Amiparen

AMIPAREN
10% AMINO ACID INJECTION

AMIPAREN is a new sterile injection solution of total amino acids intended for use in hyperalimentation and general parenteral nutrition.
AMIPAREN contains relatively larger amounts of branched chain amino acids (leucine, isoleucine and valine), which suppress protein breakdown and promote protein synthesis in the muscle^1-3 and smaller amounts of aromatic and acidic amino acids. A series of preclinical and clinical studies established that AMIPAREN was effective in sparing protein in various types of insults and malnutritional state.
AMIPAREN was also carefully formulated to contain no chloride ions and minimum sodium ions to facilitate easy supplementation of electrolytes.

COMPOSITION:
Each 1000 mL AMIPAREN contains:

L-Leucine	14	g	L-Tyrosine	0.5	g
L-Isoleucine	8	g	L-Arginine	10.5	g
L-Valine	8	g	L-Histidine	5	g
Lysine Acetate	14.8	g	L-Alanine	8	g
(L-Lysine equivalent)	(10.5	g)	L-Proline	5	g
L-Threonine	5.7	g	L-Serine	3	g
L-Tryptophan	2	g	Aminoacetic acid	5.9	g
L-Methionine	3.9	g	L-Aspartic acid	1	g
L-Phenylalanine	7	g	L-Glutamic acid	1	g
L-Cystein	1	g
Total free amino acids	100	g
Essential amino acids (E)	59.10	g
Non-essential amino acids (N)	40.90	g
E/N ratio	7.2
Branched chain amino acids	30.0	w/w%
Total nitrogen	15.7	g
Sodium	2	mEq*
Chloride	-
Acetate	120	mEq*

*Approx
Sodium bisulfite is added as a stabilizer

INDICATIONS
AMIPAREN is indicated for amino acid supply in the following instances: hypoproteinemia, malnutrition and pre and lor postoperative condition.

DOSAGE AND ADMINISTRATION
Central vain infusion :
The usual adult dosage is 400 - 800 mL per day by drip infusion via the central vein.
The dosage may be increased or decreased depending on the patient's age, symptoms and body weight.

Peripheral vein infusion:
The usual adult dosage is 200 - 400 mL per dose by drip infusion via the peripheral vein. The usual peripheral infusion rate is such a rate as to provide about 10 g of amino acids over 60 minutes of infusion in order to achieve optimal physiological utilization of amino acids. A typical infusion rate in adults is 100 mL over 60 minutes (about 25 drops per minute), and the rate should be adjusted downward in the case of children, elderly patients and severely ill patients.
The dosage may be increased or decreased depending on the patient's age, symptoms and body weight.
Combination of AMIPAREN with a carbohydrate solution is highly recommended for efficient utilization of amino acids in the body.

PRECAUTIONS

1. Use is contraindicated in the following instances:
   1. Patients with hepatic coma or a risk of hepatic coma
   2. Patients with severely impaired renal function or a risk of hypernitremia 
   3. Patients with abnormal amino acid metabolism
2. The solution should be infused with care in the following instances:
   1. Patients with severe acidosis
   2. Patients with congestive heart failure 
   3. Patients with hyponatremia
3. Adverse reactions:
   1. Hypersensitivity: Rare eruption or other hypersensitive reactions were reported, If such reactions occur, the solution should be discontinued.
   2. Cardiovascular: Occasional chest discomfort and palpitation were reported. 
   3. Gastrointestinal: Occasional nausea and vomiting were reported 
   4. Hepatic: An occasional increase in GOT, GPT and total bilirubin levels was reported 
   5. Renal : An occasional increase in blood urea nitrogen was reported 
   6. Large and acute administration: Acidosis was reported after large and acute administration of the solution
   7. Other: Occasional chills, fever, hot flush, headache and vascular pain were reported
4. Use in immature infants, newborns and infants: The safety of the solution in immature infants, newborns and infants has not been established yet.
5. Precautions in use:
   1. Acetic acid is formulated in an amount of about 120 mEq/L Concomitant use of the solution with electrolyte solutions and administration of the solution in large doses require careful supervision of electrolyte balance.
   2. Infusion should be slow.

PHARMACOLOGY
The value of AMIPAREN as a source of amino acids in the nutritional support was assessed in hyperalimentation therapy using normal rats ⁴⁾ and insulted rats ^5-7)

1. AMIPAREN promptly improved and maintained nitrogen balance and exhibited a pronounced nitrogen sparing effect in these models.^5-6)
2. The solution promoted synthesis of plasma total protein and albumin.^{4, 5)}
3. The urinary 3-methylhistidine / creatinine ratio, an indicator of protein catabolism in the muscle under insult, was low after infusion treatment, indicating a very potent inhibitory effect of the solution on muscle protein breakdown. ^6-7)
4. The plasma concentrations of free amino acids including branched chain amino acids showed minor fluctuation during infusion treatment. Amino acid metabolism was judged to be steady during AMIPAREN therapy. ^4-6)

CLINICAL STUDIES
Clinical studies of AMIPAREN were conducted in a total of 546 patients undergoing central of peripheral venous nutritional management. ^8-10)
These studies provided evidence of the high clinical value of the solution as a source of amino acids in terms of major protein metabolism - related indexes including nitrogen balance, serum total protein and albumin levels, rapid turnover protein level, and urinary 3-methylhistidine/creatinine ratio.

Adverse reactions and abnormal laboratory values
In 546 patients treated, 17 cases of side effects were reported. Complaints included vascular pain (0.4%) and nausea and vomiting (0.4%). Abnormal laboratory tests showed an increase in GOT and/or GPT (0.7%), an increase in BUN (0,5%) and an increase in total bilirubin (0.4%)


PRECLINICAL STUDIES

1. Pharmacokinetics ¹¹⁾
   • ¹⁴C-Amino acids formulated in AMIPAREN were readily taken up into plasma protein fractions after intravenous infusion in all normal rats at 3,7 and 57 weeks of age. The radioactivity was distributed in higher concentrations to protein fractions of the spleen, liver and kidneys as well as muscles.
   • Respiratory excretion accounted for 37.1 % - 44.2% over 72 hours post-infusion. As other major routes of elimination, 3.9% - 5.2% and 1.2% - 3.1 % of the radioactivity were recovered from the urine and feces, respectively.
   • Amino acid fractions in the urine contained only 1.1 % - 1.5% of the amino acids given. The overall retention of amino acids in the body amounted to more than 98.5% of the dose.
2. Toxicity
   • Acute toxicity ¹²⁾ : LD₅₀ values (intravenous, infusion rate: 4 mL/ min), 107 mL/ kg male rabbits, 120 mL/ kg female rabbits
   • Long term toxicity studies (rabbits, intravenous, 13 weeks ¹³⁾ and 26 weeks ¹⁴⁾, an antigenicity study and a local irritation study did not reveal any AMIPAREN related specific toxic symptoms.

DESCRIPTION
AMIPAREN is a sterile, clear, coloriess aqueous solution for injection.
pH:
about 6.9 (average immediately after manufacture)
6.5 - 7.5 (specification)
Specific gravity (20°C): 1.032
Osmotic pressure: about 3 (ratio to saline solution)

STORAGE AND HANDLING
Precaution :

1. A crystalline precipitate may form due to temperature changes during storage. Shake the solution at temperature of 15 - 25° C to dissolve precipitate before use.
2. Do not use the product if the solution is discolored, or a precipitate that cannot be dissolved by shaking has formed.
3. Do not use if the solution is cloudy.
4. Glass bottle product are not equipped with internal air-venting tube. Glass products should be punctured with air needle immediately before use to prevent contents from leaking.

Storage: in a cool place, away from direct sunlight.
Expiration date: use before the expiration date noted on the container.

HOW SUPPLIED:
250 mL X 12 bottles per case
500 mL X 12 bottles per case

REGISTERED NO:
250 mL DKL 9218703649A1
500 mL DKL 9218703649A2

HARUS DENGAN RESEP DOKTER

Manufactured by :
PT. Otsuka Indonesia,
Lawang - East Java
Indonesia

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