Clinimix N9g15e

Leaflet accompanying the packaging: information for the user

CLINIMIX N9G15E

Infusion solution

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so you can read it again if you need to.
• In case of any doubts, you should 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, or 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 adjust the dose or add additional nutrients, such as fats, vitamins, electrolytes, and trace elements, if 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 (intravenous catheter) in the patient's vein. The doctor will closely monitor the patient to detect any signs of infection. Using aseptic procedures when inserting and maintaining the catheter and during the 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 particles may form. In cases of severe malnutrition requiring intravenous nutrition, it is recommended to start parenteral nutrition slowly and with caution. From the beginning 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 vein irritation, 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 it from light.

CLINIMIX and other medicines

The patient should tell 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 particles may form. 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. If there are any 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 much medicine or the infusion is too fast, it may lead to an increase in fluid volume in the circulatory system or the blood may become too acidic. The glucose contained in the product may increase blood and urine glucose levels. Administering 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. If there are any further doubts about using 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 well-being 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 (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
• Vein inflammation at the injection site, 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, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, 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 out of sight and reach of 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. 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 ingredients 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 packs of 8, 1500 ml bags – packaged in packs of 6, 2000 ml bags – packaged in packs of 4. Not all pack sizes may be marketed.

Marketing authorization holder

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

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 ingredients 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). The infusion rate should be determined by the doctor, taking into account the dose, the characteristics of the administered solution, the total volume of fluids administered in 24 hours, and the duration of the infusion. The infusion should last more than 8 hours. Usually, the infusion rate is gradually increased over the first hour to a maximum value of 3 ml/kg body weight/hour, and the maximum daily dose is 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) 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 the composition of the administered nutrition bag.

3. SPECIAL WARNINGS AND PRECAUTIONS FOR USE

WARNINGS

When using CLINIMIX products, hypersensitivity reactions/infusion reactions, including hypotension, hypertension, peripheral cyanosis, tachycardia, dyspnea, vomiting, nausea, rash, itching, flushing, sweating, fever, and chills, have been reported. 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. Patients allergic to corn or corn products should be cautious when administering glucose-containing solutions, if 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. Cases of distant precipitation and suspected in vivo precipitation have also been reported. Clinical complications associated with pulmonary vessel precipitation, such as acute respiratory distress syndrome, pulmonary embolism, and interstitial pneumonia, can occur. 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 receiving amino acid solutions, increased blood ammonia levels and hyperammonemia can occur. In some patients, this may indicate congenital amino acid metabolism disorders (see section 4.3 of the Summary of Product Characteristics) or liver failure. Blood ammonia levels should be measured frequently in children under 2 years of age to detect hyperammonemia, which may indicate congenital amino acid metabolism disorders. Depending on the concentration and etiology, hyperammonemia may require immediate intervention. Too rapid infusion of amino acids can cause nausea, vomiting, and chills. In such cases, the infusion should be stopped immediately. In general, caution should be exercised when choosing a dose for the elderly, due to the higher frequency of liver, kidney, or heart function disorders, as well as concomitant diseases and the use of other medicines. 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, especially after adding trace elements and/or vitamins, may have an adverse effect on clinical outcomes in infants, resulting in the formation of peroxides and other degradation products. When used in infants and children under 2 years of age, CLINIMIX should be protected from light until the end of administration.

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

PREPARATION FOR ADMINISTRATION AND DISPOSAL OF THE PRODUCT

WARNING: 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, with the hanger facing upwards.

Lift the bag by the hanger to remove the liquid from the top of the bag. Twist the bag with both hands, starting from the top, 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 spike of the administration set firmly into the injection site. 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 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 it from light.

Additional ingredients

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

• 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 should be thoroughly mixed with the added ingredient by gently shaking until a homogeneous emulsion is obtained before administration. Additional ingredients must be added under aseptic conditions. Additional ingredients can be added using a syringe or administration set with a needle.

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

Incompatibilities

Additional ingredients may cause incompatibilities. For detailed information, please contact the marketing authorization holder. If the addition of other ingredients is necessary, their compatibility with the solution should be checked and the stability of the mixture monitored. Due to the possibility of pseudoagglutination, the solution should not be administered before, during, or after blood transfusion using the same administration set. CLINIMIX N9G15E contains calcium ions, which increase the risk of coagulation in blood or blood components preserved with citrate. As with any parenteral nutrition mixture, attention should be paid to the calcium-to-phosphate ratio. Adding excessive calcium and phosphate, especially in the form of mineral salts, can lead to the precipitation of calcium phosphate.

As with other calcium-containing infusion solutions, simultaneous administration of ceftriaxone and CLINIMIX N9G15E is contraindicated in newborns (≤ 28 days of age), even if separate infusion sets are used (due to the risk of death from precipitation of ceftriaxone calcium salts in the infant's circulation). In patients over 28 days of age (including adults), ceftriaxone should not be administered simultaneously with intravenous solutions containing calcium, including CLINIMIX N9G15E, through the same infusion set (see Warnings). 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 breaking the seals separating the contents of the 2 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 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 ingredients to the mixture, from a microbiological point of view, such a 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 should not normally exceed 24 hours at a temperature of 2°C to 8°C. If longer storage of the prepared mixture is necessary, the manufacturer can be contacted, as stability data for chemical and physical stability for 7 days at a temperature of 2°C to 8°C and then 48 hours at a temperature below 25°C are available for the aforementioned products. Baxter, Clinimix, and ClinOleic are trademarks of Baxter International Inc.