MM Reg No: 2406AA4745

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Approved: December 2019

- Total Amino Acid Infusion Solution for Renal Failure -Designated drug, prescription drug*
Storage: Store below 30°C.
Expiration date: Indicated on the package and plastic bag.
* Caution: Use only as directed by a physician.

CONTRAINDICATIONS (Neoamiyu is contraindicatedin the following patients.)
1. Patients with hepatic coma or possible hepatic coma
[Imbalance of amino acids may be promoted with the useof the drug, resulting in the development or aggravationof hepatic coma.]
2. Patients with hyperammonaemia [Hyperammonaemia
may aggravate due to nitrogen overload.]
3. Patients with congenital amino acid metabolism
abnormality [The condition may aggravate due to failureof the metabolism of amino acid administered.]

DESCRIPTION
1. Composition
Neoamiyu contains the following ingredients per 200 mL.
Active Ingredients
L-isoleucine
L-leucineL-lysine acetate
L-methionine
L-phenylalanine
L-threonine
L-tryptophan
L-valine
L-alanineL-arginine
L-aspartic acidL-glutamic acidL-histidine
L-proline
L-serine
L-tyrosine
GlycineAmino acids totalTotal concentration of amino acidsContent per 200 mL bag
1.500 g2.000 g1.400 g1.000 g1.000 g0.500 g0.500 g1.500 g0.600 g0.600 g0.050 g0.050 g0.500 g0.400 g0.200 g0.100 g0.300 g12.200 g
6.100 w/v%

Inactive Ingredients
L-cysteine
Sodium hydrogen sulfite
Glacial acetic acid (pH regulator)

Content per 200 mL bag
0.050 g0.050 gq.s.

Total nitrogen: 8.1 mg/mL
Total concentration of free amino acid: 5.90 w/v%
Essential amino acid/nonessential amino acid: 3.21Electrolytes
Na+: ca. 2 mEq/L
CH3COO−: ca. 47 mEq/L

D４０１１０２

2. Product description
Neoamiyu is a clear and colorless aqueous solution forinfusion.
pHOsmotic pressure ratio

6.6 - 7.6ca. 2

3. Plastic bag
The specification of the plastic bag used for this product is
as follows:
Specification

Reserve capacity of the plastic bag

200 mL plastic bag
ca. 250 mL(When the solution is poured from a height of 45 cm)

INDICATIONS
Neoamiyu is indicated for the provision of amino acids in thefollowing instances in patients with acute or chronic renal
failure: hypoproteinemia, malnutrition, and before and aftersurgery.

DOSAGE AND ADMINISTRATION
1. Chronic Renal Failure(1) When administered via a peripheral intravenous line inadults, Neoamiyu should be injected slowly at 200 mL
once daily in patients with chronic renal failure. The
usual intravenous infusion rate is 120 to 180 min. per
200 mL, and a slower rate is recommended for children,
elderly patients, and patients with a serious condition.
The dose may be adjusted according to the patient’s age,condition , and body weight. In patients on dialysis,
Neoamiyu should be injected into the venous side of thedialysis circuit from 90 to 60 minutes before completionof dialysis.
Regarding calories, more than 1500 kcal per day isrecommended to be provided for the efficiency of aminoacid utilization.
(2) When administered via total parenteral nutrition inadults, Neoamiyu should be injected in the central vein
by intravenous drip at 400 mL once daily. The dose may
be adjusted according to the patient’s age, condition, andbody weight. More than 500 kcal of nonprotein calories
should be administered per 1.6 g of nitrogen (200 mL ofthis product) for the efficiency of amino acid utilization.

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2. Acute Renal Failure
In adults, Neoamiyu should be administered via total
parenteral nutrition in the central vein by intravenous drip
at 400 mL once daily. The dose may be adjusted according
to the patient’s age, condition, and body weight. More than
500 kcal of nonprotein calories should be administered per
1.6 g of nitrogen (200 mL of this product) for the efficiencyof amino acid utilization.

PRECAUTIONS
1. Careful Administration (Neoamiyu should beadministered with care in the following patients.)(1) Patients with impaired cardiovascular function [The useof the product is associated with increased amount ofblood circulation, which may lead to overload of theheart and resultant aggravation of the patient’scondition.](2) Patients with impaired hepatic function or
gastrointestinal hemorrhage [Excessive accumulation ofamino acids or hyperammonemia may develop with theuse of the product.](3) Patients with marked electrolyte abnormality orabnormal acid-base balance [The patient’s condition may
aggravate with the use of the product.]
2. Important Precautions(1) Neoamiyu should be used in patients who needparenteral nutrition due to inability or insufficience oforal food intake.
(2) It has been reported that the use of essential amino acidproducts for renal failure may be associated withhyperammonemia or loss of consciousness if theseproducts are used as the only source of nitrogen.
Therefore, the use of this product should be discontinued
immediately if poor response to voice or otherabnormalities such as decreased spontaneous speech andactivities are noted during treatment.
3. Adverse Reactions
In clinical studies of Neoamiyu, 15 adverse reactions(4.7%) were reported in 10 (3.1%) of 318 patients. At thetime of approval of the drug, main adverse reactions
included nausea··queasy (1.9%), vomiting (0.6%), headache(0.6%), and metabolic acidosis (0.6%). Abnormal
laboratory changes included decreased bicarbonate ionlevel 3 events (0.9%), increased AST (GOT) 1 event(0.3%), and increased blood ammonia level 1 event (0.3%).
(As of the end of approval)
In post-marketing surveillance, adverse reactions (including
abnormal laboratory changes) were reported in 98 (3.34%)
of 2,936 patients. Main adverse reactions included
increased blood urea nitrogen 23 events ( 0.78%), increased
AST (GOT) 20 events (0.68%), increased ALT (GPT) 17events (0.58%), hepatic disorder 13 events (0.44%), nausea
11 events (0.37%), increased blood creatinine level 8 events(0.27%), hyperammonemia 7 events (0.24%), metabolic
acidosis 6 events (0.20%), vomiting 4 events (0.14%), andanorexia 4 events (0.14%).(As of the end of there-examination)

Other adverse reactions
Appropriate measures should be instituted, such as
discontinuation of treatment, if any of the following
adverse reactions are observed.
0.1 to <5%Hypersensitivity
Gastrointestinal
HepaticRenal
Cardiovascular
Large dose andrapidadministration
Other

Nausea, vomiting,anorexia
Hepatic disorder
Increased blood
creatinine level,
increased blood urea
nitrogen<0.1%
Pruritus, redness

Incidence unknown
Generalized
urticaria

Chest discomfort Palpitations
Acidosis

Metabolic acidosis,
Fever, headache,
hyperammonemia,
nasal congestion,
decreased bicarbonate nasal discharge
ion level

Chills, hot feeling,burning sensationin the head,vascular pain

4. Use in the Elderly
Since the elderly have a physiological hypofunction ingeneral,Neoamiyu should be carefully administered,such as
reduceing the dose.
5. Use during Pregnancy, Delivery or Lactation(1) Neoamiyu should be used in pregnant women or women
having possibilities of being pregnant only if theexpected therapeutic benefit is evaluated to outweigh thepossible risks. [The safety of this product in pregnant
women has not been established.](2) Use of Neoamiyu in nursing mothers is notrecommended. If use of Neoamiyu is judged to beessential, breast feeding must be discontinued during
treatment. [The safety of this product in nursing mothers
has not been established.]
6. Pediatric Use(1) The safety of Neoamiyu in children has not been
established.(No sufficient clinical data has been available
in this population.)(2) Infants, especially low birth weight babies and neonates,
have immature amino acid metabolism. Caution should
be exercised if Neoamiyu is used in such patients, bymonitoring the patient’s clinical condition and laboratory
results, as well as administrating the product at a slower
rate and a reduced dose.
7. Precautions Concerning Use(1) Before administration:
1) If any crystalline substances are present in the solution,these substances should be dissolved at a temperaturefrom 50 to 60°C followed by cooling the solution down
to around body temperature before infusion.
2) Do not use the solution if it is cloudy or contains
particles.
3) The solution should be immediately used after opening
the package, and any residual solution should bediscarded.
(2) During administration:1) In patients with chronic renal failure who are not ondialysis, the amount of protein contained in diet prior totreatment should be reduced by 5 to 10 g per 200 mL ofdose of the product to be administered.

32) Neoamiyu contains sodium and acetic acid at ca. 2mEq/L and ca. 47 mEq/L, respectively. If the product isadministered in large dose or in combination with theelectrolyte solution, the paitent’s electrolyte balanceshould be monitored during treatment.
(3) Dosing rate:
Neoamiyu should be injected slowly into a vein.

CLINICAL STUDIES
1. Comparative trial
An active-controlled study of Neoamiyu versus AMIYU, anessential amino acid preparation for infusion for renal
failure, was performed in patients with chronic renal failure
who were on dialysis.
As shown in the table below, the efficacy and usefulness ofNeoamiyu were demonstrated in the study.

Neoamiyu (66 patients)
AMIYU (72 patients)

Efficacy rate
(defined as effectiveor higher)
78.8% (52/66)
68.1% (49/72)

Usefullness rate
(defined as useful orhigher)
78.8% (22/29)
66.7% (48/72)

2. General Clinical Studies(1) Administered via a peripheral intravenous line:
1)The efficacy and usefulness of Neoamiyu administered in
56 patients on dialysis were as follows:

200 mL (29 patients)
300 mL (27 patients)

Efficacy rate
(defined as effectiveor higher)
75.9% (22/29)
70.4% (19/27)

Usefullness rate
(defined as useful orhigher)
75.9% (22/29)
70.4% (19/27)

2)The efficacy and usefulness of Neoamiyu administered in
23 non-dialysis patients were as follows:

Non-dialysis (23 patients)

Efficacy rate
(defined as effectiveor higher)
73.9% (17/23)

Usefullness rate
(defined as useful orhigher)
73.9% (17/23)(2) Administered in the central vein:
The efficacy and usefulness of Neoamiyu administered in
58 patients with chronic renal failure and 11 with acuterenal failure were as follows:

Chronic (58 patients)
Acute (11 patients)

Efficacy rate
(defined as effectiveor higher)
86.2% (50/58)
100.0% (11/11)

Usefullness rate
(defined as useful orhigher)
91.4% (53/58)
100.0% (11/11)

PHARMACOLOGY
1. Neoamiyu was administered intraperitoneally in a rat modelof chronic renal failure on a low-protein diet for 12 weeks.
Improvement of nutrition was observed while maintaining
the renal function in these rats.
2. The administration of Neoamiyu in the central vein of acuteand chronic renal failure rats was not found with increased
plasma ammonia level, which has been reported with theuse of essential amino acid products. In addition, changes inplasma free amino acid level were almost within the normalrange.
3. The reduction of plasma protein level was suppressed bytreatment with Neoamiyu, when administered in the central
vein of chronic renal failure rats on peritoneal dialysis.

4. The administration of Neoamiyu in the central vein of rats
with chronic renal failure increased uptake of 15N-labeledleucine into the plasma and muscular protein, while
decreasing urinary 3-methylhistidine excretion. (Data onfile)
5. Neoamiyu infused via the central vein in dogs with chronic
renal failure improved nitrogen balance while maintaining
low plasma urea nitrogen level. In addition, no adverse
events such as nausea and vomiting, which have beenreported with the use of essential amino acid products, wereobserved in these dogs.

PRECAUTIONS FOR HANDLING
1. Do not use the product if any discoloration or leakage of thesolution is noted, or the outer bag is wet.
2. Do not open the outer bag until use to prevent discolorationof the solution (a deoxidizer is included in the productpackage to ensure the stability of the product).
3. Care should be exercised not to break the outer bag, which
can cause discoloration of the solution.
4. Neoamiyu can be injected without using an air vent needle.
5. Do not use the product if the seal covering the rubber plugof the plastic bag is not in place.
6. A needle should be vertically inserted at the needle insertion(concave) portion of the rubber plug. If the needle isobliquely inserted, the drug solution may be contaminatedwith a broken piece of rubber plug or outlet inner wall, or
the needle may penetrate through the plastic bag, resulting
in leakage of the solution. In addition, a needle should not
be inserted repeatedly at the same site.
7. The scale printed on the plastic bag should be used only as aguide.
8. Neoamiyu cannot be administered by the tandem systemusing a connecting U-shaped tube. If two plastic bags of thisproduct are used at the same time or sequentially, use a
Y-shaped transfusion set.

PACKAGING
200 mL plastic bags: Packages of 30 bags

Exported by:
EA Pharma Co., Ltd.
1-1, Irifune 2-chome, Chuo-ku, Tokyo, Japan

Manufactured by:
AY PHARMACEUTICALS CO., LTD.
Headquarters: 31-1, Nihonbashi-hamacho 2-chome, Chuo-ku,Tokyo, Japan
Shimizu Plant: 235, Miyakami, Shimizu-ku, Shizuoka-shi,Shizuoka, Japan