration of infusion, and composition of the nutritional bag.
Bags must not be connected in series to avoid air embolism caused by residual air in the first bag.

PRECAUTIONS
Severe water-electrolyte imbalances, severe dehydration, and severe metabolic disturbances should be corrected before initiating infusion.
Metabolic disturbances may occur if the amount of administered nutrients is not adapted to the patient's needs or if the metabolic capacity for any of the nutritional components is not accurately assessed. Adverse metabolic effects may result from excessive or inappropriate nutrient administration or from an inappropriate composition of additional components relative to the patient's individual needs.
Appropriate monitoring during treatment includes frequent assessment of clinical status and laboratory tests, including electrolyte panel and renal and liver function tests.
Patients receiving parenteral nutrition solutions should have their electrolyte requirements carefully assessed and monitored, especially when receiving solutions without electrolytes.
Glucose intolerance is a common metabolic complication in critically ill patients. This may lead to hyperglycemia, glycosuria, and hyperosmolar syndrome following infusion. Blood and urine glucose levels should be routinely monitored, and insulin dosage appropriately adjusted in diabetic patients.
Caution is advised when using this product in patients with renal insufficiency, particularly in cases of hyperkalemia, due to the risk of developing or worsening metabolic acidosis and hyperazotemia if additional extrarenal removal of metabolites is not performed. Fluid and electrolyte status should be carefully monitored in these patients. In cases of severe renal insufficiency, amino acid solutions with a special composition should be preferentially used.
Caution is advised when administering CLINIMIX solution to patients with adrenal insufficiency.
Care should be taken to avoid circulatory overload, especially in patients with pulmonary edema, compensated or uncompensated heart failure. Fluid balance should be monitored during treatment.
In patients with a history of liver disease or hepatic insufficiency, in addition to routine liver function tests, the possibility of hyperammonemia symptoms should be considered.
Liver and biliary tract disorders, including cholestasis, fatty infiltration, fibrosis, and cirrhosis, potentially leading to liver failure, as well as cholecystitis and gallstones, have been observed in some patients on parenteral nutrition. The etiology of these conditions is considered multifactorial and may vary among individual patients. Patients who develop laboratory abnormalities or other signs of liver or biliary tract disorders should be evaluated as early as possible by a physician knowledgeable in liver diseases to determine the cause and initiate appropriate treatment.
Elevated ammonia levels and hyperammonemia may occur in patients receiving amino acid solutions. In some patients, this may indicate inborn errors of amino acid metabolism (see section 4.3 of the Summary of Product Characteristics) or liver failure. Blood ammonia levels should be frequently measured in children under 2 years of age to detect hyperammonemia, which may indicate inborn errors of amino acid metabolism.
Depending on concentration and etiology, hyperammonemia may require immediate intervention.
Infusing amino acids too rapidly may cause nausea, vomiting, and chills. In such cases, infusion should be stopped immediately.
Dosage should generally be selected with caution in elderly patients, due to the higher prevalence of impaired liver, kidney, or cardiac function, concomitant diseases, and use of other medications.

Children and adolescents

• No studies have been conducted in children and adolescents.
• Regarding monitoring of hyperammonemia in children under 2 years of age – see above.

Exposure of parenteral nutrition solutions to light, particularly after addition of trace elements and/or vitamins, may adversely affect clinical outcomes in infants due to the formation of peroxides and other degradation products. When used in infants and children under 2 years of age, the medicinal product CLINIMIX must be protected from light until administration is complete.

4. PRACTICAL INFORMATION ON PREPARATION FOR USE OF THE MEDICINAL PRODUCT AND DISPOSAL OF REMAINDERS

Note: Administer only after breaking the seal and mixing the contents of both chambers.

Remove the protective packaging from the top. Remove the front part of the protective packaging to expose the CLINIMIX bag. Place the bag on a flat, horizontal, clean surface with the handle facing toward you. Discard the protective packaging and the oxygen-absorbing sachet.

Lift the bag by the handle to move fluid from the upper chamber. Squeeze the bag with both hands, starting from the top, until the seals are broken (approximately halfway along their length). Mix the contents by rotating the bag at least 3–5 times. Hang the bag. Remove the plastic cover from the site for puncture with the administration set spike. Firmly insert the spike into the port.

Do not use if the solution is not clear, colorless or slightly yellow, or if the container is damaged.
Before administration, bring CLINIMIX to room temperature.
The contents of both chambers of the CLINIMIX bag may be mixed before or after removal of the protective packaging.
For single use only.
Do not store partially used containers; discard all equipment after use.
Do not reconnect partially used bags.
Do not connect bags in series.
When used in infants and children under 2 years of age, protect from light until administration is complete. Exposure of the medicinal product CLINIMIX to light, particularly after addition of trace elements and/or vitamins, leads to the formation of peroxides and other degradation products, which can be minimized by providing protection from light.

Additional components
Patients receiving long-term parenteral nutrition require additional supplementation with lipids, vitamins, and trace elements.
If addition of other components is necessary, their compatibility with the solution should be checked and the stability of the mixture controlled.
All additional components should be added only after breaking the seal (after mixing the contents of both chambers). CLINIMIX may be supplemented with the following components:

• lipid emulsions (e.g., CLINOLEIC 20%) in a volume of 50 to 250 ml per 1 liter of CLINIMIX.

• electrolytes: per 1 liter of CLINIMIX

• trace elements: per 1 liter of CLINIMIX

• vitamins: per 1 liter of CLINIMIX

Information on the stability of the CLINIMIX mixture with other available fat emulsions and
with other additives and nutritional components is available upon request.
If slight separation of the mixture is observed, gently shake the solution containing the added
component thoroughly until a homogeneous emulsion is obtained prior to administration.
Additives must be introduced under aseptic conditions.
Additives may be added using a syringe or an infusion set with a needle.

• Adding an additive using a syringe or an infusion set with a needle:
  o Prepare the injection port (single port, see Fig. 1 in the Summary of Product Characteristics).
  o Pierce the port and inject the additive.
  o Mix the solution with the added components thoroughly.

Incompatibilities
Additives may cause pharmaceutical incompatibilities. For detailed information, please contact the marketing authorization holder.
If addition of other components is necessary, their compatibility with the solution must be verified and the stability of the mixture monitored.
Due to the risk of pseudoagglutination, the solution must not be administered before, during, or after blood transfusion using the same infusion set.
CLINIMIX N17G35E contains calcium ions, which pose an additional risk of clotting in blood or blood components preserved with citrate.
As with any parenteral nutrition mixture, care must be taken regarding the calcium-to-phosphate ratio. Excessive addition of calcium and phosphates, especially in the form of mineral salts, may lead to precipitation of calcium phosphate.
As with other intravenous solutions containing calcium, concomitant administration of ceftriaxone and CLINIMIX N17G35E is contraindicated in neonates (≤ 28 days of life), even if separate infusion sets are used (due to the risk of death caused by precipitation of calcium-ceftriaxone salts in the infant's circulation).
In patients older than 28 days of life (including adults), ceftriaxone must not be administered simultaneously with intravenous solutions containing calcium, including CLINIMIX N17G35E, via the same infusion set (see Warnings section).
If the same infusion set is used for sequential infusions, it must be thoroughly flushed with a compatible fluid between infusions.

5. SHELF LIFE

2 years if stored in the protective packaging.
It is recommended that the product be used immediately after opening the dividing seals between the two compartments. However, it has been demonstrated that after mixing the contents of both compartments (i.e., after breaking the internal seal separating the compartments), the resulting mixture maintains chemical and physical stability for 7 days at a temperature of 2 °C to 8 °C, followed by 48 hours at a temperature below 25 °C.
When additional components are introduced into the mixture, from a microbiological standpoint, the mixture should be used immediately. If the mixture is not used immediately after preparation and supplementation was not performed under controlled, validated, and sterile conditions, the user is responsible for determining the storage time and conditions prior to use. This storage time should generally not exceed 24 hours at a temperature of 2 °C to 8 °C. In exceptional cases where longer storage of the ready-to-use mixture is required, the manufacturer may be contacted, as stability data for chemical and physical stability over 7 days at 2 °C to 8 °C, followed by 48 hours below 25 °C, are available for the products listed in the previous section.
Baxter, Clinimix, ClinOleic are trademarks of Baxter International Inc.