Clinimix n9g15e

Package leaflet: Information for the user

CLINIMIX N9G15E
concentrate for solution for infusion
Please read all of this leaflet carefully before use, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or nurse.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or nurse. See section 4.

Contents of the leaflet

1. What CLINIMIX is and what it is used for
2. Important information before use of CLINIMIX
3. How to use CLINIMIX
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 appropriate.
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 the 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 increased lactate levels)
• if the patient's blood levels of sodium, potassium, magnesium, calcium and (or) phosphorus are too high (hypernatremia, hyperkalemia, hypermagnesemia, hypercalcemia and (or) hyperphosphatemia)
• ceftriaxone must not be administered together with intravenous fluids in children under 28 days of age, as insoluble particles may form.

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

Warnings and precautions

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

If any unusual symptoms or signs of allergic reaction occur, such as fever, chills, skin rash, breathing difficulties, 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.

Some 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. The doctor will carefully monitor the patient to detect any signs of infection. Maintaining aseptic technique (ensuring absence of microorganisms) 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 formation of particles.

In cases of severe malnutrition requiring intravenous administration of nutrients, 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 metabolism of carbohydrates, fats, proteins and salts (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 case 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, especially 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 used, 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 can 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 the infusion (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 dose required by the patient and the duration of administration. This will depend on the patient's age, body weight and height, clinical condition, daily fluid balance, energy requirements, and nitrogen requirements.
CLINIMIX must always be administered exactly as prescribed by the physician. In case of any doubts, consult the physician.
Treatment may be continued as long as clinically necessary, depending on the patient's condition.
The infusion of one bag usually takes between 8 and 24 hours.

Administration of a higher than recommended dose of CLINIMIX
If too high a dose of CLINIMIX is administered or the infusion rate is too fast, it may lead to increased intravascular fluid volume or the blood pH may become too acidic.
The glucose contained in the product may increase blood and urine glucose levels. Excessive volume of infused solution may cause nausea, vomiting, chills, and electrolyte disturbances. In such cases, the infusion must be stopped immediately.
In some severe cases, to assist the patient's kidneys in eliminating excess CLINIMIX, the physician may initiate temporary dialysis.
To prevent such situations, the physician will regularly monitor the patient's condition and check blood parameters.

If you have any further questions regarding the use of this medicinal product, consult your 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 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 observed, occurring with varying frequency, include:

• Anaphylaxis (severe, sudden allergic reaction which may be life-threatening)
• Increased blood levels of glucose, ammonia, and nitrogen-containing compounds
• Liver function disturbances, abnormal blood test results assessing liver function
• Inflammation of the gallbladder, presence of gallstones in the gallbladder
• Inflammation of the veins at the administration 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 may also be reported to the Marketing Authorisation Holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store CLINIMIX

Keep the medicine 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.
Keep in the outer cardboard packaging.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the package and other information

What Clinimix N9G15E contains
The amount of active substances in each bag after mixing the contents of both chambers:

Other ingredients:

• 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 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 overwrap containing an oxygen-absorbing sachet.
Pack sizes:
1000 ml bags – pack of 8
1500 ml bags – pack of 6
2000 ml bags – pack 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 for 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 chambers.
Dosage and infusion rate
Dosage should be adjusted according to individual nutritional and fluid requirements, energy expenditure, clinical condition, body weight, and the ability to metabolize 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 progressively decrease with age.
In adults, the 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, the 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 requirements range between 25 and 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 (dose) must take into account the resulting impact on the dosing of all other nutritional components of CLINIMIX. The infusion rate and volume 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 preterm or term newborns, or for children under 2 years of age.
The infusion rate should be adjusted according to dose, characteristics of the infused solution, total volume of fluids administered over 24 hours, and duration of infusion.
Infusion should last longer than 8 hours. Typically, the infusion rate is gradually increased during the first hour to a maximum of 3 ml/kg body weight/hour, with a maximum daily dose of 40 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 administration is complete.
Route of administration
The choice between peripheral or central venous access 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, erythema, 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 hypersensitivity or infusion reaction, the infusion must be stopped immediately.
Caution should be exercised when administering glucose-containing solutions to patients with corn allergy or sensitivity to corn products, if administered 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 has also been reported downstream of the filter in the infusion line and suspected in vivo precipitation.
Clinical complications associated with pulmonary vessel precipitates may occur, such as acute respiratory distress syndrome, pulmonary embolism, and interstitial pneumonitis. If symptoms of acute respiratory distress occur, the infusion should be stopped immediately and a medical evaluation performed. In addition to checking the solution, the infusion set and catheter should be periodically inspected for the presence of precipitates.
Ceftriaxone must not be administered simultaneously with intravenous solutions containing calcium, including the medicinal product CLINIMIX N9G15E, through the same infusion set (e.g., via a Y-connector) in patients older than 28 days of life (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 parenterally fed patients 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 aid in early recognition of infection.
The frequency of infection-related complications can be reduced by emphasizing strict aseptic techniques during catheter placement and maintenance, as well as during the preparation of the nutritional product.
Repletion of nutritional deficiencies in severely malnourished patients may induce refeeding syndrome, characterized by intracellular shifts of potassium, phosphate, and magnesium as anabolic metabolism begins to dominate. Thiamine deficiency and fluid retention may also occur. Careful monitoring and gradual increase in nutrient intake, avoiding overfeeding, may prevent these complications.
Hypertonic solutions administered via peripheral veins may cause venous irritation. The choice between peripheral or central venous access 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 should not be connected in series to avoid the risk of air embolism due to residual air in the first bag.

PRECAUTIONS
Severe fluid and electrolyte imbalances, severe dehydration, and severe metabolic disturbances should be corrected before initiating infusion.
If the amount of nutrients administered is not matched to patient needs or the metabolic capacity for any nutritional component is not accurately assessed, metabolic disturbances may occur. Undesirable metabolic effects may result from excessive or inappropriate nutrient administration or from an inappropriate composition of additional components relative to the individual patient's needs.
Appropriate monitoring during treatment includes frequent assessment of clinical status and laboratory tests, including serum electrolyte levels and kidney and liver function tests.
Patients receiving parenteral nutrition should have their electrolyte requirements carefully determined and monitored, especially when receiving solutions that do not contain electrolytes.
Glucose intolerance is a common metabolic complication in critically ill patients. Infusion may lead to hyperglycemia, glycosuria, and hyperosmolar syndrome. Blood and urine glucose levels should be routinely monitored, and insulin dosing appropriately adjusted in diabetic patients.
Caution is advised when using this product in patients with renal insufficiency, particularly in the presence of hyperkalemia, due to the risk of developing or worsening metabolic acidosis and hyperazotemia if extrarenal removal of metabolic products is not performed. Fluid and electrolyte status should be closely monitored in these patients. In cases of severe renal failure, amino acid solutions with a special composition should preferably be used.
Caution should be exercised 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, steatosis, fibrosis, and cirrhosis, potentially leading to liver failure, as well as cholecystitis and gallstones, have been observed in some patients receiving parenteral nutrition. The etiology of these conditions is considered multifactorial and may vary among individual patients. Patients who develop abnormal laboratory results 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 hepatic insufficiency. 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, the infusion should be stopped immediately.
In general, caution should be exercised when selecting dosage 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 should be protected from light until administration is complete.

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

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. Mix the contents of the bag by rotating it at least three times. Hang the bag. Remove the plastic cover from the site intended for puncture by the spike of the infusion set. Firmly insert the spike of the infusion set.
Do not use if the solution is not clear, colorless, or slightly yellow, or if the container is damaged.
Before administration, CLINIMIX should be brought 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 chronic parenteral nutrition require additional supplementation with fats, vitamins, and trace elements.
If addition of other components is necessary, their compatibility with the solution and the stability of the mixture should be verified.
All additional components should only be added after breaking the seal (after mixing the contents of both chambers). CLINIMIX may be supplemented with the following components:

• fat emulsions (e.g., CLINOLEIC 20%) in amounts 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 CLINIMIX mixture with other available fat emulsions and
other additives and nutritional components is available upon request.
If slight separation of the mixture is observed, the solution with added component should be thoroughly mixed by gentle shaking until a homogeneous emulsion is obtained prior to administration.
Additives must be introduced under aseptic conditions.
Additives may be added using an injection needle or an infusion set.

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

Incompatibilities
Additional components may cause pharmaceutical incompatibilities. Please contact the marketing authorization holder for detailed information.
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 N9G15E contains calcium ions, which pose an additional risk of precipitation in blood products or blood components preserved with citrate.
As with any parenteral nutrition mixture, care should 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 N9G15E is contraindicated in neonates (≤ 28 days of life), even when 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 age (including adults), ceftriaxone must not be administered simultaneously with intravenous solutions containing calcium, including CLINIMIX N9G15E, through the same infusion set (see Warnings section).
If the same infusion set is used for sequential administration, it must be thoroughly flushed between infusions with a compatible fluid.

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 between 2°C and 8°C, followed by 48 hours at a temperature below 25°C.
From a microbiological standpoint, if additional components are introduced into the mixture, it 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 responsibility for storage time and conditions prior to use lies with the user. This time should generally not exceed 24 hours at a temperature between 2°C and 8°C. In exceptional cases where longer storage of the prepared mixture is necessary, contact the manufacturer, as data on chemical and physical stability for 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.