Amino Acids

Registered South African indications: 

• Supply of amino acids as part of parenteral nutrition therapy

Contraindications

South African manufacturer recommendations

134g/1000ml IV sol. inf

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Severe renal impairment
• Hepatic impairment
• Inborn errors of amino acid metabolism
• Children
• Metabolic acidosis
• Fluid overload
• Unstable life-threatening circulatory conditions (shock)
• Hypoxia
• Electrolyte disturbances
• Hyperlactataemia
• Increased serum osmolarity
• Pulmonary oedema
• Decompensated heart failure

114g/1000ml IV sol. inf

• Hypersensitivity to the active ingredient or any of its excipients
• Renal impairment
• Hepatic impairment
• Uraemia when dialysis facilities are not available
• Inborn errors of amino acid metabolism

N(2)-L-alanyl-L-glutamine formulations

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Children
• Metabolic acidosis

80g/1000ml (8%) IV sol. inf

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Renal impairment
• Children
• Disturbances of amino acid metabolism
• Fluid overload
• Hyponatraemia
• Hyperkalaemia
• Serious cardiac function disorders

100g/100ml (infant) IV sol. inf

• Hypersensitivity to the active ingredient or any of its excipients
• Renal impairment
• Hepatic impairment
• Disturbances of amino acid metabolism
• Inborn errors of amino acid metabolism
• Metabolic acidosis
• Fluid overload
• Hyperkalaemia
• Hyponatraemia
• Unstable life-threatening circulatory conditions (shock)
• Acid-base disturbances
• Hypoxia
• Electrolyte disturbances
• Hyperlactataemia
• Increased serum osmolarity
• Pulmonary oedema
• Decompensated heart failure

International manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Congenital abnormality of amino acid metabolism

Cautions

South African manufacturer recommendations

134g/1000ml IV sol. inf

• Mild to moderate renal impairment
• Elderly
• Infusion via peripheral veins

114g/1000ml IV sol. inf

• Pregnancy
• Breastfeeding
• Elderly
• Infusion via peripheral veins

N(2)-L-alanyl-L-glutamine formulations

• Elderly

80g/1000ml (8%) IV sol. inf

• Breastfeeding
• Elderly

100g/100ml (infant) IV sol. inf

• Infusion via peripheral veins

International manufacturer recommendations

• Pregnancy
• Breastfeeding
• Renal impairment (certain formulations are contraindicated in severe renal impairment)
• Hepatic impairment (certain formulations are contraindicated in severe renal impairment)
  - Pre-existing liver disease
  - Liver insuffiiciency
• Elderly
• Immunosuppression
• Hyperglycaemia
• Malnutrition
• Underlying disease
• Refeeding severely undernourished patients
• Hypertonic infusion solutions
• Inadequate or excessive nutrients or inappropriate composition of an admixture for a particular patient's needs
• Presence of a congenital disorder of amino acid metabolism
• Pulmonary oedema
• Heart failure
• Severe water and electrolyte disorders
• Severe fluid overload states
• Severe metabolic disorders

Forms avail. in SA and covered in this monograph: inf

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Parenteral nutrition therapy
- For supply of amino acids when oral or enteral nutrition is impossible, insufficient or contraindicated

134g/1000ml IV sol. inf

• IV: 1-1.4g amino acids/dipeptides/kg/day (7-11ml/kg/day); Recommended infusion rate: 0.45-0.5ml/kg/hr; Treatment duration: 7 days

- For supply of amino acids especially to those with highly increased requirements who are unable to receive sufficient amounts of protein enterally

114g/1000ml IV sol. inf

• IV: Max: 1L/24hrs, infused slowly, depending on patient requirements; Max rate: 1L/8hrs; Adjust rate if used simultaneously with IV fat emulsion formulation

- As a supplement to amino acid solutions which do not already contain glutamine

200g/1000ml IV sol. inf (N(2)-L-alanyl-L-glutamine formulation) 

• IV: 0.3-0.5g N(2)-L-alanyl-L-glutamine/kg/day (1.5-2.5ml/kg/day); Max rate: 0.1g amino acid/kg/hr; Max dose: 0.5g/kg/24hrs; Max duration: 2 weeks

- To provide protein in patients with hepatic insufficiencies

80g/1000ml (8%) IV sol. inf

• IV: 1-1.1g amino acids/kg/day (1.3-1.5ml/kg/day); Max dose: 1.5g/kg/24hrs

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In parenteral nutrition regimens, amino acid solution should always be administered in combination with adequate amounts of energy supplements (carbohydrate solutions, fat emulsions), electrolytes, vitamins and trace elements

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134g/1000ml IV sol. inf: No experience is available to date regarding administration for >2 weeks

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N(2)-L-alanyl-L-glutamine formulation: The supply of alanine and glutamine should be taken into consideration in the calculation: the proportion of the amino acids supplied through N(2)-L-alanyl-L-glutamine formulation should not exceed approx. 30% of the total supply
The N(2)-L-alanyl-L-glutamine formulation is an infusion solution concentrate which is not designed for direct administration. Dosage depends on the severity of the catabolic state and on amino acid requirement

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The maximum daily dose of 0,5 g N(2)–L-alanyl-L-glutamine/kg should be administered in combination with at least 1,0g amino acids/kg/day. With the amino acids from the N(2)-L-alanyl-L-glutamine formulation included, this results in a daily dosage of at least 1,5g amino acids/kg body weight

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Administer via central venous route as a continuous infusion

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See additional prescribing points

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International manufacturer recommendations

Parenteral nutrition therapy
- For supply of amino acids as part of a parenteral nutrition regimen

• IV: Recommended daily dietary allowance: 70kg: 56g, dly

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An associated source of non-protein energy should be administered in a quantity not less than 0.75 megajoules (180kcal) per gram of nitrogen. In the initial treatment of severe trauma or in the presence of marked malnutrition, higher doses of amino acids with correspondingly larger quantities of carbohydrate will be necessary to promote adequate patient response to therapy. The degree of negative nitrogen balance being treated is the primary consideration in determining replacement therapy

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The solution is for administration by IV infusion through a central venous catheter with the tip located in the central vena cava

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The flow rate should be increased gradually during the 1st hour. The flow rate must be adjusted taking into account the dose being administered, the daily volume intake, and the duration of the infusion. Use of a final filter is recommended during administration of all parenteral nutrition solutions

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The total daily dose of the solution depends upon the patient's metabolic requirement and clinical response. The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual nitrogen requirements

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In addition to meeting nitrogen needs, the rate of administration is governed, especially during the first few days of therapy, by the patient's ability to tolerate glucose. Daily intake of amino acids, electrolytes and glucose should be increased gradually to the maximum required dose as indicated by frequent determination of urine and blood sugar levels
See additional prescribing points

Paed. forms avail. in SA and covered in this monograph: inf

Paed. dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Partial parenteral nutrition therapy
- When oral or enteral nutrition is impossible, insufficient or contraindicated

100g/100ml (infant) IV sol. inf

Younger than 1 year

• IV: No information available

Between 1-2 years

• IV: Max: 1.5-2.5g amino acids/kg/day (15-25ml/kg); Max infusion rate: 1ml/kg/hr; Treatment duration: As long as parenteral nutrition is  required

Between 2-5 years

• IV: Max: 1.5g amino acids/kg/day (15ml/kg); Max infusion rate: 1ml/kg/hr; Treatment duration: As long as parenteral nutrition is required

Between 6-14 years

• IV: Max: 1g amino acids/kg/day (10ml/kg); Max infusion rate: 1ml/kg/hr; Treatment duration: As long as parenteral nutrition is required

Older than 14 years

• IV: See adult dosage

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No specific dosages for adolescents >14 years provided in South African manufacturer recommendations

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For parenteral nutrition of infants, small children and children, paediatric amino acid preparations should be used, together with required amounts of carbohydrates and fat as energy sources as well as vitamins, electrolytes and trace elements, the composite solution may serve for total parenteral nutrition

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Amino acid solution 10% should be used with sterile transfer equipment immediately after opening. Any unused solution should be discarded. Only clear, particle-free solutions in undamaged containers should be used

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For long-term parenteral nutrition with amino acid 10% essential fatty acids, vitamins and trace elements should be substituted

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Administer as a constant IV infusion via a central vein

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International manufacturer recommendations

Parenteral nutrition therapy
- For supply of amino acids as part of a parenteral nutrition regimen

• IV: Recommended daily dietary allowance: From 2.2g/kg, dly for infants

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In children, the dosage of parenteral nutrition should be individually tailored to the amino acid, electrolyte and energy requirements of the patient

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When used in neonates and children <2 years, the solution (in containers and administration sets) should be protected from light exposure after admixture through administration

Pregnancy

South African manufacturer recommendations

Recommendations are formulation dependent, check Professional Information before administration decision is made

• Caution (114g/1000ml IV sol. inf)
• The risk/benefit relationship should be considered before administering amino acid solutions during pregnancy
• Contraindicated
• Safety and efficacy have not been demonstrated in pregnancy

International manufacturer recommendations

• Caution
• There are no adequate data from the use of amino acid solutions in pregnant women
• Carefully consider the potential risks and benefits for each specific patient before administering

Breastfeeding

South African manufacturer recommendations

Recommendations are formulation dependent, check Professional Information before administration decision is made

• Caution (114g/1000ml IV sol. inf)
• The risk/benefit relationship should be considered before administering amino acid solutions during breastfeeding
• Caution; no information available (80g/1000ml (8%) IV sol. inf)
• Contraindicated
• Safety and efficacy have not been demonstrated in breastfeeding

International manufacturer recommendations

• Caution
• There are no adequate data from the use of amino acid solutions in breastfeeding women
• Carefully consider the potential risks and benefits for each specific patient before administering

Renal Impairment

South African manufacturer recommendations

Recommendations are formulation dependent, check Professional Information before administration decision is made

• Mild to moderate: Caution no information available (134g/1000ml IV sol. inf)
• Severe: Contraindicated (134g/1000ml IV sol. inf) 
• Contraindicated

International manufacturer recommendations

• Caution; dose adjustment recommended 
  Dose adjustment may be necessary
  Certain formulations are contraindicated in severe renal impairment

Hepatic Impairment

South African manufacturer recommendations

• Contraindicated 
  - Except for 80g/1000ml (8%) IV solution indicated for patients with hepatic insufficiencies

International manufacturer recommendations

• Caution; dose adjustment recommended 
  Dose adjustment may be necessary
  Certain formulations are contraindicated in severe renal impairment

Elderly

South African manufacturer recommendations

Caution; no information available

International manufacturer recommendations

• Caution; no dose adjustment recommended 
  Dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy

Porphyria Information

• Not porphyrinogenic (NP) 

Drugs in Sport

• Permitted - No warnings 
  - Prohibition applies to: IV infusions and/or injections of more than a total of 100ml per 12hr period except for those legitimately received in the course of hospital treatments, surgical procedures or clinical diagnostic investigations

Central Nervous System Disorders

• Headache

Cardiovascular Disorders

• Hypotension
• Hypertension
• Infusion site thrombophlebitis
• Venous irritation
• Infusion site:
  - Pain
  - Erythema
  - Warmth
  - Swelling
  - Induration

Respiratory Disorders

• Pulmonary vascular precipitate

Hepatobiliary Disorders

• Hepatic failure
• Hepatic cirrhosis
• Hepatic steatosis
• Hepatic fibrosis
• Cholestasis 
• Hepatic steatosis
• Cholecystitis
• Cholelithiasis
• Increased blood bilirubin
• Increased hepatic enzyme

Endocrine and Metabolic Disorders

• Hyperammonaemia

Musculoskeletal Disorders

• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Rash
• Pruritus
• Erythema

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Anaphylactic/ anaphylactoid reactions
  - Skin, gastrointestinal and severe circulatory (shock) and respiratory manifestations
• Fever
• Azotemia

No information available

• Electrolytes
• Serum osmolarity
• Renal function
• Hepatic function
• Fluid status
• Blood and urine glucose
• Ammonia levels
• Full blood count
• Coagulation parameters
• Acid-base balance

Specific cases may require

• Lipid profile
• Bone density
• Vitamin A levels

Additional observations

• Signs and symptoms of:
  - Infection (leukocytosis, fever, hyperglycaemia)
  - Hypersensitivity
• Infusion site

Administration directions

South African manufacturer recommendations

100g/100ml (infant) 10% IV sol. inf

• Because of the increased risk of microbiological contamination and incompatibilities, amino acid solutions should not be mixed with other medicines
• Should it become necessary to add other nutrients like carbohydrates, lipid emulsions, electrolytes, vitamins or trace elements to 100g/1000ml IV infusion (10%) for complete parenteral nutrition, aseptic admixing, good blending and, in particular, compatibility are absolute requirements
• 100g/1000ml IV infusion (10 %) should not be stored after the addition of other components. Unless stability data is available, mixtures should be used within 24hrs

114g/1000ml IV sol. inf

• When the 114g/1000ml IV solution is infused simultaneously with 500ml IV fat emulsion 20% over 8 hours the drip rate should be adjusted to about 40 drops/mins for amino acids; 20 drops /min for fat emulsion
• The following electrolytes can be added to 1000ml of 114g/1000ml IV solution without risk of precipitation: 480mmol Na⁺ and 480mmol K⁺ as chlorides, 24mmol Ca²⁺ as glubionate and 48mmol Mg²⁺ as sulphate
• The contents of the bottle are for a single infusion only. Any remaining solution must be discarded. Use only additives of known compatibility. Do not use if bottle is leaking or if solution is cloudy or contains a precipitate

134g/1000ml IV sol. inf

• The 134g/1000ml IV infusion should be administered by the central venous route due to its high osmolarity (above 800mosm/litre)
• Most of the clinical experience so far is limited to 7 days of 134g/1000ml IV infusion administration
• No experience is available to date regarding administration for >2 weeks

International manufacturer recommendations

• Electrolyte supplementation may be indicated according to the clinical needs of the patient
• Fat emulsion coadministration should be considered when prolonged parenteral nutrition is required in order to prevent essential fatty acid deficiency (EFAD)
• As indicated on an individual basis, vitamins and trace elements and other components (including glucose and lipids) can be added to the parenteral nutrition regimen to meet nutrient needs and prevent deficiencies and complications from developing
• The osmolarity of a specific infusion solution must be taken into account when peripheral administration is considered
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration

The amino acids are all naturally occurring physiological compounds. Parenterally administered amino acids enter the body pool of free amino acids and all subsequent metabolic pathways. The amino acids enter the plasma pool of corresponding free amino acids. From the intravascular space, amino acids distribute to the interstitial fluid and are individually regulated for each single amino acid into the intracellular space of different tissues as required.

COMBINATION PREPARATIONS

Infusion (per 1000ml) 80g

• Aminosteril N-Hepa 8% (Fresenius) originator

Infusion (per 1000ml) 100g

• Aminoven infant 10% (Fresenius) originator

Infusion (per 1000ml) 114g

• Vamin 18 (electrolyte free)

Infusion (per 1000ml) 134g

• Glamin (Fresenius) originator

Infusion (per 100ml) 20g

• Dipeptiven (Fresenius) originator