LIVAMIN L-Isoleucine / L-leucine / L-Valine 952mg / 1.904g / 1.144g per 4.15g Oral Granule 4.5g 1's
RXDRUG-DR-XY43160
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
For the improvement of hypoalbuminemia in patients with decompensated hepatic cirrhosis presenting with hypoalbuminemia despite adequate dietary intake.
Dosage/Direction for Use
The usual adult dose for oral use is one sachet three times a day after meals or as prescribed by the physician.
To be taken with liquid (e.g. glass of water), not to be reconstituted with water or other fluids.
To be taken with liquid (e.g. glass of water), not to be reconstituted with water or other fluids.
Overdosage
No information is available.
Administration
Should be taken with food: Take w/ liqd, do not dissolve on water or other fluids.
Contraindications
Patients with congenital branched-chain amino acid metabolic abnormality. The use of this product may induce convulsions or respiratory disturbances in patients with maple syrup urine disease.
Special Precautions
This drug is indicated for use in patients presenting with hypoalbuminemia despite adequate dietary intake or in whom total dietary calories and protein (amino acids) intake is restricted due to complicated diabetes mellitus or hepatic encephalopathy, among patients with decompensated hepatic cirrhosis presenting with hypoalbuminemia as indicated by a serum albumin level of 3.5 g/dL or less with current or a history of ascites/oedema or hepatic encephalopathy. A dietetic instruction should be provided to the patient in case of dietary deficiency despite the patient being amply capable of food ingestion in the absence of diabetes mellitus and hepatic encephalopathy. If the patient is deficient in dietary intake due to development of hepatic encephalopathy, a drug containing calories and protein (amino acids) should be administered.
This product should not be administered to the following patients with markedly advanced hepatic cirrhosis since such patients may not respond to this drug therapy: Patients with stage III or more in the severity of coma due to hepatic encephalopathy; Patients with a total bilirubin level of 3 mg/dL or more; Patients with a markedly depressed hepatic function for protein synthesis.
This drug consists of branched-chain amino acids alone and does not contain all amino acid required for protein synthesis. Therefore, the patient taking this drug must ingest the amount of protein (amino acids) and calories required (daily protein intake, 40 g or more; and daily calorie intake, 1000 kcal or more) in the diet according to the patient's condition. If the patient is on restricted protein intake, in particular, caution must be exercised in that the patient may not respond this drug therapy and, moreover, long-term use of this product may lead to aggravation of nutriture unless the minimum protein and calorie requirements are secured.
If abnormal blood urea nitrogen (BUN) or blood ammonia is noted following administration of this drug, caution must be taken because it may be attributable to overdose.
Caution should also be observed regarding long-term overdosage since it may give rise to aggravation of nutriture.
If no improvement in hypoalbuminemia is attained in 2 months or longer with the use of this drug, appropriate measures should be taken such as replacement with other therapy.
Use in Children: The safety of this drug in children has not been established (no clinical experience).
Use in Elderly: This drug should be administered to elderly patients with caution since such patients often have decreased physiological functions, and metabolic disorders such as blood ammonia elevation can be more sensitive to develop during this drug therapy.
This product should not be administered to the following patients with markedly advanced hepatic cirrhosis since such patients may not respond to this drug therapy: Patients with stage III or more in the severity of coma due to hepatic encephalopathy; Patients with a total bilirubin level of 3 mg/dL or more; Patients with a markedly depressed hepatic function for protein synthesis.
This drug consists of branched-chain amino acids alone and does not contain all amino acid required for protein synthesis. Therefore, the patient taking this drug must ingest the amount of protein (amino acids) and calories required (daily protein intake, 40 g or more; and daily calorie intake, 1000 kcal or more) in the diet according to the patient's condition. If the patient is on restricted protein intake, in particular, caution must be exercised in that the patient may not respond this drug therapy and, moreover, long-term use of this product may lead to aggravation of nutriture unless the minimum protein and calorie requirements are secured.
If abnormal blood urea nitrogen (BUN) or blood ammonia is noted following administration of this drug, caution must be taken because it may be attributable to overdose.
Caution should also be observed regarding long-term overdosage since it may give rise to aggravation of nutriture.
If no improvement in hypoalbuminemia is attained in 2 months or longer with the use of this drug, appropriate measures should be taken such as replacement with other therapy.
Use in Children: The safety of this drug in children has not been established (no clinical experience).
Use in Elderly: This drug should be administered to elderly patients with caution since such patients often have decreased physiological functions, and metabolic disorders such as blood ammonia elevation can be more sensitive to develop during this drug therapy.
Use In Pregnancy & Lactation
The safety of this drug in pregnant women and nursing mothers has not been established. Therefore, the product should not be used in pregnant women, and women suspected of being pregnant, and nursing mothers unless the expected benefits outweigh any potential risk.
Adverse Reactions
Among 420 cases studied prior to the time of approval, 40 adverse reactions were reported in 27 cases (6.4%). The commonly reported adverse reactions by the time of approval included abdominal distension (9 reactions, 2.1%), diarrhea (5 reactions, 1.2%) and constipation (4 reactions, 1.0%).
267 adverse reactions were reported in 178 cases (6.2%) of 2,877 cases surveyed in the post marketing surveillance. The commonly reported adverse reactions included hyperammonemia (23 reactions, 0.8%), queasy (15 reactions, 0.5%), diarrhea (14 reactions, 0.5%), increased BUN (14 reactions, 0.5%) and abdominal pain (12 reactions, .4%).
63 adverse reactions were reported in 41 cases (12.3%) of 334 cases in postmarketing clinical studies (including long-term studies). The commonly reported adverse reactions included abdominal distension (13 reactions, 3.9%), constipation (9 reactions, 2.7%), diarrhea (5 reactions, 1.5%), itching (4 reactions, 1.2%), queasy (3 reactions, 0.9%) and vomiting (3 reactions, 0.9%). (See table).
267 adverse reactions were reported in 178 cases (6.2%) of 2,877 cases surveyed in the post marketing surveillance. The commonly reported adverse reactions included hyperammonemia (23 reactions, 0.8%), queasy (15 reactions, 0.5%), diarrhea (14 reactions, 0.5%), increased BUN (14 reactions, 0.5%) and abdominal pain (12 reactions, .4%).
63 adverse reactions were reported in 41 cases (12.3%) of 334 cases in postmarketing clinical studies (including long-term studies). The commonly reported adverse reactions included abdominal distension (13 reactions, 3.9%), constipation (9 reactions, 2.7%), diarrhea (5 reactions, 1.5%), itching (4 reactions, 1.2%), queasy (3 reactions, 0.9%) and vomiting (3 reactions, 0.9%). (See table).
Storage
Store at temperatures not exceeding 30°C.
Protect from light and store in a tight container.
Protect from light and store in a tight container.
Action
Pharmacology: The effects of this drug were investigated in rats with carbon tetrachloride-induced chronic liver damage as a rat model of hepatic cirrhosis with malnutrition (hypoalbuminemia).
Rats were fed diets containing the same composition of branched-chain amino acids as this drug at concentrations of 0, 2.5, 5.0 and 10.0% ad libitum. The results showed that 2.5% branched-chain amino acid supplementation group was most superior among other supplementation groups in respect of nutritional parameters such as nitrogen balance, nitrogen balance efficiency, plasma total protein levels and plasma albumin levels, and exhibited an adequate correction of plasma Fischer ratio.
Rats were fed free access to diets supplemented with different branched-chain amino acids composition ratios as follows: L-isoleucine:L-leucine:L-valine composition ratio, I (2:1:1), II (1:2:1.2), and III (1:1:2). The results revealed that rats receiving the diet containing the same branched-chain amino acids composition (II) as this drug displayed better about nitrogen balance, plasma total protein levels and plasma albumin levels than the other composition ratio groups, and exhibited an adequate correction of plasma Fischer ratio.
Rats were fed ad libitum on diets supplemented with the same branched-chain amino acids composition as this drug or with a combination of essential amino acids comparable to this drug in terms of nitrogen quantity and amount of energy. Greater nutritional effects were observed in the branched-chain amino acid diet group, compared with the essential amino acid diet group. In addition, suppression of thrombocytopenia and decreased liver weight was noted in the branched-chain amino acid diet group.
The effect of this drug was examined in rats with portacaval shunt as an animal model of hepatic encephalopathy. Plasma and brain amino acid levels and the brain monoamine level normalized in rats receiving the same composition of branched-chain amino acids as this drug, whereas a trend of aggravation rather than improvement was observed in rats administered a combination of essential amino acids equivalent in nitrogen quantity and amount of energy to this product.
Pharmacodynamics: Clinical Studies: A six-month open clinical trial performed in hypoalbuminemic patients with decompensated hepatic cirrhosis revealed resolution of hypoalbuminemia as indicated by increased serum albumin levels, improvement in nutritional parameters such as serum total protein, transferrin and body weight, and improvement of malaise and fatigability during 2-weeks to 2-months period of the study treatment. Subsidence in ascites was noted at the fifth month. These improvements kept on until the completion of the study. The usefulness rate of this drug, determined based on overall assessment of data regarding subjective symptom, objective symptom, nutriture, psychoneurological symptoms, quality of life, and safety, was 51.2% (104/203 patients). A subsequent survey on prognosis of these patients revealed a more favorable life prognosis in those showing improvement in nutriture after the study and in patients receiving long-term therapy of this drug.
A 12-week double-blind placebo-controlled clinical study was conducted in hypoalbuminemic patients with decompensated hepatic cirrhosis. Treatment with this drug increased the serum albumin level, the primary endpoint, by 0.2 g/dL on average, and 31.5% of patients treated (17/54 patients) showed serum albumin levels increased by 0.4 g/dL or more, indicating a significantly greater improvement as compared with the placebo treatment. The total improvement rate, determined based on overall assessment of data regarding subjective and objective symptoms, , psychoneurological symptoms, and quality of life, was 45.8% (38/83 patients) for the BRANCHED-CHAIN AMINO ACIDS-treated group and 17.3% (14/81 patients) for the placebo group. The usefulness rate, determined based on evaluation of safety in addition to the above variables, was 49.4% (42/85 patients) for the BRANCHED-CHAIN AMINO ACIDS-treated group and 18.1% (15/83 patients) for the placebo group.
An open-label follow-up clinical trial was performed for 2 years to investigate the relationship between serum albumin levels and clinical manifestations and prognosis for survival. The results revealed that changes in serum albumin levels over time were significantly correlated with status of ascites, oedema and performance status. As for the relationship to prognosis for survival, the risk of mortality (hazard ratio) per unit time based on no change group in serum albumin levels invariance was estimated to be 0.77 for subjects showing a serum albumin level increased by 0.2 g/dL, and to be 0.59 for those showing a serum albumin level increased by 0.4 g/dL in a year.
To evaluate the effect of this drug on the prognosis for survival, randomized controlled clinical trials were conducted for at least 2 years by comparison with dietary treatment in terms of study treatment time to discontinuation or dropout using significant events related to the prognosis for survival such as exacerbation of hepatic insufficiency in patients with liver cirrhosis, as indicated by occurrence of ascites, oedema, hepatic encephalopathy, and jaundice; rupture of oesophageal varices (rupture of gastric varices); development of hepatic cancer; and death, which were determined as serious complications occurring in association with advancing hepatic cirrhosis. The results showed that Branched-Chain Amino Acids significantly inhibited the development of the above serious complications of hepatic cirrhosis among 622 patients included in the analyses (308 and 314 patients in dietary-treated patients and Branched-Chain Amino Acids-treated patients, respectively). The hazard ratio for Branched-Chain Amino Acids-treated patients against dietary-treated patients was 0.67 with 95% confidence interval ranging from 0.49-0.93. (See figure.)
Rats were fed diets containing the same composition of branched-chain amino acids as this drug at concentrations of 0, 2.5, 5.0 and 10.0% ad libitum. The results showed that 2.5% branched-chain amino acid supplementation group was most superior among other supplementation groups in respect of nutritional parameters such as nitrogen balance, nitrogen balance efficiency, plasma total protein levels and plasma albumin levels, and exhibited an adequate correction of plasma Fischer ratio.
Rats were fed free access to diets supplemented with different branched-chain amino acids composition ratios as follows: L-isoleucine:L-leucine:L-valine composition ratio, I (2:1:1), II (1:2:1.2), and III (1:1:2). The results revealed that rats receiving the diet containing the same branched-chain amino acids composition (II) as this drug displayed better about nitrogen balance, plasma total protein levels and plasma albumin levels than the other composition ratio groups, and exhibited an adequate correction of plasma Fischer ratio.
Rats were fed ad libitum on diets supplemented with the same branched-chain amino acids composition as this drug or with a combination of essential amino acids comparable to this drug in terms of nitrogen quantity and amount of energy. Greater nutritional effects were observed in the branched-chain amino acid diet group, compared with the essential amino acid diet group. In addition, suppression of thrombocytopenia and decreased liver weight was noted in the branched-chain amino acid diet group.
The effect of this drug was examined in rats with portacaval shunt as an animal model of hepatic encephalopathy. Plasma and brain amino acid levels and the brain monoamine level normalized in rats receiving the same composition of branched-chain amino acids as this drug, whereas a trend of aggravation rather than improvement was observed in rats administered a combination of essential amino acids equivalent in nitrogen quantity and amount of energy to this product.
Pharmacodynamics: Clinical Studies: A six-month open clinical trial performed in hypoalbuminemic patients with decompensated hepatic cirrhosis revealed resolution of hypoalbuminemia as indicated by increased serum albumin levels, improvement in nutritional parameters such as serum total protein, transferrin and body weight, and improvement of malaise and fatigability during 2-weeks to 2-months period of the study treatment. Subsidence in ascites was noted at the fifth month. These improvements kept on until the completion of the study. The usefulness rate of this drug, determined based on overall assessment of data regarding subjective symptom, objective symptom, nutriture, psychoneurological symptoms, quality of life, and safety, was 51.2% (104/203 patients). A subsequent survey on prognosis of these patients revealed a more favorable life prognosis in those showing improvement in nutriture after the study and in patients receiving long-term therapy of this drug.
A 12-week double-blind placebo-controlled clinical study was conducted in hypoalbuminemic patients with decompensated hepatic cirrhosis. Treatment with this drug increased the serum albumin level, the primary endpoint, by 0.2 g/dL on average, and 31.5% of patients treated (17/54 patients) showed serum albumin levels increased by 0.4 g/dL or more, indicating a significantly greater improvement as compared with the placebo treatment. The total improvement rate, determined based on overall assessment of data regarding subjective and objective symptoms, , psychoneurological symptoms, and quality of life, was 45.8% (38/83 patients) for the BRANCHED-CHAIN AMINO ACIDS-treated group and 17.3% (14/81 patients) for the placebo group. The usefulness rate, determined based on evaluation of safety in addition to the above variables, was 49.4% (42/85 patients) for the BRANCHED-CHAIN AMINO ACIDS-treated group and 18.1% (15/83 patients) for the placebo group.
An open-label follow-up clinical trial was performed for 2 years to investigate the relationship between serum albumin levels and clinical manifestations and prognosis for survival. The results revealed that changes in serum albumin levels over time were significantly correlated with status of ascites, oedema and performance status. As for the relationship to prognosis for survival, the risk of mortality (hazard ratio) per unit time based on no change group in serum albumin levels invariance was estimated to be 0.77 for subjects showing a serum albumin level increased by 0.2 g/dL, and to be 0.59 for those showing a serum albumin level increased by 0.4 g/dL in a year.
To evaluate the effect of this drug on the prognosis for survival, randomized controlled clinical trials were conducted for at least 2 years by comparison with dietary treatment in terms of study treatment time to discontinuation or dropout using significant events related to the prognosis for survival such as exacerbation of hepatic insufficiency in patients with liver cirrhosis, as indicated by occurrence of ascites, oedema, hepatic encephalopathy, and jaundice; rupture of oesophageal varices (rupture of gastric varices); development of hepatic cancer; and death, which were determined as serious complications occurring in association with advancing hepatic cirrhosis. The results showed that Branched-Chain Amino Acids significantly inhibited the development of the above serious complications of hepatic cirrhosis among 622 patients included in the analyses (308 and 314 patients in dietary-treated patients and Branched-Chain Amino Acids-treated patients, respectively). The hazard ratio for Branched-Chain Amino Acids-treated patients against dietary-treated patients was 0.67 with 95% confidence interval ranging from 0.49-0.93. (See figure.)
Pharmacokinetics: (For Reference) Absorption, Distribution, Metabolism and Excretion in Rats: The branched-chain amino acids administered to rats were rapidly absorbed, reaching a peak concentration in plasma and whole blood 4 hours after dosing, followed by a slow decline. The branched-chain amino acids in plasma were promptly utilized for protein synthesis. The branched-chain amino acids absorbed were distributed extensively to the whole body, conspicuously in those tissues actively involved in protein synthesis. During a 168-hour period after dosing, the branched-chain amino acids administered was excreted in urine and feces, and in expired breath, 4% and 41%, respectively. It indicated that the branched-chain amino acids administered were utilized in part as a source of energy. It was also demonstrated that their absorption, distribution and excretion were not significantly affected in repeat-dose studies).
In hepatically impaired rats, absorption of the branched-chain amino acids administered proceeded slower than in normal rats, but their transition to plasma protein, distribution in tissues and excretion in urine and feces were essentially comparable with those seen in normal rats. It was thus indicated that the branched-chain amino acids administered were effectively utilized as substrates for protein synthesis in hepatically impaired rats as well. Compared with normal rats, the excretion in expired breath was greater in the hepatically impaired rats, in which the branched-chain amino acids administered were thus more efficiently utilized as a source of energy).
In hepatically impaired rats, absorption of the branched-chain amino acids administered proceeded slower than in normal rats, but their transition to plasma protein, distribution in tissues and excretion in urine and feces were essentially comparable with those seen in normal rats. It was thus indicated that the branched-chain amino acids administered were effectively utilized as substrates for protein synthesis in hepatically impaired rats as well. Compared with normal rats, the excretion in expired breath was greater in the hepatically impaired rats, in which the branched-chain amino acids administered were thus more efficiently utilized as a source of energy).
MedsGo Class
Cholagogues, Cholelitholytics & Hepatic Protectors
Features
Brand
Livamin
Full Details
Dosage Strength
952 mg/1.904g/1.144g / 4.15g sachet
Drug Ingredients
- Amino Acid
Drug Packaging
Oral Granule 4.5g x 1's
Generic Name
Amino Acid
Dosage Form
Oral Granule
Registration Number
DR-XY43160
Drug Classification
Prescription Drug (RX)
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