Clinimix N17g35e

Leaflet accompanying the packaging: information for the user

CLINIMIX N17G35E

Infusion solution

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or nurse.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Table of contents of the leaflet

• 1. What is CLINIMIX and what is it used for
• 2. Important information before using CLINIMIX
• 3. How to take CLINIMIX
• 4. Possible side effects
• 5. How to store CLINIMIX
• 6. Contents of the packaging and other information

1. What is CLINIMIX and what is it used for

CLINIMIX is an infusion solution. It is supplied in a dual-chamber bag. 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 breakable seal. The contents of both chambers should be mixed just before administration, by squeezing or twisting the bag from the top to break the seal. CLINIMIX is administered intravenously to provide nutrients to adults and children when oral nutrition is not appropriate. CLINIMIX can only be administered under medical supervision.

2. Important information before using CLINIMIX

When not to use CLINIMIX

• if the patient has a known hypersensitivity to any of the ingredients of the medicine (listed in section 6)
• if the use of certain amino acids causes problems for the patient's body
• if the patient has high blood sugar levels (severe hyperglycemia)
• if the patient's blood has an acidic pH (metabolic acidosis caused by increased lactate levels)
• if the patient's blood has high levels of sodium, potassium, magnesium, calcium, and/or phosphorus (hypernatremia, hyperkalemia, hypermagnesemia, hypercalcemia, and/or hyperphosphatemia).
• in children under 28 days of age, ceftriaxone should not be administered simultaneously with intravenous fluids, as insoluble particles may form.

In each case, the doctor's decision to administer this medicine to the patient will depend on factors such as age, body weight, clinical condition, including the results of any tests performed.

Warnings and precautions

Before starting treatment with CLINIMIX, the patient should discuss it with their doctor or nurse. If unusual symptoms or signs of an allergic reaction occur, such as fever, chills, rash, difficulty breathing, excessive sweating, nausea, or headache, the patient should inform their doctor or nurse immediately: the infusion will be stopped immediately. The doctor will monitor the patient's condition during treatment and may recommend a change in dosage or addition of other nutritional components, such as fats, vitamins, electrolytes, and trace elements, if deemed necessary. Certain medications and diseases may increase the risk of developing infections or sepsis (presence of bacteria in the blood). There is a particular risk of infection or sepsis associated with the insertion of a venous catheter (central venous catheter). The doctor will closely monitor the patient to detect any signs of infection. Using aseptic procedures during catheter insertion and maintenance, as well as during preparation of the nutrition mixture, can reduce this risk of infection. CLINIMIX with electrolytes contains calcium. It should not be administered simultaneously with the antibiotic ceftriaxone, as this may lead to the formation of particles. In cases of severe malnutrition requiring intravenous nutrition, it is recommended to start parenteral nutrition slowly and with caution. From the start of the infusion, the doctor will monitor the patient's condition, especially if they have liver, kidney, adrenal, or circulatory problems. The doctor should also be informed about severe diseases affecting carbohydrate, fat, protein, and salt metabolism in the body (metabolic disorders). If any unusual symptoms occur, including phlebitis, the infusion should be stopped immediately. During treatment, the doctor will perform clinical tests and laboratory tests to check the effectiveness and safety of the treatment. 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 dosing may need to be adjusted.

Children and adolescents

When used in infants and children under 2 years of age, the solution (in the bag and administration set) should be protected from light until the end of administration (see section 2). Exposure of CLINIMIX to light, especially after adding trace elements and/or vitamins, leads to the formation of peroxides and other degradation products, which can be limited by protecting from light.

CLINIMIX and other medicines

The patient should inform their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. CLINIMIX with electrolytes contains calcium. It should not be administered simultaneously with the antibiotic ceftriaxone, as this may lead to the formation of particles. Due to the potassium content in CLINIMIX, special caution should be exercised in patients taking potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene), ACE inhibitors, angiotensin II receptor antagonists, or immunosuppressive drugs such as tacrolimus or cyclosporine, due to the risk of hyperkalemia.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine.

3. How to take CLINIMIX

Before administration, the seal between the two chambers should be broken and the contents of both chambers mixed. 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) should be protected from light until the end of administration (see section 2). CLINIMIX is an infusion solution for intravenous administration.

Dosage - Adults and children

The doctor will decide what dose the patient needs and for how long it will be administered. This will depend on the patient's age, weight, and clinical condition, daily fluid balance, energy requirements, and nitrogen requirements. CLINIMIX should always be taken exactly as prescribed by the doctor. In case of doubts, the patient should consult their doctor. Treatment can be continued for as long as necessary, depending on the patient's clinical condition. The infusion of one bag usually lasts between 8 and 24 hours.

Overdose of CLINIMIX

If the patient is given too high a dose of the medicine or if the infusion is too rapid, it may lead to an increase in fluid volume in the circulatory system or an acidic blood reaction. The glucose contained in the product may increase blood and urine glucose levels. Administration of too much solution may cause nausea, vomiting, chills, and electrolyte disturbances. In such cases, the infusion should be stopped immediately. In some severe cases, to support the patient's kidneys in eliminating excess CLINIMIX, the doctor may use temporary dialysis. To prevent such situations, the doctor regularly monitors the patient's condition and checks blood parameters. In case of any further doubts about the use of this medicine, the patient should consult their doctor.

4. Possible side effects

Like all medicines, CLINIMIX can cause side effects, although not everybody gets them. If the patient notices any changes in their condition during or after treatment, they should inform their doctor or nurse immediately. Tests performed by the doctor during treatment should minimize the risk of side effects. If any unusual signs or symptoms of an allergic reaction occur, such as abnormal blood pressure, blue or purple discoloration of the skin, rapid heart rate, breathing difficulties, vomiting, nausea, rash, elevated body temperature, excessive sweating, or chills, the infusion will be stopped immediately. Other side effects have also been observed, which occurred with greater or lesser frequency:

• Anaphylaxis (a severe allergic reaction that can be life-threatening)
• Increased blood glucose, ammonia, and nitrogen-containing compounds
• Liver function disorders, abnormal liver function test results
• Gallbladder inflammation, presence of gallstones in the gallbladder
• Phlebitis, vein irritation, pain, irritation, warmth, swelling
• Glucose in the urine
• Diabetic coma
• Formation of small particles (precipitate) blocking blood vessels in the lungs

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych, Al. Jerozolimskie 181 C, 02-222 Warszawa, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. Reporting side effects can help gather more information on the safety of the medicine.

5. How to store CLINIMIX

Store in a place invisible and inaccessible to children. When used in infants and children under 2 years of age, the solution (in the bag and administration set) should be protected from light until the end of administration (see section 2). Do not administer this medicine after the expiry date stated on the label of the bag and outer packaging (MM/RRRR). The expiry date refers to the last day of the specified month. Store at room temperature. Do not freeze. Store in the outer carton packaging. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer need. This will help protect the environment.

6. Contents of the packaging and other information

What CLINIMIX contains

The active substance content in each bag after mixing the contents of both chambers:

Other ingredients are:

• acetic acid, hydrochloric acid (to adjust the pH of the solution),
• water for injections.

What CLINIMIX looks like and what the packaging contains

CLINIMIX is an infusion solution supplied in a dual-chamber bag, which is a multi-layer plastic bag. The inner (contact) layer of the bag is made of polymers (a mixture of polyolefin copolymers) that are compatible with the solution components and permitted additives. The other 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, colorless, or slightly yellow. After mixing, the solution is also clear, colorless, or slightly yellow. To protect against oxygen, the bag is placed in a protective packaging that contains an oxygen-absorbing sachet. Packaging sizes: 1000 ml bags - packaged in 8 units; 1500 ml bags - packaged in 6 units; 2000 ml bags - packaged in 4 units. Not all packaging types may be marketed.

Marketing authorization holder

Baxter Polska Sp. z o.o., ul. Kruczkowskiego 8, 00-380 Warszawa

Manufacturer

Baxter S.A., Boulevard René Branquart, 80, 7860 Lessines, Belgium

Date of last revision of the leaflet:

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Information intended for healthcare professionals only:

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 and mixing the contents of both chambers.

Dosage and infusion rate

Dosage should be adjusted to the individual nutritional and fluid needs of the patient, 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. Additionally, with age, the daily requirement for fluids, nitrogen, and energy decreases. In adults, the requirement is from 0.16 g of nitrogen/kg body weight/day (about 1 g of amino acids/kg body weight/day) to 0.32 g of nitrogen/kg body weight/day (about 2 g of amino acids/kg body weight/day). In children under 2 years of age, the requirement is from 0.16 g of nitrogen/kg body weight/day (about 1.0 g of amino acids/kg body weight/day) to 0.40 g of nitrogen/kg body weight/day (about 2.5 g of amino acids/kg body weight/day).

In adults and patients aged 12 to 18 years, energy requirements range 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. The infusion rate should be determined by the doctor, taking into account the patient's individual needs, the composition of the administered bag, and the duration of the infusion. The infusion should last more than 8 hours. The infusion rate is usually increased gradually over the first hour to a maximum value of 1.4 ml/kg body weight/hour, and the maximum daily dose is 30 ml/kg body weight/day. In cases where the patient requires other amounts of nutrients than those in the composition of the medicinal product CLINIMIX, any corrections to the volume (dose) must take into account the resulting effect on the dosing of all other nutrients in the medicinal product CLINIMIX.

Method of administration

When used in infants and children under 2 years of age, the solution (in the bag and administration set) should be protected from light until the end of administration.

Route of administration

The choice of peripheral or central vein depends on the final osmolality of the mixture. It is generally accepted that mixtures with an osmolality of up to approximately 800 mOsm/l can be administered into peripheral veins, but this varies significantly depending on the patient's age, overall condition, peripheral vein condition, infusion duration, and composition of the administered bag.

3. SPECIAL WARNINGS AND PRECAUTIONS FOR USE

WARNINGS

When using CLINIMIX products, reports of hypersensitivity reactions/infusion reactions, including hypotension, hypertension, peripheral cyanosis, tachycardia, dyspnea, vomiting, nausea, rash, urticaria, pruritus, flushing, diaphoresis, fever, and chills, have been received. Anaphylactic reactions have been reported with the use of other parenteral nutrition products. At the start of each intravenous infusion, close clinical monitoring is necessary. If any unusual symptoms occur, such as a hypersensitivity reaction/infusion reaction, the infusion should be stopped immediately. In patients allergic to corn or corn products, caution should be exercised when administering glucose-containing solutions, if they are administered at all. In patients receiving parenteral nutrition, precipitation in pulmonary vessels has been observed, which can be fatal. The risk of precipitation is increased by excessive calcium and phosphate intake. Cases of precipitation have been reported even in the absence of phosphate salts in the solution. Reports have also been made of precipitation occurring away from the filter on the infusion line and suspected in vivo precipitation. Clinical complications associated with pulmonary vessel precipitation may occur, such as acute respiratory distress syndrome, pulmonary embolism, and interstitial pneumonia. If symptoms of acute respiratory distress occur, the infusion should be stopped and a medical examination performed. In addition to checking the solution, the infusion set and catheter should also be periodically checked for precipitation. In patients over 28 days of age (including adults), ceftriaxone should not be administered simultaneously with intravenous fluids containing calcium, including CLINIMIX N17G35E, through the same infusion set (e.g., through a Y-connector). If the same infusion set is used for subsequent administration, it should be thoroughly flushed with a compatible fluid between infusions. Infection and sepsis can occur in patients receiving parenteral nutrition due to the use of central venous catheters, inadequate catheter care, or contaminated solutions. Immunosuppression and other factors such as hyperglycemia, malnutrition, and underlying disease may predispose patients to complications in the form of infections. Close monitoring of symptoms and laboratory test results to detect fever/chills, leukocytosis, technical complications related to vascular access devices, and hyperglycemia may help in the early detection of infection. The risk of complications due to infection can be reduced by increasing the emphasis on aseptic techniques during catheter insertion and maintenance, as well as during preparation of the nutrition mixture. When using CLINIMIX in infants and children under 2 years of age, the product should be protected from light until the end of administration. Exposure of parenteral nutrition solutions to light, especially after adding trace elements and/or vitamins, can have an adverse effect on clinical outcomes in infants due to the formation of peroxides and other degradation products.

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

AND ITS RESIDUES

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

Break the protective packaging
from the top.
Remove the front part of the
protective packaging to expose
the CLINIMIX bag.
Discard the protective packaging
and oxygen-absorbing sachet.
Place the bag on a flat, horizontal,
and clean surface, holding it by
the handle.

Lift the bag by the handle to
remove the liquid from the top
of the bag. Twist the bag with
both hands, starting from the
top of the bag, until the seals
are broken (about halfway
through their length).
Mix the contents of the bag by
turning it at least 3 times.
Suspend the bag. Remove the
plastic cover from the injection
site of the administration set.
Insert the administration set
needle firmly into the injection
site. Do not use if the solution
is not clear, colorless, or slightly
yellow and the container is
damaged. Before administration,
bring CLINIMIX to room temperature.
The contents of both chambers of
the CLINIMIX bag can be mixed
before or after removing the
protective packaging. For single
use only. Do not store partially
used bags and 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 the end of
administration. Exposure of CLINIMIX
to light, especially after adding
trace elements and/or vitamins,
leads to the formation of peroxides
and other degradation products,
which can be limited by protecting
from light.

Additional components

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

• fat emulsions (e.g., CLINOLEIC 20%) in a quantity 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

Data on the stability of the CLINIMIX mixture with other available fat emulsions and other additives and nutrients are available upon request. If a slight separation of the mixture is observed, the solution with the added component should be thoroughly mixed by gently shaking until a homogeneous emulsion is obtained before administration. Additional components must be added under aseptic conditions. Additional components can be added using a syringe or administration set with a needle.

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

Incompatibilities

Additional components may cause pharmaceutical incompatibilities. For detailed information, please contact the marketing authorization holder. If the addition of other components is necessary, their compatibility with the solution and the stability of the mixture should be checked. Due to the risk of pseudoagglutination, the solution should not be administered before, during, or after blood transfusion using the same administration set. CLINIMIX N17G35E contains calcium ions, which pose an additional risk of coagulation in blood products or blood components preserved with citrate. As with any parenteral nutrition mixture, attention should be paid to the calcium-to-phosphate ratio. Adding excess calcium and phosphate, especially in the form of mineral salts, can lead to the formation of a calcium phosphate precipitate. As with other calcium-containing infusion solutions, simultaneous administration of ceftriaxone and CLINIMIX N17G35E is contraindicated in newborns (≤ 28 days of age), even if separate infusion sets are used (due to the risk of death from precipitation of calcium ceftriaxone salts in the infant's circulation). In patients over 28 days of age (including adults), ceftriaxone should not be administered simultaneously with intravenous fluids containing calcium, including CLINIMIX N17G35E, through the same infusion set (e.g., through a Y-connector). If the same infusion set is used for subsequent administration, it should be thoroughly flushed with a compatible fluid between infusions.

If the same infusion set is used for subsequent administration, it should be thoroughly flushed with a compatible fluid between infusions.

5. SHELF LIFE

2 years, if stored in the protective packaging. It is recommended to use the product immediately after opening the seals separating the chambers. However, it has been demonstrated that after mixing the contents of both chambers (i.e., after breaking the internal seal separating the chambers), the resulting mixture retains its chemical and physical stability for 7 days at a temperature of 2°C to 8°C and then for 48 hours at a temperature below 25°C. When adding other components to the mixture, from a microbiological point of view, the mixture should be used immediately. If the mixture is not used immediately after preparation and supplementation did not take place under controlled, validated, and aseptic conditions, the user is responsible for the storage time and conditions before use. This time, usually, should not exceed 24 hours at a temperature of 2°C to 8°C. If, in exceptional cases, longer storage of the prepared mixture is necessary, the manufacturer should be contacted, as stability data for the aforementioned products are available for 7 days at a temperature of 2°C to 8°C and then 48 hours at a temperature below 25°C. Baxter, Clinimix, and ClinOleic are trademarks of Baxter International Inc.