BFluid

Amino acid, glucose, electrolytes, vitamin B₁.

The upper chamber contains an amino acid solution with electrolytes and the lower chamber contains a glucose solution with electrolytes and vitamin B₁. This product contains the following ingredients: see Tables 1, 2, 3 and 4.

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Pharmacology: BFLUID Injection was administered to intact rats and dogs and laparotomized vitamin B₁-starved rats, and its effects in the provision of vitamin B₁ and electrolytes and its nutritional effects were compared against those of AMINOFLUID Injection. In intact rats and dogs, blood levels of vitamin B₁ remained at preadministration levels in the BFLUID Injection group. In laparotomized vitamin B₁-starved rats, recovery of vitamin B₁ levels to the normal range was observed after BFLUID Injection infusion. Therefore, it was concluded that BFLUID Injection is useful for the provision of vitamin B₁. BFLUID Injection and AMINOFLUID Injection were found to be comparable in terms of the provision of electrolytes and nutrition.
Pharmacokinetics: (Reference data in rats): BFLUID Injection containing ¹⁴C-labeled glucose was administered intravenously to intact rats. The radioactivity was rapidly distributed throughout the body, with particularly high levels observed in the liver (which plays an active role in glucose metabolism) and in the brain (which utilizes a large amount of glucose). The main route of excretion of the administered radioactivity was in the expired air as ¹⁴CO₂, accounting for 62.8% of the administered dose up to 24 hr. Radioactivity was also excreted in the urine (4.9%). The glucose was utilized mainly as an energy source and expired in the breath.
CLINICAL STUDIES: A comparative clinical study of BFLUID was conducted at 16 institutions in Japan. This study included a total of 110 patients who had undergone gastrointestinal surgery. The clinical effects were evaluated in 97 of the 110 patients (46 patients in the BFLUID group and 51 patients in the control group). Blood levels of vitamin B₁ were maintained in the BFLUID group, in contrast to the decreased levels of vitamin B1 observed in the control group. Levels of serum proteins (total protein, albumin, prealbumin, transferrin, and retinol-binding protein) showed similar trends in both groups.
Safety was evaluated in 102 of the 110 patients (50 patients in the BFLUID group and 52 patients in the control group). Adverse events were defined as findings related to signs and symptoms, abnormal changes in vital signs, abnormal changes in laboratory data, and metabolic acidosis. Adverse events for which a relationship to administration of the study drug could not be ruled out were defined as adverse reactions.
For vital signs and laboratory data, adverse events were also defined as values outside the normal range (the standard range for healthy subjects at each facility) after the start of infusion in comparison with postoperative preinfusion values. In addition, if the Investigator or the Co-investigators noted any abnormal changes in outcome variables not specified in the protocol, the changes were handled as adverse events.
A total of 17 (34.0%) of the 50 patients in the BFLUID Injection group experienced 32 adverse reactions, showing no statistically significant difference with the findings in the control group (17 of 52 subjects [32.7%], 36 adverse reactions).
Adverse events are also commonly observed after surgical procedures for gastrointestinal diseases, and their frequencies were comparable to the results for the control group. (Refer to the tables as follows.)
Vitamin B₁ deficiency was not observed in either the BFLUID Injection group or the control group during the 5-day infusion period. (See Table 5.)

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With special regard to the deviations of laboratory values shown in the tables previously, all deviations cannot be judged to be "medically significant adverse reactions" because postoperative fluctuations in laboratory values were not taken into consideration. Therefore, an "abnormal value for which treatment was required" was defined as a "medically significant adverse reaction". A total of 8 (16.0%) of the 50 patients in the BFLUID Injection group experienced 11 medically significant adverse reactions, showing no statistically significant difference with the findings in the control group (8 of 52 patients [15.4%], 10 adverse reactions). (See Table 6.)

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Provision of amino acids, electrolytes, vitamin B₁, and water via a peripheral vein to patients with mild hypoproteinemia or mild malnutrition due to inadequate oral intake, and before and after surgery.

Immediately before use, break the center seal between the two chambers and mix the two solutions thoroughly. The usual adult dosage is 500 mL per dose, infused via a peripheral vein. The usual infusion rate in adults is 500 mL administered over 120 min. The infusion rate should be reduced in the elderly and in critically ill patients. The dosage should be adjusted according to the patient's condition, body weight, and age. The maximum dosage is 2500 mL per day.

Patients with hepatic coma or at risk of developing hepatic coma. [Due to impaired amino acid metabolism, the patient's clinical condition may deteriorate.]
Patients with serious renal dysfunction or azotemia. [The amounts of water and electrolytes may be excessive, causing the patient's clinical condition to deteriorate. Urea and other amino acid metabolites may be retained, which may cause the patient's clinical condition to deteriorate.]
Patients with congestive heart failure. [An increase in the circulating blood volume may cause a burden on the heart, resulting in the patient's clinical condition to deteriorate.]
Patients with severe acidosis (hyperlactacidemia etc.). [The patient's clinical condition may deteriorate.]
Patients with abnormal electrolyte metabolism. [Administration may cause the patient's clinical condition to deteriorate.]
Patients with hyperkalemia (oliguria, Addison's disease etc.).
Patients with hyperphosphatemia (hypoparathyroidism etc.).
Patients with hypermagnesemia (hypothyroidism etc.).
Patients with hypercalcemia.
Patients with reduced urine output due to obstructive uropathy. [Water and/or electrolyte overload may occur, causing the patient's clinical condition to deteriorate.]
Patients with abnormal amino acid metabolism. [Since the infused amino acids are not adequately metabolized, the patient's clinical condition may deteriorate.]
Patients with known hypersensitivity to thiamin chloride hydrochloride.

Careful Administration (BFLUID Injection should be administered with care in the following patients: Patients with hepatic dysfunction. [Abnormalities in water and electrolyte metabolism may be exacerbated.]
Patients with renal dysfunction. [Since these patients have impaired water and electrolyte metabolism, the solution should be administered with care.]
Patients with cardiovascular dysfunction. [An increase in the circulating blood volume may cause a burden on the heart, resulting in the patient's clinical condition to deteriorate.]
Patients with acidosis. [The patient's clinical condition may deteriorate.]
Patients with diabetes mellitus. [Impaired uptake of glucose into the tissues may result in hyperglycemia, which may cause the patient's clinical condition to deteriorate.]
Patients with known hypersensitivity to drugs.
Important Precautions: BFLUID Injection contains 15 g of amino acids (2.35 g nitrogen) and 150 kcal (nonprotein calories) in 500 mL. However, daily caloric requirements cannot be met by administering this solution as the sole source of nutritional support. This solution should therefore be used only for short-term nutritional therapy.
When used as a nutritional supplement in patients in whom oral intake is inadequate, the solution should be administered based on an overall assessment of the patient's nutritional requirements and oral intake.
When this solution is used alone in postoperative patients, its use should be limited to 3-5 days and oral/enteral nutrition or other regimens should be instituted as soon as it is feasible to do so.
BFLUID Injection contains 0.96 mg of thiamin chloride hydrochloride (vitamin B₁) as a vitamin source in 500 mL. Additional vitamin B₁ or other vitamins should be administered, depending on the patient's condition.
Use only as directed by a physician.
Use in Children: The safety of this product in children has not been established (no clinical experience).
Use in the Elderly: Since elderly patients often have reduced physiological function and associated hepatic, renal, or cardiac dysfunction, it is advisable to take measures such as reducing the dose by decreasing the infusion rate under careful supervision.

BFLUID Injection should be used in pregnant women and in women who may possibly be pregnant only if the expected therapeutic benefits outweigh the potential risks associated with administration. (The safety of this product in pregnant women has not been established.)
It is advisable to avoid using this product in nursing mothers. If use of this product is judged to be essential, breast feeding should be discontinued during administration. (The safety of this product in nursing mothers has not been established.)

Reported incidence rates are based on the results obtained for 50 patients who had undergone gastrointestinal surgery in a phase III clinical study. With regard to adverse events (clinically significant adverse reactions), a total of 8 patients (16.0%) experienced 11 adverse reactions, including vascular pain (3), phlebitis (4), and chest discomfort (1) in a total of 7 patients as subjective or objective manifestations and elevated serum AST (GOT) levels (1), elevated serum ALT (GPT) levels (1), and elevated serum ALP levels (1) in a total of 1 patient as abnormal changes in laboratory data. (These data were obtained at the time of drug approval in Japan, 2006.) Refer to the Pharmacology: CLINICAL STUDIES under Actions.
Clinically significant adverse reactions: Shock^[Note] (frequency unknown): Shock may occur. Patients should be closely monitored, and if any signs or symptoms such as decreased blood pressure, chest discomfort, or dyspnea occur, administration should be discontinued immediately and appropriate measures should be taken.
Note: Adverse reactions commonly associated with thiamin chloride hydrochloride injections.
Other adverse reactions: If other adverse reactions are observed, take appropriate measures such as discontinuing administration. (See Table 7.)

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Preparation: Open the outer wrap immediately before use, break the center seal between the two chambers, and mix the two solutions thoroughly. The solution in one chamber should not be administered alone without mixing it with the solution in the other chamber.
Method of mixing two solutions (Never fail to mix two solutions): Be sure to press the lower chamber to break the center seal between the two chambers. When the upper chamber is pressed, the checker does not open. (See Table 8.)

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Precautions at the time of preparation: 1) Physicochemical changes in the solution, such as precipitation, may occur if this product is combined with the following drugs. The product should be carefully observed for such changes.
a) Drugs that are stable under acidic or alkaline conditions.
b) Drugs that are slightly soluble in water.
c) Drugs that contain calcium salt or phosphate.
2) Since the solution contains calcium salt, blood coagulation may occur if it is mixed with citrated blood.
3) After opening the outer wrap and mixing the two solutions, the mixed solution should be used promptly.
Precautions before administration: 1) Be sure to confirm that the center seal between the two chambers has been broken.
2) When administering BFLUID Injection, it is recommended that urine output be maintained at more than 500 mL per day or more than 20 mL per hr.
3) To minimize the risk of infection, perform all procedures under aseptic conditions (disinfection of patient's skin and devices).
4) Use the solution after warming it to near body temperature if it is to be used under cold environmental conditions.
5) After use, discard all unused solution.
Precautions during administration: 1) The usual adult dose is 500 mL administered over 120 min. The administration rate should be reduced in the elderly and in seriously ill patients.
2) If vascular pain occurs, use an alternate infusion site or discontinue administration.
3) Since skin necrosis and ulceration, which are considered to be caused by extravasation of the solution, have been reported, observe the injection site carefully. After confirming the clinical signs of extravasation (e.g., redness, infiltration, or swelling) at the injection site, immediately discontinue administration and institute appropriate treatment.
4) A light-resistant cover should be used or other appropriate measures should be taken to avoid photochemical decomposition of the vitamin B₁ in the solution, although such photochemical decomposition does not occur in a very short time.
When other vitamins are added, a light-resistant cover should also be used or other appropriate measures should be taken to avoid photochemical decomposition of vitamins.
PRECAUTIONS FOR HANDLING: 1. An oxygen absorbent is enclosed between the bag and the outer wrap to maintain stability of the product. Do not remove the outer wrap until immediately before use.
2. A crystalline precipitate may form in the upper chamber solution (amino acid solution) due to changes in environmental temperature. Shake the solution at a temperature of 15°C-25°C to dissolve all precipitate before use.
3. Do not use the solution if the outer wrap covering the product has been damaged, the solution is discolored, or a precipitate that cannot be dissolved by shaking has formed.
4. If the two solutions contained in the chambers have already been mixed together for any reason or if the center seal between the two chambers appears white in color (the seal appears white if it is not intact), do not use the product.
5. Puncture the rubber stopper vertically with a needle in the marked circle. If the stopper is not pierced vertically, the needle may pass through the neck of the container, resulting in leakage of the contents.
6. Soft bag products may not be infused in tandem using a connection tube.
7. If droplets of water or leakage of the contents is noted inside the outer wrap or if the solution is discolored or cloudy, do not use the solution.
8. The volume markings on the container may not be accurate. Use them only as a rough guide.

Store below 30°C, protected from light.
Shelf-life: 24 months from the date of manufacture.

Parenteral Nutritional Products

V06DE - Amino acids/carbohydrates/minerals/vitamins, combinations ; Used as general nutrients.

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