Clinimix N9G15E solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Clinimix N9G15E infusion solution

Read this entire leaflet carefully before starting administration of this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are 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 administration of CLINIMIX
3. How CLINIMIX is administered
4. Possible adverse reactions
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 an infusion solution. It is supplied in a dual-chamber bag. One chamber contains an amino acid solution with electrolytes, and the second chamber contains a glucose solution with calcium chloride. The chambers are separated by a non-permanent seal. The contents of the chambers must be mixed immediately before administration by rolling the top portion of the bag to break the seals.

CLINIMIX is administered to provide nutrition to adults and children through a tube connected to a vein when normal oral feeding is not appropriate.

CLINIMIX must only be administered under medical supervision.

2. What you need to know before starting administration of Clinimix

CLINIMIX must not be administered if:

• you are allergic to the active substances or to any of the other components of this medicine (listed in section 6),
• your body has difficulty utilizing certain amino acids,
• you have too much sugar in your blood (severe hyperglycemia),
• your blood is excessively acidic (metabolic acidosis due to lactate excess),
• you have too high a level of sodium, potassium, magnesium, calcium and/or phosphorus in your blood (hypernatremia, hyperkalemia, hypermagnesemia, hypercalcemia and/or hyperphosphatemia),
• in children under 28 days of age, ceftriaxone must not be co-administered with intravenous solutions containing calcium, as particles may form.

In all cases, your doctor will decide whether you should be given this medicine based on factors such as age, weight, and clinical condition, together with the results of all tests performed.

Warnings and precautions

Talk to your doctor or nurse before you are given CLINIMIX.

If any abnormal signs or symptoms of an allergic reaction occur, such as fever, chills, skin rash, difficulty breathing, excessive sweating, nausea, or headache, inform your doctor or nurse immediately: the infusion will be stopped immediately. Your doctor will monitor your condition during administration of this medicine and may adjust the dose or add other nutrients such as lipids, vitamins, electrolytes, and trace elements as appropriate.

Certain medicines and diseases may increase the risk of developing an infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (intravenous catheter) is placed into your vein. Your doctor will carefully monitor you for any signs of infection. The use of aseptic techniques (germ-free) when inserting and maintaining the catheter and when preparing the nutritional formulation can reduce the risk of infection.

CLINIMIX with electrolytes contains calcium. It must not be administered together with the antibiotic ceftriaxone because particles may form.

If you are severely malnourished and require intravenous feeding, parenteral nutrition should be started slowly and carefully.

Your doctor will monitor your condition at the start of the infusion, especially if you currently have liver, kidney, adrenal, heart or circulatory problems. Your doctor should also be aware of any serious conditions affecting how your body handles sugars, fats, proteins, or salts (metabolic disorders). If any abnormal signs occur, including venous irritation, the infusion should be stopped.

To monitor the effectiveness and safety of treatment, your doctor will perform laboratory and clinical tests while you are receiving this medicine. If you are receiving this medicine for several weeks, your blood will be tested regularly. In particular, in cases of glucose intolerance, blood and urine glucose levels will be routinely monitored, and if you are a diabetic patient, your insulin dose may need to be adjusted.

Children and adolescents

When used in newborns and children under 2 years of age, the solution (in bags and administration sets) must be protected from exposure to light until administration is complete. Exposure of Clinimix to ambient light, especially after mixing with trace elements and/or vitamins, may generate peroxides and other degradation products, which can be minimized by protecting from light exposure.

Interaction of CLINIMIX with other medicines

Inform your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines.

CLINIMIX with electrolytes contains calcium. It must not be administered together with the antibiotic ceftriaxone because particles may form.

Due to the potassium content of CLINIMIX, special caution is required in patients treated with potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene), angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, or the immunosuppressants tacrolimus or cyclosporine, due to the risk of hyperkalemia.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

3. How Clinimix is administered

Before administering the product, the non-permanent seal between the two compartments must be broken and the contents of both compartments mixed.

CLINIMIX can be administered to adults and children.

It is an infusion solution administered through a plastic tube connected to a vein in your arm or a large vein in your chest.

When used in newborns and children under 2 years of age, the solution (in the bags and administration sets) must be protected from light exposure until administration is complete (see section 2).

Dosage – Adults and children

Your doctor will determine the dose you need and the duration of treatment, based on your age, weight and height, clinical condition, daily fluid volume, and energy and nitrogen requirements.

Follow exactly the administration instructions for CLINIMIX provided by your doctor. If you have any doubts, consult your doctor.

Administration may continue for as long as necessary, depending on your clinical condition.

The infusion of one bag usually lasts between 8 and 24 hours.

If you are given more CLINIMIX than you should

If the administered dose is too high or the infusion rate too fast, it may increase your blood circulation volume or make your blood excessively acidic. The glucose content may increase your blood and urine glucose levels. Administration of an excessive volume may cause nausea, vomiting, tremors, and electrolyte disturbances. In such situations, the infusion must be stopped immediately.

In some severe cases, your doctor may need to perform temporary renal dialysis to help your kidneys eliminate the excess product.

To prevent such occurrences, your doctor will regularly monitor your condition and perform blood tests.

If you have any further questions about the use of this product, ask your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. If you notice any change in how you feel during or after treatment, inform your doctor or nurse immediately.

The tests your doctor will perform while you are receiving this medicine should minimize the risk of adverse effects.

The infusion will be stopped immediately if any abnormal signs or symptoms of an allergic reaction develop, such as abnormally high or low blood pressure, appearance of blue or purple skin discoloration, abnormally high heart rate, breathing difficulty, vomiting, nausea, skin rashes, increased body temperature, excessive sweating, and chills.

Other adverse effects have been observed, occurring with varying frequency:

• Anaphylaxis (a severe, rapidly developing allergic reaction that may be fatal).
• High levels of glucose, ammonia, and nitrogen-containing compounds in the blood.
• Impaired liver function, abnormal blood tests of liver function.
• Inflammation of the gallbladder, presence of gallstones in the gallbladder.
• Inflammation of the veins at the infusion site, venous irritation, pain, irritation, burning, swelling.
• Presence of glucose in the urine.
• Diabetic coma.
• Formation of small particles that block the pulmonary blood vessels.

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Clinimix

Keep this medicine out of the sight and reach of children.

When used in newborns and children under 2 years of age, the solution (in bags and administration sets) must be protected from exposure to light until administration is complete (see section 2).

Do not use this medicine after the expiry date stated on the container and outer packaging (MM/YYYY). The expiry date refers to the last day of the month indicated.

Do not freeze.

Keep the container in the outer packaging.

Do not dispose of medicines via wastewater or household waste. If you are in doubt, ask your pharmacist how to dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the package and additional information

Composition of Clinimix

The active substances in each bag of the reconstituted solution are:

Active Ingredients	1 L	1.5 L	2 L
L-alanine	5.70 g	8.54 g	11.39 g
L-arginine	3.17 g	4.75 g	6.33 g
Glycine	2.84 g	4.25 g	5.67 g
L-histidine	1.32 g	1.98 g	2.64 g
L-isoleucine	1.65 g	2.48 g	3.30 g
L-leucine	2.01 g	3.02 g	4.02 g
L-lysine (as lysine hydrochloride)	1.60 g (2.00 g)	2.39 g (2.99 g)	3.19 g (3.99 g)
L-methionine	1.10 g	1.65 g	2.20 g
L-phenylalanine	1.54 g	2.31 g	3.08 g
L-proline	1.87 g	2.81 g	3.74 g
L-serine	1.38 g	2.06 g	2.75 g
L-threonine	1.16 g	1.73 g	2.31 g
L-tryptophan	0.50 g	0.74 g	0.99 g
L-tyrosine	0.11 g	0.17 g	0.22 g
L-valine	1.60 g	2.39 g	3.19 g
Sodium acetate 3H2O	2.16 g	3.23 g	4.31 g
Dipotassium phosphate	2.61 g	3.92 g	5.22 g
Sodium chloride	1.12 g	1.68 g	2.24 g
Magnesium chloride 6H2O	0.51 g	0.77 g	1.02 g
Anhydrous glucose (as monohydrated glucose)	75 g (83 g)	113 g (124 g)	150 g (165 g)
Calcium chloride 2H2O	0.33 g	0.50 g	0.66 g

The other components are:

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

Appearance of CLINIMIX and contents of the pack

CLINIMIX is an infusion solution presented in a multilayer plastic dual-chamber bag. The material of the inner layer (in contact) of the bag is made of polymers (a mixture of polyolefinic copolymers) compatible with the components and authorized additives. Other layers are made of EVA (ethylene-vinyl acetate) and a copolyester.

Before reconstitution, the glucose and amino acid solutions are clear, colourless or slightly yellowish. After reconstitution, the solution is also clear, colourless or slightly yellowish.

To avoid contact with atmospheric oxygen, the bag is packaged inside an overpouch acting as an oxygen barrier, which contains an oxygen absorber.

Pack sizes

1000 ml bag: cardboard box containing 8 bags
1 bag of 1000 ml

1500 ml bag: cardboard box containing 6 bags
1 bag of 1500 ml

2000 ml bag: cardboard box containing 4 bags
1 bag of 2000 ml

Only some pack sizes may be marketed.

Marketing Authorisation Holder

Baxter S.L.
Pouet de Camilo 2,
46394 Ribarroja del Turia (Valencia), Spain

Manufacturer

Baxter SA, Boulevard René Branquart, 80, 7860 Lessines, Belgium

This medicinal product is authorised in the European Economic Area member states under the following names:

Clinimix N9G15E, infusion solution

In some countries it is registered under another name, as indicated below:

Germany: Clinimix 3% GE

The latest revision of this leaflet was in September 2021

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

---

This information is intended for healthcare professionals only:

1. Quantitative composition

After mixing the contents of the two compartments, the composition of the binary mixture for all available bag sizes provides the following:

	1 l	1.5 l	2 l
Nitrogen (g) Amino acids (g) Glucose (g)	4.6 28 75	6.8 41 113	9.1 55 150
Total calories (kcal) Calories from glucose (kcal)	410 300	615 450	820 600
Sodium (mmol) Potassium (mmol) Magnesium (mmol) Calcium (mmol)	35 30 2.5 2.3	53 45 3.8 3.4	70 60 5.0 4.5
Acetate (mmol) Chloride (mmol) Phosphate as HPO4 2- (mmol)	50 40 15	75 60 23	100 80 30
pH Osmolarity (mOsm/l)	6 845

1. Dosage and method of administration.

Before administering the product, the temporary seal between the two compartments must be broken and the contents of both compartments mixed.

Dosage and infusion rate

The dosage should be individualized according to the patient's nutritional/fluid requirements, energy expenditure, clinical status, body weight, and ability to metabolize the components of Clinimix, as well as additional energy or protein administered orally/enterally. Furthermore, daily requirements for fluids, nitrogen, and energy continuously decrease with age.

In adults, requirements range between 0.16 g nitrogen/kg/day (approximately 1 g amino acid/kg/day) and 0.32 g nitrogen/kg/day (approximately 2 g amino acid/kg/day).

In infants, requirements range between 0.16 g nitrogen/kg/day (approximately 1 g amino acid/kg/day) and 0.40 g nitrogen/kg/day (approximately 2.5 g amino acid/kg/day).

In adults and patients aged 12 to 18 years, caloric requirements range between 25 kcal/kg/day and 40 kcal/kg/day, depending on the patient's nutritional status and level of catabolism. Patients under 12 years of age may have higher requirements.

There may be clinical situations where patients require nutrient amounts differing from the composition of Clinimix. In such cases, any adjustment in volume (dosage) must take into account the resulting effect on the dosing of all other nutritional components in Clinimix. The rate and volume of infusion must be determined by a prescribing physician experienced in pediatric intravenous fluid therapy.

This medicine does not contain the amino acids cysteine and taurine, considered conditionally essential for neonates and infants.

This medicine is not recommended for premature and term newborns and for children under 2 years of age.

The rate of administration should be adjusted according to the dose, characteristics of the infused solution, total volume intake over 24 hours, and duration of infusion.

The infusion time should exceed 8 hours. Typically, the administration rate is gradually increased during the first hour without exceeding 3 ml per kilogram of body weight per hour, and the maximum dose is 40 ml per kilogram of body weight per day.

Method of administration

When used in newborns and children under 2 years of age, the solution (in bags and administration sets) must be protected from exposure to light until administration is complete.

Route of administration

It should be administered via peripheral or central intravenous route depending on the final osmolarity of the mixture. Generally, the accepted limit for peripheral infusion is approximately 800 mOsm/L, but this varies considerably depending on age, the patient's general condition, and characteristics of the peripheral veins.

1. Warnings and special precautions for use

WARNINGS

Hypersensitivity/infusion reactions, including hypotension, hypertension, peripheral cyanosis, tachycardia, dyspnea, vomiting, nausea, urticaria, rash, pruritus, erythema, hyperhidrosis, fever, and chills, have been reported with CLINIMIX formulations.

Anaphylaxis has been reported with other parenteral nutrition products.

Special clinical monitoring is required when initiating any intravenous infusion. If any abnormal sign or symptom occurs, for example, a hypersensitivity reaction or infusion reaction, the infusion must be stopped immediately.

Solutions containing glucose should be used with caution, in any case, in patients with known allergy to corn or corn-derived products.

Pulmonary vascular precipitates have been reported in patients receiving parenteral nutrition.

In some cases, fatal outcomes have occurred. Excessive addition of calcium and phosphate increases the risk of calcium phosphate precipitate formation. Precipitates have been reported even in the absence of phosphate salts in the solution. Precipitation distal to the in-line filter has also been reported, and in vivo precipitate formation is suspected.

If signs of pulmonary distress occur, the infusion must be stopped and medical evaluation initiated.

In addition to inspection of the solution, the infusion set and catheter should also be periodically checked for precipitates.

In patients over 28 days of age (including adults), ceftriaxone must not be administered intravenously at the same time as calcium-containing solutions, including CLINIMIX N9G15E, via the same infusion line. If the same infusion line is used for sequential administration, it must be carefully flushed with a compatible fluid between infusions.

The use of intravenous catheters to administer parenteral formulations, poor catheter maintenance, or contaminated solutions may lead to infection and sepsis.

Immunosuppression and other factors such as hyperglycemia, malnutrition, and/or underlying disease state may predispose patients to infectious complications.

Symptomatic care and laboratory monitoring of fever/chills, leukocytosis, technical complications with the access device, and hyperglycemia may help detect early infections.

The occurrence of septic complications may be reduced by placing greater emphasis on the use of aseptic techniques in catheter placement, maintenance, and nutritional formula preparation.

Refeeding severely malnourished patients may lead to refeeding syndrome, characterized by shifts in intracellular potassium, phosphate, and magnesium as the patient enters an anabolic state. Thiamine deficiency and fluid retention may also occur. Strict monitoring and gradual nutrient intake, avoiding overfeeding, can prevent these complications.

Hypertonic solutions may cause venous irritation if infused through a peripheral vein. The choice between a peripheral or central vein depends on the final osmolarity of the mixture.

The generally accepted limit for peripheral infusion is about 800 mOsm/L, but this varies considerably with age, the patient's general condition, and characteristics of the peripheral veins.

Do not connect plastic containers in series in order to avoid gas embolism due to possible residual air in the primary container.

PRECAUTIONS

Before initiating infusion, severe disturbances in water and electrolyte balance, severe fluid overload states, and severe metabolic disorders should be corrected.

Metabolic complications may occur if nutrient intake is not adapted to patient requirements, or if the metabolic capacity for any nutritional component is not accurately assessed. Adverse metabolic effects may result from inadequate or excessive nutrient administration, or from a mixture composition inappropriate for the patient's specific needs.

Frequent clinical assessments and laboratory determinations are essential for proper monitoring during administration. These include ionogram determination and kidney and liver function tests.

Electrolyte requirements of patients receiving these solutions must be carefully determined and monitored, especially in the case of electrolyte-free solutions.

Glucose intolerance is a common metabolic complication in severely stressed patients. Infusion of this solution may lead to hyperglycemia, glycosuria, and hyperosmolar syndrome. Blood and urine glucose should be routinely monitored, and insulin dosage adjusted as necessary for diabetic patients.

Use with caution in patients with renal insufficiency, especially if hyperkalemia is present, due to the risk of development or worsening of metabolic acidosis and hyperazotemia if extrarenal waste elimination is not occurring. Fluid and electrolyte status must be carefully monitored in these patients. In cases of severe renal insufficiency, specially formulated amino acid solutions should be selected.

Caution should be exercised when administering Clinimix to patients with adrenal insufficiency.

Circulatory overload should be avoided, especially in patients with pulmonary edema, heart insufficiency, and/or heart failure. Fluid status must be carefully monitored.

In addition to routine liver function tests, patients with pre-existing liver disease or hepatic insufficiency should be monitored for possible signs of hyperammonemia.

Hepatobiliary disorders, including cholestasis, hepatic steatosis, fibrosis, and cirrhosis, which may lead to liver failure, as well as cholecystitis and cholelithiasis, are known to occur in some patients receiving parenteral nutrition. The etiology of these disorders is believed to be multifactorial and may differ among patients. Those who develop abnormal laboratory parameters or other signs of hepatobiliary disorders should be rapidly evaluated by a clinical expert in liver diseases to identify potential causal and contributing factors and possible therapeutic and prophylactic interventions.

In patients receiving amino acid solutions, blood ammonia levels may increase, leading to hyperammonemia. In some patients, this may indicate the presence of a congenital amino acid metabolism disorder (see Section 4.3 of the Summary of Product Characteristics) or hepatic insufficiency.

Blood ammonia levels should be frequently measured in newborns and infants to detect hyperammonemia, which may indicate the presence of a congenital amino acid metabolism abnormality.

Depending on severity and etiology, hyperammonemia may require immediate intervention.

Infusing amino acids too rapidly may cause nausea, vomiting, and chills. In such cases, the infusion must be stopped immediately.

In general, dosage for elderly patients should be cautious, taking into account the higher frequency of hepatic, renal, or cardiac insufficiency, concomitant diseases, or concomitant drug therapy.

Paediatric population

• No studies have been conducted in the paediatric population.
• See above regarding monitoring for hyperammonemia in paediatric patients.

Exposure to light of intravenous parenteral nutrition solutions, especially after mixing with trace elements or vitamins, may have adverse effects on clinical outcomes in newborns due to the generation of peroxides and other degradation products. When used in newborns and children under 2 years of age, Clinimix must be protected from ambient light until administration is complete.

1. Practical information on preparation and handling

Precaution: Administer the product only after breaking the seal and mixing the contents of the two compartments.

1.		2.		3.
	Break from the top to open the overpouch.	Remove the front portion of the overpouch to access the Clinimix bag. Discard the overpouch and the oxygen-absorbing sachet.	Place the bag on a clean, flat surface with the handle facing toward you.
4.		5.		6.
	Lift the hanger area to remove the solution from the top portion of the bag. Firmly roll the bag until the seal is fully opened (approximately halfway).	Mix the contents by inverting the bag at least three times.	Hang the bag. Rotate the protector to remove it from the administration port. Securely connect the spike connector.

Use the solution only if it is clear, colorless or slightly yellowish, and if the container is undamaged.

CLINIMIX must be at room temperature before use.

Activation of CLINIMIX can be performed either within the overpouch or after its removal.

For single use only.

Do not store partially used containers and discard all equipment after use.

Do not reconnect a partially used bag.

Do not connect in series.

When used in newborns and children under 2 years of age, protect from light exposure until administration is complete. Exposure of Clinimix to ambient light, especially after mixing with trace elements or vitamins, may generate peroxides and other degradation products, which can be minimized by protecting the product from light.

Supplementation

Lipids, vitamins, and trace elements should be provided to patients receiving parenteral nutrition over a prolonged period.

If additive administration is required, compatibility must be verified and mixture stability monitored.

Supplementation may be performed after opening the non-permanent seals, for all additives (once the two solutions have been mixed). CLINIMIX may be supplemented with:

• Lipid emulsions (e.g., ClinOleic) at a rate of 50 to 250 mL per liter of CLINIMIX

	CLINIMIX N9G15E 1 l + 100 ml of Lipids 20%*	CLINIMIX N9G15E 1.5 l + 100 ml of Lipids 20%*	CLINIMIX N9G15E 2 l + 250 ml of Lipids 20%*
Nitrogen (g) Amino acids (g) Glucose (g) Lipids (g)	4.6 28 75 20	6.8 41 113 20	9.1 55 150 50
Total calories (kcal) Calories from glucose (kcal) Lipid calories (kcal) Glucose/lipid ratio	610 300 200 60/40	815 450 200 69/31	1320 600 500 55/45
Sodium (mmol) Potassium (mmol) Magnesium (mmol) Calcium (mmol) Acetate (mmol) Chloride (mmol) Phosphate as HPO4 2- (mmol)	35 30 2.5 2.3 50 40 15	53 45 3.8 3.4 75 60 23	70 60 5.0 4.5 100 80 30
pH Osmolarity (mOsm/l)	6 795	6 810	6 785

• Electrolytes: per liter of CLINIMIX

Up to a final concentration of	Sodium	Potassium	Magnesium	Calcium
80 mmol	60 mmol	5.6 mmol	3.0 mmol

• Trace elements: per liter of CLINIMIX

Up to a final concentration of	Copper	10 μmol	Zinc	77 μmol
Chromium	0.14 μmol	Manganese	2.5 μmol
Fluoride	38 μmol	Cobalt	0.0125 μmol
Selenium	0.44 μmol	Molybdenum	0.13 μmol
Iodine	0.5 μmol	Iron	10 μmol

• Vitamins: per liter of CLINIMIX

Up to a final concentration of	Vitamin A	1750 IU	Biotin	35 μg
Vitamin B6	2.27 mg	Vitamin B1	1.76 mg
Vitamin D	110 IU	Folic acid	207 μg
Vitamin B12	3.0 μg	Vitamin B2	2.07 mg
Vitamin E	5.1 mg	Vitamin C	63 mg
Vitamin PP	23 mg	Vitamin B5	8.63 mg
Vitamin K	75 μg

Stability data for CLINIMIX supplementation with other marketed lipid emulsions and other additives or nutrients are available upon request.

If a slight creaming is observed, thoroughly mix the solution by gentle agitation to obtain a uniform emulsion prior to infusion.

Additions must be performed under aseptic conditions.

Additions may be performed using a syringe or a transfer device.

• Addition using a syringe or transfer device with a needle.

• Prepare the injection port (the single tube, see Figure 1).

• Pierce the tube and inject.

• Mix the solution and additives thoroughly.

Incompatibilities

Additives may be incompatible; consult the manufacturer for further details.

If additives are required, compatibility must be reviewed and the stability of the mixtures monitored.

This solution must not be administered with, before, or after blood administration through the same administration set due to the risk of pseudoagglutination.

CLINIMIX N9G15E contains calcium ions, which pose an additional risk of coagulation in citrate-anticoagulated/conserved blood or its components.

As with any parenteral nutrition mixture, the ratios of calcium and phosphate must be considered. Excessive addition of calcium and phosphate, especially in the form of mineral salts, may lead to the formation of calcium phosphate precipitates.

As with other infusion solutions containing calcium, concomitant administration of ceftriaxone and CLINIMIX N9G15E is contraindicated in neonates (≤ 28 days of age), even if separate infusion lines are used (risk of fatal precipitation of calcium-ceftriaxone salt in the neonate's bloodstream).

In patients older than 28 days (including adults), intravenous ceftriaxone must not be administered simultaneously with calcium-containing solutions, including CLINIMIX N9G15E solutions, through the same infusion line (see section Warnings).

If the same infusion line is used for sequential administration, it must be thoroughly flushed with a compatible fluid between infusions.

1. Shelf life

2 years if stored in the overpouch.

It is recommended to use the product immediately after opening the non-permanent seal between the two chambers. However, once reconstituted (i.e., after opening the internal non-permanent seal), the reconstituted solution has been shown to be stable for up to 7 days at 2 °C to 8 °C, followed by up to 48 hours at a temperature not exceeding 25 °C.

From a microbiological standpoint, mixtures should be used immediately after additives have been added. If not used immediately, the in-use storage duration and conditions prior to use are the responsibility of the user and should not exceed 24 hours at 2–8°C, unless the additions were performed under controlled and validated aseptic conditions. If longer storage periods under exceptional circumstances are required, the company may be contacted, as stability data (physical and chemical) are available for use up to 7 days at 2–8°C followed by 48 hours at temperatures below 25°C for the products indicated in the previous section.